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Trickett Wendler Right to Try Act of 2017

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"Another problem with right-to-try laws is that they are extremely inequitable. Basically, right-to-try laws limit who can access them by wealth."
Using rich human guinea pigs rather than poor (company paid) human guinea pigs is unfair.

What if you cannot charge money until approved by the FDA? Which means "right-to-try"="wrong-to-charge".

Aside from breeding false hopes, it would save the imaginary lives endangered by the approval process.

As long as the right-to-try does not come with a non-disclosure agreement, I can see companies being very very reluctant to allow use of their drugs that have not passes phase 2 trials. Imagine the results of your drug killing some sweet little child, and the national media picking up the story. That drug would cease to exist very quickly, all in response to the sell-off of that companies stock.

Well that is as much of a bright side as I can see in this silliness.

@ Anonymous pseudonym--What you say makes perfect sense, but I think what happens is the parents of that child are so grateful for the chance to try what they perceive as a cutting edge drug that they won't raise a fuss when their child dies. An all-too-familiar example of this are the pediatric patients of Burzynski. You don't often hear parents complaining after their child dies (and sadly it seems even when they do it doesn't make a difference even if it makes the media, as Burzynski keeps chugging along.

AP@3: One of the many problems with "right-to-try" laws is that they explicitly protect the doctors and pharma companies involved from lawsuits by patients who are administered these drugs under these laws. It's still possible that the pharma company could be hit with adverse publicity, but the claims would be (and cannot be) legally proven.

If the drug companies are not allowed to charge for the drug, they HAVE to follow the Stan Burzynski model and charge for administrative fees or whatever. Producing a Phase 2 drug for a right to try patient is going to be prohibitively expensive.

And with the quacks picking up on the Burzynski model, we're just legitimizing quackery. It will have real human consequences.

All because some politicos don't like regulation by reflex.

There are very real lives being lost in the approval process. But the solution isn't to throw it all out. It's to seriously ramp up funding for the FDA and also organizations like the NIH that can help fund clinical trials for drugs that don't have a profit motivation to push them. Let's face it -- sildenafil is an amazing lifesaver for blue babies, but it was never gonna get to market if someone hadn't stumbled upon its very intriguing and extremely profitable side effect as a bona fide impotence treatment.

Profit can be a great motivator, but when it comes to saving lives, we can't let profit be the *only* motivator. Unfortunately, removing FDA protections will only aggravate this problem.

if you speak out against right-to-try, you will be painted as painted as being in the pocket of big pharma.

Sheesh, where do these painters think the Goldwater Institute and pols like Ron Johnson are getting their funding support? That's right – the pharmas are among their biggest backers; not necessarily directly but through intermediaries like ALEC, etc.

All because some politicos pharmaceutical executives don’t like regulation by reflex.

FTFY.

Actually, it's far more complicated than that. Pharmaceutical companies actually like predictability. PhRMA, the lobbying arm or the pharmaceutical industry, isn't thrilled with right-to-try (hence its lack of endorsement) but doesn't want to piss off pols who who have reliably carried pharma's water for years (hence its lack of a clear statement of opposition). Right-to-try adds an element of unpredictability that drug companies actually do not like. Also, before, drug companies could point to the FDA as the reason why they wouldn't provide their experimental therapeutics to desperate patients. With right-to-try the onus falls totally on pharma, and when right-to-try requests are refused (for whatever reason) it's bad publicity for pharma, which is portrayed as driven only by profits and uncaring about patients.

Unfortunately, removing FDA protections will only aggravate this problem.

That's a feature, not a bug. The modus operandi of libertarian types, such as the Goldwater Institute, is to claim that government doesn't work, and they try to get people elected who will proceed to prove that claim. In this case, if the FDA can't protect patients from being harmed by unproven drugs, why should we have an FDA? Of course, they are setting up the false dichotomy of FDA-as-constrained-by-law vs. no FDA, rather than FDA-as-it-should-be vs. no FDA. Most of us would prefer FDA-as-it-should-be over no FDA. FDA-as-constrained-by-law is a much harder sell, especially when the laws prevent it from doing what it was intended to do.

It appears that this is a direct you shall do this law to an agency instead of the usual US Code (USC) that provides the framework for an agency to write regulations around the law. If FDA could write regulations, they could hamstring the law if they tried. Dorit could answer this better than I can.

Sorry, sadmar, I stand by what I said. Pharmaceutical execs might dislike certain regulations, but the Goldwater Institute dislikes ALL regulations of any kind. They live in a fantasy world of free market capitalism thinking that free markets will correct bad drugs because no one will buy from companies that make bad drugs, and companies will prevent bad things from happening to avoid bad publicity.

It's patently false, as the fungi contaminated steroid scandal clearly shows. As the sulfa and thalidomide scandals show. As the fraudsters like Stan Burzynski show.

Maybe they're well meaning. But trying to achieve their libertarian utopia will come with a high price tag in blood, and I will not let them off the hook by laying the blame solely on corporate executives.

trying to achieve their libertarian utopia will come with a high price tag in blood

Not only that, but they will never achieve their libertarian utopia, because like Karl Marx, they have completely unrealistic expectations of human behavior under the scenario they envision. The people who have power will do what it takes to tilt the system in their favor, and the people who advocate for libertarian causes seem not to realize that they won't necessarily be the people with power.

One of the primary purposes of government is to constrain the ability of powerful people to inflict arbitrary harm on the less powerful, in exchange for assurances that the less powerful will not gang up on the more powerful and overpower them with sheer numbers. This actually makes most people more free in that they don't have to worry about reprisals for real or imagined slights. Without a government to constrain people who would do egregious harm to others, you have a much higher likelihood of suffering egregious harm.

A similar bill was passed in the UK last year, dubbed the Saatchi Bill. More on that here: http://www.stopthesaatchibill.co.uk/not-this-day/

This makes me think of the Charlie Gard Case and also the Doctor in NOLA who is charging patients for HBOT but it appears is also "enrolling them in a study". He is treating patients with TBI most especially kids with anoxic and hypoxic injuries.

I was talking about this with my SO this morning and his comment was "well the FDA has a marketing problem because I've never heard of compassionate-use trials".
I didn't even know how to respond to that.

And to that tweet about "holding back innovation"? You don't innovate on people! You 'innovate' in the lab! You want more 'innovation'? Yeah, that's called research, and if you'd please fund the NIH then maybe you'd get your 'innovation'. Argh.

The FDA doesn't have a marketing problem. The last thing we want is for people to flood pharmaceutical companies demanding compassionate use, especially when the current rates usually don't get it anyway.

kidsnursern: the thing that make me absolutel apoplectic about Charlie Gard was that a**hat American neurologist Dr. Hirano, because he offered this "treatment" to those poor parents without examining Charlie first, without reviewing his medical records, and didn't disclose his financial interests.

It was the height of unethical behavior and he ought to be severely sanctioned by Columbia University Medical Center, the New York Medical Board, to include restrictions on how human subjects are recruited for clinical studies he is an investigator on (even if he is not the principal investigator).

I didn't mean to suggest there's no complexity. It's more complicated than any of our short comments could express. We all get sucked into the trope of 'Big Pharma', treating the pharmas as if they're some monolith, but they're not. First of all, the various firms all compete with one another. Business strategies and best interests differ. Second, each giant firm has many divisions, and between these divisions there are also different strategies and interests. Thus, different parts of a single firm may be on different sides of this or that issue simultaneously.

For a more nuanced discussion then, I'd note that while overall the pharmas fall on the anti- side of the regulation scale, that doesn't mean every executive in every division has the same reflex, or that different firms don't have different policy objectives or don't go about those they share in different ways.

I know some pharma execs "like predictability." I don't doubt RtT represent the problems Orac discusses, and that some influential voices within the pharmas have expressed concerns about the legislation. But other very influential forces within at least some of the pharmas want an easier path to get new high-profit meds to market, and want to ease regulation as a result. They're willing to suffer and problems from RtT as part of a process to soften up the FDA, and get more influence over the regulatory process.

I say these things because I've done a bit of 'follow the money'. enough to give me some good hypotheses. I started looking into where and how the pharmas spend on politics to confirm for myself that the anti-vax etc. accusations of Big Pharma shills protecting profits by covering-up vaccine conspiracies was a load of nonsense. And what I found did surprise me: there's a lot of pharma funding in conservative GOP anti-guvment politics, and plenty of it has gone to pols that act sympathetic to AVs. That's how little the pharmas care about their vaccine profits – they get in bed with AV fellow travelers as long as they're deregulators as well. But I have to say my sources I found weren't detailed enough to break down which of the pharmas are contributing what to groups like ALEC, or what strings each one may be pulling in return for their investments.

Now Orac knows the pharmas are better off with FDA regulation. I know it. Some people fairly high up in the pharmas know it. But there are definitely some people with a lot of juice in pharma-land who think their bottom line will grow the more 'freedom' they have. They have the hubris common among the powerful that you usually find behind libertarian ideologies. That is, they think they know their business best, and can regulate themselves, including generating their own predictability, and whatever level of responsibility and safety they think they require. They're wrong, but that's why it's called hubris.

So, I think whoever in the pharmas is backing RtT and other pieces of the de-regulatory agenda is aiming a gun at the corporate foot. I feel sorry for the more conscientious voices within the pharmas who support the FDA as is. I wish it were otherwise, but it's not.

If nothing else, we can verify that overall the pharmas are chill with RtT by what they haven't done, meaning they haven't put any serious resources into opposing it. Pharma bucks are important enough to anti-guvment groups like ALEC that if the pharmas actually made a stink the pols would cool their jets more than they do. The pharmas aren't worried about pissing-off the pols. They're too busy sticking their hands out toward the deep pockets.

PhRMA’s low-profile on right-to-try hurt detractors from the outset. The industry group never took a formal position on the state right-to-try laws or earlier federal proposals. But it consistently reiterated its concerns about any approach to experimental medicines that sought to bypass the FDA and the clinical trial process. Of the major drug makers, only Merck formally came out against the earlier Johnson bill. “It’s huge,” NYU’s Bateman-House said of PhRMA’s reluctance to take a stronger public stance. “When I speak with legislators, they say, ‘Well if it’s that bad, why isn’t pharma speaking against it?’”

So the lobbying arm takes the weakest possible corporate stance to mollify the conscientious elements in the firms, and the 'free-dumb' anti-regulation bean counters let it be with a wink, and slough off some more contributions that will wind up in the coffers of pols like Ron Johnson, if not the Goldwater Institute itself.

Panacea: I'm sorry if my use of a strike tag suggested I was dropping all the blame on pharma execs and giving the Goldwater gang a pass. I just want to make the point that. some powerful folks in the pharmas are complicit here. On the whole, we can easily say The Goldwater Institute or ALEC are much scummier than the pharmas. But these groups exist exactly as channels for the scummy anti-government activities of a variety of Big Money players. It just doesn't do to stop the inquiry at these policy tanks. The folks at Goldwater may be acting on sincerely held ideologies, but we wouldn't be hearing about any of it if there wasn't serious money behind it. merican politics, principle gets nowhere without principal.

In the vast majority of cases, the principal is backing the principle because it comes from sources who expects to make bank if the agenda advances. I'm not at all surprised Merck is the only pharma to come out against Johnson's bill. From what I've read, Merck's business model is based more in long-term stability, and less on big wins from new 'cutting edge' meds than their competitors, e.g. Pfizer, iirc.

I get that sbm advocates are keen to avoid feeding 'Big Pharma' conspiracy nonsense, and I'd guess the folks in the pharmas they know personally or work with are good people. As I said, I only looked into the real pharma shills because I suspected the CTs were bunk, and I wanted some verification from legitimate watchdogs of corporate shilling who would not cut the pharmas slack they didn't deserve. And all I found was that the pharmas are notorious for funding these right-wing political groups. And since the individual pols supported by these groups are generally pretty bad on science (yup, some of the AGW deniers and creationists are getting $$ originating in pharma land) the only explanation for that really is the desire for de-regulation and weakening the FDA...

There's something to be said for truth. I like being able to have cred in debunking those Big Pharma CTs by showing I'm hardly a fan, and I know some things about how they work and where their political influence money actually goes. "No, they don't do that. The dirt, such as it is, is over here on this whole other very different thing..."

...ALEC, for those who may be unfamiliar, is best known for pushing for, and actually drafting the language of, "stand your ground" legislation. So much for Big Pharma trying to profit by making people ill. If the firms supporting ALEC wanted to make more profits from more patients, they wouldn't bankroll the gang looking to make more corpses.

Sadmar: we can definitely agree that ALEX is scummier than Big Pharma.

Hey Panacea:

I'll go you one better. ALEC is scummier in every aspect than any of the pharmas at their worst. And that's saying a lot, and nothing for the pharmas to be proud of. Overall, while the pharmas have a somewhat higher than average scummy quotient for multinationals, and there's no excuse for some of the scummy things some of them have done, overall they're not all that bad or outrageously scummy. Pretty much any giant corporation is so large that there's some bad, some good, and a lot of in-between just by the law of averages for human failings. Apple's great in lots of ways, unless you work in one of the Asian factories where they make the i-stuff; Ford killed people with exploding Pintos, but has also put some great vehicles on the road, and so on.

None of which means we should give any corporation a pass for bad behavior. But it does mean that bad behavior by one firm in one endeavor doesn't necessarily characterize even that firm's nature as a whole, much less the whole of 'Big Pharma'.

(i happened to be an up close and personal witness to some outrageously scummy behavior by one of the big pharmas, but it had absolutely nothing to do with medical safety or anything like that. Basically a real estate and tax swindle that forced working-class people out of their homes, and left their already financially struggling municipality holding a big bag of debt.)

Sen. Ron Johnson threatens to obstruct passage of the bill funding the FDA if "right-to-try" language isn't added

oracknows — Mon, 17 Jul 2017 05:00:53 +0000

Sen. Ron Johnson threatens to obstruct passage of the bill funding the FDA if "right-to-try" language isn't added

Here we go again.

It's been a while since I've written about the cruel sham that is known as "right to try." Anyone who's been reading this blog a while (or even read the first sentence of this paragraph) knows that I'm not a fan of right-to-try laws. Basically such laws, which have sprung up like kudzu since the movement to pass them gained momentum three years ago, claim to allow terminally ill patients the “right to try” experimental therapeutics. Thus far, they have been sold to the public as giving terminally ill patients “one last shot” and touting how such laws could save some of their lives. As a result, as I’ve grimly quipped on multiple occasions, to politicians opposing right-to-try laws has become very much akin to opposing motherhood, apple pie, and the American flag. So most of them, even ones with misgivings, find that it's much easier to go along than to explain to the voters, the vast majority of whom do not understand the drug approval process and therefore do not understand why right-to-try laws are harmful to the very patients their proponents purport to be helping. So at the state level, right-to-try advocates have basically won. As of this writing, 37 states have passed such laws in a mere three years, and I wouldn’t be surprised if the remaining 13 states without a right-to-try law pass their own versions within the next year or two. I like to recount how when Governor Jerry Brown vetoed California’s first attempt at a right-to-try law, I was surprised that he had the guts to do it. Thus far, he’s the only governor to have vetoed a right=to-try bill, and even then the California legislature passed another one a year later that he signed. Basically, in any state where a right-to-try law is introduced, it passes.

Part of the reason why I like ot refer to right-to-try as "placebo legislation" is because states don't have the power to regulate drug approval; that is, unless a drug is entirely developed and marketed only within one state, which is basically never the case. The federal government does, and that process is controlled by the U.S. Food and Drug Administration. The libertarian "think tank" the Goldwater Institute, which developed the model legislation upon which virtually all state-level right-to-try laws are based, is quite blatant about understanding that, as a practical matter, state right-to-try laws do, in essence, nothing. Indeed, right-to-try laws, despite over three years on the books for the oldest ones, have thus far been a miserable failure in getting experimental drugs to patients, their claimed purpose, the claims of their proponents notwithstanding. Basically, no patient represented as having gotten drugs under right-to-try did not already have access to the FDA's expanded access program.

Of course, the purpose of state laws is not really to make it easier for experimental therapeutics to reach terminally ill patients. Even the Goldwater Institute knows that states alone can do very little to do that; the real purpose behind these laws is to build pressure on Congress to pass a federal law and, at the same time, to gut the regulatory power of the FDA. As a byproduct, because such laws allow very early stage experimental therapeutics to be "tried," such laws also have the potential to encourage quackery like Stanislaw Burzynski's antineoplastons.

Thus far, right-to-try advocates have tried twice that I know of to pass a federal right-to-try law, first in the form of the Compassionate Freedom of Choice Act in 2014 and then last year in the form of the Trickett Wendler Right to Try Act of 2016. Neither went anywhere. But, like naturopaths seeking state licensure, right-to-try advocates are as relentless as the Terminator. So it's not surprising that Senator Ron Johnson (R-WI), who introduced the last right-to-try bill, is at it again:

Sen. Ron Johnson is threatening to hold up a bill funding the Food and Drug Administration unless the House sends the Senate a version of the bill that expands terminally ill patients' access to experimental drugs.

Johnson, R-Wis., is hoping the House includes the so-called "right to try" language in a funding bill it will take up on Wednesday under a suspension of House rules. But if not, he said he expects to prevent quick passage of the bill in the Senate once the upper chamber receives it.

"If the House bill comes to the Senate without ‘right to try' language in it, I will have no choice but to object to any unanimous consent agreements related to it or any related bill unless right to try is added or the Senate is given an opportunity to vote on my right to try bill as an amendment," Johnson said in a statement obtained first by the Washington Examiner. "It is time to stand up for terminally ill patients who just want reclaim their freedom by having the right to try and save their own lives – who want the right to hope."

Sen. Johnson published a longer statement on his website.

The bill to which Sen. Johnson is recurring is the the Prescription Drug User Fee Act (PDUFA), which is is the law that allows the FDA to collect user fees from drug companies to fund the drug approval process. It turns out that the current legislative authority for the PDUFA expires at the end of September and needs to be renewed before then if the FDA is to continue to function. Right-to-try proponents thus see an opportunity to sneak a provision into the PDUFA renewal that would serve their ends as well as a federal right-to-try law—better, in fact, because getting a "right-to-try" provision into PDUFA would "bake" right-to-try into the FDA for at least the next seven years in its very funding. I first noted this effort three months ago.

Of course, Sen. Johnson isn't just limiting his efforts to PDUFA. He's resurrected his previous right-to-try bill, as well:

Johnson's efforts on advancing right-to-try stalled in the Senate last year, something he blamed at the time on then-Minority Leader Harry Reid. Johnson's 2017 version of the bill has 46 co-sponsors, including bipartisan support from Democratic Sens. Joe Donnelly and Joe Manchin of Indiana and West Virginia, respectively, and independent Sen. Angus King of Maine.

"I have spoken with House leadership and Chairman Walden over the last several weeks and encouraged them to support incorporating right-to-try legislation in the FDA reauthorization bill that is set to pass the House on Wednesday," Johnson said. "It is my hope that they will support the millions of Americans and their families suffering from terminal illnesses by including right to try language in this bill."

Notice how much Sen. Johnson oversells right-to-try in the form of his proposed amendment to PDUFA and, now, the S. 204, the Trickett Wendler Right to Try Act of 2017. He paints it as something that could potentially help millions of Americans suffering from terminal illnesses. Of course, the vast majority of Americans suffering from terminal illnesses suffer from diseases that derive from one thing: Old age. We're talking heart failure, stroke, cancer, and in the coming years, dementia, such as Alzheimer's disease. These are diseases for which granting access to experimental therapeutics before they're approved is incredibly unlikely to save lives and very unlikely even to prolong very many lives. No one doubts that the legislators sponsoring such legislation feel real compassion for terminally ill patients and want to help. It's just that they're going about it in the wrong way. To see why, let's step back and review the issues with state and federal right-to-try laws.

The basic premise behind right-to-try laws is that people are dying in droves because the FDA is too slow, bureaucratic, and hidebound to allow dying patients access to experimental drugs that are still undergoing clinical trials to be approved by the FDA. No, really, that’s the argument libertarians, at least, actually make, that the FDA is literally (yes, I mean literally—just ask Nick Gillespie and Ronald Bailey) “killing” people. Enter right-to-try, laws that purport to allow terminally ill patients (or, in some cases, patients with life-threatening but not necessarily terminal illnesses) to access experimental therapeutics in a desperate bid to save their lives.

It all sounds reasonable on the surface, right? What is very intentionally not emphasized are other aspects of these laws that are potentially profoundly harmful to patients. For instance, there is no mechanism in most right-to-try laws to help patients seeking to access experimental therapeutics financially. Indeed, as I've pointed out every time I've written about right-to-try, if you look at the language of the actual bills you'll see that they go of their way to emphasize that health insurance companies do not have to pay for right-to-try treatments. Indeed, the language is often such that the laws could easily be interpreted to absolve health insurance companies from paying for the treatment of complications arising from the use of right-to-try drugs or devices! Given that such bills also allow pharmaceutical companies to charge for experimental therapeutics and such expenses can be very high, this effectively means that only the rich or those skilled (or whose families are skilled) at using social media to raise a lot of money fast could potentially access right-to-try.

All such bills also explicitly eliminate or very much limit the right of patients to sue for malpractice and the power of state medical boards to go after the license of physicians who use right-to-try. If something goes wrong that's the physician's, not the drug's, fault, the patient using right-to-try basically has no recourse. Nor can drug manufacturers be sued; right-to-try gives them immunity. So, basically these laws tell terminally ill patients: Good luck. You’re on your own. Given that right-to-try laws also only require that experimental therapeutics have passed phase I trials and still be in clinical trials to be eligible, there’s a high probability of adverse events and harm. Indeed, I not uncommonly laugh derisively and contemptuously (and contemptuously and derisively) whenever I hear a Goldwater Institute flack claim with a straight face that right-to-try only allows drugs that have been shown to be safe to be used, because phase I trials generally only have a few dozen patients followed briefly. Let’s just put it this way: No one who knows what he’s talking about views drugs that have passed phase I trials as having been "shown to be safe." At best, such drugs have been shown not to be obviously dangerous.

Of course, as I've discussed at least twice, a federal right-to-try law would be so much worse than state right-to-try laws because it would actually do something. It would not be placebo legislation; it would be harmful. Basically, it would federalize right-to-try, but that's not all it would do. Let's review the 2017 version, which is virtually identical to the 2016 version. As all previous versions have done, the 2017 version would make it impossible to sue any "producer, manufacturer, distributor, prescriber, dispenser, possessor, or user of an experimental drug, biological product, or device for the production, manufacture, distribution, prescribing, dispensing, possession, or use of an experimental drug, biological product, or device that is in compliance" with this law. This clause basically removes federal liability from physicians and drug companies that offer a drug under right-to-try. If a patient suffers because of the inappropriate use of such a drug, the patient (or, given that the patients under this bill have terminal illnesses, the family) has no recourse to sue the manufacturer under federal law, in addition to having no recourse under state law. That's bad enough. Even worse is that the use of experimental drugs under right-to-try, unlike the use of experimental drugs under "compassionate use" or early access programs, is not overseen by an Institutional Review Board (IRB), the committee at each institution doing human subjects research whose function is to protect patient interests. If anything, the federal version even more anti-patient than state right-to-try laws.

Then there's this:

(2)No use of outcomes
Notwithstanding any other provision of law, the outcome of any production, manufacture, distribution, prescribing, dispensing, possession, or use of an experimental drug, biological product, or device that was done in compliance with subsection (a) shall not be used by a Federal agency reviewing the experimental drug, biological product, or device to delay or otherwise adversely impact review or approval of such experimental drug, biological product, or device.

Obviously, this clause is intended to reassure drug and device manufacturers, whose main concern is that if a patient suffers a complication from an experimental medication or device approval of that drug or device could be in jeopardy. So what does Sen. Johnson do? He adds instructions in his bill to the FDA not to use outcomes data from patients using right-to-try drugs in its deliberations on approving drugs. Even if a patient death—heck, make it dozens or even hundreds of patient deaths—can be clearly attributed to the use of an experimental drug, if that drug was used under right-to-try in all the cases this law would tell the FDA that it has to turn a blind eye to all the carnage in considering whether the drug can be approved. I kid you not. Think I'm exaggerating? Look at the language of the bill!

Horrifyingly, given the change in administrations, this bill very well might pass.

Basically, right-to-try is based on two myths, as Alison Bateman-House, Kelly McBride Folkers, and Arthur Caplan describe:

Although promoted in many cases by individuals with benevolent intentions, the right-to-try approach is based on two myths. The first is that the FDA’s expanded access program, which allows patients to use an experimental drug outside of a clinical trial if the drug’s manufacturer agrees to provide it, is slow and ineffective. In fact, it is hard to envision how the agency could provide a faster turn-around time on expanded access requests while still conducting a thorough review of a patient’s medical history and proposed treatment plan. The form that physicians must submit to the FDA for review after a company agrees to supply a patient with an experimental drug requires less than one hour to complete. The FDA approves more than 99 percent of these requests, and it does so, on average, within four days. For emergency requests, the agency responds in one day or less. And this is no “rubber stamp” review: A recent study found that FDA reviewers weighed in with valuable suggestions about how to improve the proposal, making it more likely to help than hurt the patient.

The second myth—one that is especially pernicious—is that right-to-try legislation will allow patients faster and more guaranteed access to experimental drugs by cutting out the bureaucratic “middleman” (the FDA). Indeed, the central objective of right-to-try legislation is to end FDA oversight over the use of experimental drugs. For terminally ill patients, ending FDA oversight over experimental drugs would expose the patients to exploitation without guaranteeing access to the drugs they seek. And weakening the FDA puts everyone else who takes drugs or uses medical devices or vaccines at grave risk.

Exactly. Right-to-try is a Trojan horse designed to gut the FDA's authority to regulate and approve experimental therapeutics. It's also the "foot in the door" for more deregulation. Imnagine, for instance, that right-to-try is approved. You can bet that in a couple of years (or even sooner) the Goldwater Institute will start asking why right-to-try is restricted only to "terminally ill" patients. Why, it will ask, shouldn't patients with serious medical conditions that are not immediately life-threatening "reap the benefits" of right-to-try?

The NYU School of Medicine Working Group on Compassionate Use and Pre-Approval Access has published a three-page fact sheet about right-to-try. Most important is to strengthen and streamline the FDA's Expanded Access Program while at the same time making it appealing to drug companies to participate. Right-to-try might fails on all these counts. It is the very epitome of H.L. Mencken's maxim, "For every complex problem there is an answer that is clear, simple, and wrong." In the case of right-to-try, unfortunately, this answer is not only clear, simple, and wrong, but it's incredibly appealing because is uses the compassion we all feel for the terminally ill to short circuit our critical thinking abilities for a purpose (gutting the FDA) that most of the bill's sponsors and supporters don't understand but that the Goldwater Institute does.

oracknows Mon, 07/17/2017 - 01:00

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Prescription Drug User Fee Act

right to try

Ron Johnson

Trickett Wendler Right to Try Act of 2017

http://www.nytimes.com/2011/01/28/opinion/28fri3.html

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The FDA manages to adhere to the concept of do-no-harm under the most difficult circumstances (e.g., lethal injections).

The right-to-try concept must have checks and balances, thereafter, making the FDA indispensable.

I appreciate this and join you in opposing "right to try" as extremely patient-hostile legislation that will not let patients gain access to investigational products.

Just wanted to point out that Hawaii also vetoed a right to try bill, SB 2181, in April 2016:
http://www.capitol.hawaii.gov/Archives/measure_indiv_Archives.aspx?bill…

A new bill, SB 1110, was introduced in Jan 2017 but hasn't moved, and the session is in recess till Jan 2018.

Regards,
Lisa Kearns

Lisa Kearns, MS, MA
Senior Research Associate
Member: Working Group on Compassionate Use and Pre-Approval Access
Division of Medical Ethics
NYU School of Medicine

OT: Over the day I got error messages along the line "too many requests" when I tried to open a post. Was there an attempted DoS attack today, did the Slashdot effect hit or was the problem likely on my side?

@ aairfccha
I got exactly the same messages for a large part of the weekend and today, so I suppose the problem wasn't on your side.

And the problem still hasn't disapeared.

@MJD: As the bill is written, the FDA would have no say whatsoever in right-to-try cases. And the patient explicitly has no recourse should anything go wrong. The only people who could prevent a drug being used in a right-to-try case are the manufacturers, who could choose not to make it available (as it is, they typically make enough for the current trial phase, with some allowance for spoilage, but not more). And then to tell the FDA that they cannot consider outcomes of right-to-try cases is a mockery of evidence-based judgment: they are being explicitly ordered to ignore evidence.

@aairfccha: You are not alone; I have been getting that same error message since Saturday at home, and today here at work. This post is the first SB content I have seen since Friday afternoon. Orac, you may want to have the corporate (non-pharma) overlords at SB look into this, if they aren't already. Another possibility is that there is malicious code in one of the ads being served, because I shouldn't be getting such a result by simply surfing over to this site, and I have.

This will be a second attempt at posting this comment, because I got that error message again on the first attempt.

This will be a secondthird attempt at posting this comment, because I got that error message again on the first two attempts.

