Validating the use of registries and claims data to support randomized trials: Rationale and design of the Extending Trial-Based Evaluations of Medical Therapies Using Novel Sources of Data (EXTEND) Study

Strom, Jordan B.; Tamez, Hector; Zhao, Yuansong; Valsdottir, Linda R.; Curtis, Jeptha P.; Brennan, James M.; Shen, Changyu; Popma, Jeffrey J.; Mauri, Laura; Yeh, Robert W.

doi:10.1016/j.ahj.2019.02.007

Cited by 24 publications

(16 citation statements)

References 37 publications

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“…Trial cohort patients were linked to the CathPCI Registry from 2009 to 2011 using indirect identifiers and a deterministic algorithm based on the matching of age or date of birth, sex, PCI date, stent type, hospital discharge date, and a hospital identifier, as part of the broader EXTEND-DAPT Study (Extending Trial-Based Evaluations of Medical Therapies Using Novel Sources of Data). 12 The overall goal was to reweight the trial cohort to resemble the registry cohort regarding all measured covariates, and then to reestimate the randomized treatment effects in this reweighted sample (Figure 1). 10,11 To do so, we first pooled the linked trial cohort with the registry cohort and estimated models to predict the probability of trial participation for each individual based on sociodemographic information, medical history, cardiovascular history, presentation, and procedural characteristics captured in the CathPCI Registry using logistic regression.…”

Section: Methodsmentioning

confidence: 99%

Estimation of DAPT Study Treatment Effects in Contemporary Clinical Practice: Findings From the EXTEND-DAPT Study

et al. 2022

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Background: Differences in patient characteristics, changes in treatment algorithms, and advances in medical technology could each influence the applicability of older randomized trial results to contemporary clinical practice. The Dual Antiplatelet Therapy (DAPT) Study found that longer duration DAPT decreased ischemic events at the expense of greater bleeding, but subsequent evolution in stent technology and clinical practice may attenuate the benefit of prolonged DAPT in a contemporary population. We evaluated whether the DAPT Study population is different from a contemporary population of US patients receiving percutaneous coronary intervention (PCI), and estimated the treatment effect of extended duration antiplatelet therapy after PCI in this more contemporary cohort. Methods: We compared characteristics of drug-eluting stent (DES)-treated patients randomized in the DAPT Study to a sample of more contemporary DES-treated patients in the NCDR CathPCI Registry from July 2016-June 2017. After linking trial and registry data, we employed inverse-odds of trial participation weighting to account for patient and procedural characteristics and estimated a contemporary "real-world" treatment effect of 30 vs. 12 months of DAPT after coronary stent procedures. Results: The US DES-treated trial cohort included 8864 DAPT Study patients and the registry cohort included 568,540 patients. Compared to the trial population, registry patients had more comorbidities and were more likely to present with myocardial infarction and receive 2nd generation DES. After reweighting trial results to represent the registry population, there was no longer a significant effect of prolonged DAPT on reducing stent thrombosis (reweighted treatment effect: −0.40, 95% CI: −0.99%, 0.15%), major adverse cardiac and cerebrovascular events (reweighted treatment effect: −0.52, 95% CI: −2.62%, 1.03%), or myocardial infarction (reweighted treatment effect: −0.97%, 95% CI: −2.75%, 0.18%), but the increase in bleeding with prolonged DAPT persisted (reweighted treatment effect: 2.42%, 95% CI: 0.79%, 3.91%). Conclusions: Differences between patients and devices used in contemporary clinical practice compared with the DAPT Study were associated with attenuation of benefits and greater harms attributable to prolonged DAPT duration. These findings limit applicability of average treatment effects from the DAPT Study in modern clinical practice.

