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 post-marketing requirements for cardiac leads but they have several limitations. OBJECTIVES: The authors conducted a proof-of-concept study of alternative methods that utilize real-world data (RWD) to evaluate lead safety in large patient populations. METHODS: Abbott patient device databases were linked with Medicare Fee-For-Service (FFS) claims to identify lead complications among 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 subjects who were enrolled in Medicare FFS. Agreement between methods was evaluated using McNemar's test and Cohen's kappa. Survival free from complications at 3 years was compared between the PAS and RWD cohorts using an equivalence acceptance criterion of ±2.5%. RESULTS: There were 1,171 PAS patients and 5,804 Medicare FFS patients who received an Optisure™ lead between August 27, 2014 - June 14, 2016. Patients were followed through December 31, 2018. Complete agreement was found between PAS-reported and claims-detected complications (McNemar's p-value=1.00, Cohen's Kappa = 1.0). Survival free from complications at 3 years using the RWD method was 98.4% (95% CL: 98.0%-98.7%), which was within the acceptable range of the PAS 98.4% (95% CL: 97.6%-99.0%). CONCLUSION: These results show a close agreement between RWD-detected and PAS-reported lead complication rates, which highlight the potential benefits of RWD-based methods to enhance the generation of clinical evidence for lead safety.

Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000-2020).

Pharmacogenomics (PGx) is a key subset of precision medicine that relates genomic variation to individual response to pharmacotherapy. We assessed longitudinal trends in US FDA approval of new drugs labeled with PGx information. Drug labels containing PGx information were obtained from Drugs@FDA and guidelines from PharmGKB were used to compare the actionability of PGx information in drug labels across therapeutic areas. The annual proportion of new drug approvals with PGx labeling has increased by nearly threefold from 10.3% (n = 3) in 2000 to 28.2% (n = 11) in 2020. Inclusion of PGx information in drug labels has increased for all clinical areas over the last two decades but most prominently for cancer therapies, which comprise the largest proportion (75.5%) of biomarker-drug pairs for which PGx testing is required. Clinically actionable information was more frequently observed in biomarker-drug pairs associated with cancer drugs compared to those for other therapeutic areas (n = 92 (59.7%) vs. n = 62 (40.3%), p < 0.0051). These results suggest that further evidence is needed to support the clinical adoption of pharmacogenomics in non-cancer therapeutic areas.