BIOTRONIK's Solia S cardiac lead has demonstrated long-term safety and reliability, according to final results from the first cardiac lead post-approval study (PAS) utilizing real-world data (RWD). The study, conducted under the Electrophysiology Predictable and Sustainable Implementation of National Registries (EP PASSION) project, marks a significant shift towards more efficient and cost-effective post-market device surveillance.
The transition from traditional clinical trials to RWD methodologies, leveraging Medicare claims data and device tracking, has been validated through a proof-of-concept analysis and a comprehensive final report. This approach addresses limitations of conventional long-term studies, such as high costs and follow-up attrition, while maintaining rigorous scientific standards.
Proof-of-Concept Validation
Prior to the full-scale transition, a proof-of-concept analysis compared lead complication rates derived from RWD with those reported in the original Solia S clinical study (NCT01791127). The analysis included 896 patients with fee-for-service Medicare coverage. Results showed no statistically significant difference (p = 0.0833) in identifying lead complications between the two methods, with an overall agreement of 99.7%. Notably, RWD methodologies identified three additional lead complications missed in the original study due to patient loss to follow-up, highlighting a key advantage of using comprehensive claims data.
Final Study Results
The final Solia S EP PASSION PAS included 1,015 patients (1,841 leads) meeting eligibility criteria. The mean age of patients was 77.3 years, with the majority being male (54.7%) and white (91.4%). Over a total follow-up time of 7,228.3 lead-years, 33 chronic lead complications attributable or possibly attributable to the study lead were identified, resulting in a complication rate of 0.005 complications per lead-year. Kaplan-Meier analysis estimated a 98.1% freedom from complications at 1,521 days. The complication-free rate at 5 years post-implant was 97.19% (95% CI: 96.1%, 98.1%).
Implications for Post-Market Surveillance
The successful transition of the Solia S study to RWD methodologies has several important implications for post-market surveillance of cardiac devices. According to the study, the elimination of the resource burden on clinical sites to recruit and manage long-term follow-up in a PAS translated to a significant resource savings for BIOTRONIK as well as clinical research infrastructure. This resource savings along with the improved follow-up attrition, shortened study duration, and opportunity to expand patient populations compared to traditional PAS conduction confirmed that the goals of EP PASSION were met. The FDA's approval of these methodologies demonstrates future applications for new products going through the FDA approval cycle.
Limitations and Future Directions
The authors acknowledge limitations of using RWD, including the lack of detailed complication information compared to traditional clinical studies. The claims-based information is collected for billing purposes and not research. Currently, these methods do not provide enough details to confidently identify specific types of lead complication. Also, the methodology primarily captures complications requiring invasive intervention and focuses on chronic events occurring more than 30 days post-implant. Future refinements, such as incorporating remote monitoring data, could enhance the detection of a broader range of complications. The study also notes that Medicare data reflects an older patient population, necessitating exploration of other RWD sources for younger patients.
Broader Impact
The success of the Solia S study has paved the way for similar transitions in other BIOTRONIK studies, including the Protego DF4 PAS (NCT02243696) and QP ExCELs PAS (NCT03155724). Other CIED observational studies have since utilized CMS data with similar methodologies such as a validation study of Boston Scientific’s HeartLogic PAS results and Medtronic’s leadless pacemaker studies (ClinicalTrials.gov ID: NCT03039712 and NCT04235491), Abbott’s leadless pacemaker studies (ClinicalTrials.gov ID: NCT05336877, NCT05932602, NCT06100770), and BIOTRONIK’s ICD lead PAS, Pamira.
The transition to RWE represents a promising advancement in cardiac lead surveillance, demonstrating the potential of routine clinical data for more efficient post-market device evaluation.
