Abigail Alliance

The cruel sham of "right to try" comes to Michigan

oracknows — Thu, 14 Aug 2014 02:00:28 +0000

The cruel sham of "right to try" comes to Michigan

There are times when supporting science-based health policy and opposing health policies that sound compassionate but are not are easily portrayed as though I’m opposing mom, apple pie, and the American flag. One such type of misguided policy that I’ve opposed is a category of bills that have been finding their way into state legislatures lately known as “right to try” bills. Jann Bellamy over at SBM and I have both written about them before. With the passage of the first such bill into law in Colorado in May, followed by Missouri and Louisiana, and its heading to the voters of Arizona as a referendum in November, I had been meaning to revisit the topic. Although “right-to-try” laws are a bad policy idea that’s not new, versions of such bills having been championed by, for example, the Abigail Alliance for at least a decade, the recent popularity of the movie Dallas Buyers Club appears to have given them a new boost, such that Colorado state Senator Irene Aguilar even frequently referred to her state’s right-to-try bill as the “Dallas Buyers Club” bill. It’s a topic I’ve been meaning to revisit at least since the news out of Colorado in May, but apparently I needed a nudge, given that it’s two months later now.

Unfortunately, that nudge came in the form of a right-to-try bill (Senate Bill 991) introduced into the legislature in Michigan by Senator John Pappageorge. It was unanimously passed, almost without comment, by the Michigan Senate Health Policy Committee, and certainly there was minimal news coverage. Moreover, I just learned that it was being taken up by the Senate yesterday. In parallel, the same legislation (House Bill 5651) has been introduced into the Michigan House of Representatives.

I joke (somewhat grimly) about seeming to be opposing mom, apple pie, and the American flag (not to mention apparently also about wanting to disembowel puppies) when I discuss right-to-try bills, but there’s a reason for that. These bills tend to have not just broad bipartisan support in the legislature, because opposing such laws seems on the surface to be the equivalent of denying dying patients a last ditch chance at life, but broad support among the public because of the seemingly reasonable question, “What’s the harm?” Unfortunately, disaster can result when normal human compassion for fellow suffering humans is yoked to misinformation and misunderstanding of science (in this case how clinical trials work), who really controls drug development and regulation in the US, and the real harm that using such drugs prematurely can cause. For right-to-try, the result is perniciously popular legislation that provides lots of false hope and virtually no benefit to terminally ill patients. In the face of this, even politicians with a reasonable understanding of the science, why such laws represent nothing but false hope, and why, even if they go into effect without objection by the FDA, would be far more likely to harm patients than help them, hesitate.

Right-to-try in Colorado

Before I get to my own state, let’s look at Colorado’s right-to-try law, since it was the first to pass. One thing that I feel obligated to point out again is that virtually all the recent “right-to-try” bills introduced into state legislature have been based on model legislation designed by the Goldwater Institute, a libertarian think tank whose specious and misleading arguments for such legislation I’ve discussed before . In her previous post on right-to-try bills, Jann Bellamy mentioned that there is “nothing like a touching anecdote to spur a politician into action,” and she’s right. That’s why the Goldwater Institute’s web page on its right-to-try initiatives is populated with intentionally emotionally manipulative heart-wrenching testimonials of (mostly) cancer patients arguing that, if only they had had access to experimental drugs, they might survive or of dead patients whose family or friends tearfully argue that “if only”—if only—right to try had been passed before their loved one died that loved one might still be alive. In the wake of the passage of Colorado’s right-to-try law in May, anecdotes ruled, heart-wrenching anecdotes such as this one about Nick Auden, a Colorado man with stage IV melanoma who died six months before the legislation passed:

Who isn’t moved by the struggles of a father who wants to survive for his children? Who wouldn’t want to help this man? What kind of monster am I to oppose a law that would provide brave suffering patients like Nick Auden another shot at life, no matter how slim the chance? Such is the level of discourse directed at those who have the temerity to point out that right-to-try laws are a sham, false hope, and far more likely to harm terminally ill patients than help them; that is, if they have any effect whatsoever, which is unlikely. They are what I like to call placebo laws in that they make the body politic feel better but have no real effect on the underlying problem that they are meant to address. Indeed, as Jann Bellamy pointed out, a much less emotion-driven analysis of these so-called “right-to-try” bills currently before several state legislatures reveals disturbing truths about the false promises behind these bills, promises which in some cases appear to be driven more by political ideology than genuine concern for patients.

This can be seen by a simple comparison of the text of the Goldwater Institute model legislation and the final text of the Colorado right-to-try law as enacted. The Colorado law, in fact, bears a very close similarity to the Goldwater Institute model legislation. Some differences between the Goldwater Institute template and the actual Colorado law that leapt out at me included that the Colorado law:

Adds a mention that the drug approval process in the US “protects future patients from premature, ineffective, and unsafe medications and treatments over the long run, but the process” (not in the Goldwater template text) and “often takes many years” (in the Goldwater text)
Alters eligibility to include patients who have “been unable to participate in a clinical trial for the terminal illness within one hundred miles of the patient's home address for the terminal illness, or not been accepted to the clinical trial within one week of completion of the clinical trial application process”
States that “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 eligible patient; except that coverage may not be denied for a preexisting condition and for coverage for benefits which commenced prior to the time the eligible patient begins use of such drug, biologic product or device”

There are other differences, of course, but they’re mostly wording and Colorado-specific language about state statutes effected. I tend to interpret #1 as having been added to make it sound less as though the FDA approval process is useless, as the Goldwater text does. My guess about #2 is that it was undoubtedly added in order to exclude patients who just want experimental drugs but aren’t interested in enrolling in a clinical trial. Finally, I’m not completely sure how to interpret #3 and would welcome a lawyer’s input (particularly if it’s a health lawyer), but it sounds rather ominous in that it allows insurers to deny new coverage to a patient for a six month period from the time the patient starts use of an investigational drug, but can’t deny coverage for a preexisting condition (i.e., the condition that led the patient to be terminally ill, and any other preexisting conditions) or any benefits that commenced prior to the time the patient starts using an experimental drug or device. On the other hand, to me the language implies that insurance companies can deny coverage for any complications that arise from the use of experimental therapy under right-to-try, whether caused by that therapy or not. So if the patient develops a complication from the treatment, he’s out of luck. If he happens to be hit by a car, he might be out of luck. Thus, a bill that sounds compassionate appears to have a cruel, punishing twist embedded in it.

That is not in the least bit surprising. This law is very “libertarian” in that it says that patients can try an experimental therapy that’s passed phase I trials to phase II or beyond, but anything that happens after that is all on the patient. (Indeed, my interpretation of right-to-try is that it would allow access to a drug that's only passed phase I, even if the phase II trial hasn't accrued a single patient yet, as long as there's a phase II trial open.) The doctor recommending the treatment is off the hook, no matter how bad his decision to recommend the experimental therapy was. The drug company is off the hook, no matter how many problems the drug might have. The insurance companies appear to be off the hook, complete with a potential loophole to let them refuse to cover various treatments in terminally ill patients. Basically, if you’re rich, you can bypass clinical trials (if the company is willing) and buy up experimental drug for yourself. If you’re poor, or even just not rich (remember, these drugs will cost big time), you’re, as they say, SOL. You can have the hope dangled in front of you and just die. No wonder the Goldwater Institute flew a flack to Lansing last month to testify about the bill, as it appears to be doing for every state considering right-to-try legislation.

At this point, I think it’s a good idea for me to remind my readers once again that that these right-to-try laws cover any drug, treatment, or experimental device that has passed phase I clinical trials. Indeed, in the video above, the reporter made a highly misleading statement when she stated that the Colorado “right-to-try” law “only applies to drugs that have been deemed safe by the FDA.” That statement is so wrong it’s not even wrong, as skeptics sometimes like to say. Just because a drug has passed phase I clinical trials does not—I repeat, does not—mean that the drug has been “deemed safe by the FDA.” Phase I trials, also known as “first in human” trials, don’t enroll very many patients. Sometimes it’s as few as 20 patients, sometimes even less. That is not enough to adequately determine safety, nor is it intended to. That’s because phase I trials are designed primarily to identify major side effects and to use a process known as dose escalation to determine what is commonly referred to as the “maximum tolerated dose” (MTD). It is utterly impossible for such a small clinical trial to adequately assess the safety of a drug. All it can do is to make sure there are no unexpected major adverse events, that the expected side effects are tolerable, and that the drug has a side effect profile that isn’t grossly more unsafe than the disease itself. Phase II and phase III trials are needed to confirm safety. That’s why the premature diffusion of unapproved drugs has the potential to increase morbidity from adverse events and even hasten death. One example is amonifide for treating breast cancer. The drug made it through phase I trials, but serious life-threatening hematologic toxicity emerged during phase II trials.

Think of phase I trials as a screening test looking for the most obvious toxicities, with phase II and III studies confirming them. Indeed, even phase III trials can’t always adequately demonstrate that a drug is safe; it’s not uncommon for less common adverse effects not to show up until post-marketing surveillance, when much larger numbers of patients receive the drug. Moreover, only 5% of all cancer drugs that enter clinical testing are ultimately approved for patient use. Among drugs tested in phase II trials, only 30% go on to phase III. So, to equate having passed phase I clinical trials with having been “deemed safe by the FDA” betrays a profound misunderstanding at the heart of the bill of what a phase I trial is and what passing it means. The potential for disaster is there.

The false hope of right-to-try metastasizes to Michigan

I’ll discuss more of what’s wrong with right-to-try laws and how misguided they are, but first I want to take look at the right-to try bills currently under consideration in the Michigan legislature. Oddly enough, I was completely unaware that a right-to-try bill had been introduced into the Michigan legislature until last month, when I got a message from a concerned person. It had basically already passed committee. Before that contact, as hard as it is to believe right now, I had heard absolutely nothing about these bills, but I’m a fast learner. I didn’t have much help, though, because there was very little media notice taken of the Senate hearing about this bill other than a Detroit Free Press article that I found days after the hearing and self-serving articles on John Pappageorge’s website touting mistakenly how this bill would allow “access to potentially life-saving treatments.” Either that, or I missed it because I was out of town at TAM in the days leading up to the hearing. Now, I hear that the bill is being debated in the Senate, but yesterday I couldn’t find a single news article about it. It was sneaked in, apparently, and I only heard about it because an interested activist let me know.

Now, going back to look over the coverage, I found that the Freep article bought in the same compassionate but incorrect framing as was the case in the other states considering such laws:

Arlene Kalley has lived with terminal cancer for years — and with each new drug she uses to keep the disease at bay, her options dwindle.

Earlier today, the Michigan Senate’s health policy committee approved a bill that would offer Kalley and other terminally ill patients in Michigan better access to experimental medication.

It doesn’t require manufacturers to provide the drug nor does it require insurers to cover the costs. But it gives patients a “right to try,” said Sen. John Pappageorge, R-Troy, whose first wife died of cancer in 1993.

He introduced the bill earlier this year after speaking with Terry Kalley, a partner with Global Logistics Strategies in Bloomfield Hills.

And this is how the idea for introducing bill came about:

His wife, Arlene, was taking Avastin in 2011 to keep metastatic breast cancer at bay when the U.S. Food and Drug Administration yanked its approval of the drug, questioning its safety and efficacy.

Ultimately, Arlene Kalley was able to keep taking Avastin because it still was being used to treat other cancers, but the experience got the Kalleys thinking about what could happen if Arlene Kalley’s current treatment is no longer effective one day.

While I can understand why this case might have led the Kalleys to wonder about right to try, I must point out here that Avastin was a very different case than situations envisioned in right-to-try legislation. Specifically, Avastin had undergone randomized clinical trials (RCTs) beyond phase I and had already been approved for other cancers before being approved by the “fast track” approval process for advanced breast cancer. Its approval for advanced breast cancer was based on two RCTs that showed a modest increase in progression-free survival (PFS) when Avastin was added to chemotherapy, but no effect on overall survival (OS). In 2008, based on a program to “fast track” promising drugs that was developed in 1990s, the FDA gave provisional approval to Genentech to market Avastin for metastatic breast cancer with the condition that Genentech had to perform additional studies to verify the results upon which the original approval had been based. At the time, there was a great deal of argument over whether this was a wise decision, particularly given how expensive Avastin is and the lack of evidence that it improved quality of life or overall survival. Unfortunately, the results of those additional clinical trials were very disappointing to all of us who take care of breast cancer patients. The AVADO trial only found an increase in PFS of less than a month when Avastin was added to docetaxel with no increase in OS, while the RIBBON-1 trial found an improvement in PFS of 2.9 months when added to capecitabine, and 1.2 months when added to anthracycline-based chemotherapy. That’s why in July 2010 the FDA advisory committee revoked the fast track approval.

In other words, although I realize that Arlene Kalley was simply worried about what her options would be if her current treatment regimen ceases to keep her cancer in check, in a manner of speaking she is inadvertently comparing apples and oranges in a way that could lead those unfamiliar with the Avastin saga to believe that Avastin and right-to-try are related by anything other than the fact that she has done well on Avastin thus far. I bring this up because the saga of Avastin for breast cancer is relevant to right-to-try bills, but not in the manner implied. Contrary to the arguments made in favor of right-to-try laws that a single phase I trial is enough for a treatment to be deemed "safe," even though Avastin was FDA-approved for other cancers and provisionally approved for breast cancer, in the subsequent clinical trials for advanced breast cancer there was evidence of harm due to Avastin. That harm likely accounted for why the increase in PFS did not translate into an improvement in OS. Specifically, the drug’s toxicity likely “took back” those gains in PFS. As Fran Visco of the National Breast Cancer Coalition put it, “The FDA should never have approved Avastin for breast cancer to begin with. We don’t see evidence of benefit, but we do see evidence of harm.” And that was just Avastin, not a drug with much less extensive testing, such as the experimental therapies right-to-try bills propose releasing “into the wild,” so to speak.

So what do the Michigan bills SB 991 (Senate) and HB 5651 (House) propose? It’s basically very similar to the Colorado law and the Goldwater Institute boilerplate, with a couple of notable exceptions. For example, SB 991 requires:

A statement in the “written informed consent” for using the experimental drug that informs the patient that “the patient's eligibility for hospice care may be withdrawn if the patient begins curative treatment and that care may be reinstated if the curative treatment ends and the patient meets hospice eligibility requirements.”
A statement in the “written informed consent” for using the experimental drug that attests that the “patient understands that he or she is liable for all expenses consequent to the use of the investigational drug, biological product, or device and that this liability extends to the patient's estate, unless a contract between the patient and the manufacturer of the drug, biological product, or device states otherwise.”

The first of these is odd and unnecessary in that hospices tell patients up front that if they undertake curative treatment again they are no longer eligible to be in hospice while undergoing the treatment. Including such a provision in SB 991 strikes me as redundant, a duplication of law and policy that already exists for hospices. The second of these is to me quite objectionable. Not only does it put the patient on the hook for any expenses or debt that he incurs using experimental treatments, but it seems custom-made for drug companies, to make sure that they get their money for experimental therapies administered under “right-to-try,” no matter what, even letting them go after a deceased patient’s estate, something that will frequently be necessary because patients eligible for "right-to-try" by definition have a terminal illness. The vast majority of even the most promising drugs will likely only prolong their life at best, not save it. Either way, both of these Michigan provisions make a bad bill even worse.

In fairness, though, there is also a provision that explicitly states that a patient’s heirs are not liable for outstanding debt related to the treatment or lack of insurance and specifies that this act “does not affect any mandatory health care coverage for participation in clinical trials under the insurance code of 1956, 1956 PA 218, MCL 500.100 to 500.8302,” which, unlike the truly vile language in Colorado’s law, means that insurance companies must continue to cover all treatments not related to the experimental treatment. Also in fairness, SB 991 does add a provision to the usual Goldwater Institute boilerplate that states that “an official, employee, or agent of this state shall not block or attempt to block an eligible patient's access to an investigational drug, biological product, or device” by adding that “counseling, advice, or a recommendation consistent with medical standards of care from a licensed health care provider is not a violation of this section.” As faculty at a state institution, I would have been very worried about the part about not blocking access as a provision that might get me in trouble if I were simply to voice my medical opinion.

