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The Compassionate Freedom of Choice Act: Ill-advised “right to try” goes federal

Not too long ago, I expressed alarm at a series of bills that were popping up like so much kudzu in various state legislatures, namely “right to try” bills. Both Jann Bellamy and I warned that these bills gave a false illusion of hope to patients with terminal illnesses. Basically, these laws claim to grant the “right” of patients with terminal illnesses to access promising experimental medicines that have not yet been approved by the FDA. Indeed, these investigational drugs need merely to have passed phase I trials, and these “right to try” laws would allow them to be used in pretty much any human with a terminal illness who can persuade a pharmaceutical company to let them have such drugs. Of course, as I pointed out, such laws are based on a false premise, namely that there are lots of promising drugs out there that could save lots of lives of terminally ill patients, if only the hidebound FDA would get out of the way and let the people try them. The problem (besides the false assumption behind such laws) is that they are all state laws, and the FDA and federal law still trump state laws with respect to drug approval.

Apparently, advocates of “right to try” laws have gotten around to trying to take care of that little obstacle, too. I’m referring to a federal law under consideration in the House of Representatives and championed by the usual suspects, including the Alliance for Natural Health USA, a “health freedom” group that has yet to see a pro-quackery bill it doesn’t like.

In any case, at the time I originally learned about this bill, HR 4475, which was introduced by Rep. Morgan Griffith (R-VA) and entitled “The Compassionate Freedom of Choice Act of 2014,” its text hadn’t yet been published to the Congressional website. I did learn that the bill has been floating around for a while in various forms (for instance, former Representative Ron Paul (R-TX) apparently introduced it.) Now its text has been published, as Guy Chapman has noted. He calls it a “quack’s charter,” and he’s only off by a bit. The bill doesn’t go quite as far as he believes, but the bill is still plenty bad, man. If enacted, HR 4475 would amend the Food, Drug, and Cosmetic Act by inserting after section 561 (21 U.S.C. 360bbb) the text of HR 4475. This section of the Food, Drug, and Cosmetic Act is entitled “Expanded Access to Unapproved Therapies and Diagnostics,” and it’s the section of the act that regulates exactly that. The interesting thing is that this particular section of existing law is the framework under which the whole system of single patient INDs (also known as “compassionate use exemptions”) is already based. As I’ve described before, single patients can receive promising unapproved drugs under what’s known as a single patient IND, which has to be approved by the Institutional Review Board and the FDA and allows single patients to receive unapproved drugs. You can (and many have) argued that the single patient IND process is too cumbersome and restrictive, but HR 4475 seeks to (mostly) nuke this requirement. You’ll see what I mean in a minute.

First, the law states that:

Nothing in this Act or section 351 of the Public Health Service Act prevents or restricts, and the Food and Drug Administration shall not implement or enforce any provision of law preventing or restricting, the manufacture, importation, distribution, or sale of an investigational drug or device intended for use by a terminally ill patient in accordance with subsection (b).

Guy Chapman went a bit beyond what the law would actually permit in his analysis, I’m afraid. HR 4475 clearly does not authorize the use of quackery like Hoxsey therapy, Gerson therapy, or anything else like that in terminally ill patients, although I suppose it is theoretically possible that advocates could get an IND for one of these quackeries and then carry out a phase I clinical trial, after which the quackery would fall under the definition of an investigational drug or device according to HR 4475. (In this, perhaps the Gonzalez protocol would qualify, given that it’s undergone two clinical trials, the last of which was disastrously negative, but it was a clinical trial.) HR 4475 does, however, basically allow unfettered access by “terminally ill” patients to any “investigational” drug or device, which is defined as a drug or device that “(1) has not yet been approved, licensed, or cleared for commercial distribution under section 505, 510(k), or 515 of this Act or section 351 of the Public Health Service Act, and cannot otherwise be lawfully marketed in the United States; and (2) is or has been the subject of one or more clinical trials.” In other words, it’s very much like one of those “right to try” laws that are such a horrible idea but nonetheless are popping up like kudzu in state legislatures.

Again, however, the difference is that “right to try” laws in states would have little or no effect, because the FDA would still rule supreme over drug approval, and federal law trumps state law. HR 4475 would in essence codify “right to try” in the federal law under which the FDA works, which would do many orders of magnitude more harm to cancer patients and terminally ill patients. Basically, this law would allow any “terminally ill” patient access to any investigational drug with an IND that’s gone through at least phase I trials. I’ve explained before in great detail why that’s such a horrible idea, but it’s worth briefly repeating the following point. Most investigational drugs that make it past phase I trials still end up failing. The chances for doing harm far exceed any chance for benefit. Drugs with seemingly miraculous activity against cancer, like Gleevec, that show up in phase I clinical trials are exceedingly rare. Indeed, HR 4475 says nothing about whether the clinical trials the investigational drug or device being to be used in terminally ill patients has undergone even need to show promise or not. Under HR 4475, a drug that completely failed in phase I clinical trials by showing unacceptable toxicity (for example) could be distributed to a terminally ill patient as long as the patient is told that the drug failed phase I clinical trials.

Next up in HR 4475, there’s this:

  • (b) Patient Requirements.–In order for an investigational drug or device to be intended for use in accordance with this subsection, such drug or device must be intended for use by a patient who has–
    • (1) been diagnosed with a terminal illness by a licensed physician;
    • (2) been informed by a licensed physician that no drug or device that is lawfully marketed in the United States is likely to cure the illness; and
    • (3) executed a written informed consent document that states–
      • A) the known and potential risks and benefits of such drug or device; and
      • B) any indications of the illness for which a drug or device is lawfully marketed, or for which treatment is otherwise available, in the United States.
  • c) Prohibition on Requiring the Disclosure, Collection, and Reporting of Certain Information by Food and Drug Administration.–
    • (1) In general.–The Commissioner of Food and Drugs may not require the disclosure, collection, or reporting of–
      • (A) any information related to the delivery, administration, or use of an investigational drug or device pursuant to this section; or
      • (B) any information related to the clinical outcomes experienced by a terminally ill patient supplied an investigational drug or device pursuant to this section.
    • (2) Exception.–Nothing in this subsection prevents the sponsor of a clinical trial from voluntarily disclosing, collecting, or reporting information to the Food and Drug Administration.

