A Causal Perspective on "Appropriate Implementation of ICH E9(R1) Addendum Strategies" (Comment on Fleming et al.)

Area of Science:

• Biostatistics
• Clinical Epidemiology
• Causal Inference

Background:

• Fleming et al. recently shared opinions on delivering "rigorous causal inference on meaningful estimands."
• This commentary presents differing perspectives on this topic.

Purpose of the Study:

• To offer alternative perspectives on achieving rigorous causal inference for meaningful estimands.
• To propose a more robust pathway incorporating clinical, causal, and statistical reasoning.
• To introduce criteria for evaluating the practical utility of intercurrent event strategies.

Main Methods:

• Depicting a robust pathway for causal inference.
• Suggesting a tangibility criterion for intercurrent event strategies.
• Illustrating the utility of causal inference methods with hypothetical strategies.

Main Results:

• A more robust pathway for rigorous causal inference is presented.
• A tangibility criterion is proposed to assess the practical usefulness of intercurrent event strategies.
• Causal inference methods demonstrate utility in providing robust estimates when aligned with clinical objectives.

Conclusions:

• Advocating for a balanced approach considering the trade-offs between an estimand's relevance and required assumptions.
• Highlighting the importance of integrating clinical, causal, and statistical reasoning for robust causal inference.
• Emphasizing the practical utility of causal inference in clinical research when applied appropriately.