There was also a curious substitution resulting in a “substituted bill” for SB 991 that stops referring to “terminal illnesses” and instead refers to such illnesses as “advanced illnesses”:

(a) "Advanced illness" means a disease or medical or surgical condition with significant functional impairment that is not reversible even with administration of current federal drug administration approved and available treatments that is expected to result in death or a state of unconsciousness from which recovery is not expected. For purposes of this act only, advanced illness has the same general meaning as terminal illness has in the medical community.

For the life of me, I can’t figure out why this change was made, when the substituted bill states that for the purposes of this bill “advanced illness has the same general meaning as terminal illness has in the medical field.” I can’t help but get a sneaking suspicion, which could be wrong, that perhaps the bill’s sponsors are already thinking ahead to eventually expand eligibility for right-to-try to patients who are not terminally ill by laying the groundwork to have “advanced illness” associated with right-to-try rather than just terminal illness. That would fit in with the general anti-FDA tenor of the Goldwater Institute and much of the movement pushing these bills. Remember, the Goldwater Institute wants to turn back the clock at least 50 years, stripping the FDA of its powers gained after the thalidomide tragedy. I could be wrong, of course, but I don’t think so. Alternatively maybe there’s some regulatory or political reason for the substitution. Either way, the Michigan right-to-try bills are in some ways worse and in some ways not as bad as the Colorado right-to-try law. That doesn’t change how much these laws are flawed in their very conception.

The problem with right to try

I can understand the desperation of families, at least, facing the loss of a loved one to a terminal disease, be it cancer or something just as bad or even worse, such as amyotropic lateral sclerosis (ALS), more commonly known to the public as Lou Gehrig’s disease. After all, it was only five years ago that my wife and I faced the death of her mother from metastatic triple negative breast cancer, including brain metastases. Knowing, as all cancer doctors do, that it could happen to me (particularly now that I’m on the wrong side of 50), I can’t even guarantee that I wouldn’t be tempted by the siren call of right-to-try were one of these bills, or some variant thereof, to be passed into law in Michigan and I later was diagnosed with a terminal illness.

Even so, when people ask, “What’s the harm? and “How can it get worse?” I know that there is harm and it can get worse. If there’s anything worse than dying prematurely of a terminal illness, it’s accelerating your demise, suffering unnecessarily during the little time you have left, and/or emptying your bank account while doing either or both of these things. Compassion impels us to want to help terminally ill people in any way we can, but a less emotional analysis of right-to-try bills, coupled with a knowledge of the science and conduct of clinical trials reveals that these laws, as currently constituted, are almost universally a bad idea. Indeed, with such a low bar for a drug or device to qualify for right-to-try (a single phase I trial), it’s almost guaranteed that such laws are highly unlikely to help, at the cost of a not-insignificant risk of causing harm. These laws would be less odious if the bar had been raised a bit, for instance requiring that at least a phase II trial before a drug is eligible, but that's not what any of these bills propose, including Michigan’s.

Right-to-try laws also provide false hope. For one thing, these laws rest on a faulty assumption that there are all sorts of “miracle drugs” out there that can save the lives of terminally ill patients if only the FDA would get out of the way and let the patients have them. This assumption becomes rapidly apparent perusing the Goldwater Institute’s pages on right to try, which is packed with loaded language about the FDA and terminally ill patients, with every experimental drug apparently “potentially life-saving” and patients dying because they can’t get these drugs. Besides the greater likelihood of resulting in patient harm than help, contrary to what their advocates promise, right-to-try laws won’t deliver increased access to experimental drugs. The reason, as Jann and I have both explained at more length before, is because the federal government, through the FDA, controls drug approval, and federal law trumps state law. State right-to-try laws have no power over the FDA, and nothing states can do can compel the FDA to abide by their right-to-try laws. Moreover, drug companies are understandably reluctant to allow just anyone the use of investigational drugs still in clinical trials, because if something bad happens it could very well affect their application for approval:

However, companies and regulators alike have expressed some hesitancies about the program. For companies, expanded access means letting products out of tightly controlled and heavily monitored environments, potentially subjecting the product to incorrect use and previously-unknown adverse events, which would still need to be reported to FDA. Such incidents could potentially raise questions for regulators, thereby harming the chance of a product getting to market. Further, some companies have expressed their fears about expanded access programs robbing their clinical trials of some patients, which could reduce the statistical validity of a trial and potentially harm other patients by delaying a drug's path to market.

Another issue is a practical one. Manufacturing a new drug for the first time is expensive, which is why, quite often, only enough is manufactured to supply approved clinical trials to be used to support an application for FDA approval. “On-demand” manufacturing would not be easy to implement, particularly if enough patients asked for the drug under right-to-try. This could be a particular problem for small biotechnology companies, which often can barely scrape together the capital to do the necessary clinical trials to support FDA approval. Given that these small biotech companies are often the most innovative and least likely to be seeking approval for “me-too” drugs, the effect of right-to-try on the pharmaceutical industry’s already weak innovation could be significant.

It’s also important to note that right-to-try laws are more about ideology than science. Proponents and supporters of right-to-try tend to use arguments very similar to those used by the “health freedom movement” that rely on questions like, “Who owns you?” and appeals to the belief that the government shouldn’t tell people how they should manage their health. For instance, the Alliance for Natural Health USA, a key “health freedom” organization that advocates relaxing laws regulating the practice of medicine, the better to let quackery (particularly “natural treatments” flourish, is very much in favor of a federal version of “right-to-try,” which is every bit as much a bad idea as the state right-to-try laws, given that it would actually do something. As I alluded to above but did not explain, the Goldwater Institute, in an article promoting right-to-try, gives itself away by bemoaning the expansion of FDA authority in the 1960s by the Kefauver-Harris Amendments that required that the FDA not just require demonstration of safety but of efficacy as well before approving new drugs. This expansion of FDA power was in reaction to the thalidomide debacle, leading the Goldwater Institute to make the 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.”

Unfortunately, right-to-try bills and laws are nothing but feel-good measures that provide the illusion of actually doing something without actually doing anything substantive to help desperately ill patients, particularly given that the FDA already has an expanded access program to allow patients to use drugs outside of clinical trials. There are estimated to be 1,000 requests per year now, and it is uncommon for the FDA to deny a request for expanded access. Indeed, in FY2013, only three such requests were denied; in 2012, four; in 2011, one; and in 2010, sixteen. If, as proponents of these bills believe, expanded access programs aren’t easy enough to access, the answer is not to pass state right-to-try laws. It’s to reform the FDA’s expanded use program, something that’s occurred before and is ongoing, just as the FDA has developed a “fast-track” approval program, the same one under which Avastin was approved.

As David Kroll pointed out, true compassionate use reform will require that we as a society come to an agreement about the balance between access and scientific rigor, realizing that unapproved drugs, particularly the biologicals, such as monoclonal antibodies (which are very tricky to manufacture), are often in short supply. It doesn’t help terminally ill patients if patients demanding right-to-try put companies in a dilemma in which they either surrender some of their precious stock of investigational drug for “right-to-try” requests, thus endangering the company’s ability to conduct proper clinical trials, nor does it help patients to spend their life’s savings on investigational drugs that are unlikely to help them and could hurt them. Although their supporters are well-meaning and sincerely think they are helping the most desperate of their fellow human beings, right-to-try laws are a cruel sham perpetrated on terminally ill patients and should be opposed wherever they metastasize.

oracknows Wed, 08/13/2014 - 22:00

Categories

Technology

Maurice Saatchi (see http://en.wikipedia.org/wiki/Maurice_Saatchi,_Baron_Saatchi), A former advertising executive, given a seat in the UK House of Lords in recognition of his support for the Conservative party, has submitted a bill along these lines in the UK. The bill has been promoted with the full weight of an advertising company behind it - including an editorial article written by the promoters of the bill (but without declaring the COI, so it would appear they were written by an independent journalist).

Fortunately, there has been a considerable reaction on twitter as well as in the medical press (e.g. http://www.bmj.com/content/348/bmj.g3464) and the mainstream media (e.g. http://www.theguardian.com/science/brain-flapping/2014/may/21/saatchi-m…).

Yeah, the last time I discussed right to try, I included a section on the Saatchi bill, which is clearly cut from the same cloth as American right to try bills:

http://scienceblogs.com/insolence/2014/03/06/right-to-try-laws-are-meta…

The main difference in the US is that right to try is clearly intended as a step towards neutering the FDA and bringing us back to a libertarian paradise in which the FDA has minimal power over drugs and drug companies will, through the power of the market, magically make sure their drugs are safe and effective, because, you know, the market. They also say that the tort system will keep drug companies in line, which is hilarious, because the Goldwater Institute also does its best to neuter consumer protection laws that would let people harmed by drugs sue the manufacturer. I also note that the Goldwater Institute template for right to try laws explicitly eliminates liability for drug companies and doctors for almost anything associated with the use of experimental therapeutics.

One point I'm missing....would the drug companies be required to provide the drugs...even if they are still unapproved and in short supply? Couldn't companies just say they are not available? I'm not sure I'm seeing how this bill would transfer the drugs from clinical trials to "me to" patients.

Other than that point, I'm so glad you are addressing these "feel-good" bills. Thanks.

Regarding item 2 in the Colorado law, the 100 mile radius provision isn't facially absurd, because people who are seriously ill often can't travel long distances. Except that the people who live in those places are overwhelmingly likely to be poor, so the "caveat emptor" wording of item 3 is a major problem. I'm assuming that trial sites would tend to be hospitals or clinics in big cities and/or affiliated with major universities, which in Colorado basically means the Front Range region (Pueblo to Fort Collins, including metro Denver)--most of the money in the state is either there or in the mountain resort towns, and the latter have a high concentration of second homes. As for enrolling within one week, that depends on how long it typically takes to enroll a patient (on which point I have no knowledge), but if the paperwork normally takes more than a few days, yes, that's a problem.

As for these John Galt wannabes who think we should do an end run around the FDA: The FDA exists for a reason, and the reason has to do with the outcomes of the last time we had the sort of regulatory regime they advocate.

I have familiarity with some research protocols. I'm not sure I get the one week thing.

Usually they know right away if you meet the eligibility criteria or not and consent you right away (although depending on the trial it may take more than a week from consent to your first study visit as it depends on the schedule of the doctors/clinics involved as they usually see regular patients as well so only have so many study visits per week). Although sometimes you do get what is called a deferred status if you are waiting for medical records from a facility or a visit with one of your other doctors before they can know if you are eligible or not.

Most of the time patients aren't spontaneously registering for your trial on a website or mailing in an application then waiting for weeks or months to find out if they are in or out. Most of the time it is the study staff spending a lot of time tracking down individuals who are on lists of possibly eligible people (like a cancer registry list or a list given to the study by a doctor or clinic), as well as hanging out in the clinic in case someone eligible comes in that day.

Like I said sometimes there is a delay between when you say yes you want to be in it and they have all the medical test results needed to confirm you are eligible. One study I was a guinea pig for took awhile because one medical test they wanted the results for was done at an outside clinic and not the main hospital and especially in the paper record days it took awhile for them to get the record sent as it wasn't needed immediately and the people with stat requests always go first when copying/ faxing/mailing

Thanks, KayMarie. It sounds like a one week delay in enrolling in a study would be commonplace, depending on details, so allowing a patient to skip the process on those grounds is unreasonable.

Can you blame people for being somewhat skeptical of the FDA, when stuff like the MelaFind debacle happens?

I don't think the FDA should relinquish any role in determining safety, although I think they should take a looser role in determining efficacy.

Are there not Federal laws (FDA) that would nullify or take precedent over these state measures? Certainly a company in New Jersey has no obligation to offer an investigational new drug to a Colorado citizen. These laws if they can be applied will only affect companies within the state borders but again I would think they would be superseded by federal law.

"State right-to-try laws have no power over the FDA, and nothing states can do can compel the FDA to abide by their right-to-try laws." Never mind. Should have read more carefully.

A Right to Try bill has been introduced into both the Senate and Assembly in NJ in June and referred to their respective Health, Human and Senior Services Committees.

http://www.njleg.state.nj.us/2014/Bills/A3500/3474_I1.PDF
http://www.njleg.state.nj.us/2014/Bills/S2500/2186_I1.PDF
(Identical Bills)

I plan on writing some strongly worded letters. Future schedules for each committee have not been posted yet but in the case of the senate both sponsors are on the committee, one of whom is the chair, so I don't have high hopes.

It is fine line between encouraging innovation & letting dangerous products on to the market....

I'm sorry, but I'm not seeing a 'debacle' documented at the site you linked to. The device was narrowly approved, due to real concerns--principally the high rate of false positives which would result in unnecesary biopsies and the fact that it's not designed to detect large melanomas, colorless melanomas, and other types of skin cancer (such as basal and squamous cell carcinomas) all of which are detecatble by standard dermatoscope examination.

I think a very good lesson in Right To Try comes from the experience with AZT. It's a great case study in the difficulties faced by FDA to do their due diligence to ensure that a product is safe enough to release to the public while moving fast enough to keep good products from being unduly delayed.

The short story is this: word got out about a possible AIDS drug that was being studied, but had not yet completed clinical trials. AIDS patient advocacy groups became very vocal, pressuring FDA to allow this drug to be used immediately. The FDA ended up caving to pressure and approved AZT before trials were completed and adequate safety and dosing information was in. Lots of AIDS patients began taking the drug, and lots suffered very serious side effects. Over the following years, as more data came in, the dosing was adjusted down to the point that it was finally tolerable and still effective. The advocacy groups admitted that they were wrong to pressure for AZT's immediate approval and acknowledged that the FDA (surprise, surprise) was actually useful and not simply being obstructionist.

The switch from "terminal" to "advanced" is curious. The two are not only not interchangeable, but they don't mean the same thing at all. My husband is terminal, but not advanced - I.e. there is no cure for his cancer, and it will eventually kill him (unless one of the new drugs coming down the pike does the trick - he's in a phase 2 trial right now), but he's not advanced - he has a single known metastasis, which currently has little-to-no effect on his daily life or ability to function. Push comes to shove, his brother is sicker than he is - except for the fact that his brother can expect to live for about 30 more years, while his life expectancy is about 3-5 years.

Brett, I agree with JGC, that is kind of a non-story. Plus it was about detection, and there is an issue with misleading diagnostic tests.

Plus it has nothing to do with "right to try." What they want the "right to try" are experimental pharmaceuticals may not help, and could cause further harm... plus hamper real research into actual effective treatments. As noted by Todd W. and AZT.

More like "Right to Die" as opposed to "Right to Try"

Rob says "One point I’m missing….would the drug companies be required to provide the drugs…even if they are still unapproved and in short supply? Couldn’t companies just say they are not available? I’m not sure I’m seeing how this bill would transfer the drugs from clinical trials to “me to” patients."

Imagine you're an ethical pharmaCEO. A member of the public petitions you for access to an investigational drug per this type of law. Your company says 'no'. Good luck pleading restricted supply, safety concerns or anything else when the s*** hits the public relations fan. You may have no politically-digestible means to avoid releasing the drug for these cases. That is, while still a bad idea it becomes the lesser evil.

And the way the law is written, if said drug causes the person to die, there is no recourse for the family to sue.....

Good luck pleading restricted supply, safety concerns or anything else when the s*** hits the public relations fan.

In this scenario, you have a public relations firm available to fight fire with fire. Have them ask among your clinical patient trials for a few cases who would be willing to go public (privacy laws require this step). Point out that these patients, who unlike the petitioner were willing and able to play by FDA's rules, need the drug too, and because they are playing by the rules, they get priority. Everybody else can join the queue.

No, this is not going to persuade narcissistic libertarian kooks (pardon the redundancy). But normal people (who we hope are most of the population) will understand that limited resources must be distributed according to some rules, and as long as those rules are clear and fair, most people will accept the results.

Sounds like we are already seeing how that issue with supply plays out with the potential Ebola drugs. Sure we can let the companies give it out (and it isn't like we really can let them infect people with Ebola for clinical trials and who knows when the next outbreak will hit).

