Where Do Target Trials Come From? Specifying the Protocol of a Target Trial When Repurposing Data for Causal...

Area of Science:

• Epidemiology
• Causal Inference
• Health Data Science

Background:

• The target trial framework often assumes upfront knowledge of the trial protocol.
• In practice, observational data constrains and shapes the target trial protocol, especially when using pre-existing databases.
• Iterative development of the target trial protocol is common as investigators interact with available data.

Purpose of the Study:

• To examine how investigators adapt their initial causal questions and index trial protocols to available observational data.
• To understand the process leading to a final target trial protocol that is influenced by both the original question and the data.
• To address the implications of data-driven protocol adaptation for prespecification and transparency.

Main Methods:

• Conceptual analysis of the target trial framework in the context of real-world data use.
• Examination of the adaptive process in developing target trial protocols from observational data.
• Discussion of the challenges posed by data-dependent protocol specification.

Main Results:

• The target trial protocol is typically adapted iteratively based on available observational data.
• The final protocol depends on both the initial causal question and insights gained from data inspection.
• Prespecification of an emulatable target trial protocol is often not feasible due to expected data-driven adaptations.

Conclusions:

• The adaptive nature of target trial protocol specification necessitates careful consideration of permissible data examinations.
• Transparent reporting of adaptations and their rationales is crucial.
• Further research is needed on prespecifying rules for data-driven protocol modifications.