One notes that “terminal illness” is not defined. I could go all Orac-style snarky on you and point out that life itself is a terminal illness (one that’s sexually transmitted, as well). We all die eventually. On the other hand, there are other diseases that are arguably terminal that can take a long time to kill. Even metastatic breast cancer is now potentially survivable for several years, even longer if it’s an indolent type with a low volume of metastatic tumor. Where do you draw the line in defining “terminal”? Normally, for purposes of laws, “terminal illness” is defined according to a certain estimated prognosis for life expectancy, be it six months, a year, or whatever. Even Abraham’s law did that. My guess is that this is to allow the widest number and variety of people with “terminal” illnesses access to unapproved treatments as possible. All you have to do is to find a doctor to say you’re terminal and there are no approved drugs or devices that can save you, and you’re good to go! Really? Any licensed physician, regardless of specialty? Moreover, under these circumstances, as described in this bill, “informed consent” is a joke, a cruel parody of real informed consent. In clinical trials, even in single patient INDs, the informed consent process is lengthy and detailed. In any event, the bill reads as though it were written specifically for Stanislaw Burzynski, as it would allow someone like him to abuse the IND process without even the threat of the FDA bothering him.

Now here’s the kicker. One of the criticisms of “right to try” laws is that drug and device companies won’t want to allow patients to have access to their investigational drugs or devices because adverse outcomes might affect their application for approval to the FDA. HR 4475 has that covered:

  • (c) Prohibition on Requiring the Disclosure, Collection, and Reporting of Certain Information by Food and Drug Administration.–
    • (1) In general.–The Commissioner of Food and Drugs may not require the disclosure, collection, or reporting of—
      • (A) any information related to the delivery, administration, or use of an investigational drug or device pursuant to this section; or
      • (B) any information related to the clinical outcomes experienced by a terminally ill patient supplied an investigational drug or device pursuant to this section.
    • (2) Exception.–Nothing in this subsection prevents the sponsor of a clinical trial from voluntarily disclosing, collecting, or reporting information to the Food and Drug Administration.

In other words, the drug and device companies who allow “terminally ill” patients to use unapproved drugs and devices don’t even have to collect data on the outcomes patients who take their unapproved drugs or use their unapproved devices under this law, and, if they choose to do so, don’t have to report those outcomes to the FDA. It’s all voluntary. It’s hard to imagine a provision more irresponsible than this. Add to the parody of “informed consent” in this law is the fact that the law basically makes any reporting of patient response or adverse events completely voluntary. Basically, if you’re a terminally ill patient, this law strips away all the copious protections for human subjects in research that the law currently provides. You’re completely on your own, and the drug company is not responsible for anything, so much so that the law even ends with this provision:

Except in the case of gross negligence or willful misconduct, any person who manufactures, imports, distributes, prescribes, dispenses, or administers an investigational drug or device in accordance with section 561A shall not be liable in any action under Federal or State law for any loss, damage, or injury arising out of, relating to, or resulting from–

  1. the design, development, clinical testing and investigation, manufacturing, labeling, distribution, sale, purchase, donation, dispensing, prescription, administration, or use of the drug or device; or
  2. the safety or effectiveness of the drug or device.

In other words, if something goes wrong, the terminally ill patient or his surviving relatives can’t even sue, unless there’s obvious gross negligence or willful misconduct, whatever that is, even if there turns out to be an obvious defect in the design of the drug or device. In other words – terminally ill patients, you’re completely on your own. Masquerading as a “health freedom” law that will let terminally ill patients have access to experimental drugs under a process less difficult than currently existing IND procedures, HR 4475 is a stealth assault on the very heart of clinical trial ethics. Remember, one of the main principles of the Common Rule and other statements of principles regarding human research subject protection is that vulnerable groups need more, not less protection. Those particularly vulnerable groups are traditionally defined as children, prisoners, and students, the former of whom rely on parents to exercise judgment and the latter two of whom are subject to potential coercion. I would argue that terminally ill patients are a particularly vulnerable population in that they are desperate and prone to grasp at anything represented as having a chance of saving their lives. If anything, they need more, not less, protection.

Basically, HR 4475 is a solution in search of a problem. It’s based on the assumption that there are just oodles and oodles of new investigational drugs out there that could save the lives of lots and lots of terminally ill patients, if only the government would get out of the way and let the people have access to them. This is libertarian magical thinking at its most pernicious; there’s no compelling evidence for this assumption and plenty of evidence against it. (And, no, my characterization of this assumption underlying HR 4475 is not a straw man.) Even if you view the IND process as being in dire need of liberalization, it’s still a “solution” that won’t fix the process but will, in essence, destroy the process. It’s also clearly one of a number of attempts by the health freedom movement to get a “foot in the door.” If successful, then similar arguments will be made to expand the “right to try” principle and decrease regulation on investigational agents for larger and larger populations. Although HR 4475 is clearly not explicitly designed to aid quacks who peddle treatments like Gerson therapy or the Gonzalez protocol, it would be a godsend to someone like Burzynski, and it could potentially be a boon to unethical drug and device companies, who would be free to peddle their investigational drugs and devices, both promising and even those that failed, to that most vulnerable of patient populations, patients with no hope of survival. Health freedom, indeed. Apparently “health freedom” means the freedom of pharmaceutical companies to provide treatments whose efficacy is unknown and that are unlikely to make a significant difference in outcome (or even might be toxic) without actually having to learn anything from the exercise.

