On the use of extreme value tail modeling for generalized pairwise comparisons with censored outcomes

• Published in: Pharmaceutical statistics : the journal of the pharmaceutical industry 2023-03, Vol.22 (2), p.284-299
• Main Authors: De Backer, Mickaël, Legrand, Catherine, Péron, Julien, Lambert, Alexandre, Buyse, Marc
• Format: Article
• Language: English
• Subjects: Bias; clinical trial; Clinical trials; Comparative studies; Computer Simulation; generalized pairwise comparisons; generalized Pareto distribution; Humans; Kaplan-Meier Estimate; Kaplan–Meier; multi‐criteria analysis; Survival Analysis
• ISSN: 1539-1604; 1539-1612
• DOI: 10.1002/pst.2271

In randomized clinical trials, methods of pairwise comparisons such as the ‘Net Benefit’ or the ‘win ratio’ have recently gained much attention when interests lies in assessing the effect of a treatment as compared to a standard of care. Among other advantages, these methods are usually praised for delivering a treatment measure that can easily handle multiple outcomes of different nature, while keeping a meaningful interpretation for patients and clinicians. For time‐to‐event outcomes, a recent suggestion emerged in the literature for estimating these treatment measures by providing a natural handling of censored outcomes. However, this estimation procedure may lead to biased estimates when tails of survival functions cannot be reliably estimated using Kaplan–Meier estimators. The problem then extrapolates to the other outcomes incorporated in the pairwise comparison construction. In this work, we suggest to extend the procedure by the consideration of a hybrid survival function estimator that relies on an extreme value tail model through the Generalized Pareto distribution. We provide an estimator of treatment effect measures that notably improves on bias and remains easily apprehended for practical implementation. This is illustrated in an extensive simulation study as well as in an actual trial of a new cancer immunotherapy.