For a lot of these more unique compounds they are made by small start up type companies that don't have the resources to make huge vats of the stuff.

Of course the Ebola companies are damned if they do damned if they don't. If the give them only to Africans then we are just being colonial and using them for our own ends. If we give them to Americans we don't care about anyone but our own.

I can't agree with you on this one. Your primary argument is that the likelihood that an as-yet-unapproved drug will help a patient is small, and thus giving them access to those drugs is a "false hope". It seems to me that the patients would very likely know this, however, and are willing to gamble. You say that degrading the time they have left and emptying their bank accounts is a worse outcome -- but that's strictly a matter of opinion. And frankly, it smacks of paternalism. As long as all parties are going into this with their eyes open, they should be allowed to.

Your point about the FDA being federally run and thus not beholden to state law is certainly valid. But all that does is make me think that we need a federal right-to-try law.

Ebola:
(1) it seems from what I've read that giving the zMapp product to four people has exhausted the world supply of it; and
(2) the FDA didn't seem to have any problem with allowing it to be used.

But, more generally, it's one thing for physicians to prescribe approved drugs "off-label" for a condition for which they are not approved - the Kalley situation, as Orac notes - it's both legal and I understand widely accepted under appropriate circumstances; but it's quite another to take anything that's been through Phase 1 and remove all state-level restrictions on its prescription. It's an invitation to the Burzynskis of the world, and we surely don't need more of them.

Daniel @21
The patients consent means little; these patients won't have their eyes wide open because the risks are UNKNOWN.
As far as the financial liability, many of these patients will also not likely realize the impact of what they are agreeing to. They are desperate and under tremendous emotional stress, and they rarely [probably never] take an attorney along with them to a clinic. These situations are not the same as applying for an adjustible rate mortgage.
In circumventing hospital review boards, this law removes the advocate for the patient. Not only are patients under great stress, they absolutely cannot do their due diligence because they have no data. The laboratory studies are proprietary.
It isn't paternalistic to require that a drug have an adequate safety profile, its responsible government.

Orac, except for the substitution of "advanced illness," the Michigan bill wording is the same as the final Colorado bill--you may have been looking at a version of the Co. bill before it was amended.

Perhaps Jann is the person to ask--is there any one who would have standing to challenge these laws and get them thrown out?

Orac wrote:
" it seems custom-made for drug companies, to make sure that they get their money for experimental therapies administered under “right-to-try,” no matter what, even letting them go after a deceased patient’s estate."

IMHO, the political-economy argument in Orac's post is right on the, er, money. At the beginning of the article I was thinking, 'yeah, this is bad science, but not that harmful, so maybe not a priority.' But then, as Orac unpacked the Libertarian Kool-Aid behind all this, I changed my mind. What we have here is pseudo-science performing it's typical economic function: letting greedhead scum fill their pockets with profits by sucking dry people facing pain and death. Except this is WORSE in an way than the lies of the NAM-scammers because it writes some very scary things into law, establishing precedent that can be more widely applied, and so on.

The recurring theme of my posts here is that the fight against pseudo-science will not be won by applying the methods of science. It's a political problem, a persuasion problem, and thus rhetorical strategy is key to the outcome. From the standpoint of rhetorical analysis, the question is not whether a given claim is true in any absolute sense, but how well it works in terms of the audience in question. The whole "SBMers are just shills for Big Pharma," schtick has a lot of purchase, for reasons that 'make sense' I shan't detail here. So when Orac makes statements like the one quoted above, the rhetorical value is immense, as they provide effective ammunition to counter an effective discursive tool used by the bad-guys. This ammo is all the more useful as the issue of profiteering is especially a concern to people who are more-or-less on-the-fence on some of these questions, and politics typically swing on whether and where the 'uncommited' may fall.

In short: Bravo, Orac! Good stuff.

Good luck pleading restricted supply, safety concerns or anything else when the s*** hits the public relations fan.

In this scenario, you have a public relations firm available to fight fire with fire.

This notion didn't exactly pan out for Chimerix.

For what it's worth, my Michigan House representative is on the Committee on Health Policy and was not one of the cosponsors of the legislation. I actually passed your writeup on the problems with right-to-try legislation along to one of his staffers, so if' we're lucky that might slow things down a bit.

Thanks. I'm under no illusions about our ability to stop this awful bill. As I morbidly joked in the post, to most people opposing this law is akin to advocating a law mandating puppy disembowelment. You're viewed as the killjoy, the cruel, insensitive guy so uncaring about real patients that he doesn't care that he's "taking hope away from dying patients," rather than as the person trying to protect dying patients from abuse. I spoke with one of the only people who testified against this bill when it went before the Senate health committee. He said the looks he got from supporters of the law were vicious.

That the bill will pass the Senate is already pretty much a foregone conclusion, particularly the way they're sneaking it through without any fanfare. (I still haven't seen any new news accounts since last month.) If it's going to be stopped, the House is where the stand will have to be made. My representative gave me a respectful hearing. He is a cosponsor of the House version, but it is clear to me from his comments that he really didn't know what he was signing on to, which is probably true of most of the cosponsors.

While there are surely issues with the bills, I personally disagree with the extreme opposition argued here. Clean data is good but too many people don't have an option to wait for clean data.

Most such patients would realize it's a 'hail Mary' situation but that's all they have. They don't have time to see scientific verification proceed at its necessarily measured pace.

People are entitled to take their own risks, especially when it's their life on the line. "I'm sorry, we are not ready to be sure this drug is safe enough for you" doesn't cut it. Waiting patiently for scientific rigor is not an option.

@Jay - and when these "untested" treatments start killing people - because we don't know proper dosing or all of the potential side-effects, what will you say then?

How about a potentially life-saving treatment that is rushed through (via this bill) and kills a bunch of people, but it turns out that if testing had been done, those effects could have been avoided (but now the drug is blacklisted in the public's mind, because of the first series of incidents).

Just because people can make an emotional appeal does not mean the government needs to be party to what may be, in effect, assisted-suicide.

I am the wife/caregiver of a terminally ill patient. My husband has stage IV lung cancer. For the most part, I disagree with your argument.

Assigning a big picture secret libertarian motive to the bill is no worse than CAM people insisting that 'Big Pharma doesn't want to find the cure so they can continue to make money on chemo." The intent of the bill is not a libertarian takeover, but rather a means to provide terminally ill patients access to medication that could help them extend their lives.

Your false hope argument is offensive for a couple of reasons. First of all terminally ill people aren't stupid. They are acutely aware of their limited time to be alive. Even though my husband had a complete response to chemo, we understand the cancer is lurking and will come back and kill him. False hope is for the rest of you who don't have to face your mortality. Have you made a will, bought cemetery plots, checked into your life insurance, bought a suit to be buried in, asked a friend to sing "Amazing Grace" at your funeral? Probably not. There's no denial or false hope here. That being said, we can't live our lives in death mode all the time. It's all about quality of life--and good news and hope improve quality of life. When you are terminally ill, the idea that something can extend your life is comforting. Thank God there's always someone like you ready and eager to pull that pillow out from under dying patients' heads. God forbid they may actually think there's hope.

The approval process takes too long. For example, Nivolumab, an immunotherapy drug, still isn't approved for use. Phase 3 trials are done and the results demonstrate that it works in a certain percentage of patients. It's still not available. I think it's finally been approved in Japan, but not here. The rumor mill predicts Nivolumab will be approved in late 2015. That's 160K LC deaths from now.

You argued allowing terminally ill patients access to meds isn't equitable due to wealth and other factors. I agree. But please remember that these same inequities already apply in the trial process. Although the medications are free, the trial process is only available to those who either live near a trial or can afford to travel to one. Also, certain hospitals participate in more trials and it's usually hospitals that accept a variety of insurances. If you're at an HMO that isn't at a comprehensive cancer center or University, chances are your doctor may not have access or knowledge of all available trials. People in most poor countries don't have access at all. Does that mean we should stop doing trials? Of course not. We shouldn't fight to exclude the wealthy, we should fight to include the poor.

Finally, people with certain preexisting conditions are precluded from participating in trials. Drug companies want their drugs to succeed (rightly) so they set very specific guidelines for whom can participate. If you have an autoimmune disease, you probably aren't going to be accepted into a trial. Loosening the noose around these restrictions would give access to potentially life extending drugs to those who were excluded from trials due to somewhat arbitrary guidelines. And unlike chemo, many of the new drugs have fewer side effects and therefore improve quality of life.

I don't disagree with you entirely. We need restrictions and guidelines. Perhaps Phase 1 is too early. Maybe we could up it to stage 2 and insist the decision to try a medication be made with the approval of a doctor.

@jay

The likelihood that this bill will allow someone to get access to a lifesaving drug is vanishingly small. The vast majority of drugs that go into clinical testing will never come to market, and of the ones that do only a tiny, tiny minority will be drugs capable of providing a cure to a terminally ill person. The majority of people who get access to a drug through this kind of legislation will end up wasting their time and money on drugs that, at best, do nothing and at worst make them sicker or even kill them sooner. This is why Orac calls it a cruel sham. The law should protect people from harm, not encourage it.

For example, Nivolumab, an immunotherapy drug, still isn’t approved for use. Phase 3 trials are done and the results demonstrate that it works in a certain percentage of patients. It’s still not available.

The reason why it's not been approved? Bristol Meyers hasn't yet submitted it to the FDA for approval. BM expects to do so later this quarter, which will still be months ahead of the predicted timeline. Hard to see how you can blame the regulatory process for a decision made by the company developing the drug.

I'll also note that Merck's pembrolizumab, a competing anti PD-1 antibody, is about 8 months ahead of Nivolumab in teh approval process, so it's not like Nivolumab is the only game in town.

Does this mean I can dust off the drugs we've thrown in the trash the last 20 years, open phase II's on them that I secretly plan to recruit 1 patient per year (at most) for, and start pushing them on patients at astronomical prices and without any risk to myself. Will it make a garden where a thousand Burzynskis can bloom?

How about if my friends open the phase II more than 100 miles away - I forgot about that part.

Assigning a big picture secret libertarian motive to the bill is no worse than CAM people insisting that ‘Big Pharma doesn’t want to find the cure so they can continue to make money on chemo.” The intent of the bill is not a libertarian takeover, but rather a means to provide terminally ill patients access to medication that could help them extend their lives.

I’m terribly sorry for you and your husband. Lest you think I don’t have any personal experience with this sort of situation, my wife quit her job just under six years ago to take care of her mother, who was dying with stage IV breast cancer, complete with liver, lung, bone, skin, and brain metastases. She observed first hand on a daily basis what happened, and I observed less frequently (but as frequently as I could) because my wife actually moved in with her mother for a few months to do this. It was not an easy time for either of us. So I am not entirely unfamiliar with the personal issues you bring up, although fortunately not (yet) personally or with my wife.

That being said, it is not a “conspiracy theory.” As someone who is knowledgeable about the “health freedom” movement, I recognize in the Goldwater Institute a lot of the same code words that are more about neutering the FDA and allowing the free market to determine what drugs are sold, particularly the part where they discuss having the FDA only assure safety and not efficacy (the Kefauver-Harris Amendments). The arguments made by the Goldwater Institute are also riddled with misrepresentations of the clinical trial process, the law, and the likelihood that patients will be helped by drugs administered off of clinical trial. Note that all of the current right-to-try laws and all of the right-to-try bills being considered by legislatures (such as in Michigan and New Jersey) were written, sometimes word-for-word, from a template produced by the Goldwater Institute. Certainly, the Michigan and Colorado laws are, with only slight variations. Also, if the Goldwater Institute isn’t such a driving force, why is it that it’s flying its representatives to every state legislature considering such bills to testify in their favor. That’s what happened in Michigan.

My analysis of the situation, taken in context with my long time study of “health freedom” advocates, leads me to conclude that the Goldwater Institute and “health freedom” advocates are using terminally ill patients to further their antigovernment agenda, holding out the false hope of “right to try” laws out to attract terminally ill patients to endorse it and to portray opponents who point out that there’s nothing in such bills that is likely to help terminally ill patients as cruel, cold, uncaring monsters who want to deny hope to the terminally ill. Certainly, I’ve been portrayed that way on Twitter by a Missouri right-to-try advocate and by Christine Sandefur of the Goldwater Institute herself. Nothing could be further from the truth. It is because I don’t want to see such patients taken advantage of that I do what I do, even as I know I’m likely to be attacked, perhaps viciously, in social media and elsewhere, for bringing a science-based, rather than Goldwater Institute misinformation-based view to the issue. A particularly good example of Goldwater Institute misinformation is its claim that only drugs “deemed safe” by the FDA would be eligible. Sorry, Ms. Sandefur. Phase I is not an adequate standard for “safety,” even for terminally ill patients, for the reasons I explained in the post.

Your false hope argument is offensive for a couple of reasons. First of all terminally ill people aren’t stupid. They are acutely aware of their limited time to be alive. Even though my husband had a complete response to chemo, we understand the cancer is lurking and will come back and kill him. False hope is for the rest of you who don’t have to face your mortality.

No one said that terminally ill people are stupid, least of all me.

Have you made a will, bought cemetery plots, checked into your life insurance, bought a suit to be buried in, asked a friend to sing “Amazing Grace” at your funeral? Probably not. There’s no denial or false hope here. That being said, we can’t live our lives in death mode all the time. It’s all about quality of life–and good news and hope improve quality of life. When you are terminally ill, the idea that something can extend your life is comforting. Thank God there’s always someone like you ready and eager to pull that pillow out from under dying patients’ heads. God forbid they may actually think there’s hope.

Whether you realize it or not, you have just very eloquently described why even the most rational and intelligent person who is terminally ill can still be very much prone to pitches that provide false hope, like right-to-try. As I said in this very post, I can’t even 100% guarantee that I wouldn’t be tempted by such a hope if I were to be diagnosed with a terminal illness. I would hope, however, that someone with a more objective perspective would try to stop me, if it were ever to come to that.

You argued allowing terminally ill patients access to meds isn’t equitable due to wealth and other factors. I agree. But please remember that these same inequities already apply in the trial process. Although the medications are free, the trial process is only available to those who either live near a trial or can afford to travel to one. Also, certain hospitals participate in more trials and it’s usually hospitals that accept a variety of insurances. If you’re at an HMO that isn’t at a comprehensive cancer center or University, chances are your doctor may not have access or knowledge of all available trials. People in most poor countries don’t have access at all. Does that mean we should stop doing trials? Of course not. We shouldn’t fight to exclude the wealthy, we should fight to include the poor.

I’m aware of the issues with clinical trials, working, as I have, in two different NCI-designated comprehensive cancer centers for my entire post-training career. Several years ago, when I worked in NJ, it was a big deal that the state came to an agreement with insurers that they would pay for clinical trial care. I would also agree that access to clinical trials should be expanded. Here’s the difference. Given our limited resources, where should we as a society spend our money? On expanding access to clinical trials that are likely to produce generalizable knowledge validating new treatments? Or on using untested, potentially dangerous drugs in a far less controlled manner, in a way that is likely to be very expensive and even less likely to help patients than the most longshot clinical trial? Expand access to clinical trials, yes. Right-to-try is the wrong way to go about it, particularly given the hidden agenda to weaken the FDA that is clearly part of the reason for these right-to-try bills and the observation that such programs are far more likely to harm patients than to help.

Finally, there already is an expanded access program. We can discuss whether it’s too difficult (and, yes, the paperwork load is onerous for a doctor who wants to put a patient on an investigational drug through expanded access), although it is rare for an expanded access request to be turned down by the FDA if the company is willing. If there is to be reform, that is where it should be, not in state right-to-try laws, which will only serve to make such issues even more difficult to resolve than they are. It also needs to be understood that clinical trials are always an uneasy tug of war between scientific rigor and ethics. We want to include as many patients as possible, but being too liberal often decreases the odds that a meaningful result will come out of the trial. It’s a question clinical trialists wrestle with every time they design a clinical trial. There’s a reason why I called right-to-try laws “placebo” laws. They don’t actually do much of anything (other than confuse things) but make legislators feel good that they think they’ve done something to help the terminally ill.

