Novartis Pharma AG, Basel, Switzerland.
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Clin Pharmacol Ther. 2022 May;111(5):1050-1060. doi: 10.1002/cpt.2488. Epub 2021 Dec 13.
The point at which clinical development programs transition from early phase to pivotal trials is a critical milestone. Substantial uncertainty about the outcome of pivotal trials may remain even after seeing positive early phase data, and companies may need to make difficult prioritization decisions for their portfolio. The probability of success (PoS) of a program, a single number expressed as a percentage reflecting the multitude of risks that may influence the final program outcome, is a key decision-making tool. Despite its importance, companies often rely on crude industry benchmarks that may be "adjusted" by experts based on undocumented criteria and which are typically misaligned with the definition of success used to drive commercial forecasts, leading to overly optimistic expected net present value calculations. We developed a new framework to assess the PoS of a program before pivotal trials begin. Our definition of success encompasses the successful outcome of pivotal trials, regulatory approval and meeting the requirements for market access as outlined in the target product profile. The proposed approach is organized in four steps and uses an innovative Bayesian approach to synthesize all relevant evidence. The new PoS framework is systematic and transparent. It will help organizations to make more informed decisions. In this paper, we outline the rationale and elaborate on the structure of the proposed framework, provide examples, and discuss the benefits and challenges associated with its adoption.
从早期阶段向关键试验过渡的临床开发项目是一个关键的里程碑。即使看到早期数据呈阳性，仍可能对关键试验的结果存在较大的不确定性，并且公司可能需要为其投资组合做出艰难的优先级决策。项目的成功率（PoS）是一个关键的决策工具，它是一个用百分比表示的单一数字，反映了可能影响最终项目结果的多种风险。尽管其重要性，公司通常依赖于可能由专家根据未记录的标准进行“调整”的粗略行业基准，并且这些基准通常与用于推动商业预测的成功定义不一致，导致对预期净现值的计算过于乐观。我们开发了一个新的框架，在关键试验开始之前评估项目的 PoS。我们的成功定义包括关键试验的成功结果、监管批准和满足目标产品概况中概述的市场准入要求。拟议的方法分为四个步骤，并使用创新的贝叶斯方法来综合所有相关证据。新的 PoS 框架是系统和透明的。它将帮助组织做出更明智的决策。在本文中，我们概述了基本原理，并详细说明了拟议框架的结构，提供了示例，并讨论了采用它的好处和挑战。
