J Clin Epidemiol. 2006 Mar;59(3):254-64. Links . Department of Medicine， University of Pennsylvania School of Medicine， Philadelphia， PA， USA. tannen@mail.med.upenn.edu

 OBJECTIVE: To determine the validity of outcome research using a primary care practice database by comparing a randomized controlled trial (RCT) with a simulated one.

STUDY DESIGN AND SETTING: A cohort from the United Kingdom General Practice Research Database (GPRD) was used to simulate the Systolic Hypertension in Europe (Syst-Eur) trial， a study of antihypertensive therapy of isolated systolic hypertension， by replicating all aspects of that RCT (selection criteria， study time frame， treatment， and outcomes) except randomization.

RESULTS: The exposed and unexposed groups in the GPRD study exhibited similar baseline characteristics. Stroke， the primary RCT outcome， decreased significantly in both the RCT (incidence rate ratio IRR = 0.58) and the GPRD study (IRR = 0.68). Myocardial infarction decreased nonsignificantly but similarly in both studies (RCT IRR = 0.70; GPRD IRR = 0.74). With the GPRD study extended for 3 years more， myocardial infarction decreased significantly， comparable to findings from the Systolic Hypertension in the Elderly Program (SHEP)， another RCT similar to Syst-Eur.

CONCLUSIONS: The findings support the potential value of clinical databases to investigate treatment effectiveness. RCT simulation using the GPRD may be the most feasible way to assess observational study validity in comparison to RCTs. The extended GPRD study shows the feasibility of using a simulated study to supplement the results of an RCT of limited duration.