Randomized clinical trials remain the foundation of evidence generation in medicine. Their strength lies in internal validity: carefully selected patient populations, controlled treatment exposure, and rigorous follow-up allow investigators to estimate causal treatment effects with high confidence. The price of this control is selectivity. Patients enrolled in clinical trials often represent only a fraction of those encountered in routine clinical practice. Older individuals, patients with multiple comorbidities, heavy healthcare utilization, or complex medication histories are frequently excluded. This analysis explores whether findings observed in trial-like populations remain consistent in broader real-world populations using a synthetic healthcare population generated with Synthea.
