In the past several decades, it is recognized that increasing spending of clinical research does not reflect an increase of the success rate of drug development. Moreover, the pharmaceutical industry has realized that the classical structured clinical trials do not offer enough flexibility to make use of continuously emerging knowledge that is generated as trial progresses.
One of the innovations strongly recommended by the authorities is the use of adaptive designs in clinical trials and the potential use of Bayesian approach in clinical research. Although planning such trials comes at the cost of additional operational complexity, adaptive designs offer the benefit of flexibility to update trial design and objectives as data accrue.
In this white paper, we will explore a two-stage adaptive design called the “Sequential Parallel Comparison Design” (SPCD) for enrichment of placebo non-responders.
The placebo response has progressively increased over time in clinical trials for psychiatric disorders. High placebo response reduces the ability of trials to detect the treatment effect, resulting larger rates of failed and negative trials. The sequentially parallel comparison design (SPCD) invented in 2003 at Massachusetts General Hospital by Dr Fava and Dr Schoenfeld (Fava et al., 2003) is an effective approach for reducing both the high placebo response and the required sample size. Due to the two-stage design, the inference procedure of the SPCD is not straightforward. The aim of this white paper is to walkthrough the computation of a P value, a confidence interval and an estimate of the overall treatment effect at the termination of the two-stage trial.
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