experimental therapeutics

A victory and a more substantial defeat for the cruel sham known as "right to try"

oracknows — Fri, 30 Sep 2016 02:00:59 +0000

A victory and a more substantial defeat for the cruel sham known as "right to try"

I’ve referred to so-called “right to try” laws as a cruel sham.on more than one occasion. Since 2014, these laws, all based on a template provided by the libertarian Goldwater Institute, have been proliferating at the state level with the help of lobbying by the aforementioned Goldwater Institute and a concept that makes it pitifully easy to caricature opposition to these laws as wanting to heartlessly snatch away from terminally ill patients the last chance at life while laughing and twirling one’s mustache like Snidely Whiplash. Not surprisingly, state legislatures all over the country have found such laws irresistible, leading to their passage in over 30 states in just two and a half years. Over the last week, right-to-try has had a major victory in that, contrary to what he did last year and contrary to the hope of science advocates, California Governor Jerry Brown signed the right-to-try bill (AB-1668) that was passed earlier this month. However, it has also suffered a major defeat in that a couple of days ago the federal right-to-try bill was blocked in the Senate.

The basic premise behind right-to-try laws is that people are dying in droves because the FDA is too slow and too 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 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. Sounds reasonable on the surface, right? What is assiduously not mentioned are other libertarian-based aspects of these laws. For instance, there is no mechanism in most right-to-try laws to help patients seeking to access experimental therapeutics financially. Indeed, pointedly, such bills go out of their way to state that health insurance companies do not have to pay for suc treatments and can be interpreted to state that they don’t have to pay for treating 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.

These laws also explicitly remove patient protections in that most of them state that doctors recommending right-to-try can’t be sued for malpractice or disciplined by their state medical boards, seemingly no matter how inappropriate or incompetently executed such a request might be. Nor can drug manufacturers be sued. Basically, these laws tell terminally ill patients: Good luck. You’re on your own. And don’t sue if things go bad, no matter what. 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 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 have high levels of life-threatening toxicity.

Of course, the biggest flaw in these laws is that it is federal law, not state law, that controls drug approval. Right-to-try laws can say that terminally ill patients have the “right” to access experimental therapeutics, but it is the FDA that determines whether they, in fact, do. Companies are understandably reluctant to grant access to experimental therapeutics without the FDA’s prior approval because (1) the FDA will not look kindly upon it and they want FDA approval and (2) if there are any adverse events it could harm their chances of winning approval for their drugs. Also, the FDA does have what it calls its Expanded Access Program (sometimes referred to as Compassionate Use) already to allow terminally ill patients to access experimental therapeutics, and it does it without removing patient protections under Institutional Review Board (IRB) supervision. Moreover, the FDA already grants the overwhelming majority of Expanded Access requests. Indeed, as I pointed out, thus far, after two and a half years of existence, right-to-try has been a miserable failure. The Goldwater Institute can’t identify a single patient who has received an experimental drug under a state right-to-try law, although it claims to know of 40-60. Meanwhile a quack like Stanislaw Burzynski has abused right-to-try. Meanwhile, the only patient I’ve been able to find who actually used right-to-try died.

So it was that I was very disappointed to learn that Governor Jerry Brown had betrayed the citizens of the State of California by buckling under this time:

Terminally ill patients in California will be able to try potentially life-saving medication before it passes FDA final review thanks to a new piece of legislation inspired by the movie "Dallas Buyers Club."

The bill, dubbed the "Right to Try" law, makes California the 32nd state to allow patients with terminal illnesses to try drugs that have passed the FDA's Phase 1, but haven't been fully approved.

Phase 1 is the first stage of drug testing in human patients. Drugmakers earn approval to conduct clinical trials on people after presenting the results of successful trials on animals, according to the FDA. After presenting the data -- and a plan for human trials -- the FDA determines whether drug companies can go forward with additional testing.

Patients can try experimental treatments only after exhausting all other options, according to the libertarian think tank Goldwater Institute, and the patients' treatments with Phase 1 drugs cannot be included as data in ongoing clinical trials.

Of course, as I pointed out before when I discussed the California bill, this description is utter bollocks. In a way, the California bill (now law) is worse than the average state right-to-try law. It doesn’t actually require that the patient be terminally ill, only that he has an “immediately life-threatening disease or condition.” As I put it at the time, that’s incredibly broad. A severe case of pneumonia could be “immediately life-threatening.” A heart attack is definitely “immediately life-threatening.” A stroke is “immediately life-threatening.” “Immediately life-threatening” is not the same thing as “terminal.” Yet AB-1668 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.

You could ask, quite reasonably: Why does this matter? One reason is that it’s California, the most populous state in the country. Any law passed in California matters. California is always the biggest prize, and right-to-try advocates were bitterly disappointed when Gov. Brown vetoed a previous right-to-try bill last year.

Unfortunately, the Goldwater Institute has been very effective in co-opting terminally ill patients to use the considerable justified sympathy voters and legislators feel for them to lobby for right-to-try:

In a guest column for the Washington Post, 32-year-old Matthew Bellina says Right to Try laws are an improvement on the FDA's Expanded Access program because they stipulate that the FDA won't shut down or delay clinical trials if an experimental treatment goes wrong.

Because derailing clinical trials can deal a significant blow to drug companies that have poured millions of dollars into research and development, drug companies are less likely to sponsor terminally ill patients without guarantees that the FDA won't retaliate for failed treatment.

Bellina, a military veteran and father who has terminal ALS -- amyotrophic lateral sclerosis, also called Lou Gehrig's disease -- testified before the Senate on a federal version of Right to Try.

Turning down someone dying of Lou Gehrig’s disease is pretty much close to impossible for a politician, even if the legislation being proposed is profoundly anti-patient, as right-to-try is. Also, this is one of the most pernicious aspects of right-to-try, as you will see. So let’s segue to the federal right-to-try bill. Gov. Brown might have buckled and signed what I like to refer to as “placebo legislation,” which makes legislators feel good and believe that they’ve done something when in reality they’ve done nothing, but the federal bill is where the action is because that’s the real goal of the Goldwater Institute, to weaken and then ultimately neuter the FDA. The Goldwater Institute is politically savvy enough not to come right out and explicitly say this, but other libertarians are not.

A week ago, hearings were held on a federal right-to-try bill, S.2912, known as The Trickett Wendler Right to Try Act of 2016. This is a bill being pushed by Republican U.S. Sen. Ron Johnson. Interestingly, as the bill has been US Senate Committee on Health, Education, Labor, and Pensions, Johnson used his position as committee chair of the US Senate Committee on Homeland Security and Government Affairs to hold hearings on the bill, even though it has nothing to do with his committee’s purview. Sen. Johnson’s opening statement is basically a rehash of Goldwater Institute talking points, complete with the usual anecdotes about patients with terminal illnesses who might have been saved:

Despite the legal uncertainty there are doctors willing to jeopardize their practice to give patients needed, but unfortunately unapproved, treatments. One of them is Houston oncologist Dr. Ebrahim Delpassand. Even though the FDA has told him no, he bravely continues to treat patients under his state’s law. Now nearly 80 patients, whose chance of survival would be, as he puts it, “close to none,” are alive thanks to his treatment.

This caught my attention, as this is a potentially verifiable claim. There is a video of Dr. Delpassand giving a statement included in the testimony:

Whoa. He’s with Excel Diagnostics, the very same company that I discussed when I looked into the one patient in Texas whom I could find who had accessed right-to-try and who had not been saved. Contrary to Sen. Johnson’s claims, he is not an oncologist; he is a radiologist. Of course, nothing Dr. Delpassand claims in his video statement shows that 80 patients who would have died have been saved, thanks to his being a brave maverick doctor willing to buck the FDA. One notes a highly one-sided account designed to make Dr. Delpassand look as good as possible. In any case, the therapy discussed by Dr. Delpassand does have potential, as I mentioned before. However, one thing that stood out to me was how the Goldwater Institute reached out to Dr. Delpassand. So basically, right-to-try allowed Dr. Delpassand to charge for the use of his treatment, even though it is not FDA-approved. Not surprisingly, the Goldwater Institute is painting this example as the nefarious FDA preventing patients from saving their lives, even though this treatment is not curative, as I described. He’s also a flack for the Goldwater Institute, having participated in a promotional video touting right-to-try:

So his evidence is that “many of these patients were given three or six months to live” and are alive a year later? Seriously? Stanislaw Burzynski uses the same argument about the patients he treats.

In any case, as I pointed out three weeks ago, the federal right-to-try bill is even worse than state right-to-try bills because (1) it would actually do something and (2) what it would do would be very, very bad for patients indeed. For example, it would forbid the FDA from considering adverse events suffered by patients utilizing experimental drugs under right-to-try when considering a drug for approval. Seriously, it says that. A patient could die, clearly as a result of an experimental drug, and the FDA would be explicitly barred from considering that information when deciding whether to approve the drug or not.

Speaking of Stanislaw Burzynski, I couldn’t help but note the testimony of Peter Lurie, MD, MPH. He repeated the same points about how the FDA’s Expanded Access Program rarely rejects requests and then notes:

However, even patients with serious or life-threatening diseases and conditions require protection from unnecessary risks, particularly as, in general, the products they are seeking through expanded access are unapproved – and may never be approved. Moreover, FDA is concerned about the ability of unscrupulous individuals to exploit such desperate patients. Thus, with every request, FDA must determine that the potential patient benefit from the investigational drug justifies the potential risks and that the potential risks are not unreasonable in the context of the disease or condition to be treated.

“Unscrupulous individuals”? That would well describe Stanislaw Burzynski. It could also describe pharmaceutical companies willing to profit off of drugs that made it through phase I studies but are not approved yet.

Fortunately, for now at least, the federal right-to-try bill has been blocked:

Republican U.S. Sen. Ron Johnson's push for a right-to-try bill ran up against the reality of hardball politics Wednesday.

Johnson's measure to allow terminally ill patients to receive experimental drugs not approved by the Food and Drug Administration was blocked by Senate Minority Leader Harry Reid (D-Nev.).

Johnson sought to move the bill through unanimous consent, meaning one senator could halt its progress. And that's what Reid did, blunting a Johnson initiative for the second time in recent months. In July, Reid blocked Johnson's bill to protect federal whistleblowers from retaliation.

