Introduction
RWE as a complement to CVOTs
EMPRISE as a complementary study to EMPA-REG OUTCOME
Minimising confounding
Key aspects of the EMPRISE study design | |
PS matching
| Patients are 1:1 matched with a “nearest neighbour” based on 140 predefined baseline characteristics (“covariates”) Covariates include key factors relating to disease severity (such as # antidiabetic medications), comorbidities (such as CVD history) and many other clinical and demographic characteristics |
Appropriate comparator choice
| The most commonly prescribed DPP-4 inhibitor is the chosen active comparator to empagliflozin, owing to the similar position of DPP-4 inhibitors to SGLT2 inhibitors in the treatment pathway Using a comparator with a similar position is designed to maximise the similarity of disease severity between cohorts |
No overlap between comparators
| Patients are excluded if they had received any SGLT2 inhibitor or DPP-4 inhibitor in the year preceding cohort entry, and follow-up is terminated if a patient switches to the comparator Minimises the potential for immortal time bias |
Sequential enrolment
| PS matching is performed independently for each enrolment Ensures that study arms are balanced not just across the full cohort, but also for temporally matched populations |
“As-treated” approach
| Follow-up captures only outcomes occurring during treatment exposure + 30 days Minimises bias from confounding events not related to treatment |
Assessing balance between cohorts
Data used to independently confirm robustness of PS matching approach | |
Baseline laboratory scores
| A range of laboratory scores at baseline are available for a subset of the population, including Hb1Ac, cholesterol and creatinine levels These scores are not used for PS matching, and so can provide an independent indication of equivalence between study arms |
Sensitivity analyses
In each case, the conclusions regarding HHF benefit with empagliflozin were unchanged | |
High-dimensional PS matching
| PS matching with 100 additional covariates |
Alternative comparator
| The sitagliptin cohort is replaced with a cohort composed of patients receiving any DPP-4 inhibitor |
Subgroup analyses
| Subgroup analyses include: With/without CVD at baseline With/without HF at baseline Gender Empagliflozin dose |
Alternative HHF definition
| Broadening the definition of HHF from hospitalisation with HF in the primary discharge position to hospitalisation with HF in any discharge position |
Control outcome
| An outcome with an expected null finding (flu vaccination) |
The EMPRISE study—what have we learned so far?
A balanced study population with a broad spectrum of CV risk
Before PS matching | After PS matching | ||||
---|---|---|---|---|---|
Sitagliptin (N = 201,839) | Empagliflozin (N = 18,880) | Sitagliptin (N = 16,443) | Empagliflozin (N = 16,443) | ||
Diabetes medication | ⟶ PS matching | ||||
# antidiabetic drugs (mean) | 2.2 | 2.3 | 2.2 | 2.2 | |
Treatment naïve (%) | 13% | 7% | 8% | 8% | |
CV risk factors | |||||
Any CVD (%) | 37% | 24% | 25% | 25% | |
CAD (%) | 26% | 18% | 18% | 18% | |
Stroke (%) | 10% | 5% | 6% | 6% | |
PAD (%) | 10% | 5% | 5% | 5% | |
HF (%) | 11% | 5% | 5% | 5% | |
Lab results (not used for PS matching) | |||||
HbA1c (mean) | 8.3 | 8.5 | 8.6 | 8.5 |