Contributor Post Created with Sketch. The Other Drug War

 

Earlier this month, the Food and Drug Administration rejected the application of Biomarin Pharmaceutical to market its drug Kyndrisa™ (drisapersen) for use in the treatment of Duchenne muscular dystrophy. The FDA, as is often the case when it rejects a drug application, listed all sorts of technical reasons why the data presented was not sufficient to establish by respectable scientific means that the drug in question was safe and effective in its intended use. Without question, much evidence from the clinical trials revealed serious complications from the drug’s use, including blood-platelet shortages that were potentially fatal, kidney damage, and severe injection-site reactions. But the no-treatment alternative could prove far worse.

Duchenne is a rare but fatal genetic disorder that attacks only young boys, roughly 1 in 3,500 to 5,000. Typically, it first manifests itself between two and five years of age. With time, it relentlessly weakens the skeletal muscles that control movement in the arms, legs, and trunk. Most of its victims are wheelchair-bound between the ages of seven and 13. By 20, many have died.

The source of the problem is the absence from the cell of the key chemical dystrophin, which is needed to control muscular movement. The proposed treatment is known as “exon-skipping,” which allows the body to produce the needed quantities of dystrophin. At present no drugs are on the market to fix the genetic defect. But other drugs are also under investigation. If the door is closed for drisapersen, it remains ajar for an unnamed drug produced by Sarepta Therapeutics, which will be reviewed by the FDA shortly. But, based on early rumblings from the FDA, it is likely that this drug too will be kept from the marketplace.

As might be expected, the decision by the FDA has left parent groups and their physicians tied up in knots. You can get a sense of their frustration by looking at the desperate petition of a mother whose son has the disease. Tonya Carlone wrote a public letter to the FDA pleading for the drug to be allowed on the market: “This medication has allowed my son, Gavin, to be able to ride a 2 wheel bike, to play on a soccer team, to run and play with his healthy 10 year old peers. Dr. Craig McDonald of UC Davis Medical Center and a Duchenne expert of over 30 years, has stated that he has never seen a boy with Duchenne at the age of 10 have as much function as Gavin.”

All irrelevant, says the FDA. But it’s critical to understand why parents like Ms. Carlone and physicians like Dr. McDonald are right and why the FDA is dead wrong. The FDA thinks the problem lies in the merits of a particular drug when it really lies in its deeply flawed approval process. That process got started in the early 1960s after Thalidomide was taken off the market for causing serious birth defects and deaths among children.

In its rush to judgment after the incident, Congress passed the 1962 Kefauver Harris Amendments, which initiated the modern system of drug review that featured two major reforms. The first changed an FDA rule that was on the books since 1938 that allowed drugs to reach the market if the FDA did not ask to review them within 60 days after they were ready for market. The second required the FDA to review these new drug applications prior to approval not only for safety, but also for effectiveness. Now for a drug to reach market it must be supported by “substantial evidence” which is “evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved.” As the Supreme Court observed in 1973, the FDA’s “strict and demanding standards, barring anecdotal evidence indicating that doctors ‘believe’ in the efficacy of a drug, are amply justified by the legislative history.”

The FDA still treats the 1962 law as a triumphant moment that “revolutionized drug development” because its scientific safeguards ensure “that consumers will not be the victims of unsafe and ineffective medications.” And therein lies the problem. The FDA celebrates the supposed advantages of Kefauver-Harris, but it ignores the major monkey wrench that it has introduced into drug development. Its proclamation looks at only the benefits of the drug-approval process, but wholly ignores its attendant costs by tacitly assuming that the only drugs that the FDA keeps off the market are unsafe and ineffective.

Regrettably, in this, as in all other regulatory endeavors, there are two kinds of error. The FDA is keen to note the bad drugs that are kept off the market. But it downplays the good drugs caught inside its web that are kept off the market. In some cases, there are deadly delays in getting good drugs onto the market. As the period for drug review becomes longer, the cost of getting a drug onto the market rises. Taking into account both the time value of money and out-of-pocket expenditures, that cost has been estimated to be $2.6 billion. That figure, of course, does not include the social losses from drugs that never get through to clinical trials because of the heavy obstacles that the FDA places in the path of their development—nor does it include the number of lives lost or compromised as a result of the FDA’s regulatory hurdles.