Does this mean I can dust off the drugs we’ve thrown in the trash the last 20 years, open phase II’s on them that I secretly plan to recruit 1 patient per year (at most) for, and start pushing them on patients at astronomical prices and without any risk to myself. Will it make a garden where a thousand Burzynskis can bloom?

The answer is yes, as far as I've been able to ascertain. Right-to-try basically legalizes that. Its only requirements are that the drug has to have passed phase I and still be in clinical trials. However, you might run afoul of the FDA. That shouldn't be a major concern, though, as we all know from the history of the FDA's dealings with Burzynski. You could certainly get away with it for a decade at least before the FDA makes even a half-hearted attempt to shut you down. And you could go after the estates of your victims patients to collect. The Michigan bill explicitly allows that. You and any doctor helping you couldn't be sued, either.

Its basically a license to print money on the backs of terminally-ill patients....

The reason why it’s not been approved? Bristol Meyers hasn’t yet submitted it to the FDA for approval. BM expects to do so later this quarter, which will still be months ahead of the predicted timeline. Hard to see how you can blame the regulatory process for a decision made by the company developing the drug.

I’ll also note that Merck’s pembrolizumab, a competing anti PD-1 antibody, is about 8 months ahead of Nivolumab in teh approval process, so it’s not like Nivolumab is the only game in town.

There's no game in town right now. They aren't available. That's the big point and the unfortunate truth. Why hasn't BM submitted their data for approval? I don't want to believe it's for financial reasons. I don't buy the 'big pharma' crap for a second, but something is keeping it from being released. What is it? And whether or not it's Merck or BM, doesn't matter. There are drugs that can extend the life of certain lung cancer patients (160K dead a year) but for whatever reason, be it bureaucratic red tape or corporate sludginess, they aren't available. Lung cancer, the deadliest cancer, is one of the least funded due to stigma. Lung cancer patients rely on gains made for more "deserving" cancer. Sad but true.

I apologize if my comments came across as a slight to the FDA. That wasn't the intention. My intention was to highlight how there are effective drugs that aren't available to people.

Polly

There’s no game in town right now. They aren’t available.

You're missing my points, perhaps deliberately.

First, as Bristol meyers has not yet applied to the FDA for approval of Nivolumab, I don't see how one can reasonably argue its failure to have reached the market is a function of a failed approval process.

Second, Nivolumab is is not the only anti PD-1 antibody in development and on track toward approval. At least one other that I'm aware of is also in development and is actually several months ahead in the approval process.

Nivolumab is also not unique in targeting the PI 3 Kinase
T-cell activation pathway: FDA approved Yervoy (Ipilimumab), an anti CTLA-4 antibody, targets the same pathway.

While I agree it would be great if the Nivolumab had demonstrated safety and efficacy and was aready approved, I don't see how the approval process is to balme for its failure to already be approved.

You say that the approval process takes too long: how exactly would you change it to reduce the time required< while still ensuring tht potential new drugs demonstrated sufficiently that they were both safe and efficacious?

The approval process always takes time - whether it be one week or several months....time is time.

If the drug is approved on Tuesday, then people will have died on Monday waiting for it - you're never going to satisfy everyone.

I got your point. Did you read my response? My point is this: It doesn't matter why it takes so long, whether it's due to "bureaucratic red tape or corporate sludginess". I'm not looking to blame anyone or anything only to inspire change. The point is that life-saving or life-extending drugs exist but are not available. There's a lengthy space of time after a medication is proven effective until it actually hits the market. In the case of Nivolumab, we're talking a couple of years. Considering the median survival for lung cancer with treatment is 8 months, that's too long, whatever the reason. There should be a way to make the meds available in that space between. (actually there is, but it's very limited)
As for Yervoy, last I read it was in clinical trials for NSCLC and not fda approved for anything other than melanoma.
Believe it or not, these drugs, at this point most likely won't help my situation. My dh is a chemo-responder and I've spent most of the summer enjoying the hell out of his company. :) Chemo responders are LESS likely to respond to immunotherapy. I'm hoping future research shows why.

And finally, I am not asking for false hope, but actual real hope. Immunotherapy drugs have evidence behind them. They aren't Gerson or homeopathy or chiropractors, which are sadly (ironically?) easily available and not restricted by law.

"That being said, it is not a “conspiracy theory.” As someone who is knowledgeable about the “health freedom” movement, I recognize in the Goldwater Institute a lot of the same code words that are more about neutering the FDA and allowing the free market to determine what drugs are sold, particularly the part where they discuss having the FDA only assure safety and not efficacy (the Kefauver-Harris Amendments)."

I have to give you this point. I don't know enough about it. For my demographic, it's not about politics. It's about access.

When Joe was first diagnosed with cancer I was repeatedly given two bits of really bad medical advice. The first was to banish all sugar from his diet. The second was to consider not "poisoning" Joe's body with chemo. I researched both issues and discovered the sugar advice was unfounded but basically harmless. For the chemo issue I found this article: http://scienceblogs.com/insolence/2009/05/20/chemotherapy-versus-death-… And from then on, your blog became one of the voices I counted on with " a more objective perspective". I totally appreciate your blog for this reason. Anytime I hear about a new treatment, I look it up on your blog.

However, I believe that making access easier to SOME drugs could extend the lives of many nsclc stage iv patients. (and probably other patients I don't know anything about). It's not false hope if they actually work. If the bill is bad, can it be rewritten so it makes sense?

<blockquote. I’m not looking to blame anyone or anything only to inspire change.

Inspire what type of change, however--what changes do you believe could be enacted that would accelerate drug approval without compromising safety and ensuring efficacy with respect to identified indications?

There’s a lengthy space of time after a medication is proven effective until it actually hits the market.

I’d argue that until the developer has submitted all required documents to the FDA, detailing all results from all pre-clinical and Phase I, II and III clinical trials, and the FDA has the time to not only perform an independent audit and review of the evidence but also to respond the developer and request additional information or direct additional studies be completed, and they finally actually approve the drug for sale, it hasn’t been proven safe and effective.

Considering the median survival for lung cancer with treatment is 8 months, that’s too long, whatever the reason.

If the basis for concluding that it’s too long is that people who might be saved if it were available now will not survive, surely any regulatory process that goes beyond a simple rubber-stamp procedure must be considered ‘too long’.

I cannot at this point think of changes to the regulatory system that would have shortened the approval process with respect to Novimulab. Bristol Meyers cannot submit the drug for approval until they’ve prepared and validated their documents (a long, detailed and highly technical undertaking) and the study was completed quite recently (results were announced in June 2014). The FDA certainly can’t act until they receive the completed submission package. It seems to me both BM and the FDA are moving with all appropriate haste (and, it’s important to recall, are actually months ahead of schedule.)

As for Yervoy, last I read it was in clinical trials for NSCLC and not fda approved for anything other than melanoma.

The Phase III clinical trial showing Novimulab to be effective was also with respect to melanoma, and if approved at this time it also would be approved only for melanoma.

However, I believe that making access easier to SOME drugs could extend the lives of many nsclc stage iv patients. (and probably other patients I don’t know anything about). It’s not false hope if they actually work. If the bill is bad, can it be rewritten so it makes sense?

There probably are some who may be helped by the few drugs that are well into phase III so we may have enough data to know if there is more hope than false hope.

Unfortunately that isn't the way the people pushing for these bills want and sadly in today's political climate I don't think we can get a common sense bill.

It is either going to be all or none, and all is really bad, especially when we don't yet know with much certainty what kind of dosing regime may be effective and safe enough you don't cause way too much damage to the person. While we try to make drugs specific to tumors, you usually kill some healthy cells along the way and not knowing at all what kind of dose may be effective (just what didn't kill a dozen or so healthy people) it is really scary.

Especially with way too many doctors promising cures with inappropriately dosed drugs along with the woo they peddle. Give them access to a much bigger range of drugs, it may hurt a lot more people than it helps.

A few drugs, under pretty tightly controlled conditions may be OK, but the free for all the bills being written are...and the people supporting those bills are not likely to support something reasonable. The reason the bill isn't reasonable now is they don't want something scientifically rational and reasonable and will fight against that tooth and nail, IMO.

JGC,

Maybe I should clarify. The fda approval process is only too long for people with terminal diseases. We don't need to alter the fda approval process. It's important that data is reviewed and scrutinized. However, we need to find exceptions for terminally ill patients to access drugs that aren't yet on the market but have been proven effective. That's the change that needs to be made. I understand there needs to be very, very specific guidelines. We have something in place now called compassionate use but it is so limited.

As to the "can't win, don't try argument'. That's a terrible argument. The goal in medicine should be to heal. Obviously, you can't save everyone (or anyone for that matter), but the goal is to heal as many as possible. The fact that some people die waiting for medication is an outcome we can change. Procedural improvements are made all the time to improve outcome. That's the whole point of medical science, isn't it? Could you imagine if a doctor said, "Well, no matter how successful bypass surgery is, people will still continue to die from clogged arteries. Therefore we shouldn't do bypass surgery." It sounds ridiculous. Do want to have a doctor who says, "Wear gloves? Why? No matter what I do, I can't stop every infection so why should I wear gloves?" There are a million ways procedural changes have improved outcomes in medicine.

Right now (expecially now with this the immunotherapy ball is really rolling) we can make a change that will improve the outcome for stage iv lung cancer patients. I believe we should find a way to make that change. I agree with Orec that this bill oversteps. While it might improve some people's lives, it could potentially cause great harm to others. However, let's not throw out the baby with the bathwater. If the crazy libertarians have a bill, counter it with something better.

Why can't there be a two-step approval process? Step 1 patients wait for the drug. Step 2 patients can receive a drug that has finished phase 3 trials (or phase 2 if the results are phenomenal) and is expected to be approved. Approval would be subject to dx and other conditions. (2 failed lines of chemo, supervision of board certified oncologist, release of responsiblity, etc... whatever it needs to be.) All this would do is make compassionate use more universal and it would allow drug companies to get paid for the drug prior to it's general release.

Polly

Well, there is no correct way to address this legislation that would be applicable to any / all circumstances. But, for one company that is backing this bill is Neuralstem, and if you had Lou Gehrig's disease, what choice would you have ?

Neuralstems answer is repair unhealthy or dying cells, with healthy cells, similar to what most anyone would do if they needed an organ transplant. The body understands cells, more so than it would understand most drugs. If they have passed Phase One for safety, are showing efficacy in PHASE TWO, then why should an ALS terminally ill patient wait ?

Neuralstem, as many companies emerging in the Regenerative Medicine sector are the tip of the arrow as the science progresses. Advanced Cell Technology, and their CSO Robert Lanza are sandbagging years worth of data, that will absolutely astound the medical community. With their Hemangioblast Derived Mesenchymal Cells, they have eliminated Multiple Sclerosis in animal models in six days, with just one injection. ACTC has stated these MSC's are applicable to over 100 different Auto-Immune disorders.

So, based on what vantage point you choose to see on the horizon, at least for ALS, THE Right To Try bill is Right On.

Dallas Buyers Club-inspired "right to try" laws: Good movies don't make good policy

oracknows — Thu, 06 Mar 2014 06:00:12 +0000

Dallas Buyers Club-inspired "right to try" laws: Good movies don't make good policy

One of my favorite shows right now is True Detective, an HBO show in which two cops pursue a serial killer over the course of over 16 years. Starring Woody Harrelson and Matthew McConaughey, it's an amazingly creepy show, and McConaughey is amazing at playing his character, Rustin Cohle. I'm sad that the show will be ending this week.

Unfortunately, as much as I like Matthew McConaughey as an actor, he is in part responsible for re-inspiring a movement that has the potential to do profound harm to patients and cancer research. That's because his other big role over the last year has been in an Oscar-nominated movie, Dallas Buyers Club, where he plays Ron Woodroof, an early AIDS patient who in the 1980s smuggled unapproved pharmaceutical drugs into Texas when he thought he found them effective at alleviating his symptoms, distributing them to fellow sufferers by establishing the "Dallas Buyers Club" while battling the FDA. I haven't seen the movie, and I really don't want to, given that, from everything I've heard about it, it's basically the story of a "brave maverick" who bucks the FDA, complete with all the tropes about uncaring bureaucrats who don't care if these brave patientd die. That might not be so bad if it weren't also riddled with inaccuracies and misinterpretations of the AIDS crisis in the 1980s. Worse, the real Woodruff rejected the one truly promising drug at the time, AZT as hopelessly toxic and instead smuggled drugs like Peptide T, which never panned out. Basically, what Woodruff appears to have smuggled as part of his activities for the "Dallas Buyers Club" was a mixture of useless supplements, experimental drugs that panned out, and a handful of experimental drugs that showed promise. Meanwhile, the movie portrays the FDA as the implacable enemy of theses sorts of activities, jackbooted thugs not unlike the stereotype promoted by "health freedom" quacks who don't like the FDA preventing them from selling their quackery. As far as I can tell without actually seeing the movie is that the overall message is a typical uplifting story of an underdog who fights the power and in doing so finds redemption.

Of course, Dallas Buyers Club is just a movie, no matter how good a movie it might be and how much Matthew McConaughey might have deserved an Oscar for his performance. Unfortunately, it appears that legislators in several states seem to think that it should serve as a template for health policy. This public policy, which is extremely bad policy being considered and promoted in four different states, comes in the form of laws known as "right to try" laws. Basically, "right to try" laws grant terminally ill patients the right to have access to experimental therapies. According to these laws, the drugs need only have passed phase I trials. Now, remember, phase I trials do not demonstrate efficacy. They are only designed to test for safety and toxicity, determine the maximum tolerated dose, and provide an estimate for the dose to use in real clinical trials. The concept of "right to try" bills is highly popular, because if you don't know a lot about medicine and how clinical trials work it sounds like a good idea What could be the possible harm, after all? A lot, it turns out, but I'll get to that in a moment. First, let's take a look at the rationale for Arizona's "right to try" law, which is being promoted by the Goldwater Institute:

Arizona legislators are poised to green-light legislation in committee Thursday that would pave the way for terminally ill patients to access experimental drugs not yet cleared for market. Known as the "Right to Try" Act, similar bills are currently being considered by lawmakers in Colorado, Louisiana and Missouri, and legislators in California and Massachusetts have expressed interest.

Designed by the Goldwater Institute, the Right to Try Act would enable terminally ill patients who have exhausted all of their available treatment options to access experimental drugs that have been deemed safe but whose efficacy has yet to be determined. Under the current system, even after an investigational drug has passed the Food and Drug Administration's Phase I (the testing phase during which safety is established), it can take an additional six or more years for the drug to be approved for market--even if clinical trials are yielding promising results.

And while many patients facing terminal illness attempt to get into those clinical trials, the vast majority cannot, because they are too far along in their illnesses or because of other factors. 40% of cancer patients pursue admission into clinical trials, but only 3% succeed. Last year, more than 500,000 Americans died from cancer alone.

According to Christina Corieri, a health care policy analyst at the Goldwater Institute, the tragedy is that many of the drugs terminal patients can't access today will be saving the lives of future patients just a few years from now.

“The sickest Americans don’t have the luxury of time to wait for these drugs to come to market through the traditional process,” said Corieri. "The Right to Try Act puts the decision about whether to try an experimental treatment back where it belongs: in the hands of patients and their doctors.”

This is, of course, partially true. There is always an inherent conflict between wanting to push for faster approval of drugs in order to treat patients who are dying and the need for rigorous testing to assure safety. Patients and their families ask, "What's the harm?" while advocates like Corieri sell their policy with the assumption that experimental drugs are highly likely to help these patients, or at least not so unlikely as not to be worth trying. Here's the problem. Just because a drug has passed phase I trials does not mean that it is effective. It does, however, frequently mean that the drugs have significant side effects. Indeed, determining those adverse events is part of the entire reason that we do clinical trials in the first place.

