Jiang Ce, Beji Céline, Zebachi Sonia, Hayek Ghinwa Y, Cetinyurek-Yavuz Aysun, Fayyad Muhammad Bergas N, Rodwell Laura, Roes Kit C B, Amzal Billy, Gerlinger Christoph, Porcher Raphaël, Tanniou Julien
Quinten Health, Paris, France.
Paris Cité University, Paris, France.
Clin Pharmacol Ther. 2025 Apr;117(4):978-988. doi: 10.1002/cpt.3566. Epub 2025 Feb 19.
The decision-making process in drug development involves "go/no-go" decisions, particularly at the transition from early to late-stage trials. While the decisions are solely made by drug developers, they must take into account the perspectives of multiple stakeholders-such as regulatory agencies, HTA bodies, payers, patients, and ethics committees-to ensure well-informed and robust decision-making. These perspectives influence key considerations, including resource allocation, risk mitigation, regulatory compliance, etc. To support this process, quantitative methodologies, including Bayesian and hybrid frequentist-Bayesian approaches, have been introduced to improve decision-making. However, these methodologies often do not fully account for the diverse priorities and needs of all stakeholders. This scoping review examines criteria and methods used in decision-making at the phase II to III transition, with a focus on broadening the probability of success (PoS) concept beyond efficacy alone. Our review explores PoS for different success definitions, such as regulatory approval, market access, financial viability, and competitive performance. Key themes include decision criteria selection, trial design optimization, utility-based approaches, financial metrics, and multi-stakeholder considerations in decision-making. Our findings highlight both the limitations of current methodologies and potential paths forward, including the integration of real-world data (RWD) and advanced analytics. This work complements a companion manuscript by Cetinyurek-Yavuz et al. (2025) providing a detailed review of PoS methodologies focused solely on efficacy, specifically PoS for achieving statistical significance in phase III studies, including definitions, terminologies, and analytical approaches. Together, these studies provide a foundation for advancing late-stage trial decisions toward a more balanced, data-driven, and stakeholder-aligned approach.
药物研发中的决策过程涉及“继续/终止”决策，尤其是在从早期试验向后期试验过渡时。虽然这些决策完全由药物研发者做出，但他们必须考虑多个利益相关者的观点，如监管机构、卫生技术评估机构、支付方、患者和伦理委员会，以确保决策明智且有力。这些观点会影响关键考量因素，包括资源分配、风险缓解、法规合规等。为支持这一过程，已引入定量方法，包括贝叶斯方法和混合频率主义 - 贝叶斯方法，以改进决策。然而，这些方法往往没有充分考虑所有利益相关者的不同优先事项和需求。本范围综述考察了在II期到III期过渡阶段决策中使用的标准和方法，重点是将成功概率（PoS）概念扩展到不仅仅局限于疗效。我们的综述探讨了不同成功定义下的PoS，如监管批准、市场准入、财务可行性和竞争表现。关键主题包括决策标准选择、试验设计优化、基于效用的方法、财务指标以及决策中的多利益相关者考量。我们的研究结果突出了当前方法的局限性以及潜在的前进方向，包括整合真实世界数据（RWD）和先进分析方法。这项工作补充了Cetinyurek - Yavuz等人（2025年）的一篇配套手稿，该手稿详细综述了仅专注于疗效的PoS方法，特别是在III期研究中实现统计学显著性的PoS，包括定义、术语和分析方法。这些研究共同为推进后期试验决策朝着更平衡、数据驱动和利益相关者一致的方法奠定了基础。
