Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement
Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement
复制标题
DOI：
10.1200/jco.2017.73.7916
复制
发表时间：
2017-11-20
影响因子：
45.3
通讯作者：
Schilsky, Richard L.
中科院分区：
文献类型：
--
作者：
Kim, Edward S.;Bruinooge, Suanna S.;Schilsky, Richard L.
目的资格标准的主要目的是保护试验参与者的安全并确定试验人群。过多或过于严格的资格标准可能会减缓试验的累积，危及结果的普适性，并限制对干预的益处-风险概况的理解。方法ASCO、癌症研究之友和美国食品和药物管理局检查了特定的资格标准(即脑转移、最低年龄、艾滋病毒感染、器官功能障碍和既往和同时患有恶性肿瘤)，以确定是否修改定义以将试验扩展到更广泛的人群。工作小组根据对证据的审查、对患者群体的考虑以及与研究团体的协商，制定了一致的建议。结果：经治疗或临床稳定的脑转移瘤患者应常规纳入试验，只有在有令人信服的理由时才排除。在最初的剂量发现试验中，应根据强有力的科学依据纳入儿科特定的队列。跨越成人和儿科人群的疾病的后期试验应包括年龄超过12岁的患者。健康且艾滋病相关后果风险较低的艾滋病毒感染患者应包括在没有具体理由排除的情况下。肾功能标准应允许肌酐自由清除，除非研究药物涉及肾脏排泄。应纳入既往或同时患有恶性肿瘤的患者，特别是当恶性肿瘤干扰安全性或有效性终点的风险非常低时。结论为了最大限度地提高结果的概括性，试验入选标准应争取包容性。排除患者的理由应该清楚地阐明，并反映与正在调查的治疗相关的预期毒性。(C)2017年美国临床肿瘤学会
PurposeThe primary purposes of eligibility criteria are to protect the safety of trial participants and define the trial population. Excessive or overly restrictive eligibility criteria can slow trial accrual, jeopardize the generalizability of results, and limit understanding of the intervention's benefit-risk profile.MethodsASCO, Friends of Cancer Research, and the US Food and Drug Administration examined specific eligibility criteria (ie, brain metastases, minimum age, HIV infection, and organ dysfunction and prior and concurrent malignancies) to determine whether to modify definitions to extend trials to a broader population. Working groups developed consensus recommendations based on review of evidence, consideration of the patient population, and consultation with the research community.ResultsPatients with treated or clinically stable brain metastases should be routinely included in trials and only excluded if there is compelling rationale. In initial dose-finding trials, pediatric-specific cohorts should be included based on strong scientific rationale for benefit. Later phase trials in diseases that span adult and pediatric populations should include patients older than age 12 years. HIV-infected patients who are healthy and have low risk of AIDS-related outcomes should be included absent specific rationale for exclusion. Renal function criteria should enable liberal creatinine clearance, unless the investigational agent involves renal excretion. Patients with prior or concurrent malignancies should be included, especially when the risk of the malignancy interfering with either safety or efficacy endpoints is very low.ConclusionTo maximize generalizability of results, trial enrollment criteria should strive for inclusiveness. Rationale for excluding patients should be clearly articulated and reflect expected toxicities associated with the therapy under investigation. (C) 2017 by American Society of Clinical Oncology