1 Yale University School of Medicine, New Haven, Connecticut.
2 Robert Wood Johnson Foundation Clinical Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, and Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
J Manag Care Spec Pharm. 2017 Oct;23(10):1066-1076. doi: 10.18553/jmcp.2017.23.10.1066.
Hundreds of drug products are currently marketed in the United States without approval from the FDA. The 2006 Unapproved Drugs Initiative (UDI) requires manufacturers to remove these drug products from the market or obtain FDA approval by demonstrating evidence of safety and efficacy. Once the FDA acts against an unapproved drug, fewer manufacturers remain in the market, potentially enabling drug price increases and greater susceptibility to drug shortages. There is a need for systematic study of the UDI's effect on prices and shortages of all targeted drugs.
To examine the clinical evidence for approval and association with prices and shortages of previously unapproved prescription drugs after being addressed by the UDI.
Previously unapproved prescription drugs that faced UDI regulatory action or with at least 1 product that received FDA approval through manufacturers' voluntary compliance with the UDI between 2006 and 2015 were identified. The clinical evidence was categorized as either newly conducted clinical trials or use of previously published literature and/or bioequivalence studies to demonstrate safety and efficacy. We determined the change in average wholesale price, presence of shortage, and duration of shortage for each drug during the 2 years before and after UDI regulatory action or approval through voluntary compliance.
Between 2006 and 2015, 34 previously unapproved prescription drugs were addressed by the UDI. Nearly 90% of those with a drug product that received FDA approval were supported by literature reviews or bioequivalence studies, not new clinical trial evidence. Among the 26 drugs with available pricing data, average wholesale price during the 2 years before and after voluntary approval or UDI action increased by a median of 37% (interquartile range [IQR] = 23%-204%; P < 0.001). The number of drugs in shortage increased from 17 (50.0%) to 25 (73.5%) during the 2 years before and after, respectively (P = 0.046). The median shortage duration in the 2 years before and after voluntary approval or UDI action increased from 31 days (IQR = 0-339) to 217 days (IQR = 0-406; P = 0.053).
The UDI was associated with higher drug prices and more frequent drug shortages when compared with the period before UDI action, while the approval process for these drugs did not necessarily require new clinical evidence to establish safety or efficacy.
This project was not supported by any external grants or funds. Gupta was supported by the Yale University School of Medicine Office of Student Research at the time of this study. Dhruva is supported by the Department of Veterans Affairs as part of the Robert Wood Johnson Foundation Clinical Scholars program. Ross reports receiving research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing; from Medtronic and the FDA to develop methods for postmarket surveillance of medical devices; from the FDA to establish the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation; from the Blue Cross Blue Shield Association to better understand medical technology evidence generation; from the Centers for Medicare & Medicaid Services to develop and maintain performance measures that are used for public reporting; and from the Laura and John Arnold Foundation to support the Collaboration on Research Integrity and Transparency at Yale. Fox reports travel support from Oklahoma Society of Health System Pharmacists, Premier Oncology Hematology Management Society, and SEHA-United Arab Emirates. Vizient provides some financial support to the University of Utah Drug Information Service to provide summaries of drug shortage information. Gupta and Ross were responsible for the conception and design of this work, drafted the manuscript, and conducted the statistical analysis. Gupta and Fox were responsible for acquisition of data. Ross provided supervision. All authors participated in the analysis and interpretation of the data and critically revised the manuscript for important intellectual content.
目前，有数百种药品未经 FDA 批准就在美国上市销售。2006 年未批准药品倡议（UDI）要求制造商通过证明安全性和有效性来将这些药品从市场上撤下或获得 FDA 批准。一旦 FDA 对未经批准的药品采取行动，市场上剩下的制造商就更少了，这可能会导致药品价格上涨和更容易出现短缺。需要对 UDI 对所有目标药品的价格和短缺的影响进行系统研究。
检查在 UDI 处理后，先前未经批准的处方药获得批准的临床证据，并与价格和短缺情况相关联。
确定了在 2006 年至 2015 年期间面临 UDI 监管行动或至少有一种产品通过制造商自愿遵守 UDI 获得 FDA 批准的先前未经批准的处方药。临床证据分为新进行的临床试验或使用先前发表的文献和/或生物等效性研究来证明安全性和有效性。我们确定了在 UDI 监管行动或批准后两年内，每种药物的平均批发价格变化、短缺情况和短缺持续时间。
在 2006 年至 2015 年期间，34 种先前未经批准的处方药受到 UDI 的处理。那些获得 FDA 批准的药物产品中，近 90%的药物产品得到了文献综述或生物等效性研究的支持，而不是新的临床试验证据。在有可用定价数据的 26 种药物中，自愿批准或 UDI 行动前后两年的平均批发价格中位数增加了 37%（四分位距[IQR] = 23%-204%；P < 0.001）。在自愿批准或 UDI 行动前后两年内，短缺药物的数量从 17 种（50.0%）增加到 25 种（73.5%）（P = 0.046）。自愿批准或 UDI 行动前后两年的短缺持续时间中位数从 31 天（IQR = 0-339）增加到 217 天（IQR = 0-406；P = 0.053）。
与 UDI 行动之前相比，UDI 与更高的药品价格和更频繁的药品短缺有关，而这些药品的批准过程不一定需要新的临床证据来建立安全性或有效性。
本项目未得到任何外部赠款或资金的支持。Gupta 在进行这项研究时得到了耶鲁大学医学院学生研究办公室的支持。Dhruva 得到了退伍军人事务部的支持，作为罗伯特伍德约翰逊基金会临床学者计划的一部分。Ross 报告说，他从 Johnson and Johnson 获得研究支持，以开发临床试验数据共享方法；从 Medtronic 和 FDA 开发方法，以对医疗器械进行上市后监测；从 FDA 建立耶鲁大学-梅奥诊所卓越监管科学与创新中心；从蓝十字蓝盾协会更好地了解医疗技术证据生成；从医疗保险和医疗补助服务中心开发和维护用于公共报告的绩效措施；以及从 Laura and John Arnold 基金会支持耶鲁大学的研究诚信和透明度合作。Fox 报告说，他曾得到俄克拉荷马州卫生系统药剂师协会、Premier Oncology Hematology Management Society 和 SEHA-United Arab Emirates 的旅行支持。Vizient 为犹他州药物信息服务提供了一些财务支持，以提供药物短缺信息摘要。Gupta 和 Ross 负责这项工作的构思和设计，起草了手稿，并进行了统计分析。Gupta 和 Fox 负责数据采集。Ross 提供了监督。所有作者都参与了数据分析和解释，并对关键的内容进行了批判性评估。
