Novartis Pharma AG, Basel, Switzerland.
Pfizer Inc, New York, NY, 235 E 42nd St, 10017, USA.
Ther Innov Regul Sci. 2022 May;56(3):492-500. doi: 10.1007/s43441-022-00386-0. Epub 2022 Mar 16.
The call for patient-focused drug development is loud and clear, as expressed in the twenty-first Century Cures Act and in recent guidelines and initiatives of regulatory agencies. Among the factors contributing to modernized drug development and improved health-care activities are easily interpretable measures of clinical benefit. In addition, special care is needed for cancer trials with time-to-event endpoints if the treatment effect is not constant over time.
To quantify the potential clinical survival benefit for a new patient, would he/she be treated with the test or control treatment.
We propose the predictive individual effect which is a patient-centric and tangible measure of clinical benefit under a wide variety of scenarios. It can be obtained by standard predictive calculations under a rank preservation assumption that has been used previously in trials with treatment switching.
We discuss four recent Oncology trials that cover situations with proportional as well as non-proportional hazards (delayed treatment effect or crossing of survival curves). It is shown that the predictive individual effect offers valuable insights beyond p-values, estimates of hazard ratios or differences in median survival.
Compared to standard statistical measures, the predictive individual effect is a direct, easily interpretable measure of clinical benefit. It facilitates communication among clinicians, patients, and other parties and should therefore be considered in addition to standard statistical results.
正如二十一世纪治愈法案以及最近监管机构的准则和倡议所表达的那样，人们强烈呼吁以患者为中心的药物开发。有助于实现药物开发现代化和改善医疗保健活动的因素包括临床获益的易于解释的衡量标准。此外，如果治疗效果随时间而不是恒定的，那么对于具有时间事件终点的癌症试验，需要特别注意。
如果新患者接受测试或对照治疗，量化其潜在的临床生存获益。
我们提出了预测个体效应，这是一种以患者为中心且有形的临床获益衡量标准，可以在广泛的情况下获得。它可以通过在治疗转换试验中先前使用的排名保留假设下进行标准预测计算来获得。
我们讨论了最近四项肿瘤学试验，涵盖了比例和非比例风险（延迟治疗效果或生存曲线交叉）的情况。结果表明，预测个体效应提供了超出 p 值、风险比估计或中位生存差异的有价值的见解。
与标准统计措施相比，预测个体效应是临床获益的直接、易于解释的衡量标准。它促进了临床医生、患者和其他各方之间的沟通，因此应考虑将其纳入标准统计结果之外。
