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Modern understanding of the human genome has begun to propel advances in selecting the right treatments for the right patients. Companion diagnostic (CDx) devices are an essential part of some therapeutic products in identifying its intended use population. The need to simultaneously evaluate new therapeutic and CDx products creates additional challenges and constraints on clinical study design. Sometimes the products cannot be evaluated contemporaneously due to differing development schedules, a temporary diagnostic test must be used to evaluate the therapy and a bridging study conducted later.
A basic CDx device study randomizes both CDx+ and CDx- subjects and does not adjust treatment effects impacted by false positive/false negative subjects. An alternative design screens all subjects but only randomizes CDx+. We model the effects of false positive/false negative subjects in treatment/control groups and evaluate methods of treatment effect adjustment. Specific focus has been placed on minimizing the impact of interactions between therapeutic and diagnostic components on statistical and clinical inferences. Similar analysis is performed on CDx study designs requiring bridging.
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