To make matters worse, the clinical trial format, which often works well for mainline drugs, like those used to control cholesterol and high-blood pressure, is less effective for drugs aimed to treat certain rare diseases, where too many potential drugs are chasing too few patients. Thus in the Sarepta study, both the treatment and the placebo group each enrolled only 12 patients, which enabled the FDA to challenge the comparability of the two groups, and for both parties to dispute individual patient responses. It doesn’t help that the FDA insists that individual patient and doctor reports do not count as scientific evidence because of their anecdotal nature.

Here too, the FDA errs. Individual variation in drug response is a common feature, and individual patients like Gavin Carlone are well advised to continue using the drug, no matter what the FDA’s overall evaluation of the drug’s features. The two forms of information should always be used in tandem. To be sure, the risk of adverse side effects can never be ignored, but neither can the deadly effects of Duchenne, for which there is no recourse. The FDA’s major blunder in this area is to rely exclusively on the statistical significance of various treatment options, ignoring all evidence from other sources.

Doing so became a true disaster. Under the 1962 law, drug after drug was removed from the market after years of successful use because the FDA decided that well-controlled clinical trials, for all their cost and limitation, were better than the long-term success of various drugs in the marketplace. It is for good reason that children, parents, and physicians are asking a different question from that which the FDA puts to itself: are they better off with the drug than without it? And when there is no alternative remedy, the answer is that they are better off with it.

At this point, the first question has nothing to do with abstract standards of scientific evidence. It has to do with the simple issue of who gets to decide what type of evidence, systematic or anecdotal, is most valid. American law today wrongly vests that power in the FDA on the ground that its expertise is needed on matters of public health. But Duchenne and similar genetic diseases are not communicable, as most public health concerns are. They are individual, not interconnected, tragedies.

It is simply mindboggling that the FDA should extol its naked paternalism in keeping patients from becoming “victims of unsafe and ineffective drugs,” when it is cutting them off from their only chance of salvation. The usual judicial conceit is that FDA regulation just deals with economic matters, as if a child’s fight against a deadly disease is to be treated in the same fashion as a minimum wage or maximum hour law. Both types of regulation are unwise—but, that said, no one should ignore their differential impact, as rich and poor alike are throttled by the FDA.

Fortunately, there are two developments that can help reduce the FDA’s deadly grip on pharmaceutical progress. The first is that it cannot prevent off-label uses of permitted drugs. Under current law, once a drug is approved for any purpose, physicians can prescribe it for any other purpose they please. The FDA is not allowed to regulate the practice of medicine, and thus physicians can put these drugs to use without approval.

Needless to say, by every estimate, off-label uses are common, especially in cancer cases. These uses are not unstructured, as there are many voluntary institutions, such as the National Comprehensive Cancer Network, that collate the clinical experiences that the FDA ignores and make recommendations on which drugs should be used in what sequence and in what combinations to treat various kinds of conditions. The off-label uses commonly set the standard for medical malpractice for physicians in ways that bypass the FDA approval process altogether.

Yet the inability to get that first approval forces desperate people to beg the FDA and drug companies for a compassionate license for experimental use, which often comes too late, even for cancer drugs like Erbitux, which later makes it on the market. Indeed, this off-label process was especially important for thalidomide, for once it was allowed on the market under the brand-name Thalomid to treat leprosy, its effectiveness as a miracle drug for cancer became apparent from its off-label use. Dr. Frances Kelsey of the FDA, who discovered the drug’s harmful side effects on children, should have issued stern warnings on its use in pregnancy. But, in retrospect, the FDA was wrong to ban the drug from the market.