Sorry for the duplicate posts. As I said, I continued to get the error message on my first two attempts, so I had no way of knowing that those attempts had posted.

Another possibility is that there is malicious code in one of the ads being served.

Naa, the problem is with one superflous module of the security software Wordfence. So, I'll post the solution again:

We have since back in December seen some issues on Bluehost because they install something called Endurance cache and some version of this cache is too aggressive and will actually cache the Wordfence blocked page and then serve it to every visitor to the site. This is why it doesn’t change when you deactivate Wordfence. It’s not actually Wordfence that is serving the page, it’s the cache. We believe that it is one of the early versions of Endurance cache that is faulty, but it seems like on many sites it has not been upgraded to newer versions.

The easiest way to solve this may be to contact Bluehost and ask them to remove the faulting Endurance Cache from your website. If you want to try disabling it yourself you can:

1. Look in wp-content/mu-plugins and delete the endurance cache plugins from there
2. Check your .htaccess and manually remove any trace of the Endurance cache…

“Just ran into this issue with a client using Bluehost and just wanted to add that deleting/renaming the endurance-page-cache folder did nothing for me. It just regenerated. The only way to disable was to go to Plugins > Must Use and disable there.

https://wordpress.org/support/topic/your-access-to-this-site-has-been-l…

I seem to have access to RI again, but what I did earlier today was to use my TOR browser, and reset my circuit for the site when I got the error message (happened a few times even with TOR). Clunky but it worked well enough.

An issue with right to try that bothers me greatly is the reliance of libertarian and tea party types to think that free markets are the solution to everything. "If only" we'd let the free markets "work their magic" we'd have miracle cures for everyone.

And a line of bodies miles long.

People seem to confuse a chance with any chance, not realizing the latter is so unlikely as to come to fruition, but it makes for an emotional argument under the umbrella of American determination and fighting spirit. "If you had any chance, wouldn't you take it?"

And the answer to that question, in many instances, should be "No, no I wouldn't, not if I could live longer, in less pain and more dignity by taking hospice services."

What Senator Johnson knows about modern medicine, clinical trials, ethics or biology would not fill a teacup. Out of a dollhouse.

"Passed Phase I" does not mean "safe". It means something closer to "doesn't obviously kill patients super fast".
At least one Phase II immunotherapy trial had to be halted recently because patients were dying. How on earth is dead now better than dead in 3 months?

Or what about Novartis' new immunotherapy? That treatment requires a huge amount of supportive care so the patient doesn't die of the treatment. Under "right to try" if the prescribing physician didn't arrange that care and the patient died for lack of it, the family would be SOL, even though it was clear malpractice.

Startup pharma doesn't want this; they don't have the material to spare. Ethical pharma doesn't want this, it's nuts. I'm not even sure amoral pharma would want this; there's too much risk to reputation.
And evil pharma seems to do just fine themselves.

This serves nothing but ideology. And I , for one, have no truck with that.

Sen. Johnson has been rather persistent with this issue. One wonders who is pushing this. Where is the funding? The fact that it has been introduced via many states over a short period of time implies a centralized well financed effort. Someone with big money to be made I'd wager.

Well, these laws are a product of the Goldwater Institute, which has been the single biggest promoter of right-to-try laws. Every state RTT law is based on a legislative template written by the Goldwater Institute three or four years ago. A couple of years ago when the Michigan legislature was considering RTT, the Goldwater Institute flew in its flacks and a bunch of patients with terminal illnesses and family members. Those standing up for science were hopelessly outgunned.

Unfortunately, right-to-try sounds so good; how could anyone object to giving patients more rights? For people thinking with their gut and not with their head, the answer is obvious. Since anti-intellectualism is rampant in our society right now, we run the risk of many laws being passed which don't work out very well because they try to mold reality to our beliefs.

I was having trouble connecting to Respectful Insolence via iPad. Clearing browsing history allowed access again.

Regarding funding: Jan Mayer's book, "Dark Money" details how wealthy people set up non-profit foundations so they can fund right-wing think-tanks with tax-free dollars. Some of that money can also be routed to political causes as long as it isn't their primary purpose. It's all a part of distorting our political landscape courtesy of all three branches of government.

As a widow of someone who died from Stage 4 lung cancer, I have a different perspective. I was heartbroken when my husband was diagnosed. We both understood that a Stage IV diagnosis would mean that he would be given palliative instead of curative treatment. At that time, Nivolumab was showing incredible results in phase 3 clinical trials. During his illness, the drug was approved for squamous cell NSCLC but not adeno (he had adeno). We tried several times to get into trials but there were problems (distance, PDL-1 levels, drew the taxotere straw, etc..) Because he was treated at Kaiser, he couldn't get it approved off-label even after Opdivo was approved for squamous.
We switched insurance and discovered he had brain mets. He did wbr and gk for the brain mets and then his new dr. approved Opdivo off-label. His first scan showed improvement in his lung and liver tumours, but unfortunately, the cancer had settled in his meninges. He died 15 days later.
I can never know, but I always wonder if successful, systemic treatment of his primary tumor in the beginning could have prevented his cancer from spreading to his brain. I will never know. But I do know that the current system of clinical trials and off-label use is advantageous for the wealthy who can afford better insurance and travel. (of course wealth is an advantage in everything).
I don't think 'right to try' is the answer, but damn it, can't we figure something out for incredibly promising phase 3 drugs?

Polly,

I'm so sorry for your loss.

The short answer to your question is no. Otherwise there would be no point in holding a phase 3 clinical trial. Sometimes a drug does so well, they end the trial early but that's not the norm. Opdivo was not one of those drugs.

I'm not sure what "figuring out something for incredibly promising" really even means. The problem would be, everyone would clamor for the drug and say, "why not me?" That muddles the data and maybe we end up allowing people access to a drug that isn't all that hot after all.

That happens a lot with drugs. At first it sounds great, but as more data comes in we find either the drug doesn't work well enough to justify its high costs, or the side effects aren't worth the benefits.

I'm sure there are things we can do to improve the system but the bottom line is there will always be someone who will want access to a drug undergoing clinical trials and can't have it for whatever reason. This is one of those greater good issues, which isn't easy to hear when your loved one is the one being told no for the greater good.

Thanks for your kind response. Intellectually, I understand that allowing anyone and everyone to take a medication would muddle the data. But I can't tell you how sad/frustrating/heartbreaking it is to know there's something out there working and not being able to do anything to access it. Within a few months of diagnosis, I had heard about Nivolumab. The data coming out wasn't miraculous but it was much better than chemo and with much less severe side-effects. I wish my husband could have gotten his shot at taking Nivolumab sooner. Nothing anyone's ever going to say is going to talk me out of that position.
I am so grateful for the treatment my husband did receive.His doctors, nurses, technicians, etc.., all had so much compassion and did the best they could for him. He had 20 months of high quality life after his diagnosis. He didn't spend one night in the hospital (almost unheard of for lc), and he died peacefully at home in his own bed.
I am a solid proponent of science and so was he but ...I will leave it at that.

Polly, I would never disrespect you by saying you shouldn't feel what you feel.

I'm glad he was able to pass at home. That is a dignity that was denied my father because I couldn't get the logistics to work in time :(

I’m glad he was able to pass at home.

Same here, but for my mom (Herceptin worked well for a good four years, but the final evasion was to the lungs).

Congress is back in session, and sneaking the cruel sham that is right-to-try in a must-pass bill Is on the agenda

oracknows — Mon, 24 Apr 2017 01:15:05 +0000

Congress is back in session, and sneaking the cruel sham that is right-to-try in a must-pass bill Is on the agenda

Anyone who has been reading this blog for the last three years or so knows that I'm not a fan of "right-to-try" laws. Basically such laws, which have sprung up like kudzu since 2014 and now exist in 33 states, purport to allow terminally ill patients the "right to try" experimental therapeutics. Thus far, they have been sold to the public as giving terminally ill patients "one last shot" and touting how such laws could save lives. As a result, as I've grimly quipped on multiple occasions, to politicians opposing right-to-try laws is akin to opposing motherhood, apple pie, and the American flag; you just don't do it and expect to be re-elected. It's much easier to go along than to explain to the voters, the vast majority of whom do not understand the drug approval process and therefore do not understand why right-to-try laws are harmful to the very patients their proponents purport to be helping, why they're such an astonishingly bad idea as currently formulated. That would require going into the details (which I will do shortly). So at the state level, right-to-try advocates have basically won. Just shy of 2/3 of the states have passed such laws in a mere three years, and I wouldn't be surprised if the remaining 17 states without a right-to-try law pass their own versions within the next year or two. Indeed, when Governor Jerry Brown vetoed California's first attempt at a right-to-try law, I was surprised that he had the guts to do it. Thus far, he's the only governor to have vetoed a right=to-try bill, and even then the legislature passed another one a year later that he signed. Basically, in any state where a right-to-try law is introduced, it passes.

All right-to-try laws thus far hew very closely to model legislation written and promoted by a libertarian think tank, the Goldwater Institute, with a few state-specific differences here and there, and share several key features. They also share one key shortcoming, and that's federal law. States do not regulate drug approval in the U.S.; the federal government does, through the Food and Drug Administration (FDA). In general, the FDA has not supported right-to-try laws, but has liberalized expanded access programs (also sometimes called compassionate use) to make it easier for terminally ill patients to access experimental therapeutics outside of FDA-sanctioned clinical trials. Not surprisingly, I've as yet been unable to find a single compelling example of a patient who has been helped by access to an experimental therapeutic through a state right-to-try law. I did, however, find that cancer quack Stanislaw Burzynski has taken advantage of Texas' right-to-try law to ply his quackery, just as I warned that he would three years ago. Basically, right-to-try laws are a solution looking for a problem or, as I like to call them, placebo legislation, and have been a miserable failure thus far. They make lawmakers feel good, but they do nothing concrete to help actual patients. It's also important to remember that the real purpose of right-to-try laws is not to help patients, but to neuter the FDA's ability to regulate certain drugs, consistent with the source of this legislation. Passing state right-to-try laws is part of a strategy to build pressure to pass a federal right-to-try law and thus weaken the FDA:

@gorskon Yes but I'm afraid much more support now. Goldwater's playbook was get laws in at least 25 states & then claim mandate for fed law

— Alison Bateman-House (@ABatemanHouse) August 24, 2016

Thus far, proponents have failed not once, but twice, to pass a federal right-to-try law, once in the form of The Compassionate Freedom of Choice Act of 2014 and then again last year in the form of the The Trickett Wendler Right to Try Act of 2016, which fortunately failed to pass. Now they're at it again.

If you can't pass a right-to-try law, bury it in an omnibus bill

Congress is back in session today, after a two week Easter break; thus the potential for mischief is great. With the election of Donald Trump and both houses of Congress under the control of Republicans, a decidedly deregulatory mood has overtaken the government. Moreover, Vice President Mike Pence supports right-to-try laws, having signed one into law when he was Governor of Indiana. So you'd think that right-to-try would just pass, and then President Trump would sign it. Yes, The Trickett Wendler Right to Try Act has been reintroduced this session, but proponents apparently don't want to wait that long. The Prescription Drug User Fee Act (PDUFA) is the law that allows the FDA to collect user fees from drug companies to fund the drug approval process. The current legislative authority for the PDUFA expires at the end of September and needs to be renewed before then. Right-to-try proponents thus see an opportunity to sneak a provision into the PDUFA renewal that would serve their ends as well as a federal right-to-try law:

And now, for the first time, federal legislation is gaining traction.

Congressional supporters may try to attach a measure — drafted with a unique and highly controversial restriction on the FDA — to the agency’s must-pass funding bill this year. The anti-regulatory mood dominating Washington is boosting these efforts.

More detail can be found in this account (behind a paywall, so I'll quote a bit more liberally than usual):

The 'Right to Try' movement is gaining momentum at the federal level with support from both the Trump Administration and Republicans in Congress to enact legislation that would direct FDA not to interfere with existing state laws and allow terminally ill patients to access unapproved treatments.

The “Right to Try” movement now has the explicit backing of the White House and enactment of legislation to prevent FDA from interfering with state laws in that area may now be inevitable. Vice President Mike Pence met with right-to-try advocates Feb. 7. Pence is a backer of opening up broader access for compassionate use; as governor of Indiana, he signed state “Right to Try” legislation in law in 2015 and made statements during the Presidential campaign in support of such efforts. (Indiana is one of 33 states to enact legislation.) The official “readout” of Pence’s meeting makes clear that his support for the effort is now Administration policy.

Pence’s meeting builds on statements made by President Trump before a Jan. 31 meeting with pharmaceutical CEOs, where he talked about the need to “change a lot of rules” in drug regulation. (Also see "Trump Promises Changes To 'A Lot Of Rules' At US FDA" - Pink Sheet, 31 Jan, 2017.) “One thing that’s always disturbed me is we come up with a new drug for a patient who is terminal, and the FDA says we can’t have this drug used on the patient. But the patient within four weeks will be dead,” President Trump said. “They say ‘well we still can’t approve the drug and we don’t know if the drug works or if it doesn’t work but we can’t approve the drug because we don’t want to hurt the patient.’ But the patient is not going to live more than four weeks.”

This is a fallacious argument frequently used by right-to-try advocates. Basically patients with only four weeks to live are highly unlikely to be helped by pretty much anything, experimental or otherwise. However, they can be harmed. Right-to-try proponents often ask, "What's the harm?" or "How can it get worse?" It can. A terminally ill patient could lose those four weeks with his family or could suffer far more than he would have otherwise with palliative care. Be that as it may, it's clear that right-to-try backers, having thus far been unable to use state right-to-try statutes to force the FDA to grant access to experimental therapeutics and failed to pass a federal law, are going to try to sneak a right-to-try provision into the bill that will fund much of the FDA's operations for the next four years.

To understand why this move is such a threat to patients, let's briefly review what state right-to-try laws claim to do (which is a lot) and actually do (almost nothing) and then review the federal right-to-try bill that's been re-introduced.

State right-to-try laws: Harmful placebo legislation addressing a nonexistent problem

I mentioned before that all the state right-to-try laws hew pretty tightly to an approved model legislation template originally published by the Goldwater Institute. Such legislation includes several major shared features. First is the requirement that the disease the patient has be terminal, usually defined as having a life expectancy of less than six months, although the model legislation is more vague, requiring an "advanced disease," defined as "progressive disease or medical or surgical condition that entails significant functional impairment, that is not considered by a treating physician to be reversible even with administration of current federal drug administration approved and available treatments, and that, without life-sustaining procedures, will soon result in death." Various states define this condition in somewhat different ways, but you get the idea.

One of the most problematic passages, if not the most problematic passage, is the one where the term "investigational drug, biologic product, or device" is defined:

"Investigational drug, biological product, or device" means a drug, biological product, or device that has successfully completed phase 1 of a clinical trial but has not yet been approved for general use by the United States food and drug administration and remains under investigation in a United States food and drug administration-approved clinical trial.

Every right-to-try bill or law I've read uses minor variations of the above definition. Anyone who knows anything about drug development knows that having completed a phase 1 trial is a dangerously low bar to clear to allow more widespread use of a drug. Basically phase 1 trials are small trials, usually consisting of less than 30 subjects, that look for major toxicities and adverse events. That is not enough to determine safety, nor is it intended to. Phase I trials are designed primarily to identify major side effects and to use a process known as dose escalation to determine what is commonly referred to as the “maximum tolerated dose.” It is utterly impossible for such a small clinical trial to determine the safety of a drug. Phase II and Phase III trials are needed to confirm safety. Think of phase I trials as a screening test looking for the most obvious toxicities, with phase II and III studies confirming them. Indeed, even phase III trials can’t always adequately demonstrate that a drug is safe; it’s not uncommon for less common adverse effects not to show up until post-marketing surveillance, when much larger numbers of patients receive the drug. Moreover, only 5% of all cancer drugs that enter clinical testing are ultimately approved for patient use. Among drugs tested in phase II trials, only 30% go on to phase 3. I like to point to the cautionary example of amonifide for treating breast cancer. The drug made it through phase I trials, but serious life-threatening hematologic toxicity emerged during phase II trials.

Right-to-try laws limit who can access them by wealth. The reason is that all of them have a provision that says that health insurance companies do not have to pay for such treatment. They can pay if they so desire, but what's the likelihood of an insurance company paying for an experimental treatment? However, nearly all right-to-try laws also say that the company providing the experimental therapeutic under right-to-try can charge the patient for it. (One notable exception, as I learned a year ago, is Texas, where the right-to-try law bars charging the patient.) A terminally ill patient could easily go bankrupt before he died paying for drugs accessed through right-to-try laws, and many couldn't access experimental therapeutics through such laws in any event because they simply don't have the money or the fundraising wherewithal to do so.

In Michigan, the requirement is particularly suspect in that it requires “written informed consent” for using the experimental drug that attests that the “patient understands that he or she is liable for all expenses consequent to the use of the investigational drug, biological product, or device and that this liability extends to the patient’s estate, unless a contract between the patient and the manufacturer of the drug, biological product, or device states otherwise.” This puts the patient on the hook for any expenses or debt that he incurs using experimental treatments, but also seems custom-made for drug companies, to make sure that they get their money for experimental therapies administered under “right-to-try,” no matter what. Basically, they can go after a deceased patient’s estate, something that will frequently be necessary because patients eligible for “right-to-try” by definition have a terminal illness, and the vast majority of even the most promising drugs will, at the very best, prolong their life, not save it. It goes beyond that, though. If a patient uses a right-to-try drug and suffers complications, these laws basically state that the insurance company doesn't have to pay for care resulting from that complication, and all such laws state that patients undergoing right-to-try therapies lose their coverage for hospice.

As you can see, these state laws are potentially very harmful, but they're easy to demagogue. Anyone supporting them can easily paint himself as the champion of terminally ill patients with no hope left, while those of us who oppose such laws have the difficult task of explaining clinical trials and how these laws harm patients. Indeed, when right-to-try came to Michigan, I was endlessly frustrated by how pretty much none of our major medical schools or cancer centers would speak out. Flacks from the Goldwater Institute, complete with patients with compelling stories, were there in abundance, though.

I called state right-to-try placebo legislation because it basically does nothing while making everyone feel better. That's why federal legislation is in the works.

Federal right-to-try

Two of the biggest hurdles to actually utilizing state right-to-try laws include the authority of the FDA, which preempts state laws, and the fact that the FDA has thus far taken a dim view of companies using experimental therapeutics outside the auspices of an FDA-sanctioned clinical trial or under its expanded access program. Enter federal right-to-try bills. The most recent ones are S. 204: Trickett Wendler Right to Try Act of 2017, introduced into the Senate by Ron Johnson (R-WI) and H.R. 878: Right to Try Act of 2017, introduced by Rep. Andy Biggs (R-AZ). Both are basically the same as the bill introduced last year. They both have two main provisions:

(1)No liability
Notwithstanding any other provision of law, no liability shall lie against a producer, manufacturer, distributor, prescriber, dispenser, possessor, or user of an experimental drug, biological product, or device for the production, manufacture, distribution, prescribing, dispensing, possession, or use of an experimental drug, biological product, or device that is in compliance with subsection (a).

(2)No use of outcomes
Notwithstanding any other provision of law, the outcome of any production, manufacture, distribution, prescribing, dispensing, possession, or use of an experimental drug, biological product, or device that was done in compliance with subsection (a) shall not be used by a Federal agency reviewing the experimental drug, biological product, or device to delay or otherwise adversely impact review or approval of such experimental drug, biological product, or device.

These provisions are pretty self-explanatory. These bills would prevent federal lawsuits against drug or device manufacturers, dispensers, users, or physicians prescribing or administering right-to-try. The more pernicious part of the bill is the second provision, which would explicitly bar the FDA from considering any adverse events that occur in patients using right-to-try laws in its decision whether to approve or reject an application for approval to market. This clause is clearly intended to address the concern of drug and device manufacturers that if they provide an experimental therapeutic to a patient under right-to-try and the patient suffers complications due to the treatment, the approval of its product might well be jeopardized. This, of course, is not an unreasonable concern on the part of manufacturers, given that it can easily cost $1 billion to bring a drug or device to market, and by the time the product has passed phase I clinical trials a great deal of that cost has already been invested in development. However, this clause goes way too far. Basically, it says that even if a patient death is clearly due to use of an experimental drug under right-to-try, that death should not be considered by the FDA in deciding whether to approve the drug. Think of it this way. Let’s say dozens of patients die from using an experimental drug under right-to-try. This bill, if passed, would bar the FDA from even considering those deaths during its deliberations regarding whether to approve the drug for marketing or not. This is not a good thing for patients.

Basically, the Trickett Wendler Right to Try Act of 2017 would not help terminally patients. It would endanger them. Proponents often ask, “What does a terminally ill patient have to lose?” The answers are simple. They can lose money, perhaps their life savings, given that accessing right-to-try could easily cost tens or hundreds of thousands of dollars. That’s because, when you come right down to it, “right to try” is a misnomer. It’s really “right to buy.” If you’re terminally ill and don’t have the money or the means to raise it, right-to-try will not help you. Worse, thanks to right-to-try, terminally ill patients can lose some of their precious quality time remaining with their loved ones if they suffer complications that place them in a hospital or prematurely kill them.

The New York University School of Medicine Working Group on Compassionate Use and Pre-Approval Process has published an excellent bullet-point summary of the problems with right-to-try, as well as policy suggestions going forward.

Right-to-try against patients

As I wrote this, I contemplated a simple question: Which federal action is worse? Would passing the Trickett Wendler Right To Try Act of 2017 be worse, or would sneaking a right-to-try provision into the must-pass PDUFA be worse? The answer is not obvious. Trickett Wendler would prevent the FDA from considering outcomes in patients undergoing right-to-try treatments in its approval deliberations, which would have the potential to be disastrous, particularly if right-to-try usage of experimental therapeutics becomes more widespread. Meanwhile adding right-to-try to the bill that funds the FDA, in essence baking-in a ban on interfering with patients seeking experimental therapeutics under state right-to-try has the potential to cause a lot of harm, because state right-to-try bills do not prevent the FDA from considering outcomes of patients accessing experimental therapeutics. At least, I don't think it does but can't be sure. The specific language of the right-to-try provision of PDUFA hasn't been revealed yet. If that language contains a Trickett Wendler-like ban on the FDA using outcomes from right-to-try patients in its considerations of drug approval, then the PDUFA approach will be equally, if not more, harmful. Basically, both the PDUFA and Trickett Wendler bills are plenty bad.

As has been the case since 2014, I remain frustrated by the relative lack of pushback by the medical community against such ill-advised right-to-try bills and efforts. I'm not the only one. Beth E. Roxland, senior adviser on law, ethics, and policy at NYU Langone Medical School agrees:

Roxland, the NYU ethicist, is watching, dismayed, as the right-to-try bills sweep the country.

“What I see is, unfortunately, very little pushback in terms of what the downsides could be,” she said. “If anything, it’s just picking up steam.”

Roxland said she has spoken to medical industry leaders and policymakers who support the rights of patients to seek potentially lifesaving treatments, but who feel the right-to-try laws, as written, will ultimately harm patients. She said these leaders are frequently reluctant to to [sic] express nuanced objections in the face of more emotionally charged arguments. “It’s hard to argue against when it’s framed as the terminally ill having the right to save their lives,” she said. “How do you argue against that?”

This could be one reason why the FDA and major trade groups, including the American Medical Association and the Pharmaceutical Research and Manufacturers of America, have taken no public stance on the legislation.

Roxland's experience mirrors my own. Everyone in academia or pharma with whom I've ever discussed right-to-try thinks these laws are a horrible idea that will harm patients, but no one wants to be the one to speak out, for the reasons listed by Roxland above or, as I put it, because they don't want to be perceived as yanking a dying patient's last hope away. Of course, that's not what we're doing, but that's what right-to-try advocates have successfully portrayed us as doing.

For instance, it wasn't until earlier this month that the largest oncology professional society, the American Society of Clinical Oncology (ASCO) finally—finally!—came out forcefully against right-to-try. In a statement, ASCO noted:

As the leading medical society for physicians involved in cancer treatment and research, the American Society of Clinical Oncology (ASCO) supports access to investigational drugs outside of clinical trials when there are adequate patient protections in place. However, ASCO is concerned that existing and proposed RTT laws do not adequately protect patients, do little to facilitate patient access to such therapies, and potentially interfere with recent reforms that are already streamlining patients’ access to investigational agents.

Comparing the existing system for expanded access to right-to-try laws, ASCO finds many problems:

ASCO is concerned that most RTT laws, while well intentioned, are not an effective mechanism for improving access to investigational drugs for terminally ill patients and may cause unintended harms, for the following reasons:

Right-to-try laws do not include an enforcement mechanism to provide access, since they do not require or compel drug manufacturers to provide investigational products. As such, these laws do not remove a frequent barrier to access.

These laws place no legal obligations on insurers to pay for the routine care costs associated with delivery of treatment – unlike coverage requirements that do exist for patients who participate in clinical trials. As a result, RTT laws establish no new rights or protections for patients.

Independent review of the potential safety and efficacy of investigational drugs is important for patient safety. Under the expanded access program, the FDA conducts a prompt review of the available data and makes an independent assessment on behalf of the patient. Such review is bypassed in RTT laws.

And:

Moreover, these laws as currently envisioned and enacted will interfere with already- streamlined and effective protocols, potentially putting patients at high risk for unclear benefit. Specifically, these measures will:

Jeopardize insurance coverage for the cost of patient care associated with the use of investigational drugs, particularly in the case of complications caused by these drugs;

Circumvent the government’s responsibility to monitor and protect the safety of patients seeking access to investigational products; and

Fail to provide adequate transparency, in part due to a lack of reporting requirements, on how patients respond to investigational drugs under a right-to-try scenario.

In addition to their lack of patient protections, RTT laws do not mitigate the delays that can occur during the expanded access application process. For example, regardless of whether under RTT or the FDA process, applicants must determine a sponsor’s willingness to provide the investigational drug. Providers and patients consistently report difficulty locating information about drug manufacturer contacts for such requests, significant delays in response and even denial of the request altogether.

Sound familiar? This is exactly what I've been saying for three years now, along with every other opponent of right-to-try who actually spoke up. ASCO goes on to describe strategies by which expanded access programs can be strengthened and patients provided more access to experimental therapeutics, complete with current protections. Unfortunately, ASCO is a day late and a dollar short. Actually, it's three years late. The time for oncology professional associations to speak up was in 2014, as the first right-to-try bills were wending their ways through state legislatures, not now. Then, ASCO might have influenced the debate in a positive way. Now, it's almost certainly too late.

All along, too few people have been willing to point out that right-to-try is not about helping patients. Consider the source of right-to-try, after all. Rather, it's about this:

But the increased momentum is raising alarms, with opponents saying that such laws largely offer false hope. That’s because many drug companies are reluctant to provide medications outside of clinical trials — and why critics insist that the FDA is not the problem. In 2016, they note, the agency revamped its “expanded access” program to speed unapproved drugs to patients who have no alternatives and can’t get into clinical trials. The FDA approves almost all such requests, the data shows.

“A lot of this is smoke and mirrors for some other agenda,” said Andrew McFadyen, executive director of the Toronto-based Isaac Foundation, which assists U.S. and Canadian patients seeking access to medications. “A weaker FDA is what they are after.”

Exactly. Kudos to Mr. McFadyen for stating the obvious. Right-to-try is a strategy by libertarians to neuter the FDA, as could be seen rather plainly during the Ebola scare, when libertarians openly argued that the FDA was "killing patients" and that right-to-try was the answer.

I've pointed out before how the entire justification for “right to try” laws rests on a misperception that there are “miracle drugs” out there that we will have to wait years for because the FDA is too slow to approve them. Not only is this a myth (the FDA is actually pretty fast at approving new drug applications compared to, for example, its European counterpart), but if there really were such a “miracle drug” that was amazingly effective compared to anything we have now, a large randomized phase III trial would not be necessary to detect its efficacy. Indeed, its efficacy could show up in even a small phase I trial or, at the latest, in phase II trials, and, under previous policy and even more so under the 21st Century Cures Act, the FDA can consider that evidence in approving a drug. There would be examples of clinical trial subjects demonstrating amazing tumor shrinkage or even outright cures. In reality, we don’t see these things in phase I trials, because there are no miracle drugs, at least not yet. (The closest to a "miracle drug" I can think of is Gleevec, and drugs like Gleevec are rare.)

"Right to try” laws rest on a fantasy, and it’s a fantasy of false hope. Indeed, these bills serve an ideological purpose rooted in libertarian politics, free market fundamentalism that claims that deregulation is the cure for everything, and the desire to weaken the FDA that flows from such beliefs. Unfortunately, because stakeholders in medicine who recognized this were too timid to speak up, it is probably too late to stop some form of a federal "right-to-try" bill or provision from becoming law. Let that be a lesson to us.

oracknows Sun, 04/23/2017 - 21:15

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Skepticism/Critical Thinking

Trickett Wendler Right to Try Act of 2017

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I have to admit to being on the fence on this one. On the positive side, the medical intervention shows promise, that is scientifically viable. It is in the early stages of being trialed, so is not proven one way or the other. If someone has nothing else to try, why not. I assume that the clinicians will take the data resulting from this "Hail Mary" into account in their trial results, so it is another data point that can either support or refute the interventions use.
As you point out however, the patient is truly on their own financially, and sign away any-rights if the intervention makes things radically worse. I'm actually surprised that a company would risk allowing their drug/intervention to be tested outside of the clinical trial, just on the chance that it does fail spectacularly in that case. Pretty hard to market an intervention when the first use of it kills the patient, and the patients friends and relatives set up a web page proclaiming that to the world.
Free choice implies the right to do stupid things as well as reasonable things. The ass covering of the drug/intervention developer is way off, but I sort-of kind-of agree with the idea.

