The trials of interpreting clinical trials - A Bayesian perspective Colchicine in secondary cardiovascular prevention
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Objectives
Evidence based medicine (EBM) places systematic reviews and meta-analyses, at the top of the evidential pyramid. Bayesian methods may assist in better understanding uncertainties and improve interpretations and harmonization.
Design
A 2022 meta-analysis concluded that colchicine reduced the cardiac risk in secondary prevention. Nevertheless, a large, RCT (CLEAR) continued to randomize acute patients to colchicine or placebo and in 2025 published their findings of no benefit. Bayesian sequential analyses and hierarchical meta-analysis can inform the decision to complete this trial and augment the nuances surrounding its interpretation.
Setting
RCTs of coronary artery disease (CAD) patients with an acute coronary syndrome admission undergoing percutaneous coronary intervention (PCI).
Interventions
Randomization to colchicine or placebo.
Main outcomes
The primary outcome was major adverse cardiovascular events (MACE), a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization.
Results
A published 2022 meta-analysis suggested a statistical MACE decrease with colchicine (RR 0.73 [95% confidence interval (CI) 0.62, 0.86]), but a Bayesian reanalysis showed a 95% credible interval (95% CrI 0.26, 1.70) for the next study, justifying continuing the CLEAR tiral. CLEAR results were eventually interpreted as “negative” (HR, 0.99; 95% confidence interval [CI], 0.85 to 1.16). Bayesian sequential re-analyses using a vague prior (i..e. result dominated by CLEAR), an all-inclusive prior (based on the previous meta-analysis), and a focused prior (considering only the largest and most similar previous RCT) showed 58%, 100% and 92% probabilities respectively of a MACE decrease with colchicine. The probabilities of clinically meaningful decreased, based on > absolute 15% MACE reduction, were more modest, between 2% - 41%.
Conclusions
Bayesian analyses offer advantages in clinical trial design and interpretation. The worked example strongly suggests some benefit for colchicine in secondary cardiovascular prevention, but it is unlikely to be of clinical importance.
