Revista de biometría y bioestadística

Adaptive Randomization Study Design in Clinical Trials for Psychiatric Disorders

Abstract

Roberto Gomeni and Navin Goyal

Abstract
Background: Uncontrolled placebo response has been one of the major culprits in the failure of randomized clinical trials for depression. A major drawback associated with the presence of high placebo response is the increased noiseto- signal ratio that in a majority of cases prevents the detection of treatment effect. The aim of this work was to propose an adaptive randomization study design based on band-pass filtering and evaluate this approach when compared to the traditional study designs.
Results: Clinical trial simulations demonstrated that an adaptive randomization approach always outperformed the conventional study designs in improving the signal-to-noise ratio. The improvement directly correlated with the level of placebo response and the variability in response across centers. The proposed strategy does not warrant any unblinding of data.
Conclusions: The use of the adaptive randomization design provides a novel methodological approach for signal detection in clinical trials where placebo represents a known confounding factor. The improvement in signal detection was directly proportional to the level of placebo response, the degree of heterogeneity across recruitment centers with a reduced sample size as compared to the traditional study design. These findings support the use of the band-pass filtering approach in an adaptive randomization design as an efficient way to minimize the impact of uncontrolled placebo response and provide rational go/no-go decision criteria in the development of new medicines for psychiatric disorders.