The Arizona law is the template for laws that are metastasizing to other states, such as Colorado; so I'll look at it. The text of the law is available online. The major provisions of the law include a definition of the eligible patients that includes:

1. "ELIGIBLE PATIENT" MEANS A PERSON WHO MEETS ALL OF THE FOLLOWING:
(a) HAS A TERMINAL ILLNESS.
(b) HAS CONSIDERED ALL OTHER TREATMENT OPTIONS CURRENTLY APPROVED BY THE UNITED STATES FOOD AND DRUG ADMINISTRATION.
(c) HAS RECEIVED A PRESCRIPTION OR RECOMMENDATION FROM THE PERSON'S PHYSICIAN FOR AN INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE.
(d) HAS GIVEN WRITTEN INFORMED CONSENT FOR THE USE OF THE INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE OR, IF THE PATIENT IS A MINOR OR LACKS THE MENTAL CAPACITY TO PROVIDE INFORMED CONSENT, A PARENT OR LEGAL GUARDIAN HAS GIVEN WRITTEN INFORMED CONSENT ON THE PATIENT'S BEHALF.
(e) HAS DOCUMENTATION FROM THE PERSON'S PHYSICIAN THAT THE PERSON HAS MET THE REQUIREMENTS OF THIS PARAGRAPH.

The bill defines an "investigational" drug as a drug that's passed phase I trials but has not yet been FDA-approved. The law doesn't require manufacturers of an investigational drug to make it available, but basically allows them to do so if they so choose. Worse, it doesn't require that the manufacturer provide the drug for free, as it must to patients undergoing clinical trials in order to achieve FDA approval:

A. A MANUFACTURER OF AN INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE MAY MAKE AVAILABLE THE MANUFACTURER'S INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE TO ELIGIBLE PATIENTS PURSUANT TO THIS ARTICLE. THIS ARTICLE DOES NOT REQUIRE THAT A MANUFACTURER MAKE AVAILABLE AN INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE TO AN ELIGIBLE PATIENT.

B. A MANUFACTURER MAY:
1. PROVIDE AN INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE TO AN ELIGIBLE PATIENT WITHOUT RECEIVING COMPENSATION.
2. REQUIRE AN ELIGIBLE PATIENT TO PAY THE COSTS OF OR ASSOCIATED WITH THE MANUFACTURE OF THE INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE.
C. THIS ARTICLE DOES NOT REQUIRE A HEALTH CARE INSURER TO PROVIDE COVERAGE FOR THE COST OF ANY INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE. A HEALTH CARE INSURER MAY PROVIDE COVERAGE FOR AN INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE.

And, to top it all off, the law prohibits the state medical board (or any other state regulatory board) from going after the license of any physician or health care practitioner who recommends and/or administers such investigational agents to patients while making any state official or employee who attempts to block access of an eligible investigational drug to an eligible terminally ill patient potentially guilty of a class 1 misdemeanor. If the bill passes both chambers in Arizona, it would next go to the voters in November. My guess is that if the bill makes it onto the ballot this fall, it will likely pass. I can picture the ads now. They'll feature cute, terminally ill children and brave adults battling fatal diseases invoking their right to choose what goes into their body and begging voters to "give them a chance to live" and asking, "What's the harm?" Against such images it will be hard for science-based medicine to prevail.

Currently, similar laws are wending their ways through the legislatures of multiple states, including Colorado (of course!), Missouri (where legislators recently listened to emotional testimony and the bill is sponsored by a legislator, Jim Neely, whose daughter suffers from stage IV colon cancer), and Louisiana, while states as disparate as Utah, Oklahoma, Massachusetts, and California are showing early interest in such laws. The draft laws under consideration are basically all based on the Goldwater Institute's template (indeed, the Arizona law is almost verbatim the same), which is based on this policy report available on the Goldwater Institute's website, deceptively entitled Everyone Deserves the Right to Try: Empowering the Terminally Ill to Take Control of their Treatment.

The report itself is loaded with emotionally charged language about the FDA and terminally ill patients and highly dubious statements. For example, it's hard not to notice that every experimental drug is apparently "potentially life-saving," at least the ones that made it through phase I trials. There's so much loaded language, coupled with so many dubious assertions, that I can only hit the "high" points, such as they are. For instance, 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"?

Another highly dubious argument follows:

Phase I involves administering the investigational drug to a small group of 20 to 80 volunteers to test for toxicity and immediately observable side effects.30 The major emphasis of Phase I testing is safety. Over 60 percent of investigational drugs in Phase I testing are deemed safe enough to move on to Phase II.

Seriously? Phase I trials can be as few as 20 patients. That is not enough to determine safety, nor is it intended to. Phase I trials are designed primarily to identify major side effects and to use a process known as dose escalation to determine what is commonly referred to as the "maximum tolerated dose." It is utterly impossible for such a small clinical trial to determine the safety of a drug, and even the Goldwater Institute inadvertently undermines its own argument. Note how the report says that over 60% of investigational drugs pass phase I testing and are determined to be "safe enough to move on to phase II." That's the standard: No unexpected major adverse events and a side effect profile that isn't grossly more unsafe than the disease itself. Phase II and Phase III trials are needed to confirm safety. That's why the premature diffusion of unapproved drugs has the potential to increase morbidity from adverse events and even hasten death. One example is amonifide for treating breast cancer. The drug made it through phase I trials, but serious life-threatening hematologic toxicity emerged during phase II trials.

Think of phase I trials as a screening test looking for the most obvious toxicities, with phase II and III studies confirming them. Indeed, even phase III trials can't always adequately demonstrate that a drug is safe; it's not uncommon for less common adverse effects not to show up until post-marketing surveillance, when much larger numbers of patients receive the drug. Moreover, only 5% of all cancer drugs that enter clinical testing are ultimately approved for patient use. Among drugs tested in phase II trials, only 30% go on to phase III.

The Goldwater Institute also doesn't like the current expanded access programs, not because it doesn't like expanded access programs, obviously. (After all, what are "right to try" laws other than much more liberal expanded access programs?) No, what the Goldwater Institute doesn't like is the current system because of all those nasty regulations. Under current law, the Food and Drug Administration Modernization Act (FDAMA) of 1997, single patient INDs (we're discussed these before in the context of Stanislaw Burzynski patients), which are basically compassionate use exemptions, can only be granted if:

The patient’s physician determines the patient has no comparable or satisfactory alternative therapy;
the FDA determines there is sufficient evidence of safety and effectiveness to support the use of the investigational drug;
the FDA determines that provision of the investigational drug will not interfere with the initiation, conduct, or completion of clinical investigations to support marketing approval; and
the sponsor or clinical investigator submits information sufficient to satisfy the IND requirements.
the sponsor of the investigational drug must also be willing to supply the drug to the patient.

If all of these conditions are met, then the treating physician or drug sponsor submits an IND application, a proposed treatment plan, and a commitment to obtain informed consent from the patient and permission from the Institutional Review Board (IRB). No one denies that the process could be more streamlined. The report lists some of the burdens of the IND process and bemoans the FDA's veto power over single patient INDs. Here's what's particularly disturbing about what the Goldwater Institute advocates, though, is its attack on the FDA's requirement for a full IRB review of single patient IND applications as being a bad thing that keeps patients from accessing drugs. The language sounds as though it could have been written by Stanislaw Burzynski himself. Particularly Orwellian is the part of the report that demands that legislators must "act to protect patients." I don't know about you, but I'm not sure how, basically, stripping all restrictions on letting patients have access to drugs that have passed only phase I trials "protects patients," but then I'm not a libertarian.

The Goldwater Institute justifies its proposal through still more dubious assertions. For instance, the report starts out with patient anecdotes in which patients with terminal cancers exhausted all conventional therapies and then applied for experimental therapies, which they either couldn't get or had to wait too long to get. In each case, the stories are told in such a way as to suggest that "if only" these patients had had access to experimental drugs sooner they might have survived. This is, of course, nonsense. All these patients had stage IV cancer. Barring the incredibly unlikely possibility that an experimental drug is a miracle cure for advanced cancer even better than Gleevec for chronic myelogenous leukemia or than what the quacks claim in Tijuana for their treatments, these unfortunate patients would have died anyway. True, if the drug were effective, they might have gotten a few more weeks or months, but they would have died. Using such stories is nothing more than tugging at the reader's heartstrings. It is not a good scientific argument.

Actually, there isn't a single good scientific argument in the entire report. There's a survey of orthopedic surgeons cited in which a majority of them have said they thought that the slow FDA approval process had hurt patients. This is well nigh meaningless for a discussion like this one because (1) most orthopedic surgeons don't take care of cancer patients (orthopedic oncology is a subspecialty, and, fortunately, orthopedic malignancies are rare) and (2) orthopedic surgeons are much bigger into medical devices than drugs. Moreover this survey is bundled in a table with other with results of other surveys that range from 1995 to 2007. Finally, the reference cited is from the Competitive Enterprise Institute, a free market "non-profit public policy organization dedicated to advancing the principles of limited government, free enterprise, and individual liberty." I will admit that I'm a bit disappointed that between 68% and 73% of physicians would support a proposal to change FDA law so that unapproved drugs or medical devices could be made available to physicians as long as they carried a warning label about their unapproved status.

Wow. Talk about a boon to pharmaceutical companies! Why bother with those pesky and expensive phase II and phase III trials if you could market your drugs direct to doctors to use on patients after phase I trials instead?

Now, given how bad an idea this law is, here's the funny thing: It almost certainly won't do what it is designed to do. The reason is simple. It's nothing but state laws, and the FDA controls drug approval. Arizona can say as much as it wants that patients can get any investigational drug they want, but it's meaningless as long as the FDA says that you have to have a single-patient IND approved for patients to have access to an investigational agent outside the auspices of a clinical trial being undertaken to win approval for the drug, what the state says is meaningless. Because the FDA exercises a lot of its power through the federal government's power to regulate interstate commerce, perhaps the only way I can imagine for a state to get around this would be if the pharmaceutical company is in the same state as the patient. If the company ships an investigational drug across state lines in violation of federal law, it's screwed. Of course, even this might not be enough, because a lot of states have a "mini-FDA" act, which bans the use of drugs that haven't been FDA-approved. Indeed, the only reason Stanislaw Burzynski managed to get away with administering antineoplastons to patients early in his career is because at the time Texas didn't have a mini-FDA act, and Burzynski was very careful never to ship antineoplastons across state lines.

Even more pertinent, drug companies need their drugs to be FDA approved to recoup their investment in drug development and make a profit, because without FDA approval they can't sell the drug. The Arizona "right to try" law requires that the "investigational drug" (1) have passed phase I trials and (2) still be in the clinical trial process. There's only one reason for a drug to be still in clinical trials after phase I trials, and that's because the drug company still wants FDA approval for its drug; i.e., that it hasn't abandoned development. That means the investigational drug is still under FDA regulation. A single patient IND would still be required. Pharmaceutical companies providing drugs to patients in "right to try" states without proper INDs would be violating FDA regulations and would thus endanger their chances of ultimate FDA approval. In other words, these "right to try" laws are nothing but feel-good placebos. They have no real effect because reputable pharmaceutical companies will not cross the FDA by providing an investigational drug to patients without a proper IND. That means that they only companies that might take advantage of "right to try" laws would be disreputable companies like Stanislaw Burzynski's institute. Like Burzynski, "right to try" laws offer nothing to cancer patients but false hope. In fact, I'm hard-pressed to think of anyone whom these laws would benefit other than Burzynski, which makes me wonder if his minions have anything to do with promoting them.

Worse, making essentially untested drugs more widely available, as these "right to try" laws propose to do will be far more likely to harm the individual patient than to help him. Advocates of these bills ask, "What's the harm?" I'll tell you: If there’s anything worse than dying of a terminal illness. It’s dying of a terminal illness and suffering unnecessary complications or pain for no benefit and having to pay for the medications causing the complications yourself. Remember, these laws allow the pharmaceutical companies to charge for their investigational medications. They don't all necessarily require the company to provide the drug for free, as current law does in the case of single patient INDs. For example, as discussed before, the Arizona law doesn't require drug companies to provide the investigational agent for free; the Colorado bill is being amended to have that requirement by its cosponsor Janak Joshi.

Worse, Dallas Buyers Club-style "right to try" laws risk undermining our entire clinical trial enterprise, which is a major part of the scientific basis for evidence-based medicine. After all, if early stage experimental drugs were made widely available outside of clinical trials and taken for a wide variety of cancers, the signal-to-noise ratio would become very low. It would become very difficult to tell which drugs were working and for which cancers (and which were not), particularly since it would be reasonable to expect that such a policy would result in enrollments in clinical trials plummeting. And what would be the potential payoff for the shredding of patient protections proposed in these bills, even if the FDA didn't put the kibosh on widely providing experimental drugs early in clinical testing (and, make no mistake, only having passed a phase I trial is early in clinical testing)? Very little at best, if even any at all. In reality, the likelihood of saving the lives of even a handful cancer patients by giving them access to early-stage investigational agents is quite low and hard to justify on a moral and practical basis, given the high likelihood of potential harm or premature death to so many other patients through the damage or destruction of a system that has been built up at such cost over several decades.

The entire justification for "right to try" laws also seems to rest on a misperception that there are “miracle drugs” out there that we will have to wait years for because the FDA is too slow to approve them. However, if there really were such a “miracle drug” that was amazingly effective compared to anything we have now, a large randomized phase III trial would not be necessary to detect its efficacy. Indeed, its efficacy could show up in even a small phase I trial or, at the latest, in phase II trials. There’d be examples of clinical trial subjects demonstrating amazing tumor shrinkage or even outright cures. In reality, we don’t see these things in Phase I trials, because there are no miracle drugs, at least not yet (if there ever will be). Dallas Buyers Club-style "right to try" bills rest on a fantasy, and it's a fantasy of false hope. Indeed, these bills serve an ideological purpose rooted in libertarian politics far more than they serve patients. It's not coincidental that virtually the only sign of opposition to the Missouri "right to try" bill was from lobbyists representing the hospice community, who warned lawmakers that such legislation raises false hopes for patients when further treatment is likely futile.

These bills seem new, but they're just the latest wrinkle on an old story. We've been down this road before. For example, the Abigail Alliance has been lobbying for similar "right to try" laws for a decade now. Libertarians love these bad ideas because, you know, the market cures all. So does the press because of the human interest stories coupled with the "little guy" battling the FDA. Even though expanded access programs could definitely use some tweaking, never forget that the reason the laws we have exist is to protect the public against drugs that don't work or are too toxic and, just as importantly, from companies that would sell such drugs with no evidence of efficacy or safety and from "investigators" like Stanislaw Burzynski.

And Dallas Buyers Club is just a movie, nothing more. It might be a really great movie (given its Oscar nominations and McConaughey's winning Best Actor, it almost certainly is), but it's a terrible model for health policy and highly unlikely to help patients with terminal diseases.

ADDENDUM: Jann Bellamy has written about "right to try" laws from a legal perspective.

oracknows Thu, 03/06/2014 - 01:00

Categories

Policy

Libertarians love these bad ideas because, you know, the market cures all.

Uh-oh. Batten down the hatches.

"we don’t see these things in Phase I trials, because there are no miracle drugs"

Imatinib (Glivac) for CML?

Exactly my point. Results like what were seen in three early stage phase I/II trials for Gleevec in CML are incredibly rare. In fact, before Gleevec, such results were unprecedented:

Two years later, this chemical, which was called ST1571 and eventually renamed Gleevec, entered its first clinical trial: a small phase I trial involving just 31 patients. Remarkably, all 31 individuals experienced complete remission; in other words, their blood counts returned to normal. In some of these patients, there was also cytogenetic remission, meaning that the Philadelphia chromosome was no longer found in their blood cells. As Druker noted, "That was virtually unheard of in a phase I clinical trial. Usually in a phase I clinical trial, if you see a 20% response rate, that's remarkable. We had a drug that was extremely well-tolerated and had a 100% response rate. It was absolutely incredible to see this unfold" (Taubes, 2003). Subsequent clinical trials produced results just as astonishing.

And Gleevec was an unusual drug from a mechanistic standpoint as well because CML depended upon a single mutation that it could target:

In a way, Gleevec is an exceptional case, and the same success is not likely to be achieved with other cancers any time soon. Unlike most other cancers, which are caused by a multitude of complex interacting genetic and environmental factors and therefore have many targets, CML is caused by a single aberrant protein related to a consistent chromosomal translocation. Scientists were thus able to focus all of their efforts on this single target. Nonetheless, the Gleevec story is no less an excellent and, some would say, beautiful example of how knowledge of the biological functioning of a cell can lead to life-saving medical treatment.

