Vaduganathan Muthiah, Butler Javed, Roessig Lothar, Fonarow Gregg C, Greene Stephen J, Metra Marco, Cotter Gadi, Kupfer Stuart, Zalewski Andrew, Sato Naoki, Filippatos Gerasimos, Gheorghiade Mihai
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Heart Fail Rev. 2015 Jul;20(4):393-400. doi: 10.1007/s10741-015-9485-8.
With one possible exception, the last decade of clinical trials in hospitalized heart failure (HHF) patients has failed to demonstrate improvement in long-term clinical outcomes. This trend necessitates a need to evaluate optimal drug development strategies and standards of trial conduct. It has become increasingly important to recognize the heterogeneity among HHF patients and the differential characterization of novel drug candidates. Targeting these agents to specific subpopulations may afford optimal net response related to the particular mode of action of the drug. Analyses of previous trials demonstrate profound differences in the baseline characteristics of patients enrolled across global regions and participating sites. Such differences may influence risks for events and interpretation of results. Therefore, the actual execution of trials and the epidemiology of HHF populations at the investigative sites must be taken into consideration. Collaboration among participating sites including the provision of registry data tailored to the planned development program will optimize trial conduct. Observational data prior to study initiation may enable sites to feedback and engage in protocol development to allow for feasible and valid clinical trial conduct. This site-centered, epidemiology-based network environment may facilitate studies in specific patient populations and promote optimal data collection and clear interpretation of drug safety and efficacy. This review summarizes the roundtable discussion held by a multidisciplinary team of representatives from academia, National Institutes of Health, industry, regulatory agencies, payers, and contract and academic research organizations to answer the question: Who should be targeted for novel therapies in HHF?
除了一个可能的例外情况，过去十年针对住院心力衰竭（HHF）患者的临床试验未能证明长期临床结局有所改善。这种趋势使得有必要评估最佳药物研发策略和试验开展标准。认识到HHF患者之间的异质性以及新型候选药物的差异特征变得越来越重要。将这些药物靶向特定亚群可能会根据药物的特定作用方式提供最佳净反应。对先前试验的分析表明，全球各地区和参与试验地点所招募患者的基线特征存在显著差异。这些差异可能会影响事件风险和结果解读。因此，必须考虑试验的实际执行情况以及研究地点HHF人群的流行病学情况。参与试验地点之间的合作，包括提供针对计划开展的研发项目量身定制的登记数据，将优化试验开展。研究启动前的观察性数据可能使各试验地点能够反馈并参与方案制定，以确保临床试验可行且有效。这种以试验地点为中心、基于流行病学的网络环境可能会促进针对特定患者群体的研究，并推动最佳数据收集以及对药物安全性和疗效的清晰解读。本综述总结了由来自学术界、美国国立卫生研究院、制药行业、监管机构、医保支付方以及合同和学术研究组织的代表组成的多学科团队举行的圆桌讨论，以回答以下问题：HHF的新型疗法应以谁为目标人群？
