Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Health Qual Life Outcomes. 2013 May 15;11:83. doi: 10.1186/1477-7525-11-83.
The purpose of this research was to fully explore the impact of endpoint type (primary vs. nonprimary) on decisions related to patient-reported outcome (PRO) labeling claims supported by PRO measures and to determine if nonprimary PRO endpoints are being fully optimized.This review examines the use of PROs as both primary and nonprimary endpoints in support of demonstration of treatment benefit of new molecular entities (NMEs) and biologic license applications (BLAs) in the United States in the years 2000 to 2012.
All NMEs and BLAs approved by the Food and Drug Administration (FDA) between January 2000 and June 2012 were identified using the FDA Drug Approval Reports Web page. Generic products granted tentative approvals were excluded. For all identified products, medical review sections from publicly available drug approval packages were reviewed to identify PRO endpoint status. Product labels (indication, clinical trials sections) were reviewed to determine the number and type of PRO claim.
A total of 308 NMEs/BLAs were identified. Of these, 70 NMEs/BLAs (23%) were granted PRO claims. The majority of product claims were for disease- or condition-specific signs and symptoms. Of the 70 products with PRO claims, a PRO was a primary endpoint for the vast majority (57 [81%]). A total of 19 of the 70 products were granted a PRO claim based on a nonprimary endpoint. While nonprimary endpoints were used most often to support claims of improved signs or symptoms, nonprimary endpoints were much more likely to support claims of higher order impacts.
Successful PRO labeling claims are typically based on primary endpoints assessing signs and symptoms. Based on this research, studies with PROs as primary endpoints are far more likely to facilitate positive regulatory review and acceptance of PROs in support of labeling claims. Although inclusion of PROs as nonprimary endpoints in clinical trials has its challenges, recent PRO labels granted by the FDA show that they can indeed be candidates for PRO labeling claims as long as they are supported by evidence.
本研究旨在全面探讨终点类型（主要与非主要）对支持患者报告结局（PRO）测量的 PRO 标签主张相关决策的影响，并确定非主要 PRO 终点是否得到充分优化。本综述考察了 PRO 作为主要和非主要终点在支持美国新分子实体（NME）和生物制品许可申请（BLA）治疗获益中的应用，时间范围为 2000 年至 2012 年。
使用 FDA 药物批准报告网页，确定 2000 年 1 月至 2012 年 6 月期间 FDA 批准的所有 NME 和 BLA。排除给予暂定批准的仿制药。对于所有确定的产品，审查可公开获得的药物批准包中的医学审查部分，以确定 PRO 终点状态。审查产品标签（适应证、临床试验部分），以确定 PRO 主张的数量和类型。
共确定 308 个 NME/BLA。其中，70 个 NME/BLA（23%）获得 PRO 主张。大部分产品主张针对特定疾病或病症的体征和症状。在 70 个有 PRO 主张的产品中，绝大多数（57 [81%]）的 PRO 是主要终点。19 个产品获得了基于非主要终点的 PRO 主张。虽然非主要终点主要用于支持体征或症状改善的主张，但非主要终点更有可能支持更高阶影响的主张。
成功的 PRO 标签主张通常基于评估体征和症状的主要终点。基于本研究，以 PRO 为主要终点的研究更有可能促进 PRO 监管审查和接受，以支持标签主张。虽然在临床试验中纳入 PRO 作为非主要终点存在挑战，但 FDA 最近授予的 PRO 标签表明，只要有证据支持，它们确实可以作为 PRO 标签主张的候选。
