Canadian Centre for Applied Research in Cancer Control (CC-ARCC), Vancouver, British Columbia, Canada.
Canadian Centre for Applied Research in Cancer Control (CC-ARCC), Vancouver, British Columbia, Canada. Electronic address: https://www.twitter.com/AdamR_UBC.
J Cancer Policy. 2021 Dec;30:100311. doi: 10.1016/j.jcpo.2021.100311. Epub 2021 Oct 29.
Women continue to be underrepresented in oncology clinical trials, leading to poor, underpowered subgroup analyses that cannot be generalized to cancer patients in practice. In 2014, the US Food and Drug Administration (FDA) released an Action Plan, which included actions to improve the quality and reporting of demographic subgroup data. We sought to evaluate the five-year progress since the release of this report by assessing the credibility of sex-specific subgroup analyses in oncology clinical trials.
We reviewed the FDA Hematology/Oncology Approvals website for New Molecular Entities (NMEs) that were approved for adults from 2015 to 2020. Publications and their supplementary indexes were reviewed by two authors (K.J. & A.R.) against ten criteria that gauge the credibility of subgroup analyses by assessing factors related to study design, analysis, and context. One point was awarded for each criteria met, for a maximum score of 10.
We identified a total of 73 NMEs approved for cancer treatment between 2015-2020, of which 61 met our eligibility criteria. Of these, 32 studies (52 %) reported a subgroup analysis by sex and were included in our analysis. Phase 2 (41 %) and Phase 3 (53 %) studies represented most studies. No study met ≥3 credibility criteria.
Only half the studies included in our analysis reported outcomes by sex, which suggests the activities stipulated in the 2014 US FDA Action Plan might be ineffective. This is concerning as uncredible sex-specific subgroup analyses can lead to wrongful clinical decision-making and poor patient outcomes.
Our findings suggest sex-specific subgroup analyses in oncology are not credible and users of these data should interpret results with caution. Regulatory bodies, such as the US FDA, ought to mandate subgroup analyses by demographic groups in drug applications. Peer-reviewed journals could ensure investigators disclose study results by sex as a condition for publication.
女性在肿瘤临床试验中的代表性仍然不足，导致亚组分析数据不足且缺乏效力，无法推广至实际癌症患者。2014 年，美国食品药品监督管理局（FDA）发布了行动计划，其中包括了提高人口统计学亚组数据质量和报告的措施。我们试图通过评估肿瘤临床试验中性别特异性亚组分析的可信度，来评估该报告发布五年以来的进展。
我们在 FDA 血液学/肿瘤学批准网站上审查了 2015 年至 2020 年批准用于成人的新型分子实体（NME）。两名作者（K.J. 和 A.R.）对出版物及其补充索引进行了审查，根据十项标准评估了亚组分析的可信度，这些标准通过评估与研究设计、分析和背景相关的因素来衡量亚组分析的可信度。每个符合标准的项目得 1 分，最高得分为 10 分。
我们共确定了 73 种在 2015 年至 2020 年期间批准用于癌症治疗的 NME，其中 61 种符合我们的入选标准。在这些研究中，有 32 项（52%）研究报告了性别亚组分析，并纳入了我们的分析。二期（41%）和三期（53%）研究占大多数。没有研究符合≥3 项可信度标准。
我们分析中纳入的研究中只有一半报告了按性别划分的结果，这表明 2014 年美国 FDA 行动计划中的活动可能无效。这令人担忧，因为不可信的性别特异性亚组分析可能导致错误的临床决策和较差的患者结局。
我们的研究结果表明，肿瘤学中的性别特异性亚组分析不可信，使用者应谨慎解释这些数据的结果。监管机构，如美国 FDA，应该在药物申请中强制要求按人口统计学亚组进行分析。同行评议期刊可以确保研究人员按性别披露研究结果，作为发表的条件。
