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.

Days at Home After Transcatheter vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients

“…The SURTAVI trial was a randomized clinical trial that occurred from June 19, 2012, to June 30, 2016, and involved data collected from 87 centers in the US, Europe, and Canada. Among 1660 participants in the present analysis, 355 (21.4%) were excluded (aged <65 years, index procedure at a Veterans Affairs or non-US hospital) and 1005 (60.5%) were successfully linked to Medicare claims as previously described . This study was approved by the institutional review board at Beth Israel Deaconess Medical Center, Boston, Massachusetts, with a waiver of informed consent given the use of deidentified data.…”

Comparison of Unibody and Non-Unibody Endografts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries: The SAFE-AAA Study

“…10 Furthermore, they have the potential to augment prospective clinical trials and data capture in registries. 34,35…”

Treatment effects in randomised trials using routinely collected data for outcome assessment versus traditional trials: meta-research study

“… 29 Direct comparisons of treatment estimates based on separate ways of outcome ascertainments are helpful to understand better the underlying mechanisms of outcome measurements. 30 In contrast with such research, we did not aim to isolate the “clean” effect of using compared with not using routinely collected data within the same trial as alternative data ascertainment methods. Conversely, we aimed to empirically describe how results from trials designed to provide randomised real world evidence 31 (by using real world data) agree with those from traditionally designed trials relying on their own, active data collection procedures.…”