title: A Bayesian adaptive blinded sample size adjustment method for risk differences.
abstract: Adaptive sample size adjustment (SSA) for clinical trials consists of examining early subsets of on trial data to adjust estimates of sample size requirements. Blinded SSA is often preferred over unblinded SSA because it obviates many logistical complications of the latter and generally introduces less bias. On the other hand, current blinded SSA methods for binary data offer little to no new information about the treatment effect, ignore uncertainties associated with the population treatment proportions, and/or depend on enhanced randomization schemes that risk partial unblinding. I propose an innovative blinded SSA method for use when the primary analysis is a non-inferiority or superiority test regarding a risk difference. The method incorporates evidence about the treatment effect via the likelihood function of a mixture distribution. I compare the new method with an established one and with the fixed sample size study design, in terms of maximization of an expected utility function. The new method maximizes the expected utility better than do the comparators, under a range of assumptions. I illustrate the use of the proposed method with an example that incorporates a Bayesian hierarchical model. Lastly, I suggest topics for future study regarding the proposed methods.
authors.affiliation: Biostatistics, PPD, 929 N Front St, Wilmington, NC, 28401, USA.
authors.forename: Andrew Montgomery
authors.initials: AM
authors.lastname: Hartley
mesh_terms: D001499:Bayes Theorem; D015982:Bias; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D012306:Risk; D018401:Sample Size
keywords: Bayesian analysis; adaptive designs; sample size adjustment; sample size re-estimation