If there's a drug that's shown as incredible a result in an early phase I trial as Gleevec, I am unaware of it. Again, that's the point. Gleevecs of the world are rare, but Dallas Buyers Club "right to try" legislation rests on the assumption that they are much more common than they are and that thousands of patients with terminal cancer would be saved if only FDA officials weren't such prigs about insisting on evidence of efficacy and safety.

Gleevec/Glivac/Glivec, Yeah very rare event but marvelous. I agree this is the exception to the rule. Ph chromosome gone completely - wow.

Advocates of these bills ask, “What’s the harm?” I’ll tell you: If there’s anything worse than dying of a terminal illness. It’s dying of a terminal illness and suffering unnecessary complications or pain for no benefit and having to pay for the medications causing the complications yourself. Remember, these laws allow the pharmaceutical companies to charge for their investigational medications.

Along with "what do you have to lose?", I consider it a thought-stopping cliche. It's not hard to come up with a list of things to lose:

1. Inheritance that could be passed along to the patient's loved ones instead of wasted on a lottery ticket treatment.
2. Palliative comfort for spending quality time with loved ones.
3. Palliative lucidity for tending to final affairs and last wishes.
4. A head start for all those involved to grieve and accept the inevitable, rather than be trapped in a state of denial because some greedy ghoul promises a miracle cure. It saves them the emotional whiplash of going from news of alleged improvement to "suddenly" dealing with a death.
5. A peaceful death, as opposed to one wracked with morbid side effects.
6. The chance to turn their loss into a positive contribution to our knowledge of medicine. As Orac pointed out, without a clinical trial setting, the noise drowns out the signal of any treatment that did indeed work. The spin quacks and drug marketers perform also sow mass confusion for those who don't know how to do proper scientific research.

I could probably come up with a few more over time. It didn't take me long to think of these, which is pretty much why they need the thought stopping implication that there isn't anything to lose.

The entire justification for “right to try” laws also seems to rest on a misperception that there are “miracle drugs” out there that we will have to wait years for because the FDA is too slow to approve them. However, if there really were such a “miracle drug” that was amazingly effective compared to anything we have now, a large randomized phase III trial would not be necessary to detect its efficacy. Indeed, its efficacy could show up in even a small phase I trial or, at the latest, in phase II trials. There’d be examples of clinical trial subjects demonstrating amazing tumor shrinkage or even outright cures. In reality, we don’t see these things in Phase I trials, because there are no miracle drugs, at least not yet (if there ever will be).

Speaking of the typical trollish libertarianism, I think that's how a lot of them think science advances. They often seem to think we're still in an era where overnight breakthroughs that fundamentally change how we view the world are still likely. Like the free energy device in Atlas Shrugged.

It's sad to say we're past the era of such exciting and "easy" breakthroughs. Specific to medicine, the human body is an intricately complex set of interactions that can go wrong in so many ways, and there are about 7 billion different variations on the design out there. We've got all the broad brush strokes down, and we're left with very nuanced problems that need nuanced solutions obtained through careful observation. That's not exactly something you can expect to stumble on through brute forcing, and yet they want to encourage patients to blindly gamble on it.

One thing I find frustrating and entertaining about all the anti-regulation rhetoric is that the people who spout it don't seem to realize that what's good for their pet quackery is also good for encouraging the abuses they attribute to pharmaceutical companies. If you legalize reckless, unregulated, unscientific human experimentation, you're removing an important incentive for the greedy members of pharmaceutical companies to restrain themselves. Regulations exist so that they have to prove safety and efficacy just to put a drug on the market in the first place. Before that, they have to go through the trouble of satisfying ethics regulations on human experimentation to find out if it works. Remove those prerequisites, and all they need to make a profit is a slick propaganda campaign. Altie culture has already proven the propaganda approach works.

@ Bronze Dog

the people who spout it don’t seem to realize that what’s good for their pet quackery is also good for encouraging the abuses they attribute to pharmaceutical companies.

Ah, but that's different, they are the good guys. They won't allow themselves to stoop to that level of chicanery.
After all, bad things only happen to other people, isn't it?

(yes, sarcasm inside)

If you look at the change.dot.org website, you'll see how the success of The Dallas Buyer's Club film, has given new impetus to the many petitions for release of cancer drugs in phase I clinical trials. When the cancer patient dies from their terminal disease, it is the fault of those mean bastards at *Big Pharma* and at the FDA.

@Helianthus: Definitely a common attitude. Black and white thinking makes it so easy to think of people as either monolithic angels or demons, rather than diverse and conflicted humans.

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Speaking of movies with bad medical lessons, I recall seeing a preview for one. The premise appalled me: A high school student from a rich family has a psychiatrist(?) who's disturbingly eager to throw pills at any stated problems of the day. The student, knowing this, plays psychiatrist and pharmacist for his not-so-rich classmates: They tell him their problems, he claims to experience those problems to his own psychiatrist, and gives the students the pills. I think it's implied he does some light research on the field so that he can control what the psychiatrist dispenses.

There's the obvious practice of medicine without a license by a high school student to complain about. On top of that, is the issue of the psychiatrist's competence and his role as a straw man for people to rail against the science of psychology and neurology. If a psychiatrist is such a quack that he'll frequently dispense new prescriptions for problems seemingly without regard for what he's already prescribed, would you trust him to be able to solve other kid's problems by proxy while being ignorant of the deception that's being played on him? I would hope that such a psychologist would get in deep trouble for his prescribing habits.

Addendum: Wouldn't the pharmacists who fill all those prescriptions start to get suspicious when they see how many drugs he's allegedly on?

"Among drugs tested in phase II trials, only 30% go on to phase III."

And the number one reason they fail PhIII? Yep, lack of efficacy (Nature Reviews Drug Discovery, v10, 87).

(Being in PD Biomarkers, that article gave me a lovely quote to use when I'm pushing for biomarkers in trials: "The way to improve Phase III success rates is to avoid wishful thinking and to rely on high-quality scientific evidence by fully testing mechanisms against each target indication, using well-defined end points in the right patient population in Phase II trials." Which, to the point of this post, requires the trials be done...!)

Orac hit on one of the huge flaws in this legislation: what's the point of completing the clinical trials process? Sure, there's the benefit of being able to actually market the drug, but drop a word here or there and you can get people clamoring for the drug without the marketing. Money saved on advertising, tons of money saved on those pesky, and very expensive, clinical trials. If the legislation weren't so quack-friendly, I imagine that all those people terrified of Big Pharma would be up in arms protesting the bill.

Also, if I recall my Regulatory Affairs education correctly, when AZT came about, AIDS advocacy groups pressured FDA to approve the drug before it had completed clinical trials. FDA caved and the patients got what they were asking for: an effective drug that was insufficiently tested but riddled with adverse side effects. They admitted afterward that they jumped the gun and that, just maybe, it should have gone through more testing before it was released to the market. This is from memory, so I may be a little off, but I'm pretty confident.

Wouldn't these right-to-try laws lead to all kinds of litigation after some optimist tries something, fails to thrive and then they (or their heirs-and-assigns) try to sue the hind legs off the drug company and/or the FDA?

There's another motivation in the shadows: this would be a been to create an industry sector of Burzinksis.

For a moment, stop looking at this from the perspective of gullible patients. Look instead for the organisms that will adapt behaviour to feed on the newly unguarded flock. Flock of willing fools, a terminal disease is highly effective to soften up the average mark.

It’s sad to say we’re past the era of such exciting and “easy” breakthroughs.

I sometimes wish I'd entered the pharmaceutical industry in the 50's, when all the low-hanging fruit was still available for discovery...

Isn't this awfully reminiscent of the John Birch Society and the Committee for Freedom of Choice in Cancer Therapy (aka Committee for Freedom of Choice in Medicine) and the push for Laetrile in the 1970s? http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/laetrile.html

I'm a cancer patient and my cancer won't ever be cured. I can't begin to describe how naive and insulting this legislation is from my point of view. It's an invitation to abuse people who have more than enough problems already, with absolutely no consequences to the abuser.

Excellent point. When I repost a modified version of this post on my not-so-secret other blog, I'll have to add a couple of sentences mentioning this.

Not directly related, but it would be nice if we could encourage a little more of this kind of support for cancer patients.
http://msn.foxsports.com/detroit/story/very-special-guest-to-accompany-…

The entire justification for “right to try” laws also seems to rest on a misperception that there are “miracle drugs” out there that we will have to wait years for because the FDA is too slow to approve them.

Or, if you are prone to donning tinfoil headgear, you may think that the FDA is in cahoots with Big Pharma to suppress such "miracle drugs".

while making any state official or employee who attempts to block access of an eligible investigational drug to an eligible terminally ill patient potentially guilty of a class 1 misdemeanor

Does this include the IRB members who are required by Federal law to evaluate the criteria? Many medical schools are attached to state universities, making those professors arguably state officials. (At least in my state, state university employees are considered state officials whenever it is convenient for the state to so consider them.) In states where this legislation passes, IRBs could be unable to comply with both state and federal law.

I did see the movie. As fiction and drama it is well made. As science it is pretty weak. I don't know whether the depiction of the federal agencies is historically accurate or not, and it would be nice if somebody here could clue me in. The depiction of the doctors is fairly one dimensional, with the lead researcher being shown as a mercenary jerk, with his female assistant being shown as a saint in training, and with a defrocked American doctor running a Mexican clinic shown as scientifically superior to the medical experts in the US.

The movie contains fairly explicit attacks on the pharmaceutical industry, particularly in terms of AZT being pushed as a profit center.

There's absolutely nothing in the picture about the development of scientific knowledge about virology, about the development of protein structure determination, or how real science led to the protease inhibitors. The movie was a snapshot of a period not long after the disease was discovered and the virus identified. There is a plot line that argues that AZT is so toxic that many AIDS patients died of drug toxicity rather than the underlying disease. I believe that the film's authors believe that and I would like to ask whether there is any truth to this assertion.

It's curious how the two lead characters go down opposite paths in their disease progression, with the Woodroof character seemingly robust and vigorous after his initial brush with an early death. It's only in a final title card that the film reveals Woodroof's death at 7 years following his initial diagnosis.

As to the "right to try" law, I wonder if it would be possible to have some variant in which people who are not eligible for clinical trials could get onto some medication that is being used in a clinical trial. When I looked at the story of the drummer's wife who has a rapidly progressing brain tumor, it became obvious that the clinical trials are aimed at children. She and her husband would like to maintain some level of hope, and it seemed to me at the time that the FDA could allow her to try some treatment that has some rational chance of helping, and simultaneously deny the Burzynskis of the world any chance to peddle their snake oil.

@Johanna: Re lawsuits -- I don't think so. The law is pretty strict about rejecting lawsuits that are filed after the statute of limitations has passed, and the courts are pretty good about rejecting lawsuits that involve violating some previous agreement to accept risk. If I understand correctly, there would have to be a finding that the informed consent was based on a falsity, or that the drug company intentionally withheld important information about risk. Since the forms include general warnings about all sorts of risks including death, it seems unlikely that any such action would succeed.

@Bob: I read this just after I saw the movie, as I was also curious about the accuracy of the depiction of the FDA and of the story line in general. http://www.slate.com/blogs/browbeat/2013/11/01/dallas_buyers_club_true_…

The movie was well made, and McConoughey gave an excellent performance which stood out against his previous romantic comedy roles. But the movie had a 1985 ideology leaving out important facts. Fact 1 was that AZT has actually been pretty darn effective and was approved very rapidly after six months in the first clinical trials. In the film, the character uses DDI which is a very similar drug with a similar spectrum of activity and toxicity. The response of the scientific community to the appearance of AIDS was in fact amazing and very successful. Of course, every journey into the unknown has some misteps, but the AIDS story is one of triumph of the system. I was at a meeting when Magic Johnson announced his HIV status, and my colleagues and I thought that he was doomed to die within about six months based on our past experience...this was in 1991. I am retired now, but I still run into old AIDS patients; they are on the stairmaster next to me at the gym trying to keep their weight down! The movie missed the story; it is a story that shows the system working. AZT has played a huge role in saving lives.

Here are some other articles criticizing the history and facts as presented in Dallas Buyers Club:

The movie distorts the facts about AZT, for instance, to make Woodroof seem heroic for his murderous advice to others not to take it. It's true that there were HIV deniers and AZT deniers in our midst who were pushing vitamins and herbs, even regular gusts of ozone up the butt, and clearly AZT had serious toxicities at the dosage tested. It was also clear that AZT worked. Unflagging pressure from Marty and ACT UP and so many others led to expedited approval, before an optimal dose could be established. And why not, since the course of HIV without treatment had already been demonstrated thousands of times?

http://www.huffingtonpost.com/patrick-mulcahey/dallas-buyers-club_b_426…

Woodroof also sued the FDA for not allowing him in the initial trial of AZT, a drug he publicly campaigned against: “Look at AZT (one of the few government-approved AIDS treatments). I don’t know if I wouldn’t prefer giving a shot at eating Comet cleanser. I’m serious. That stuff will eat you up.”

http://entertainment.time.com/2013/11/08/the-true-story-of-dallas-buyer…

In the film, Dallas Mercy Hospital is having a randomized controlled trial to test AZT's effectiveness. Unable to be sure he's getting the drug rather than a placebo in the trial, Woodroof bribes a hospital employee to supply him with AZT, to which he reacts very badly. Throughout the rest of the movie, he and other characters denounce the drug as "toxic," and Woodroof recommends that customers of the buyers club dispose of what AZT they have and never take it again. At one point, a news broadcast is heard which emphasizes that AZT was the most expensive drug ever produced at that point. One could be forgiven for coming away with the sense that the medical community was poisoning HIV/AIDS patients with the drug, and keeping them from other, safer, therapies.

The trouble is that AZT is actually a very effective therapy against HIV/AIDS. "People who were consistently using AZT prolonged life for one year," says Jonathan Engel, a medical historian at Baruch College and author of "The Epidemic: A History of AIDS." That may not sound like a lot, but at a time when the disease had a mortality rate of 100 percent, anything that delayed death was valuable.

This is not to say that Woodruff and others were imagining things. The dosages at which the drug was prescribed really were too high, but that was because of worries that a lower dose wouldn't be enough to meaningfully slow the virus.

Peter Staley, a longtime HIV/AIDS activist and co-founder of the Treatment Action Group who informally consulted on "Dallas Buyers Club," notes that though later studies showed that half the original dose worked just as well, researchers didn’t know this in the early days of the epidemic, and they only figured it out by comparing a lower dose to the original dose and finding the two had same rate of deaths. "They basically had to guess at a dose to use and decided to 'hit hard.'" Staley says. "It was not some government conspiracy that picked a high dose of AZT; it was a fear that hitting the virus too lightly wouldn't do the trick."

And:

At Staley's insistence, the film ends with a title-card noting that AZT went on to save millions of lives as part of HAART. But for the other two hours of the film's running time, the drug is spoken about in overwhelmingly negative terms.

http://www.washingtonpost.com/blogs/wonkblog/wp/2013/12/10/what-dallas-…

Mayim Bialik (known for endorsing anti-vaxxers, homeopathy, and homebirth) cited Dallas Buyers Club as a reason for why she endorsed one of the petitions for antineoplastons and Burzynski https://www.facebook.com/official.mayim.bialik/posts/10153635921890008

For those who don't know what Mike is talking about with respect to Mayim Bialik's quack tendencies:

http://scienceblogs.com/insolence/2012/02/21/say-it-aint-so-amy-farrah-…

So sad for a PhD neuroscientist to be so prone to quackery.

I've worked for pharma companies, and I can't imagine them wanting to just ship clinical candidates off willy-nilly to people who ask for them. The companies need the data from clinical trials to get approval, so they don't want to compromise clinical trial enrollment; and they don't want liability concerns (and it'd be difficult to argue the validity of any waiver of right to sue in the case of a drug with just Phase I data - "informed" consent??). And no pharma company will want to put its clinical candidates in the hands of a Burza, profiteering on the helpless: it needs doctor goodwill, or at least doctor credibility down the road. It's a lose-lose. Real compassionate use, real single-patient INDs, OK - "suck it and see", no way.