Posted in: Clinical Trials, Politics and Regulation

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57 thoughts on “The Compassionate Freedom of Choice Act: Ill-advised “right to try” goes federal

  1. Ron Paul, MD, and Rand Paul, MD are two of the primary supporters of this bill. So am I, a board-certified (ABT and ABMT) toxicologist, trained at MD Andersons, who published some of the primary papers on the toxicity and action of the adria, platinum, and bleo-type drugs.

    True, most chemotherapy agents are pretty poisonous. But at least a couple are not. Such agents have completed phase1-2 trials and would qualify under the bill. One off-the.shelf agent (tempol) shows wide-efficacy against a variety of animal cancers. Much of this work was done at the NCI, as are ongoing clinical trials. Likewise, researchers at the FDA (!) have shown efficacy in human breast cancer explants, about as close as you can get to the real thing.

    Tempol agent is essentially non-toxic. In “toxicity” studies, animals treated with the drug live longer than controls. BTW, it may well be that tempol does not work well in advanced cancer. However, with minimal cost and toxicity, don’t terminal cancer patients deserve the right to be treated as they wish?

    BTW, I have patent claims to this drug for other indications, These involve non-lethal diseases, so I would not benefit from this legislation.

    Now watch the ad hominems and straw arguments begin….

    1. David Gorski says:

      Ron Paul, MD, and Rand Paul, MD are two of the primary supporters of this bill. So am I, a board-certified (ABT and ABMT) toxicologist, trained at MD Andersons, who published some of the primary papers on the toxicity and action of the adria, platinum, and bleo-type drugs.

      Appeals to authority do not impress, particularly when they are appeals to one’s own authority.

      Tempol agent is essentially non-toxic. In “toxicity” studies, animals treated with the drug live longer than controls.

      Citation needed.

      However, with minimal cost and toxicity, don’t terminal cancer patients deserve the right to be treated as they wish?

      Unless Tempol is a truly amazing drug whose efficacy is so great that it can be demonstrated without a control group (e.g., Gleevec), a clinical trial would be needed to demonstrate efficacy. Has Tempol undergone clinical trials? What were the results?

      BTW, I have patent claims to this drug for other indications, These involve non-lethal diseases, so I would not benefit from this legislation.

      Yes, fibrocystic breast condition (we tend not to call it “fibrocystic disease” any more because it’s not a disease) is not a lethal condition.

      1. Sawyer says:

        “Appeals to authority do not impress”

        I don’t accept the premise that they are even authority figures to begin with. I have seen zero evidence that when science and medical evidence contradict political ideology, either of the Pauls will go with the science rather than their beliefs. Didn’t Ronny make some idiotic comments about HPV vaccines in the past few years? I don’t know if he’s ever even bothered to make it clear that banning thalidomide was a good idea, and considering he’s an obstetrician, I think that would be theexperimentum crucis in determining whether his medical credentials are worthy of respect or completely useless.

        Whoops, I’m talking about people’s actions and irrational beliefs that have an huge impact on the real world. Shame on me for resorting to these horrible strawman arguments.

        1. Sawyer says:

          Why do I try to italacize Latin phrases? It never work out for me. Sic semper tyrannis to this site for not letting me preview my posts!

      2. Peter H Proctor, PhD MD says:

        Not just fibrocystic “condition”. Also for other things, pending. One I can mention is perimenstrual syndrome. For the ladies. Anyway, nothing potentially lethal. So this legislation is not relevant.

        I have given extensive references on the vitamin-c thread and see no need to repeat. E.g. Wilcox’s review (2010) notes the seeming lack of toxicity. From Georgetown. Search tempol on pubmed for further education. There are several reviews. Also search fda and tempol. They have an active research program.

        Again, it is wrong to assume that all anticancer agents are poisons. The ones which are not should be treated differerently.

      3. CommonSenseBoulder says:

        re: “Appeals to authority do not impress, particularly when they are appeals to one’s own authority.”

        I agree, the problem is that you fail to consistently apply that concept, your whole argument is based around “appeals to authority”.

        There are many skeptical libertarians, many of us likely agree with any critique you would have of junk alternative medicine, and think many of them deserve to be in jail for fraud. Unlike you however we take that skepticism further to be skeptical of anyone who attempts to legally anoint themselves or others the “chosen” “authorities” who get to have final control over all the rest of us. There seems to be an incredibly naive wish on your part that those “authorities” will be infallible, or at least that they will agree with you and implicitly by proxy will impose an “authority” you agree with on others.

        The widespread legal approval and even government funding of quack approaches should have been evidence to counter your the theory that government is an appropriate “authority” to trust to control medical decisions. Unfortunately true believers seem to be unwilling to skeptically examine their worldview no matter how much evidence they see of its flaws.

        Nobel laureate economists have won prizes for things like public choice theory and regulatory capture theory which explain how various forms of government failure are to be *expected*, they aren’t aberrations. Yet just as alternative medical practitioners don’t tend to wish to learn about real science, you don’t seem to wish to learn to understand the real world of government. Wishful thinking based on emotionally appealing sound bites is much easier than thinking, whether in the realm of medicine or the study of the functioning of government. There are alternative approaches to helping protect the public, but just like scientific medicine they require more study and thought than the simplistic “feel good” views those like you push who rely implicitly on an anti-intellectual view of government.