The second major development deals with the ability of drug companies to present truthful information about off-label uses to physicians and patients. The FDA has long vigorously asserted that it is a criminal offense for a drug company to make any statements or distribute any information that tends to promote the use of an approved drug for an off-label use. Its view was that these statements made false representations that the drug had been approved for that purpose. The FDA could not prevent the identical statements from being made in medical journals or by individual physicians, but its ban on truthful company promotion obviously slowed down the adoption of off-label uses. Two recent cases have broken the FDA’s stranglehold on information on off-label uses: one in 2012, dealing with drug promotion by individual sales representatives, and a second in 2015, dealing with a company’s publication of the full record of its futile negotiations with the FDA to get formal approval for a new permitted use for a drug already on the market.

The FDA’s richly deserved defeat on this front is consistent with the general libertarian view that government agencies have ample power to prevent fraud and misbranding, but none to prevent speech that is neither false nor misleading. The current First Amendment law thus breaks down the FDA’s monopoly over information. But it does nothing to break down the FDA’s monopoly over the licensing of new drugs, which are all too often kept in limbo with endless haggling over clinical trials. That situation has to change now.

Congress should strip the FDA of its power to keep individuals from receiving drugs for experimental purposes before they receive FDA approval. If not, the courts should do it on constitutional grounds, holding that the current legal regime is an intolerable interference of personal autonomy. No one would ever let the FDA use its now formidable police powers to force people to take medicines that it thinks appropriate. That same logic should not prevent informed patients, with the aid of their own physicians, from taking medicines that they think offer the best opportunity for their restored health and survival.

© 2016 by the Board of Trustees of Leland Stanford Junior University

There are 21 comments.

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  1. Bryan G. Stephens Thatcher
    Bryan G. StephensJoined in the first year of Ricochet Ricochet Charter Member

    Well said!

    If we want cheaper drugs, the FDA should get out of the way. All around the world, people use drugs we do not have access too. How on Earth is a clinical trial better information than decades of use in real life.

    • #1
    • January 26, 2016, at 12:02 PM PST
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  2. Morituri Te Inactive

    Since it is increasingly accepted by courts and legislatures that people have an unlimited right to be killed by their physicians, why can’t they be allowed to obtain and take any medication they like, if it might help them? As a society, we no longer seem to care if people are intentionally put to death by doctors. Isn’t all this concern about safety and effectiveness a bit quaint?

    • #2
    • January 26, 2016, at 12:59 PM PST
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  3. MarciN Member

    Richard Epstein: Congress should strip the FDA of its power to keep individuals from receiving drugs for experimental purposes before they receive FDA approval. If not, the courts should do it on constitutional grounds, holding that the current legal regime is an intolerable interference of personal autonomy. No one would ever let the FDA use its now formidable police powers to force people to take medicines that it thinks appropriate. That same logic should not prevent informed patients, with the aid of their own physicians, from taking medicines that they think offer the best opportunity for their restored health and survival.

    Agreed.

    Wish you could make this come to pass.

    • #3
    • January 26, 2016, at 1:39 PM PST
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  4. donald todd Inactive

    Back in the day, Great Britain allowed the use of thalidomide by pregnant women. The unborn children were visited with great harm, born with various handicaps.

    I have no idea about Kyndrisa™. I don’t know about the testing regime enforced on that company. I don’t know the results beyond Richard’s statement “much evidence from the clinical trials revealed serious complications from the drug’s use, including blood-platelet shortages that were potentially fatal, kidney damage, and severe injection-site reactions. But the no-treatment alternative could prove far worse.”

    I understood that the prognosis for this is poor without treatment, but might the treatment be even worse? One presumes we’ll find out because someone somewhere will get access to this treatment and use it for all it is worth.

    We keep getting mixed messages on tv about wonder drugs that might do more harm than good, almost to the point where if it doesn’t kill you it may cure you.

    Having an acquaintance go through that, ending up killing himself and leaving a widow and two children, there might be something to be said for caution.

