Advantages of Bayesian monitoring methods in deciding whether and when to stop a clinical trial: an example of a neonatal cooling trial.

Document Type

Article

Publication Date

7-22-2016

Abstract

BACKGROUND: Decisions to stop randomized trials are often based on traditional P value thresholds and are often unconvincing to clinicians. To familiarize clinical investigators with the application and advantages of Bayesian monitoring methods, we illustrate the steps of Bayesian interim analysis using a recent major trial that was stopped based on frequentist analysis of safety and futility.

METHODS: We conducted Bayesian reanalysis of a factorial trial in newborn infants with hypoxic-ischemic encephalopathy that was designed to investigate whether outcomes would be improved by deeper (32 °C) or longer cooling (120 h), as compared with those achieved by standard whole body cooling (33.5 °C for 72 h). Using prior trial data, we developed neutral and enthusiastic prior probabilities for the effect on predischarge mortality, defined stopping guidelines for a clinically meaningful effect, and derived posterior probabilities for predischarge mortality.

RESULTS: Bayesian relative risk estimates for predischarge mortality were closer to 1.0 than were frequentist estimates. Posterior probabilities suggested increased predischarge mortality (relative risk > 1.0) for the three intervention groups; two crossed the Bayesian futility threshold.

CONCLUSIONS: Bayesian analysis incorporating previous trial results and different pre-existing opinions can help interpret accruing data and facilitate informed stopping decisions that are likely to be meaningful and convincing to clinicians, meta-analysts, and guideline developers.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01192776 . Registered on 31 August 2010.

Publication Title

Trials

ISSN

1745-6215

Volume

17

Issue

1

First Page

335

Last Page

335

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