Sequential Monte Carlo for response adaptive randomized trials.

Response adaptive randomized clinical trials have gained popularity due to their flexibility for adjusting design components, including arm allocation probabilities, at any point in the trial according to the intermediate results. In the Bayesian framework, allocation probabilities to different treatment arms are commonly defined as functionals of the posterior distributions of parameters of the outcome distribution for each treatment. In a non-conjugate model, however, repeated updates of the posterior distribution can be computationally intensive. In this article, we propose an adaptation of sequential Monte Carlo for efficiently updating the posterior distribution of parameters as new outcomes are observed in a general adaptive trial design. An efficient computational tool facilitates implementation of more flexible designs with more frequent interim looks that can in turn reduce the required sample size and expected number of failures in clinical trials. Moreover, more complex statistical models that reflect realistic modeling assumptions can be used for analysis of trial results.