    • #4
    • January 26, 2016, at 1:39 PM PST
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  5. Tom Meyer, Common Citizen Contributor

    Richard Epstein:At this point, the first question has nothing to do with abstract standards of scientific evidence. It has to do with the simple issue of who gets to decide what type of evidence, systematic or anecdotal, is most valid. American law today wrongly vests that power in the FDA on the ground that its expertise is needed on matters of public health. But Duchenne and similar genetic diseases are not communicable, as most public health concerns are. They are individual, not interconnected, tragedies.

    Very well put.

    There’s a valid concern — especially given how much snake-oil is peddled to desperate people — about wanting to give things as far above board as possible in terms of empirical standards.

    But as Epstein says at the end, there are other ways of doing that that don’t have this effect of shutting out people who are informed of the risks from doing what they believe is best for their own health.

    • #5
    • January 26, 2016, at 1:42 PM PST
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  6. James Gawron Thatcher
    James GawronJoined in the first year of Ricochet Ricochet Charter Member

    Richard,

    You have stepped up the level of this debate and asked very fundamental questions pertaining to rights in a free society. For this I applaud you. However, I must try to get myself oriented on this one as this is a very sophisticated situation. That said it doesn’t mean that I won’t be coming down on your side but that I need to take it one step at a time.

    I think the law you are referring to set up what was called phase I, phase II, and phase III testing. Phase III was a massive test taking 5-7 years with upwards of 10,000 participants. Its real purpose was to uncover long-term side effects. Phase II was the traditional sized efficacy test taking 1-3 years with 500-1,000 participants. Phase I was the type of test you are talking about with under 100 participants.

    I wrote before about the totally bizarre situation during the early 80s where drugs were being forced through phase III before they were allowed to be used at all. Phase II testing was completely adequate to establish a drug’s strong efficacy and anyone facing a disease that was much worse than whatever side effects might crop up obviously should be allowed to use it. Needless to say the hard phase III rule was dropped. Hopefully, there is nobody that insanely doctrinaire left around who actually thinks the hard phase III rule was a good idea.

    What you are talking about here is very different. The problem for drugs with only phase I testing completed is no statistical significance of efficacy. Thus the term anecdotal evidence. What I would like to hear is that if we are not going to insist upon hard statistical proof of efficacy before allowing experimental use, do we have a standard by which to judge the phase I situation or are you suggesting that the rights of patients to choose overrides all?

    Regards,

    Jim

    • #6
    • January 26, 2016, at 1:50 PM PST
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  7. Tom Meyer, Common Citizen Contributor

    donald todd:Back in the day, Great Britain allowed the use of thalidomide by pregnant women. The unborn children were visited with great harm, born with various handicaps…

    Having an acquaintance go through that, ending up killing himself and leaving a widow and two children, there might be something to be said for caution.

    Yes, there is a case for caution. The question is whether we are being overly cautious, especially when it comes to drugs for conditions in such small numbers that it’s extremely difficult to do the kind of studies the FDA requires for drugs that would be made available broadly.

    • #7
    • January 26, 2016, at 1:54 PM PST
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  8. James Gawron Thatcher
    James GawronJoined in the first year of Ricochet Ricochet Charter Member

    Tom Meyer, Ed.:

    donald todd:Back in the day, Great Britain allowed the use of thalidomide by pregnant women. The unborn children were visited with great harm, born with various handicaps…

    Having an acquaintance go through that, ending up killing himself and leaving a widow and two children, there might be something to be said for caution.

    Yes, there is a case for caution. The question is whether we are being overly cautious, especially when it comes to drugs for conditions in such small numbers that it’s extremely difficult to do the kind of studies the FDA requires for drugs that would be made available broadly.

    Tom,

    So one of the aspects of this kind of argument is that if the total number of sufferers of the disease is low it makes it almost impossible to do the statistically significant studies necessary for current FDA experimental approval.

    Again, I’ll ask you instead of Richard. Do you have a standard in mind, non-statistical, for these situations? How would you properly document an anecdotal request? Obviously, the only concern would be to protect people from fraudulent abusers.