        Rather than granting people the freedom to do what they wish with their own bodies (as pro-choice thinking should consistently advocate), you wish an “authority” to be able to take away that freedom. You article contains the phrase: “to grant the ‘right’ of patients” where your use of quotes around “right” seems to indicate a disparagement of the idea that people have a right to do what they wish with their own bodies, presumably thinking that it is “authorities” who should have the final say.

      4. CommonSenseBoulder says:

        PS, as I suggested on a prior page, I’d suggest considering what laws you would wish to see exist if the alternative medicine crowd got control of the FDA and started approving quack treatments and disapproving scientific ones. I suspect you would wish to be able to see scientific based practitioners not bound by an unscientific FDA anointed as an “authority”. Rational design of government policies should take into account the possibility of those who disagree with your views getting control.

        I should note that I referred to nobel laureate economists regarding the work they won their prizes for merely to establish the credibility of their work as something to examine. It wasn’t intended to be an “argument by authority” in the sense of claiming their views are apriori the final word on the topics. Their views could be overturned, but the first step is understanding them, which most in the public haven’t bothered doing, they merely implicitly ignore their ideas (likely knowing nothing about them, just like quacks ignore scientific approaches they know little about).

        Most of the public just blindly believes in the positive therapeutic effect of a government treatment for a problem. Just as many who fall for alternative medicine don’t realize the gaps they have in their understanding of science, many who propose government approaches to problems don’t realize the gaps in their understanding of things like organizational behavior and economics of government failure, and of free market alternatives. Many who understand little about alternative ideas and the details of free market approaches mock suggestions of private alternatives in a juvenile anti-intellectual fashion to dismiss them out of hand without due consideration of the possibility that there may be more evidence and logic supporting them than they are aware of. They fail to understand that there may be more arguments against the government approaches than they are aware of.

    2. MadisonMD says:

      Likewise, researchers at the FDA (!) have shown efficacy in human breast cancer explants, about as close as you can get to the real thing.

      I call BS. The FDA doesn’t perform research, they regulate. See Q2 here. This is why I suppose Proctor will prevaricate when asked to provide citation backing up the claim. It is a pattern so I won’t bother asking.

  2. Windriven says:

    I have a hard time justifying federal restrictions on what treatments adults should be allowed to pursue – even if those treatments are as clearly bogus as Laetrile or neoplastons. Besides, a few nitwits getting caught in the fan blades of woo may well serve an important memetic role for the broader population.

    This is not as flippant as it sounds. Claims of agency bring responsibilities for its appropriate exercise. Laws that protect nitwits from themselves are in a sense counterproductive because those laws are never perfect but their mere existence gives a false sense of security and an excuse not to do one’s own due diligence.

    1. David Gorski says:

      Do you have a problem with quacks saying that things like Laetrile or antineoplastons can cure cancer? Because patients wouldn’t be interested in trying either of these bogus therapies if there weren’t quacks out there selling them by making such claims.

      1. Windriven says:

        “Do you have a problem with quacks saying that things like Laetrile or antineoplastons can cure cancer? Because patients wouldn’t be interested in trying either of these bogus therapies if there weren’t quacks out there selling them by making such claims.”

        I do have a problem with quacks saying that antineoplastons cures cancer. I am less troubled by claims of belief.

        The statement: “Laetrile cures cancer” is clearly fraudulent.

        The statement: “there is no robust clinical evidence that ascorbate is useful in treating cancer but I believe that it may be” is not.

        I disagree that it follows that patients wouldn’t be interested. Some people are naturally drawn to the naturalistic fantasy fallacy, some have exhausted the resources of medicine. Their motivations aren’t particularly important to me so long as it is clear that there is no compelling scientific evidence.

        1. David Gorski says:

          The statement: “Laetrile cures cancer” is clearly fraudulent.

          The statement: “there is no robust clinical evidence that ascorbate is useful in treating cancer but I believe that it may be” is not.

          If it’s coupled with a sales pitch for vitamin C for cancer or if it’s said by someone offering vitamin C for cancer, I would consider the latter statement fraudulent as well.

      2. Peter H Proctor, PhD MD says:

        We are in agreement here. But under the proposed law, such seems limited. Anyway, “If just saves one fool”. Can be used to justify anything.

        With commercial speech the significant government interest is preventing economic damage and drug toxicity. As I note, there are agents with minimal toxicity. As for economic damage, a money-back guarantee solves the problem. Per court rulings, any limitations must be to the most limited extent necessary.

    2. Missmolly says:

      Wow, Windriven, I usually love your posts but this really makes me sad.
      You and I are amazingly lucky that we have been educated enough in critical literacy that we can understand that the ‘studies’ these charlatans quote aren’t good evidence. To people who haven’t studied how to read studies, ie most people, they all look pretty convincing. It is not easy for most people to figure out what is real and what is just marketing, wishful thinking and ‘woo’.
      Then add a terminal illness into the mix, and critical literacy flies out the window. These people are desperate, in shock, and often not processing particularly clearly. They need protection from the cynical mfs who play on their emotions and would encourage them to mortgage their home in order to afford bogus/untried/potentially catastrophically toxic therapies.
      I am a paediatric oncologist and palliative care physician in Melbourne Australia, and our health policies thankfully remain fairly conservative and evidence based compared with what I’ve read here regarding US policy.
      My patients and their parents aren’t ‘nitwits’ – they’re trying to comprehend an impossibly awful situation, trying to maintain hope in whatever way they can, and desperately vulnerable. They don’t deserve to be fodder for unethical alt med pedlars, or sober ‘lessons’ for other sick kids and their families. They need protection under the law because in their current state, they can’t protect themselves.
      Guess I don’t consider myself a libertarian :)

      1. Windriven says:

        @Missmolly

        You make several very good points. I would hasten to point out that I specifically cited adults (intending to exclude minors) and I specifically decried fraudulent claims – though I will admit that where one draws the line of intent to defraud is subjective.

