New advancements in exposure-response analysis to inform regulatory decision making

Abstract

To date, Exposure-Response (E-R) analyses have been recognized and routinely utilized in regulatory reviews, mainly to address key questions such as whether the proposed dosing regimen for a new drug is optimal or is warranted for further adjustment in specific populations in the context of the overall risk/benefit profile. This chapter will start from a summary of E-R methods commonly used in current applications followed with new methodology development and applications of E-R analyses on other aspects of reviews. Reporting on new methodology development is focused on case-control analyses when drug exposure is confounded with baseline disease status for several antibody oncology drugs. Reporting on applications of E-R analysis in new areas of review falls into using E-R analysis to derive the effect size for the noninferiority trial and subgroup analyses to identify favorable risk/benefit profile in specific population(s). The chapter also mentioned the potential role of E-R analysis in precision medicine by leveraging individual drug exposure to achieve balanced risk/benefit at the individual level.