Randomized Trial Fantasies

 In Preventive Medicine Column

Chewing on The Randomized Trial Fantasy

There is a fantasy taking over the world of nutrition, especially acute in the aftermath of the contentious Dietary Guidelines release, that nobody really knows anything. The arguments are made at times by seemingly expert people, although we often find they are either not the experts they pretend to be, or are badly conflicted. Or, sometimes, both.

One of the shibboleths with which this camp routinely differentiates itself is the contention that all reliable knowledge- in science, at least- results from randomized, controlled trials (RCTs). Implied, if not stated, is that RCTs are not just necessary and better, but presumably, infallible. The argument continues that such trials are glaringly absent in nutrition, and then finishes with the flourish: we therefore know nothing about nutrition. I can only guess how much Big Food loves this sequence.

It is, however, nonsense, from start to finish. We know plenty about the basic care and feeding of Homo sapiens, in part from excellent RCTs, but by no means limited to them.

I suppose I might be more expert in randomized controlled trials if I had ever had the actual opportunity to fetch a pail of water without one when my foot caught on fire, as I’ve said I would do. I can’t say I’m sorry that hasn’t happened.

I feel qualified to opine on the topic just the same. I have designed, conducted, and published, dozens of such trials. I have written two textbooks about them, too, one addressing details of methodology, the other addressing both that, and its application to clinical decisions. I know a thing or two about randomized trials.

But I know a thing or two without a need for one, too. For starters, RCTs do only a very specific job, although admittedly, they can do it uniquely well. They are designed to answer questions when there is considerable uncertainty about the best or right thing to do. In the absence of such uncertainty, RCTs quickly bog down in ethical problems. We have, for instance, no RCTs of treating gunshot wounds to the chest or abdomen, versus watching them bleed to see what happens. We have no RCTs of actual versus sham emergency surgery in this circumstance, or comparisons of trauma surgery to Gregorian chants.

Such silly examples aren’t as silly as they seem. They point out two serious flaws in the RCT fantasy: (1) for ethical reasons, you simply cannot always run a RCT, and (2), when you do run one, the answer is only ever as good as the question.

RCTs have decided strengths. But they have rather profound limitations, too. They tend to require rather large treatment effects in relatively short periods of time. If we are looking for effects over a lifetime, in a study of, say, longevity, and feel we need a RCT- then our RCT will need to last 100 years. Those aren’t done very often.

The strict stipulation of inclusion and exclusion of RCTs makes them quite robust in one way, but very contrived in another. The result is that: what happens in a RCT may stay with the RCT. In other words, people who agree to participate and play by the trial rules may look too little like the rest of the world to tell us much of anything applicable to it. And as noted, ethics alone preclude RCTs in many circumstances.

Importantly, RCTs can get it wrong, badly wrong. This can happen because the trial is flawed in some way, or the question is misguided; or it can happen because the results are sound, but misinterpreted by scientists, the media, or a bit of both. I won’t repeat the tale here, but colleagues and I discovered that what we thought we knew about hormone replacement at menopause based on observational trials was a bit wrong in one direction, while what we thought we learned from subsequent RCTs was at least as wrong in a different direction.

Just about everything currently passing for wisdom about RCTs and nutrition is wrong. The claim that we have no RCTs is wrong; we have many, and some quite dazzling. The claim that other forms of evidence are inevitably lesser is wrong; sometimes other data sources are all there is. Blue Zone populations have not been randomly assigned to live as they do, but how absurd to ignore their shining example for that reason. Results at the level of whole populations over a span of generations trump just about anything we could hope for in even the most lavish of RCTs. The idea that RCTs are themselves infallible is every bit as silly as the questions they are sometimes designed to answer.

And finally, and most importantly: you don’t need me or anyone else to tell you that you know some things pretty darn well in the utter absence of evidence from randomized trials. Just ask yourself what you would do about it if your foot ever caught on fire.

-fin Dr. David L. Katz;www.davidkatzmd.com; author, Disease Proof; founder, True Health Initiative

Dr. David L. Katz
DAVID L. KATZ MD, MPH, FACPM, FACP, FACLM, is the founding director (1998) of Yale University's Yale-Griffin Prevention Research Center, and current President of the American College of Lifestyle Medicine. He earned his BA degree from Dartmouth College (1984); his MD from the Albert Einstein College of Medicine (1988); and his MPH from the Yale University School of Public Health (1993). He completed sequential residency training in Internal Medicine, and Preventive Medicine/Public Health. He is a two-time diplomate of the American Board of Internal Medicine, and a board-certified specialist in Preventive Medicine/Public Health. He has received two Honorary Doctorates. Dr. Katz has published roughly 200 scientific articles and textbook chapters, and 15 books to date, including multiple editions of leading textbooks in both Preventive Medicine, and nutrition. Recognized globally for expertise in nutrition, weight management and the prevention of chronic disease, he has a social media following of well over half a million. In 2015, Dr. Katz established the True Health Initiative to help convert what we know about lifestyle as medicine into what we do about it, in the service of adding years to lives and life to years around the globe.
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