Pragmatic Clinical Trials in the Rubric of Structural Causal Models
This work addresses a definitional gap in clinical trial design for researchers, but it is incremental as it extends existing SCM methods to a specific trial type without introducing new paradigms.
The paper tackles the lack of a standardized representation for pragmatic clinical trials (PCT) within structural causal models (SCM) by proposing a generalized SCM framework for PCT, enabling the application of do-calculus and related techniques to clinical datasets.
Explanatory studies, such as randomized controlled trials, are targeted to extract the true causal effect of interventions on outcomes and are by design adjusted for covariates through randomization. On the contrary, observational studies are a representation of events that occurred without intervention. Both can be illustrated using the Structural Causal Model (SCM), and do-calculus can be employed to estimate the causal effects. Pragmatic clinical trials (PCT) fall between these two ends of the trial design spectra and are thus hard to define. Due to its pragmatic nature, no standardized representation of PCT through SCM has been yet established. In this paper, we approach this problem by proposing a generalized representation of PCT under the rubric of structural causal models (SCM). We discuss different analysis techniques commonly employed in PCT using the proposed graphical model, such as intention-to-treat, as-treated, and per-protocol analysis. To show the application of our proposed approach, we leverage an experimental dataset from a pragmatic clinical trial. Our proposition of SCM through PCT creates a pathway to leveraging do-calculus and related mathematical operations on clinical datasets.