Internal Medicine Department, Yale University School of Medicine, 367 Cedar Street, 4th Floor, New Haven, CT, 06520, USA.
Cushing/Whitney Medical Library, Yale University, 333 Cedar Street, Box 208014, New Haven, CT, 06520, USA.
BMC Health Serv Res. 2022 Jul 29;22(1):970. doi: 10.1186/s12913-022-08272-z.
Repurposing is a drug development strategy receiving heightened attention after the Food and Drug Administration granted emergency use authorization of several repurposed drugs to treat Covid-19. There remain knowledge gaps on the root causes, facilitators and barriers for repurposing.
This systematic review used controlled vocabulary and free text terms to search ABI/Informa, Academic Search Premier, Business Source Complete, Cochrane Library, EconLit, Google Scholar, Ovid Embase, Ovid Medline, Pubmed, Scopus, and Web of Science Core Collection databases for the characteristics, reasons and example of companies deprioritizing development of promising drugs and barriers, facilitators and examples of successful re-purposing.
We identified 11,814 articles, screened 5,976 for relevance, found 437 eligible for full text review, 115 of which were included in full analysis. Most articles (66%, 76/115) discussed why promising drugs are abandoned, with lack of efficacy or superiority to other therapies (n = 59), strategic business reasons (n = 35), safety problems (n = 28), research design decisions (n = 12), the complex nature of a studied disease or drug (n = 7) and regulatory bodies requiring more information (n = 2) among top reasons. Key barriers to repurposing include inadequate resources (n = 42), trial data access and transparency around abandoned compounds (n = 20) and expertise (n = 11). Additional barriers include uncertainty about the value of repurposing (n = 13), liability risks (n = 5) and intellectual property (IP) challenges (n = 26). Facilitators include the ability to form multi-partner collaborations (n = 38), access to compound databases and database screening tools (n = 32), regulatory modifications (n = 5) and tax incentives (n = 2).
Promising drugs are commonly shelved due to insufficient efficacy or superiority to alternate therapies, poor market prospects, and industry consolidation. Inadequate resources and data access and challenges negotiating IP are key barriers to repurposing reaching its full potential as a core approach in drug development. Multi-partner collaborations and the availability and use of compound databases and tax incentives are key facilitators for repurposing. More research is needed on the current value of repurposing in drug development and how to better facilitate resources to support it, where valuable, especially financial, staffing for out-licensing shelved products, and legal expertise to negotiate IP agreements in multi-partner collaborations.
The protocol was registered on Open Science Framework ( https://osf.io/f634k/ ) as it was not eligible for registration on PROSPERO as the review did not focus on a health-related outcome.
在食品和药物管理局批准几种重新利用的药物紧急用于治疗Covid-19 之后，重新利用作为一种药物开发策略受到了高度关注。对于重新利用的根本原因、促进因素和障碍，仍然存在知识差距。
本系统评价使用受控词汇和自由文本术语，在 ABI/Informa、Academic Search Premier、Business Source Complete、Cochrane Library、 EconLit、Google Scholar、Ovid Embase、Ovid Medline、Pubmed、Scopus 和 Web of Science Core Collection 数据库中搜索了公司优先考虑开发有前途的药物和障碍的特征、原因和示例，以及成功重新利用的障碍、促进因素和示例。
我们确定了 11814 篇文章，筛选了 5976 篇相关文章，发现了 437 篇符合全文审查标准的文章，其中 115 篇进行了全文分析。大多数文章（66%，76/115）讨论了为什么有前途的药物被放弃，原因包括疗效或优于其他疗法不足（n=59）、战略商业原因（n=35）、安全问题（n=28）、研究设计决策（n=12）、研究疾病或药物的复杂性质（n=7）和监管机构要求提供更多信息（n=2）。重新利用的主要障碍包括资源不足（n=42）、试验数据获取和废弃化合物透明度问题（n=20）和专业知识（n=11）。其他障碍包括对重新利用价值的不确定性（n=13）、责任风险（n=5）和知识产权（IP）挑战（n=26）。促进因素包括形成多方合作的能力（n=38）、化合物数据库和数据库筛选工具的获取（n=32）、监管修改（n=5）和税收激励（n=2）。
有前途的药物通常因疗效或优于替代疗法不足、市场前景不佳和行业整合而被搁置。资源不足、数据获取和谈判 IP 方面的挑战是重新利用充分发挥潜力作为药物开发核心方法的主要障碍。多方合作以及化合物数据库的可用性和使用以及税收激励是重新利用的关键促进因素。需要更多研究来了解重新利用在药物开发中的当前价值，以及如何更好地为支持它提供资源，特别是在有价值的情况下，特别是为放弃许可的搁置产品提供财务、人员配备和法律专业知识，以进行多方合作中的 IP 协议谈判。
该方案在开放科学框架（https://osf.io/f634k/）上进行了注册，因为它不符合 PROSPERO 的注册资格，因为该审查不侧重于健康相关结果。