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Section: Methodsmentioning

confidence: 99%

Estimation of DAPT Study Treatment Effects in Contemporary Clinical Practice: Findings From the EXTEND-DAPT Study

et al. 2022

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“…Details on this linkage have been published previously. 12 Data from patients included in the US CoreValve HiR (High Risk trial), SURTAVI (Surgical or Transcatheter Aortic‐Valve Replacement in Intermediate‐Risk Patients) trial, and single‐arm CAS (Continued Access Study) who could be successfully linked to US Centers for Medicare and Medicaid Services Medicare Provider Analysis and Review data set with procedure dates February 2, 2011, to September 30, 2015, were included. The CoreValve HiR randomized individuals at high surgical risk with severe aortic stenosis to undergo TAVR with the Medtronic CoreValve bioprosthesis versus SAVR.…”

Section: Methodsmentioning

confidence: 99%

“… 9 Moreover, in contrast to well‐defined and validated frailty metrics using in‐person measurements, physicians’ subjective assessments of frailty may not significantly predict risk in TAVR. 9 As such, retrospective ascertainment of frailty status, using claims algorithms developed on the basis of such validated metrics of frailty, has been advocated to improve risk prediction, 10 assessment of hospital care quality, 11 and evaluation of study generalizability 12 when frailty assessment using these validated techniques has not been performed. While we have previously demonstrated that a claims‐based frailty index (CFI) identifies individuals undergoing TAVR at higher risk of adverse outcomes than comorbidities alone using nationwide claims data, 10 whether it identifies individuals with a greater burden of frailty‐related health deficits and similarly identifies an increased risk of adverse outcomes in a clinical trial population remains uncertain.…”

Section: Figurementioning

confidence: 99%

Identification of Frailty Using a Claims‐Based Frailty Index in the CoreValve Studies: Findings from the EXTEND‐FRAILTY Study

Strom

Orkaby

et al. 2021

JAHA

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Background In aortic valve disease, the relationship between claims‐based frailty indices (CFIs) and validated measures of frailty constructed from in‐person assessments is unclear but may be relevant for retrospective ascertainment of frailty status when otherwise unmeasured. Methods and Results We linked adults aged ≥65 years in the US CoreValve Studies (linkage rate, 67%; mean age, 82.7±6.2 years, 43.1% women), to Medicare inpatient claims, 2011 to 2015. The Johns Hopkins CFI, validated on the basis of the Fried index, was generated for each study participant, and the association between CFI tertile and trial outcomes was evaluated as part of the EXTEND‐FRAILTY substudy. Among 2357 participants (64.9% frail), higher CFI tertile was associated with greater impairments in nutrition, disability, cognition, and self‐rated health. The primary outcome of all‐cause mortality at 1 year occurred in 19.3%, 23.1%, and 31.3% of those in tertiles 1 to 3, respectively (tertile 2 versus 1: hazard ratio, 1.22; 95% CI, 0.98–1.51; P =0.07; tertile 3 versus 1: hazard ratio, 1.73; 95% CI, 1.41–2.12; P <0.001). Secondary outcomes (bleeding, major adverse cardiovascular and cerebrovascular events, and hospitalization) were more frequent with increasing CFI tertile and persisted despite adjustment for age, sex, New York Heart Association class, and Society of Thoracic Surgeons risk score. Conclusions In linked Medicare and CoreValve study data, a CFI based on the Fried index consistently identified individuals with worse impairments in frailty, disability, cognitive dysfunction, and nutrition and a higher risk of death, hospitalization, bleeding, and major adverse cardiovascular and cerebrovascular events, independent of age and risk category. While not a surrogate for validated metrics of frailty using in‐person assessments, use of this CFI to ascertain frailty status among patients with aortic valve disease may be valid and prognostically relevant information when otherwise not measured.

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“…Fifth, and finally, more data are needed for other cardiovascular devices and settings in which "real world" evidence could be used in the regulatory process. 10…”

Section: Next Stepsmentioning

confidence: 99%

Putting Theory to the Test

Strom

Yeh

2019

Circ: Cardiovascular Interventions

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Validating the use of registries and claims data to support randomized trials: Rationale and design of the Extending Trial-Based Evaluations of Medical Therapies Using Novel Sources of Data (EXTEND) Study

Cited by 24 publications

References 37 publications

Estimation of DAPT Study Treatment Effects in Contemporary Clinical Practice: Findings From the EXTEND-DAPT Study

Estimation of DAPT Study Treatment Effects in Contemporary Clinical Practice: Findings From the EXTEND-DAPT Study

Identification of Frailty Using a Claims‐Based Frailty Index in the CoreValve Studies: Findings from the EXTEND‐FRAILTY Study

Putting Theory to the Test

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