Zhou Shuang, Qi Karen, Nugent Bridget M, Bersoff-Matcha Susan J, Struble Kimberly
Food and Drug Administration Office of Women's Health Center for Drug Evaluation and Research, Division of Antivirals.
Center for Drug Evaluation and Research, Office of Biostatistics.
AIDS. 2023 May 1;37(6):895-903. doi: 10.1097/QAD.0000000000003478. Epub 2023 Jan 6.
To examine female participation and the observed efficacy and safety by sex from phase 3 HIV-1 trials submitted to the United States Food and Drug Administration (FDA) to support approval or a major labeling change.
Our analyses were based on phase 3 trials in HIV-1 infected treatment-naive adults submitted to FDA since 2010.
We evaluated enrollment of treatment-naive females in 18 clinical trials for HIV-1. Participation to prevalence ratio (PPR) was calculated as the percentage of females among trial participants divided by the percentage of females in the disease population. PPR between 0.8 and 1.2 reflects similar representation of females in the trial and the disease population. Sex differences in efficacy (virologic response rates) and selected safety events were evaluated.
United States (US) females, particularly US Black females were not adequately represented in clinical trials. The PPR for US females overall was 0.59 and for US Black females was 0.63. Statistically significant sex differences favoring males were observed for efficacy outcomes in both the global population and US participants. Statistically significant sex differences were observed for some safety outcomes.
US females are underrepresented in phase 3 HIV-1 clinical trials. Underrepresentation was not likely due to enrollment criteria. Statistically significant sex differences were noted for efficacy and selected safety outcomes; however, some differences were not clinically relevant. The ability to detect sex differences was hindered by low numbers of female participants overall and within subgroups. Additional research into innovative approaches to recruit and retain females in clinical trials should continue.
审查提交给美国食品药品监督管理局（FDA）以支持批准或重大标签变更的3期HIV-1试验中的女性参与情况以及按性别观察到的疗效和安全性。
我们的分析基于自2010年以来提交给FDA的针对未接受过治疗的HIV-1感染成年患者的3期试验。
我们评估了18项HIV-1临床试验中未接受过治疗的女性的入组情况。参与患病率比（PPR）的计算方法是试验参与者中女性的百分比除以疾病人群中女性的百分比。PPR在0.8至1.2之间反映了试验和疾病人群中女性的代表性相似。评估了疗效（病毒学反应率）和选定的安全事件中的性别差异。
美国女性，尤其是美国黑人女性在临床试验中的代表性不足。美国女性总体的PPR为0.59，美国黑人女性为0.63。在全球人群和美国参与者中，在疗效结果方面均观察到有利于男性的具有统计学意义的性别差异。在一些安全结果方面也观察到了具有统计学意义的性别差异。
美国女性在3期HIV-1临床试验中的代表性不足。代表性不足不太可能是由于入组标准。在疗效和选定的安全结果方面注意到了具有统计学意义的性别差异；然而，一些差异在临床上并不相关。总体女性参与者以及亚组内女性参与者数量较少阻碍了检测性别差异的能力。应继续对在临床试验中招募和留住女性的创新方法进行更多研究。