AP: sure we have the right to do stupid things. That's why society has rules to restrain our worst impulses. Just because some people are stupid . . . or desperate . . . doesn't mean we should enable the behavior.

I don't think the ass covering of the drug companies is way off. I think it's prudent. Lawsuits often succeed when the provider ignores the established standard of care, and experimental drugs do not meet any standard of care.

I guess we're going to have to go through another Sulfa scandal to get the general public to clue in.

Panacea: If the drug company is willing to allow the use of their phase 1 trial drug, they should be willing to accept responsibility as well. If is succeeds, you know they would trumpet it from every possible pulpit, so conversely, if it fails, they should also have to own it as well. After all, they are the ones who agree to let someone try their experimental drug. As far as I can see, the law doesn't require them to make it available, just gives people the option of asking for it.

The problem is, with patients paying the full cost, then you can imagine the pressure being put on both patients and their families for 'one last try', at a time when their resistance is at it's weakest.

Remember that free choice requires both reliable information and the ability to act rationally, both of which are going to be in short supply in this kind of situation.

Orac writes,

I’ve as yet been unable to find a single compelling example of a patient who has been helped by access to an experimental therapeutic through a state right-to-try law.

MJD says,

When that first example occurs and others benefit thereafter what a great story it will be.

Natural experimental-therapeutics may be the first big winner in the right-to-try law.

https://bioaccent.org/cancer-sciences/cancer-sciences25.pdf

Andrew: That is the reason that I am on the fence. To my mind, the scales are tipped to far to the side of the drug/intervention developer. The patient is bearing the vast majority of the burden.

One reason why these laws have done so little, is that companies are loath to risk what could be a very promising drug or treatment in situations where they have little to no control.

The bad press that could be generated by the families, should these patients die (even as a natural course of their conditions) would probably be enough to, at minimum, set back development by some period of time & potentially be a huge black eye when going through the actual FDA approval process.

This has the potential to backfire significantly against the industry - and I note that few, if any, pharmaceutical companies are actually supporting these bills.

The way I see it, "right to try" just means drug companies can use desperate people as guinea pigs and force them to pay for the drug company's testing.

patients paying the full cost

Which isn't cheap, because there are no economies of scale in manufacturing drugs at this stage of the approval process. Insurance won't cover it, because it's an experimental treatment (this is why in most drug trials the patients are not charged for the cost of the medication; otherwise the cost would be a significant incentive for people to drop out if they thought it wasn't helping them).

Another thing to keep in mind is that in the overwhelming majority of cases, the reason for the existence of regulation X is, "People died and/or were badly hurt when regulation X was not in place." Most libertarians, such as the Goldwater Institute, either never learned this or choose to ignore it. The reason for the current FDA approval process is that it serves to minimize the amount of unnecessary death and injury from new drugs. IIRC, new drugs are not shown to be both safe and effective before they have completed a successful Phase 2 trial if not a successful Phase 3 trial.

Another reason why we have laws is to prevent the powerful from exploiting the desperate, as AD@4 mentions. Patients with an advanced cancer diagnosis, and their families, can be quite desperate. Stanislaw Burzynski, among others, makes a good living exploiting exactly these people. IANAL, but I would think that if federal right-to-try were enacted, what Burzynski is doing would become explicitly legal. He is, after all, treating patients with a drug (antineoplastons) which has passed a Phase 1 trial. Never mind that ANPs have failed to get past Phase 2.

It's worse than that Terrie - I don't believe there is any obligation for the companies to incorporate the results of any "right to try" situations.

Eric -

Yes.. all you need is a bit of in-vitro activity, however dubious, a phase I trial to show that patients don't drop dead instantly, a big marketing budget and a bloodsucking legal team.. and you'll have plenty of estates to plunder. Don't even need the Mexican clinic now..

AP: the drug companies have different burdens of their own. All those bad outcomes (since the drugs are unlikely to help them but bound to uncover problems in sick people) means many drugs will never make it to a Phase II clinical trial, that might have made it there, and might have been given the opportunity to work those bugs out.

Terrie: the drug companies don't want this. They're not asking to do this. It's the patients experimenting on themselves, and wrecking the scientific process in a bid that is highly unlikely to give them any real benefit.

However, the quacks, like Stanislaw Burzynski, are doing just that and making a ton of money doing it. And killing people; his antineoplastins have a tendency to cause a profound and lethal hypernatremia.

Lawrence: the drug companies canNOT ignore data from right to try. It has to be included. Problem is, it really complicates evaluating the results. We could end up giving up on a drug too early, or not giving up on a drug soon enough.

Eric: What Burzynski is doing has become implicitly legal, thanks to the cowardice of the Texas BOM.

These patients are being lied to. They're being told there's hope when that hope really doesn't exist. They will sooner, and in more pain, than if they had chosen the hospice route. Hospice patients live longer and report more satisfaction than terminally ill patients who seek aggressive care after efforts become futile.

Normally I don't wish ill on people. But I hope those Goldwater hacks are someday hoist by their own petard.

Hey, industry has to have _some_ way to sell the stuff that would otherwise be expensive to dispose of in toxic waste dumps.

"Fracking fluid" was a good way to package the garbage to sell.

Why not try putting it in pills?

33 states in three years is quite a rapid pace. I dont think this is a grassroots movement. This is being pushed.

So where is the funding coming from? Who is funding GOldwater to push this legislation?.

If I had to guess, there are few Silicon Valley billionaire libertarians who are eager to push their views...and this is exactly the kind of thing they'd put their money behind.

In fact, Orac has written about at least one of these guys recently, who was on DJT's short list for the FDA.

These bills would prevent federal lawsuits against drug or device manufacturers, dispensers, users, or physicians prescribing or administering right-to-try.

From just the quoted subsection, it sounds broader than that. I don't know whether such "preemption" would pass constitional muster. (Paging Professor Reiss – please come to the blue courtesy phone.)

I dont think this is a grassroots movement. This is being pushed.

There is a term for this: astroturfing. The people pushing this want politicians to perceive a grassroots movement behind this, whether or not that grassroots support actually exist (and I agree, it probably doesn't).

It doesn't take a Ph.D. in political science to figure out that while libertarianism may be appealing in theory, it is not compatible with realistic assumptions about human behavior. (Communism and libertarianism are very much alike in that way.) This is why libertarian "think tanks" often have to create astroturf movements to get their wish lists enacted. To be a libertarian you would have to be rich enough, deluded enough, or (most likely) both, to think that you would come out ahead in such a world, and there aren't that many people who meet this criterion.

Oh, it's definitely being astroturfed. The Goldwater Institute devised right-to-try as the first volley in its effort to neuter the FDA. Its leaders know that state-level right-to-try laws will have no effect because the FDA controls drug approval. The idea is that, once a critical mass of states pass right-to-try, the pressure on Washington will be too much to resist to pass some sort of federal right-to-try bill. The Goldwater Institute has been relentless in this. For example, when right-to-try came to Michigan a couple of years ago, the Goldwater Institute flew in sympathetic patients to serve as witnesses, while the biomedical research community remained largely silent. The bill passed under the radar, and the governor had signed it before I even knew that it had passed. So it has been in other states. Libertarian and free market fundamentalist think tanks have been promoting right-to-try.

I don't know where their funding comes from. It's probably not from pharmaceutical companies, though, because pharmaceutical companies have been noticeably cool to right-to-try. Big pharma (also even little pharma) likes predictability, and right-to-try adds an element of unpredictability that is unsettling to them. Also, quite understandably, they don't want to be besieged with requests from desperate patients every time they have a promising drug in the pipeline. Right now they can paint the FDA as the bad guy, the gatekeeper. Right-to-try would put that role all on them. So pharma doesn't like it.

I also missed the section where they had to include the results in their clinical trial data - that's another reason for them not to want to participate in this.

A good bet for funding would be alt-med people. Once the bill is past they can legally kill people with no litigation issues.

Rich: Maybe. Libertarians may or may not be into pseudoscience.

For them it's an anti-regulation issue. These people hate rules of any kind. They figure that all conflict will sort itself out one way or another; it's a Might makes Right way of thinking. Libertarians assume that people will follow rules of conduct free from regulation. It assumes that people won't cheat or steal, and if they do, it will be dealt with on a societal basis.

That's what Eric was talking about. Libertarianism and Communism both assume that man is virtuous by nature, that given the chance he'll do the right thing by his neighbors. It's a uniquely naive way of looking at the world, and as history amply shows, it doesn't reflect reality.

Libertarians just figure they can enforce the rules at the end of a gun. It leads to anarchy.

Communism also figures they can enforce the rules at the end of a gun. It leads to totalitarianism.

If I were involved in development of a new drug I think I would want to make its use under right-to-try as patient-hostile as I possibly could. I would certainly absolutely refuse to supply such drugs unless everyone involved in the attempted use were sworn, on very severe penalty, to remain absolutely silent about the attempt to anyone outside of those who were of-necessity involved. No communication with other potential users. No communication with the media. No blogging. No communication with great aunt Blabberty. No chit-chat in the nurses lounge. Lips very tightly zipped/glued/sutured/stapled. I might soften my attitude a little if the drug were well on in phase 2 trials.

Once any sort of word got out, I think it would become much harder to maintain the objectivity that is the intent of double-blind* investigation.

I haven't followed this topic at all closely, and I imagine Orac has covered this detail before, but lacking good data my suspicion is that rescuing terminally-ill patients, who have already tried existing therapies, with a new drug is almost unknown. Rescuing someone who has developed rabies symptoms is almost unknown. Rescuing someone in systemic toxic shock is not too likely. In either case, acting before "terminally ill" gets into the conversation can be very successful. Once the patient qualifies for a right-to-try, hope is extraordinarily faint. I don't want my new drug tried in such circumstances. I don't want word to get out that everyone who tried it died and therefore find it impossible to enroll anyone in proper trials. I don't want anyone who does enroll to drop out at the first sign of a tummy upset (actually the fault of the shrimp sandwich from the truck stop vending machine) because they're afraid the drug is going to kill them. I don't want the people who work at one of my trial sites to be hyper-vigilant because of something one of them heard on the elevator.

* I can't remember the equivalent term used in one paper I read, but it wasn't "double blind" - I don't know if that was because of the country of origin of the research or because it was about something in ophthalmology

A dying person will clutch any straw. That's why we don't need to legalize selling $100,000 straws to the dying with little or no accountability for the seller.

I would certainly absolutely refuse to supply such drugs unless everyone involved in the attempted use were sworn, on very severe penalty, to remain absolutely silent about the attempt to anyone outside of those who were of-necessity involved.

So you want everybody involved to sign a non-disclosure agreement. So far, so good. The conundrum is, how do you enforce the NDA? The patient will typically have multiple physicians and multiple nurses, all of whom need to know. The patient's immediate family all need to know as well. At this point you've got too many people to hide a conspiracy. The family, having spent eleventy thousand dollars on this desperate gamble, will in many cases not have enough remaining assets to be worth pursuing. The patient will likely be dead and therefore not care about your NDA. And if the blabbermouth turns out to be somebody at the clinic, you'll have a hard time proving which one spilled the beans.

The pharma companies are generally against right-to-try laws for essentially the reason you describe. I don't think they'll be able to NDA their way out of this dilemma.

... how do you enforce the NDA?

That, of course, is a huge and, in practical terms, virtually insoluble problem. Even in ordinary circumstances NDAs are typically not worth the paper they're printed on. I was thinking in terms of roving bands of assassins, which are generally frowned upon - and somewhat at odds with the notion of trying to save someone.

If I were involved in development of a new drug I think I would want to make its use under right-to-try as patient-hostile as I possibly could.

During the years when it was my responsibility to address requests to use the unlicensed new drugs that I was involved in developing, I viewed it differently: I wanted to make it as patient-friendly as possible. That's why I tried to respectfully but clearly communicate why such requests could not be accomodated. One of those drugs turned out to be both safe and more effective than comparators--it has indeed saved lives since it was approved by FDA--but reasonable alternatives were available. Because alternatives were already available for a second drug, nobody really requested it, anyway, and I might have been the only one who really cared when it was dropped after two succsessful and expensive Phase III trials had consumed so much of my life. The third drug, for a cancer therapy still in trials, was the most difficult call, because the requests that I declined were from patients who, like the patients in our clinical trials, were desperate; such trials take long years to sort out, and the cost-benefit calculation is impossible if both the costs and the benefits are unknown.

On how very thin a straw a desperate person will grasp for:
A friend was getting an engineering PhD doing research on a surgical robot. At that time the robot was only half built, had a tendency to randomly lash out with one arm, and had never done "surgery" on anything other than a dead pig.
One day the lab gets a call. It's from the parents of a young man who is dying of a brain tumor. Could they please bring the young man down to have surgery by the robot?
"No, no, I'm very sorry, the robot doesn't work yet, and it's never intended for the brain."
After the call ended (and everyone felt like a heel) someone searched around to try and figure out why on earth the parents had called *them*. Somewhere deep in the bowels of the Internet was an article written years before about how some day in the future, robotic surgeries may be able to address this kind of brain tumor.

There are no real benefits in right-to-try for a drug company--first, any data that they get from these uncontrolled unblinded treatments will be useless. If the right-to-try patients run into troubles that could have been avoided in a proper trial, the legit trials could get derailed because everybody (FDA, company, & public) freaks out.
The company may not even be able to recruit patients for the controlled trials. No sane company would invest in making more than the amount of drug required for clinicals, so there isn't going to be any drug to spare before its actually approved. A small company could easily be bankrupted by right to try.
This assumes that the company isn't charging for the drug, which is generally not done for investigational drugs in clinical trials. Allowing the Shkrelis of this world to get around this would be a real nightmare.

Elliott @28: You're totally right. The only companies that would actually make use of this are ones who aren't actually going to do a Phase II trial. I can see a supplement company doing this as an excuse to charge 1000X over the usual price of whatever they're making, but no legitimate biotech or pharma would take the risks.

These folks at the Goldwater Institute pushing for this really ought to take the next plane to Mogadishu. There’s their libertarian paradise for them.

It strikes me that the RTT approach is not something a lot of pharma, big or small might want to endorse since, even if the FDA is legally required not to include RTT adverse effects, there is nothing at all to preclude other drug approval organizations assessing it even as anecdotal evidence.

A few nasty rumours out of the USA could hold up approval in the EC or other major markets for an indefinite period.

Various ideologues who detest government regulation strike me as possible funders.

@ Doug

Exactly.

Is it possible to write a right-to-try law in such a way as to tie the hands of a potential future anti-vaccine administration that tries to ban vaccines?

#30: I hear enough of that rhetoric from the alt-right.

@32: No. Because the President does not have the authority to ban vaccines as things stand now. He can try to hide scientific data, like he's trying to do over at the EPA and people fear he will try to do at the CDC. But he can't just come out with an EO to ban vaccines. Congress would not stand for it (even in our hyper-polarized political situation), and the courts definitely would not stand for it in the lawsuits that would follow.

In any case, RTT on its face is a bad idea. I would not support (as a citizen) an effort to pass RTT with an amendment saying that Congress can't ban vaccines in the future, and any such amendment could easily be undone by a future Congress anyway. There's no upside to such an amendment, and all downside (the farce that RTT is, and the way it weakens the FDA).

"Right to try": A miserable failure thus far

oracknows — Thu, 08 Sep 2016 04:45:28 +0000

"Right to try": A miserable failure thus far

I’ve frequently called “right to try” laws that are popping up in various states like so much kudzu, to the point where 31 states have passed them in a little over two years, an amazing pace, a cruel sham, given how incredibly unlikely they are to help a single patient. Basically, state-level right-to-try laws are the brainchild of the libertarian Goldwater Institute and all based on a template that it produced. Their purpose is not, as the Goldwater Institute claims, to help patients, but rather to weaken and ultimately neuter the FDA’s power to regulate drug approval and thereby help to usher in a libertarian utopia in which drugs don’t need approval and the free market magically guarantees safety and efficacy through various “independent” testing labs. Unfortunately, in order to achieve its ultimate aim of neutering the FDA, the Goldwater Institute has made promises to patients that right-to-try can’t keep, enlisting them as their most effective foot soldiers to get such legislation passed. Unfortunately for patients, it’s been an incredibly effective tactic, because opposing right-to-try has successfully been framed as being heartless and taking away the last hope of desperate patients, all the while twirling one’s moustache, to the point where opposing right-to-try is viewed as being akin to being for burning the American flag while eviscerating puppies. No wonder politicians have, by and large, not even tried to stop right-to-try, other than Governor Jerry Brown.

One of the seemingly most compelling arguments in favor of right-to-try is that the FDA’s Expanded Access Program (a.k.a. Compassionate Use) is too cumbersome and doesn’t benefit very many people. I’ve addressed that trope before, pointing out that the FDA has make Expanded Access much easier and that it rarely rejects such applications. In comparison, I’ve thrown the question back at the Goldwater Institute: How many patients have benefited from right-to-try? Heck, I set an incredibly low bar and don’t even require that these patients have benefited. I ask how many patients have even received experimental treatments through a right-to-try law. Oddly enough, even though the Goldwater Institute claims it knows of 40 patients receiving experimental therapies through right-to-try (compare that to the 1200-1800 yearly who receive experimental therapeutics through Expanded Access), it never seems able to provide more details. Personally, I’ve called BS on its claims, but still periodically ask. I also note that at least one patient used right-to-try to access cancer quack Stanislaw Burzynski’s antineoplastons.

Frustrated by the professed lack of knowledge of patients who have benefited from right-to-try, even though it’s been well over two years since the first right-to-try law passed in Colorado, I decided to take matters into my own hands. Basically, the rationale for my approach was as follows. I did some searches on GoFundMe and Caring Bridge, two websites frequently used by patients to raise money for medical care. As ‘ve pointed out many times, if there were patients getting medications through right-to-try laws, given that most of these laws don’t require that drug companies provide right-to-try drugs for free, there would be some of those patients on GoFundMe and Caring Bridge asking for money. I must admit, the results were...disappointing.

First of all, a lot of what came up were comments about how various users of these two sites thought they were “right to try” to fund their efforts. In one example, a couple raising funds for in vitro fertilization stated that they thought they were “right to try.” In others, patients were raising funds for standard therapy but stating that they were advocating for right-to-try. This, of course, made finding true “hits” very difficult. Even so, basically I could find only two potential hits, and of those only one really seemed credible. For example, look at Patrick Sheridan, a man with pancreatic cancer:

I want to make something clear. This thing is only in me temporarily. It is not killing me. I am killing it. It picked the wrong person to mess with.
Traditional U.S. methods for for fighting cancer with chemo, radiation, and surgery aren't viable options for me at this time. My family and loved ones who have banded together to help me win this fight and I have already begun an aggressive mix of alternative and cutting edge therapies. I'll share more about the people and the therapies soon.

Unfortunately, many of the therapies that show the most promise (and in many countries, amazing results) are not covered by insurance. Some of these therapies may be available to me in the U.S. under Right to Try and Compassionate Use laws. Other, may only be available outside the U.S. We are pursuing them all. Most of you know how difficult it is for me to ask for help, but I'm asking for yours. A Go Fund Me page has been set up to help us cover some of the enormous costs it's going to take to beat this. Any help is greatly appreciated.

Unfortunately, Mr. Sheridan appears to be pursuing a mixture of pure quackery (like high dose vitamin C) along with treatments ranging from the questionable to possibly useful. Reading his sites, I could find no evidence that he accessed any experimental treatment through right-to-try.

So I moved on to the other potential hit, Gail Christopher, who has a GoFundMe page. Here is her story:

My cancer journey began September 30, 2008 after being diagnosed with Stage IV pancreatic neuroendocrine tumors, that had already spread to my spleen and liver. Fast forward 7 very tough years which have included a distal pancreatectomy, splenectomy, liver wedge resection with ablation, removal of gallbladder, another liver surgery to remove 2 large tumors, 2 liver embolizations and unfortunately breast cancer surgery with a partial mastectomy. During this time I was on 7 different chemotherapy treatments and chemo is no longer working for me as the tumors have gotten very large on my liver and are pressing against my lungs and have metastasized to my
heart.

Having this rare disease, means that a lot of already scarcely available drugs will not work for me, so my treatment options are extremely limited. This cancer has been resistant to standard chemotherapy, however, I continue treatment because I am determined to fight this terrible disease to ensure I am able to look at the beautiful sunrise from my bedroom window, snuggle with my precious dog Jack and be around to see my nephews and nieces get married.

Recently, I applied for a clinical trial at Memorial Sloan Kettering to participate in an exciting new therapy called PRRT, Peptide Receptor Radionuclide Therapy. Unfortunately, my hopes were dashed during the screening checks when they shared that my tumors are too large and what is termed "poorly differentiated."

I can’t help but note that Steve Jobs died of a pancreatic neuroendocrine tumor. These tumors tend to be indolent, slow-growing, but relentless. Thus, an eight year course after diagnosis is not at all unusual for this particular tumor type. Christopher notes:

PRRT will be a huge financial burden, and that is why I am reaching out for private funding. Any donation you could generously offer will be used to pay for my treatment which alone is approximately $38K, this does not include the additional expenses of traveling out of state and accomodations for multiple extended periods.

PRRT has been available as a life-saving treatment in Europe for 15 years but sadly is not FDA approved in the US. I will be undergoing 4 PRRT treatments at Excel Diagnostics in Houston, TX every 6-8 weeks. Excel is able to offer this treatment due to a "A Right to Try" act, which states terminal patients have a right to try any medicine to prolong their life whether FDA approved or not.

So what is PRRT? It’s a therapy that is simple in concept but not in execution. In the case of pancreatic neuroendocrine tumors, PRRT uses the fact that pancreatic neuroendocrine tumors express a lot of a protein, a receptor, that binds a molecule known as somatostatin. PRRT takes advantage of that by labeling somatostatin, although it uses another molecule that binds to the same receptor, octreotide. In PRRT, octreotide is combined with a therapeutic dose of radionuclides, with the most common ones being Yttrium 90 (Y-90) or Lutetium 177 (Lu-177). Basically, the idea is to target the cancer with a radioisotope by taking advantage of a specific molecule’s affinity for a receptor unique to the cancer. The radionuclide-conjugated molecule binds to the receptor on the tumor cell and kills it, thanks to the radiation from the radionuclide.

It turns out that Excel Diagnostics is based in Houston and uses Indium-111 or Lutetium-177 Octreotide therapy. There are several clinical trials on LRRT listed on PubMed, and Excel Diagnostics is listed as an investigator in several trials. Oddly enough, most of the trials have statuses listed as “Active, not recruiting” or “unknown.” In the meantime, I note that the Texas right-to-try law has a provision that is rare:

(c) If a manufacturer makes available an investigational drug, biological product, or device to an eligible patient under this subchapter,the manufacturer must provide the investigational drug, biological product, or device to the eligible patient without receiving compensation.

Yet, according to Gail Christopher, her treatment will cost $38,000 not counting travel and lodging expenses, of which she has raised $16,665 so far, according to the GoFundMe page. It is not at all clear to me whether these charges are for the whole treatment, or if Excel Diagnostics is providing its drug free of charge but that the ancillary medical expenses will be $38,000. I have to assume that the drug is being provided free of charge if Christopher is truly accessing radionuclide-labeled somatostatin analogue through right-to-try. Given that the company’s products are in active clinical trials as part of the process for FDA approval, one can’t help but wonder whether she’s actually receiving the drug under the FDA’s Expanded Access program, because I wonder whether Excel Diagnostics would be willing to take the sort of risk of administering the drug without the FDA’s blessing.

Whatever the case, at her latest update, which is from four months ago, Christopher states:

Well, I leave again for Houston in 2 weeks for PRRT treatment number 2. This treatment is WORKING!! When I last updated everyone my cancer specialist sent me to a bone surgeon to look at resecting cancer in my frontal bone on my skull. While waiting for that appointment with the bone specialist, the tumor disappeared!! I have to believe that it's working on other tumors in my body also. Thank God!!

I've applied for a small grant to assist me with these medical expenses and will hopefully hear good news on that in June. I'm still hoping to raise almost $25K to pay for treatments 2, 3 and 4...and I want to thank everyone who has donated so far. Some have gone over and beyond and have sent in a second donation for my second upcoming treatment.

I hope that Christopher continues to do well, but the lack of an update in four months and a seemingly dormant GoFundMe page is certainly cause for concern, at least to me.

Curious, I looked up what Excel Diagnostics is offering and found this:

Excel Diagnostics & Nuclear Oncology Center is pleased to announce that after careful review the Federal Drug Administration (FDA) has approved Investigational New Drug Clinical Trial by LU-177 Octreotate for patients with Neuroendocrine cancers. Excel Diagnostics & Nuclear Oncology Center is the first research facility in North America to receive authorization to initiate this much needed cancer therapy.

This therapy can be applied to the category of neuroendocrine tumors which include Carcinoid, Islet Cell Carcinoma of the Pancreas, Oat Cell Carcinoma of the Lung, Pheochromocytoma, and Iodine refractory or Medullary Thyroid Carcinoma”.

On ClinicalTrials.gov, I found two potential trials of PRRT in neuroendocrine tumors with which Excel Diagnostics is involved: 177Lutetium-DOTA-Octreotate Therapy in Somatostatin Receptor-Expressing Neuroendocrine Neoplasms and A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours (NETTER-1). According to the Society of Nuclear Medicine and Molecular Imaging’s patient guide, PRRT is palliative, not curative, and it can be effective at slowing the progression of advanced neuroendocrine tumors and in relieving symptoms. Evidence suggests that at least one form of PRRT is most effective against well- and moderately differentiated somatostatin receptor-expressing neuroendocrine tumors (which Christopher did not have, which is why she was not eligible for the existing clinical trial).

As I said before, however Christopher received PRRT, through Expanded Access or the Texas right-to-try law, I hope she is doing well, despite the lack of recent updates on her GoFundMe page. From what I can tell of her story, she certainly looked like a good candidate for expanded access, given her history, but obviously I can’t know the details of her case other than what she has chosen to reveal. I do know, having known a friend of a friend who suffered for several years with a neuroendocrine tumor and the symptoms it caused, that, even though such tumors are usually slow-growing, they are nonetheless a nasty set of tumors because of the symptoms they cause.

I’ve said before that, if lots of patients were benefiting from right-to-try or even if it is only the 40-60 patients that the Goldwater Institute claims to know about, their social media footprint would be visible and unmistakable, given that in most states right-to-try does not require the company manufacturing the experimental therapeutic to provide it free of charge. I would expect to see patients on sites like GoFundMe asking for money to help with the expense. I’d expect to see patients who succeed in accessing drugs under right-to-try to be trumpeting their fortune on Twitter, Facebook, and other social media. What is remarkable about right-to-try is how, even more than two years after the first such law passed, there is so little evidence of such activity. Gail Christopher is the only such patient I could find so far, and she appears to have been a good candidate for Expanded Access. I hope she is still alive and still having good results with PRRT.

The Goldwater Institute and other supporters promised in their pitch for right-to-try that it would provide access to experimental therapeutics to far more patients than the FDA’s Expanded Access Program, which it consistently derided as ineffective, too slow, too bureaucratic, and, at times, literally killing people. Two and a half years later, we see that for the lie that it was. That’s because the purpose of right-to-try was never to help patients (although that’s how it was sold and if it did that would be an ancillary benefit). It was to attack the FDA.

oracknows Thu, 09/08/2016 - 00:45

Tags

Peptide Receptor Radionuclide Therapy

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Not good news.
http://www.legacy.com/obituaries/buffalonews/obituary.aspx?pid=181070640

Crap.

My condolences to the family.

Oh, geez. How did I not find that? I probably should have searched for her name + "obituary" but I didn't want to think that way and go too far down that path. I guess I was just hoping she was still alive.

@Wzrd1

Damn. So sad.

@Orac, alas, that was the search terms that I used, hoping to not find her name.

So sad to hear that. I was thinking this morning of my sister-in-law who died of cancer 6 years ago, so I truly sympathize with her family.

To be honest, I felt like a shitheel to even report her death, but, well, it had to be done.
Ask our intrepid leader on giving bad news. It has to be done.
I lack the practice on gently administering it.
Nor would I ever want to have to learn that practice.

I'm still realizing that I entirely refrained from reading DICOM imagery that I'm perfectly capable of reading of my wife's liver, after learning of her bilary cirrhosis.
I realized that late last evening, while on shift, where a DICOM viewer isn't available.
I returned home at 07:00, got distracted, it's nearly 13:00 local, still haven't reviewed the imagery.
Yeah, massive psychological block present. As I briefly reviewed the imagery for spinal issues, I suspect something is present that I'm not wanting to consciously review.
For, I know two people intimately well, to the lowest level and highest level, my wife and myself.

