Emulation of randomized trials of direct oral anticoagulants with claims data and implications for new Factor XI...

Area of Science:

• Pharmacology
• Clinical Trials
• Real-World Evidence

Background:

• Direct oral anticoagulants (DOACs) have transformed thromboembolic disorder management.
• Factor XI inhibitors represent a new class of anticoagulants nearing large-scale clinical evaluation.
• The utility of non-randomized database studies in complementing randomized controlled trials (RCTs) for these novel agents requires investigation.

Purpose of the Study:

• To evaluate the role of non-randomized database studies in expediting understanding of anticoagulant therapies.
• To assess the concordance between RCTs and emulated non-randomized claims database studies for DOACs.
• To determine if well-designed database studies can provide reliable insights into the effectiveness and safety of emerging anticoagulants like Factor XI inhibitors.

Main Methods:

• The RCT-DUPLICATIVE Initiative emulated eight DOAC RCTs using non-randomized claims database studies.
• Study design parameters and measurements were closely replicated between RCTs and database studies.
• Agreement metrics were used to compare results, with discrepancies analyzed against meta-analyses.

Main Results:

• Non-randomized database studies closely emulated RCT designs and produced highly concordant results.
• A single discordant database study aligned with a meta-analysis, suggesting the corresponding RCT result may have been an outlier.
• Well-designed database studies demonstrated similar conclusions to DOAC RCTs.

Conclusions:

• Non-randomized database studies can reliably complement RCTs for emerging anticoagulants, including Factor XI inhibitors.
• These studies can accelerate insights into effectiveness and safety in real-world clinical practice.
• Database studies offer value in assessing underrepresented populations and exploring broader indications for new anticoagulants.