Johnson faces a tough re-election fight against Democrat Russ Feingold, so any move to get legislation through by a parliamentary maneuver was always going to be difficult.

And it's even harder since Democrats are still upset that Republicans have blocked President Barack Obama's nominee to the U.S. Supreme Court, Merrick Garland.

Reid said he understood the "seriousness" of the Johnson proposal and acknowledged "the urgency that patients and their families feel when they're desperate for new treatments."

In objecting to the measure, Reid said Johnson's bill didn't have bipartisan support — there were 40 Republican co-sponsors and two Democrats. He said the bill didn't go through the hearing process where all the major players on the issue have voice. The Johnson-chaired Homeland Security & Governmental Affairs panel held two hearings on the subject.

"I think we should have had a hearing on Merrick Garland," Reid said on the Senate floor.

This is what I would call doing the right thing for the wrong reason. Unfortunately, that’s what happens in politics a lot. I’ll take it, though. If state right-to-try bills are basically symbolic rants against the FDA, the passage of a federal right-to-try bill would be a disaster for patients and the clinical trial process.

oracknows Thu, 09/29/2016 - 22:00

Tags

Clinical trials

medicine

Politics

Science

Skepticism/Critical Thinking

Ebrahim Delpassand

Excel Diagnostics

experimental therapeutics

right to try

Ron Johnson

Trickett Wendler Right to Try Act of 2016

Categories

I would be interested in learning how many are simultaneous supporters of 1) Right to Try, because it's immoral to deny Hope to the Needy and 2) the Precautionary Principle, because we just don't know if this or that novel procedure might turn out to have some horrible side effect decades down the road.

Depending on whose ox is being gored, of course.

it would forbid the FDA from considering adverse events suffered by patients utilizing experimental drugs under right-to-try when considering a drug for approval.

Great idea. So much for the rest of the world trusting the FDA when the agency approves a drug. If that idiot law passes we don't even need to invoke a "conspircy" that the US govenment is hiding information on drugs. We just need to point to the law that requires it to ignore data.

Sen. Johnson, sponsor of this bill, is up for reelection this year, and polling suggests that he is likely to lose to former Sen. Russ Feingold. There are plenty of reasons already why I would rather have Feingold than Johnson in the Senate, and this is one more.

@jrkrideau: That's a feature, not a bug. Libertarians start from the premise that all government regulation is bad, so kneecapping the FDA is considered a good thing. Never mind that the FDA exists precisely because we have previously tried the libertarian approach to drug regulation and found that people tend to die needlessly as a result.

The worst thing about crap laws like this is that even when it becomes absolutely clear that they are merely a quacks' charter, it is virtually impossible to reverse them. Like licensing magical bullshit, once the genie is out of the bottle, you won't easily get it back in.

Thanks for the update on the California law change. We'll have to look into at checking it out for an unapproved cancer drug on a trip in month or two, for the California stop.

This post focuses on less tested, expensive new drugs that might be most profitably exploited by pharma.

A more useful area for patients concerns those materials that are already approved overseas and available for personal importation, often cheap or generic. Like some drugs in the Dallas Buyers Club example.

Drugs approved overseas with more than 1-5 years satisfactory experience should be available to desperate US patients with some kind of reasonable effort. If the FDA wants to be useful, it could maintain currently updated staff reviews online about particular unapproved drugs of concern. Sometimes there is nothing wrong at all with unapproved drugs, it's purely political.

# 3 Eric Lund

@jrkrideau: That’s a feature, not a bug.

I think you missed my point. If US libertarian idiots want to mess up US agencies, oh well….

I was of the impression that drug trials and testing in the many or most of the OECD countries would be considered in any country's decision to license a drug.

My point is that we (i.e. the rest of the world) would have to discount any FDA drug approvals as being possibly based on incomplete data. We are going to waste time and money duplicating research since we would no longer be able to trust information from the USA.

And we don't even need a conspiracy theory to suggest that the FDA may be suppressing information—it's the law. It might be fun watching the libertarians and the anti-vaxers fighting that one out.

I thought the whole way life was supposed to work in a libertarian paradise is that you get to sue if something goes wrong. (Success of suit is not considered.) But these laws would *take away* the right to sue, leaving a patient with nothing. That's all new kinds of evil.

On a separate note, if the condition to be treated with these "right to try" laws is rare enough, and FDA is not allowed to consider the outcome of patients who use a treatment under "right to try", then it's entirely possible that the real clinical trial for a treatment would never be able to enroll enough patients, and therefore never get approved at all. How does that improve anything?

Fuck the FDA, DEA, and any other 'government agencies' that have letters in their name.

Intercourse the FDA, DEA, and any other 'government agencies' that have letters in their name.

{what's with the new swear filter?????}

Fuckbags! Just testing.....

Ok. '*..kbags didn't even make it through -- Stay absofuc*in' classy, 'scienceblogs'.

https://www.youtube.com/watch?v=uSEXgQ58AoM

For all you Limey's out there, did you know why London Dry Gin is more intoxicating than American Gin? I do.
α-pinene exists in two stereo-optic configurations. (-)α-pinene is produced by English Juniper trees, and (+)α-pinene is produced by American Juniper trees. The two enantiomers differ in biological biological effects:

Before death due to (−)-α-pinene, the respiratory ventilation was decreased to approximately 56%. However, a much more prominent decrease in ventilation is apparent from the decrease in respiratory rate (fig. 2) and the decrease in VT (fig. 4) with (+)-α-pinene, which did not cause death among the animals... Nevertheless, (-)-α-pinene has a higher systemic toxicity than (+)-α-pinene. The simple physicochemical parameters are similar for chiral forms, excepting optical properties, and thus the difference in their systemic toxicity should also be due to the steric properties.

Only (-)α-pinene is fatal and causes CNS depression. This is why English Gin will put you under the table, while American Gin will make you feel fabulous!

Mechanisms of Acute Inhalation Effects of (+) and(−)-α-Pinene in BALB/c Mice
http://onlinelibrary.wiley.com/doi/10.1111/j.1742-7843.2005.pto_96604.x…

Both enantiomers are known in nature; (1S,5S)- or (−)-α-pinene is more common in European pines, whereas the (1R,5R)- or (+)-α-isomer is more common in North America.

https://en.wikipedia.org/wiki/Alpha-Pinene

Gilbert does make a case for early adoption of new anti-psychotic drugs.

Someone hasn't figured out how to swear at RI.

Oh well.

In other news...

Mikey A ( Natural News) displays his comprehension/ summation skill ineptitude again in a post about the END of Civilisation
( It's the End of Civil.. as we know it... and I FEEL FINE)**

At any rate, he opines that Syrians are lean, mean fighting machines and westerners are crybully, spoiled weaklings.
It's Darwinism, stupid.

Except for Country Folk like him.

Hardworking, physical, problem solving- trained by adversity to persevere.

Says the guy who has made his money by selling stuff on the internet and scaring readers into survivalism.

** I once met two of those dudes- on an escalator in a hotel.
Nice guys.

How to swear at RI

1. Swear and wait for You-know-who to do you-know-what

2. Creative spelling and/ or typing patterns for immediate relief

I know, I know I should have not revealed the secret and let him figure it out for himself for hey, I was trained to assist people communicate/ function et al.

I know, I know I should have not revealed the secret

Not to worry, there are plenty of ways to do it, such as this famous example.

If you have the time to come up with a creative way to swear you also have the time to come up with a way to express yourself without swearing.

@13
Cool story, bro.

As a Tanqueray fan, it pained me to say that. It's sad, but true.

What is you favourite Gin Gilbert? Say Broker's and I'll die.

Lewis; I've never tried Gin. Though, based on your post, I just might as it sounds like there is more to it than just ethanol.

It’s the End of Civil.. as we know it

Good Lord.

https://www.youtube.com/watch?v=gR3s8VUYT9g

Would there be any preventive value by adding words to the effect that the purveyor has to provide detailed descriptions and mechanisms for the treatment and may not charge any money for the treatment?

Hey, G--

Everyone and everything written in the latin alphabet "has letters in its name." What's your problem with people shortening the names of things that they talk about more often? What do you have against the NWS and its parent agency NOAA? Is the British Inland Revenue better than the American IRS because it's not called the IR?

the NWS and its parent agency NOAA

There has effectively been a National Weather Service since 1890 when it was known as the United States Weather Bureau -- It was swallowed up by the creation of NOAA in 1970.

NOAA is under the Department of Commerce and, as such, is somewhat politicized. I guess my main beef with them would be taking the human subjective element out of the NexRad automated radar systems and knee-capping the instruments by consigning them to only do the full PPI scans and at only a fixed six elevations in a rigidly set time; This really trashes their spacial resolution -- and no more hi temporal and spacial resolution RHI scans focusing on a small area of interest.

That and *cough* 'global warming' data diddling *cough*.

@ rs;

Believe it or not, I do occasionally find the time to explore other avenues of expression and get paid for it.

But swearing on the internet is more fun.

re gin:

Tanqueray is great
.
One of my ancestors got rather rich selling his formulae to a larger company and funded other family business/ projects over the years from some of which I have personally benefitted
.
For unknown reasons I got extremely blasted last night from a SINGLE drink which incorporated gin and then spent two hours in a Japanese restaurant eating and earnestly discussing politics with guests who spoke barebones English whilst my Japanese is nearly as bad.
Not as bad though.

Gin is a magical essence of fluidity and lubrication.
And who doesn't want that?

How to swear at RI

You missed one. Please pardon me now while I watch the scoreboards on the last day of the regular baseball season.

@ Narad:

I know but I don't do that.

AND yes, it is all about me ( to me anyway)

"But swearing on the internet is more fun."

I wasn't trying to be a tone troll. IRL I swear an awful lot. It's just that in written expression it really isn't needed. Indeed it can be a lot more fun (and effective) to knock someone with wit alone. The kooks who visit typically have no wit (or facts) and thus quickly descend to gross insult and swearing. Let that be *their* signature.

@ rs:

You're right.

Unfortunately, RI has had a deficit of quality trolls : thus I am uninspired but I will try harder.

