The Father of Evidence-Based Medicine: Why N=1 Trials Top the Evidence Hierarchy
My interview with Gordon Guyatt
Gordon Guyatt coined the term “Evidence-Based Medicine” in 1991 and together with David Sackett and others he founded the EBM movement, formally proclaimed in the Journal of the American Medical Association (JAMA) in 1992.
He cofounded the GRADE Working Group in 2000, which has now become embedded in the World Health Organization, Cochrane, and other institutions as the authoritative distribution of EBM’s influence in the world’s institutions.
He started the authoritative textbook on EBM, Users Guide to the Medical Literature, in 2001, which reached its third edition in 2014 and remains the authority of the field.
As such there is no one else alive who speaks more authoritatively on what Evidence-Based Medicine truly means.
You may then be surprised that the familiar “pyramid” of the “evidence hierarchy,” which appears to have been created by an entirely unknown reference librarian at SUNY Downstate in 1997, is, according to Guyatt “totally confused.”
Among other reasons, properly conducted n=1 self-experiments belong at the TOP of the hierarchy, where they have appeared in the EBM textbook since 2001, remaining so in the 2014 edition. Guyatt told me that if he ever produced a fourth edition, n=1 trials would remain right at the top.
We looked together at my own randomized n=1 self-experiment comparing the impact of corn vs quinoa on my sleep and energy.
You may also be quite surprised at how Guyatt described the importance of mechanistic reasoning in interpreting the generalizability of human outcome studies. In some cases, it’s “crucial.”
We talked about how I synthesize mechanistic reasoning, animal studies, and human trials to interpret the way choline status should impact the effect of seed oils on fatty liver and Guyatt weighs in with his verdict on my reasoning.
In this interview, Guyatt and I discuss how to apply the principles of EBM to medicine, health and nutrition, and daily life, paying special attention to the less appreciated aspects of EBM, like the importance of individual values and choice, recognizing what we don’t know, understanding the limits of generalizing from RCTs, weighing mechanistic reasoning against observational studies as means of navigating uncertainty, and how Guyatt responds to critiques from public health and to John Ioannidis’s claim that EBM has been hijacked.
0:29 What was medicine based on before it was based on evidence?
3:29 What is EBM?
5:38 How individual choice is core to EBM but remains underappreciated, and how it took time for it to become a core part of EBM.
10:50 Why the “hierarchy of evidnce” pyramid is “totally confused.”
19:08 Why n=1 trials are at the TOP of the evidence hierarchy
25:09 What might change his mind on statins?
29:15 My own n=1 randomized experiment of corn vs quinoa
33:27 Do randomized controlled trials apply to individual people?
36:06 What is the role of “try it and see if it works” in EBM?
37:38 What is the role of mechanistic reasoning in extrapolating from randomized trials?
46:51 Guyatt evaluates how I synthesize mechanistic reasoning and animal experiments with human trial results to interpret the likely impact of choline status on how seed oils versus saturated fats impact fatty liver disease.
56:08 Does the fact that RCTs aren’t long enough mean that long observational studies can be high-quality evidence?
1:01:08 Whether the upcoming revisions to the GRADE framework are inappropriately reducing skepticism toward observational studies
1:07:31 How he responds to criticisms from public health
1:09:39 Is EBM in “crisis” and has it been “hijacked”?
This article is a great contradiction to the paralyzing dogma that distorts clinical care.
I'm delighted to hear that Dr. Guyatt, the father of EBM is so enthusiastic about n-of-1 trials. I've long been a fan of his sensible approach to EBM but didn't know this aspect.
The fact is that we can't provide good clinical care without going beyond what RCTs and clinical practice guidelines tell us. We have way too much uncertainty in medicine. Population based studies have a very difficult time assessing multi-variable problems.
And there is much misuse of EBM.
In 30 years of practice I've been astonished about how many clinicians have their panties in a knot around fallacies like "clinical experience does not constitute data". And don't forget the "absence of evidence = evidence of absence" fallacy. That's the way-too-common logical error that implies that if we don't have strong evidence of a phenomena or clinical effect then it doesn't exist.
Thanks for sharing this article and interviewing Dr Guyatt.
This is inspiring me to do more N=1 experiments like I did for Bio-Opt! I would love to see an article or a crowdsourced list of short-term outcomes that can be measured during a controlled experiment, in addition to glucose, lactate, and ketones, and the general “outcomes that you care about”.