Using an early outcome as the sole source of information of interim decisions regarding treatment effect on a long‐term endpoint: The non‐Gaussian case

• Published in: Pharmaceutical statistics : the journal of the pharmaceutical industry 2024-11, Vol.23 (6), p.928-938
• Main Authors: Garcia Barrado, Leandro, Burzykowski, Tomasz
• Format: Article
• Language: English
• Subjects: Data Interpretation, Statistical; efficacy stopping; Endpoint Determination - statistics & numerical data; group‐sequential design; Humans; Information Sources; interim analysis; Models, Statistical; randomized clinical trial; Randomized Controlled Trials as Topic - methods; Randomized Controlled Trials as Topic - statistics & numerical data; Research Design; Sample Size; surrogate endpoint; Time Factors; Treatment Outcome
• ISSN: 1539-1604; 1539-1612; 1539-1612
• DOI: 10.1002/pst.2398

In randomized clinical trials that use a long‐term efficacy endpoint, the follow‐up time necessary to observe the endpoint may be substantial. In such trials, an attractive option is to consider an interim analysis based solely on an early outcome that could be used to expedite the evaluation of treatment's efficacy. Garcia Barrado et al. (Pharm Stat. 2022; 21: 209–219) developed a methodology that allows introducing such an early interim analysis for the case when both the early outcome and the long‐term endpoint are normally‐distributed, continuous variables. We extend the methodology to any combination of the early‐outcome and long‐term‐endpoint types. As an example, we consider the case of a binary outcome and a time‐to‐event endpoint. We further evaluate the potential gain in operating characteristics (power, expected trial duration, and expected sample size) of a trial with such an interim analysis in function of the properties of the early outcome as a surrogate for the long‐term endpoint.