Moxey-Mims Marva M, Flessner Michael F, Holzman Lawrence, Kaskel Frederick, Sedor John R, Smoyer William E, Thompson Aliza M, Yao Lynne
Due to the number of contributing authors, the affiliations are provided in the Supplemental Material .
Clin J Am Soc Nephrol. 2016 Dec 7;11(12):2234-2243. doi: 10.2215/CJN.00540116. Epub 2016 Sep 26.
Nephrology has conducted few high-quality clinical trials, and the trials that have been conducted have not resulted in the approval of new treatments for primary or inflammatory glomerular diseases. There are overarching process issues that affect the conduct of all clinical trials, but there are also some specialty-specific issues. Within nephrology, primary glomerular diseases are rare, making adequate recruitment for meaningful trials difficult. Nephrologists need better ways, beyond histopathology, to phenotype patients with glomerular diseases and stratify the risk for progression to ESRD. Rigorous trial design is needed for the testing of new therapies, where most patients with glomerular diseases are offered the opportunity to enroll in a clinical trial if standard therapies have failed or are lacking. Training programs to develop a core group of kidney specialists with expertise in the design and implementation of clinical trials are also needed. Registries of patients with glomerular disease and observational studies can aid in the ability to determine realistic estimates of disease prevalence and inform trial design through a better understanding of the natural history of disease. Some proposed changes to the Common Rule, the federal regulations governing the ethical conduct of research involving humans, and the emerging use of electronic health records may facilitate the efficiency of initiating multicenter clinical trials. Collaborations among academia, government scientific and regulatory agencies, industry, foundations, and patient advocacy groups can accelerate therapeutic development for these complex diseases.
肾脏病学领域开展的高质量临床试验较少，而且已开展的试验并未促成针对原发性或炎症性肾小球疾病的新疗法获批。存在一些影响所有临床试验开展的总体流程问题，但也有一些特定领域的问题。在肾脏病学领域，原发性肾小球疾病较为罕见，这使得为有意义的试验招募足够的患者变得困难。肾脏病学家需要除组织病理学之外更好的方法来对肾小球疾病患者进行表型分析，并对进展至终末期肾病的风险进行分层。在测试新疗法时需要严格的试验设计，因为如果标准疗法失败或缺乏，大多数肾小球疾病患者都有机会参加临床试验。还需要开展培训项目，以培养一批在临床试验设计和实施方面具有专业知识的核心肾脏专科医生。肾小球疾病患者登记册和观察性研究有助于确定疾病患病率的实际估计值，并通过更好地了解疾病自然史为试验设计提供信息。对《通用准则》（联邦政府关于涉及人类研究的伦理行为的法规）的一些提议修改以及电子健康记录的新应用可能会提高启动多中心临床试验的效率。学术界、政府科学和监管机构、行业、基金会以及患者权益倡导组织之间的合作可以加速针对这些复杂疾病的治疗研发。