Still, we can hit them with facts or meaningful references as well as an arcane vocabulary or interesting sentience structure.

In other news...

AoA has been trumping up its autism conference featuring Jenny McCarthy and other stellar personae
BUT has kicked a reporter out. ( see AoA)

Seriously, they usually claim that they are the ones who are censored.

In other other news...

Mikey Adams claims that HRC has never done an honest day's work in her life
and that the NYT fails...

Wait, let me stop laughing so I can type.

I know how much Orac and company adore Mike's reportage and worldview.
I sometimes wonder if he is secretly laughing as well as he writes crap to stir up his rightie readers so that they'll support him and buy his dreck.

interesting sentience structure

I am intrigued and would like to learn more about the structure of Denice's sentience.

( see AoA)

Wait, Cat Jameson's son is "unable to regulate his temperature"?

AoA has been trumping up its autism conference featuring Jenny McCarthy and other stellar personae
BUT has kicked a reporter out.

This Dachelbot entry is more hilarious than you let on (boldface added):

"While Marc Ramirez at the Dallas Morning Sun tried to portray Rye Druzin as a legitimate reporter for the San Antonio Express-News interested in covering a controversial subject presented at the Dallas Autism Education Summit, the truth shows the really sinister side of the mainstream media."

What, you may ask, is "the truth"?

"Druzin wasn't really 'prepared to cover remarks by Bexar County District Attorney Nico LaHood....' I’m sure Druzin’s assignment at the Autism Education Summit was to smear everyone daring to speak out about vaccines and the link to autism and say nothing about the charge of scientific fraud at the CDC.

"I'm sure Marc Ramirez was told present Druzin as a cusading reporter wronged by anti-vaccine advocates.

"How do I know this?

"First of all,[*] none of these people EVER want to genuinely and extensively interview Andrew Wakefield, Del Bigtree or any of the other people involved in this controversy."

That's right, "the truth" is "because," full stop.

* There's no corresponding "second of all," but she does start babbling about Hearst newspapers.

“unable to regulate his temperature”?

The Lizard People walk among us!!

@ herr doktor bimler:

Ha ha! I didn't intend that but it might actually be true.
it should be.....
SENTENCE.

In other news... **

I had the great pleasure ( amidst other gleefulness of late due to a recent NYT report and having interesting work on my 'desk' ) to hear a new 'expose' of Dr Barrett courtesy of hoary, old woo-meister, Gary Null, which was read aloud today on his noontime woo-fest ( prn.fm) - starting at 18 minutes in until the end- called " Who You Gonna Call?
Quackbusters!"***

It should be posted as an article soon at prn.fm- or some other sinkhole of unreason on the internet- and I refer to it because it uses every trick in the book to 'splain why SBM is not to be trusted and hoary, old woo-meisters are.
In short, it's hilarious.

When I hear him talk about the Quackbusters ( sic), I always wonder when he will go into detail about our fearless ( and peerless ) leader, Orac, who is as perspicacious as he is perspicuous (tm). At any rate, he's been mentioned briefly a few times.

** I do this because someone has to do it. Seriously.
Fortunately, no weather and traffic.
*** not really

When I hear him talk about the Quackbusters ( sic)

That's a Patty Bolen coinage, isn't it?

Anyway, I'm reminded that it's a new quarter, so I have 15 PACERbuxx ready to burn a hole in my pocket if there are any requests for docket updates (assuming that I can get RECAP to start working again).

In response a recent tweet by You-know-who...

Why is commenting way down on recent posts?

I am certainly not an expert but I imagine that these posts do not appear to incite trolls and the minions to stomp upon them.They are concise and do not lean themselves as material for riffing on by the minions.

Also, they do not easily lend themselves to various minions' expressions of their finer tastes** involving bacon and chocolate combinations.

Everyone is still reeling from revelations in the NYT?

Actually, I think it is all about bacon and chocolate.

** in memory of lilady

@ Narad, anything new on the Merck mumps thingy?

@ Narad:

Well, yes it is!

Truly, his hoariness' article went into detail about why Barrett lost court cases by not being an 'expert' in woo. Also crap about the chiros' ancient case anti-AMA.

There was something I hadn't heard before about Barrett's CEU and other education being out of date by a judge. I expect the craptastic article will be posted somewhere soon.
I was doing other work at the time so I didn't take copious notes.

Truly, his hoariness’ article went into detail about why Barrett lost court cases by not being an ‘expert’ in woo.

Brave Sir Patty refused to post a comment recently that pointed out a Barrett victory (as well as overtly mocking Patsy). I should see whether I kept a screen shot, but I'm dog-tired today.

Hah!
Bolen's 'new and improved' website is certainly laughable.
It features posts by such luminaries as himself, Estave and Heckenlively..

Like I said previously, I've been in a rather gleeful state of mind and looking at sites like the Bolen Report increases my merriment.

Minions might want to take a peek.

I want to lift spirits. It's my job.

anything new on the Merck mumps thingy?

It's likely to be mostly procedural, but I'll update that docket once I make sure that the infrastructure is working.

Considering how important you think fact-based science is, you should be sure to get your facts straight. You wrote:

"So basically, right-to-try allowed Dr. Delpassand to charge for the use of his treatment, even though it is not FDA-approved."

The Texas Right To Try law does not allow patients to be charged at all for treatments. And do you know what treatment he is giving? A treatment that has been available in Europe for over a decade that is totally safe and completely effective. Facts. Stubborn things.

The cruel sham that is “right to try” continues to spread, part 2

oracknows — Tue, 26 May 2015 00:55:13 +0000

The cruel sham that is “right to try” continues to spread, part 2

When I wrote yesterday about the cruel sham that is "right-to-try," , one criticism (among many) that I made of these misguided, profoundly patient-unfriendly laws was that I have as yet been unable to find a single example of a patient who has managed to obtain access to an experimental therapeutic through such a law, much less been helped by it. So-called "right-to-try" laws, of course, claim to provide a mechanism by which patients with terminal illnesses can obtain access to experimental therapeutics not yet approved by the FDA but still in clinical trials. They are, as I've pointed out, a cruel sham, placebo legislation that makes lawmakers feel as though they've done something good but do nothing of substance for patients while providing them with false hope. The federal government through the FDA controls drug approval, which means that states can't compel a drug company to provide a drug to a patient, and most drug companies would not want to risk jeopardizing approval of their drug, which is what could happen if they grant access to an investigational drug under right-to-try and the patient suffers an adverse event. After all, the success rate for drugs that have passed phase 1 (which is all that right-to-try requires) in phase 3 trials is only on the order of 9-12%, meaning that that's the most optimistic probability that such drugs would benefit a patient. In reality, it's almost certainly much, much lower.

Basically, the whole right-to-try movement is built on a delusion, namely that there are scads and scads of cures out there that are only being kept from the people by the cautious bureaucracy of the FDA. If the people could just get the FDA out of the way—or so the delusions go—cures would flow to the people. Add to that the libertarian delusion of the Goldwater Institute, upon whose model legislation nearly all of these bills and laws are based, that the free market will take care of safety issues, and it's possible to see the long game being played, a strategy designed to drastically weaken the FDA's control over drug approval. Then add to that the way that right-to-try legislation strips virtually every protection away from patients in clinical trials. For instance, no IRB oversight is required in right-to-try. There is nothing in the laws that provide for paying for the experimental therapy being used. Indeed, not only don't insurance companies have to pay for right-to-try, but they don't have to pay for any care that results from complications resulting from right-to-try. If a patient chooses right-to-try and it goes on, he's completely on his own.

All of this brings me to a story I saw after I wrote yesterday's post. The story is about an unfortunate man named Bob Bardone who last summer got one of the worst pieces of news a human being can get. He found out that he had amyotrophic lateral sclerosis (ALS), and it was estimated that he probably had about two or three years to live. His story is, as is the case for most ALS patients, heartbreaking. ALS, as many of you know, is a relentlessly degenerative neurologic disease in which the patient gradually loses motor control. Ultimately, patients lose the ability to walk, to move, to speak, and, ultimately, to breathe. Indeed, if there is a disease that I fear more than cancer, it's something like ALS, which produces a nightmarish, unstoppable deterioration. There's currently only one drug approved for ALS that I'm aware of, riluzole, but it only adds at best months to life expectancy. If ever there were a disease that needs new treatments, it's ALS.

As you might recall, Missouri was one of the first states to pass right-to-try legislation. As such, and because of his past connection to the state, Mr. Bardone and his wife decided to move back there in order to be closer to family and, not coincidentally, to try to take advantage of right-to-try:

The move to St. Louis happened to bring them hope. They learned Missouri had become the third state to enact “right to try" legislation, which went into effect in August and allows terminally ill patients to try promising drugs yet to be approved by the FDA.

The family had been closely following news about a drug, GM604. Its maker reported that it significantly slowed the progression of ALS in 12 patients over 12 weeks with no dangerous side effects, though some scientists question the findings. The drugmaker, Genervon Biopharmaceuticals, is seeking fast-track approval from the FDA to sell the drug before spending years studying it in larger numbers.

“My dad had hope for the first time since diagnosed with ALS when he found out Missouri was a right-to-try state,” Connors said. “He thought that because he was moving back to Missouri, that he could try this drug.”

Bardone’s neurologist tried to get more information about the drug, and the family made emotional requests to the company. Genervon, however, refused to provide it.

After months of trying, the family is disappointed and frustrated, and Bob Bardone’s health is worsening.

“Can you imagine the hope we felt?” Connors said. “This entire process puts the most emotional time in our lives on even a more emotional roller coaster.”

The article further notes:

But right-to-try laws may be meaningless because companies can refuse to provide their experimental drugs. They may only create a false sense of hope among desperate families.

“It gives people a false impression that somehow because it’s a state law, it mandates this, but really it just gets everyone up in arms,” said Dr. John DiPersio, the deputy director of the Barnes-Jewish Hospital Siteman Cancer Center. “All it’s doing is causing commotion and confusion.”

This is, of course, exactly what I've been saying about these laws for over a year now. They are placebo legislation. They do absolutely nothing to help a man like Bob Bardone, but they do give patients like him false hope, only to cruelly take it away.

