Use of Administrative Claims to Assess Outcomes and Treatment Effect in Randomized Clinical Trials for Transcatheter Aortic Valve Replacement

Abstract

Background: Whether passively collected data can substitute for adjudicated outcomes to reproduce the magnitude and direction of treatment effect observed in cardiovascular clinical trials is not well known. Methods: We linked adults aged ≥65 in the US CoreValve Pivotal High Risk (HiR) and Surgical or Transcatheter Aortic Valve Replacement in Intermediate-Risk Patients (SURTAVI) Trials to 100% Medicare inpatient claims, 1/1/2003-12/31/2016. Primary (e.g. death and stroke) and secondary trial endpoints, were compared across treatment arms (e.g. TAVR vs. SAVR) using trial-adjudicated outcomes versus outcomes derived from claims at 1-year (HiR) or 2-years (SURTAVI). Results: Among 600 linked CoreValve HiR participants (linkage rate 80.0%), the rate of the trial's primary endpoint of all-cause mortality occurred in 13.7% of patients receiving TAVR and 16.4% of patients receiving SAVR at 1-year using both trial data (HR 0.84, 95% CI 0.65-1.09; p= 0.33) and claims data (HR 0.86, 95% CI 0.66-1.11; p = 0.34; interaction p-value = 0.80). Noninferiority of TAVR relative to SAVR was seen using both trial and claims-based outcomes (p_{noninferiority} < 0.001 for both). Among 1005 linked SURTAVI trial participants (linkage rate 60.5%), the trial's primary endpoint was 12.9% for TAVR and 13.1% for SAVR using trial data (HR 1.08, 95% CI 0.79-1.48, p = 0.90), and 11.3% for TAVR and 12.5% for SAVR patients using claims data (HR 1.02, 95% CI 0.73-1.41, p = 0.58; interaction p-value = 0.89). TAVR was noninferior to SAVR when compared using both trial and claims (p_{non-inferiority} < 0.001 for both). Rates of procedural secondary outcomes (e.g. aortic valve reintervention, pacemaker rates) were more closely concordant between trial and claims data than non-procedural outcomes (e.g., stroke, bleeding, cardiogenic shock). Conclusions: In the CoreValve HiR and SURTAVI trials, ascertainment of trial primary endpoints using claims reproduced both the magnitude and direction of treatment effect compared with adjudicated event data, but non-fatal and non-procedural secondary outcomes were not as well reproduced. Use of claims to substitute for adjudicated outcomes in traditional trial treatment comparisons may be valid and feasible for all-cause mortality and certain procedural outcomes, but may be less suitable for other endpoints.