Illustrating an Adaptive Prespecification Framework for Observational Research: Target Trial Emulations Comparing Immunomodulator Treatments for COVID-19.

ABSTRACT: Rigid prespecification can be impractical for noninterventional studies using secondary datasets, where data-driven flexibility is often required. Using target trial emulations comparing immunomodulator treatments for COVID-19, we piloted an adaptive strategy that accommodates warranted mid-course refinements within a prespecified framework. Our preregistered protocol outlined an initial study plan along with predetermined diagnostic thresholds and contingencies. Implementation proceeded through sequential phases, allowing researcher decisions to be guided by prespecified criteria under varying degrees of blinding to results. The adaptive approach led to alterations in the underlying target trial and to the analysis plan used for emulation, strengthening the plausibility of causal assumpti

SUBMITTER: Weckstein AR 

PROVIDER: S-EPMC12459141 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature