Rembrandt's The Anatomy Lesson (1630).
[All posts in this nascent series can be found at The FDA Will Kill Us All! archives.]
There are few diagnoses that are more terrifying and more certain than Metastatic Melanoma. The duration from diagnosis to death is measured in months, not years. It is the one truly dire situation that Dermatologists face int heir work and there have been many approaches over the years to find treatments that can offer hope to their pattens. In the New York Times magazine section this past Sunday was an article describing the experiences of two young cousins who both developed Melanoma at nearly the same time; from there, their stories diverged in ways which illustrate how deadly the FDA has become, all in the name of the precautionary principle combined with a fantasy of scientific certainty:
New Drugs Stir Debate on Rules of Clinical Trials
Growing up in California’s rural Central Valley, the two cousins spent summers racing dirt bikes and Christmases at their grandmother’s on the coast. Endowed with a similar brash charm, they bought each other matching hardhats and sought iron-working jobs together. They shared a love for the rush that comes with hanging steel at dizzying heights, and a knack for collecting speeding tickets.
And when, last year, each learned that a lethal skin cancer called melanoma was spreading rapidly through his body, the young men found themselves with the shared chance of benefiting from a recent medical breakthrough.
Only months before, a new drug had shown that it could safely slow the cancer’s progress in certain patients. Both cousins had the type of tumor almost sure to respond to it. And major cancer centers, including the University of California, Los Angeles, were enrolling patients for the last, crucial test that regulators required to consider approving it for sale.
“Dude, you have to get on these superpills,” Thomas McLaughlin, then 24, whose melanoma was diagnosed first, urged his cousin, Brandon Ryan. Mr. McLaughlin’s tumors had stopped growing after two months of taking the pills.
But when Mr. Ryan, 22, was admitted to the trial in May, he was assigned by a computer lottery to what is known as the control arm. Instead of the pills, he was to get infusions of the chemotherapy drug that has been the notoriously ineffective recourse in treating melanoma for 30 years.
Read the whole thing (and weep) if you wish. There is of course no way to know if Mr. Ryan might have survived had he received the experiential treatment. However, 30 years of ineffective treatment have already conclusively shown that receiving the traditional treatment would lead to his demise; unsurprisingly, Mr. Ryan is now deceased while Mr. McLaughlin remains alive. How long Me. McLaughlin will remain in remission is unknown. As the article points out, exciting developments int he treatment of Melanoma in the past have not panned out; yet it is incontrovertible that, thus far, Mr. McLaughlin's time is now a free gift from medical Science.
The FDA believes that the gold standard of medical experimentation is the double blind, controlled study. If either the patients or the researchers know who is receiving the experimental treatment and who is receiving either traditional treatment or placebo, the results could be confounded. It is a well established fact that placebo effects can be significant, even in areas of Medicine where it would be least expected. It is certainly wise to attempt to minimize the risk of approving a treatment that it little more than placebo. Yet to conclude from this that the FDA can achieve certainty about the effects of any treatment considering the limited number of subjects that any trial can reasonably include, is a fantasy, a deadly dangerous fantasy.
The precautionary principle is easy to dispose of in the case of My. Ryan. Current treatment options offered him, at maximum, an extra two months of life and would be accompanied by hugely unpleasant side effects guaranteed to impact upon his quality of life. Mr. Ryan was facing certain death from a terrible illness and was not allowed to avail himself of a possibly effective treatment (which has had minimal side effects in those patients who have already been studied) because it might harm him. This is cruel and sadistic, all in the name of bureaucratic rules.
The second idea, that FDA trials establish efficacy and safety is also an illusion, though a somewhat more supportable illusion. As Medicine becomes much more of an individualized discipline we are getting better and better at targeting treatments. A new treatment might benefit only those who have a variant of genetic constitution shared by a small fraction of the population, while another small fraction of the population might have a variant the predisposes them to dangerous side effects. if a trial includes 1000 people there may be one or two who receive impressive benefits while one fr two suffer terrible side effects. Out of 1000 people such numbers will be swamped by the placebo effects. (Just as up to 30% will benefit from a placebo, a smaller number of patients, perhaps as many as 15% in some studies, will have side effects from placebos; the mind is a powerful and mysterious structure.) Once the treatment is approved, suddenly thousands and then millions receive the treatment and one or two or ten years later, treatment emergent side effects become apparent.
[At that point the lawyers burst into action, seeing fantastic sums to extort from the health system by virtue of the vagaries of our metabolism. Ambulance chasing has achieved new heights when TV commercials troll for people harmed by drugs that have helped millions and harmed a few. Sometimes the problem is even more difficult. As an example, Zyprexa has major advantages over first generation anti-Psychotic medications. As a result it has become an important medication for patients with psychosis and, at low doses, refractory depression. It does not cause Tardive Dyskinesia, an often permanent neurological movement disorder that can be caused by the traditional anti-Psychotics; on the other hand it can cause weight gain and metabolic changes and may increase the risk of Type II diabetes. We are then left with the choice of offering the risk of a neurological movement disorder, Diabetes, or untreated psychosis; whatever the Psychiatrist does, a clever lawyer can easily assign blame for any untoward outcome. I attempt to offer the Patient the opportunity to make an informed consent and monitor what I can, but the concept of "informed consent" is terribly flawed and for Psychiatric Patients, the lawyers can eviscerate the concept in the interest of extracting their pound of flesh.
Obamarcare will make all of these problems worse. Bureaucratic panels will be set up to determine which treatments are cost effective and safe; while this sounds good in theory, in practice bureaucrats always follow the first rule of bureaucracy, CYA. As a result risky, leading edge treatments, which also tend to cost a great deal more than mature technologies, will have even higher regulatory hurdles to jump over in order to become available. There is, however, one group that should do very well under Obamacare: Administration Considering Big Payback to Trial Lawyers.]
I do not mean to be nihilistic about this. Controlled studies are the best option, when they are appropriate. However they must be understood to come with some caveats. They are often incorrect and only a long time with many opportunities for replication can make that determination (does avoiding the sun save more lives by minimizing the possibility of developing skin cancer or does it increase mortality and morbidity by causing people to have relative Vitamin D deficiencies?); they are often extremely limited in the information they proffer, typically completely missing the nature of the individual biochemistry's interaction with the metabolic manipulation (consider Vioxx); they may be uneccessary and inappropriate when a "control" group already has existed for 30 years, ie if 30 years of ineffective treatment are insufficient to serve as a control, the model for the trial might be problematic.
The FDA (and their allies in the tort bar) has become the arbiter for what risks American adults will be allowed to assume. Since they have thus become the risk takers and their goal is to minimize their risk, all of us will play it safe right up until we die.
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