    Regards,

    Jim

    • #8
    • January 26, 2016, at 2:06 PM PST
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  9. Timothy Patton Inactive

    donald todd:Back in the day, Great Britain allowed the use of thalidomide by pregnant women. The unborn children were visited with great harm, born with various handicaps.

    Milton Friedman spoke directly to the issue of thalidomide and the justification for the FDA. Interviewed no less by our very own Peter Robinson.

    • #9
    • January 26, 2016, at 2:20 PM PST
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  10. Tom Meyer, Common Citizen Contributor

    James Gawron:So one of the aspects of this kind of argument is that if the total number of sufferers of the disease is low it makes it almost impossible to do the statistically significant studies necessary for current FDA experimental approval.

    Exactly. If there’s only a handful of people who have the disease, it’s really hard to do a valid trial. The numbers are just too small.

    Again, I’ll ask you instead of Richard. Do you have a standard in mind, non-statistical, for these situations? How would you properly document an anecdotal request? Obviously, the only concern would be to protect people from fraudulent abusers.

    I’d rather one of our doctors answer but I think part of it would be to have very strong disclosure agreements. Also, you could still have reasonably strong regulations regarding who is able to do such trials. This may be a case where it makes more sense to focus on the practitioners than on the product.

    • #10
    • January 26, 2016, at 2:42 PM PST
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  11. George Savage Contributor

    Richard Epstein: Congress should strip the FDA of its power to keep individuals from receiving drugs for experimental purposes before they receive FDA approval. If not, the courts should do it on constitutional grounds, holding that the current legal regime is an intolerable interference of personal autonomy.

    Amen.

    Clinical trials assess the probability of benefit versus risk for a population. However, in the end, we treat individual patients–family, friends, co-workers–not populations.

    • #11
    • January 26, 2016, at 3:02 PM PST
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  12. George Savage Contributor

    Interesting aside: I gained admission to medical school, way back in 1981, on the basis of arguing strenuously against the Kefauver Harris amendment to the Food, Drug and Cosmetics Act.

    The professor interviewing me was waxing rhapsodic about the many benefits of the FDA and I, of course, held to a less-well-informed version of the Epstein position. I recall thinking that I was about to throw away my chance of admission to this particular school, but could not resist joining in the argument. We had a thoroughly enjoyable conversation.

    Sadly, the Kefauver Harris amendment remains with us to this day.

    • #12
    • January 26, 2016, at 3:08 PM PST
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  13. MarciN Member

    Couldn’t there be a phased-in process? Such that people who wanted to try it could be given it, perhaps as part of a clinical trial?

    If a person is out of options and is looking for hope without a guarantee, shouldn’t that person, as long as the risks are fully disclosed, be allowed to assume the risk?

    So the patient is told “This drug has not been approved by the FDA.”

    People are taking experimental drugs all the time through clinical trials, right?

    I think Professor Epstein is right here.

    • #13
    • January 26, 2016, at 4:48 PM PST
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  14. MJBubba Inactive

    The European model is sometimes held up as a better way. But didn’t France just halt a drug test after some otherwise healthy test volunteers died suddenly?

    There is a reason for bureaucratic cautions when considering new wonder drugs.

    • #14
    • January 26, 2016, at 5:22 PM PST
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  15. James Gawron Thatcher
    James GawronJoined in the first year of Ricochet Ricochet Charter Member

    George Savage:

    Richard Epstein: Congress should strip the FDA of its power to keep individuals from receiving drugs for experimental purposes before they receive FDA approval. If not, the courts should do it on constitutional grounds, holding that the current legal regime is an intolerable interference of personal autonomy.

    Amen.

    Clinical trials assess the probability of benefit versus risk for a population. However, in the end, we treat individual patients–family, friends, co-workers–not populations.

    George,

    I just got back to Ricochet. How would you write such legislation? Would you leave any controls at all? I agree that there are fundamental rights involved and I am tired of letting the left win the argument every time they can make an emotional appeal concerning health care. Still I’d like get your opinion. When it came to Obama Care I asked every physician I knew and shut up and let them talk. Nothing could have been more clear. I couldn’t find one, many who had voted for Obama and some twice, who had the first good thing to say about the ACA.

