Charting New Territory by Simulated Modeling of a Clinical Trial

Cardiovascular disease (CVD) remains one of the most common comorbidities and causes of death among patients who are treated for ESRD by hemodialysis (1). On the basis of an extensive body of clinical trial evidence, across a spectrum of high CVD risk states from prevalent disease to primary prevention, statin therapy for LDL cholesterol lowering has emerged as one of the most important strategies to reduce risk in populations without ESRD (2–5). By logical extension, two clinical trials to date (Die Deutsche Diabetes Dialyze Studie [4D Study] and A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events [AURORA]) evaluated whether statin therapy was effective for CVD risk reduction in patients with hemodialysis-treated ESRD (6,7). Neither study found a statistically significant benefit on the primary outcomes, whereas some indication of harm related to statin therapy emerged.The intent of the article published in this issue of CJASN by Chan et al. (8) was to substantiate—or not—outcomes of statin therapy among hemodialysis patients who have diabetes and are being treated in everyday medical practice by means of a simulated clinical trial model. Their innovative approach was enabled by a large clinical sample, electronic medical records, and advanced software programs that provided more complete control for covariates and residual confounding (especially as related to statin indication and dosage) compared with more traditional statistical analyses. The authors were clear to point out that these types of studies, which are observational and retrospective in nature, do not replace clinical trials. Rather, such approaches provide opportunity to strengthen or generate hypotheses for prospective testing and to validate clinical trial results in a “real world” environment.By using the same eligibility criteria as in the …