Female underrepresentation and adverse events reporting biases in lung cancer clinical trials: a systematic review...

Despite regulatory initiatives to improve female representation in clinical trials, sex-based disparities persist, particularly in oncology. This is of concern given the rising burden of lung cancer in women. We aimed to quantify female representation in lung cancer clinical trials over the past three decades and to examine whether trial-level differences in female enrolment were associated with differences in reported adverse events (AEs).

We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating drug therapies for lung cancer, identified through PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1993, to April 1, 2025. Two reviewers independently assessed study eligibility, extracted data, and evaluated risk of bias. Enrolment incidence disparity (EID) was calculated to assess female representation. Reported incidence of AEs was analysed in relation to female representation across treatment settings. This study is registered with PROSPERO (CRD42024537925).

Among 44,915 records identified, 636 studies comprising 265,989 participants were included. Most studies were judged to be at low risk of bias (83%), whereas 3% were at high risk. The pooled EID was -3.17% (95% CI: 4.10, -2.24), indicating underrepresentation of women overall, particularly in trials conducted in very high Human Development Index (HDI) settings, including Europe, Oceania, and North America. Underrepresentation was also observed across several trial subgroups, including younger populations, predominantly Caucasian populations, and selected disease-stage strata. Trial-level differences in female representation were associated with differences in reported AE incidence across treatment settings.

Women remain underrepresented in lung cancer RCTs, which may limit the generalisability of trial findings to female patients. Trial-level differences in female representation were associated with differences in reported AE incidence, supporting the need for more inclusive recruitment and more transparent sex-disaggregated safety reporting.