I've scheduled it for tomorrow to review the imagery, with intent to review the liver imagery. Complete with computer annoying me until I do, lest protective routines try to interfere.
I learned a long time ago how to overcome the natural things that one's mind puts barriers in front of.

No, it did have to be done. Actually, I screwed up in not finding that obituary when the way to find it was so obvious.

Eh, we all have an off day and miss something obvious.
I've wasted hours looking at something, but seeing what I was expecting, rather than a mistyped bit of code.

The "stories" of "right to try" web page ( http://righttotry.org/patient-stories/ ) by the Goldwater Institute is less than inspirational to me. I'm sorry if I sound like some hard-hearted bastard, but these "stories" (including a 5 y/o boy with DMD who even with current therapies should have another 15 years at least ahead of him but parents want to experiment on him anyhow) don't tell the whole story, and you're right, Orac--after 2+ years you think they'd have more to trumpet.

Resonating well with me, while I eagerly await my next echo of my abdominal aorta, which was 2.2 cm enlarged. Hit around 3 cm, things start to get interesting, hit 3.5 cm. Erm, Google Dead.

None of these stories actually used right-to-try, as far as I can tell. Some of them used FDA Expanded Access. One told of parents moving overseas to access a drug approved in another country but not the US. One told of a patient recently diagnosed with colon cancer with no mention of experimental therapeutics. Basically, this is some really thin gruel, given that it's been almost two and a half years since the first right-to-try law passed in Colorado.

I'll give them one thing, Orac.
No chance, vs slim chance.

Seriously, no chance or try, which would you try?
I'd honestly try a chance. Well, save when someone's trying to make serious money.
I'm also a realist.
An even money chance, I'd take that chance.
Not a good chance, but it's a chanceish.

popping up in various states like so much kudzu

But I'm sure you're not advocating stamping out kudzu since it shows promise as good medicine?

Alcoholism. Early research suggests that heavy drinkers who take kudzu extract for 7 days consume less beer when given a chance to drink. ...

Heart attack (myocardial infarction). Early research suggests that injecting puerarin, a chemical in kudzu, intravenously (by IV) along with usual treatment might help some people after a heart attack. Puerarin injection products are not available in North America.

http://www.webmd.com/vitamins-supplements/ingredientmono-750-kudzu.aspx…

I'd think the true intent of 'right to try' may not apply so much for pharma experimentals as it does for (herbal) treatments not available in the US.

@Gli, considering my own ethanol intake each week, perhaps a comparative survey should be in order.
I will admit to an ethanol intake that is quite literally legendary, which is obviously unhealthy. I'm astonished that my wife has a liver problem long before mine started to flag!
Although, now, I have a physician who's willing to prescribe for pain. I'm still adjusting.
Yes, dead serious. As in, 3.5+ liters of distilled spirits each and every week kind of serious.
*Finally*, pain is being addressed, but not the ethanol, I'm working that issue. Although, I can "cold turkey" it and not have anything beyond sleep disturbances, that's worrisome enough.

Or more simply, I drink more than quite a few alcoholics, habituated to it even, interrupt it, I have problems sleeping for a while.
Food is far more important. :)
Pain relief, less important than food, albeit, I'd eat a fair amount less.
Treat pain, zero high, I'd be the happiest creature on this planet. Fix the problem, I'd be in Xanadu.
Alas, insurance company regulations create problems that make me want to send a B-52 after...

My wife was just turned down for Osteoporosis injections, as there's an "oral substitute" that's far less effective.
She currently is healing from several vertebral fractures and has a pair of new fractures.
Pissed off is mild in my emotional chain right now, I'm thinking city erasure rage.
Sorry, but this just, quite literally came in.
Angry?! No, I want to vivisect someone. For anyone not knowing the term, it's dissecting an individual alive.
Which also makes me want to vomit.
I passed rage on the left, accelerated hard and found nothing.

I apologize, but, I'm at a loss, both for words and a plan.
Her spinal issues are severe, even life threatening at the beginning edge.
This crap ads in additional risk of terminal problems, due to delay of treatment.
Add in a flagging liver, secondary to an ignored gallstone condition until it became a massive problem, plus decades of APAP in every goddamned medicine, think that I'm enraged?!
I'd beat the dogcrap out of the Incredible Hulk right now.
While my mind whirls with zero ideas!

Welcome to Doctor's land. Bad news, no idea for good news, try for the best.
The reality of it is, I still am considering, hours later, how best to taste a bullet if I lose her after 34+ years.

Welcome to reality, not something you hear about, very, very real world.

I apologize, but news came in earlier today. I'm usually good at hiding such things, but, screw that.
For the third time in my life, I'm crying, the other two times was for the death of each parent.

So, please, out of some modicum of decency, take you politics out, then insert it up your ass sideways. Twice.
While I try to figure out how to move onward for our grandchildren.

I think I would gave gone with right to try when my wife was diagnosed with advanced MBC. However, after watching my sister in law struggle with a Phase I clinical trial (the drugs almost killed her; a lower dose has allowed her to return to work) as well as a friend who has survived PNT for over 10 years dealing with extremely harsh side effects of his regimen, RTT, in my opinion, would lead to premature death for most patients. Not to mention quality of life. I've certainly changed my stance on this issue.

I'm not surprised you had such a low signal-to-noise ratio looking for RTT cases on GoFundMe. Many quacks charge their patients/clients hefty sums of money for unproven treatments, too, and there are some (*cough* Stanislaw Burzynski *cough*) who deliberately try to blur the line between genuine experimental treatments and woo. Somebody has to support Stan in the lifestyle to which he has become accustomed.

Looking at the right-to-try website stories, it seems more like they are stories of people who right to try could maybe, possibly help. Maybe. Almost all of them could be equally assisted by increased FDA funding earmarked for hiring more people to handle expanded access requests so the process can be speeded up.

Wow, Wzrd1.

Add in a flagging liver, secondary to an ignored gallstone condition until it became a massive problem

http://www.lifeextension.com/magazine/2010/5/n-acetyl-cysteine/page-01

Inositol
Choline**
P-5-P (a form of b6)

**alcohol doesn't damage the liver, malabsorption of choline caused by alcohol does --

Endurance athletes and people who drink a lot of alcohol may be at risk for choline deficiency and may benefit from choline supplements. Studies on a number of different populations have found that the average intake of choline was below the adequate intake...

When deprived of choline in their diets, 73% of postmenopausal women given a placebo developed liver or muscle damage

https://en.wikipedia.org/wiki/Choline

Actually, I suspect that my hyperthyroidism is responsible for my lack of liver injury. Choline isn't the only pathway that can potentially cause problem, fat processing as well can create problems.
Still, I dealt with bones and plumbing in emergency situations, for the most part. Endocrinology lacks both. ;)

fat processing as well can create problems.

That's what the inositol is for.

Choline and myo-inositol have been shown to prevent abnormal or excessive liver accumulation of cholesterol and triglycerides in choline and myoinositol deficient rats.

http://www.ncbi.nlm.nih.gov/pubmed/7751073

http://knowledgeofhealth.com/how-simple-dietary-supplement-can-quell-mo…

NAC is availible over the counter and is what they give in the hospital for acetaminophen toxicity -- The number one cause of acute liver failure in the US. Like so much denatured alcohol, it's in every damn thing.

Indeed, APAP is in so damned many things and has caused severe injuries in the US.
Considering how narrow its therapeutic window is and how hepatotoxic it is, honestly, I'm for banning the crap.

That said, my liver function is still excellent. Surprisingly so.

I'll share this little bit of good news I noticed in the morning's articles here since it's the latest cancer related blog.

http://medicalxpress.com/news/2016-09-brain-cancer-childhood-killer.html

There are still more new cases of leukemia each year than new cases of brain cancer, but it no longer accounts for the most deaths. That's due to advances in leukemia treatment over the past few decades and because leukemia is easier than brain cancer to treat, experts said.
"Some types of leukemia that a generation ago were almost universally fatal are now almost universally treatable," said Curtin, a statistician who worked on the report.
But the rate of death from brain cancer for children has held at about the same level for at least 15 years, according to the CDC report.
The trends are similar for adults, too, according to the American Cancer Society.
Leukemia is a type of cancer that affects the blood. That makes it easier for doctors to get to it and fight it with treatments like chemotherapy.
The brain is protected by a barrier which helps keeps many dangerous chemicals—including many cancer drugs—from getting to brain tissue or brain tumors. Surgery is difficult and sometimes impossible, depending on where the tumor is located in the brain. Radiation treatment can damage the development of a child's brain.
"There's survival, and then there's survival at a price," said Dr. Katherine Warren, an expert in pediatric brain tumor research at the National Cancer Institute.
Another factor is that scientists have only recently begun to understand that pediatric brain cancers may be biologically different from adult versions, and could require different approaches to treatment.
In 2014, the brain cancer death rate was about 0.7 per 100,000 children ages 1 through 19. The leukemia death rate was about 0.6. The overall pediatric cancer death rate dropped by about a fifth between 1999 and 2014, the CDC reported, helped by the reduction in leukemia deaths.

Progress is slow but it's real.

w/r/t my post (#10), this just popped up in my email today regarding accelerated FDA approval of the first medication approved to treat DMD (Duchenne Muscular Dystrophy) : http://www.managedhealthcareconnect.com/content/fda-grants-accelerated-…

Good news (and really argues strongly against RTT)!

"Right to try" goes federal, thus far unsuccessfully

oracknows — Tue, 06 Sep 2016 01:00:52 +0000

"Right to try" goes federal, thus far unsuccessfully

It's been nearly two weeks since a new "right to try" bill (AB 1668) passed the California legislature with overwhelming support and was sent to Governor Jerry Brown's desk to be signed. Thus far, he has not signed it, which is good, but neither have I seen a story that he has vetoed it either. In the meantime I learned some more about a federal version of the bill, which I will discuss after a brief recap of why right-to-try is such bad policy, which will lead into a discussion of the federal bill.

For those unfamiliar with right-to-try, such bills claim to allow terminally ill (or, in some states, "seriously ill") patients to bypass the FDA and receive potentially promising new experimental drugs that have passed phase I clinical trials and are still being tested in phase II or III clinical trials. I've discussed in detail why such "Dallas Buyers Club" laws are a cruel sham that is unlikely to help terminally ill patients and in the process strip patients of critical protections, such as the right to sue the recommending physician for malpractice or the company for negligence, and in some cases insurance coverage and access to hospice care. Worse, in some cases such laws leave the field open to quacks like Stanislaw Burzynski to use right-to-try to bypass the FDA. Basically, right-to-try is really right-to-buy. If you have a lot of money or can raise a lot of money, you can potentially access it. If you don't and can't, tough luck. Basically, as I've discussed so many times before, you have to remember that the function of right-to-try was never to actually help patients. Right-to-try was the brainchild of the libertarian Goldwater Institute, whose interest is far more in weakening and ultimately neutering the FDA, so that patients can be left to the tender mercies of the free market, which libertarians are deluded enough to believe can do a much better job of ensuring patient safety and drug efficacy than any government regulations. (Seriously, libertarians not infrequently falsely argue that the FDA is killing people by being so slow at approving drugs. I guess they forgot the time before the Food, Drug, and Cosmetics Act. Certainly they forgot the potential harms to patients whose desperation they enlisted to turn right-to-try into a cause few politicians can afford to be seen opposing.

Be that as it may, as you recall, at the time I pointed out that, although Gov. Brown had vetoed a prior version of this bill last fall, this time he might sign it. The reason is that his rationale for vetoing the bill last year was that he wanted to wait and see how well reforms of the Expanded Access/Compassionate Use program worked out. Although I argued that in fact the reforms have been quite successful thus far, for right-to-try advocates, anything short of allowing terminally ill patients unfettered access to experimental drugs. Again, remember, the real driving force behind right-to-try is to neuter the FDA; so expanding access to experimental therapeutics through the FDA just won't do, because the FDA would then still remain the primary determiner of what drugs are approved and who can get experimental drugs. If you don't believe me, ask the Goldwater Institute if any patients have managed to receive experimental therapeutics through right-to-try over the last two and a half years since the first such laws were passed. They'll tell you they're aware of 40 patients but will assiduously decline to provide any more information, as I found out when I took to Twitter to ask for more. In comparison, since 2009, the FDA has granted between 936 and 1,873 Expanded Access requests a year and approves the overwhelming majority of requests, including a 300% increase in emergency INDs, which are requests for single patients who don't have time to complete the regulatory paperwork. Right-to-try, even if it works as the Goldwater Institute claims it wants it to, is having a negligible effect compared to the FDA's already existing policies—just as I've told you it would many times.

Besides undermining the authority of the FDA, another purpose of state level right-to-try laws is to build pressure for a federal law weakening the FDA, and to provide a pretext for lawsuits designed to challenge the FDA's authority to regulate drugs. As Alice Bateman-House puts it:

@gorskon Yes but I'm afraid much more support now. Goldwater's playbook was get laws in at least 25 states & then claim mandate for fed law

— Alison Bateman-House (@ABatemanHouse) August 24, 2016

Unlike the case at the state level, the Goldwater Institute and right-to-try advocates have had a harder time achieving their aims at the federal level. For example, when right-to-try laws were first starting to be passed at the state level, the Compassionate Freedom of Choice Act of 2014 was introduced. It was basically a quack manifesto, and fortunately it didn't go anywhere. Of course, the Goldwater Institute's intent had been the long game all along. So it's not surprising that another federal bill has been introduced:

A bill introduced in the US Senate on Tuesday becomes the latest legislative effort to expand the ability of terminally ill patients to gain access to experimental medicines. The legislation, which joins a companion bill that was introduced in the House last summer, would prohibit the federal government, including the US Food and Drug Administration, from taking any action to prevent patient access.

The bill, which was introduced by Senator Ron Johnson (R-Wis.), comes after 28 states have passed so-called "Right to Try" laws. These allow patients to leapfrog a drug-development process that takes years before new treatments become available. And the laws reflect rising frustration with an FDA program called expanded access, in which people who are seriously ill can obtain a drug under development, even though they aren't enrolled in a clinical trial.

This story is from May; since then three more states have passed right-to-try, to bring the total number of states with such laws to 31. The federal bill, submitted to the Senate, is S.2912, The Trickett Wendler Right to Try Act of 2016. Fortunately, thus far the bill has been languishing in the US Senate Committee on Health, Education, Labor, and Pensions, as its companion bill, H.R.3012, The Right To Try Act of 2015 has been languishing in the relevant House committee since last summer. Given that this is an election year and not much of anything is happening legislatively (heck, Congress can't even seem to pass a budget), this bill is unlikely to pass this Congress, but it's not hard to imagine its being introduced next year, with much more support. Let's take a look at what it does.

I'm not a lawyer, as we say, but this law is clear enough that I understand what it could do. First, it explicitly states that state right-to-try laws trump the Federal Food, Drug, and Cosmetic Act and the Controlled Substances Act:

(a) IN GENERAL.—Notwithstanding the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.), the Controlled Substances Act (21 U.S.C. 801 et seq.), and any other provision of Federal law, the Federal Government shall not take any action to prohibit or restrict—

(1) the production, manufacture, distribution, prescribing, or dispensing of an experimental drug, biological product, or device that—

(A) is intended to treat a patient who has been diagnosed with a terminal illness; and
(B) is authorized by, and in accordance with, State law; and

(2) the possession or use of an experimental drug, biological product, or device—
(A) that is described in subparagraphs (A) and (B) of paragraph (1); and
(B) for which the patient has received a certification from a physician, who is in good standing with the physician's certifying organization or board, that the patient has exhausted, or otherwise does not meet qualifying criteria to receive, any other available treatment options.

In other words, this bill, if passed, would explicitly federalize each state's right-to-try law, in the process eliminating the FDA's ability to protect terminally ill patients from what could be dangerous or inappropriate drugs. Worse, it trusts the states not to produce right-to-try laws that are too dangerous, the sole exception is that it requires that the illness being treated be "terminal." The problem, of course, is that this bill does not define "terminal."

Next up:

(1) NO LIABILITY.—Notwithstanding any other provision of law, no liability shall lie against a producer, manufacturer, distributor, prescriber, dispenser, possessor, or user of an experimental drug, biological product, or device for the production, manufacture, distribution, prescribing, dispensing, possession, or use of an experimental drug, biological product, or device that is in compliance with subsection (a).

This clause basically removes federal liability from physicians and drug companies that offer a drug under right-to-try. If a patient suffers because of the inappropriate use of such a drug, the patient (or, given that the patients under this bill have terminal illnesses, the family) has no recourse to sue the manufacturer under federal law, in addition to having no recourse under state law. Add to that the lack of oversight by an IRB, and this law is profoundly anti-patient—just like state right-to-try laws.

Finally:

(2) NO USE OF OUTCOMES.—Notwithstanding any other provision of law, the outcome of any production, manufacture, distribution, prescribing, dispensing, possession, or use of an experimental drug, biological product, or device that was done in compliance with subsection (a) shall not be used by a Federal agency reviewing the experimental drug, biological product, or device to delay or otherwise adversely impact review or approval of such experimental drug, biological product, or device.

This clause is clearly intended to address the concern of drug and device manufacturers that if they provide an experimental therapeutic to a patient under right-to-try and the patient suffers complications due to the treatment, the approval of its product might well be jeopardized. This, of course, is not an unreasonable concern on the part of manufacturers, given that it can easily cost $1 billion to bring a drug or device to market, and by the time the product has passed phase I clinical trials a great deal of that cost has already been invested in development. However, this clause goes way too far. Basically, it says that even if a patient death is clearly due to use of an experimental drug under right-to-try, that death should not be considered by the FDA in deciding whether to approve the drug. Think of it this way. Let's say dozens of patients die from using an experimental drug under right-to-try. This bill, if passed, would bar the FDA from even considering those deaths during its deliberations regarding whether to approve the drug for marketing or not.

Basically, the Trickett Wendler Right to Try Act of 2016 would not help terminally patients. It would endanger them. Proponents often ask, "What does a terminally ill patient have to lose?" The answers are simple. They can lose money, perhaps their life savings, given that accessing right-to-try could easily cost tens or hundreds of thousands of dollars. That's because, when you come right down to it, "right to try" is a misnomer. It's really "right to buy." If you're terminally ill and don't have the money or the means to raise it, right-to-try will not help you. Worse, thanks to right-to-try, terminally ill patients can lose some of their precious quality time remaining with their loved ones if they suffer complications that place them in a hospital or prematurely kill them.

The California right-to-try bill being considered by Gov. Jerry Brown and the Trickett Wendler Right to Try Act of 2016, like all of the other right-to-try laws based on the Goldwater Institute template and passed by other states, are profoundly anti-patient. Like the equally ill-advised 21st Century Cures Act, right-to-try bills are based on the delusion that there are oodles and oodles of cures for deadly diseases out there that could save thousands of lives if only the evil government and FDA would step aside and get out of the way of the free market. I say "delusion" because the FDA, despite being underfunded, is actually pretty efficient at new drug approvals, evaluating nearly all new drug applications within 6 to 10 months, an impressive turnaround for such complex assessments. Indeed, the FDA actually acts more rapidly than its European counterparts approving new drugs. Basically, there is no evidence that the FDA hampers overall medical innovation, nor is there evidence that the FDA's current requirements lead to higher drug prices or cost lives.

None of this is to say that the FDA is perfect. Far from it. Certainly there is a discussion to be had about how, in the case of desperate patients with terminal illnesses, we as a society should balance individual rights versus risk/benefit considerations in making decisions about how freely we allow experimental therapeutics to be used to try to save these patients. It's not as though we haven't had this discussion before, either. We had it in the 1980s during the AIDS epidemic, and we've periodically revisited it since then. This is another such time, and the FDA has actually responded by vastly simplifying its procedure for granting Expanded Access, and the vast majority of such requests are granted.

It must be reiterated that, as much as right-to-try is enormously popular because no one wants to deny a terminally ill patients his or her "last chance," the purpose of right-to-try was never to help terminally ill patients. There is no evidence, at least none that the Goldwater Institute has yet produced or that I've been able to find anywhere, that right-to-try has not, as far as I've yet been able to ascertain, allowed a single terminally ill patient to access an experimental drug or helped him or her to live longer, much less that it has saved a single life. (True, I have found one possible patient who might be receiving treatment under right-to-try, but I need to look into the case more before I feel comfortable blogging about it.) Unfortunately, right-to-try has been a cynically successful strategy to weaponize sympathetic patients and basic human empathy for patients facing imminent death to attack and ultimately greatly weaken the FDA.

oracknows Mon, 09/05/2016 - 21:00

Tags

Trickett Wendler Right to Try Act of 2016

http://arstechnica.com/science/2016/09/new-opioid-douses-pain-without-b…

Categories

Policy

The wording of the bill is so transparent that it is hard to see how anybody could fail to see its intent.

Remind me again how its skeptics who are pursuing an industry-driven agenda?

If anything should be able to kill these bills, it should be the "No liability" and "No outcomes" clauses. And yet, we see incredible myopia on the part of legislatures.

@ 2 Todd W.

I'm relatively okay with the no liability clause. It's a bit like the MS study at the Ottawa Hospital where the consent form was described along the lines of "every second paragraph said that this treatment may kill you ".

The "No outcomes" clause is clearly insane. Whom the gods ...

And the rest of the world is going to have to figure out a way to monitor these instances as presumably CDC or FDA or whoever will not be doing so.

@jrkrideau

My problem with the no liability clause is that even if the manufacturer knows that the risks of the product outweigh any potential benefits, and fails to disclose that to the patient, the patient or their family has no legal recourse available to them. They cannot sue the manufacturer for damages. So even the libertarian's answer to everything, lawsuits, can't be used to correct the situation.

@Todd: Not only are there risks, but the law is designed to stop the manufacturer from ever having to declare what those risks are. They can continue to lie about the risks and the one agency tasked with assessing how accurate such claims are, will be prevented, by law, from doing so.

I want to know who drafted this bullshit. The most evil pharma corporate exec in the world would sure not be this brazen. Only quacks would do this. I suspect chronic lyme charlatans, personally.

I’m relatively okay with the no liability clause. It’s a bit like the MS study at the Ottawa Hospital where the consent form was described along the lines of “every second paragraph said that this treatment may kill you “.

It's one thing to waive liability in the context of informed consent. The patient is told that the treatment is experimental and has certain risks. Likewise, if I go cross-country skiing on trails for which I am expected to pay a trail fee, I have to sign a piece of paper saying that I know that skiing is inherently dangerous and if I get hurt, it's not the ski area's fault. But that usually only applies to risks that a patient or a skier can reasonably foresee. If there are dangers that the company running the drug trial knows about but didn't disclose, or the ski area puts a novice rating on a trail that should have been marked as a double-diamond run, the patient or skier may have recourse. RTT laws eliminate that possibility.

God knows what happens to clinical trials in the midst of that kind of free for all. They'd be be pretty much screwed, I guess.

Certainly we know that, in placebo controlled trials, participants often get tested to see if they're on placebo, and many lie about what they're taking on the side.

And the way recruitment of treatment-naive participants would dry up means it would be hard to mount them in any kind of timely manner.

Hell, I guess you'd just have to let people take whatever they want. As was said back in the days of high dose AZT in the 1980s: "they're gonna die anyway."

So even the libertarian’s answer to everything, lawsuits, can’t be used to correct the situation.

Funny how libertarians always say that product liability suits will keep the free market "honest" but then always seem to oppose laws that make suing easier and support policies that make it harder for consumers to sue manufacturers. Yes, funny that.

What if the last clause (no use of outcomes) got reversed, and there was instead an obligation to disclose and publish every treatment with experimental drugs, with the name of the person/clinic that prescribing treatment, the name of the substance, the manufacturer, the expected outcome and the actual outcome?

@VDG: That's only a slight improvement. Yes, we'd know about adverse outcomes. But anybody who was taking an experimental medication under a RTT regime is unlikely to be following a rigorously controlled regime, so all you would get out of this is anecdata. That may be of some use to fans of so-called pragmatic trials, but our host is on record as opposing pragmatic trials, for reasons I generally agree with (to the extent a non-expert like me is entitled to an opinion).

So, to someone like me, the answer to fixing the FDA is somewhat obvious. Instead of hamstringing them and then complaining about the poor job they do ( which is the libertarian MO but leaving that aside) they should put more money in to hire more people and increase efficiency. Only makes sense to me.

Besides, that way the FDA becomes a job creator.

Here's an open letter I wrote a couple years ago, when there were only 5 states with RTT laws on the books.

Brian Deer reminds me of another possible negative outcome of this sort of Federal legislation: creating a disincentive for completing clinical trials to get FDA approval. After all, clinical trials are freakin' expensive. If you can sell your product without having to go through the rigors of phase 2 and 3 trials, why bother? Especially since under RTT you could actually charge patients for the product, rather than the more ethical and usual practice of providing the experimental treatment for free. While the bill would require the product to be in trials, there is no requirement that those trials actually need to progress. So you could have people like Burzynski who register their trials, then let them just sit open for decades with no end in sight.

Todd W:
"After all, clinical trials are freakin’ expensive. If you can sell your product without having to go through the rigors of phase 2 and 3 trials, why bother? "

Bingo. Especially with the undefined "terminal" qualifier, which I could easily see being the target of later right-to-try legislation, softening it under the guise of "what's the harm?" combined with freedom of choice.

Well it seems clear that this draft is bad. But the idea isn't to me, we should be at least coming up with an alternative that could work and was fair.

What about incorporating it in with the clinical trials, once people get diagnosed as terminal, offer them 3-5 different experimental treatments. The companies get cost of materials only, capped at $500, it's a non profit obligation, call it Phase 1b or 2b. Limit it to a one year window per treatment to limit abuse from both sides. EVERYTHING gets reported, though allow patients to mix and match, that might still be interesting data. For actual clinical trials people get treated for free, though the government should part subsidise this part of the trial.

Actually I forgot, I wrote the above based on the UK's National Health Service, with all this being free to the end user.

But maybe if it was capped at something reasonable, it could help drive some of the outrageous prices down.

I read a great Science Fiction series once that opined that the government should maintain a nationalised industry in every endeavour to prevent private business from mischief, like monopolies, overcharging and bad worker treatment.

Nationalize "Right to Try"!

@Jay

We already have an alternative to the RTT laws that are popping up: the FDA expanded use and compassionate use regulations.

The FDA does everything these laws propose to do with the following benefits: data must be gathered from these one-off uses to factor into the risk-benefit analysis; charging patients for the "privilege" of being guinea pigs must be reasonable and justifiable (and more of an exception than the rule); manufacturers, etc. can still be sued if they engage in malfeasance.

the Controlled Substances Act

That one needs abolishing. It certainly is a boon to somebody with all the 'no studies to show'.

First cannabis and now kratom. The ban on kratom, which alleviates pain and staves off opiod withdrawl comes concurrent with a cracking down on pain meds. So now there will be buprenorphine and, ohh, maybe

BU08028 was able to alleviate pain in a dozen monkeys just as well as other opioid painkillers, such as morphine. Yet, unlike every other opioid drug, BU08028 showed no signs of being addictive.

Mmm, mmm. I'll bet it will be real expensive to.

Oh my gilbert wants to abolish the controlled substances act.
Quelle surprise!!

Thanks Todd, please pardon my British ignorance. So this Bill is double useless for actual patience then,

To continue..

, so glad we have the NHS.

So, time for another letter to my senator (who happens to be the ranking member on this committee)?

Something along the lines of "This bill will kill patients, and destroy the biotech industry. Please vote no, and let all the researchers, clinicians and biotech/pharma workers keep working to ethically provide treatments that work."

@Jay

No worries. There's a lot of similarity between this bill and the Saatchi bill, since you mention Britain.

@VDG #9: An outcomes clause would be useful for determining the who is using total quack therapies under "right to try" like those of Burzynski ( that is assuming Burzynski actually reported it , given how little of anything he reports.)

@Todd #21

Luckily for Britain, by the time the "Saatchi" bill passed, it had been so modified that it no longer had any practical provisions. See here:
http://www.quackometer.net/blog/2016/03/the-saatchi-bill-when-only-the-…

@DrBollocks

Thanks for sharing that. I hadn't really followed it too much after its first death. While I'm glad to see that Saatchi's original provisions completely and utterly failed, as they should have, what a colossal waste of time!

I won't comment too much on this specific legislation, INAL, I certainly support concepts for individuals (with friends and family) to try to save themselves, without necessarily giving Merck, Pfizer, Roche, et al a free pass for a new blockbuster like Vioxx, with their New Drug Entities.

However,
...for which the patient has received a certification from a physician, ..., that the patient has exhausted, or otherwise does not meet qualifying criteria to receive, any other available treatment options... is actually over restrictive to my eyes.

