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

Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Pablo J. Sánchez

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Article number335
JournalTrials
Volume17
Issue number1
DOIs
StatePublished - Jul 22 2016

Keywords

  • Bayesian methods
  • Factorial trial
  • Hypothermia
  • Phase III trial
  • Stopping rules
  • Trial monitoring

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

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