Robust meta-analytic-predictive priors in clinical trials with historical control information

Biometrics. 2014 Dec;70(4):1023-32. doi: 10.1111/biom.12242. Epub 2014 Oct 29.


Historical information is always relevant for clinical trial design. Additionally, if incorporated in the analysis of a new trial, historical data allow to reduce the number of subjects. This decreases costs and trial duration, facilitates recruitment, and may be more ethical. Yet, under prior-data conflict, a too optimistic use of historical data may be inappropriate. We address this challenge by deriving a Bayesian meta-analytic-predictive prior from historical data, which is then combined with the new data. This prospective approach is equivalent to a meta-analytic-combined analysis of historical and new data if parameters are exchangeable across trials. The prospective Bayesian version requires a good approximation of the meta-analytic-predictive prior, which is not available analytically. We propose two- or three-component mixtures of standard priors, which allow for good approximations and, for the one-parameter exponential family, straightforward posterior calculations. Moreover, since one of the mixture components is usually vague, mixture priors will often be heavy-tailed and therefore robust. Further robustness and a more rapid reaction to prior-data conflicts can be achieved by adding an extra weakly-informative mixture component. Use of historical prior information is particularly attractive for adaptive trials, as the randomization ratio can then be changed in case of prior-data conflict. Both frequentist operating characteristics and posterior summaries for various data scenarios show that these designs have desirable properties. We illustrate the methodology for a phase II proof-of-concept trial with historical controls from four studies. Robust meta-analytic-predictive priors alleviate prior-data conflicts ' they should encourage better and more frequent use of historical data in clinical trials.

Keywords: Adaptive design; Adaptive randomization; Bayesian inference; Clinical trials; Exponential family; Meta-analysis; Mixture distribution; Robustness.

MeSH terms

  • Algorithms*
  • Bayes Theorem*
  • Clinical Trials, Phase II as Topic
  • Computer Simulation
  • Data Interpretation, Statistical
  • Humans
  • Meta-Analysis as Topic*
  • Models, Statistical*
  • Pattern Recognition, Automated / methods
  • Prognosis
  • Randomized Controlled Trials as Topic*
  • Sample Size