The time to start if you have advanced therapies is much sooner, not later. Clinical medicine lags many years behind the literature for various low risk opportunities that seem to work fine in aggregate, just not as a single magic bullet.
-----
The FDA should not be allowed to criminalize seriously ill individuals or their families for getting important medicines overseas. Right now, bringing in approved cancer medicines from overseas is a crime, subject to immediate seizure at anytime while in the US, even if fatal. FDA and ICE merely have a policy of "forebearance" for your "crimes".

My "science project" has more than triple the maximal OS estimate from an MD Anderson oncologist and over 4x the normal OS average, using drug and therapies not commercially available in the US. Also, I will note the maximal OS examples that I have tracked down, either had "whimpy biomarkers" or massive immunological events e.g. Coley's examples. Neither apply.

So I think many views here are ill informed and dangerous to me and mine.

people claim to use the plant as a sort of herbal Suboxone to treat their chronic pain or opioid addiction....

After three years’ worth of research, Majumdar thinks Kratom might be the most promising opioid alternative we’ve got...

"Frankly, a lot of the Controlled Substances Act just doesn’t seem to be well-thought-out,”...

That such a drug could one day hold the key to ending opioid addiction probably never occurred to President Nixon when he signed the act. That signature marked the dawn of the modern drug war

http://www.slate.com/articles/health_and_science/medical_examiner/2016/…

the DEA noted that there have been 15 deaths linked to kratom since 2014. "[The decision is] based on evidence that we’ve collected from the medical and scientific community throughout the world in terms of deaths associated with kratom,"

Fifteen deaths world wide vs:

America faces an opioid crisis: 78 people die daily of overdoses

http://www.theverge.com/2016/9/22/13003014/kratom-opioid-ban-dea-schedu…

Why are they doing this?

So why would the DEA worry about a beneficial plant that is pretty much harmless? The answer is quite clear — Big Pharma.

Cannabis is a schedule one substance but the pharmaceutical industry can manufacture a synthetic version of the same active ingredient in cannabis, THC, and it magically becomes legal.

Currently, the pharmaceutical industry is using kratom alkaloids to manufacture synthetic opioids.

As Cassius Kamarampi points out, three synthetic opioids, in particular, were synthesized from the alkaloids in kratom from 2008- 2016: MGM-9, MGM-15, and MGM-16.

They were synthesized from kratom’s alkaloids Mitragynine and 7-Hydroxymitragynine: to make what is essentially patentable, pharmaceutical kratom.

http://thefreethoughtproject.com/pharma-kratom-dea-patent/

Interesting to note that although Kratom contains dozens of active alkaloids the DEA is only addressing two of them with this emergency action. The very two alkaloids that are used to make this new patentable pharmaceutical drug (trial drug name MGM-16)...

The DEA is preparing the US market for this new drug by outlawing the very plant material it is being synthesized from. Because of this there will be thousands of people with medical ailments in the USA unexpectedly forced off there medicine at the end of this month...

Chuck Rosenberg (Head of the DEA) just very recently used work for Hogan & Hartson which lobby's for the pharmaceutical industry. Hogan & Hartson's big Pharma client list includes Johnson & Johnson, PhRMA and Glaxo Wellcome. The Janssen Pharmaceutical company (Division of J&J) is in the process of creating a synesthetic version of Kratom. The principal scientist for PZM21 (Henry Lin) works for Janssen Pharmaceuticals and also received a pre-doctoral fellowship from the PhRMA foundation.. which again are both clients of Hogan & Hartson

https://board.freedomainradio.com/topic/48199-kratom-and-dea-militarize…

Chuck Rosenberg is a fuckbag^2

Systemic administration of MGM-16 produced antinociceptive effects in a mouse acute pain model and antiallodynic effects in a chronic pain model. The antinociceptive effect of MGM-16 was approximately 240 times more potent than that of morphine in a mouse tail-flick test, and its antiallodynic effect was approximately 100 times more potent than that of gabapentin in partial sciatic nerve-ligated mice

http://jpet.aspetjournals.org/content/348/3/383.full

Why are they doing this?

So why would the DEA worry about a beneficial plant that is pretty much harmless? The answer is quite clear — Big Pharma.

Cannabis is a schedule one substance but the pharmaceutical industry can manufacture a synthetic version of the same active ingredient in cannabis, THC, and it magically becomes legal.

Currently, the pharmaceutical industry is using kratom alkaloids to manufacture synthetic opioids.

As Cassius Kamarampi points out, three synthetic opioids, in particular, were synthesized from the alkaloids in kratom from 2008- 2016: MGM-9, MGM-15, and MGM-16.

They were synthesized from kratom’s alkaloids Mitragynine and 7-Hydroxymitragynine: to make what is essentially patentable, pharmaceutical kratom.

http://thefreethoughtproject.com/pharma-kratom-dea-patent/

Interesting to note that although Kratom contains dozens of active alkaloids the DEA is only addressing two of them with this emergency action. The very two alkaloids that are used to make this new patentable pharmaceutical drug (trial drug name MGM-16)...

The DEA is preparing the US market for this new drug by outlawing the very plant material it is being synthesized from. Because of this there will be thousands of people with medical ailments in the USA unexpectedly forced off there medicine at the end of this month...

Chuck Rosenberg (Head of the DEA) just very recently used work for Hogan & Hartson which lobby's for the pharmaceutical industry. Hogan & Hartson's big Pharma client list includes Johnson & Johnson, PhRMA and Glaxo Wellcome. The Janssen Pharmaceutical company (Division of J&J) is in the process of creating a synesthetic version of Kratom. The principal scientist for PZM21 (Henry Lin) works for Janssen Pharmaceuticals and also received a pre-doctoral fellowship from the PhRMA foundation.. which again are both clients of Hogan & Hartson

https://board.freedomainradio.com/topic/48199-kratom-and-dea-militarize…

Chuck Rosenberg is a really swell guy.

Like the poorly-made Walmart key breaking off in the lock, This is what happens when one fakes nature for a patent instead of allowing one to use something perfectly safe they can grow in the back yard:

Six men were hospitalized — and one of them was pronounced brain-dead — after a drug trial in northwestern France, the country’s health minister said on Friday...

The drug is intended to help with mood, anxiety and motor problems linked to neurodegenerative diseases by having an effect on the endocannabinoid system

http://www.nytimes.com/2016/01/16/world/europe/french-drug-trial-hospit…

The same kind of thing happens with 'K2' or 'spice', synthetic thc. There is a natural alternative which already works. Sick. Greedy sick peddlers.

But Krypton isn't straight kratom -- it was adulterated with O-Desmethyltramadol, a more intense version of the painkiller Tramadol. See, this is where things get complicated. ...

So yes, in a perfect world, there would be some middle ground between "SWAT team kicks down your door" and "a totally unregulated market in which the seller might be a front for the Russian mafia selling you the ashes of a murdered informant." This is not a perfect world -- right now, kratom is regulated as a "dietary supplement," which is the same classification as the silver people keep shooting up their butts until they turn blue...

Dr. Grundmann told me that the medical kratom advocates he's spoken with very much wanted some regulation -- you'd think there'd be plenty of ground for compromise. But the DEA isn't allowed to compromise, because somewhere along the line, we decided our law enforcement agencies should have more rigid programming than the goddamn Terminator...

Of course, the DEA argues that regulation is absolutely a possibility. That's why this is only a temporary scheduling -- to give scientists time to study it...It's the same "criminalize until we are 100 percent sure it's safer than oatmeal" attitude that has been stuffing the prisons with drug offenders for about a century now...

Baer was adamant that kratom's scheduling would have no impact on research into the drug. "We're trying to remove roadblocks. We did it in the case with marijuana, and we're encouraging the scientific medical community to apply for research registrations to move the ball forward." ...

In fact, the U.S. government has a long tradition of banning drugs and setting back research by decades.

http://www.cracked.com/personal-experiences-2391-how-kratom-became-next…

http://www.painnewsnetwork.org/stories/2016/9/28/an-open-letter-to-dea-…

It is disgusting. Wikipedia locked the page after the DEA deflowering/raping.

compare and contrast

kratom poses a risk of illness or injury, stating that "[C]onsumption of kratom can lead to a number of health impacts, including respiratory depression**, ...
https://en.wikipedia.org/wiki/Mitragyna_speciosa

Especially missing is a recant of the history:

In 2010, the Thai Office of the Narcotics Control Board proposed decriminalizing kratom and affirmed its use as an integral part of Thai culture. The ONCB concluded that decades of non-problematic use, and an absence of health and social harm, make prohibiting the leaf unnecessary and counterproductive. According to the ONCB's report, kratom was in fact banned for economic reasons, not for health or social concerns. The Transnational Institute stated:

In Thailand, kratom was first scheduled for control in 1943 under the Kratom Act. At the time, the government was levying taxes from users and shops involved in the opium trade. Because of the increasing opium costs, many users were switching to kratom to manage their withdrawal symptoms. However, the launch of the Greater East Asia War in 1942 and declining revenues from the opium trade pushed the Thai government into action to curb and suppress competition in the opium market by making kratom illegal.

https://en.wikipedia.org/w/index.php?title=Mitragyna_speciosa&oldid=732…

So here we are again. There is an opiate epidemic in america killing upwards of 130 a day. It wouldn't be prudent for the explosive popularity of kratom to cut into that fine flower in the big pharma hat. It is more effective for pain than the addictive 'legal' (save for a prescription wall) alternatives. Sick Sick Sick.

** An absolute lie. That is the beauty of it; Managing pain without the risk of taking a break from breathing.

Kruegel said mitragynine and 7-hydroxymitragynine preliminarily appear "similar in terms of pharmacology" to a drug called Oliceridine that is undergoing Food and Drug Administration-approved Phase III trials in humans – something that fuels kratom advocate claims that corporations simply want to ban a natural rival.

http://www.usnews.com/news/articles/2016-09-30/kratom-will-remain-legal…

http://www.trevena.com/news-details.php?id=147

Same ol', same ol'.

"The research indicates that this is a pretty mild substance," he said. "Criminalizing kratom use is insane to me."

https://www.washingtonpost.com/news/wonk/wp/2016/09/15/the-dea-wants-to…

Many Kratom products are spiked with caffeine, Tramadol (a synthetic opioid pain medication) or other pharmaceuticals. Ironically, the greatest danger of Kratom these days is from fake products contaminated with substances approved by the FDA.

Kratom’s image has suffered from the unregulated distribution of dubious materials that are advertised as Kratom.

http://www.alternet.org/drugs/kratom-cbd-opioids

As of May 10, 2016 SB226 makes kratom a schedule 1 controlled substance in Alabama.

There has been an explosive increase of the rate of overdoses from heroin, fentanyl, and prescription opiates since the ban went into effect -- Extrapolating from just this one county in Alabama, I predict an increase from 129 deaths per day nationwide to 300-500 deaths per day (It is hard to know how many have been using kratom to supplant heroin and pharma) starting in a month, or so -- Heckuvajob Rosenburg.

Though the DEA ban is not in effect yet, the threat of it has haulted commerce in kratom. While many have 'stocked up' for a month to a year, It's still a good bet to set the watch for today being the start of the pharma-induced (Rosenburg was a lobbyist for drug companies) apocolypse.

between the first day of this year to June 30th, 103 people have died from overdosing on heroin (46) and fentanyl (34). Some even died from overdosing on both at the same time. 11 were from prescription opioids. The leftover cases are still going through toxicology...

There were only three drug-related deaths the first five months of this year, which made us hopeful that there might be a decrease for 2016.

http://thealternativeexaminer.com/lawmakers-alabama-cost-citizens-lives/

Birmingham Fire and Rescue Service responded to 101 overdoses last month alone, said Capt. Bryan Harrell. That was up significantly from 56 in May and 47 in April. Countywide, there were 25 overdose deaths – 11 from heroin and 14 from Fentanyl – in June 2016.

http://www.kratomliteracyproject.com/2016/07/drug-policy/

While the DEA is autonomous with there asshattery, Congress can defund them:

https://petitions.whitehouse.gov/petition/remove-federal-funding-dea

The cruel sham that is "right-to-try" has returned to California

oracknows — Wed, 24 Aug 2016 03:00:02 +0000

The cruel sham that is "right-to-try" has returned to California

Here we go again.

Remember how I frequently say that naturopaths are relentless, how, whenever they attempt to get a naturopathic licensing bill passed in a state and fail, they’re soon back to try again. Basically, they keep trying until they succeed, and once they succeed, it’s game over for keeping their quackery from having the imprimatur of the state. Perhaps my favorite metaphor for this is that of the killer in a 1980s slasher flick, like Jason or Michael Myers, who frequently "dies" ta the end of one movie, only to come back the next movie to mow down another bunch of hapless teens. The difference, of course, is that right-to-try bills rarely die; most of them pass.

It turns out that advocates of “right-to-try” laws are a lot like that. Right-to-try laws have been proliferating with kudzu throughout the US since 2014. It’s not surprising, as you will see. They give the illusion of helping terminally ill patients, and voting for them lets legislators feel good about themselves without actually confronting hard choices, not to mention to appear to be doing something helpful when they are not. So I wasn’t surprised to learn that, after Governor Jerry Brown did the right thing and vetoed a right-to-try bill in California last fall, a new bill appears on the verge of finding its way to his desk again, with its supporters hoping that this time will be different, that this time Gov. Brown will sign the bill. They might be right. The rationale Gov. Brown used when vetoing the bill was that he wanted to given the FDA an opportunity to reform its Compassionate Use program as it has been doing.

It’s been a while since I’ve written about “right-to-try.” In fact, the last post about it appears to be the one I wrote praising Gov. Brown’s veto (time flies!), noting that he was the only Governor thus far with the courage to veto this ill-advised bill. In any case, right-to-try is a a movement started a couple of years ago by the libertarian Goldwater Institute, ostensibly to let terminally ill patients try experimental treatments without interference from the FDA. In reality, right-to-try is a cruel sham. Such laws give the illusion of providing potential cures to desperately ill and dying patients in the form of experimental drugs when in reality it does nothing of the sort, raising the hopes of the patients rallying to persuade their lawmakers to pass these laws and then basically doing nothing for them.

There are several reasons why right-to-try laws are a cruel sham. The first thing you should know about them, though, is that they all follow the same basic template originated by the Goldwater Institute. Next, states do not have authority over drug approval. The FDA does, and federal law and regulations trump state law. It’s also incredibly rare that an experimental drug will make the difference between life and death in a terminally ill patients. Yet it is that hope that supporters of right-to-try laws, in particular the Goldwater Institute, have shamelessly exploited to persuade legislators to pass these laws all over the nation. Worse, the requirements are risibly low and betray a total lack of understanding of how drug development works in that they only require that the experimental drug (1) have passed phase I trials and (2) still be in clinical trials. Of course, phase I trials are not designed to test efficacy. Their purpose is to work out optimal dosage, identify the maximal tolerated dose, and identify major side effects. Worse, they usually only consist of a few tens of patients, often less than 30. To propose letting seriously ill patients drugs that have been tested in so few people and not demonstrated to be efficacious and safe is to invite disaster. Finally, consistent with their libertarian origin, right-to-try laws provide no financial support for patients, who are basically on their own when it comes to paying what can be the substantial financial charges. They also strip away patient protections, making it virtually impossible for a patient injured using such a drug to sue either the drug company or the physician administering the drug. Finally, given that the FDA, not the states, controls drug approval, drug companies will be highly reluctant to offer such drugs without the approval of the FDA, and the FDA already has programs for single patient INDs, also known as compassionate use, to allow patients access to experimental drugs.

I once challenged the Goldwater Institute and right-to-try supporters to produce a single example of a terminally ill patient who had benefitted from right-to try or who had even been granted access to an experimental drug, basing my challenge on the case of Bob Bardone, who had amyotrophic lateral sclerosis, a fatal degenerative neurological disease also known as Lou Gehrig’s disease. This was a man who moved to Missouri because of its right-to-try law, hoping to gain access to experimental therapies. He didn’t. I did a bit of Googling to see if in the interim there had been any patients who received experimental medication under right-to-try. I couldn’t find any. Maybe I’ll Tweet at the Goldwater Institute’s flacks again and see if they can provide me with an example. The last time I did that, the excuse was that the laws were new. They’re not so new any more. It’s been two and a half years since the first one was passed. There are now 30 of them or so. That excuse won’t fly any more. In reality, the purpose of right-to-try laws is to undermine the authority of the FDA, build pressure for a federal law weakening the FDA, and to provide a pretext for lawsuits designed to challenge the FDA’s authority to regulate drugs. Oh, and to stoke hostility directed at the FDA. That’s very important to the Goldwater Institute.

In any event, I was surprised to note that I haven’t written a post that is primarily about “right to try” laws in 2016. It’s been almost a year since I discussed the issue. So now is as good a time as any, and the progress of the California law is as good an excuse as any to write about this scam again. So let’s circle back to what’s happening in California:

A bill that would allow terminally ill people to obtain experimental drugs appears headed to Governor Brown's desk for the second year in a row. Brown vetoed a similar measure last year, but supporters believe conditions are right for him to sign it this time around.

Brown said he vetoed last year’s "Right-to-Try" measure because he wanted time to see how changes to the FDA’s "Compassionate Use" program streamlined the process of getting experimental drugs to terminal patients.

Nearly a year later, the new bill’s supporters say it's time for California to step in with its own solution, because the modified federal initiative has not reduced the minimum 30-day wait for drugs.

"The process may have to start over if the FDA has even one question," said the bill's author, Assembly Majority Leader Ian Calderon (D-Whittier). "Terminally ill patients can still end up waiting weeks and months" for an approval.

Calderon's measure would allow drug manufacturers to give certain terminally ill people access to drugs not yet approved by the FDA.

Let’s take a look at the bill, AB-1668 Investigational drugs, biological products, and devices. Reading it over, I see that it’s the same old nonsense, except that it goes even further than a typical right-to-try law. For example, look at the definition of “eligible patient” for right-to-try in AB 1668:

(b) “Eligible patient” means a person who meets all of the following conditions:

(1) Has an immediately life-threatening disease or condition.

(2) Has considered all other treatment options currently approved by the United States Food and Drug Administration.

(3) Has not been accepted to participate in the nearest clinical trial to his or her home for the immediately life-threatening disease or condition identified in paragraph (1) within one week of completion of the clinical trial application process, or, in the treating physician’s medical judgment, it is unreasonable for the patient to participate in that clinical trial due to the patient’s current condition and stage of disease.

(4) Has received a recommendation from his or her primary physician and a consulting physician for an investigational drug, biological product, or device.

(5) Has given written informed consent for the use of the investigational drug, biological product, or device, or, if he or she lacks the capacity to consent, his or her legally authorized representative has given written informed consent on his or her behalf.

(6) Has documentation from his or her primary physician and a consulting physician attesting that the patient has met the requirements of this subdivision.

“Immediately life-threatening disease or condition”? That’s incredibly broad. A severe case of pneumonia could be “immediately life-threatening.” A heart attack is “immediately life-threatening.” A stroke is “immediately life-threatening.” “Immediately life-threatening” is not the same thing as a terminal illness. Yet this bill tries to have it both ways, as it defines “immediately life-threatening disease or condition” as “a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months.” That implies something less acute, but “within a matter of months” encompasses more immediately life-threatening diseases as well. Basically, the definition is the very definition of vague double talk that would likely result in court battles over interpretation if anyone ever actually tried to invoke it who didn’t have an undeniable terminal illness. Maybe that was the intention. In any case, this bill, if passed, would be far broader than most of the ones I’ve reviewed.

Consistent with the libertarian origins of the bill, AB 1688 doens’t do what we in the biz call jack shit to help terminally ill patients access experimental drugs. Check it out:

11548.2. (a) Notwithstanding Section 110280, 111520, or 111550, a manufacturer of an investigational drug, biological product, or device may make available the manufacturer’s investigational drug, biological product, or device to an eligible patient pursuant to this article. This article does not require that a manufacturer make available an investigational drug, biological product, or device to an eligible patient.

(b) A manufacturer may do both of the following:

(1) Provide an investigational drug, biological product, or device to an eligible patient without receiving compensation.

(2) Require an eligible patient to pay the costs of, or associated with, the manufacture of the investigational drug, biological product, or device.

(c) (1) This article does not expand the coverage provided under Sections 1370.4 and 1370.6 of this code, Sections 10145.3 and 10145.4 of the Insurance Code, or Sections 14087.11 and 14132.98 of the Welfare and Institutions Code.

(2) This article does not require a health benefit plan to provide coverage for the cost of any investigational drug, biological product, or device, or the costs of services related to the use of an investigational drug, biological product, or device under this article. A health benefit plan may provide coverage for an investigational drug, biological product, or device made available pursuant to this section.

So basically AB 1668 allows drug companies to charge whatever they want for a drug that’s only passed the most basic of basic clinical trials, Phase I. It doesn’t require health plans to cover the charges for these experimental drugs. It doesn’t require state government to cover the costs of right-to-try drugs. It also does this:

111548.3. (a) Notwithstanding any other law, a state regulatory board shall not revoke, fail to renew, or take any other disciplinary action against a physician’s license based on the physician’s recommendation to an eligible patient regarding, or prescription for or treatment with, an investigational drug, biological product, or device if the recommendation or prescription is consistent with protocol approved by the physician’s institutional review board or an accredited independent institutional review board.

And this:

111548.5. This article does not create a private cause of action, and actions taken pursuant to this article shall not serve as a basis for a civil, criminal, or disciplinary claim or cause of action, including, but not limited to, product liability, medical negligence, or wrongful death, against a manufacturer of an investigational drug, biological product, or device, or against any other person or entity involved in the care of an eligible patient for harm done to the eligible patient or his or her heirs resulting from the investigational drug, biological product, or device, or the use or nonuse thereof, if the manufacturer or other person or entity has complied with the terms of this article in relation to the eligible patient, unless there was a failure to exercise reasonable care.

In other words, a doctor who recommends an experimental drug under right-to-try can’t be sued or disciplined by the state medical board. Neither drug manufacturers nor doctors recommending right-to-try drugs can be sued for liability. Basically, this bill is a travesty for patients. Under the guise of providing them access to potentially life-saving drugs (which it doesn’t do), AB 1668 basically puts patients with life-threatening illnesses completely on their own. Not very patient-friendly at all. Basically, it tells patients, “You’re completely on your own.”

Perusing other websites about right-to-try, I found nothing to disabuse me of this conclusion. In fact, looking at the FAQ on the Right-to-Try website, I find the same misinformation and lies about right-to-try that I found two years ago. For example:

Q: SOME CRITICS SAY RIGHT TO TRY IS JUST “FEEL GOOD” LEGISLATION THAT WON’T ACTUALLY HELP ANYONE. IS THIS TRUE?

A: No. Right To Try laws give people with terminal illnesses the legal right to use investigational medications years before they might otherwise be available on the market. No one can guarantee that a particular treatment will be effective, but these laws return choice and control over treatment options to where it is most effective: with patients and their doctors.

Actually, it is true. Right-to-try is just “feel good legislation” that won’t help anyone, much less terminally ill patients. Same as it ever was.

Here’s hoping that Gov. Brown shows the same political courage now that he showed last year when the previous right-to-try bill came across his desk. Contrary to how they are portrayed, right-to-try laws are among the most cynical, patient-hostile laws there are. Under the guise of helping terminally ill patients pursue hope, they strip them of many legal protections, open them up to exploitation by drug companies, and sell them false hope.

And they’re enormously popular because everyone wants to help terminally ill patients and so few patients understand clinical trials and drug development. I don't know if Gov. Brown will have the courage to veto the bill a second time, and, even if he does, it'll be back next year, and the year after that, and eventually a future governor will likely sign it. The sham will continue to deceive patients with terminal illnesses and their families.

oracknows Tue, 08/23/2016 - 23:00

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(2) Has considered all other treatment options currently approved by the United States Food and Drug Administration.

I can envision a woo-prone doctor telling a cancer patient, "You can be cut, you can be poisoned, you can be burned, or you can try this experimental treatment." There. The patient has now "considered" the approved treatment options.

And IANAL. If the wording in the rest of the bill is similarly vague, it ought to be possible for a decent lawyer to find other ways to weasel out of whatever minimal protections remain if it passes.

If I were to run a Phase I trial involving a dozen healthy people and wave my hands* over them to ascertain how much hand-waving would cause them harm, would I then be free in a 'right to try' state to charge tens of thousands of dollars for waving my hands over terminally-ill, desperate and/or woo-credible patients, with no liability?

*Assumes hand-waving counts as a device. If necessary, to fulfil the letter of the law, I'm willing to sellotape a healing crystal to each palm (in the correct orientation, obviously -- I'm not an idiot).

That's a lot of words to complain about something and not offer any suggestions for help.

So I'm puzzled: You don't like these laws because they provide hope to people and dying people shouldn't have hope? Or because that hope has YET to be anything but false hope?

Or is it because the bills are poorly worded?

Or is it because people should not have the opportunity to try alternative paths for their own healthcare?

This blog entry is a perfect example of what's wrong with the Internet. Instead of advocating for something that you truly think will help, you spent all those rambling words complaining about something, offering no solution. You know, like IDENTIFY the problem and then OFFER SOLUTION. Identifying problems is very easy to do, we don't need any more words floating around the Internet that simply identify problems.

Note: Like my comment to you. You won't like reading it, probably. But maybe you'll take it to heart the next time you're compelled to write 1,000 words complaining and save 200 of them for: here's how the bills WOULD help...

All of the above were reasons, plus more that I enumerated. Right-to-try bills won't help. There isn't a single good thing for patients in them that I can see, and I didn't even discuss how quacks could abuse such laws. That's why the solution is simple. Don't pass them.

If you don't like what I wrote, no one's forcing you read.

@Jason Deegan: Orac has written here many times about Right-to-try bills and what's wrong with them. There are also excellent posts at Science-Based Medicine about RTT bills that you might find interesting.

The biggest problem is that RTT bills remove all protections from a patient. Get injured by a treatment or die sooner? Tough toodles, dearie, the law forbids you (essentially) from suing. The company wants to charge you 1 million dollars per dose? That's fine, too. And even if it's effective for you, if they decide to up the cost, you get to pay for it if you want to stay on it.

And no, your insurance doesn't *have* to pay for any investigational/experimental services. In fact, most insurances have specific exclusions for such. And guess what? If that treatment injures you (causes bleeding, stroke, whatever) and you need treatment? Insurance won't cover THAT, either, because it was caused by a non-covered service. So that's MORE money out of the poor patient's pocket.

But all the stories don't go into that. They are all testamonial "SEE??? THIS WORKED FOR ME!" and no one asks them how much in debt they are. No one asks the families whose loved one died what horrible debts are left.

Orac isn't against clinical trials. He's against the RTT laws that strip all the protections that people currently have to save them.

And, the bills WON'T help. They'd need to be totally re-written, to help. That's part of the point...

But maybe you’ll take it to heart the next time you’re compelled to write 1,000 words complaining and save 200 of them for: here’s how the bills WOULD help…

The bills won't help. That's the point.

(Dawn, you beat me to it.)

Hope is important, but should not be masked by outrageous claims. The beauty of science based medicine is the search for evidence and the explanation of the meaning of that evidence. J.Groopman wrote neatly years ago. Now, some oncologists faced with a near terminal patient say to the patient we can try this even though no data support it helping.Offering choices as in the earlier statement is not involvement in decision making. That some choose to wager against the odds is different from saying odds not good I'll try something the man preaches with confidence will,help, though he has no data

(2) Has considered all other treatment options currently approved by the United States Food and Drug Administration.

In addition to the giant whopping loophole of item #1 (the non-defined "life-threatening disease or condition"), this is huge too. The patient has to have considered all other treatment options -- but no particular reason is required for why the patient decided not to use them. In theory, this could even encompass rejecting antibiotics for a child's pneumonia in favor of cupping because the parent doesn't believe in using drugs. Or, more bluntly, rejecting them because the doctor misled them in order to be able to sell them something with less oversight and more personal profit. Really, the ONLY protection this bill offers is the expertise and good will of the doctor, and if the California legislature thinks all doctors are perfectly beneficent and competent, then I have some oceanfront property in North Dakota to sell them.

Well, docs selling fake medical exemptions to SB 277 vaccine requirements shows that not all California docs are perfectly beneficent and competent. :-)

The bills help. They help drug companies exploit desperate patients. These are not "right to try." These are "right to charge."

@Terrie: One of the many issues with RTT bills is that companies with a drug in clinical trials usually won't have extra supplies available to patients who are not enrolled in the trials. The drugs are relatively expensive to manufacture because they are not mass-produced, so they make what they expect to need for the next phase of clinical trials, and little if any extra. There is also a massive amount of R&D at risk here: if somebody outside of a clinical trial has a bad reaction, the company is likely to get a large amount of bad publicity, if not a federal lawsuit (remember, the laws tend to protect the doctor from lawsuits, so the manufacturer is the only party the patient can sue). Whereas if a bad result happens in a clinical trial, they can quietly stop the trial--these things happen, and the patients were informed of the risks.

The real bottom line is that people with highly fatal illnesses are unable to access beneficial generic drugs and even nutrients, long available in other advanced jurisdictions.

