Applying the Estimands Framework to Non-Inferiority Trials: Guidance on Choice of Hypothetical Estimands for Non-Adherence and Comparison of Estimation Methods.

ABSTRACT: A common concern in non-inferiority (NI) trials is that non-adherence due, for example, to poor study conduct can make treatment arms artificially similar. Because intention-to-treat analyses can be anti-conservative in this situation, per-protocol analyses are sometimes recommended. However, such advice does not consider the estimands framework, nor the risk of bias from per-protocol analyses. We therefore sought to update the above guidance using the estimands framework, and compare estimators to improve on the performance of per-protocol analyses. We argue the main threat to validity of NI trials is the occurrence of "trial-specific" intercurrent events (IEs), that is, IEs which occur in a trial setting, but would not occur in practice. To guard against erroneous conclusions of non-infe

SUBMITTER: Morgan KE 

PROVIDER: S-EPMC11806244 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature