The Role of Assignment in Defining and Identifying Causal Effects in Randomized Trials

Area of Science:

• Biostatistics
• Epidemiology
• Clinical Trials

Background:

• The per-protocol effect in randomized trials is often misinterpreted.
• It's sometimes viewed as solely reflecting the treatment strategy's effect, ignoring assignment.

Purpose of the Study:

• To clarify the distinction between the per-protocol effect and the treatment strategy effect.
• To demonstrate scenarios where these causal estimands differ and require assignment information for identification.

Main Methods:

• Examination of causal structures in randomized trials.
• Use of examples to illustrate conceptual differences and identification requirements.

Main Results:

• The per-protocol effect encompasses both treatment strategy and assignment effects.
• Identification of both estimands may necessitate assignment data, even in randomized settings.
• Equality of estimands depends on specific assumptions, such as the exclusion-restriction assumption.

Conclusions:

• Treatment assignment plays a crucial role in defining and estimating causal effects in randomized trials.
• Interpretation of trial results requires careful consideration of assignment's influence.
• Statistical analysis must account for assignment to avoid misinterpretation of treatment effects.