Performance Status Restriction in Phase III Cancer Clinical Trials.
Performance Status Restriction in Phase III Cancer Clinical Trials.
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DOI：
10.6004/jnccn.2020.7578
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Ludmir EB
中科院分区：
文献类型：
--
作者：
Abi Jaoude J;Kouzy R;Mainwaring W;Lin TA;Miller AB;Jethanandani A;Espinoza AF;Pasalic D;Verma V;VanderWalde NA;Smith BD;Smith GL;Fuller CD;Das P;Minsky BD;Rödel C;Fokas E;Jagsi R;Thomas CR;Subbiah IM;Taniguchi CM;Ludmir EB
体能状态（PS）良好的患者在随机临床试验（RCT）中往往更受青睐，这可能会限制试验结果的普遍性。我们旨在描述与使用PS入选标准相关的试验相关因素，并按PS分析患者入组情况。
通过ClinicalTrials.gov确定了成人、治疗性、多臂Ⅲ期癌症特异性RCT。从文章中提取PS数据。确定了PS限制为东部肿瘤协作组（ECOG）评分≤1的试验。确定了与PS限制相关的因素，并分析了PS限制的使用随时间的变化。
总共纳入了600项试验，238213名患者有PS数据。在这些试验中，527项研究（87.8%）规定了PS限制界限，其中237项（39.5%）有严格的入选标准（ECOG PS≤1）。基于PS（ECOG PS≤1）的入选标准限制在企业支持的试验（P<0.001）和肺癌试验（P<0.001）中更为常见。近一半获得美国食品药品监督管理局（FDA）批准的试验包括严格的PS限制。所有试验中入组的大多数患者ECOG PS为0 - 1（96.3%）。即使在允许ECOG PS≥2患者入组的试验中，入组患者中只有8.1%体能状态较差。肺癌、乳腺癌、胃肠道癌和泌尿生殖系统癌症的试验中，体能状态差的患者均<5%。最后，在导致后续FDA批准的试验中，只有4.7%的入组患者体能状态差。
肿瘤学RCT中普遍使用PS限制，体能状态差的患者入组极少。选择性招募更健康的患者有可能严重限制和扭曲试验结果。未来的试验应考虑更广泛的癌症人群，并密切监测毒性，以确保结果的普遍性，同时保障患者安全。
Patients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We aimed to characterize trial-related factors associated with the use of PS eligibility criteria and analyze patient accrual breakdown by PS. Adult, therapeutic, multiarm phase III cancer-specific RCTs were identified through ClinicalTrials.gov. PS data were extracted from articles. Trials with a PS restriction ECOG score ≤1 were identified. Factors associated with PS restriction were determined, and the use of PS restrictions was analyzed over time. In total, 600 trials were included and 238,213 patients had PS data. Of those trials, 527 studies (87.8%) specified a PS restriction cutoff, with 237 (39.5%) having a strict inclusion criterion (ECOG PS ≤1). Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (P<.001) and lung cancer trials (P<.001). Nearly half of trials that led to FDA approval included strict PS restrictions. Most patients enrolled across all trials had an ECOG PS of 0 to 1 (96.3%). Even among trials that allowed patients with ECOG PS ≥2, only 8.1% of those enrolled had a poor PS. Trials of lung, breast, gastrointestinal, and genitourinary cancers all included <5% of patients with poor PS. Finally, only 4.7% of patients enrolled in trials that led to subsequent FDA approval had poor PS. Use of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring to ensure the generalizability of results while maintaining patient safety.
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DOI：
10.1136/bmj.b2535
发表时间：
2009-07-21
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Moher D;Liberati A;Tetzlaff J;Altman DG;PRISMA Group
通讯作者：
PRISMA Group
影响因子：
3.1
作者：
Batista Correa, Gefter Thiago;Bandeira, Gabriela Alencar;Batista De Paula, Alfredo Mauricio
通讯作者：
Batista De Paula, Alfredo Mauricio
影响因子：
6.2
作者：
Gronlund, B;Hogdall, C;Engelholm, SA
通讯作者：
Engelholm, SA
影响因子：
158.5
作者：
Perry, James R.;Laperriere, Normand;Mason, Warren P.
通讯作者：
Mason, Warren P.
影响因子：
45.3
作者：
Jin, Susan;Pazdur, Richard;Sridhara, Rajeshwari
通讯作者：
Sridhara, Rajeshwari