Quantifying factors for the success of stratified medicine

Key Points Co-developing a drug with a diagnostic to create a stratified medicine presents challenges for product developers, regulators, payers and clinicians. With the aim of developing a shared framework and tools for understanding the impact of these challenges, here we present an analysis using data and modelling from case studies in oncology and Alzheimer's disease. Key findings are summarized below. A prospective stratified development and market-based approach created positive net economic value for the drug developer in all three case studies examined. A stratification approach following an all-comers trial does not always create value owing to the time delays and increased costs it incurs. Three key factors from a stratified medicine approach serve as the most crucial determinants of the potential economic value for a developer: the therapeutic effect, predictive biomarker prevalence and the clinical performance of the companion diagnostic. Relatively small study sizes (< 300 patients) are required to discover predictive biomarkers with similar performance characteristics of the KRAS mutational status (for epidermal growth factor receptor inhibitors) or HER2 gene expression level (for trastuzumab). Co-developing a stratified medicine presents multiple challenges, including an inherent timing mismatch, because the science underlying the predictive biomarker usually trails that of the therapeutic, and a relatively low economic value is typically associated with the companion diagnostic. Multiple variable simulations demonstrate that developmental, regulatory and commercial factors are frequently multiplicative rather than additive, resulting in complementary virtuous or spiralling negative cascades of the economic value for the developer of the therapeutic. This article illustrates how such analyses can aid the coordination of diagnostic and drug development, and the selection of optimal development and commercialization strategies. It also illustrates the interplay of key factors on the economic feasibility of a stratified medicine, which may have important implications for public policy makers.