Posted on Wednesday 11 June 2014

In 1962, I was in college and even though I was applying to medical school at the time, the Kefauver·Harris Amendment  to the Federal Food, Drug, and Cosmetic Act was hardly on a college guy’s radar. But I sure knew about Frances Kelsey PhD, the FDA Reviewer who refused to approve Thalidomide and became a national hero. We had all seen those pictures of the Thalidomide Babies. Kefauver was a Senator from the Great State of Tennessee, and we all knew him as the guy with the coon-skin cap, not as a medication reformer. I’m a Tennessean who met Estes Kefauver several times as a kid, but I first read about those Kefauver Hearings in the recent writings of Dr. David Healy [Pharmageddon, The Lasagna Series, etc].

Although it was in the area of Adverse Events that Frances Kelsey became a hero, worrying if Thalidomide crossed the placental barrier and holding up its approval, the main change in the  Kefauver·Harris Amendment had to do with adding proof of efficacy – ultimately meaning the Randomized Clinical Trials, championed by Dr. Louis Lasagna [from the first ever Department of Clinical Pharmacology - Johns Hopkins]. This is from a 50 year retrospective of the Kefauver–Harris Amendment in 2012:
by Jeremy A. Greene, M.D., Ph.D., and Scott H. Podolsky, M.D.
New England Journal of Medicine. 2012 367:1481-1483.

By the time Kefauver began his investigation into the pharmaceutical industry in the late 1950s, the escalating expense of lifesaving prescription drugs was illustrating that the free-market approach to medical innovation had costs as well as benefits. From the development of insulin in the 1920s, through the “wonder drug” revolutions of sulfa drugs, steroids, antibiotics, tranquilizers, antipsychotics, and cardiovascular drugs in the ensuing decades, the American pharmaceutical industry had come to play a dominant role in the public understanding of medical science, the economics of patient care, and the rising politics of consumerism. For Kefauver, the “captivity” of the prescription-drug consumer in the face of price gouging and dubious claims of efficacy under-scored the need for the state to ensure that innovative industries worked to the benefit of the average American.
Sound familiar? How did it happen that this landmark reform legislation has us reading this description of the problem fifty years ago and thinking it could’ve been written yesterday? about today? I’m not going to quote this article as much as it deserves because I’m about a particular topic here, but this short retrospective, along with the Wikipedia article and Dr. Healy’s  The Lasagna Series, all deserve a full reading by anyone interested in the topic of Randomized Clinical Trials, or for that matter, anything about Evidence-Based Medicine.

If you’re reading this, you’re likely already convinced that the last twenty years of Randomized Clinical Trials, Treatment Guidelines, and the cry of Evidence-Based Medicine have lead to some of the more egregious misadventures in the history of Medicine and Science itself. And you likely support one or another versions of Clinical Trial Data Transparency schemes currently fighting to be heard as a way of dealing with the widespread corruption. I’ve been vocal enough about my own take on the topic, most recently in in the details…, achilles’ heel…, the wrong compromise…, and repeal the proprietary data act…. I would be wearing out my welcome to say it yet again.

But there’s another larger point that can and does get lost in the shuffle – a point made by Dr. Healy in the background to much of his writing [iincluding his current four part series]. There’s something else very wrong with the modern preoccupation with Randomized Clinical Trials, Standardized Treatment Guidelines, and the overall concept of Evidence-Based Medicine over and above being conduits for corruption [as if that weren't enough] – something that’s apparently difficult to articulate. Many try to explain it in terms of the loss of the human relationship between doctor and patient:

    Originally conceived to help physicians make enlightened decisions, evidence-based medicine in North America and elsewhere has become a risk management method fostering the standardization of medical practice and the dehumanization of relations between doctors and patients.
Of course that’s right, but it’s not a definitive scientific argument. For one thing, Randomized Clinical Trials, Standardized Treatment Guidelines, and Evidence-Based Medicine itself are based on the notion that all subjects are represented by the mean – that what is statistically favored for a group is good for its individuals as if they are all the same. They aren’t, so in a given patient, it’s only a maybe, often a very weak maybe. The statistical universe created by Randomized Clinical Trials and Evidence-Based Medicine is a simplified and homogenized virtual space devoid of reality’s confounds, or even the actual variance seen in the studies that defined it. The models created are to the cases seen in medical practice as model airplanes are to the modern airbus fleet. Likewise…
The amendments granted the FDA the power to demand proof of efficacy — in the form of “adequate and well-controlled investigations” — before approving a new drug for the U.S. market. They also led to a retrospective review of all drugs approved between 1938 and 1962 [the Drug Efficacy Study Implementation program], which by the early 1970s had categorized approximately 600 medicines as “ineffective” and forced their removal from the market.
…the major intent of the Kefauver·Harris Amendment was to remove inert medications from the pharmacopeia, not to certify drugs as effective for clinical use. At the time…

The American Medical Association firmly opposed the regulation of efficacy by a government agency, arguing that “the only possible final determination as to the efficacy and ultimate use of a drug is the extensive clinical use of that drug by large numbers of the medical profession over a long period of time."

…which is as true today as it was in 1962. One would’ve never set out fifty years ago by saying that short-term Randomized Clinical Trials conducted by the company that manufactures and sells the drug should become the benchmarks for clinical medicine, incorporated as dogma into practice guidelines [not only for treatment but for reimbursed patient contacts]. You wouldn’t have said that even if the RTCs were guaranteed to be reported with pristine accuracy [which they decidedly aren't]. The minimal standards of the FDA were created to minimize fraudulent medications being approved. Over time, they’ve been declared the paradigm for Evidence-Based Medicine carrying a federal government seal of approval. What began as a firewall against fraudulent claims has become their principle conduit. The current version of Evidence-Based Medicine is a Svengali casting a spell over much of medical practice. We’re losing more than the human relationship between doctor and patient, we’re losing the doctor as a thinking scientist as well…
    June 11, 2014 | 1:58 PM

    Rather off track just here Mickey, but thought this comment by Prof Charles Oppenheim, Loughborough University, interesting in context of EMA agreement hampering data transparency:
    “The just passed changes to UK copyright law mean that anyone in the UK CAN copy such materials, and/or text or data mine them, as long as one has legal access to the documents in the first place and the purpose of the copying/text mining/data mining is non-commercial research or private study, IRRESPECTIVE OF ANY CONTRACTUAL CLAUSES THAT SAY THE CONTRARY. This only applies to UK citizens, not to the rest of the EU though.”

    June 11, 2014 | 2:01 PM

    Excellent posts


    Here are my views on the subject

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