    You tell me.

    Regards,

    Jim

    • #15
    • January 26, 2016, at 7:00 PM PST
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  16. PsychLynne Inactive

    James Gawron:What you are talking about here is very different. The problem for drugs with only phase I testing completed is no statistical significance of efficacy. Thus the term anecdotal evidence. What I would like to hear is that if we are not going to insist upon hard statistical proof of efficacy before allowing experimental use, do we have a standard by which to judge the phase I situation…

    Phase I trials are powered to look at toxicity only with no promise of cure of improvement. However, if a patient responds, I support the continued use of the drug for that patient. And rare diseases always post a statistical challenge.

    George Savage:

    Clinical trials assess the probability of benefit versus risk for a population. However, in the end, we treat individual patients–family, friends, co-workers–not populations

    This is really the key. Population statistics do an excellent job describing populations, however, we don’t know where the patient in front of falls in that population. Precision medicine is causing the FDA’s head to spin because (no surprisingly) they don’t know how to respond to that type of individualized treatment.

    MarciN:Couldn’t there be a phased-in process? Such that people who wanted to try it could be given it, perhaps as part of a clinical trial

    The current process is phased in with strict guidance about what types of evidence each level provides.

    • #16
    • January 27, 2016, at 3:36 AM PST
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  17. James Gawron Thatcher
    James GawronJoined in the first year of Ricochet Ricochet Charter Member

    PsychLynne: The current process is phased in with strict guidance about what types of evidence each level provides.

    PsyL,

    This is very interesting. Could you describe the “strict guidance” for us.

    Regards,

    Jim

    • #17
    • January 27, 2016, at 7:03 AM PST
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  18. George Savage Contributor

    James Gawron:George,

    I just got back to Ricochet. How would you write such legislation? Would you leave any controls at all? I agree that there are fundamental rights involved and I am tired of letting the left win the argument every time they can make an emotional appeal concerning health care. Still I’d like get your opinion. When it came to Obama Care I asked every physician I knew and shut up and let them talk. Nothing could have been more clear. I couldn’t find one, many who had voted for Obama and some twice, who had the first good thing to say about the ACA.

    You tell me.

    Regards,

    Jim

    Jim, welcome back!

    I would prefer to repeal the 1962 amendments in their entirety. Ideally, FDA would require drug makers to publish a drug’s safety profile, would stand ready to intervene in the event of calamitous problems, but would otherwise leave efficacy determination to the market.

    I recognize that this is extremely unlikely to happen, so at a minimum I favor Peter Huber’s proposed reforms aimed at bringing the definition of “substantial evidence” into the 21st century. For instance, we now know that clinically identical cancers often differ from one another on a genetic level. What is needed is an updated definition of “efficacy” to mean a demonstrated effect against a marker or pathway, rather than a standalone clinical outcome.

    Consider that tumors have redundant pathways for survival (by definition, if a cell depends upon a single pathway for survival, it is unlikely to survive very long). Anti-cancer therapy relies on exploiting differences between healthy cells we need to preserve in order to target and kill only abnormal cells. However, genetic differences mean that different tumors need to be addressed using a variety of approaches tailored for that individual. Rather than a single blockbuster “cure,” we are more likely to employ multi-drug customized cocktails.

    Precision medicine requires the FDA to approve drugs based upon adequate safety and performance against the molecular target. Leave clinical outcomes to oncologists and other physicians who will experiment with the right mix for the right patient.

    This is how the war against HIV was largely won — a death sentence when I entered training is now, thankfully, just another chronic disease to manage across a long lifespan–by focusing on approving tools rather than cures.

    • #18
    • January 27, 2016, at 9:15 AM PST
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  19. PsychLynne Inactive

    James Gawron:

    PsychLynne: The current process is phased in with strict guidance about what types of evidence each level provides.

