the why of it…

Posted on Friday 31 July 2015

For as much time as I’ve spent thinking about Randomized Clinical Trials in my retirement years, I never gave them a moment’s thought in two different medical careers. I didn’t really have much of an idea how drugs became approved, or how drug patents worked. As odd as that may sound, I expect that was true for the overwhelming majority of my contemporaries. In Internal Medicine, I learned about medications from textbooks rather than journal articles. In psychiatry, a person like me practicing psychotherapy doesn’t write many prescriptions, and I still relied on textbooks or review articles rather than looking at Randomized Clinical Trials. With rare exceptions, I rode on the "trailing edge" of medications, waiting until drugs were in widespread use before learning about them or prescribing them. The concept of a "pipeline" delivering a stream of new medications wasn’t even in my consciousness. I guess I thought that new medications came along when and if they were discovered. Writing this makes me feel incredibly naive – but I think that’s just the way it was. The only class of drugs I can recall actively keeping up with were the antibiotics – and that was because of those microbes’ incredible ability to become resistant.

So, in my oft told story, five years after retiring I had started volunteering some and was completely horrified at the drug cocktails the patients were taking. Then one morning, I read this over a cup of coffee:
New York Times
October 3, 2008

One of the nation’s most influential psychiatrists earned more than $2.8 million in consulting arrangements with drug makers from 2000 to 2007, failed to report at least $1.2 million of that income to his university and violated federal research rules, according to documents provided to Congressional investigators. The psychiatrist, Dr. Charles B. Nemeroff of Emory University, is the most prominent figure to date in a series of disclosures that is shaking the world of academic medicine and seems likely to force broad changes in the relationships between doctors and drug makers…
The chairman of the department I’d been a part of for then thirty-four years? arrangements with drug makers? a crook!? So that’s when I started to learn about Randomized Clinical Trials, and drug approval processes, and PHARMA, and more corruption than I would have thought possible.

Flash forward to the present. Over the intervening seven years, I’ve learned a lot about RCTs. About halfway back, I realized that the pharmaceutical companies being able to keep the raw data secret, or being able to simply not publish results they didn’t like, were an essential ingredients in the problem and I’ve spent a lot of my time involved in the fight for Data Transparency. There’s a lot more wrong – things like the alliance between academic medicine and industry, guest authors and ghost authors, the intrusions of third party carriers into medical care, etc. But frankly, I’ve spent so much time learning the ropes [with the help of some really good teachers], that it has been hard to get far enough away from the details to have an overall perspective on the big picture.

When I first read David Healy’s book, Pharmageddon [2012], I was still learning about Randomized Clinical Trials [RCTs], and I had looked at a number of them in as much depth as I could given the inaccessibility of the actual trial data. I could see how much subtle distortion there had been in the analyses and presentations in journal articles. The book added the history of RCTs and gave me a valuable perspective on how this tangled system had come into being  over the years. But there was one point that I didn’t intuitively grasp at the time. He seemed to be saying that there was a basic flaw in the RCT system over and above the distortions. At the time, It seemed to me that if the RCTs were properly conducted, properly analyzed, and properly reported that everything would be fine. I could tell he thought otherwise, but I just didn’t get the why of it on first reading. 

And I might as well add Evidence-Based Medicine and Measurement-Based Medicine in here along with RCTs. On the one hand, what is the alternative to evidence-based medicine? Wild guesses? And yet, every time I hear Evidence-Based Medicine [EBM], I wince involuntarily. The one that gets the biggest wince is Evidence-Based Psychotherapy [which means Cognitive Behavior Therapy (CBT)]. Well, I get it now – what’s wrong with RCTs – what Healy was saying. Rather than talk about the the why of it, I’ll refer you to the horse’s mouth, because Dr. Healy is in the middle of talking about it again on his blog:
If I had thought about my own experience as a physician [that introductory italicized paragraph that I started with], I might have gotten the why of it sooner. There’s a lot to say about this point, but I’m going think about it for a bit. In the meantime, you might take a look at Dr. Healy’s blogs, or even order the book if you don’t intuitively get it [like I didn’t]…
    July 31, 2015 | 9:55 PM

    Healy is right, we live in an era of cultural fragmentation and medicine is the worse for it.

    The Alzheimer’s drug gold rush — told you so.

    August 4, 2015 | 8:57 PM

    I can well understand how a practicing psychiatrist might have seen the landscape very differently from a patient or student… or dilettante, as I might more accurately describe myself during the go-go years of big Pharma, from the early ’80s until about five years ago.

    To me, it seemed like psychiatrists who practiced from an analytic and gestalt perspectives were just more my kind of people. I always thought, “Gee, if I get into this field, I want to do it like THAT.” As they say in 12-step programs, I wanted what they had. These were people who thought clearly, and were kind and pleasant and interesting. When they explained things to me in therapy, or at my mother’s cocktail parties, their reasoning seemed sharp and on point, even if the metaphors and terminology seemed needlessly arcane at times.

    Early on, I dismissed the people who prescribed and consumed antidepressants on a regular basis as, simply, lightweights who were not to be taken seriously. It seemed obvious the drugs didn’t work very well and were pretty unpleasant to take. Sure, a few people I knew tried them, but most discontinued almost immediately. I couldn’t imagine that anyone else wouldn’t do the same.

    By the mid ’90s, I had done a couple of freelance jobs copyediting puff pieces for pharma marketing firms, and one of my best friends was in medical publishing. He was deeply disturbed by the literature many of the presentations were based on, and he often talked about how vapid and uninteresting some of the people were. By this point, both of us had also tried SSRIs briefly with pretty disastrous results, and we knew more friends who had tried them or even gotten stuck on them. (And “stuck” turned out to be very much the right word, because most of those folks made little or no noticeable progress in their professional or personal lives over the next ten years.)

    It was obvious something was pretty deeply wrong with the drug approval process. I didn’t understand what an RCT was until about five years ago, but by the turn of the century, I do remember reading some of the literature and thinking that everyone must be pretending that researching a psychiatric medication was no different from researching an antibiotic. And wondering if anyone really believed that.

    I guess for us, as outsiders, we didn’t feel so much naive as much as spectators at some terrifying slow-motion train wreck. (My friend did leave the medical PR business, and is much happier now.)

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