        I do have a libertarian impulse, though I have moved pretty far from the doctrinaire libertarianism of my youth. I continue to struggle with issues of agency in the face of a political system that, though generally benign, favors sometimes illusory security over freedom*. And I do worry that a state that arrogates choices to itself that should be made by individuals, dumbs down its electorate and makes it less able or inclined to think for itself.

        But again, your points are well made and give me cause to rethink this issue.

        *Except their own. In the US, lawmakers often carve exemptions for themselves in everything from labor law to retirement benefits.

        1. Andrey Pavlov says:

          <blockquote.though I will admit that where one draws the line of intent to defraud is subjective.

          Agreed. And the only (or at least very, very few) points on which you and I (and perhaps others) may quibble. And, IMHO, a fair point for intelligent and intellectually honest folk to quibble about, for there can never be a fixed and objective conclusion on such matters.

        2. Missmolly says:

          Sorry, missed your mention of ‘adults’ (my own bias in action!). And I completely agree that there’s a substantial risk of disempowering people by legislating to make it easy for them to avoid critical thought. I think we should actively prioritise educating people (ideally from primary school) in how to critically assess the information they’re presented with. Then we can feel confident that they at least have the tools to make good decisions- even if they continue to make retarded ones against all reason!
          I suspect we’d all agree, though, that if we’re going to allow every-flavour practitioners to encourage that people try *insert DrOz crap of the moment here* to ‘ameliorate’ cancer, we ought at least to insist that they gather data about the effects of said intervention? Then at least it’s not totally pointless.
          Also, please give me a firm face-punching when I sound all ‘omg, won’t somebody PLEASE think of the CHILDREN?!!’ I hate that!

          1. Windriven says:

            “I suspect we’d all agree, though, that if we’re going to allow every-flavour practitioners to encourage that people try…”

            I suspect you are right.

          2. Andrey Pavlov says:

            And I completely agree that there’s a substantial risk of disempowering people by legislating to make it easy for them to avoid critical thought. I think we should actively prioritise educating people (ideally from primary school) in how to critically assess the information they’re presented with.

            Absolutely agreed. In precisely the same way that I would rather my patients actually make lifestyle changes and lose weight to control hypertension and diabetes. But in some cases, we need to provide drugs to control these things in the meantime, to prevent irreversible long term damage while they are achieving those goals (and/or until they actually motivate to doing so; it is not easy and I speak from firsthand experience and now have an enlarged right atrium with an atrial ectopic focus that leads to paroxysmal sustained SVT at the ripe age of 31).

            It is an ever changing balancing act with no clear cut right answer. But I also think we should take into account the fact that even with proper critical thinking and analysis skillsets, it is simply impossible to do the legwork on all things at all times. As I commented elsewhere here, I am indeed smart enough to do it for car safety standards. But I would much rather have legislation that mandates minimum standards such that I don’t have to try and figure out if the car I am about to buy brand new is a death trap or not. Furthermore, we should recognize that both because this is how we have (reasonably, IMHO) structured our society and because of common human propensities, people will look at the legal status of something as a proxy measure of its inherent validity. Many people will say that they think homeopathy works not because they can’t critically evaluate the premise behind it, but because it is legal, indirectly endorsed by the FDA, and, most importantly, sold on the shelves at pharmacies. I’ve told the story of my friend’s parents; professional chemists who started using homeopathic treatments for precisely that reason. It was not a lack of ability to critically think or understand, for once they were told in 5 sentences what homeopathy actually is they were incredulous that such a thing would be offered as it is so profoundly absurd.

            Yes, there is a balance and when in doubt I feel we should err on the side of autonomy. But we mustn’t ignore the reality of what a legal status or licensure or ability to sell in pharmacies actually implies to the average consumer, critical thinking or not.

  3. David Gorski says:

    Besides, a few nitwits getting caught in the fan blades of woo may well serve an important memetic role for the broader population.

    Oh, and when has a “nitwit getting caught in the fan blades of woo” ever served an “important memetic role for that broader population”? Quite frankly, such incidents rarely register and are quickly forgotten on the uncommon occasions when they do.

    1. Windriven says:

      “Quite frankly, such incidents rarely register and are quickly forgotten on the uncommon occasions when they do.”

      Often they don’t, I suppose. You can lead a horse to water but you can’t stop it from drowning in it.

  4. mho says:

    Sawyer, just an FYI,–It doesn’t matter a whit for this discussion.

    Rand Paul is an ophthalmologist who’s board certification has lapsed.

    1. Sawyer says:

      Ophthalmologist? That just means he can see clearer than anyone else how to fix modern medicine. Because he’s an eye doctor.

      Checkmate Dr. Gorski!

  5. Peter H Proctor, PhD MD says:

    Hell, we even let the average person vote. Why not let them chose their treatment, or not. True, as with voting, some will screw up.

    Otherwise treatments get chosen by some sort of central committee. We all know how that tends to turn out.

    1. Egstra says:

      “Why not let them chose their treatment, or not. True, as with voting, some will screw up.”

      I have no problems with that. I just have problems with false advertising.

      1. MadisonMD says:

        @Egstra

        I just have problems with false advertising.

        Like this, for example?

        1. Windriven says:

          Holy crap! Did you see what that stuff costs???

  6. Sean Duggan says:

    I was recently reading Mary Roach’s Bonk and I’ll admit that it put a lot of this “right to try” stuff in perspective. There was approximately a decade of people doing xenotransplants of baboon testicles into humans because the theory sounded plausible at the time. And, of course, virility is such a high stakes game (I do not exaggerate when I say that, for many, it trumps life and death decisions, as can be seen by all of the people taking nitrates who insisted on also getting their Viagra prescription filled), that there were plenty of people who really wanted to believe. These were doctors who fully believed in their product and thought that they’d found evidence to support it, but we nonetheless look back on what they did as surgical butchery that had only negative effects.

