Jarow Jonathan P, Lemery Steven, Bugin Kevin, Lowy Naomi
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Ther Innov Regul Sci. 2017 Mar 1;51(2):246-249. doi: 10.1177/2168479016679214.
The purpose of this study was to describe the role of the US Food and Drug Administration (FDA) in ensuring the safety of patients receiving investigational drugs under expanded access.
To better define FDA's role in the review of requests for expanded access, multiple queries of FDA's Center for Drug Evaluation and Research (CDER) document tracking system were performed. The queries identified reasons for, and outcomes of, expanded access requests for investigational drugs that were either not allowed to proceed or denied over a 10-year time period. An in-depth review of a random sample of single-patient, non-emergency investigational new drug (IND) applications that were allowed to proceed was also conducted.
Overall, 99.3% of the applications for almost 9000 expanded access of an investigational drug were allowed to proceed. There were 62 requests that were either denied (38 emergency INDs) or not allowed to proceed (24 non-emergency INDs). The most common reasons for denying emergency INDs was that the patient was stable on current therapy and that it was not deemed an emergency. The most common reasons for not allowing non-emergency expanded access INDs to proceed were incomplete application, unsafe dosing, demonstrated lack of efficacy for intended use, availability of adequate alternative therapies, and inadequate information provided in the application on which to base a decision. A review of a random sample of 150 single-patient, non-emergency INDs revealed that FDA recommended changes to dosing, safety monitoring, or informed consent in 11%.
FDA plays a significant role in the protection of patients who receive investigational drugs under expanded access. An extremely small percentage of applications received are not allowed to proceed; however, FDA provides significant input based on information that may not be available to treating physicians in order to ensure patient safety under the applications that do proceed.
本研究的目的是描述美国食品药品监督管理局（FDA）在确保接受扩大使用范围的研究性药物的患者安全方面所起的作用。
为了更好地界定FDA在审查扩大使用范围申请中的作用，对FDA药品评价和研究中心（CDER）的文件追踪系统进行了多次查询。这些查询确定了在10年期间未被批准进行或被拒绝的研究性药物扩大使用范围申请的原因及结果。还对一组随机抽取的获准进行的单患者、非紧急研究性新药（IND）申请进行了深入审查。
总体而言，近9000项研究性药物扩大使用范围的申请中有99.3%被批准进行。有62项申请被拒绝（38项紧急IND）或未被批准进行（24项非紧急IND）。拒绝紧急IND的最常见原因是患者在当前治疗下情况稳定且不被视为紧急情况。不批准非紧急扩大使用范围IND进行的最常见原因是申请不完整、给药不安全、已证明对预期用途缺乏疗效、有足够的替代疗法可用以及申请中提供的用于决策的信息不足。对150项单患者、非紧急IND的随机样本进行审查发现，FDA在11%的申请中建议对给药、安全监测或知情同意进行修改。
FDA在保护接受扩大使用范围的研究性药物的患者方面发挥着重要作用。获得的申请中只有极小比例未被批准进行；然而，FDA根据治疗医生可能无法获得的信息提供了重要意见，以确保在获批进行的申请下患者的安全。