People die sooner, they die broke, in great pain because simple molecule or old generics aren't available in the US. Many things that are available in the US are priced 100x or more higher than in a competitive market. Even with \high abilities and advantages, getting basic life and QOL supporting drugs and nutrients can be extremely difficult or prohibitively expensive. It seems like we always have 1-2 supply crises going at any given time. Mostly I blame the FDA type laws.

This specific proposal may not exactly address all these problems, but people are sick of being smothered to death by the FDA and the corrupt cartelization that has occurred. Alter it (favorably) or abolish it...

@prn: go away and infest your usual haunts. You lie there, you're lying here. Your supplements, IV vitamin C, homeopathic crap is out of the question.

You can't treat everything with your freakin' supplements that you sell for way-over-their worth, and have no proof that they actually contain what they are supposed to contain, thanks to Big Supplement tying the FDA's hands over testing.

Yes, the US FDA tests things that may be available in other countries more carefully because of the thalidomide debacle. I know you are WAY too young (or lacking in intelligence) to remember such a thing.

"favorably" to whom?

The FDA has very little actual oversight of supplements & you can pretty much get anything you might want, off the shelf or online, at just about any price for that matter.

Lawrence, several examples.

The FDA specifically "disappeared" pyridoxamine, a cheap B6 vitamin. some years ago by reclassification as an expensive orphan drug with a startup company that financially failed. Injectable vitamin C has ongoing harrassment problems with both the FDA and many of the states. Leucovorin is a form of vitamin B9, where a tablet might be $25 when there isn't a spot shortage, instead of 10 cents and plentiful.

DSHEA did not "free all the prisoners".

MI Dawn, lots of errors and wrong assumptions. I am not selling supplements. The FDA sucks balls at testing in many ways. Testing for many simple molecules simply can't account the cost increases but cartelization effects can. I don't think even Orac would accuse me of being "homeopathic" since you all look so homeopathic to me. It is ***your*** aggressive, arrogant ignorance that is the problem here. Otherwise I wouldn't even be here.

@prn: The FDA isn't ALLOWED to monitor supplements, remember. Because the FDA is mean and all governmenty, and wants guarantees that a pill actually contains the chemicals claimed on the side of the bottle (which most Big Supp doesn't want to list anyway) AND that they are in the amounts listed AND that they actually do what the seller CLAIMS they do.

What's wrong with that? If I buy a bottle of aspirin, that says each pill has 325 mg of aspirian, then I expect each pill will contain that dose. The FDA tests it, so it can guarantee that. I know that aspirin has been tested, is useful for certain illnesses/problems, and is not useful for others. It has risks and side effects, all of which are documented. It warns me what to do if I take too much.

If I buy a bottle of Vitamin D, I have no such guarantees. I could be paying for expensive sawdust. I could be paying for 1/2 or 4 times the dose listed. There are no listings of the risks and side effects. There are no warnings about overdoses. I can't be sure that what I'm using it for is appropriate.

If Vitamins and other supplements were as monitored as a simple drug known as aspirin, people who care about science and medicine might feel happier about their use.

I pains me to say it; but I have a certain sympathy for what prn is saying.
This side of the Pond Big Pharma would never get away with charging such outrageous prices. If a script is written, it's usually for the generic drug.

But maybe you’ll take it to heart the next time you’re compelled to write 1,000 words . . .

Hah! I say again, hah! A thousand words you say? Hugely have you failed in even a scant examination of our kind host's other posts, even on the same subject. Why, our Machine Mind Master could toss off a veritable torrent of words fourfold greater than that while polishing his perspex case in the morning.

Re-reading this blog post and determining what was actually said or strongly implied is left as and exercise for the student.

prn:

Many things that are available in the US are priced 100x or more higher than in a competitive market.

You have it backwards. The US is the competitive market, which means the manufacturers can charge whatever the market will bear. Countries where prices are kept lower are those with government price fixing and/or single payer health insurance (which has far superior negotiating powers than the mottled patchwork that we have here).

Just a quick word to say that I'm alive, sort off well but currently, this is my first migraine ever to land me at the hospital ever (50+ migraines back in 2007-2008, none landed me at the hospital).

Currently in rehab in Sherbrooke city for the next 22 weeks, will have intertoob access in the next 3 weeks.

Big al

Yikes, Alain! Was it a complex migraine? That is what landed my son into the hospital. They are truly scary.

Hope all goes well.

Chris,

Yes, it was a complex one but I guess the cause is a sunburn of the head

Wow. We have no idea what caused son's complex migraine. Best wishes for a full recovery, and not a repeat of that experience.

For lurkers: it is a migraine that is so bad it mimics a stroke. It even causes severely slurred speech, or no speech (the 911 dispatcher heard my son trying to speak in the background, which caused her to make sure paramedics were called immediately). Plus, which was an issue since my son has a heart condition, it effects motor control, etc. My son's left arm went numb.

In short: not "just a headache." While I had learned quite a bit about migraines from hubby's family and having a kid with them, none of us ever knew a "complex migraine" existed until son spent a day in the hospital (his speech was still quite slurred for a while, he even got a few weeks of insurance paid speech therapy).

Hi Alain, missed you. So sorry that sounds dreadful and hope you recover soon.

Calli, competition takes place under many conditions. In the US, the FDA effectively eliminates most of the prescription competitors and competitive alternatives. International prices for the same Chinese/Indian API based generic with adequate QC can be quite different.

I think we have different definitions of adequate quality control, prn. There have been an awful lot of horror stories about Chinese and Indian generic medications.

I'm not going to deny there are problems. There are. But the FDA is little more than a convenient fall guy for these problems, and eliminating regulation will not be the panacea you think it will be. If we want real competition with generics, we need to start seriously publicly funding medical research, I think. Not just the pittance we already spend. We should be spending as much public money on clinical trials as we currently spend on NASA. NASA spending has paid off handsomely in the form of advances in our aerospace industry and technological capacity; why not apply that public investment model to medicine as well?

The only reason more generics aren't able to get into the market is they can't afford to run the trials themselves. So they piggyback off of the trials run by the original manufacturers. But manufacturers are very clever, and they know how to game this, so that this will not always be feasible. Take Ritalin XR. Methylphenidate's been available generic for ages . . . but Ciba was shrewd enough to wait until their patent protection was about to run out before introducing an extended-release version. This happens all the time, where a clearly superior version just so happens to come out right when they're about to lose patent protection. Generic manufacturers may decide it's not worth the bother and expense to chase the old generic.

When it comes to things with devices, they have even more games they can play to elbow generic manufacturers out of the way. Inhaler manufacturers waited until the last possible minute to get approval of their non-CFC inhalers. The law was forcing the switch, but it gave them an opportunity to shut out all the generic manufacturers, who would not yet be able to make the HFA inhalers due to patent protection. Of course the one most in the news right now is the damn EpiPen. There are only two auto-injector manufacturers in the US, and the EpiPen has a clear market dominance as theirs is easier to use. The medication in it is easily eligible for generic status, but the device itself is another matter. Things get muddled when the drug is both a drug and a device, and the rules are different for devices, which as manufacturers of everything have known for a long time, can be controlled by many means, including branding the hell out of them so that you can even use trademark protection to control your competition.

Looks like the only person this might help is Burzynski

Who exactly is a manufacturer under this proposed law? Could I cook up a concoction , call myself a manufacturer of a drug, and offer to sell it to very sick people as an experimental treatment?

@Alain:

(Though it sounds like you're away from the Internet for a few weeks):

Good to hear from you!

Governor Jerry Brown protects patients by vetoing California's right-to-try bill

oracknows — Tue, 13 Oct 2015 04:00:43 +0000

Governor Jerry Brown protects patients by vetoing California's right-to-try bill

When last I discussed the cruel sham that is the tide of "right-to-try" laws that has been flowing through state legislatures to become law over the last year and a half. "Right-to-try" laws, as I pointed out when I first noted the earliest ones being promoted in Colorado, Louisiana, Arizona, and Missouri, referring to them as Dallas Buyers Club bills based on their seeming inspiration from that movie and pointing out how they are very, very bad policy that, contrary to the claims of its proponents, are far more likely to harm patients than help them. In every state in which such bills have been introduced they have passed with little opposition. I expected the same thing to happen with the right-to-try bill (AB 159) introduced in California, and it seemed to be happening, with the bill passing the legislature with relative ease.

Then Governor Jerry Brown did something unprecedented. He vetoed AB 159:

Gov. Jerry Brown vetoed a measure Sunday that would have allowed terminally ill patients easier access to experimental treatments that have not yet been approved by the federal government.
The measure by Assemblyman Ian Calderon (D-Whittier), dubbed the "right-to-try" act by supporters, would have authorized drug manufacturers to let patients facing imminent death obtain drugs that are still undergoing review by the Food and Drug Administration.

The FDA does allow for such patients to apply for "compassionate use" access to medications that are still in clinical trials, but proponents of the "right-to-try" legislation say the application can take too long for the gravely ill.

Brown, in his veto message of AB 159, noted the FDA recently streamlined the "compassionate use" program.

"Before authorizing an alternative state pathway, we should give this federal expedited process a chance to work," Brown wrote.

I was amazed. I was awed. My respect for Gov. Brown, which had been rather low when he added an unnecessary signing statement to a law designed to make nonmedical exemptions to school vaccine mandates, thus neutering it, and recovered when he signed SB 277 into law, eliminating nonmedical exemptions altogether, took another tick upward. The reason is that his veto indicates an understanding of why right-to-try laws are a cruel sham, coupled with real political courage. The reason right-to-try laws have been passing so easily is that their proponents have successfully co-opted the terms of the debate, pitting suffering, terminally ill patients who believe that their only hope to live is an experimental drug against the cold, seemingly uncaring bureaucracy of the FDA. What politician wants to be portrayed as taking hope away from such patients? Not many. Indeed, California Bill AB 159 is even worse than most in at least one aspect: It doesn't limit access to terminally ill patients but rather to patients with an "immediately life-threatening disease or condition," defined as "a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months."

Basically, right-to-try laws all follow the same template provided by a libertarian think tank, the Goldwater Institute. The idea is to make it easier for terminally ill patients to access experimental drugs and devices. The requirements are risibly low and betray a total lack of understanding of how drug development works in that they only require that the experimental drug (1) have passed phase I trials and (2) still be in clinical trials. Of course, phase I trials are not designed to test efficacy. Their purpose is to work out optimal dosage, identify the maximal tolerated dose, and identify major side effects. Worse, they usually only consist of a few tens of patients, often less than 30. To propose letting seriously ill patients drugs that have been tested in so few people and not demonstrated to be efficacious and safe is to invite disaster. In addition, they provide no financial support for patients, who are basically on their own when it comes to paying what can be the substantial financial charges. In addition, right-to-try laws strip away patient protections, making it virtually impossible for a patient injured using such a drug to sue either the drug company or the physician administering the drug. That's even leaving aside the fact that drug approval is controlled by the federal government, and drug companies will be highly reluctant to offer such drugs without the approval of the FDA, and the FDA already has programs for single patient INDs, also known as compassionate use, to allow patients access to experimental drugs.

Over the last year and a half, state legislature after state legislature, believing, based on the dishonest propaganda of advocates who claim that the FDA is killing people and the Goldwater Institute cynically featuring the sympathetic stories of dying patients (particularly those with Lou Gehrig's disease) to advance its agenda, has fallen under the spell of right-to-try. It passed in Michigan last year, sneakily pushed through the legislature. Over the last year, state after state passed these ill-advised laws. Not surprisingly, several months ago and more than a year after the first of these laws passed, right-to-try advocates couldn't point to a single patient helped by these laws, and even patients were starting to realize that they've been sold a bill of goods in the name of an antiregulatory fervor to weaken the FDA, which was the real reason all along for these laws. The Goldwater Institute just used terminally ill patients to lobby state legislatures, that and the fact that most people don't understand drug development and think that the arguments for right-to-try sound reasonable because of it. It's no wonder that patients feel betrayed and disappointed. Right-to-try laws, by their very design, create false expectation and false hope.

Because of the widespread misunderstanding of drug approval (specifically the primacy of the FDA over any state law) and the lack of attention paid to the patient-hostile provisions of the Goldwater Institute template for right-to-try laws that strip away legal protections and greatly weaken the right to legal recourse in the case of harm, these laws have passed 24 states. California would have been the 25th. No one seems to realize that the true purpose of right-to-try laws is to build a political consensus to weaken the FDA (as libertarian Nick Gillespie basically admits). Indeed, the Tenth Amendment Center virtually explicitly says as much:

Back in 1996, California voters recognized that keeping medicine away from sick people was a federal policy they could no longer ignore, and they passed Prop. 215 to legalize medical marijuana. The Right to Try Act is based on the same principle. And when enough people and enough states say no to federal bans, there’s not much that Washington D.C. can do about it.

And:

“The Right to Try Act is a no-brainer,” Maharrey said. “When someone is on their deathbed, the fact that FDA regulations would let them die rather than try, has got to be one of the most inhumane policies of the federal government. Every state should nullify the FDA like this.”

Actually, as compelling as this sounds, this argument is far more about appealing to emotion rather than reason. In actuality, given the small proportion of drugs that make it successfully through the whole regulatory process after phase I, patients with terminal illnesses are far more likely to be harmed then helped by releasing experimental drugs that have only passed phase I trials. The frequent retort is that these patients are terminally ill and things can't get worse, but there is something worse than being terminally ill. It's being terminally ill and exhausting the last of your finances and even going into debt. It's being terminally ill and harming yourself so that your are less able to do what you want to do in your short remaining time. It's being terminally ill and dying sooner than you have to.

Moreover, as Gov. Brown noted, the FDA already has a compassionate use program that it is modernizing to make the process less onerous. It's a process that is inherently superior than any state "right-to-try" process because patients who go through it do not give up any of their legal protections, must be monitored the same way clinical trial subjects receiving the experimental drug are, and remain under the regulation of an institutional review board (IRB), which protects human subjects and provides ethical oversight. Gov. Brown is correct; it is foolish for state legislatures to try to interfere with that process until it can be evaluated whether the changes the FDA has proposed in its draft guidance have had an effect. These guidelines even include a provision that, if the application process is still too slow for a particular patient, in an "emergency situation that requires the patient to be treated before a written submission can be made, the request to use the investigational drug for individual patient expanded access may be made by telephone (or other rapid means of communication) to the appropriate FDA review division, and authorization of the emergency use may be given by the FDA official over the telephone," provided the physician explains how the use of the experimental drug meets the statutory requirements and a written submission is sent to FDA within 15 working days of the authorization to use the drug.

I mentioned earlier that, as of several months ago, no one has yet been able to identify a patient whom a right-to-try law had helped to obtain an experimental drug:

However, more recently, a number of questions have been raised as to whether these bills have actually brought experimental treatments to the patients in need, and whether they're even necessary because of a more simplified FDA compassionate use program.

Dr. Arthur Caplan, director of the Division of Medical Ethics at New York University's Langone Medical Center, who's also part of the NYU Working Group on Compassionate Use and Pre-Approval Access, told reporters in late August: "It's fair to say we haven't yet found a case where right to try laws have facilitated access to anything."

Caplan and several others also previously wrote in Health Affairs that although the "laws have created an expectation that terminally ill patients will be able to quickly access potentially life-saving treatments by being exempted" from FDA rules, "this expectation is, quite simply, false.

"Putting aside the invalidity of RTT laws [because of federal law preempting state law] and the false hope they create, these laws also fail to address more fundamental health and safety issues. RTT laws seek to grant vulnerable patients access to unproven and potentially harmful drugs or other medical products without any expert safeguards, such as scientific or ethical review by an Institutional Review Board or similar body," Caplan and others wrote.

Exactly.

Right-to-try laws sound on the surface to be compassionate and reasonable. They are nothing of the sort. Unfortunately, it's not at all a given that Gov. Brown's veto will stand. The bill passed the California Senate by a vote of 40-0 (even the normally science-based Senator Arthur Pan, co-author of SB 277, voted for it) and the Assembly by a vote of 76-2. Not surprisingly, its supporters are already lobbying the legislature to override Gov. Brown's veto. It wouldn't surprise me if they succeed, but I hope that they don't. Either way, Gov. Brown has shown us that it is possible to say no to this onrushing madness.

oracknows Tue, 10/13/2015 - 00:00

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given the small proportion of drugs that make it successfully through the whole regulatory process after phase I, patients with terminal illnesses are far more likely to be harmed then helped by releasing experimental drugs that have only passed phase I trials.

Precisely.
We are not talking about fast-tracking clinically tested drugs into general availability, but about drugs taken from a much earlier stage of the trial gauntlet.
(cherry on the cake: the provider may start wondering, why even bother completing the trial, if he is already allowed to sell his stuff)
A few failed drugs turned out to kill the patient along his cancer. That's not the sort of medicine one would like to facilitate access to.

Helping these terminally ill patients into joining existing clinical trials may be a more efficient approach, for all people concerned - these patients with an urgent need, the medical/scientific community, and all the future patients.

In short, the Tenth Amendment Center is making a big assumption in its approach:

keeping medicine away from sick people

Until they prove their effectiveness around phase III trials, drugs and protocols under scrutiny are not "medicine".
Circular reasoning and appeal to emotion all-in-one.

The Goldwater guy said:

Every state should nullify the FDA like this.

The word "nullify" should create a big echo on people's wingnut radar.

This weekend Governor Brown also signed SB792 into law, requiring that daycare workers get MMR, TDaP and the influenza vaccine.

Good run of protecting people's health.

The Yellow Water Institute for Flappy Paddle Babies will not be happy about this.

Good.

Let these mendacious shitheels volunteer as the Phase I test subjects if they want research to move faster. That way the seriously ill patients they are so concerned about can go on the safer Phase II trials instead, once the worst toxic effects have been figured out on truly deserving cases.

I'm sorry, I'm finding this needlessly paternalistic and seemingly motivated by a distaste for who's pushing the law than its merits. How is this substantively different from the FDA's compassionate use program? Why do you object so strongly to having two different pathways to that?

@ Hal_10000

I’m finding this needlessly paternalistic

How so? Be specific.

Why do you object so strongly to having two different pathways to that?

I believe Orac was very clear on that.
In no particular order, this proposed second "pathway"
- is providing mostly false hope, by giving the illusion of access to effective treatments, whereas most of these treatments are most likely non-effective, if the usual pattern of 1 drug out of 10 getting approved is any indicator

- is being set on a lower threshold of acceptance than the FDA's; thus, more risky/unproven drugs getting in

- is circumventing the FDA compassionate use's pathway; and thus, weakening or neutering the FDA actions

- is allowing untested treatments to jump ahead of rigorous scientific/medical scrutiny (a scattering of unsupervised individual patients is not providing as much and good information as a full-fledged clinical trial).
Thus, in the long-term, Right-to-try is actually detrimental to patients because it will take longer to distinguish between a truly efficient drug and a oddball one with hidden flaws (imagine Vioxx provided as RTT).

HAL10000 -- Orac already said it well:

The frequent retort is that these patients are terminally ill and things can’t get worse, but there is something worse than being terminally ill. It’s being terminally ill and exhausting the last of your finances and even going into debt. It’s being terminally ill and harming yourself so that your are less able to do what you want to do in your short remaining time. It’s being terminally ill and dying sooner than you have to.

In other words, even if these patients are dying, it's not true that they have "nothing to lose".

It’s a process that is inherently superior than any state “right-to-try” process because patients who go through it do not give up any of their legal protections, must be monitored the same way clinical trial subjects receiving the experimental drug are, and remain under the regulation of an institutional review board (IRB), which protects human subjects and provides ethical oversight.

The failure of RTT laws to provide these protections really betrays the health freedom beliefs underlying them. If it were actually about the patients they could easily incorporate these protections into the state laws. But it's all part of the libertarian agenda to weaken any kind of government regulation.

@HAL10k: Orac explained the difference between the FDA compassionate use program and right to try:

[The FDA compassionate use program] is inherently superior than any state “right-to-try” process because patients who go through it do not give up any of their legal protections, must be monitored the same way clinical trial subjects receiving the experimental drug are, and remain under the regulation of an institutional review board (IRB), which protects human subjects and provides ethical oversight.

A drug that has not passed clinical trials is still an experimental drug, so by definition any treatment program that uses such a drug is a medical experiment. There is a reason medical experiments are strictly regulated (e.g., the Tuskeegee syphilis experiment, not to mention you-know-who across the pond). These "right-to-try" laws encourage, and in some cases require, doctors to perform unethical medical experiments.

Eric -- Nice dodge of a Godwin there! [golf clap]

Why do you object so strongly to having two different pathways to that?

Because one (right to try) is a sham that gives patients false hope and strips basic ethical and legal protections away from patients. The other (compassionate use) does not.

And in other news, our equivalent over here (the Saatchi Bill) is re-appearing in yet another form as a private member's bill soon...

I am so looking forward to a new set of misinformation about what this bill proposes, rather than what it is, i.e. a Trojan Horse for untested and very likely ineffective treatments and outright quackery...

A link, should anyone be interested:

http://www.stopthesaatchibill.co.uk/

Huh. I see that the initiative campaign against sb277 decided to crash and burn.
http://www.latimes.com/local/political/la-me-pc-vaccine-law-foes-fall-s…

I would think that any state that passes a RTT law would be opening the state up to a large liability law suit. Regulating drugs, I believe, is well within the police powers of the federal government and does not reside in the states.

Scenario: Someone with cancer finds a company that is testing laetrile and lives in a state with a RTT law. We know laetrile is a wooist drug and the FDA would never approve it. The person takes laetrile (under the RTT) and dies. The state has given tacit approval to a drug that is known to be a fraud. Would the state then be liable for this death?

Would the state then be liable for this death?

IANAL, but no because:
- Sovereign immunity, as codified in the 11th amendment to the Constitution.
- Not forbidding you access to a treatment does not equal approval, even tacit. Otherwise, any death caused by something that's legal - even if it is regulated - would be the subject of a lawsuit. Likewise, any libel suit would include the state as a defendant, since the state allows people to publish things without prior approval.

Not to mention that the RTT laws could be the death knell for small biotech and pharma companies. Usually you only make enough of a new treatment/drug to run your clinical trials. You calculate *exactly* how many people you need in a trial to show safety and efficacy, and no more.

Because making treatments/drugs is expensive, especially if you don't know if it is going to work. So to be told "you must give the drug to so-and-so who can't be part of your clinical trial because they don't meet the inclusion criteria" could mean "you can't complete this trial properly, and therefore can't get approval, you're all laid off".

Would the state then be liable for this death?

IANAL either, but as MO'B says, the state is probably immune.

The prescribing physician, OTOH, is likely to be in a world of trouble. As I said upthread, he would arguably have conducted an unethical medical experiment. So unless the state law specifically excludes it, he could be sued for that. Alternatively, he--and the hospital or institute with which he is affiliated--could find themselves subject to a federal investigation. With penalties up to and including suspension and debarment. That's potentially bad news if the doctor is affiliated with a medical school--at almost every university with a medical school, the medical school is the leading procurer of external research funds, and the overhead that comes with those funds. If an institution were debarred, that would blow a big hole in their budget.

@JustaTech: Again, IANAL, but my guess is that Little Pharma would have recourse if a state tries to coerce them into providing an experimental drug under RTT. Federal law trumps state law, so if they cannot comply with both, they must comply with federal law. Unlike the next-of-kin in Rich Bly's scenario, the company would have grounds and standing to sue the state.

So to be told “you must give the drug to so-and-so who can’t be part of your clinical trial because they don’t meet the inclusion criteria” could mean “you can’t complete this trial properly, and therefore can’t get approval, you’re all laid off”.
Right to Try doesn't require the drug company actually provide the drug. It just permits the drug company to do so.

Nick Gillespie make it quite clear in his writing that he wants the FDA completely gone. He insists that market forces will do better to protect patients than regulation, apparently completely unconcerned of the realities of the US drug market before the FDA, or the current reality in nations with lax regulatory oversight.

I don't know if he simply hates regulation more than he cares about patients, or if he really is this bad at critical thinking. But I'd trust his opinion on patient safety about as much as I'd trust a fox arguing in favor of free-range chickens.

Yes, until fairly recently I never seriously believed that there were people who actually thought that there should be, in essence, no regulation of drugs and that the free market would protect patients. Normally, the argument is made in the form of something like this: Without the FDA, private companies or organizations would take over the function of assuring drug safety, the way UL does for electrical products. It's an utterly nonsensical argument, of course, given history and what drug development was like before the FDA, but people like Nick Gillespie really believe it.

Orac,

I do seriously believe such irrational peoples can and do exist. For years. Of course, they are at the 6th sigma of the bellcurve or irrationality but then, it's the extreme end of the population's behavior for which, the extreme subject, I've been studying because they give a really good example of the population's behavior because they are extremely overt about what the rest of the population may want to hide. I hate to use that context to pitch in my blog but I just wrote about it:

http://www.securivm.ca/2015/10/social-engineering-using-scientific.html

More often than not, I am in error and I do think about my hypothesis of the population having the same belief at a far lower level as compared to extremists but I am always working on my mistakes and learning. You can see why in my blog post.

Alain

I am thrilled to read this--someone in Brown's office either read the bill, or listened to someone who had.

"He insists that market forces will do better to protect patients than regulation, apparently completely unconcerned of the realities of the US drug market before the FDA, or the current reality in nations with lax regulatory oversight."

Ah yes, what I like to call the market fairy. The magical market fairy solves all problems, no matter how complex.

Nick Gillespie make it quite clear in his writing that he wants the FDA completely gone. He insists that market forces will do better to protect patients than regulation,

Imagine my surprise to discover that the same libertarians pushing for the abolition of the FDA are also pushing for "tort reform", to make it harder for customers claiming to have been injured by products to sue the suppliers thereof, as apparently such abusive lawsuits are holding back innovation.
If a free-market medication kills you, or just lets you die from ineffectiveness, the approved libertarian response is not to sue, but simply not to buy that product again.

@ hdb

If a free-market medication kills you, or just lets you die from ineffectiveness, the approved libertarian response is not to sue, but simply not to buy that product again.

Eh, it's so logical, my grandma can do it, why can't you commie/liberals/sheeple do it and you insist on being a slave of the government?

The FDA (or similar European organizations) may be slow to react, but I'm afraid the invisible hand of the market is even slower and less effective.
To start with, the market doesn't care about effectiveness, just about sales figures.
As long as you keep changing your snake oil name to keep selling it, and/or blame the harmed customers for not having followed the protocol scrupulously enough (plus, this little matter of the cheeseburger you ate 10 years ago, or your granddad having been vaccinated), you will stay in business.
That's actually something Big Pharma is doing, if one wants to be honest, at least in the cosmetic/vitamin fields. Let's add some vit E to our anti-aging cream, glue a new fancy name on the box, and voila. A whole new product, totally not like our previous brand.

I have also seen the theory that there is no need for the FDA or the option of tort law, because no-one company would sell a product that kills customers (or even lets them die) -- to do so would lower the company's future income. Market forces will prevail!
Sometimes it is even the same people as subscribe to conspiracy theories in which the pharm companies are suppressing the real cure for cancer, to maximise their income, because of those evil market forces.

@ hdb

no-one company would sell a product that kills customers (or even lets them die)

Well, it's true it's gratifying for one's ego to produce something which is working, and having customers staying alive so they can come back is not a bad business model, either.

But how people would know, if no-one is looking at the product's effects?
Libertarians seem to ascribe the god-like power of omniscience to the customers.

Under this libertarian model, Vioxx and the thalidomide racemic would still be happily sold to an unsuspecting audience.

The FDA (or similar European organizations) may be slow to react, but I’m afraid the invisible hand of the market is even slower and less effective.

Something something Dan Savage something.

Bob@22:

[Nick Gillespie] insists that market forces will do better to protect patients than regulation

The invisible hand of the free market promised to give me a reach-around, but all I got was my pocket picked and a lot of bloody stool.

no-one company would sell a product that kills customers (or even lets them die) — to do so would lower the company’s future income.

The continued existence of companies that sell tobacco products is disproof of this proposition. The US Surgeon General has been warning for more than 50 years that cigarette smoking causes lung cancer. You can still buy cigarettes in the US, as long as you are at least 18 years old. And in some countries, the fraction of the population that smokes is still increasing--China and Indonesia in particular.

As for the "invisible hand of the market": I am reminded of an old New Yorker cartoon with the caption, "There it is again--the invisible hand is giving us the finger."

On the same line, an old joke:
Q: How many Chicago School economists does it take to change a light bulb?
A: None. If the light bulb needed changing the market would have already done it.

" no-one company would sell a product that kills ( or even lets them die)"

And YET we have Burzynski, Clement, Gonzalez, Gerson and various entrepreneurial woo-meisters** who promise cancer/ other cures without SBM

** one of whom is opening a spa/ health resort/ medical counselling service in Texas

@ perodatrent:

Ha ha!

We got my son indo a medical device study under Compassionate use.

It did not seem to me an onerous process. Although I know I was shielded very well by his Docs.

Said device is now approved so he actually did help advance medical science. Yay!

It took a couple of months, but since we saw this coming from way out, it was well planned

I would hesitate to sign him up for another device that was in a much earlier stage.

So many questions so many risks. I understand the allure, and as compared to a drug, his device is pretty simple. But there has be deliberate debate and understanding of benefits and risks.