Long time reader, first time poster... I really like your blog and appreciate the incredible energy on these topics. I find your analysis okay here but I also think you should consider:
(1) this legislation is probably least important to oncology, where there are already huge incentives for Big Pharma to develop and approve new medicines, i.e there are clear clinical endpoints, relatively short trials, surrogate imaging biomarkers, handsome financial rewards for even minor improvements in clinical standard of care, etc. This type of trial-and-error seems much more useful for pursuing less sought after clinical endpoints, or maybe things like sarcopenia that aren't necessary even readily accepted as a clinical endpoint by FDA;
(2) People with sarcopenia or clinical endpoints that take longer to test of course aren't "terminal". So it seems possible that "right to try" legislation might actually be most helpful if extended beyond "terminal" patients;
(3) Yes, this type of legislation could "change the rules of the game", and open the unsuspecting public up to charlatans. Yes, it appears Pharma could to some extent get away with selling drugs before they've really proven safety and efficacy and so there would be some disincentive to pay for and conduct rigorous Phase II/III studies. But, markets do work, and changes to market structure can really work, especially when market participants are aware of when the rules of the game are being changed and how they're being changed. Passing this type of legislation in Colorado or a few states and seeing the FDA allow them to be implemented would definitely change the market dynamics, but I don't see how anyone could tell what the long-term impact would be. State laws are the laboratories of democracy, and if there is any measured/responsible way this could be done in the US (rather than it occurring through overseas medical tourism), it would likely be done in some very similar way to what is now being proposed... limited roll out in select states first.
(4) Consider for a moment that having FDA-approved drugs available sooner in select states and backed by decent science, although not perfect, could provide a respectable outlet that actually acts to crowd out snake oil salesmen... e.g. if you're one prone to experiment on yourself, you move to Colorado where you at least can experiment with quasi-legit medicine, instead of being forced to settle for almost guaranteed to be worthless nutraceuticals. My two cents!

State laws are the laboratories of democracy

When the same legislative changes pop up on the agenda of half-a-dozen states simultaneously, perhaps it's more accurate to call them "the lab rats of lobbyists".

Totally off-topic, and I apologize in advance, but for those who liked Matthew McConaughey's work in the film, "True Detective" is riveting.

Herr Doktor @27 -- The great Charles Pierce, the main political commentator on Esquire.com -- has a recurring feature called "This Week in the Laboratories of Democracy", featuring (of course) boneheaded legislative initiatives from various states -- "Where the real work of governmentin' gets done!".

Fergus@2 and @4
You point out that imatinib was a miracle drug. Yet it is poor example to support right-to-try. Imatinib was approved by the FDA based on the phase I trial. See study here. See FDA approval notice here.

So this is actually an example of why right-to-try is not needed for miracle drugs.

To clarify:
imatinib = Gleevec = STI571

(Apologies-- I've trained myself to use generic names.)

if you’re one prone to experiment on yourself, you move to Colorado where you at least can experiment with quasi-legit medicine, instead of being forced to settle for government approved safe and effective medicine.

I just wanted to outline some of careless/false statements you made in this post.

"According to these laws, the drugs need only have passed phase I trials."

Phase I must be complete, and trials must be ongoing.

"There is always an inherent conflict between wanting to push for faster approval of drugs in order to treat patients who are dying and the need for rigorous testing to assure safety."

You are right to some extent, but mostly only if you consider that the FDA creates this conflict by requiring RCTs to be conducted on dying patients for drug approval. Bayesian analysis would lead to quicker, more accurate results because a lot more than 3% of patients would be able to try the treatments.

"Patients and their families ask, “What’s the harm?” while advocates like Corieri sell their policy with the assumption that experimental drugs are highly likely to help these patients, or at least not so unlikely as not to be worth trying."

In the hearing in Missouri, no dying patients or caretakers said "What's the harm?" They said that they thought themselves (or their dead children) would have preferred to try an experimental treatment after they ran out of FDA approved options. Also, can you show me where somebody has said that the experimental drugs made available through this law are highly likely to help these patients?

If I had a 1% chance of dying, I'd (reasonably) be scared as hell. About 13% of new oncology drugs go on to be approved. That number is higher for the Right To Try drugs, because they have already moved into phase II. Why is it wrong or unscientific for a cancer patient to want to try a new drug that has a (non-negligible) chance of helping them?

Furthermore, I've witnessed plenty of oncologists convincing patients to enroll in trials based on "promising early results". Hell, I've seen a doctor totally flip that speech around when a patient asked if she could get an investigational drug outside of the trial so she didn't have to risk getting placebo.

"And, to top it all off, the law prohibits the state medical board (or any other state regulatory board) from going after the license of any physician or health care practitioner who recommends and/or administers such investigational agents to patients"

No. The law prohibits the state medical board (or any other state regulatory board) from going after a physician's license based solely on the physician’s recommendation to an eligible patient regarding prescription for or treatment with an investigational drug, biological product, or device.

I'd appreciate it if you'd be more cautious when writing about these matters in the future.

“According to these laws, the drugs need only have passed phase I trials.”

Phase I must be complete, and trials must be ongoing.

"Passed phase I trials" means phase I must be complete. Seriously, did you bother to read? Also, while it's true in Arizona that trials must be ongoing, not all versions of these laws require that. Note the plural "laws." Of course, if you want to be pedantic, you could have said that I should have said "proposed laws" or "bills."

You are right to some extent, but mostly only if you consider that the FDA creates this conflict by requiring RCTs to be conducted on dying patients for drug approval. Bayesian analysis would lead to quicker, more accurate results because a lot more than 3% of patients would be able to try the treatments.

Citation needed.

Also, the FDA does not always require RCTs to approve (or fast track approve) drugs. The aforementioned example of Gleevec, for instance. There are also drugs that have been fast track approved based on phase II trials that weren't strictly randomized trials. I realize you're a newbie here, but it's not as though I haven't discussed this before several times while discussing, for example, Stanislaw Burzynski.

If I had a 1% chance of dying, I’d (reasonably) be scared as hell. About 13% of new oncology drugs go on to be approved. That number is higher for the Right To Try drugs, because they have already moved into phase II. Why is it wrong or unscientific for a cancer patient to want to try a new drug that has a (non-negligible) chance of helping them?

You do realize, don't you, that this doesn't even make sense. Just because 13% of drugs go on to be approved does not imply that a drug that's only passed phase I has a non-negligible chance of helping, particularly when administered outside of the carefully controlled auspices of a clinical trial.

“And, to top it all off, the law prohibits the state medical board (or any other state regulatory board) from going after the license of any physician or health care practitioner who recommends and/or administers such investigational agents to patients”

No. The law prohibits the state medical board (or any other state regulatory board) from going after a physician’s license based solely on the physician’s recommendation to an eligible patient regarding prescription for or treatment with an investigational drug, biological product, or device.

How about I cite the Arizona law itself, verbatim, given that's what I was clearly discussing when I wrote that?

"NOTWITHSTANDING ANY OTHER LAW, A STATE REGULATORY BOARD MAY NOT REVOKE, FAIL TO RENEW OR TAKE ANY OTHER ACTION AGAINST A PHYSICIAN'S LICENSE ISSUED PURSUANT TO TITLE 32, CHAPTER 13 OR 17 BASED SOLELY ON A PHYSICIAN'S RECOMMENDATION TO AN ELIGIBLE PATIENT REGARDING OR PRESCRIPTION FOR OR TREATMENT WITH AN INVESTIGATIONAL DRUG, BIOLOGICAL PRODUCT OR DEVICE"

Quite simply, my interpretation is demonstrably correct. Yours is demonstrably incorrect. And I'm the one who should be more cautious?

Wouldn’t these right-to-try laws lead to all kinds of litigation after some optimist tries something, fails to thrive and then they (or their heirs-and-assigns) try to sue the hind legs off the drug company and/or the FDA?

The FDA? No. The drug company, you bet your sweet bippy. Disparities in bargaining power are targets for the enforceability of waivers, and the proposed law above does not appear to make any provision for preemption of tort claims.

@Josh

Furthermore, I’ve witnessed plenty of oncologists convincing patients to enroll in trials based on “promising early results”. Hell, I’ve seen a doctor totally flip that speech around when a patient asked if she could get an investigational drug outside of the trial so she didn’t have to risk getting placebo.

Encouraging patients to enroll in a clinical trial is the right way to go. Encouraging them to get the drug without going into a clinical trial jeopardizes clinical trials, which in turn jeopardizes drug approval, meaning fewer people would be able to get it in the long run.

Also, when it comes to terminal illnesses, placebos are generally considered unethical. Instead, an active control is used; generally that's whatever the current gold standard approved treatment is. The only time a placebo would be used is if there was no other treatment at all for the disease or condition.

Madison #30
I completely agree. It was just that Orac stated that miracle drugs don't exist.

Imatinib to work just had to disable one aberrant protein which is unusual. However there might be more out there.

I would actually really appreciate it if Orac or someone with a similar science-based background wrote a post on Dallas Buyers Club. Bob G provided some interesting insights above but I haven't really read much that discusses the films factual accuracy from a scientific perspective.

I saw it a few weeks ago, so my memory is a little hazy. It is a well made film and I can understand the critical reaction to it. But....it really came across as anti-evidence based medicine, whilst promoting the role of the lone crusader sticking it to the system. Obviously in the case of the main character, but also the guy in Mexico with his offbeat personality and mish-mash of supplements and the doctor with a conscience who quits (Hilary Swanks character). It also seemed to portray RCT's as a cold and uncaring approach to establishing whether a treatment works or not whereas just taking a load of anything without knowledge of efficacy, side effects, dose control etc. is the way to go.

Perhaps I'm overreacting. But I can imagine an audience leaving the film thinking good for him for sticking it to 'Big Pharma'. In fact my girlfriend said 'see, his supplements worked!'. Despite there being a bit of text at the end saying 'Oh AZT was effective at a low dose and saved millions of lives plus Ron died 7 years after the diagnosis', which to me seemed to undermine the overall narrative of the film.

The problem I have is that, as a well-made and critically respected film, it has the potential to distort people perspectives regarding the era and what the medical communities role really was. I'm not saying it was perfect. In fact it probably wasn't. But I would be interested in reading a take on the film that explores its portrayal of the science at the time, it's success, failures and complexities.

The only good which might come out of this experiment would be if the patients involved were intensively (and consistently) monitored, with well-trained nurses taking blood/urine/etc samples and logging vital signs and other developments. Family members saying, "Granny seemed to get better around the second week but then the cramps started again" won't help researchers or other patients.
The most useful change in testing policies that comes to my little (lay) brain would be expanding phase II & III trials so that more could participate. Of course, that would require subsidies, and thus either increased deficits or (gasp!) making billionaires pay taxes at rates comparable to us plebes. This would face relentless opposition from Goldwater Institute flacks and their fans, medical progress be damned.

Out of curiosity. How hard is it to get into a Phase II or Phase III clinical trial? I guess the problem with actually being in a trial is that one might get the placebo.

Don W, you can read the requirements for thousands of clinical trials at http://clinicaltrials.gov/. The requirements vary widely depending on the purpose of the trial. I think the common denominator for the people who would want a "right to try" is that many trials require that the patient be expected to live for a certain number of months -- long enough to collect meaningful data. Depending on the chemical involved, they often require a certain minimum level of liver function, kidney function, etc. There are generally specific reasons for those limitations -- if a patient is on the brink of liver failure and you know the chemical is a liver toxin, most doctors wouldn't use it in patients who are likely to be thrown into crisis. If the patient already has atrial fibrillation doctors won't use a chemo that exacerbates the condition. It's often not simply a question of whether it will kill the patient or not -- it's an issue of causing pain and suffering until death. The Phase I safety evaluations are conditional -- my liver, heart, and kidneys are very healthy so far, so I'm not limited in the chemotherapies I can use. A year from now my situation may be very different. It troubles me that these proposed bills seem to allow any physician to recommend things with no check on their expertise.

I guess the problem with actually being in a trial is that one might get the placebo.

Which is ethical and sensible when one might be better off with the placebo. Some drugs do bad things.

(And incidentally control arm is usually placebo+standard of care, so nobody receives less than standard; in fact, placebo and blinding are not even needed when survival is the endpoint)

"Right to try" = right to lie. The floodgates of snake oil salesmen are always brimming with potential pathways for eschewing Federal guidelines regarding levee safety. A deluge of opportunists will invariably ensue.

Why I love BigPharma-
www.healthcareforamericanow.org/2013/04/08/pharma-711-billion-profits-p…
www.nytimes.com/2013/10/13/us/the-soaring-cost-of-a-simple-breath.html?…

Interesting links, anon.

Do you wish to explain the relevance they have to the current topic, or are you under the impression that as soon as you've said "Here's Big Pharma doing something bad", every suggested alternative magically becomes a good idea?

Anon seems to have problems expressing what he means in complete sentences, or staying on topic.

#45 Watchdogs for both are ablsolutely necessary.
#46 Chris, did I not read about curries, thai ,wines and other gustatory delights on another blog??? I'm sorry you have difficulty with my posts. I recommend you ignore them.

Watchdogs for both what are absolutely necessary?? Your behavior is very rude; you want us to consider your opinion and conclude that it's right, but you can't be arsed to do more than copy-paste a few links and leave us to figure out the connections you think we should follow you in drawing?

As for the issue of going off-topic, there's all the difference in the world between following the conversation as it drifts onto a pleasant or interesting side-topic, and trying to artificially *force* a change of topic. If we had already been talking about other misdeeds of pharmaceutical companies, or other ill effects to society produced by our current IP laws, then your contribution would be on-topic. As it is, however, it comes across as you essentially saying "I want to stop the current discussion, because I want to talk about Big Pharma being the villain instead! It doesn't matter if you have something to say about how Hollywood likes to sell a narrative of 'underdog who fights a cruel and unfeeling system' and how that narrative can feed people's distrust of systems which are, in fact, actually trying to protect their best interests! I want to talk about how Big Pharma is bad, bad, bad, and you have to defer to my choices in this matter!" If you truly can't see the difference between the two, it means you really have no idea how rude you're being.

I think this is on-topic, actually: does anyone have more information about what's going on in the case of Josh Hardy? http://www.digitaljournal.com/life/health/op-ed-drug-company-responds-t… I oly heard of this for the first time today; a number of people I care about have already gotten emotionally on board with the 'the drug company could easily save this child's life, but they won't just because they're greedy bastards' narrative. Knowing how easily such narratives spring from misunderstanding of the whole process, I'm hoping that someone can explain whether that's really what's going on or if there's another side to the story.

I’m hoping that someone can explain whether that’s really what’s going on or if there’s another side to the story.

The fact that they used the now-discontinued EAP as promotional copy doesn't cast Chimerix in the greatest light.

They also pitched the earlier emergency INDs to investors.

I'm absolutely in favor of the principle of "right to try" type laws. Largely because I think people should have the right to be stupid and injure themselves due to their own stupidity.

Trying to protect people from their own stupidity just makes people mad. Protect people from *other people's* stupidity, certainly, but allow people to injure themselves due to *their own* stupidity.

Frankly, I'd rather go back to the Pure Food and Drug Act of 1909 regime, under which drugs had to be what they said they were, but if you were fool enough to buy cyanide and take it, well, that was your problem.

Orac, I wonder if you've considered this public policy point. Should we allow people to injure themselves (as opposed to others)? I say yes.

"After all, if early stage experimental drugs were made widely available outside of clinical trials and taken for a wide variety of cancers, the signal-to-noise ratio would become very low. It would become very difficult to tell which drugs were working and for which cancers (and which were not), particularly since it would be reasonable to expect that such a policy would result in enrollments in clinical trials plummeting. "

This is your only valid argument here. Accordingly, a sensible law would allow access to any drug which does *not* have funded clinical trials. Eh?

"If there’s a drug that’s shown as incredible a result in an early phase I trial as Gleevec, I am unaware of it."