  7. Peter H Proctor says:

    Madisonmd.. Once again, you confuse the fact you never heard of something with how it is. Google dickey, mitotempol, and fda. The first link is to a recent paper on tempol and breast cancer from the fda. Would give the link, but this device does not do cut and paste well.

    In fact, the fda does have an inhouse research program. One purpose is to research agents like tempol that fall between the regulatory cracks. Often, this because lack of patent protection dissuades corporate investment. The least they could do.

    1. Peter H Proctor says:

      Jennifer Dickey*, et al “Mito-Tempol and Dexrazoxane Exhibit Cardioprotective and Chemotherapeutic Effects through Specific Protein Oxidation and Autophagy in a Syngeneic Breast Tumor Preclinical Model” http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0070575

      *Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, United States of America

    2. Windriven says:

      While technically correct that FDA does research, its portfolio is constrained to the conformational and supplementary rather than the innovative.

      “FDA scientists conduct laboratory, clinical and statistical research to proactively address knowledge gaps created by advances in drug development and healthcare technologies, or to address safety questions that arise during post-market drug monitoring. Known as regulatory science, this research utilizes cutting-edge analytical tools and techniques to answer questions that apply directly to the evaluation of product safety, efficacy and quality.”

      http://www.fda.gov/drugs/scienceresearch/default.htm

    3. MadisonMD says:

      Peter, I stand corrected. You are right on this. FDA does do regulatory science research, in this case testing the ability of mito-Tempol to reduce doxorubicin-induced cardiomyopathy, and observing anti-cancer effect of high-dose mito-Tempol given as a single agent in this model.

  8. Peter H Proctor says:

    The big fashion nowdays is “autonomy”. That is patients are the ultimate deciders. This holds even if the decision is to refuse life-saving treatment or stay in dangerous conditions. Recent article on this in nejm with respect to elders.

    If a patient can chose to die by refusing treatment, how can you arbitrarily refuse them a particular treatment because “We know best”. Total abrogation of patient autonomy.

  9. Bob says:

    I have a few thoughts that I’d like to share.

    First, I think all those that have commented are in agreement that protecting vulnerable patients from fraudulent marketing of unapproved therapies is a good thing. However, this article and several of the comments seem to imply that all therapies that have yet to be approved are, by definition, snake oil. This seems rather myopic, and certainly not keeping with good critical analysis. Approval status of a therapy is just that, approval by some regulatory authority. A therapy does not suddenly become effective or safe just because the FDA, EMA, TGA, HC, or other regulator decides it is worthy of commercial sale. Some therapies are approved in one country, but rejected in others. Is the therapy’s effectiveness then geographically contingent? Of course not. Some therapies are released for sale, but later removed from the market. Did the therapy suddenly lose effectiveness or increase toxicity? Of course not.

    A therapy is effective and/or toxic based on it’s function regardless of regulatory status. Regulatory status is simply a governmental mechanism where in a learned intermediary assess the avaiable data on a compound’s safety and effectiveness as it applies to a general or specific population so it may be released for commercial sale with a certain level of assurance that it will perform as stated for the defined use. That’s it.

    This is a risk based decision for the benefit of a population. It is not the establishment of a scientific fact. Scientific data is used in the decision, certainly, but it is ultimately a risk/benefit analysis. (We could also go into the relevence of group data, such as a clinical trial data, to specfic patients and their individual circumstances, but that is a larger discussion.)

    Second, a regulatory decision that a product is safe and effective is only for the stated intended use. However, physcians frequently prescribe medicines off-label. They will see an unmet or underserved need in a patient and proscribe a medicine with an appropriate mechanism of action and reasonable toxicity profile, regardless of their actual approved indications.

    If you have an unapproved therapy that has some mechanistic and safety data behind it and the data supports a likelihood that it may work in a particular patient’s individual circumstances, is this really that different? Certainly, the risks are greater, but we’re not talking apples and oranges. This is the very cornerstone of individualized treatments and personalized medicine. Does the inherent capabilities of a compound match the individual circumstances of the particular patient?

    Finally, I find the implied premise that patients that are terminally ill have somehow become mentally difficient, incapable of rational decision making, and require others to make their choices to protect them from exploitation to be offensive. Unless they have some mental disease or defect, becoming terminally ill does not automatically remove their mental faculties, nor their right to make decisions about their own treatment. Are they more emotionally charged? Probably. Do they have different criteria for weighing their risk/benefit decisions? Absolutely. However, neither of these remove the patient’s right to make choices on their own health care.

    1. Harriet Hall says:

      “all therapies that have yet to be approved are, by definition, snake oil.”

      We don’t assume that. Nor do we assume that government regulation equals safety and efficacy. But we do study the history of medicine, and it has taught us a valuable lesson. We can predict that few of the therapies that have yet to be approved will prove safe and effective when properly tested. Plausibility and testimonials are not enough; proper controlled studies are essential. Patients are statistically more likely to be harmed and waste their time and money than to benefit. They are welcome to take their chances based on guesswork, but it doesn’t seem fair for those guesses to be based on misleading claims by marketers. The same goes for the terminally ill: they are at their most vulnerable, and are more likely to be persuaded by false and incomplete information.

