Bayes’ Rule and Being Ready To Change Our Minds
Many of the clinical studies funded by NIH do not show the expected benefit. I have discussed this before on NCCAM’s blog. Surprises—positive expectations, negative results—are common in clinical research.
Every once in a while the opposite happens.
Over the course of the last year, the team that conducted the Trial to Assess Chelation Therapy (TACT) has completed a series of analyses detailing their findings.1 The most recent, published in the American Heart Journal (AHJ) compared patients with diabetes who had received both chelation and high-dose vitamins with those receiving placebo chelation and placebo vitamins.2 The authors found that those receiving the active treatment clearly fared better than those receiving placebo. The accompanying editorial in the AHJ reminds readers about the value of equipoise and the need to “test our beliefs against evidence.”3
Most physicians did not expect benefit from chelation treatment for cardiovascular disease. I readily admit, initially, I also did not expect we would find evidence that these treatments reduce heart attack, strokes, or death. So, the evidence of benefit coming from analyses of the TACT trial has been a surprise to many of us. The subgroup analyses are suggesting sizable benefit for diabetic patients—and also, importantly, no benefit for the non-diabetic patient. Clearly subgroup analyses, even if prespecified, do not give us the final answer. But it is also clear that more research is needed to test these important findings.
And TACT findings are indeed a reminder of the importance of retaining equipoise, seeking further research aimed at replicating the findings, and neither accepting nor rejecting findings based on personal biases. The scientific process is designed to weed out our preconceived notions and replace them with evidence.
Bayesian methods are getting a lot of attention in the clinical research literature these days. The Bayes rule involves estimating the probability of a result—the prior—then modifying it with each round of new evidence. Another editorialist, a statistician, examined the TACT results, using a Bayesian approach, and comments: “If we start from a position of skepticism, the results of the TACT trial reduces the degree of skepticism. This is exactly how Bayes analysis helps modify prior beliefs by incorporating new evidence and upgrading knowledge.”4
Or to quote Sharon Bertsch McGrayne, an insightful writer on science and the scientific method, Bayes’ rule commits us to “an unrelenting commitment to changing our minds in the face of new knowledge.”5 So, TACT is a reminder—an open mind is at the center of the scientific method.
1 Lamas GA, Boineau R, Goertz C, et al. Oral high-dose multivitamins and minerals after myocardial infarction: a randomized trial. Annals of Internal Medicine. 2013;159(12):797–805.
Lamas GA, Goertz C, Boineau R, et al. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. JAMA. 2013;309(12):1241–1250.
Escolar E, Lamas GA, Mark DB, et al. The effect of an EDTA-based chelation regimen on patients with diabetes mellitus and prior myocardial infarction in the Trial to Assess Chelation Therapy (TACT). Circulation. Cardiovascular Quality and Outcomes. 2014;7(1):15–24.
Lamas GA, Boineau R, Goertz C, et al. EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: the factorial group results of the Trial to Assess Chelation Therapy. American Heart Journal. 2014; In press.
2 Lamas GA, Boineau R, Goertz C, et al. EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: the factorial group results of the Trial to Assess Chelation Therapy. American Heart Journal. 2014; In press.
3 Maron DJ, Hlatky MA. Trial to Assess Chelation Therapy (TACT) and equipoise: when evidence conflicts with beliefs. American Heart Journal. 2014. In press.
4 Kaul S. Are concerns about reliability in the trial to assess chelation therapy fair grounds for a hasty dismissal? An alternative perspective. Circulation. Cardiovascular Quality and Outcomes. 2014;7(1):5–7.
5 Sharon Bertsch McGrayne. The Theory That Would Not Die: How Bayes' Rule Cracked the Enigma Code, Hunted Down Russian Submarines, and Emerged Triumphant from Two Centuries of Controversy. New Haven, CT: Yale University Press; 2011.