Sample Size Estimation Using a Partially Clustered Frailty Model for Biomarker-Strategy Designs With Multiple Treatments

Pharm Stat. 2024 Nov-Dec;23(6):1084-1094. doi: 10.1002/pst.2407. Epub 2024 Jul 16.

Abstract

Biomarker-guided therapy is a growing area of research in medicine. To optimize the use of biomarkers, several study designs including the biomarker-strategy design (BSD) have been proposed. Unlike traditional designs, the emphasis here is on comparing treatment strategies and not on treatment molecules as such. Patients are assigned to either a biomarker-based strategy (BBS) arm, in which biomarker-positive patients receive an experimental treatment that targets the identified biomarker, or a non-biomarker-based strategy (NBBS) arm, in which patients receive treatment regardless of their biomarker status. We proposed a simulation method based on a partially clustered frailty model (PCFM) as well as an extension of Freidlin formula to estimate the sample size required for BSD with multiple targeted treatments. The sample size was mainly influenced by the heterogeneity of treatment effect, the proportion of biomarker-negative patients, and the randomization ratio. The PCFM is well suited for the data structure and offers an alternative to traditional methodologies.

Keywords: biomarker‐strategy; frailty model; heterogeneity; randomized; sample size.

MeSH terms

  • Biomarkers*
  • Cluster Analysis
  • Computer Simulation
  • Humans
  • Models, Statistical*
  • Randomized Controlled Trials as Topic / methods
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Research Design* / statistics & numerical data
  • Sample Size

Substances

  • Biomarkers