Improving interventional causal predictions in regulatory risk assessment.

Abstract In 2022, the US EPA published an important risk assessment concluding that “Compared to the current annual standard, meeting a revised annual standard with a lower level is estimated to reduce PM2.5-associated health risks in the 30 annually-controlled study areas by about 7–9% for a level of 11.0 µg/m3… and 30–37% for a level of 8.0 µg/m3.” These are interventional causal predictions: they predict percentage reductions in mortality risks caused by different counterfactual reductions in fine particulate (PM2.5) levels. Valid causal predictions are possible if: (1) Study designs are used that can support valid causal inferences about the effects of interventions (e.g., quasi-experiments with appropriate control groups); (2) Appropriate causal models and methods are used to analyze the data; (3) Model assumptions are satisfied (at least approximately); and (4) Non-causal sources of exposure-response associations such as confounding, measurement error, and model misspecification are appropriately modeled and adjusted for. This paper examines two long-term mortality studies selected by the EPA to predict reductions in PM2.5-associated risk. Both papers use Cox proportional hazards (PH) models. For these models, none of these four conditions is satisfied, making it difficult to interpret or validate their causal predictions. Scientists, reviewers, regulators, and members of the public can benefit from more trustworthy and credible risk assessments and causal predictions by insisting that risk assessments supporting interventional causal conclusions be based on study designs, methods, and models that are appropriate for predicting effects caused by interventions.