How to avoid concerns with the interpretation of two primary endpoints if significant superiority in one is sufficient for formal proof of efficacy

• DOI: 10.1002/pst.2314
• Publication Date: 2023-05-22T23:58:18Z
• Authors: Anika Großhennig; Nele Henrike Thomas; Werner Brannath; Armin Koch
• Keywords: Clinical endpoint

Abstract Formal proof of efficacy a drug requires that in prospective experiment, superiority over placebo, or either at least non‐inferiority to an established standard, is demonstrated. Traditionally one primary endpoint specified, but various diseases exist where treatment success needs be based on the assessment two endpoints. With co‐primary endpoints, both need “significant” as prerequisite claim study success. Here, no adjustment study‐wise type‐1‐error needed, sample size often increased maintain pre‐defined power. Studies use at‐least‐one concept have been proposed claimed if for endpoints This sometimes also called dual concept, and appropriate required. not covered European Guideline multiplicity because can shows significant superiority, despite possible deterioration other. In line with Röhmel's strategy, we discuss alternative approach including hypotheses testing avoids obvious contradictions proper decision‐making. leads back assessment, has advantage minimum requirements modeled flexibly several practical needs. Our simulations show that, planning assumptions are correct, additional improve interpretation only limited impact power, is, size.