OBJECTIVES: To demonstrate replication of the quantification of relationships between surrogates and endpoints as well as reconciliation with previous epidemiological studies; original studies for heart rate as a surrogatefor all-cause mortality,  pain management and gastrointestinal adverse events, and treatment for diabetes and HbA1c and HbA1c and complications. METHODS: For heart rate, three epidemiological studies from three countries using a Weibull survival analysis and Generalized Estimating Equations were used; namely, the Coronary Artery Surgery Study (CASS), the Copenhagen City Heart Study (CCHS) and the General Practitioner Research Network (GPRN).  These equations reproduced a meta-regression and meta-analysis of all available placebo-controlled clinical trials with heart rate as a prognostic factor for all-cause mortality. For pain, data consisted of 2005 Health Care Utilization Project (HCUP) and Premier.  Logistic regressions were used to obtain evaluate and compare odds-ratios. In diabetes, Generalized Estimating Equations (GEE) allowing serially correlated behavior with repeated HbA1c reading at variable frequencies and durations between their measurement. RESULTS: Heart is consistently prognostic for all-cause mortality.  Moreover, its quantification is consistent, 0.00694 (P<0.001) in CASS and 0.00683 (P<0.001) in CCHS (1981-1983) and 0.00717 in CCHS (1991-1993) with the Weibull.  With the GEE, the coefficient is 0.0268 (P=0.006) in GPRN, 0.0249 (P=0.008) in the meta-regression of controlled clinical trials, and 0.01595 in the GEE with CCHS data.  All three equations reproduced the published clinical trials with odd-ratios within 1/100ths.Conditional odds-ratios  were replicated in measure between the two datasets for fecal impaction, post-operative illeus, other bowel obstruction, vomiting and abdominal pain. The diabetic equations were replicated exactly in 3 countries, treatment and HbA1c and complications with coefficients within 1/100th in patients with newly diagnosed T2DM.   CONCLUSIONS: These are three studies where the quantification of the relationship between a surrogate and and endpoint have beed replicated with precision and subsequently applied to clinical trials.