Keywords: Adaptive seamless PK and efficacy design, Biosimilar infliximab, Clinical trials, Sample size recalculation.
Recently, numerous pharmaceutical sponsors have expressed a great deal of interest in the development of biosimilars. A reduction in healthcare costs for patients can be expected if a biosimilar is approved by regulators and placed on the market. Pharmacodynamics (PD) may be used in evaluating efficacy if there are relevant PD markers available. However, in their absence, it is necessary to set the associated clinical trials to include efficacy measures as the primary endpoint. In this talk, an adaptive seamless PK and efficacy design will be discussed. Here, we consider the clinical development of biosimilars including their evaluation in patients rather than healthy volunteers under a situation where both PK and efficacy parameters are required to demonstrate equivalence. The original idea of the proposed method was to organize a clinical trial that includes the statistical analysis of PK as an interim analysis, with sample size recalculation of the efficacy data. This proposal provided useful aspects, such as a shorter time period, additional cost savings, and a smaller number of patients required. The method will be illustrated with the motivating example of biosimilar infliximab.