I can anticipate right now one objection. Why did Genervon Biopharmaceuticals refuse to give Mr. Bardone access to the drug? There are quite a few reasons why companies might not want to do this. This story, for instance, reports that Genervon has been overwhelmed by requests for its drug from ALS patients. Therefore, it chose to concentrate on getting fast track approval from the FDA, which “would give immediate access to all ALS patients, require doctors to prescribe and monitor patients’ progress, allow us to continue gathering data ... and the cost would be supported by health insurance.” This is, of course, a perfectly reasonable justification, particularly given that if a patient had an adverse reaction to its drug outside of its clinical trials, something that is more likely if the drug is given outside of the controlled setting of a clinical trial, it could delay or even scuttle approval of the drug by the FDA. Also, some companies are small venture companies with inadequate resources to dedicate to fulfilling right-to-try requests. Indeed, some of these smaller companies might just barely have raised enough capital to make enough drug to do the clinical trials necessary to gain FDA approval. These are, of course, exactly the sorts of companies that we want to encourage, not impede, because they aren't the big pharma behemoths and tend to be more imaginative and daring.

The Goldwater Institute's response to these problems with right-to-try shows just how clueless or disingenuous it is. Basically its flacks argue that the FDA should assure companies that outcomes of patients who receive drugs for compassionate use will not negatively affect a drug’s approval. Seriously? That response basically indicates to me that the Goldwater Institute knows that right-to-try is a sham and has no power over the FDA, given that it's reduced to suggesting that the FDA do something that it knows the FDA cannot do legally or ethically. Besides, the FDA already has a compassionate use program that rarely turns down a request. Also, as I've described, even the problem with how onerous the forms are for a physician to fill out is being dealt with. As this story notes, most applications are dealt with in four days, and the FDA has drafted a new form for such requests that, when finalized, should take a physician 45 minutes or less to complete.

There's an excellent summary of the problems with right-to-try laws that was published on Friday on the Health Affairs Blog that I missed before but won't now. It's by David Farber, Preeya Noronha Pinto, Arthur Caplan, and Alison Bateman-House. They are quite blunt, noting that, contrary to the name given these laws, they provide no new rights to patients. They also point out that these laws have created an expectation that terminally ill patients will be able to quickly access life-saving experimental drugs by being exempted from FDA oversight but that that expectation is "quite simply, false." They also note that legally:

If RTT laws are understood as actually providing a right to direct access to an investigational product without FDA approval or oversight, they would be “preempted” by federal law, meaning the federal laws are so powerful as to effectively nullify their state RTT counterparts. Indeed, several federal courts have already concluded that FDA’s comprehensive regulatory regime governing the manufacturing, approval, labeling, and distribution of drug products preempts state laws designed to legislate in this area. If challenged in court, we anticipate RTT laws will be similarly treated.

And:

It is only a matter of time before courts nullify RTT laws. In the meantime, these laws offer vulnerable patients misplaced hope and do not attempt to minimize the serious health and safety risks inherent in treatment with unproven treatments. State legislatures still evaluating the merits of RTT laws should think twice. Patients facing terminal illnesses have enough issues to navigate without being given false hope through legislation that is ethically, legally, and clinically flawed.

I don't know if it's definitely a matter of time before the courts nullify right-to-try laws, but that would seem to be a likely outcome. Of course, as I've discussed before, the purpose of right-to-try laws is not what is ostensibly claimed. Rather, it's a long game in which—or so it is thought—the buildup of pressure through the states will force the FDA to loosen its grip on drug approval. Some of the more "open" libertarians will even argue for the neutering or even outright abolition of the FDA, claiming that the free market will take care of drug safety and efficacy.

I do find one thing hopeful. Over a year ago, when the very first of these laws were wending their way through state legislatures, few, if any, medical groups spoke out against them or openly opposed them. Indeed, as I described in my very own state, when our right-to-try bill came before the legislature, none of the major medical societies or cancer centers openly opposed it, and I was definitely discouraged from doing so. Again, as I've said so many times before, opposing right-to-try can easily be painted to be akin to opposing mom, apple pie, and the American flag and having a propensity to drop kick puppies through flaming goal posts. Never mind that right-to-try laws are profoundly anti-patient laws.

That time seems to be coming to an end. After a year, people are starting to realize that, as far as it goes to right-to-try, the emperor has no clothes. The story about Bob Bardone is one indication. I don't recall seeing such a skeptical story about right-to-try in a long time, if ever, complete with a human interest story that demonstrates quite effectively what a sham these laws are. Then there's this story about the right-to-try law introduced into the California legislature:

The California bills have drawn opposition from the California Medical Association and from groups representing nurses and oncologists. A group representing pharmaceutical manufacturers has sent a letter warning against skirting the FDA’s established channels.

“We have serious concerns with any approach to make investigational medicines available that seeks to bypass the oversight of the Food and Drug Administration and clinical trial process, which is not in the best interest of patients and public health,” a letter from Pharmaceutical Research and Manufacturers of America says.

And:

The California Medical Association states that they have significant patient safety concerns with allowing access to unproven drugs outside of the FDA's clinical trials and compassionate use programs. They further argue that offering unapproved therapies without credible scientific rationale or controlled monitoring could lead to not only endangering terminally ill patients further but potentially exploiting their hopes and circumstances. The Association of Northern California Oncologists cite the difficulty of identifying a terminally-ill patient, the danger a "right to try" policy outside the context of a clinical trial would present to adult clinical trial enrollment and the lack of an informed consent process to protect patients seeking investigational drugs as reasons for establishing their oppose position on the bill. The California Nurses Association/National Nurses United (CNA) maintain that this bill does nothing to address the real barriers to "compassionate use" revealed in a recent article in the NEJM entitled Practical, Legal, and Ethical Issues in Expanded Access to Investigational Drugs, specifically stating that nothing in this legislation impacts the availability of drugs to terminally ill patients unless the manufacturer of the drugs allow it to be used in advance of FDA approval. The CNA goes on to state instead of taking on the cost of drugs and challenging drug manufacturers that charge excessive prices for all drugs sold in California, this bill reinforces the status quo for investigational drug costs.

These are all good points. However, it's probably too little, too late, given that the CMA refused to take a stand on this legislation initially. Indeed, there remain editorials trotting out the same Goldwater Institute talking points. Contrary to these dubious arguments, right-to-try laws sell terminally ill patients and legislators a bill of goods. they promise access to life-saving experimental drugs while leaving vulnerable, desperate patients open to false hope, lack of the oversight that patients in clinical trials receive, huge medical bills, and loss of medical coverage for any complications that might result from trying unproven drugs. People seem to be finally waking up to the sham that is right-to-try, but too late.

oracknows Mon, 05/25/2015 - 20:55

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Someone with something to say:

http://tinyurl.com/k6zpawf

As opposed to: "Gosh, some guy somewhere mistakenly thought he could get this experimental drug, and he sure was disappointed when he couldn't."

Beam, mote.

Which is, of course a non sequitur. Just because there are problems with research at the University of Minnesota does not mean my criticisms of right-to-try aren't valid.

How not to argue, by Zebra:

Orac: right to try laws are a cruel sham. State laws cannot trump federal regulations and patients with terminal illnesses are given false hope for cures that never materialize and left on their own to deal with complications from untried drugs that, at best, have a 10% chance of having any positive impact.

Zebra: Here's a link that shows that the Institutional Review Board at the University of Minnesota is corrupt and ineffective and suggests that IRBs should be replaced by independent regulatory bodies unconnected with the institutions doing the research. I win!

Thanks for the follow-up. It answers my question from yesterday that FDA authority basically overrides these state laws. Of course, the Goldwater Institute might be gearing up to try passing a federal "right to try" statute.

And while the previous post mentions this, Mr. Bardone's story makes abundantly clear that we aren't just talking about Big Pharma. My guess is that companies like Genervon Biopharmaceuticals, which are running on venture capital and therefore have just enough resources to produce just enough product to get through standard clinical trials, would be where most of the action is--"Little Pharma", if you will. Most of those companies will go belly-up when their experimental drug fails to clear clinical trials. Perhaps a Big Pharma company will buy out a Little Pharma company that makes it through clinical trials.

Incidentally, I know some people who play the VC game, and they tell me that successful VCs only expect about 10% of their bets to pay off (the payoff from the successes is more than enough to make up for the failures). That's right in the 9-12% success rate quoted for drugs in clinical trials.

@2 Orac,

See my comment on the previous post.

All these issues you discuss are the result of the problems that exist in the mainstream.

You say something like "it may be too late"; yep, you didn't fix the FDA process and someone is taking advantage of that.

You are blaming the mosquito because you didn't fix the window screens. And using it as a distraction from fixing them.

@Nigel: Yep. zebra's argument seems to boil down to this: If one IRB is corrupt then they all must be and therefore being under IRB oversight is no advantage and therefore right-to-try must be OK.

Of course, problems with IRBs are not the main driving force behind the right-to-try movement. Indeed, I bet that most of the politicians and people supporting such bills are, at most, only vaguely aware of what an IRB is and does, if even that. That's why zebra's argument is such a lovely non sequitur.

#6 Orac,

The Strawman is about the most pathetic form of rhetorical fallacy.

If you want to be a crusader/writer, I refer you the author of the cited NYT article as an example-- it takes skill and discipline, and a broad view with a clear sense of priorities.

Or, there's always the Dr. Oz paradigm.

zebra, you'd have a better chance at being understood if you didn't spend your time being deliberately incomprehensible.

With the recent animal model success into developing the EV vaccines, I was particularly discouraged by the push to "fastrack" anything around the FDA safety protocols. 'See? This is the way to do it...we don't need due diligence & arm's length oversight -- everyone be "buddy buddy" etc..'

Ugh. Yes 10+ years to get a worthwhile therapy on the market is brutal, but these safeties and evidence-based protocols are supposed to mean something. Anyone recall the giant push to empower women by offering the morning sickness pill in the 70s? Can you imagine the pressure on the FDA doctor who decided NOT to approve it? Kinda like saying you'd ban Viagra, at the time. Obviously, we would have been dealing with thousands of birth defect cases in this country had such an end-around been used. Tell you what though, that doc had some serious cahonnes.

The Strawman is about the most pathetic form of rhetorical fallacy.