      1. CommonSenseBoulder says:

        re: “But we do study the history of medicine, and it has taught us a valuable lesson. ”

        This debate is not primarily about medicine in detail, it is about policy. When dealing with policy issues it is appropriate also to understand the lessons of scholarly work regarding government failure and the lessons of nobel laureate economists (among others) who have studied it. It is useful to learn the lessons of history that you folks have observed regarding the trend of quacks gaining political influence and legislative endorsement of their approaches via licensing and a seemingly inappropriate level of funding. I addressed what those lessons suggest in posts earlier on this page.

        Unfortunately too often some professionals like doctors are appropriately concerned about understanding scholarly work in their own field, but discount what they might learn from understanding scholarly work in other fields. They leap to superficially plausible intuitive seeming conclusions while neglecting to consider that sometimes in depth consideration leads to conclusions which are contrary to the simplistic conclusions most people draw who don’t have enough background knowledge about a topic. Doctors skeptical about popular “wisdom” regarding alternative medicine often aren’t skeptical enough about popular “wisdom” regarding political approaches to addressing problems.

    2. Andrey Pavlov says:

      As Dr. Hall alluded, I don’t think anyone here is saying that regulatory approval is what is needed. Merely scientific evidence. The reality is that without any further information it is indeed a reasonable first approximation to say that all untested therapies are snake oil. True, many are not. But they comprise such a small portion of the totality out there, that it becomes a rounding error.

      Off label use is informed by scientific evidence. We would similarly be against off-label use that has no rational basis for implementation. Giving montelukast off-label for COPD is an entirely different beast than giving it off-label for depression. And when you have an untested therapy, it is not much more likely to work for any random given indication than that.

      And no, terminally ill patients are not mentally deficient they are more vulnerable. It is easier to convince someone to spend a fortune on rank quackery if they are dying than if they have the time and means to fact check carefully, with no pressing need for anything you may be promising them. That is a very important distinction, one which Dr. Gorski made.

  10. Peter H Proctor says:

    The antiexcitoxin Riluzole is a good example of a relatively non-toxic potential anticancer agent.. By chance, it has regulatory approval for als. So docs can use it off-label. But what if this were not the case?

    In the brain, the action of the same glutaminergic receptors is antagonized by tempol. So riluzole and tempol may work on the same redox-dependent systems in cancer, tho tempol is likely broader -acting because it limits oxidative stress from other sources. Point is, where do you draw the line?

    1. Calli Arcale says:

      Good question. And it makes me wonder: how do you feel about antineoplastons and Dr Burzynski? His ANP treatment has been classed as an investigational new drug for decades, since he keeps filing for new clinical trials but almost never gets around to publishing anything (and what he does publish is pretty poor quality). It’s almost as if he doesn’t *want* to prove whether the stuff works or not, which suggests to me that it doesn’t and he knows it. He just wants to keep selling it. Wouldn’t legislation like this enable him? Right now, the FDA has put a hold on all trials involving ANPs because there have been deaths. Wouldn’t a law like this enable patients to get around that, because they wouldn’t be in a clinical trial at all? And if so, do you think that’s a good thing?

      You keep citing this drug that you say has few side effects and could be a godsend, but what about the drugs that have many side effects and might not do any good whatsoever? If you open it up to good, well-informed doctors suggesting compassionate use of unapproved medications that just haven’t had time to prove themselves yet, I fear you also open it up to charlatans and to the incompetent. Is it worth that risk? Will we save more lives or cost more lives?

      1. Peter H Proctor says:

        Physicians are not exactly children, who can be easily fooled, most anyway. Historically, docs made the therapeutic decision.

        In contrast, the fda has few clinically-trained individuals and a predominately regulatory-oriented ethos. That is, they may not know the science, but they know the law. Who would you prefer makes therapeutic decision?

        Btw, the case of riluzole makes me think this law would not change things much. Even tho riluzole has apparent anticancer activity, low toxicity, and can be used off-label, there seems to be no great rush to use it.

        1. Andrey Pavlov says:

          Physicians are not exactly children, who can be easily fooled, most anyway.

          Last I checked, physicians are people. And people of all ages can rather easily be fooled, particularly when they fool themselves. You should read/watch Richard Feynman more.

          1. PeterH Proctor says:

            “The race may not always go to the swift, nor the contest to the strong. But that’s the way to bet.”

            Point is, the opinion of a physician may not always be right, but is more likely to be right than some non-clinically-trained type. There is a reason they pay us docs the big bucks.

            1. MadisonMD says:

              Why did doctors prescribe DES and thalidomide to pregnant women? They should know the science better than the FDA. After all they are the ones making the big bucks.

              1. Peter H Proctor,PhD,MD says:

                Ancient history. These days, the principle is never to use a new drug on a pregnant female or a woman of child-bearing age not on contraception except for a very compelling reason.

                DES was thought to keep the fetus alive. This use ceased over 40 years ago. http://www.cancer.gov/cancertopics/factsheet/Risk/DES#r1

                Thalidomide, because 50 years ago nobody checked drug toxicity in multiple pregnant female animal models. Long since corrected, BTW. And thalidomide is still in clinical use, e.g., for leprosy and myeloma.

                Retinoids are currently used to treat cystic acne. But only after multiple steps to confirm that the patient is not pregnant.

                None of these are relevant to the law at issue….

              2. MadisonMD says:

                Your point was that doctors know more than regulators.
                My point was they don’t, and I gave you specific examples. In fact a FDA regulator kept US physicians from using thalidomide in pregnant women.

                Your other points are irrelevant. It is not relevant that thalidomide has other medical utility. it is not relevant that doctors and regulators have become more aware of the risks of drugs during pregnancy. The point is not particular to thalidomide nor to pregnancy. It is an example that refutes your assertion that doctors should be able to do whatever they want because doctors know more than regulators.

                And yes it is history*. So what? It is a history that refutes your assertion. If you ignore history you are condemned to repeat it.

