Considering Sex and Gender in Therapeutics throughout the Product Life Cycle: A Narrative Review and Case Study of Gilteritinib.

Abstract

Background: Biological sex-related factors influence pharmacokinetic, pharmacodynamic, and disease processes that may affect the predictability of drug dosing and adverse effects, which may in turn have clinical consequences for patients' lives. Nonetheless, sex-related factors are not always taken into account in clinical trial design or clinical decision-making, for multiple reasons, including a paucity of studies that clearly and objectively study and measure sex-disaggregated and sex-related outcomes, as well as gaps in regulatory and policy structures for integrating these considerations.

Objectives: To complete a narrative review and use a case study to understand available evidence, inform future research, and provide policy considerations that incorporate information on sex- and gender-related factors into clinician-facing resources.

Methods: A comprehensive review of available literature was conducted using a sex- and gender-based analysis plus (SGBA Plus) approach to identify sex- and/or gender-disaggregated information for gilteritinib, a chemotherapeutic agent. Systematic searches were performed in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Wiley), International Pharmaceutical Abstracts (Ovid), Scopus, and ClinicalTrials.gov, from inception to March 18, 2021. The information was then summarized and compared with the Canadian product monograph for this drug.

Results: Of 311 records screened, 3 provided SGBA Plus information as a component of outcomes, rather than just as categories or demographic characteristics. Of these, 2 were case studies, and 1 was a clinical trial. No studies from the ClinicalTrials.gov database that were in progress at the time of this review provided details about sex-disaggregated outcomes. The Canadian product monograph did not include sex-disaggregated outcome data.

Conclusions: The available evidence from clinical trials, other published literature, and guidance documents does not provide details about sex-disaggregated outcomes for gilteritinib. This paucity of available evidence may create a challenge for clinicians who are making decisions about the efficacy and safety of prescribed therapies in sex-specific populations that have not been well studied.