I take it that you're apologizing for this?

As opposed to: “Gosh, some guy somewhere mistakenly thought he could get this experimental drug, and he sure was disappointed when he couldn’t.”

That's very gracious of you. I encourage and applaud it.

@MarkN - correct, FDA clinical trials and safety protocols exist for that very reason. This push to circumvent those rules - even in cases were we are dealing with terminal patients, undercuts the entire process and could lead to more problems down the road.

I had heard the companies don't like these laws, since the single or small use cases are entirely unprofitable & can cause issues with the regular trial process - though in most cases, these new "laws" exempt the companies themselves from any harm that may come from the untested treatment.

I find it ironic that it is a lot of the same people that claim the FDA isn't doing enough to maintain the safety of medicine are asking the same agency to back away from safety.

This push to circumvent those rules – even in cases were we are dealing with terminal patients, undercuts the entire process and could lead to more problems down the road.

This is how it begins. Terminal patients are vulnerable, and it's an emotionally appealing argument to say that they have "nothing to lose" and therefore should be able to try whatever they want or take on whatever risks they want, asking "How could it be any worse?" Of course it can always be worse. You could not just have a terminal disease, but you could also have bankrupted yourself and your family paying out of pocket for a drug that's unlikely to help you. You could also have suffered complications from that treatment, making your brief remaining time more miserable than it has to be or even shortening it, while losing your health insurance coverage to treat that complication.

Don't think that these laws are just designed for the terminally ill. That's what they say, but they are a wedge to widen the population bypassing FDA approval or compassionate use programs.

You say something like “it may be too late”; yep, you didn’t fix the FDA process and someone is taking advantage of that.

You are blaming the mosquito because you didn’t fix the window screens.

I take it that the whole preemption part failed to sink in.

(What kind is a separate question.)

@Orac - I agree wholeheartedly...the "terminal" cases are merely the front of the emotional appeal to open up compassionate use to anyone who can afford (or not, as the case may be) treatments that haven't undergone the FDA vetting and testing process.

Orac, thank you for bringing this up again and relating the story of Mr. Bardone. Seems like a good time to point back to my open letter to legislators. Feel free to use it in communication with your state reps.

Wikipedia:

The FDA approves a drug for prescription use, and continues to regulate the pharmaceutical industry's promotional practices for that drug through the work of the Office of Prescription Drug Promotion (OPDP, formerly the Division for Drug Marketing, Advertisement and Communication (DDMAC).[14] The FDA does not have the legal authority to regulate the practice of the medicine, and the physician may prescribe a drug off-label. Contrary to popular notion, it is legal in the United States and in many other countries to use drugs off-label, including controlled substances such as opiates. Actiq, for example, is commonly prescribed off-label even though it is a Schedule II controlled substance. While it would be legal for a physician to independently decide to prescribe a drug such as Actiq off-label, it is illegal for the company to promote off-label uses to prescribers. In fact, Cephalon, the maker of Actiq, was fined for illegal promotion of the drug in September 2008.[15] Under the Food, Drug, and Cosmetic Act (FDCA) at U.S.C. 21 §§301-97, manufacturers are prohibited from directly marketing a drug for a use other than the FDA-approved indication. However, in December of 2012, the United States Second Circuit Court found that promotion of off-label uses by a company sales representative was considered to be protected speech per the First Amendment.

So, no clinical trials needed, no scientific evaluation of relative risks to benefits. And insurance may or may not cover it.

Who needs wedges and slippery slopes?

@zebra - those are all drugs that already went through FDA approval, as opposed to "compassionate use" or right to try, which have not.

A fact that seems to have eluded zebra.

Lawrence, Orac,

Talk about non-sequitur.

What's the difference, apart from perhaps some better knowledge about safety/side effects?

Is zebra really arguing a form of tu quoque, albeit pooh-poohing a significant difference?

It isn't a non-sequitur (unless you are calling your own statement a non-sequitur - which it pretty much is)....as again, off-label uses are for drugs that have already been proven for safety and effectiveness.

Very little, if any of that information is available for the types of drugs covered under these bills....

At this point I have to wonder if zebra is being deliberately obtuse if he can't see the difference between right-to-try and off-label prescribing.

At this point I have to wonder if zebra is being deliberately obtuse if he can’t see the difference between right-to-try and off-label prescribing.

"Being deliberately obtuse" is a pretty good description of the Zorse's general modus operandi. Either that, or Z. is simply obtuse.

@ Zebra

What’s the difference, apart from perhaps some better knowledge about safety/side effects?

You will have a hard time convincing us that's a trivial difference.

@Orac

At this point I have to wonder if zebra is being deliberately obtuse if he can’t see the difference between right-to-try and off-label prescribing.

If I recall correctly, zebra once boasted about being deliberately obscure to promote critical thinking, or some such. In reality, all zebra accomplishes is nonsensical arguments and being able to claim we're arguing against a straw man when people try to make sense of it's digital spewings.

There was a certain other commenter who used the same technique, but I forget who it was.

Talk about non-sequitur.

What’s the difference, apart from perhaps some better knowledge about safety/side effects?

You really never learn, do you? The field considered is different,* but the discussion in Oullette v. Mills gives the basics of preemption, which I had already brought up in the comments to part 1.

* Although not unrelated.

For all the libertarians out there, Genervon's refusal to use this legislation to sidestep the FDA is a perfect example of market forces at work .

It's just not working the way they think it should work.

Genervon’s refusal to use this legislation to sidestep the FDA is a perfect example of market forces at work

They may well have also taken note of the fact that being shielded from a state tort action in Missouri is no great shakes. Or it could be something else.

It's interesting how history seems to be repeating itself here. About 20-25 years ago, there were complaints that FDA was moving too slowly, holding up the approval of new drugs. So FDA created the fast track approval system. The number of new drug approvals went up, along with an increase in recalls of newly approved drugs (e.g., dexfenfluramine), prompting outcries that FDA was approving drugs too quickly. I can see a similar set of events playing out in the near future. There may be a different set of parties to "blame", but it'll likely come about.

The Genervon story gets better.

While patients often say that this drug represents their only hope, [Steve Perrin, president and chief scientific officer of the ALS Therapy Development Institute] has been quick to point out that there are a number of ALS drugs in the clinic. And if the patient campaign were to succeed, patients taking the drug would be excluded from trials for a drug that might actually work.

FierceBiotech followed up by asking Genervon CEO Winston Ko a simple question: Has the company actually filed a new drug application--which would be necessary for any kind of approval, accelerated or otherwise, that it's been demanding--and how has the FDA responded? If an NDA was filed, then the agency would have had a chance to see if the application was acceptable for review, or not.

The company, which is based in Pasadena, CA, and has cited biblical prophecy as an inspiration for its work, did not answer this question in a reply to FierceBiotech Friday afternoon. In an e-mail, Genervon did say it was considering the FDA's request, then repeated its demand for an immediate approval in order to save the lives of tens of thousands of patients.

Oh, dear. I might have to look into Genevon's drug and clinical trial a little more closely this week...

I am formally requesting a higher quality of troll at RI: if this should keep up, we might get lazy- which is not at all efficacious.
Thank you. Merci.

OT but are crunchy moms organising to save innocent children from the ravages of GMO crops ((shudder)) ever TRULY OT at RI?
PLUS it's late and I'm suffering miserably from allergies...

For the past few weeks, I keep metaphorically running into ZEN Honeycutt, of Mission Viejo, a mother to 3 with have autism and allergies betwixt them who have been aided immensely by a GMO-free, organic diet.
OK, she's associated with BOUGHT!, will be featured at Fearless Parent Radio tomorrow and initiated Mums 'Cross 'Murka ( actually, Moms Across America.com).
She's on You Tube, met Stephanie Seneff at Autism One, was on Oz' show and wants to change the world.
Then, there's her name. ( She's not referenced at RI search)

Therefore, [Genervon] chose to concentrate on getting fast track approval from the FDA

Just not enough to file an application.

Very interesting - as it appears that this "right to try" legislation could be viewed by some unscrupulous companies as a means to market and sell untested products without the need for FDA approval......

Lawrence @35: And viewed by scrupulous companies as a way to get totally screwed.

If you announce promising results from your Phase I trial in the media, you get swamped by RTT requests.

If you fulfill the requests you don't have enough product (or possible research patients) to do a proper phase II.

If you don't fulfill the requests then you're evil and denying people life-saving drugs.

If you don't announce your Phase I results in the media, then you'll never get enough good press to get the VC funding you need to complete the phase II.

You're just screwed all the way around.

Very interesting – as it appears that this “right to try” legislation could be viewed by some unscrupulous companies as a means to market and sell untested products without the need for FDA approval

This was touched on at In the Pipeline. Personally, I don't think it really has a shot except, again, at the intrastate level.

^ To wit.

@Narad

Personally, I don’t think it really has a shot except, again, at the intrastate level.

Agreed. Keeping it in-state skirts some Federal regulations that would otherwise apply. But then, they don't need RTT for that.

This also reminds me of the drama around the experimental Ebola meds. It would have been great to get them out in quantities faster--but you can't expect small biotechs to have the capacity to do QCed drug production on a large scale suddenly. You just can't--they don't have the capacity, and you can't pretend that somehow they suddenly will.

This is what irks me about the Pharma haters. They have no grasp of drug development, nor of drug production and distribution. What do they think--just because Derpcola can sell you snake-oil by the buckets that some small biotech can? Or do they really think academic labs would have the ability?

There are a lot of non-trivial steps in the process of getting legit compounds to people. Even if they haven't passed all the safety studies.

Mary M: Exactly! It's like those chain e-mails about the 'ingredient' costs of common drugs. "Cholesterol-be-gone costs 3 cents to make, why are you playing 75 cents?!"

They never take any kind of QC into account.

I often give the QC folks at my work crap about being incredibly conservative about everything (related to work), but at the same time I know it's their job to be cautious.

