The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study programme: Design and exposure accrual for an evaluation of empagliflozin in routine clinical care

Endocrinol Diabetes Metab. 2019 Nov 26;3(1):e00103. doi: 10.1002/edm2.103. eCollection 2020 Jan.

Abstract

Background: The EMPA-REG OUTCOME trial showed that empagliflozin reduced the risk of cardiovascular death and hospitalization for heart failure (HHF) in diabetic patients with cardiovascular disease. EMPRISE is a study programme on the effectiveness, safety and healthcare utilization of empagliflozin in routine care, leveraging real-world data from two commercial and one federal US data sources from 2014 to 2019.

Objectives: To describe rationale and design of EMPRISE, assess ability to minimize confounding and evaluate the time to reach sufficient statistical power for a key study outcome, HHF, using baseline information from the first year of EMPRISE.

Methods: In 3 claims data sets, we identified a 1:1 propensity score (PS)-matched cohort of diabetic patients ≥18 years initiating empagliflozin or a dipeptidyl peptidase-4 inhibitor (DPP4i), resulting in 6643 total pairs. The PS model included >140 baseline covariates. We measured covariate balance via standardized differences (SD) and postmatching c-statistic. We computed the incidence rate (IR) of HHF, predicted exposure accrual over time and calculated expected power.

Results: After PS matching, patient characteristics were balanced with SD <0.1 and c-statistic between 0.54 and 0.59. The population IR of HHF was 4.4 per 1000 person-years using a specific HHF definition and 14.8 using a broader HHF definition. In our projection, 80%-powered analyses would require a minimum of 169 HHF events, expected to accumulate by year 3 (specific definition) or year 2 (broader definition).

Conclusion: Baseline information from EMPRISE provided evidence of solid confounding control and adequate exposure accrual with expected powered analyses for the primary outcomes.

Keywords: comparative effectiveness; confounding (epidemiology); empagliflozin; heart failure; real‐world data; study validity; type 2 diabetes.