QUEST Center for Responsible Research, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
Br J Clin Pharmacol. 2023 Jan;89(1):340-350. doi: 10.1111/bcp.15503. Epub 2022 Aug 31.
Research ethics committees and regulatory agencies assess whether the benefits of a proposed early-stage clinical trial outweigh the risks based on preclinical studies reported in investigator's brochures (IBs). Recent studies have indicated that the reporting of preclinical evidence presented in IBs does not enable proper risk-benefit assessment. We interviewed different stakeholders (regulators, research ethics committee members, preclinical and clinical researchers, ethicists, and metaresearchers) about their views on measures to increase the completeness and robustness of preclinical evidence reporting in IBs.
This study was preregistered (https://osf.io/nvzwy/). We used purposive sampling and invited stakeholders to participate in an online semistructured interview between March and June 2021. Themes were derived using inductive content analysis. We used a strengths, weaknesses, opportunities and threats matrix to categorize our findings.
Twenty-seven international stakeholders participated. The interviewees pointed to several strengths and opportunities to improve completeness and robustness, mainly more transparent and systematic justifications for the included studies. However, weaknesses and threats were mentioned that could undermine efforts to enable a more thorough assessment: The interviewees stressed that current review practices are sufficient to ensure the safe conduct of first-in-human trials. They feared that changes to the IB structure or review process could overburden stakeholders and slow drug development.
In principle, more robust decision-making processes align with the interests of all stakeholders and with many current initiatives to increase the translatability of preclinical research and limit uninformative or ill-justified trials early in the development process. Further research should investigate measures that could be implemented to benefit all stakeholders.
研究伦理委员会和监管机构根据研究者手册（Investigator's Brochures，IBs）中报告的临床前研究来评估拟议的早期临床试验的收益是否超过风险。最近的研究表明，IB 中报告的临床前证据的报告并不能进行适当的风险收益评估。我们采访了不同的利益相关者（监管机构、研究伦理委员会成员、临床前和临床研究人员、伦理学家和元研究人员），了解他们对增加 IBs 中临床前证据报告的完整性和稳健性的措施的看法。
本研究已预先注册（https://osf.io/nvzwy/）。我们使用了目的性抽样，并邀请利益相关者在 2021 年 3 月至 6 月期间参加在线半结构化访谈。使用归纳内容分析得出主题。我们使用优势、劣势、机会和威胁矩阵对我们的发现进行分类。
27 名国际利益相关者参与了研究。受访者指出了一些提高完整性和稳健性的优势和机会，主要是对纳入研究进行更透明和系统的论证。然而，也提到了一些劣势和威胁，这些劣势和威胁可能会破坏使评估更彻底的努力：受访者强调，当前的审查实践足以确保首次人体试验的安全进行。他们担心 IB 结构或审查过程的改变会给利益相关者带来过重的负担，并减缓药物开发的速度。
原则上，更稳健的决策过程符合所有利益相关者的利益，也符合许多当前增加临床前研究可翻译性并在开发过程早期限制无信息或不合理试验的倡议。进一步的研究应调查可以实施的措施，以使所有利益相关者受益。