    This is very interesting. Could you describe the “strict guidance” for us.

    Jim, with the significant caveat that I’m not a treatment/cures researcher. I’m a psychologist and focus on cognition, emotion, decision making usually post-treatment and end of life. However, my work has given me lots of exposure to the clinical trials system.

    The standards for what types of questions are answered by a clinical trial are summarized here; Phase 1 are basically very small numbers, examining dosing and toxicities. They aren’t statically powered for cure. The vast majority of these trials, whether funded by Pharma or federal dollars are done in academic research hospital or lab settings. So, it is unlikely, though not impossible thanks to technology, that your local community cancer center is not providing this type of trial.

    The trial design and analyses much be constructed with given lab controls, reporting and clinical resources, as well as design and analysis appropriate to the type of question being asked at each phase.

    The guidance is strict and then is reviewed by the FDA, so multiple hands touch it and have a interest in it.

    Is that helpful?

    • #19
    • January 27, 2016, at 10:55 AM PST
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  20. James Gawron Thatcher
    James GawronJoined in the first year of Ricochet Ricochet Charter Member

    PsychLynne:The trial design and analyses much be constructed with given lab controls, reporting and clinical resources, as well as design and analysis appropriate to the type of question being asked at each phase.

    The guidance is strict and then is reviewed by the FDA, so multiple hands touch it and have a interest in it.

    Is that helpful?

    Phase 1

    Purpose:

    To find a safe dose
    To decide how the new treatment should be given (by mouth, in a vein, etc.)
    To see how the new treatment affects the human body
    Number of people taking part: 15–30

    Phase 2

    Purpose:

    To determine if the new treatment has an effect on a certain cancer
    To see how the new treatment affects the body
    Number of people taking part: Less than 100

    Phase 3

    Purpose:

    To compare the new treatment (or new use of a treatment) with the current standard treatment
    Number of people taking part: From 100 to several thousand

    Some researchers design trials that combine two phases (phase 1/2 or phase 2/3 trials) in a single protocol. In this combined design, there is a seamless transition between trial phases, which may allow research questions to be answered more quickly or with fewer patients.

    There are also very early (phase 0) and later (phase 4) phase clinical trials. These trials are less common. Phase 0 trials are very small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness. They take place after a new treatment has been approved and is on the market.

    Updated: November 2, 2012

    _________________________

    PsyL,

    Yes, very helpful. Immediately I realize that I’m just remembering a very old version of this. It has been streamlined and much improved. The big bugaboo of the 80s obsessive Phase III has been moved completely to Phase IV where the drug is already on the market. Meanwhile, Phase I, II, & III have been supercharged to be more effective. I’d be interested in what they mean by Phase Zero.

    Now I’m starting to feel like my feet are on the ground. So I’ll ask you the next question. Do you feel given the FDA regime in place or even with any minor improvements still fails the Freedom Test? In other words is a fundamental right of the patient to choose being subverted by FDA even if the regs are as rational as you can imagine them to be?

    Regards,

    Jim

    • #20
    • January 27, 2016, at 11:21 AM PST
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  21. donald todd Inactive

    Timothy Patton:

    donald todd:Back in the day, Great Britain allowed the use of thalidomide by pregnant women. The unborn children were visited with great harm, born with various handicaps.

    Milton Friedman spoke directly to the issue of thalidomide and the justification for the FDA. Interviewed no less by our very own Peter Robinson.

    Noted, and thank you. But I wasn’t even thinking of this interview when I read the post. I do have a position. I think at times the FDA is in a damned-if-you-do and damned-if-you-don’t position. Given the small number of sufferers of this disease, each individual is essentially a clinical trial. I don’t know if the FDA will be involved but actually hope so because someone should be keeping abreast of how well or ill the drug worked – at least for this particular individual. Having at least the beginning of an idea about how and when this might work and what dosages should be meted out might benefit the next patient; and the FDA might be the agency making that information available to the next doctor facing the next diseased patient.

    • #21
    • January 27, 2016, at 1:48 PM PST
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