                ——
                *Incredible irony of your statement: “it’s ancient history.” Most of your braggadacio in posts here regarding expertise, scientific prowess, and time at an actual university is derived from your brief career in academic science in the late ’60′s and 70′s. Isn’t that about 50 years ago?

  11. thor says:

    I found my new calling. Invent a drug but keep it in clinical trials. Never intend to market it. Patient target are the critically ill. This way I do not have to do any informed consent, cannot be sued and never have to publish my results. Insurance will not cover it so it will be cash only.

    1. Peter H Proctor, PhD,MD says:

      As I note above, physicians don’t use riluzole for cancer, even though it meets most of the criteria covered under the law, with the additional advantage that it is FDA-approved for ALS and thus can be used “off-label”.

      For fun, on another doctor chat group, I brought up the subject of Riluzole for treatment of ca. As expected, I was soundly put down in the very kind of terms you see here. Ironic, since this is Dr Gorski’s drug. One clinical oncologist even suggested that you could be sued if it made a patient unduly sedated.

      Point being, this law will not change treatment much.

      However, cancer treatment is moving toward individualized therapy based upon genotyping the patient and the tumor. So, in an extension of what is being done already, treatment will involve multiple agents, some effective only against tumors which bear a particular gene lesion.

      This does not lend itself to double-blind placebo-controlled trials. So what the law may really do is facilitate access to such targeted drugs.

      1. MadisonMD says:

        For fun, on another doctor chat group, I brought up the subject of Riluzole for treatment of ca. As expected, I was soundly put down in the very kind of terms you see here. Ironic, since this is Dr Gorski’s drug.

        David may be investigating the possible utility of this drug in his laboratory. I highly doubt he is using this off-label to treat his patients. You don’t understand the difference?

  12. PeterH Proctor, PhD, MD says:

    Thalidomide and DES were primarily issues of toxicity and occurred before many here were even born. I was a PhD pharmacologist/toxicologist before I became an MD and thus similar to most doctoral-level folks in the FDA. Except that many of them are PharmD’s. Medical training was a real eye-opener.

    Due to such criticisms, the FDA now uses physician panels specifically-because it lacks medical expertise. This helps some. BTW, I have been on ad hoc FDA panels.

    Was at a talk given by the FDA-director at the time of thalidomide. He said the lady concerned was more or less incompetent and just lucked out when her inability to get her work done stalled thalidomide enough that the birth defects started to appear. We have been plagued by the results ever since. Again, an issue of toxicity, fixed by requiring multiple animal models.

    Last week I was in Washington. Went by the Smithsonian to visit our gadget, the original transistor-like organic electronic device ( http://smithsonianchips.si.edu/proctor ) and why I am semifamous in melanoma research. Was given a guided tour by the curator of the electrical collection. Our device is stored in a relatively small climate-controlled room a couple of steps from Morses’ first telegraph sender and a static generator attributed to Benjamin Franklin.

    1. Sawyer says:

      Dr. Proctor, I bet a lot of people here would be much more interested in your work if you weren’t so incredibly arrogant about it. Or if you at least made an effort to avoid a Ron Burgundy level non-sequitur. “I’m kind of a big deal in melanoma research … people know me” does not have anything to do with thalidomide.

      And if you want to spread hearsay about Frances Kelsey, you could at least have the courtesy to use her name instead of “that lady”.

      1. David Gorski says:

        Yeah, Proctor’s bit about melanoma research makes me want to ask some people I know who are in melanoma research now, one of whom is a collaborator of mine, whether or not they’ve ever heard of him.

    2. MadisonMD says:

      David will have great trouble identifying a melanoma specialist who has ever heard of Proctor.

      Proctor’s arrogant assertion is that Kelsey was incompetent. Kelsey has a President’s Award by Kennedy, is in the National Women’s Hall of Fame, and the FDA annually presents an award in her name.

      Proctor, on the other hand, doesn’t even have a Wikipedia page despite several years of writing one himself with the help of his sockpuppet army. He fancies himself a genius who made seminal contributions to the world and was robbed of a Nobel prize. But in actuality, he’s just a very very arrogant fellow who purveys quack hair loss remedies to make a fast buck off the gullible.

      Proctor is a legend in his own mind… and nowhere else.

  13. Peter H Proctor, PD,MD says:

    You can’t really complain if I respond to ad hominem attacks by pointing out my credentials.

    As for melanoma– while at MD Anderson, we solved the electronic structure of melanin. The experimental apparatus is now in the Smithsonian, as above. After lots of vetting.

    Re: melanin:

    “Aside from camouflage, its other roles can be brought together by a unifying hypothesis as first proposed by Proctor and McGinness nearly 20 years ago. ” Hill HZ. “The function of melanin or six blind people examine an elephant.” Bioessays. 1992 Jan;14(1):49-56. http://www.ncbi.nlm.nih.gov/pubmed/1546980

    Likewise: “Also in 1974 came the first experimental demonstration of an operating molecular electronic device that functions along the lines of the biopolymer conduction ideas of Szent-Gyorgi.” in: Hush, NS (2003). “An overview of the first half-century of molecular electronics”. Annals of the New York Academy of Sciences 1006: 1– 20.

    As for Kelsey, I only repeat what seems to be common knowledge and is attested to by the FDA director at the time. The rest was bureaucratic cover.

    Re, the proposed legislation: It is pure magical behavior to assign special insight to the FDA apparat, any more than to any other governmental institution. They do have some very competent people.

    However, often enough, best to think of the postal service and the VA. Plus, nobody gets in trouble for the morbidity and mortality resulting from not approving a drug.

  14. Mike Goodman says:

    Am I missing something? There’s no mention of phase I success in the National Bill.

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