Mary M and JustaTech - Yeah, it is interesting to watch people who hate drugs with a blind purple passion start screaming for drugs/vaccines when a new (or scary) pathogen pops up. Then they just can't figure out why we can't crank them out by the barrel full. Plus if they aren't tested even though they will be screaming for them anyway (see Ebola scare) they will scream even louder if it turns out the drug was actually harmful. Oh why didn't you say anything about it not being tested! It's a lose lose scenario all around. Having gone through H1N1 in PH I know. We reacted aggressively and tried mitigation with the tools at our disposal early on (while everyone was screaming we do SOMETHING). Then when it turned out not to be as lethal as feared (though if you run the numbers a lot of people did die and in groups who shouldn't have but not the kind of numbers that freak out the public) it was why did you do all this stuff! Overreaction! Too much money spent! You can't win.

Kiiri: Yup. Sadly, while utilitarianism is great for getting things done, it does nothing for your PR. (That's this week's topic in my MPH ethics class.)

LIMITATIONS OF RIGHT TO TRY LAWS: If a drug is already on the market for another use, the drug maker is more likely to have the financial resources to offer it for "off-label" expanded use (compassionate use). However, if the therapy is completely new, the drug produces no revenue stream and the company needs FDA approval to sell it and recover R&D costs. Insurance only pays for treatments that are FDA approved so patients would still have to come up with tens of thousands for medical staff, hospital space, lab work, monitoring, etc. even if they can get the drug. States are leading national discourse with initiatives like medical marijuana and gay marriage and forcing the federal government to respond. The Right to Try laws that are passing handily in many states could have the same impact. That is why we support them even though they are not a panacea. They are an important step in the process to change the status quo at the FDA. It's a matter of life and death for all those with a deadly disease.

Thank you for admitting that right-to-try laws are a sham, but we knew that already.

In all empathy and sympathy for patients with terminal illnesses, hooking up with the Goldwater Institute and using its template were not the best ideas because they really don't know who they're in bed with. Contrary to its airy pronouncements, the goal of the Goldwater Institute is not primarily to improve access to experimental therapeutics. That's why it doesn't really appear to care that much that right-to-try laws are a sham and will not accomplish what they claim. The Goldwater Institute is playing a long game whose end goal is ideology-based, the idea being to drastically weaken or eliminate the FDA to let the magic of the "free market" fix everything, providing (once the FDA is safely out of the way) miracle drugs to patients. Patients are merely pawns being manipulated with the false hope of right-to-try. That's why the Goldwater Institute can't tell patients that it knows right-to-try laws won't do anything to provide better access to experimental therapeutics that can't already be accomplished under the current system; it needs them to pressure legislators, who also vote for these bills because they don't understand that they don't do what they claim to do either.

Oh, wait. These laws actually do do one thing. They strip protections from patients pursuing investigational agents outside a clinical trial and tell the insurance companies that they don't have to pay for the investigational agent (which most don't now anyway) but go beyond that and say that insurance companies don't have to pay for medical care for any complications that result from the use of an experimental therapeutic under right-to-try.

Overall, they're very, very bad laws, throwing patients with terminal illnesses under the bus in the name of the long game of weakening the FDA.

You know what would really improve the access of patients to experimental therapeutics? Fully fund the FDA. The reason for a lot of the delays in drug approval as well as issues with compassionate use programs is that the FDA is underfunded and understaffed. The pay sucks (as in many other government jobs) so that the FDA has trouble retaining talented and knowledgeable people, who not infrequently leave take jobs in industry. But that would not fit in the the Goldwater Institute's narrative that there are all these miracle cures out there that would get to the people rapidly if only the evil FDA would get out of the way.

Should there be a right to try Lyme disease vaccine?

You'll have to ask the people who brought on the lawsuits that caused the company to stop making it.

Really, court has ruled freedom of speech trumps regulatory rhetoric as end run around truth in advertising requirements, so greedy corporations can say anything, make false claims, and generally lie about their product, under the protection of freedom of speech. Constitutional rights and protections were written to apply to citizens, people, not to corporations which are business entities for profit. However they typically have more money to support politicians hence the multitude of problems arising from political support of special corporate interests. Then of course, the sort of people desperate for some miraculous untested cure for terminal illness who sue for millions of dollars when it doesn't work, and the scumbag lawyers they find to represent them. Nevermind the profitable incentive of drug companies and technology to genetically create and modify diseases and germs and better ways to spread them in order to expand markets for their products (on and off label use).

Nevermind the profitable incentive of drug companies and technology to genetically create and modify diseases and germs and better ways to spread them in order to expand markets for their products

Ya' see, at this point is where you went from quasi-reasonable, if somewhat exaggerated, to full conspiracy loon. You got any proof anybody is trying to "genetically create and modify diseases and germs" to make money from causing sickness?

Really, court has ruled freedom of speech trumps regulatory rhetoric as end run around truth in advertising requirements, so greedy corporations can say anything, make false claims, and generally lie about their product, under the protection of freedom of speech.

This is the part where one traditionally points to actual case law.

so greedy corporations can say anything, make false claims, and generally lie about their product, under the protection of freedom of speech.

To the same extent as greedy non-corporate individual scammers and grifters with websites.

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.

USA TODAY flubs it big time over right-to-try laws

oracknows — Tue, 19 Aug 2014 01:00:08 +0000

USA TODAY flubs it big time over right-to-try laws

I hadn’t expected to write about this topic again so soon, but then I didn’t expect a major newspaper to have written such a boneheaded editorial about it. In a way, I hate to write this post, because USA TODAY did great things once. There, Liz Szabo wrote the single best science-based report on cancer quack Stanislaw Burzynski. Still, even usually reliable news outlets make mistakes, and in this case the editorial board of USA TODAY made a huge one when it published an editorial entitled FDA vs. right to try: Our view. Seriously, if there’s a case to be made for right-to-try laws, this editorial sure doesn’t make it. Heck, I have a hard time telling whether whoever wrote this actually bothered to read the various right-to-try laws, so off-base are the arguments used.

If you don’t know what I’m talking about, now’s as good a time as any to review the various aspects of “right-to-try” laws in the form of some old posts of mine and one by Jann Bellamy:

Now, on to the USA TODAY article. It starts out with a comparison that seems reasonable on the surface but is really comparing apples and oranges. I’m referring, of course, to the recent moves on the part of health officials in the US and Africa to try unapproved drugs to treat Ebola virus disease, citing this discussion by the WHO regarding the ethics of using unapproved treatments for Ebola. On the surface, comparing this to the sorts of patients who would be eligible for right-to-try laws seems like an appropriate comparison, but it’s not. First, there’s a big difference between Ebola virus disease and the sorts of diseases that will drive patients to seek experimental drugs under right-to-try. Ebola virus disease is not a terminal illness. As I’ve discussed before, nearly 50% of people infected with it, if they receive modern medical care, will survive. Indeed, it is for this very reason that I’m not entirely convinced that using the experimental drug ZMapp, the experimental drug consisting of three different monoclonal antibodies against proteins of the Ebola virus, is wise given a benefit-to-risk ratio that is virtually completely unknown. After all, it hasn’t even passed phase 1 trials yet, which, ironically, means that it wouldn’t be eligible for use under right-to-try, even in states where right-to-try has passed, Colorado, Missouri, and Louisiana. Also, ironically, this tells us that the FDA has broad power to grant compassionate use exemptions even more liberal than right-to-try, which more than bolsters the argument that if any reform to the compassionate use exemption/single patient IND process needs to happen at the federal level.

Another factor to be considered is that Ebola is an infectious disease that is rapidly fatal (as in days, not weeks or months), and Africa is in the middle of the largest Ebola outbreak in history. Certainly these are mitigating factors, particularly given that the sorts of drugs that would be used in right-to-try would be highly unlikely to save a life, because by the very definition of right-to-try, only patients with a terminal illness qualify. In a rapidly fatal infectious disease, the equation is different, with a higher likelihood of making a difference than in truly terminal illnesses. Again, even so, it’s not clear to me that releasing ZMapp to the two Americans was a good idea. Both got better, but we still have no idea if it was due to the ZMapp or if they were among the 45% or so who survive.

The USA TODAY editorial then regurgitates the same old talking points that right-to-try advocates have been pushing for ages:

The process for getting experimental drugs is so daunting that fewer than 1,000 people sought and got federal approval to take such drugs last year.

Food and Drug Administration rules require patients to clear a series of hurdles. First, they and their doctors must find a company to provide its drug. Many drug makers — worried that a patient's death will spur a lawsuit or harm their chances for final FDA approval — refuse.

Even then, patients still need a hospital review board to sign off, a contract between the hospital and the drug maker, and FDA approval. The FDA application process, according to its own estimates, can take up to 100 hours.

Now, the bureaucratic absurdity is generating a backlash.

Colorado, Louisiana and Missouri recently approved "right to try" laws, which seek to simplify the process. The Michigan Senate passed a bill last Wednesday; in Arizona, an initiative will appear on the November ballot.

These carefully crafted measures allow patients and their doctors to go directly to a pharmaceutical company to seek access to drugs, but only those that have cleared the first phase of clinical trials and remain in development. The laws protect drug makers from lawsuits. And, pointedly, they seek to cut out the FDA, which now has final say.

First, as has been pointed out before, the FDA approves the vast majority of compassionate use exemptions. Granted, the paperwork burden can be excessive. In particular, it’s truly off-base to include the hospital review board signing of as part of the “bureaucratic absurdity” regarding compassionate use exemptions. Either that was an oversight, or the person writing the USA TODAY editorial is utterly clueless about clinical trials and drug approval. That “hospital review board” is called an institutional review board (IRB), and its task is to protect the rights of human subjects in research. If there’s one thing you don’t want to tinker with too much, it’s IRB approval. Similarly, in this argument we see the same wishful thinking and fantasy that are always at the heart of arguments by “right to try” advocates, who seem to think that there are all manner of drugs out there that can save the lives of patients with terminal cancer or diseases like amyotropic lateral sclerosis. As I’ve pointed out multiple times, the vast majority of drugs won’t make it through clinical trials to be approved because they won’t demonstrate efficacy and/or adequate safety to be approved. so the chances of prolonging life significantly taking unapproved drugs. The chances for causing harm are therefore much greater than that the drug will help. Just as bad, testing drugs like this outside of clinical trials, unless the drug being tested is the rarest of the rare “miracle” drug, is unlikely to provide usable information about efficacy, although such use can provide information about adverse effects.