Under this libertarian model, Vioxx and the thalidomide racemic would still be happily sold to an unsuspecting audience.

Don't be silly - once all the women who had horribly deformed babies wrote terrible reviews of thalidomide on Yelp, potential customers would read them and stop buying it - the perfect market-based solution! Except for the thousands of lives that have to be sacrificed before-hand, of course.

The thing with the invisible hand is that it’s, well...invisible.

Big thumbs up to Jerry Brown!

Sarah A: Won't work. Flappy paddle babies are obviously their OWN fault for not believing hard enough.

(Hey, it works for sCAM.)

Except for the thousands of lives that have to be sacrificed before-hand, of course.

This is the thing so many of the libertarian persuasion ignore. Most regulations exist because they were designed to prevent a recurrence of practices that resulted in death or substantial harm to a bunch of people. It's not just the pharmaceutical industry, either. Lawnmowers nowadays have a dead-man switch which shuts them off when the operator lets go; when I was a kid, that switch wasn't universally present. Seat belts and airbags in cars are another example. Their purpose is to prevent needless death and injury.

Furthermore, in the case of health care, we did the experiment in this country--that was the situation before PPACA came into effect. The system was so obviously broken that even the Heritage Foundation was advocating a fix--PPACA was based on a system originally designed by the Heritage Foundation. A necessary (but not sufficient) condition for free markets to work is that buyers and sellers have all available information and can take it into account. For many medical conditions, that isn't true: you need treatment, and you need it now, even if the immediately available provider isn't the best.

The lack of any kind of regulation for consumer goods, particularly food, was the reason behind the boom in Home Economics education from the turn of the century through WWI. In addition to everything else they had to do (reading about housework prior to the invention of the vacuum cleaner and washing machine makes me shudder), women were encouraged by magazines like the Ladies' Home Journal and Modern Priscilla to become testers/researchers of canned goods, etc to protect their families.

It was considered a suitably lady-like application of the study of chemistry and the reason two generations of female undergrads interested in science were steered towards the Home Ec department.

@has (#32):

all I got was my pocket picked and a lot of bloody stool.

Maybe you should keep your wallet somewhere else..?

Under this libertarian model, Vioxx and the thalidomide racemic would still be happily sold to an unsuspecting audience.

For many years it was a refrain among libertarians that by keeping thalidomide off the market, the nanny-state FDA was denying people access to a wonder drug, when a simple warning about contraindications would have sufficed

@HDB #44

I might actually be sympathetic to that argument - with the MAJOR caveat that you can't warn people about contraindications that you don't know about because you haven't tested for them yet because you're in a rush to get a drug onto the market. I remember when I worked briefly as a pharmacy tech there was a prescription acne drug that women of childbearing age had to fill out and sign a form stating that they understood that the drug caused severe birth defects and that they were on two forms of birth control before they could get it. So obviously it is possible to sell a drug that causes birth defects if the proper precautions are taken. The problem with thalidomide, as I understand it, was that it was being marketed to pregnant women before adequate testing had been done in pregnant animals. Similarly, many people argue that Vioxx is worth the relatively small increased risk of a heart attack for a patient who is in chronic pain that doesn't respond to other drugs. The problem wasn't with the drug per se, but with the fact that Merck tried to hide the evidence that it increased heart attack risk - which is another counterexample to the claim that pharmaceutical companies can be trusted to police themselves because its in their own best interests not to sell defective products.

^Tag closing fail - only the phrase per se should be italicized

Bob @21

I don’t know if he simply hates regulation more than he cares about patients, or if he really is this bad at critical thinking.

Probably both since Gibbertarain implies a lack of both empathy and critical thinking.

@ Militant Agnostic:

But libertarian Mike Adams ( Natural News today) insists that lefties are the ones lacking higher mental functions, religion and skill with mathematics and economics. Indeed, if you de-activate a part of righties' brains, they become liberals! ( He uses the words MR amongst others).

Mike exemplifies cognition itself or so he tells us. He studied that stuff.

But libertarian Mike Adams ( Natural News today) insists that lefties are the ones lacking higher mental functions, religion and skill with mathematics and economics.

IOW, he's still projecting like a multiplex movie theater. Which I find about as surprising as news that the Pope is Catholic.

I've actually read Das Kapital. I don't see any major issues with Marx's economic analysis: he correctly identified a major trap to which capitalism is prone, and into which it did routinely fall up to and including the 1930s (and arguably during the 2008 financial crisis as well). His political analysis is another story entirely. It's unfortunate that the latter proved so much more influential than the former. I'd rather deal with Marxists of the Groucho type than the Karl type.

I'd say that communism and libertarianism are alike in two key respects: (1) They are superficially appealing political theories. (2) Successful implementation of either one requires several counterfactual assumptions about human nature.

Given that terminally ill patients would not be around long enough for Vioxx to manifest a heart condition, nor that they are likely to be pregnant, I don't understand the vehement opposition here. No one is going to ask for a random drug in testing out of the blue. There has to be some basis wherein they think there will be some benefit (like it has been approved in Europe and used off-label for a condition with some success).

This post is poorly reasoned and reactionary, using the libertarian bogey man and the specter of thalidomide to squelch an otherwise reasonable proposal. If they have months to live, and are paying for their medicine themselves, really, at that point, why not let people try?

Read the links to my previous posts on Right To Try. That's why they're there; so that I don't have to repeat my arguments in detail again. Here they are, in case you can't find them in the text:

http://scienceblogs.com/insolence/2014/03/06/right-to-try-laws-are-meta…
http://scienceblogs.com/insolence/2014/08/14/the-cruel-sham-of-right-to…
http://scienceblogs.com/insolence/2014/08/19/usa-today-flubs-it-big-tim…
http://scienceblogs.com/insolence/2014/10/28/ebola-right-to-try-laws-an…
http://scienceblogs.com/insolence/2015/05/25/the-cruel-sham-that-is-rig…
http://scienceblogs.com/insolence/2015/05/26/the-cruel-sham-that-is-rig…

Bottom line: Right to try laws are a sham. They give the illusion that the state is doing something without actually doing anything. Worse, if they were to succeed in doing anything, it would be to screw terminally ill patients by letting companies suck the last bit of their cash from them or forcing them to go on Internet fund raising drives for the short remaining rest of their lives, while stripping the protections provided by the FDA and Office for Human Research Protections provide by requiring that single-patient INDs be approved and overseen by an IRB to protect the patients' rights and interests. Even the libertarians supporting them admit now that they don't do anything. Their fallback is to actually admit what was the real purpose of these laws as if it were new and not the idea all along: To put pressure on the FDA and weaken it.

@ rogue

Given that terminally ill patients would not be around long enough for Vioxx to manifest a heart condition,

My apologies, the conversation drifted. I wanted to use examples of drugs which everybody know as having heavy side-effects in a subset of the population.

However, "terminally ill" doesn't mean you are going to die within two weeks. It's a catch-all sentence used for patients with a few weeks left as well as for people with up to 6 months left, or more.
I daresay that, for those on the higher end of the time frame, medium- to long-term effects will have time to manifest. That's not a trivial risk.

nor that they are likely to be pregnant

Nitpicking, but a few unfortunate women do find themselves with an advanced cancer - or other life-threatening illness, like AIDS - and pregnant at the same time.
Granted, in their cases, it's more about choosing between the fetus' or the mother's life, because the treatment will affect the fetus in a deleterious way, rather than the lack of access to efficient medication.
OTOH, RTT laws could grant these women access to barely tested drugs, and I'm not thrilled discovering the hard way that these drugs are inefficient AND teratogenic.

The cruel sham that is "right to try" continues to spread

oracknows — Mon, 25 May 2015 08:40:50 +0000

The cruel sham that is "right to try" continues to spread

Last year, I did several posts on what I consider to be a profoundly misguided and potentially harmful type of law known as "right-to-try." Beginning about a year and a half ago, promoted by the libertarian think tank known as the Goldwater Institute, right-to-try laws began popping up in state legislatures. I wrote about how these laws are far more likely to do harm than good, and that is a position that I maintain today. The idea behind these laws is to give terminally ill patients access to experimental drugs—in some cases drugs that have only passed phase I testing—that might help them. It's an understandable, albeit flawed argument. After all, it's perfectly understandable why terminally ill patients would fight for drugs that give them hope, and it's just as understandable why politicians and the public would see such a goal as a good thing. In practice, as I will explain again in the context of this update, such laws are far more likely to harm patients than help them. Indeed, as you will see, in the year since the first wave of right-to-try laws have passed, not a single patient that I can find has obtained access to experimental drugs under a right-to-try law, much less been helped by them.

Unfortunately, given how effectively "right to try" has been sold on grounds of providing terminally ill patients hope and as a matter of personal freedom, it's clear that this wave is not going to abate. Since Colorado passed the very first right-to-try law almost exactly a year ago today, a total of 17 more states now have passed passed similar legislation, the most recent being Tennessee, and 22 others have introduced legislation. It's a good bet that right-to-try will pass in all of those states, because, as I've explained many times before and in many interviews, if you don't understand clinical trial ethics and science, opposing the concept of right-to-try comes across like opposing Mom, apple pie, and the American flag, and leaves opponents open to false—but seemingly convincing—charges of callousness towards the terminally ill on the order of enjoying drop kicking puppies through flaming goalposts.

The con game that is "right-to-try" metastasizes

As I've pointed out many times before, opposing right-to-try is actually pro-patient, because these right-to-try laws that are passing all follow an explicit template written by the Goldwater Institute, and that template is very much a sham. For one thing, states do not control drug approval; the federal government through the FDA does. Consequently, state-level right to try laws, while giving the appearance of giving access to experimental drugs to patients, do nothing to actually achieve that goal. Worse, even if a patient were to get an experimental drug through right-to-try, these laws very much reflect the think tank that created them in that they leave the patient basically on his own. He can be charged the full cost of the investigational drug, which means that the only people who might be able to take advantage of these laws are those who are already rich or who are very good at fundraising. Worse, these laws explicitly indemnify drug companies and physicians from any liability arising from adverse outcomes, which means that even if a physician committed malpractice in advising or administering right-to-try drugs he probably couldn't be sued. Moreover, such laws explicitly bar state employees from blocking or attempting to block an eligible patient's access to an investigational drug or treatment. Even though there is a clause that says "counseling, advice, or a recommendation consistent with medical standards of care from a licensed health care provider is not a violation of this section," where does "advice" end and "blocking" begin? Certainly as a physician in what is now a right-to-try state whose law has identical language, I wonder.

Even worse still, many of these laws, such as the one in Michigan, are written such that if a patient suffers a complication from a right-to-try drug or treatment his insurance company can argue that it doesn't have to pay for the resulting care to treat that complication. Indeed, Colorado's law requires that informed consent for right-to-try must explicitly make clear that, "the patient's health insurer and provider are not obligated to pay for any care or treatments consequent to the use of the investigational drug, biologic product, or device" and that "in-home health care may be denied." Elsewhere, the Colorado right-to-try law states:

An insurer may deny coverage to an eligible patient from the time the eligible patient begins use of the investigational drug, biologic product, or device through a period not to exceed six months from the time the investigational drug, biologic product, or device is no longer used by the patient; except that coverage may not be denied for a preexisting condition and for coverage of benefits which commenced prior to the time the eligible patient begins use of such drug, biologic product, or device.

In other words, if you access an experimental treatment under right-to-try, and you suffer a complication from the investigational treatment, you could well be out of luck getting your insurance company to pay for the medical and/or surgical treatment necessary to treat that complication. If your insurance company so decides, you'll be on the hook for everything subsequent to that treatment. Indeed, to me the language in some of these bills implies that insurance companies can deny coverage for any new problems that come up after the patient starts using experimental therapy, whether caused by that therapy or not. These issues have largely been ignored in the news coverage of these laws, but the oncology community is finally waking up to them, as demonstrated by a recent article in HemeOnc Today in an article entitled "Expansion of 'Right to Try' legislation raises ethical, safety concerns":

"There are a lot of issues not addressed in the bill that make the feasibility more challenging," W. Thomas Purcell, MD, MBA, associate director for clinical services at the University of Colorado Cancer Center and executive medical director of oncology services at University of Colorado Hospital, told HemOnc Today. "If the drug is made available, who is going to administer it? Who is going to pay for any side effects related to the treatment? Are insurance companies going to cover any treatment-related complications? There are a lot of practical things that come into play with the introduction of the law, although the law doesn't address any of those things."

Actually, although he raises the same concerns I've been raising for over a year now, Dr. Purcell is about as wrong as wrong can be about one thing. The problem is not that the laws don't address these things. It's that the laws do address these things rather explicitly. Dr. Purcell seems blind to how these laws address these things, which is in a way likely to be highly detrimental to patients. In fact, I wonder if Dr. Purcell has even read his own state's law! It says right there in black and white that insurance companies don't have to pay for care or complications related to such drugs! That means that either the patient does, or we taxpayers do when patients suffering such complications are forced to go on Medicaid because they can no longer afford their medical care.

Another example of someone echoing what I've said many times appears here:

"People do not actually read the bills," Alison Bateman-House, PhD, MPH, MA, Rudin postdoctoral fellow in the division of medical ethics at New York University Langone Medical Center, told HemOnc Today. "They think 'Right to Try' sounds fantastic and allows access to treat terminally ill patients. How could you not support that? For the most part, the response that we've seen is that these laws don't do much, aside from giving people hope."

Dr. Bateman-House is also partially wrong. The problem is not that people don't read the bills. It's that people don't understand the anti-patient implications of the bills in terms of insurance coverage, eliminating the right to sue, and the like; don't understand clinical trials; and don't understand that it is the federal government, not state governments, who control drug approval and access to experimental drugs. Indeed, when I'm in a cynical mood, I wonder if Goldwater Institute flacks do understand all these things but don't care because they're playing a long game designed to weaken the FDA in the name of an ideology that, against all evidence to the contrary, preaches that the free market can assure drug safety and efficacy better than any government agency. Indeed, this intent can be seen in one version of the Goldwater Institute template (and in the Michigan right-to-try law), which changed the term "terminal illness" to "advanced illness," without really changing the definition. I would not be surprised if, a few years from now, after the majority of states have passed right-to-try, there is a push to open up "right-to-try" to serious medical conditions that are not terminal on the basis of "fairness" and "compassion." It's coming. Mark my words.

Finally, there are the issues of safety and false hope. As I've said before, as hard as it is to believe, there are things worse than suffering a terminal illness; for instance, suffering a terminal illness and then bankrupting yourself before you die or suffering a terminal illness and then suffering a major complication of an experimental treatment that you have to pay for, thus bankrupting yourself before you die. Now, consider this. The only requirement for an investigational drug or treatment to be made available under right-to-try is that it has to have passed phase I testing and still be in clinical trials (i.e., phase II or III studies). Again, as I've described before, this is an incredibly low bar for safety, given that most phase I trials include less than 30 patients and are meant mainly as screening trials to identify the worst side effects and an appropriate dose to use in phase II trials. Yet, as I described before, the Goldwater Institute blatantly describes drugs that have passed phase I testing as having had their safety adequately established. It's a lie.

Indeed, as is pointed out in the HemeOnc Today article, the risk for toxicity is actually higher in patients who would exercise right-to-try because by definition such patients have to be ineligible for a clinical trial. Remember, clinical trials are designed to minimize risks and maximize potential benefits because it is an ethical imperative in human experimentation, codified in the Common Rule and the Helsinki Declaration. One way they do that is to design the inclusion and exclusion criteria to achieve that end. Moreover, there have been cases where the use of an experimental therapy has become popular based on public pressure related to early evidence.

An excellent example of just what I've been warning about for a long time shows up in the HemeOnc Today article citing Dr. Yoram T. Unguru, a pediatric oncologist at the Herman and Walter Samuelson Children's Hospital at Sinai Hospital in Baltimore and bioethicist at The Johns Hopkins Berman Institute of Bioethics:

In multiple cases, access to an experimental therapy has been expedited due to an early benefit observed in early studies that was not substantiated in subsequent research, Unguru said. One example was the use of autologous bone marrow transplantation in women with metastatic breast cancer, based on preliminary data published in 1995 in the Journal of Clinical Oncology.

"This completely backfired," Unguru said. "In addition to being poorly designed, the study raises serious ethical concerns and, ultimately, people did much worse, including some who even died. This is why we go through the laborious, lengthy and, at times, seemingly maddening trial phases."

Although physicians and drug companies are required to report data attained from patients treated through the FDA's compassionate use program, Right to Try laws do not carry such stipulations.

And, as Colin Begg, PhD, chairman and attending biostatistician in the department of epidemiology and biostatistics at Memorial Sloan Kettering Cancer Center, adds, echoing (again) things I've been warning about for over a year:

Eliminating the FDA from the equation may have many significant consequences.

"There is good reason we have the FDA," Begg said. "The rigorous testing with scientific methods of drugs that come through the pipeline is absolutely essential. Without it, the market would be flooded with drugs that do not work. You would have a cupboard full of drugs that you would want to try, and you would have no idea which one to try because there would be no reliable evidence about the efficacy of any one of them."

Right-to-try laws may create a precedence for additional changes to drug R&D.

"If we go down this road, there might be a loosening of the standards of drug approval in the first place, and that would be bad for public health," Begg said. "This movement may ultimately lead to situations where … drugs, in general, would no longer have to go through such rigorous testing to see if they work."

Unfortunately, what Dr. Unguru and Begg apparently fail to realize is that the libertarian Goldwater Institute cares little or nothing about the difficult balancing of patient rights versus patient safety and societal good that our current clinical trial system tries to maintain, with varying degrees of success depending on the specific situation. An argument, for example, that right-to-try might make it more difficult to recruit patients to clinical trials holds exactly zero water with the Goldwater Institute and most other supporters of right-to-try. Indeed, associated as it is with the "health freedom" movement, the goals of the Goldwater Institute's right-to-try push appear to align quite nicely with the goal of some libertarians to eliminate most of the FDA's authority because of an ideology, which views any government intrusion into the free market with a jaundiced eye and even believes that the unfettered free market will take care of sorting out safety and efficacy of drugs. We all know how that worked out before the passage of the original act creating the FDA in 1906 and the Kefauver Harris Amendment of 1962 that introduced the requirement that drug manufacturers demonstrate efficacy as well as safety to the FDA before a drug is approved.

Those of us who take care of breast cancer patients remember Dr. Unguru's cautionary tale from the 1990s. Indeed, the clinical trial publication that fueled the demand for high dose chemotherapy with bone marrow transplant for advanced breast cancer was ultimately retracted. The bandwagon effect is a powerful force affecting politics and even prominent researchers and physicians before the evidence is adequate to recommend a treatment. If this can happen with a treatment as incredibly toxic and risky as bone marrow ablation with high dose chemotherapy followed by stem cell rescue, imagine how easily it can happen with less spectacular examples.

Over a year ago, when the states on the vanguard of the right-to-try movement were first seeing such legislation introduced, I learned the hard way just how willing the movement was to paint its opponents as those proverbial puppy-kicking, American flag burning, cold-hearted "scientists." Indeed, back then almost the only people I saw routinely speaking out against right-to-try were noted bioethicist Arthur Caplan and little ol' me, an insignificant blogger. When right-to-try was introduced into my own state's legislature, my interaction with my state representative, who politely thanked me for pointing out the many problems with right to try, but made it clear through his response that he was likely going to vote for it anyway, showed that, from a political standpoint at least, ethics- and science-based medicine were not likely to prevail in Michigan or anywhere else over the emotional appeal of "doing something" to help terminally ill patients. It didn't matter whether that "something" will actually do what it promises or not. Later, I met with an advocate of the biotech industry who testified against the bill. He described a scene in which he was the lone expert testifying against right-to-try versus a flack from the Goldwater Institute and patients with terminal illnesses and their families, the latter of whom all glared at him as though he were personally going to execute them or their ill family member. I learned that no one associated with a major cancer center was willing to publicly oppose right-to-try, even though they uniformly thought it was a horrible idea. If I had found out about the hearing in time to have made the trip to Lansing—as I recall, it occurred with little notice and on one of my operating room days—I honestly don't know if I would have had the wherewithal to do so myself, given the pushback I had received from my previous posts on the matter.

As I said, right-to-try is a con game perpetrated on desperate patients, offering them false hope but instead delivering nothing of value that can't be obtained under FDA compassionate use programs, as is pointed out by the opinion piece written by Dr. Jeffrey M. Peppercorn, a medical oncologist specializing in breast cancer at Massachusetts General Hospital, in a point-counterpoint forum included after the HemeOnc Today article that asks: Do the changes to the FDA's compassionate use program eliminate the need for 'Right to Try' laws? Dr. Peppercorn takes the "yes" position:

However, the question is not whether promotion of access to promising drugs for patients with terminal disease is justified, but how this can best be accomplished. The same imperative that drives Right to Try laws underlies the FDA's compassionate use program. The primary difference is that access to experimental drugs through compassionate use programs is regulated in the interest of both the patient and society. Physicians must seek FDA approval before a manufacturer provides the unproven drug, and the rationale for use of the drug, absence of alternatives, informed consent and review by an independent institutional review board must be documented. In addition, toxicities and outcomes after administration must be reported. This process promotes responsible practice of evidence-based medicine — even as the evidence evolves — and provides a chance for monitoring, both of the specific intervention and of the use of experimental therapy more generally. Although the process can be burdensome, the FDA has recently streamlined the application to allow for completion in less than 45 minutes and still allows for rapid approval of emergency access by phone when this is clinically justified.

Exactly.

The key difference between right-to-try and FDA compassionate use programs is that right-to-try strips pretty much all protections from patients who would use it; requires them to pay for the drug and any care related to the drug; prevents them from suing manufacturers and doctors if something goes wrong; prevents the state from taking action against the licenses of providers who give patients bad advice recommending right-to-try; tells insurance companies that, not only do they not have to pay for the investigational agent or device, but they don't have to pay for any complications arising from use of the investigational agent or device; and makes doctors and other health care providers working for right-to-try states leery of advising too strongly against right-to-try, lest they be prosecuted for "blocking" access to experimental drugs. FDA compassionate use programs, in marked contrast, require review and oversight by an institutional review board (IRB). The other difference was that, although 99.5% of compassionate use/expanded access requests are approved by the FDA, the process was onerous. As Dr. Peppercorn points out, that is rapidly changing, arguably eliminating the "need" for right-to-try. Yet right-to-try marches on, because the reason for right-to-try is not as represented by the Goldwater Institute. Rather, it's to weaken and ultimately neuter the FDA.

Other pernicious effects of right-to-try

Patients come first, and must always come first, which is why my key objection to right-to-try remains (and will always remain) that it is bad for patients. However, the HemeOnc Today article also points out other problems with the legislation. One is that it presents a major dilemma to industry. Now, I realize that few people are particularly sympathetic to industry, and even we "pharma shills" (at least that's what right-to-try proponents and those supporting alternative medicine, groups that not-infrequently overlap, call us) recognize that pharma is nowhere near innocent in provoking that reaction. Now that right-to-try laws are metastasizing throughout the US, oncologists are finally taking notice of the alarms that we few have been sounding:

The fact that manufacturers are not liable if a drug obtained through Right to Try fails or causes significant harm may allow pharmaceutical companies to benefit from such legislation, Unguru said.

"The way the laws are written, pharmaceutical companies are under no commitment to release these drugs, but should patients be able to access them, there is almost no consequence in the event of a bad outcome," Unguru said. "Bypassing the current regulatory system means that some drugs that may not be safe or ready for widespread use essentially get a 'free pass.' Some pharmaceutical companies might see such laws as a way to test their drugs in a way they typically would not be able to without being held accountable."

This would pose significant safety issues to society.

"It is hard to argue that individual patients who are dying and want access to a drug should not get it," Begg said. "But the concern I have is that the ability of drug companies to market drugs that have not been properly tested is not in the interest of the public."

The Texas State Senate and House have passed versions of a Goldwater Institute-inspired right-to-try law. The only difference in the two bills is that the House version would allow manufacturers to provide experimental drugs to patients at cost, whereas the Senate version would require that companies that provide such drugs donate them. Assuming the two versions are reconciled and passed and the governor signs the bill, say goodbye to any chance of shutting down Stanislaw Burzynski, as the law would explicitly bar the Texas Medical Board from pursuing its current action against Burzynski's medical license, given that he could claim his antineoplastons have passed phase I clinical trials and are in phase II, which makes them eligible for right-to-try. Even if the Senate version prevails, Burzynski's business model of providing his unproven antineoplastons for free but charging big bucks for "case management" fees would remain intact.

Most drug companies are not as unethical as Burzynski, however, which is why most do not support right-to-try and the Pharmaceutical Research and Manufacturers of America (PhRMA) is not supportive, as described in the HemeOnc Today article. Pharmaceutical companies remember incidents like this:

In the past, public pressure has forced pharmaceutical companies to grant access under compassionate use.

Last year, Chimerix denied Josh Hardy — a then 7-year-old boy who developed an adenovirus infection after undergoing a bone marrow transplant for rhabdoid tumor of the kidney — access to the experimental antiviral drug brincidofovir (CMX001). After a social media firestorm — which included death threats to the company's leadership — Chimerix commenced an open-label phase 3 trial so Hardy could enroll and receive treatment.

"This became publicized, and everyone assumed that if Josh Hardy got brincidofovir he would survive," Bateman-House said. "He did get brincidofovir, and he did survive. Thomas Duncan, the man who died of Ebola in Texas, got the same drug and died. Chimerix is a small drug company and brincidofovir is its only drug in development, and its stock took a nosedive after Duncan's death. If it were not for the fact that phase 3 trials were already close to completion, this could have killed the company. If Josh Hardy had died, that could have killed the company."

In other words:

"It can go either way — you're damned if you do and you're damned if you don't," Unguru said. "If you release the drug and it does badly, then you're going to get bad press. If you don't release it, then you risk being vilified."

And if the company charges for the drug and things go badly, it will be doubly vilified, even though small pharmaceutical companies often have just enough venture capital to make enough of the drug to do the clinical trials necessary for approval, and releasing drug jeopardizes its ability to do those trials.

Physicians are also put in a bind when a patient has exhausted everything and wants to pursue right-to-try. End-of-life discussions are very difficult to begin with, because, as I've pointed out before, no physician wants to be hope's executioner. Yet, sometimes that is our job, and the best we can offer is palliation. Given that right-to-try theoretically requires less effort than an expanded access exception, there will be enormous pressure on physicians to accede to the wishes of a terminally ill patient to pursue right-to-try even if the physician thinks it won't work. The option of right-to-try might thus actually provide a physician with an option to avoid the hard discussion that end-of-life care entails and just facilitate the patient's getting the drug. As Dr. Charles F. Levenback, professor in the department of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center, puts it:

"I've heard ethicists say physicians may go in the direction of compassionate use to avoid the difficult conversation about mortality and the limits of what we can provide," Levenback said. "All of compassionate use is predicated on the physician's responsibility to be candid about the purpose of treatment — palliative vs. curative — and setting the patient's expectations correctly."

Correct. However, some doctors are better at doing this than others.

The track record of right-to-try thus far

Given that it's now been a year, or nearly so, since the first batch of states passed their right-to-try initiatives, I asked a simple question: Has a terminally ill patient obtained an investigational agent through right-to-try yet? Note that I didn't even ask whether a single terminally ill patient has benefitted from right-to-try, because that's much more difficult to ascertain. Doing extensive Google searches, I could not find a single example, although I did come up with a lot of examples of patients expressing hope that such laws would get them access to investigational drugs (like this one). My next thought was that, if anyone would know of a case in which a terminally ill patient has been granted access to an experimental drug under right-to-try, it would be the Goldwater Institute. Fortunately, I came across this conversation on Twitter:

.@cmsandefur Except that #RightToTry laws don't really do that. False promise.

— David Gorski (@gorskon) May 6, 2015

The question was put to Ms. Sandefur:

.@cmsandefur Has anyone anywhere gotten experimental drug under #RightToTry? It's been a year now since Colorado. I know of no case. — David Gorski (@gorskon) May 6, 2015

Her response:

@gorskon these laws are just now going into effect,& it takes time to acclimate to overhaul of status quo. Offer to have a real convo stands

— Christina Sandefur (@cmsandefur) May 6, 2015

Which resulted in:

@gorskon Again,I welcome thoughtful,substantive discussion, but I'm not interested in unproductive back-and-forth. You know where to find us — Christina Sandefur (@cmsandefur) May 6, 2015

What's irritating about this exchange is that this clearly was was an attempt to engage Ms. Sandefur in a "thoughtful convo"—or, at least, as thoughtful a conversation as you can have on Twitter. In any case, I think it reasonable to assume that, if there were a patient in Colorado—or anywhere else, for that matter—who has successfully obtained an experimental drug under right-to-try, Sandefur would know about it and would not have hesitated to provide links to relevant news stories. She did not. Instead she chose to dodge the question and make excuses. Similarly, Kurt Altman, national policy adviser and general counsel for Goldwater Institute, mentioned no patients who had yet benefited from right-to-try in his "counterpoint" to Dr. Peppercorn's opinion piece. I know he would have if such a patient existed. Certainly, if I were writing in favor of right-to-try, I would use the examples of such patients if they existed.