There's a number of "pre-modern" drugs for various classes of illness, used efficaciously by physicians for long periods prior to roughly 1930, with pretty impressive results, which have never undergone any studies due to the fact that they can't be made profit centers.

The current idea in vogue is to make them profitable by allowing companies to claim exclusive rights to them just for going through clinical trials. You must know that this is ridiculous and ends up reducing access.

There's got to be a better method of funding clinical trials. For instance, direct government funding. Do that, and the clincal-trial-funding concerns about letting people use dangerous, untested drugs evaporate.

"They often seem to think we’re still in an era where overnight breakthroughs that fundamentally change how we view the world are still likely. "

It's happened fairly recently in math & physics, and also chemistry.

It doesn't happen in medicine due to the nature of biology.

The only permanently-accurate broad generalization in biology is the theory evolution, and the way evolution works means that you won't *have* any other accurate broad generalizations.

But this has *always* been true of medicine -- we never get grand revolutionary discoveries which give a great, broad picture. Even the theory of germs only accounted for *some* diseases (hello, arthritis!). Even antibiotics only worked for *some* diseases (even fewer). It isn't actually a change, it's always been like this.

There’s a number of “pre-modern” drugs for various classes of illness, used efficaciously by physicians for long periods prior to roughly 1930, with pretty impressive results, which have never undergone any studies due to the fact that they can’t be made profit centers.

This is the sort of simplistic analysis which makes me immediately conclude the author is guided by ideology rather than evidence. There are researchers who dream of fame and glory. There are insurance companies who crave ways to cut the costs they pay when their customers' health suffers. The idea that the treatments are out there just waiting to be rediscovered but that no one is following up on this obvious promise because no one could have a motive other than "I want a treatment I can sell for beaucoup bucks" is just blind cynicism fooling itself that it's wisdom.

“They often seem to think we’re still in an era where overnight breakthroughs that fundamentally change how we view the world are still likely. ”

It’s happened fairly recently in math & physics, and also chemistry.

What would you consider to be a "fairly recent" "overnight breakthrough" in mathematics or physics?

I'll settle for any "breakthrough" whatever in the latter category.

Nathanael says there are drugs from pre-1930 which were effective but are not used or tested. Drugs commonly in use before 1930 that had no major harmful effects were grandfathered in to the Pharmacopeia. He may be unaware of the NCI's chemical libraries of 140,000+ natural and synthetic compounds (total) which are regularly screened against cancer cells and other diseases. http://scs.illinois.edu/htsf/compound_collection/nci.php Universities and nonprofits use these libraries, not just for-profit companies. I'd be curious to hear about just ONE pre-1930 drug effective against disease or condition which is no longer in use today, that is better than current drugs or has fewer side effects. In other words, is this a real argument or a plausible-sounding bit of hot air accepted because it bashes BigMedicine(tm)?

I am guessing that most people here are pro-choice and should grasp that people have some right to control their own bodies.. for better or worse. I’d suggest that there should be a high barrier to straying from that concept to give government control over choices that should be up to the individual. I’ll note that on the issue of treatment choices I am firmly in the scientific medicine camp and opposed to the nonsensical “alternative” treatments you folks debunk. The cause will be won however through educating the public, not through trying to use the legal system to impose our approach.

It doesn’t make sense to push government to infringe on rights in ways that can come back to haunt you if those you hate are ever in control. Despite lack of scientific basis for alternative treatments, their providers tend to have political clout in part because not enough of the public is scientifically literate. Consider a thought experiment (even if it is fortunately never likely to happen), what if one day alternative medical providers had control of government policies and dictated the FDA approve only remedies they approve of and outlawed many treatments we’d approve of?

Even if they don’t go that far and merely have some ant-science types in the FDA, try exhibiting some empathy and placing yourself in the position of someone who is well informed and wishes to try a treatment but aren’t allowed to because of some anti-science politician that tried to make it harder for pharmaceuticals to be approved.

Part of the problem today is that the FDA is badly run, in part since it is a monopoly, so it takes a long time even for good treatments to be approved. You folks have the fantasy we can get a competent science based medicine FDA and government if we just wish hard enough and try to convince them using reason. Economists who study how governments work in reality (rather than naive fantasies of how we wish they did) suggest that is unlikely. (e.g. see regulatory capture theory, which won George Stigler his nobel prize, which argues special interests tend to control regulation by default (which slows down approval of new drugs, to benefit existing drugs). Public choice theory which won James Buchanan his nobel and which he described as “politics without the romance” also argues that government benefits special interests (including alternative med types) not necessarily the general interest). Unfortunately studies show most people are economically illiterate, and many who push sound medical science push junk economics and dismiss rational economics out of hand in your desire to believe in a fantasy model of a government that acts in our interest. Jefferson noted we hadn’t found angels in the form of kings to govern us, and today we haven’t found angels in the form of politicians and bureaucrats.

Competing private safety approval agencies would speed up the process of drug approval, with perhaps options like providing insurance backing up their assertion of safety to provide them with added incentive to get things right.

If someone is dying and wishes to try a treatment you don’t approve of, what right have you to prevent someone from putting whatever they wish into their body? Aren’t they more likely to get solid medical advice if they can choose to do so legally with a doctors advise rather than being forced to go underground and no risk talking to a competent doctor? It may be that you have science on your side, and that the bulk of treatments people wish to try are nonsense, but obviously there is a chance some new treatment will be found that will help.

People seem to forget that this is supposed to be a free country, no matter how much you would prefer to force everyone to do things the way you wish as benevolent dictator. You can argue “but more people will be harmed by granting people freedom”, but that is ignoring that individuals are supposed to have rights, including the right to make stupid decisions, and the right to save their own lives. Jewish members of the ACLU defended the right of neo-Nazis to march since they grasped that even those you despise should be granted rights. What if some group were in power that despised you and wished to take away your rights, like the right to use pharmaceuticals you approve of?

re: “Because the FDA exercises a lot of its power through the federal government’s power to regulate interstate commerce”

People should ask themselves why a constitutional amendment was needed for alcohol prohibition, yet magically the FDA these days gets away with banning whatever it feels like. The answer is that the constitution’s meaning has been distorted over time to usurp authority the federal government wasn’t intended to have, and was understood not to have for most of this country’s history. . Many people today seem unaware that the commerce clause was part of the constitution to prevent trade barriers from being enacted between states. The connotation at the time of “regulate” was to “make regular”, and the connotation of “commerce” was trade. It has been unfortunately distorted to allow micromanagement of the production of goods that are traded, which is outside of the act of “commerce”, i.e. trade itself.

When the constitution was passed there was a great deal of debate over it since the states were wary of giving away more power to a central government. There is little chance they ever would have approved a constitution they thought would allow the level of federal micromanagement of the country that that exists today. The Constitution should be amended to grant the federal government new powers, not ignored as it has been. The idea was to leave most power in the hands of the state&local governments who could compete and learn from each other to see what approaches work best.

Unfortunately many people try to suggest we have a “living constitution” and should just go with the flow. Pragmatically we may need to live with it, but we can still argue to try to change that approach over time. The problem with letting the courts get away with granting the federal government powers you like is that they may also grant it powers you don’t like, such as perhaps letting a future religious right controlled government impose their views, censorship be imposed, more spying on the public, and various other infringements of rights. A “living constitution” is a dead constitution since if it can mean anything, it means almost nothing and can’t be viewed as a safeguard for the rights you do value. The power you wish the government to have to infringe on rights to do things you like could be misused someday by a government composed of people who wish to do things you don’t like.

Just as many alternative medicine types dismiss strawman versions of science they don't really understand (often mocking science which seems counter-intuitive to them), many who don't understand economics and business dismiss simplistic strawman versions of concepts they don't understand. People that bash junk science sometimes seem to fail to consider that they may be pushing emotionally appealing junk economics, refusing to grasp that real economics can be counter-intuitive.

re: "Libertarians love these bad ideas because, you know, the market cures all. "

Economically illiterate people often push bad policies because they refuse to learn that government doesn't cure all. Despite the strawman above, educated libertarians grasp that neither markets nor government cure all.

This nationally prominent GMU economics professor (who gets published in places like the Wall Street Journal) has a blog post referring to the problem of junk economics, including on the part of some high profile economists that are comparable to what a Dr. Oz would be in the medical world:

http://cafehayek.com/2014/03/witch-doctory.html
"Witch Doctory...
To assume or to suggest (as do many economists) that governments operate more ‘perfectly’ than do markets is no more scientific than to assume or to suggest that, if your child is seriously ill and medical doctors cannot guarantee that they will cure him or her, a local witch doctor can be trusted to supply the desired cure....

The theme of Jim’s talk was that it is not only intellectually sloppy or lazy but, in fact, deeply unscholarly and unscientific for economists today to ignore public-choice analyses of political decision-making. ...
Stated differently, Jim presented powerful evidence from several current economics textbooks that an embarrassingly large number of such texts – many written by the world’s most acclaimed economists, such as Paul Krugman – are surprisingly naive and unscientific. The authors of these texts pretend to write about reality, but they instead write about a fantasy world. Far too many economists, such as Krugman – because they either ignore or are ignorant of public choice – simply assume that government somehow is not affected by the many imperfections that these economists readily find in markets. As Jim said, this continuing ignorance of public choice is embarrassing to those economists who do think seriously and realistically about their discipline and about the reality that that discipline aims to illuminate."

CommonSense Boulder

Can I have chips on the side with all that copy-pasted spam?

Re: Josh Hardy

The company has just announced that it will supply the drug. Apparently the face saving compromise they were willing to make was to call it a 20 patient open label trial.

http://www.cnn.com/2014/03/11/health/josh-hardy-drug-study/index.html?h…

Re: the CafeHayek story linked by CommonSense Boulder: What a total strawman argument the writer is making! The complaint is that textbook writers are not lauding free markets in the same light as they make a plea for government actions when markets fail. It seems to me that the standard economic textbook spends about the first half describing how markets work according to the balancing of supply and demand, and deriving various corollaries starting from that point. It's not exactly a novel point to suggest that markets provide a certain definition of efficiency and that you can correlate this efficiency with other results.

That is a useful field of study to learn, but it has nothing much to do with the fact that some efficient markets exclude whole classes of people from participation. One of those fairly efficient markets is private health insurance, which finds through its underwriting function that a substantial fraction of applicants should be denied on economic grounds.

That is an example of a market that operates efficiently according to classical economics, but would be considered to be immoral by many of us. Government intervention can change the rules of that market -- thereby making it less efficient in the classical sense and definitely less libertarian -- but will cause the market to serve the uses of lots of people who otherwise would be excluded.

Shorter version: The CafeHayek article is kind of stupid.

Another reason the article is stupid: Professional economists like Krugman spend entire careers debating the right way to tinker with the economy using governmental tools. It's implicit that there is no perfection in this approach, but rather an attempt to focus in on an increasingly improved process. The post-WWII success of Keynesian approaches to suppressing recessions speaks well for this approach, and it's obviously still being refined.

The argument that the FDA is bad because it is a "monopoly" and can regulate anything at all is absurd*. First, the FDA is an agency created by law with a clear mission, not a self-created company selling a service. It's a bad analogy. Second, the mission of the FDA is very tightly limited by law- it cannot inspect or regulate supplements (unless they make a clear medical claim to cure illness). It cannot inspect meat & poultry, that's DoAgriculture. Third, food and drug inspection cannot be set up in a for-profit competitive environment. The standards would fall to the minimum possible, compromising safety- not the minimum allowable by law, but whatever they could get away with, as a means to maximize profit. There would be an inherent conflict of interest to get business. Furthermore, the public would not know which competing stamp of approval meant a product was actually safe to eat or effective to use. Some of the existing quite valid criticisms of the FDA are due to the fact that it's funding is partly coming from user fees. Other criticism is that it is not funded to a level where it can fully do its' job. (*Most gLibertarian argument against government regulation is similarly absurd.)

re: "First, the FDA is an agency created by law with a clear mission, not a self-created company selling a service. It’s a bad analogy."

It isn't a bad analogy. Read my comment above about most people being economically illiterate. The FDA is subject to problems like regulatory capture in addition to being a monopoly. Competition works better than monopoly provision of services, despite the fantasies of some that if they just wish hard enough that a monopoly is guaranteed to do a great job. Jefferson wrote long ago that we hadn't found angels in the form of kings to govern us, nor have we found angels in the form of bureaucrats and politicians.

re: "Third, food and drug inspection cannot be set up in a for-profit competitive environment. The standards would fall to the minimum possible, "

Contrary that poorly informed comment, there are arising global private safety standards due to the low level of standards in many countries. It is bad for business to make your customers sick. Private competing safety certification labels would gain business by earning the trust of doctors and insurers. If they lose that trust they lose business. They might also compete by offering insurance against being wrong, paying out if they are.

re: "inherent conflict of interest to get business"

There is an inherent conflict of interest with revolving doors between the FDA and the private sector, and many other avenues of government failure that economists have discovered. In contrast if things are handled competitively then if a certification company seems to be in the pocket of a drug company and to be making bad decisions, they will need to pay out.

re: "Furthermore the public would not know which competing stamp of approval"

So then you can tell them, and they can decide if the believe you. The stamps of approval can be rated by others. They will have incentive to point out flaws in other stamps of approval.

re: "that it is not funded to a level where it can fully do its job"

A manager in every entity, public or private, has incentive to try to increase their budget to gain status, make their job easier, provide perks to their staff to be liked, etc. In the private sector the pursuit of profit, and competition to lower prices, counterbalances those incentives. In the public sector there is no competition to indicate how much it should cost to do its job, so costs tend to constantly rise (in contrast to the private sector which becomes more productive over time).

Certification labels can use fees from the products they certify for funding, with insurance on the results to ensure they have incentive to be accurate despite the source of funding. If they aren't accurate, insurers won't trust them and won't reimburse for products they certify, and then products won't come to them to get certified since no one will buy their product.

I'm a pharmacologist/toxicologist. All drugs are not the same. What about a "right to try" an anticancer drug effective in animal models which:

1) Unlike the usual poisons, shows no toxicity in animal trials, even at fairly-high doses. In fact, animals treated with it live longer than the controls.

2) Attacks a fundamental process that both forces and maintains the cancer cell at a very basic level.

3) Comes from the NCI (among other places)

4) Neuroprotective and prevents radiation-induced cancer.

5) The subject of more than 1600 papers over more than 30 years of work. Including some human trials.

6) Drug companies are reluctant to fund because of a lack of sufficient patent protection.

7) Cheap and, per NCI, "Off-the Shelf"

Personally, If I had cancer, I would like the opportunity to try such a drug, 'just in case".

Another example is riluzole for glutamate-receptor-positive melanoma. Presented randomly, naturally . A very beleivable scientific rationale with lots of in vitro studies,, pretty good safety, and a "phase-0" trial that showed possible efficacy. To treat a really, really deadly disease..

Yeah, I know riluzole has regulatory approval for ALS, so any doc can use it off-label. But what if this were not the case?

It's a Libertarian thing????? You don't know anything. Pretty good that there's so many opinions, when you have no clue about the shit that you're spewing on here. I'm dying & should have the right to take whatever I want. So lets weigh this out, it might hurt or kill me hmmm, I'm dying soon anyways. If it works, well that's a 100% tbetter hen I ever had. 1% better would be worth it. Anyone against it hasn't ever had death starring you in the face. I'll guarantee almost everyone against this law is a Liberal, always thinking you should be in control over everyones lives & your ideas have been destroying America. You sneak in by using the same line, it's for your safety. I pray my state passes this law. If you haven't been given a death sentence, SHUT THE HELL UP.

Kelly- I'm so sorry to hear about your prognosis, and I'm wishing you a full recovery.

The question is: Should we return to an age where any snake oil salesman (well meaning or not) can sell who-knows-what to desperate patients such as yourself? I certainly hope not.

Kelly,

There is a line between trying something that may work and being the victim of someone who preys on the dying.

Kelly, I think you have the right to take whatever you want. But I don't like the idea of con artists preying upon the desperate. There are people who will happily lie to you in order to get your money, and that I think is despicable.