USA TODAY is right about one thing. These bills are “carefully crafted,” but not to do what USA TODAY thinks. They’re usually portrayed as being a spontaneous movement among patients and patient advocates. To some extent that’s true, as right-to-try has roots in AIDS activism. There’s a reason why some of its advocates refer to it as the “Dallas Buyers Club law.” Several years ago, the Abigail Alliance promoted similar laws, efforts that resulted in a US Supreme Court ruling that patients do not have a Constitutional right to unapproved drugs. However, this latest round of right-to-try activism has the fingerprints of the libertarian Goldwater Institute all over it. Indeed, the Goldwater Institute is flying its flacks to states considering these laws. (I know it did so in Michigan last month.) If you look at the text of the right-to-try laws already passed and right-to-try bills under consideration, you will see that they are almost identical to the Goldwater Institute’s model legislation.

The intent of the Goldwater Institute can be gleaned in its policy paper, Everyone Deserves the Right to Try: Empowering the Terminally Ill to Take Control of their Treatment. Particularly obvious is the part where the Goldwater Institute bemoans the expansion of FDA authority in the 1960s by the Kefauver-Harris Amendments that required that the FDA not just to demonstrate safety but efficacy as well. This expansion of FDA power was in reaction to the thalidomide debacle, leading the Goldwater Institute to make the rather bizarre (OK, very bizarre) argument that because the issue with thalidomide was a safety problem, not an efficacy problem and because thalidomide was never approved in the US (mainly due to the FDA, let’s not forget), the expansion of FDA power in response to the thalidomide debacle was “unwarranted”? As I discussed before, the report itself is also loaded with emotionally charged language about the FDA and terminally ill patients and a whole boatload of highly dubious statements. Every experimental drug is apparently “potentially life-saving,” at least the ones that made it through phase I trials, which apparently is enough to be “deemed safe by the FDA” (at least if you are foolish enough to believe the Goldwater Institute’s talking points).

Reading the model legislation itself, one will see an extreme emphasis on protecting companies providing experimental drugs and physicians who recommend them from lawsuits. Moreover, it’s a very libertarian law. Patients are completely on their own. They have to pay for everything themselves, and that liability doesn’t end after they die. There’s a specific provision stating that the drug company can go after the patient’s estate. There’s another provision that states that “the patient's health plan or third party administrator and provider are not obligated to pay for any care or treatments consequent to the use of the investigational drug, biological product, or device,” the exception being if it’s in the contract that the health plan pay. In other words, if a patient uses an experimental drug under right-to-try and suffers a serious complication, the patient’s health insurance plan doesn’t have to pay for the medical expenses necessary to take care of that complication.

So what does this mean? Basically, it means that only the rich will be able to take advantage of the provisions of right-to-try; that is, assuming that the laws aren’t struck down as unconstitutional. Of course, what the Goldwater Institute is counting on is the same thing that’s happening in states that have legalized marijuana for recreational use: That the federal government (in this case, the FDA) will decide that it’s too much trouble to enforce the law. While it’s true that there are inequities in the clinical trial system, these tend to be based more on geography and difficulty traveling to medical centers offering clinical trials. For right-to-try, it’s a pure, free market paradise, where companies can charge as much as they want for drugs that have only passed phase I clinical trials. I could see unscrupulous pharmaceutical companies resurrecting drugs that have passed phase I but went no further, opening phase II trials to which they don’t plan on accruing very many patients. Step 3: Profit.

To get an idea of what I mean about the libertarian bent of these laws, take a look at what Christina Sandefur of the Goldwater Institute says after being challenged with an observation that what right-to-try is all about is not helping terminally ill patients but rather letting those who can afford it (i.e., the rich) have unfettered access to experimental drugs:

@gorskon @Free2Treat @joshschisler You're saying that even given that, if even one person can't afford it, we should deny the option to all?

— Christina Sandefur (@cmsandefur) August 13, 2014

Note the false dichotomy and how she ignores the likelihood that right-to-try laws will harm far more people than they are likely to help.

Bioethicist Art Caplan hammers the financial inequity in his response, FDA is not the main problem. There, he identifies this key problem with right-to-try laws, namely that they leave patients completely on their own far more than even the most lurid nightmares about our current clinical trial system promulgated by the Goldwater Institute to portray it as the worst injustice to patients known to humans. That’s the dirty little secret of “right-to-try.” What disappoints me about Caplan’s response, is that that’s the only aspect of these bills he concentrates on. Nothing about the dangers. Nothing about the exaggerations of the potential benefits and minimization of the risks. I realize he only had around 500 words, if that, but I’m not sure that financial issues were the ones to focus on, although I do give him props for this:

Right-to-try laws are basically "right to beg" laws. Begging is not what the dying and desperately ill should be asked to do. Legislators should stop enacting feel-good laws and show they care by finding the money to pay for experimental drugs and the travel and expenses involved in getting to them.

Exactly.

ADDENDUM: Looking at it again, I just noticed something about the Goldwater Institute model legislation. Remember how I was puzzled about how the Michigan right-to-try legislation had changed its wording about the disease to which it applies from “terminal illness” to “advanced illness”? Take a look at the model legislation. What does it say? Yep. “Advanced illness.” Now I know why the Senate bill in Michigan was changed. It was changed to match the new Goldwater Institute template. Does anyone wonder why this might be? I don’t. Clearly, this change in wording opens the way for such laws to apply to more than just terminal illness. Unfortunately, it was also passed by the Senate last week. True, the Michigan version states that "advanced illness" means the same thing as "terminal illness" for purposes of the bill, but that would be easy to change, and the Goldwater Institute template says no such thing now.

Does anyone still doubt that the intention of these laws is to open up right-to-try to everyone and thereby gut the FDA’s authority, bringing us back to the libertarian paradise of the days before the FDA, when wandering snake oil salesman wandered from town to town, selling their nostrums? We’re told that we don’t need the FDA because the “market” will protect us. Remember how well that worked out last time.

oracknows Mon, 08/18/2014 - 21:00

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It's even worse than last time, since at least back in the days of Nostrums you could sue in court over this, drawing attention to it even if you didn't win anything (or had to settle). Now, the special legal protections for providers of the "right-to-try" experiments almost seem unnecessary since any such provider in the US is almost certainly going to require the patient to sign an agreement agreeing to mandatory arbitration over any malpractice issues (along with an NDA).

I was a little sympathetic to "right to try" laws at first, too, for terminal patients. If they're trying these treatments out, they've already decided they don't want to simply wait for death on palliative care - they'd rather risk it and shorter life remaining on experimental care. But the FDA already has a "compassionate use" program, if you can wing it.

Does anyone still doubt that the intention of these laws is to open up right-to-try to everyone and thereby gut the FDA’s authority, bringing us back to the libertarian paradise of the days before the FDA, when wandering snake oil salesman wandered from town to town, selling their nostrums?

Also worse than last time. At least with the Snake Oil Nostrums, all you had was some con-man huckster's word on it. Want to be every single one of the treatments that shows up if Right-to-Try becomes a reality on the ground will tout about how they're "FDA approved" because they passed a Phase I trial? It's worse than mere sham and ignorance.

By law, the FDA is not allowed to regulate "Homeopathic drugs" (aka water and sugar pills) with regards to efficacy and safety. That's why every day I see parents telling me that brand so-and-so's homeopathic teething pills don't seem to help much with their infant's teething pain. When I explain the quackery that is homeopathy, a majority of parents will then ask why are homeopathic medicines allowed to be sold in pharmacies. I will then inform them it is legal thanks to the passage in the 1930's of federal legislation (sponsored by a homeopathic US senator). A lot of parents will then inquire as to why someone in Washington doesn't repeal that law so parents don't waste their money on medicines that don't work. It's a good question.

Right-to-Try effectively does the same (albeit at a state and not federal level) for drugs just entering the FDA approval process. Will people soon be asking the same questions about Right-to-Try drugs with regards to a loved one who was hurt, killed, or didn't live long on a Right-to-Try drug? Worse yet, will we start to see fewer new drugs entering the FDA pipeline due to this misguided legislation?

We are all "terminal". None of us gets out of this gig alive. But popular opinion in the US prefers to avoid the reality of unavoidable death. Popular opinion--based on clear increases in CAM and Right-to-Try laws--also wants the "quick fix" (aka the "Easy Button") when it comes to medicine and medical treatments. There is no "Easy Button". Modern science-based medicine didn't get to where it is overnight or through anecdotal drug "trials". This will be a step backwards for science-based medicine--and much more importantly patient care-- if these "Right-to-Try laws are passed.

Another downside of right-to-try: If the experience of those who acquire therapy under right-to-try laws suggests that the treatment might be effective, it becomes nearly impossible to do a real clinical trial. Who would want to be randomized to placebo? So the right-to-try laws threaten our ability ever to establish safety and effectiveness reliably.

This news is troubling to me. Yes, once in a blue moon some treatment may appear that seems to be a cure for some heretofore untreatable illness. But the risks simply don't outweigh the benefits. Add to that the very real potential of the FDA being short-circuited by these laws and it could get really dangerous. This is also the big danger to Rand-style laissez faire libertarianism -- the most ruthless are not checked by anything but the civil courts, and few of their victims will be in a position to sue.

(PS: I just noticed . . . there's a "Expose Orac" Facebook page ? you're famous! )

"(PS: I just noticed . . . there’s a “Expose Orac” Facebook page ? you’re famous! )"

Oo, and a blog too.The blogger (who really really loves Jake Crosby) attacking Orac's "anonymity" has an "about me" section featuring a blank where a photo should go, and absolutely no personal information.

The irony, it amuses.

I notice that the blog has four posts on it, the last from 2012. The Facebook page is similarly lame.

re Jake
The other day, Jake broke the so-called big news ( via Focus Autism) that CDC malfeasance has been exposed by Brian Hooker with the assistance of a whistleblower: it seems the agency covered-up an MMR-autism "link" ( African-American boys given the MMR later had less autism).NOW AoA and TMR have jumped on the bandwagon as they finally have the PROOF they require.
-btw- there's even a video from Andy compariing the CDC's malfeasance to the Tuskegee syphilis experiments.