Right-to-try laws: Bad for patients

I have little doubt that some version of right-to-try will likely pass in every state in which it has been introduced, which means we could be looking at up to 40 states, possibly more, with such laws by next year. It must be emphasized that the vast majority of legislators proposing such bills and passing them into laws and the patients lobbying for right-to-try do so with the best intentions, believing such laws will help terminally ill patients. These patients, according to mistaken popular belief, have nothing left to lose when in fact they do, even though it might not seem that way. In the idealistic desire to help the terminally ill, supporters of right-to-try either don't pay attention to or downplay the significant negative aspects of these bills, which permit the loss of insurance coverage, stripping of IRB protections that patients receiving such medications through expanded access programs, the economic injustice in which only the rich or those capable of raising large sums of money could benefit if the drug company was unwilling to provide the investigational drug for free, and the potential additional risk of harm that can come from using experimental drugs outside the rigorous design and protections of clinical trials. Most people are similarly unaware that granting less controlled access to such medications is far more likely to cause an individual patient harm than good. Moreover, liberalization of expanded access programs to vastly decrease the burden of paperwork and effort on the part of physicians and patient has already been placed in draft guidelines, rendering right-to-try unnecessary.

So why are right-to-try laws so popular? In an editorial last year published in JAMA Internal Medicine entitled "The Strange Allure of State "Right-to-Try" Laws", Patricia Zettler and Henry Greely ask the same question, noting that a recommendation from a physician is no substitute for the evidence of safety and effectiveness that comes from later-phase clinical trials:

So what is the point of these laws? A skeptic might point out that opposing experimental treatments for dying people is unpopular. Patients have publicized—and gained public support for—their efforts to obtain experimental treatments through social media. Lawmakers have little to lose politically by supporting these laws. Companies, seeing their ineffectiveness, have no powerful reasons to oppose them. And libertarians can celebrate an attack on big government. The problem is that all these efforts are unlikely to actually help the patients with life-threatening diseases. Indeed, these laws may be harmful if they draw attention and resources away from efforts to develop effective treatments, engender confusion about the FDA pathway for compassionate use of medications, or create false hopes for terminally ill patients.

All of which right-to-try laws do, and worse.

There will always be a conflict between personal freedom and protecting patients, as well as ensuring maximal societal good. We see this in opposition to school vaccine mandates, support for cancer quackery and dubious stem cell clinics, and, of course, right-to-try. Unfortunately right-to-try laws represent dangerous placebo legislation. They only give the illusion of doing something given that the FDA, not the states, controls drug approval. The reason for their existence is not so much to help patients, but as part of a long game to build a groundswell of support for policies that would ultimately hobble the FDA's ability to oversee the efficacy and safety of drugs. These laws are bad for patients, bad for doctors, bad for drug development, and bad for science. That's why going through the states is the wrong way to attack this problem. If we as a society believe that terminally ill patients should have easier access to investigational drugs, then reforming how the FDA handles compassionate use exemptions, not a patchwork of state laws with no teeth, is how it should be done.

oracknows Mon, 05/25/2015 - 04:40

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The issue is an easy one for the media to exploit. And it's a global phenomenon, across party lines: the leftish Süddeutche Zeitung in Germany has a long article just this weekend about a nine-year old girl suffering from an incurable condition for which there's a drug in testing. The pharmaceutical company concerned is also refusing to release it on a test basis.

Living here in a country with a public medical system it is less easy to shift accountability and responsibility. If the government passed such a law and there is a disastrous outcome the impact is felt in the treasury and, possibly, at the ballot box. So the politicians push back when an appeal for an exemption is made public.

That doesn't stop some from pursuing experimental drugs or surgery (or quackery) elsewhere, including in the US. The problem is when they return and trouble develops. This happens. If the ailing patient or their family goes public lively debate then ensues regarding who pays to fix the problem. That is if the patient hasn't already died.

Here is a question for the lawyers out there: Why, exactly, would giving a patient an experimental drug under one of these "right to try" laws not be considered experimenting on a human subject?

The IRB requirement exists for a reason, and that reason is previous abuses of medical experimentation on human subjects have demonstrated the need for such a process. So a related question to the above would be: is the federal requirement for IRB approval sufficiently strong to override these state laws? If I were the ORI, I would be prepared to come down as hard as the law allows on any physician or institution that performs any such research without IRB approval. Up to and including debarment from federal research funding, par encourager les autres.

The success rate for drugs entering phase 2 trials is about 30%. That's followed by a 30-40% failure rate in phase 3. Those are multiplied together to get a cumulative rate (e.g., 9-12%). See Hays et al, Nature Biotechnology 32, 40–51 (2014) for trial success rates by study phase and by indication.

"Right to Try" exposes gullible, frightened, and vulnerable patients to drugs that have approximately a 1/10 chance of being beneficial.

IANALNDIPOOT, but I would guess that the reason it's not considering experimenting is because the law says it isn't.

@Eric Lund: Experimenting on human subjects isn't illegal in itself, you just have to get informed consent. I'm not ultra-familiar with IRB law, but I would think that you don't need an IRB every time you give a patient an experimental drug, as long as you have informed consent.

IANAL either, but the legal question seems to be whether the states get to define "experimental." (The ethical question is to my mind straightforward: this would be unethical even if it turns out to be slipping through a legal loophole.)

Off topic, but a measles question has come up in a conversation with a vaccine opponent and I wanted to pick the brains of the smartest people I know:

If you look at the official figures, it appears that Great Britain has a measles mortality rate of one in five thousand cases while America has a rate of three in one thousand: fifteen times higher.

Is there a simple explanation for this difference?

Thanks.

This is a stretch even for Orac.

From the template:

"... a progressive disease or
medical or surgical condition that
entails significant functional impairment, that is not
considered by a treating physician to be reversible even with administration of current federal drug administration approved and available treatments, and that, without life-sustaining procedures, will soon result in death."

OK, where's the woo here? It's the same science-based doctor who might tell the patient to try something with a 10% chance of working, but it's OK if it's 10% but not if it's unknown?

I'm hardly a fan of pseudo-libertarian think-tank machinations, and that aspect of it is worthy of concern, but harming the patient? It might not be a choice I would take, if there were a decent right-to-die option, but give this histrionic moralizing a rest. (And note that it also absolves heirs and others of liability for costs.)

Great Britain has a measles mortality rate of one in five thousand cases

I credit the superior English diet and housing.

It might not be a choice I would take, if there were a decent right-to-die option, but give this histrionic moralizing a rest.

It's Memorial Day, not Moreirony Day.

So a related question to the above would be: is the federal requirement for IRB approval sufficiently strong to override these state laws?

The basic question is what the Common Rule, 45 C.F.R. pt. 46, applies to. The answer is provided in roundabout fashion by § 46.102(e):

"(e) Research subject to regulation, and similar terms are intended to encompass those research activities for which a federal department or agency has specific responsibility for regulating as a research activity, (for example, Investigational New Drug requirements administered by the Food and Drug Administration)."

Starting with § 46.101 helps, but I get the impression that if you're already playing IND ball with the FDA, then the whole of the machinery is in play. The only question left is whether intrastate circumvention à la old-school Scamislaw is possible, but I doubt that anyone who was seriously trying to develop a drug would be interested in pursuing it.

@8 Robert Bell
As herr doktor bimler points out the superior English diet must be a consideration. Baked beans on toast and chip butties do wonders to toughen up the children to the point that measles is a minor inconvenience. Berri-berri may be a problem but heck one cannot have everything.

Another suggestion is faster and better access to healthcare. The NHS has no co-pay, everyone is covered and, IIRC, the NHS also covers drugs so what might be a serious worry in the USA regarding expenses is irrelevant in the UK. Thus one is likely to react far more quickly in situation.

Here in Canada I was in to see my doctor for a rotor cuff (sp?) problem in January. While trapped in the office, I got stabbed with a flu vaccine needle, had my blood pressure and weight checked and got an impromptu ultra-sound on my elbow. Total out of pocket expense. CDN$ 0.00.

Of course our taxes pay for it but we pay less per capita for healthcare than the USA and, personally , I think the system encourages a proactive approach to health care. Particularly for low income families, there is no real expense to seeing a doctor before a situation becomes serious.

#8 I would say that first of all there are too few measles cases in the US thanks to vaccines to determine a specific death rate. If the incidence is 50-100 cases per year, and the death rate is at most 1 per 1000, there would be huge error bars in any estimate of the death rate.

One would also have to take into account that the US has a higher vaccination rate than the UK. This means that a larger proportion of the unvaccinated in the US are those who for medical reasons are not vaccinated. And since we all know that measles can have a much, much higher death rate if you are immunocompromised, and a larger proportion of the susceptible in the US are immunocompromised or have allergies, it is not unlikely that the death rate would be higher.

@Zebra

The problem is not with woo, or with testing unproven medications. It's that there is already a mechanism in place for providing terminally ill patients with unproven medication: it's called compassionate use (officially known by the FDA as "expanded access"), and it is chock full of patient protections.

The current onslaught of right to try laws are objectively worse in almost every respect, stripping out pretty much every patient protection the federal system employs, because removing oversight is supposed to make it better somehow.

zebra,

Orac does not limit himself to posting about woo--it's just that, unfortunately, there's a lot of woo to post about. But, as always, if a topic doesn't interest you, there's a lot else to read on the Internet.

@caryatis #6: You don't have to have an IRB for every patient but every experimental drug has to have an IRB before a clinical trial can begin.

Since these "right to try" laws require at least a Phase I trial to have been completed, an IRB would be in place. However, I doubt IRB's consider the effects of these stupid laws.

It’s that there is already a mechanism in place for providing terminally ill patients with unproven medication: it’s called compassionate use (officially known by the FDA as “expanded access”), and it is chock full of patient protections.

These are Bad Things within the zombie idyll of Endless September.

@Johanna

I would say that first of all there are too few measles cases in the US thanks to vaccines to determine a specific death rate.

True that. Small sampling effects could play some tricks on us.
When my country was hit by a measles epidemic around 2010-2012, at some point I read about 4000 cases and 5-6 deaths, so a 1-2 per 1000 death rate.
Reading about the epidemic recently, I found the European numbers, and they resolved in under 1 per 2000 death rate. Most measles-related deaths happened in my country.
Either my country's medical facilities and staffs were under par (not that improbable, being complacent could happen to anyone), or we were unlucky. Either way, determining a precise death rate is tricky and very context-dependant.
Well, it's certainly and unfortunately not zero.

Why are right-to-try laws so popular? Because terrified, dying people are often desperate to be lied to, as the Goldwater Institute For Flappy Paddle Babies is only too happy to do. After all, everybody dies: what really matters is separating them from lots of greenbacks first.

#15 Bob,

Orac says:

If we as a society believe that terminally ill patients should have easier access to investigational drugs, then reforming how the FDA handles compassionate use exemptions, not a patchwork of state laws with no teeth, is how it should be done.

Exactly. And as with many of the issues discussed here, if you leave a vacuum, they will come. Vaxxers and Wooers and Tryers represent variations on the existing system's practices, taking advantage of unfilled niches.

But it is so much more fun to bash the fringe elements than go up against the establishment, particularly if that might affect one's paycheck.

Except that in this case right-to-try is not a "fringe element." It's the mainstream.

@ zebra

Vaxxers and Wooers and Tryers represent variations on the existing system’s practices, taking advantage of unfilled niches.

OK, I will bite, at the risk of steering into OT (so let's say you only have one post on this - make it count)

You argument seems interesting, but then I would like you to elaborate:
What is this empty niche that "vaxxers" are filling, and what should be filling it instead?

(or did you meant "anti-vaxers"? or do you conflate vaxers and anti-vaxers together?)

Oh, and please left the Pharma shill gambit outside. It's very easy and very unfair to ask other people to sacrifice their own interests, especially if there is no counterbalancing benefit in sight.

--------------
(apologies in advance in case of double post, my internet seems to be misbehaving)

Yeah, zebra didn't make a lot of sense with that "empty niche" bit.

Helianthus@24:

You[r] argument seems interesting

You should subscribe to his newsletter. It's all the rage on Htrae.

AND it's 1200!!
Do I get a free drink?

OOps! How did that happen? wrong thread sorry

Yeah, zebra didn’t make a lot of sense with that “empty niche” bit.

It makes even less in the context of his whole DNR–autonoMEE trip.

I didn't realise this was one of those "template" bills doing the rounds. There was a similar bill here in the UK but it didn't pass:

http://services.parliament.uk/bills/2014-15/medicalinnovation.html

I don't get these (excuse my language) stupid fuckers. Organic raw vegan whole food diet + homeopathy (bullshittery all around) = good.
FDA = bad
Big Pharma = bad
FDA = Big Pharma Shill
Vaccines = FDA + Big Pharma = Bad
Legislation that opens a Lockheed hanger of a back door for Big Pharma - FDA - any culpability = FREEDOM!!!!!!
Do any of these fucking assholes know what the fuck they are trying to achieve other than an Orwellian wet dream?

Andrew@30:

Ah, the Saatchi Bill. The Bad Sciencers have been all over this one for some time. (And yes, the Saatchi squad's activities has been every bit as dishonest, manipulative, and evasive as its colonial cousins' - though has there ever been a salesman who was not?)

Unfortunately, the noxious little toad is determined to try it on again for the new parliamentary session. And so it goes.

...

Frankly, it's long past time all these screeching histrionic doucheholes need to be sat right down on their ridiculously spoiled, self-obsessed western asses and firmly told by a genuine grown-up:

The point of medical trials is not to stop you dying of the horrible diseases you've already got, it's to ensure your kids never will.

Because it's our children, and their children too, who will ultimately pay the real price for our cretinous generation's willfully ignorant corruption and destruction of the very systems and procedures that our parents before us, from their own blood and suffering, built to protect us all.

@caryatis #6: One of the IRBs' functions is to review informed consent forms to make sure that the patients are indeed informed. They also make sure the experiments are ethically designed (risks are commensurate with potential benefits, doesn't unnecessarily target vulnerable populations, etc.). Both of which I think would be relevant to experiments involving terminally-ill subjects.
You could avoid IRBs if you are not collecting any data (i.e. by making it not an experiment), but a company that hands out experimental drugs without wanting to collect any data in return would be very suspicious indeed.

Ebola, "right-to-try," and placebo legislation

oracknows — Tue, 28 Oct 2014 09:00:39 +0000

Ebola, "right-to-try," and placebo legislation

One of the biggest medical conspiracy theories for a long time has been that there exist out there all sorts of fantastic cures for cancer and other deadly diseases but you can’t have them because (1) “they” don’t want you to know about them (as I like to call it, the Kevin Trudeau approach) and/or (2) the evil jackbooted thugs of the FDA are so close-minded and blinded by science that they crush any attempt to market such drugs and, under the most charitable assessment under this myth, dramatically slow down the approval of such cures. The first version usually involves “natural” cures or various other alternative medicine cures that are being “suppressed” by the FDA, FTC, state medical boards, and various other entities, usually at the behest of their pharma overlords. The second version is less extreme but no less fantasy-based. It tends to be tightly associated with libertarian and small government fantasists and a loose movement in medicine with similar beliefs known as the “health freedom” movement. who posit that, if only the heavy hand of government were removed and the jack-booted thugs of the FDA called off, free market innovation would flourish and all these cures, so long suppressed by an overweening regulatory apparatus, the floodgates would open and these cures, long held back by the dam of the FDA, would flow to the people.(Funny how it didn’t work out that way before the Pure Food and Drug Act of 1906.) Of course, I can’t help but note that in general, in this latter idea, these fantastical benefits seem to be reserved only for those who have the cash, because, well, the free market fixes everything.

The idea that the FDA is keeping cures from desperate terminally ill people, either intentionally or unintentionally, through its insistence on a rigorous, science-based approval process in which drugs are taken through preclinical work, phase 1, phase 2, and phase 3 testing before approval is one of the major driving beliefs commonly used to justify so-called “right-to-try” laws. These bills have been infiltrating state houses like so much kudzu, and the Ebola outbreak has only added fuel to the fire based on the accelerated use of ZMapp, a humanized monoclonal antibody against the Ebola virus, in some patients even though it hadn’t been tested in humans yet (more on that later). Already four of these laws have been passed (in Colorado, Missouri, Louisiana, and now Michigan) with a referendum in Arizona almost certain to pass next week to bring the total to five states with such laws. Basically, these laws, as I’ve described, claim to allow access to experimental drugs to terminally ill patients with a couple of major conditions: First, that the drug has passed phase I clinical trials and second that the patient has exhausted all approved therapies. As I’ve explained before more than once, first when the law hit the news big time in Arizona and then when a right-to-try bill was introduced into the legislature here in Michigan, they do nothing of the sort and are being promoted based on a huge amount of misinformation detailed in the links earlier. First, having passed phase 1 does not mean a drug is safe, but right-to-try advocates, particularly the main group spearheading these laws, the Goldwater Institute, make that claim incessantly. Second, they vastly overstate the likelihood that a given experimental drug will help a given patient. The list goes on.

Unfortunately, a week and a half ago, the cruel sham that was the Michigan right-to-try bill was passed into law and signed by Governor Rick Snyder. It’s rather interesting how this came about. Senator John Pappageorge introduced Senate Bill 991 in the Michigan Senate over the summer. There was very little news coverage, which I considered odd, given the heavy news coverage of right-to-try bills in other states. In fact, I only happened to hear that the Michigan right-to-try bill had even been introduced into the Senate when a colleague who happens to deal with the legislature as part of his job let me know about it. I also learned that in addition to home grown patient advocates supporting the bill, there was a flack from the Goldwater Institute flown in to testify and that no one from Michigan universities or academic medical centers was particularly eager to testify against the bill due to the expected backlash.

I can totally understand the patient impetus for these laws, given that I have had family members with terminal illnesses. Unfortunately, however, forces like the Goldwater Institute are taking advantage of the very human desire not to die and not to be forced to watch one’s loved ones die, all in order to push bad legislation. Indeed, the Goldwater Institute uses terminally ill patients desperate for their lives in much the same way Stanislaw Burzynski uses them: As shields and weapons in their battle against the FDA and state medical boards. That’s why, as I’ve morbidly joked before, being against right-to-try in the eye of the public is not unlike being against Mom, apple pie, the American flag, and puppies, hence the reluctance of even doctors doing clinical trials to publicly voice opposition. The most predictable attack against anyone who dares to publicly oppose these bills has been to portray opponents as not just callous, but as practically twirling their mustaches with delight and cackling evilly while watching terminally ill patients die without hope. (I exaggerate—but only slightly.) Few are the physicians and scientists (and even fewer still the medical centers and universities) who want to risk being portrayed that way, and one who did testify against it reported enduring withering looks from patient advocates, who, like Burzynski patients and families, really do view opponents of right-to-try as enemies actively seeking to prevent them from saving their lives or the lives of family members.

Before I knew it, Senate Bill 991 had passed overwhelmingly. So, seeing what was coming next, I wrote my House Representative to urge that he oppose the bill, House Bill 5651. He was receptive and a little surprised that anyone would be against the bill, but he admitted that my arguments made him think. Even so, I was under no illusion that he was likely ever to vote against it. He didn’t. On October 1, House Bill 5651 passed the House unanimously and was signed by Governor Rick Snyder on October 17. Interestingly, despite my having tried to pay close attention to news reports and House activity, I only learned of this last week, when news stories noted that Snyder had already signed the bill! The fix appeared to have been in, as this bill passed with about as close to zero news coverage as I’ve seen for a bill this major in every other state where it’s appeared.

Not surprisingly, libertarians are declaring this a big “win” for patient’s rights. It’s nothing of the sort. The flavor of the arguments can best be seen in two articles from Reason.com’s Nick Gillespie, who is clearly clueless about clinical trials. Basically, he took to Reason.com to gloat, referencing an article from over two weeks ago that he entitled The Upside of Ebola (Yes, There May Actually Be One). It’s about as blatant a move to take advantage of the Ebola outbreak to promote bad right-to-try legislation as I’ve ever seen. The subtitle exults:

A rising death toll, mass panic, scary mortality rate—what could possibly be good about the out-of-control epidemic? It may accelerate the adoption of laws giving patients more power.

Yeah, sure. Thousands of people are dying of a horrible disease in Africa while people in the U.S. are freaking out about the possibility of the virus causing outbreaks right here at home, and Gillespie sees these events, apparently more than anything else, as an opportunity to push his libertarian agenda with respect to medicine:

Ebola’s arrival and seeming spread in America is causing mass panic, tasteless Internet jokes, and incredibly poorly timed magazine covers. Can anything good come out of the disease, which has no known cure and a terrifying mortality rate of 50 percent?

Yes. To the extent it forces a conversation about the regulations surrounding the development of new drugs and the right of terminal patients to experiment with their own bodies, Ebola in the United States may well accelerate adoption of so-called right-to-try laws. These radical laws allow terminally ill patients access to drugs, devices, and treatments that haven’t yet been fully approved by the Federal Drug Administration and other medical authorities. The patients and their estates agree not to bring legal action against caregivers, pharmaceutical companies, and insurers.

You don’t have to be a doctrinaire libertarian—though it helps—to see the value in letting people with nothing left to lose experiment on themselves. They may get a new lease on life. The rest of us get meaningful information that may speed up the development of the next great medical intervention.

Actually, you do rather have to be a doctrinaire libertarian to have a reality distortion field as powerful as Nick Gillespie’s that leads him to write drivel like this. Ebola and right-to-try laws. Hmmmm. How is one thing not like the other (or not related to the other)? First of all, Gillespie’s rationale is a complete non sequitur, clearly designed to take advantage of the Ebola panic to persuade people that right-to-try laws are a good idea, even though such laws would not have had one whit of an effect on the odd patient in the US who might be infected with Ebola. After all, Ebola, as deadly as it is, is not a terminal illness. Second, I can’t help but note that existing FDA mechanisms got ZMapp to American Ebola patients rather rapidly, no need for right-to-try laws necessary. But excuse me. What Gillespie says is that Ebola and ZMapp are “forcing a conversation.” I suppose that’s true, but it’s the wrong conversation, a profoundly deceptive conversation, in which an advocate of right-to-try laws shamelessly takes plays on people’s fears of Ebola to promote these bad laws. Claiming that there is “no good argument against right-to-try” (wrong, wrong, wrong), Gillespie also shamelessly attacks straw men, representing the primary argument against right-to-try as giving patients “false hope.” There are lots of other reasons why these are bad laws.

But Gillespie is just getting warmed up:

But what’s already cruel is the FDA’s drug-testing process. It’s massively expensive and overly long, costing between $800 million and $1 billion to bring a drug to market and taking a decade or more to complete the approval process. There’s every reason to believe that the FDA approval process is killing as many or more people than it saves, especially as the FDA doesn’t allow approvals from Europe and elsewhere to stand in for trials here.

Uh, no. There is not “every reason to believe” anything of the sort. See? Once again, there’s the myth that there are all these fantastic cures out there that the FDA, through its bureaucratic inertia, is keeping from you. I am rather grateful, though, that Gillespie, through his link, makes his intent very clear. The article to which he linkes is entitled Kill The FDA (Before It Kills Again), in which, referencing the movie Dallas Buyers Club—which I finally saw on cable and was surprised to find that, leaving aside its historical inaccuracies about the AIDS epidemic in the 1980s, taken just as a movie it was at best just OK (I was seriously disappointed)—Gillespie proclaims that the FDA “continues to choke down the supply of life-saving and life-enhancing drugs that will everyone agrees will play a massive role not just in reducing future health care costs but in improving the quality of all our lives.” And what is his rationale? Wrap your mind around this:

As my Reason colleague Ronald Bailey has written, this means the FDA’s caution “may be killing more people than it saves.” How’s that? “If it takes the FDA ten years to approve a drug that saves 20,000 lives per year that means that 200,000 people died in the meantime.”

Completely missing from Bailey’s and Gillespie’s equation is the number of drugs that the FDA doesn’t approve because they don’t show efficacy and safety that could allow even more than those 20,000 people a year to die or even actively kill some of them. As conceded by even Bailey, it was the FDA that prevented, for example, approval of Thalidomide in the US and the rash of birth defects seen elsewhere in the world. Bailey's argument is, at best, tenuous, at worse misleading. Gillespie notes:

A 2006 Government Accountability Office (GAO) study found that the number of new drug applications submitted to the FDA between 1993 and 2004 increased by just 38 percent despite an increase in research and development of 147 percent. The mismatch, said GAO, was the result of many factors, ranging from basic issues with translating discoveries into usable drugs, patent law, and dubious business decisions by drug makers. But the problems also included “uncertainty regarding regulatory standards for determining whether a drug should be approved as safe and effective,” a reality that almost certainly made pharmaceutical companies more likely to tweak old drugs rather than go all in on new medicines.

Notice how this is another non sequitur applied to right-to-try laws, given that the answer to this problem would be regulatory clarity, not state-by-state right-to-try laws. Think of it this way: What’s more uncertain? The FDA or having different laws in different states regarding “right to try”? Gillespie’s citing his previous article claiming that the FDA is killing you in an article promoting right-to-try is a very good indication what these laws are really about. They are not about helping patients. That’s how they are sold to desperately ill patients, but in reality libertarians like Gillespie and Bailey are using desperately ill patients in the same way that Stanislaw Burzynski is: As a powerful tool to sway public opinion against the FDA and towards their viewpoint.

There’s a reason that certain aspects of these laws are not as widely emphasized in the PR offensive in favor of right to try. It’s because they are pure “health freedom” and libertarian wingnuttery. For example, if you look at the Goldwater Institute template for right to try laws, which, unfortunately, has been the basis of every right to try law passed and under consideration, you’ll notice a number of highly problematic clauses. As I’ve discussed multiple times, there is the requirement that the drug or device has only passed phase 1 trials, which, given how few drugs that have passed phase 1 actually make it through to approval, is a really low bar, especially since most phase 1 trials involve fewer than around 25 patients.

More disturbing are the financial aspects. The Goldwater Institute legislative language template (to which the Michigan legislation is virtually identical) allows drug companies to charge patients, with no provision to help patients pay for exercising right-to-try. Indeed, it specifically states that the bill “does not require any governmental agency to pay costs associated with the use, care, or treatment of a patient with an investigational drug, biological product, or device” and that insurance companies do not have to pay for costs associated with the use of such therapies. You know what this means? Insurance companies could refuse to pay for care related to complications that might occur because of experimental treatments. You use an experimental drug and suffer a complication? Too bad! Your insurance company can cut you off! Now, it’s unlikely that government entities like Medicare or Medicaid would do that, but insurance companies certainly will.

Basically, what this law says is: If you can afford it yourself, no help, you can have it. If not, you’re SOL. As I’ve pointed out, if there’s one thing worse than dying of a terminal illness, it’s suffering unnecessary complications from a drug that is incredibly unlikely to save or significantly prolong your life and bankrupting yourself and family in the process. Right-to-try encourages just that. What’s more compassionate? Attacking the FDA and degrading the approval process that requires drug safety and efficacy while dangling false hope in front of patients or standing up and protecting patients from the harm such a policy could cause. Let’s just put it this way: I predict that Stanislaw Burzynski will soon be sending antineoplastons to patients in right-to-try states if, as he keeps bragging, the FDA has allowed him to reopen his clinical trials. After all, his antineoplastons would qualify just fine under right-to-try laws if they’re back under clinical trial. Indeed, if there's one thing the decades-long battle between the FDA and Burzynski tells us, it's that the FDA actually bends over way too far backwards to allow manufacturers of dubious drugs to prove themselves.

Finally, the anti-FDA rhetoric, such as linked to by Gillespie, is a very good indication that the true purpose of right-to-try legislation is to neuter the FDA's power to control drug approval, thus greatly loosening or even eliminating hurdles to the drug approval process. It is no coincidence that the strongest, richest, and most vocal proponents of these laws are the Goldwater Institute and libertarians like Nick Gillespie and Ronald Bailey, who, not coincidentally, think that the FDA is “killing us.” Those articles are a definite tell. It's also clearly a strategy to get right-to-try passed in as many states as possible and get referendums passed by wide margins to pressure the federal government to weaken the FDA.

In the end, though, right-to-try laws are what I like to call “placebo” laws in that they make people who pass them and support them feel good but don’t actually address the problem that they are supposedly intended to address. Drug approval regulatory authority lies with the FDA; it could completely ignore state right-to-try laws. The FDA also has a compassionate use program and rarely turns down such requests. Admittedly, the application process is long and probably too onerous, but the answer to that problem is not state right-to-try laws. It’s to address the issue at the federal level. I’ve also said in an interview that, now that my state government has foolishly passed a right-to-try law, one of two things is likely to happen: Either nothing, because federal authority trumps state authority, or disaster for patients, doctors, and, yes, biotech and drug companies. Everybody, myself included, wants to help terminally ill patients. After all, I’ve seen too many of them. Right to try and similar misguided efforts, however, are not the way.

oracknows Tue, 10/28/2014 - 05:00

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Clinical trials

Skepticism/Critical Thinking

Food and Drug Administration