Randomized Clinical Trial Replication Using Real-World Data for Comparative Cardiovascular and Safety Outcomes of Empagliflozin and Sitagliptin
Abstract
Background
If the same results as randomized clinical trial (RCT) can be created by conducting RWE studies, regulation decisions will be easier to assessing the effectiveness or safety of medications. In this study, we aimed to check to what extent findings from existing RCTs can be replicated in RWE study by analyzing in a reproducible process.
Methods
This study used a cohort study design to assess the effect of empagliflozin versus sitagliptin on effectiveness and safety outcomes. EMPA-REG OUTCOME trial (NCT01131676) was selected to target for replication. The inclusion/exclusion criteria and follow up method were applied as same with RCT. Major adverse cardiovascular events (MACEs) was used as a primary outcome and 15 other outcomes were also included for analysis.
Results
We followed-up (median, 2.7 years) 23,126 matched patients with type 2 diabetes mellitus (11,563 empagliflozin users and 11,563 sitagliptin users). Empagliflozin were related with a significantly decreased risk of MACEs [adjusted HR 0.87, 95% confidence interval (CI) 0.79–0.96]. The predifined estimate agreement, regulatory agreement, and standardized difference for RCT duplication were achieved. [EMPA-REG OUTCOME RCT: adjusted HR 0.86, 95% (CI) 0.74–0.99]. Of the 15 other emulation outcomes, 10 emulations were evaluated as good (all three agreements achieved), and two as moderate (two of the three agreements achieved).
Conclusions
Our study results suggest that RWE can replicate RCT results…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 23,126 participants or records.
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