A sceptic can only ask: them Are you serious?

there’s a “Expose Orac” Facebook page

Orac hasn't exactly gone to great lengths to keep his identity a secret, so such a page (or blog) wouldn't be telling us anything we didn't already have the option to know, if we chose. As he has mentioned here before, Orac has another blog on which he uses his real name. I once followed a link to the latter blog and immediately recognized his writing style. I'm sure others, critics as well as fans, have done so, too.

As for the topic at hand: Yes, it's obvious that the goal is to neuter the FDA, because an effective FDA is Evil Government Regulation. In Libertarian World, there is no other kind of government regulation. They forget why it was necessary to create the FDA (and dozens of other alphabet soup agencies) in the first place.

Libertarianism, like Communism, is an attractive political theory as long as you don't stop to consider how you would successfully implement it in a society consisting of actual human beings.

there’s even a video from Andy compariing the CDC’s malfeasance to the Tuskegee syphilis experiments

There ought to be a law.

As for the topic at hand: Yes, it’s obvious that the goal is to neuter the FDA, because an effective FDA is Evil Government Regulation. In Libertarian World, there is no other kind of government regulation. They forget why it was necessary to create the FDA (and dozens of other alphabet soup agencies) in the first place.

Indeed. The people supporting these right-to-try bills and laws genuinely think that they are making things better for terminally ill patients when really what they are being co-opted to do is to help the Goldwater Institute weaken the FDA to the point that it is an ineffective shell, barely able to guarantee the safety, much less the efficacy, of drugs and medical devices. This will make things much worse, not just for terminally ill patients, but for all patients; i.e., all of us.

Chris Hickie @2:

a homeopathic US senator

Would that be an ugly bag of even more mostly water than usual?

"Would that be an ugly bag of even more mostly water than usual?"

Yes but I would say with more alcohol than usual and a lot less sugar.

"It’s obvious that the goal is to neuter the FDA, because an effective FDA is Evil Government Regulation. In Libertarian World, there is no other kind of government regulation. They forget why it was necessary to create the FDA (and dozens of other alphabet soup agencies) in the first place."

This is not just Ron-Paul-marginal Liber-nuttery, it's been mainstream Republican doctrine since Reagan, which is to say it's neo-Coolidge, which is to say it's the ideology of pure unfettered capitalism. When conservatives blather about how we'd all be so much better off with all that regulatory interference with the supposedly self-correcting market, my brain answers with a four-letter word: TRIS. But the eleven letters of 'thalidomide' will do just as well. Even if the old Invisible Hand would 'work' sooner or later (which it doesn't; because monopoly, unequal power distribution, yada, yada) how's that supposed to comfort parents whose kids were burned to cinders by their 'flame retardant' jammies?

"The people supporting these right-to-try bills think they are making things better for terminally ill patients when really they are being co-opted to help the Goldwater Institute weaken the FDA." Damn straight! But even exposing that specific bit of bait-and-switch isn't going to address the more fundamental problem: the 'over-determined' claim of free-market ideological Kool-Aid on the American mind.

(Jargon explained: 'over-determined' is Louis Althusser's term for the the idea that prevailing ideologies have no single source, but assemble out of whole bunch of small instances, like individual thought molecules, each innocuous enough by itself evaporating into the air and gathering to form a cloud over the public mind. The term is often mis-used or misunderstood by the perception 'over' means "excessive, extra," when in fact it just means "occupying a certain space above" like a cloud...)

Still, even usually reliable news outlets make mistakes

True that.

But it's really very distressing to see a major national newspaper with -- no doubt -- its heart in the right place failing to grasp that when you see a state-level bill with "right to" in the title that's being flogged by a think tank, the first thing you should do is look for funding from the Koch brothers.

Because the odds are very high that it's their work and should be treated accordingly -- ie, examined closely with an eye to answering the question: "What filthy lies does this piece of legislation tell in order to disguise its ugly and soulless true purpose?"

Couldn't hurt.

Thoughtful consideration of the bill on its merits without reference to the Kochs would be better, of course. But that's not always possible. .

Are any of you terminal? Chronic? Perhaps not, but I won't make that assumption. I'm an MS patient, dxd 10 years ago who's been treated with my own mesenchymal stem cells. I, along with hundreds of patients, have received quality of life benefits from being treated with our own cells. This treatment is not allowed in the USA even though there are 100's of study on Pub Med that speak to it's safety and efficacy. This type of treatment is NOT a cure, but it offers improvements that no FDA approved drug on the market even comes close to. Maybe "Right to Try" legislation isn't perfect, but hey it's bringing attention to the important issue at hand! Take Alzheimer's for instance. "As our population ages, the disease impacts a greater percentage of Americans. The number of people age 65 and older will more than double between 2010 and 2050 to 88.5 million or 20 percent of the population; likewise, those 85 and older will rise three-fold, to 19 million, according to the U.S. Census Bureau." http://www.alzfdn.org/AboutAlzheimers/statistics.html
Getting a neurological condition yourself, or someone you hold dear, is a fact of life. It will literally touch EVERY American family. Another fact is there is NO cure for most neuro diseases, and time is literally running out for millions! This is really a civil rights issue. I contacted the FDA for 2 of my friends who were critical, and was told emphatically NO! They would not be considered for "compassionate care." One was being placed in a nursing home at the age of 48 for MS and the other became suicidal as she knew being treated with her own stem cells was her last hope. She was also looking at being place in a nursing home at the age of 28. Both had little time left to live. My 28 yr old friend has since traveled to Germany and received treatment. My other friend traveled to Mexico. They are both improving, but no thanks to our FDA. Medical Tourism is alive and thriving thanks to the lack of compassion for chronic, no option patients here in the USA. It's a real problem and one that's easy for most of you to talk about 2nd or 3rd hand. None of the patients I know are willing to sit back and let cruel diseases take them from their homes, family and friends. These people aren't rich. So the theory that only rich people will have access to this is entirely false. Friends and families have raised the money for them to receive these stem cell treatments. Unfortunately who will have the control over the cells from my own body and who will get to make the money on it seems to be taking medical innovation back tories! Bureaucratic agencies in Washington, making health care decisions for me is ludicrous! It should never have been their right to treat my cells like a mass produced drug! I am educated, informed and can make an extremely intelligent decision right along side my very capable physician. Outside paternalistic attitudes are extremely unnecessary and unwarranted. the dark ages. Let doctors innovate like they've been doing for cies! Bureaucratic agencies in Washington, making health care decisions for me is ludicrous! It should never have been their right to treat my cells like a mass produced drug! I am educated, informed and can make an extremely intelligent decision right along side my very capable physician. Outside paternalistic attitudes are extremely unnecessary and unwarranted.

Paternalism is alive and well. obviously. Why all the hand wringing and speculation? What do all here who are physically well really fear? How many of you have taken care of a loved one who is terminally or chronically ill? How many of you would say NO to hope if you were terminally ill? How many of you believe that you should be making decisions for others? Please, just stay well and quit preaching.

I will offer up a scenario of why "right to try" is a bad idea that might well pull promising treatments off the market.

Imagine a patient with disease X. There is currently a clinical trial of treatment Y for disease X, but the patient was not enrolled. The patient uses the "right to try" laws to get treatment Y. The patient dies horribly from effects of treatment Y (which was why the patient was not enrolled in the clinical trial in the first place). The patient's death makes the news. Even if the clinical trial is not canceled, the stock price of the company that makes treatment Y tanks. The company goes under and treatment Y is never made again.

But what if treatment Y really did work for disease X, just not in people like the patient, who had a counter-indication? What about all the other people with disease X who could have tolerated treatment Y and had years added to their lives? Because of "right to try", that would never happen.

That is actually not an likely scenario. All it takes is one really bad adverse reaction to an experimental drug under right-to-try to tank the drug. Add to that news reports of the patient spending, say tens of thousands of dollars for treatment Y under right-to-try and the pharmaceutical company going after his estate to recover its debt (which is explicitly allowed for in the Goldwater Institute template and therefore every right-to-try bill or law), and you have a disaster in the making.

Right-to-try proponents tend to argue that right-to-try will encourage innovation. I see it the opposite way. It will make pharmaceutical companies more risk-averse and therefore less likely to innovate. It will place burdens on smaller biotech firms, incubators of innovation, most of which struggle to raise the capital needed to get their products through the regulatory process, such that they will be less likely to take risks.

"How many of you have taken care of a loved one who is terminally or chronically ill?"

Many of comment here have, and if you have read this blog you will have learned that Orac's wife also has.

We just prefer to not treat our loved ones like guinea pigs. And one reason we read this blog and the not so secret other one is to learn about the issues, and how to not become a gullible mark to the latest scam.

To Barbara: I have watched my husband's grandmother and grandfather both pass (Alzheimer's and osteosarcoma respectively) and was involved in their care. So yes most everyone has been touched in some way by terminal illness. what I remember most was when my hubby's grandfather (who had been battling cancer for some time) was told it had spread to the bones of his face and skull he opted to forego any additional treatment. The family was deeply shocked, including my husband. I sat him down and explained to him as gently as possible that the doctor's had told his grandfather his illness was terminal. He had already endured radiation and chemotherapy before (with side effects) and since cure was not possible he chose to live out the remainder of his life surrounded by his family with palliative care. It was a decision I deeply respected. what we have been pointing out here is that it is cruel to dangle hope like a carrot in front of the terminally ill and get them to sacrifice their remaining health, dignity, and goods on something that almost certainly will not help them. Destroying the power of the FDA and promoting anyone with any drug that has passed a phase I trial to offer that medicine to any patient who wants it is a recipe for disaster. It will cause way more harm than good.
To Jennifer: Some of us are in good health, but by no means all. I have great sympathy for your struggle with a diagnosis like MS and wish you nothing but the best. I can't find much in my first cursory search for stem cell treatment in MS only that it is under study. I think what is probably happening as with so many other things is that some people are just opening clinics outside of the US to give a therapy that hasn't been proven to work. That is dangerous in many ways, offering false hope if it doesn't work, draining your bank account (and those of your family and friends), as well as risking unsafe or unsanitary treatment in a country where the laws may not be set up to help you. You may believe the treatment is good, you may believe you are being helped, but unfortunately as humans we are easy to fool. This is obviously something that needs more study.