Evaluating cardiac lead safety using observational, real-world data: EP PASSION proof-of-concept study

Background: Traditional post-approval study (PAS) designs have been accepted by regulatory authorities to fulfill postmarketing requirements for cardiac leads, but they have several limitations. Objective: We conducted a proof-of-concept study of alternative methods that use real-world data (RWD) to evaluate lead safety in large populations of patients. Methods: Abbott patient device databases were linked with Medicare Fee-For-Service (FFS) claims to identify lead complications in patients implanted with Abbott Optisure lead. A 1:1 comparison between the PAS method and RWD method of detecting mechanical lead–related complication events was conducted in 444 PAS participants who were enrolled in Medicare FFS. Agreement between methods was evaluated by McNemar test and Cohen κ. Survival free from complications at 3 years was compared between the PAS and RWD cohorts with an equivalence acceptance criterion of ±2.5%. Results: There were 1171 PAS patients and 5804 Medicare FFS patients who received an Optisure lead between August 27, 2014, and June 14, 2016. Patients were observed through December 31, 2018. Complete agreement was found between PAS-reported and claims-detected complications (McNemar P value = 1; Cohen κ = 1). Survival free from complications at 3 years by the RWD method was 98.4% (95% confidence limit, 98.0%–98.7%), which was within the acceptable range of the PAS 98.4% (95% confidence limit, 97.6%–99.0%). Conclusion: These results show a close agreement between RWD-detected and PAS-reported lead complication rates, which highlights the potential benefits of RWD-based methods to enhance the generation of clinical evidence for lead safety.