STATE-OF-THE-ART PAPER
Prior convictions
bayesian approaches to the analysis and interpretation of clinical megatrials
George A. Diamond, MD, FACC*,* and
Sanjay Kaul, MD*
* Division of Cardiology, Cedars-Sinai Medical Center, and the School of Medicine, University of California, Los Angeles, California, USA
Manuscript received October 1, 2003;
revised manuscript received January 2, 2004,
accepted January 12, 2004.
* Reprint requests and correspondence: Dr. George A. Diamond, 2408 Wild Oak Drive, Los Angeles, California 90068, USA.
gadiamond{at}pol.net
Large, randomized clinical trials ("megatrials") are key drivers of modern cardiovascular practice, since they are cited frequently as the authoritative foundation for evidence-based management policies. Nevertheless, fundamental limitations in the conventional approach to statistical hypothesis testing undermine the scientific basis of the conclusions drawn from these trials. This review describes the conventional approach to statistical inference, highlights its limitations, and proposes an alternative approach based on Bayes’ theorem. Despite its inherent subjectivity, the Bayesian approach possesses a number of practical advantages over the conventional approach: 1) it allows the explicit integration of previous knowledge with new empirical data; 2) it avoids the inevitable misinterpretations of p values derived from megatrial populations; and 3) it replaces the misleading p value with a summary statistic having a natural, clinically relevant interpretation—the probability that the study hypothesis is true given the observations. This posterior probability thereby quantifies the likelihood of various magnitudes of therapeutic benefit rather than the single null magnitude to which the p value refers, and it lends itself to graphical sensitivity analyses with respect to its underlying assumptions. Accordingly, the Bayesian approach should be employed more widely in the design, analysis, and interpretation of clinical megatrials.
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Abbreviations and Acronyms
| | CI | = confidence interval | | FRISC | = Fragmin and Fast Revascularization during InStability in Coronary artery disease trial | | HPS | = Heart Protection Study | | LIFE | = Losartan Intervention for Endpoint reduction in hypertension trial | | OR | = odds ratio | | PURSUIT | = Platelet Glycoprotein IIb/IIIa in Unstable Angina Receptor Suppression Using Integrilin Therapy trial | | RITA | = Randomized Intervention Treatment of Angina trial | | TACTICS TIMI-18 | = Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction-18 trial | | TIMI-IIIB | = Thrombolysis In Myocardial Infarction-IIIB trial | | VANQWISH | = Veterans Affairs Non–Q-wave Infarction Strategies in Hospital trial |
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