Melding Regulatory, Pharmaceutical Industry, and U.S. Payer Perspectives on Improving Approaches to Heterogeneity of Treatment Effect in Research and Practice

Effective pursuit of the science and management of heterogeneity of treatment effect (HTE) relies on the mutual understanding of the perspectives of, and collaboration among, the various stakeholders in health care. In this article, we compare, contrast, and endeavor to find areas of alignment across the perspectives of three such stakeholders —regulators, the biopharmaceutical and device industry, and U.S. payers. First, we discuss how evidence of HTE is generated and could be improved upon. For pharmaceuticals, much of the initial research is conducted by the pharmaceutical industry, guided by basic science but also delimited by potential markets, regulatory approval requirements, trial size considerations, and payer expectations for evidence of value. Once a drug is marketed, further evidence can be generated via combining trial data, conducting meta-analysis, and analyzing real-world results through observational research designs; we explore how these efforts can benefit from cooperation across these stakeholders. Second, we discuss the equally important utilization of HTE evidence so that physicians and patients have access to and can benefit from the learnings from this research. Research findings must be translated into actionable information and guidelines that can be incorporated into everyday practice. Doing so requires interaction and collaboration among all involved, based on facilitated communication as well as further evaluation research. We provide examples of several cross-sectorial initiatives that are under way in this area. Finally, we explore some economic aspects of HTE research as part of the drug development, marketing, and treatment process. Understanding the economic incentives present is fundamental to aligning those incentives to improve the availability and utilization of HTE evidence. Clear understandings among regulators, pharma, and payers about high-value targets, methods to efficiently generate and communicate information, and value propositions can lead to “win-win” scenarios for patients, individual payers, the health care system overall, and the future of drug development in producing new medicines.