Comparison of the Accuracy and Completeness of Records of Serious Vascular Events in Routinely Collected Data vs Clinical Trial–Adjudicated Direct Follow-up Data in the UK

Charlie Harper,Marion Mafham,William Stevens,William Herrington,Louise Bowman,Sarah Parish,Richard Haynes,Martin J Landray,Karl Wallendszus,Jane Armitage,Natalie Staplin

doi:10.1001/jamanetworkopen.2021.39748

Charlie Harper, Marion Mafham + Show 9 more

Open Access

https://doi.org/10.1001/jamanetworkopen.2021.39748

Copy DOI

Abstract

Routinely collected data could substantially decrease the cost of conducting trials. To assess the accuracy and completeness of UK routine data for ascertaining serious vascular events (SVEs) compared with adjudicated follow-up data. This was a secondary analysis of a randomized clinical trial. From June 24, 2005, to July 28, 2011, the ASCEND (A Study of Cardiovascular Events in Diabetes) primary prevention trial used mail-based methods to randomize people with diabetes without evidence of atherosclerotic vascular disease using a 2 × 2 factorial design to aspirin and/or ω-fatty acids vs matching placebo in the UK. Direct participant mail-based follow-up was the main source of outcome data, with more than 90% of the primary outcome events undergoing adjudication. Follow-up was completed on July 31, 2017. In parallel, more than 99% of participants were linked to routinely collected hospital admission and death registry data (ie, routine data), enabling post hoc randomized comparisons of different sources of outcome data (conducted from September 1, 2018, to October 1, 2021). Random allocation to 100 mg of aspirin once daily vs matching placebo and separately to 1 g of ω-3 fatty acids once daily vs placebo. The primary outcome consisted of SVEs (a composite of nonfatal myocardial infarction, ischemic stroke, transient ischemic attack [TIA], or vascular death, excluding hemorrhagic stroke). A total of 15 480 participants were randomized (mean [SD] age, 63 [9] years; 9684 [62.6%] men) and followed up for a mean (SD) of 7.4 (1.8) years. For SVEs, agreement between adjudicated direct follow-up and routine data sources was strong (1401 vs 1127 events; κ = 0.78 [95% CI, 0.76-0.80]; sensitivity, 72.0% [95% CI, 69.7%-74.4%]; specificity, 99.2% [95% CI, 99.0%-99.3%]), and sensitivity improved for SVEs excluding transient ischemic attack (1129 vs 1026 events; sensitivity, 80.6% [95% CI, 78.3%-82.9%]). Rate ratios for the aspirin-randomized comparison for adjudicated direct follow-up vs follow-up solely through routine data alone were 0.88 (95% CI, 0.79-0.97) vs 0.91 (95% CI, 0.81-1.02) for the primary outcome and 0.92 (95% CI, 0.82-1.03) vs 0.91 (95% CI, 0.80-1.02) for SVEs excluding TIA. Results were similar for the ω-3 fatty acid comparison, and adjudication did not seem to markedly change rate ratios. Post hoc analyses of the ASCEND trial suggest that routinely collected hospital admission and death registry data in the UK could be used as the sole method of follow-up for myocardial infarction, ischemic stroke resulting in hospitalization, vascular death, and arterial revascularization in primary prevention cardiovascular trials, without the need for verification by clinical adjudication.

Highlights

For serious vascular event (SVE), agreement between adjudicated direct follow-up and routine data sources was strong (1401 vs 1127 events; κ = 0.78 [95% CI, 0.76-0.80]; sensitivity, 72.0% [95% CI, 69.7%-74.4%]; specificity, 99.2% [95% CI, 99.0%-99.3%]), and sensitivity improved for SVEs excluding transient ischemic attack (1129 vs 1026 events; sensitivity, 80.6% [95% CI, 78.3%-82.9%])
Rate ratios for the aspirin-randomized comparison for adjudicated direct follow-up vs follow-up solely through routine data alone were 0.88 vs 0.91 for the primary outcome and 0.92 vs 0.91 for SVEs excluding TIA
Post hoc analyses of the ASCEND trial suggest that routinely collected hospital admission and death registry data in the UK could be used as the sole method of follow-up for myocardial infarction, ischemic stroke resulting in hospitalization, vascular death, and arterial revascularization in primary prevention cardiovascular trials, without the need for verification by clinical adjudication

Summary

Introduction

Large randomized trials in cardiovascular disease have provided reliable evidence for interventions whose widespread use has contributed to the secular declines in mortality due to cardiovascular disease.[1,2] increasing costs of conducting trials threaten our ability to generate new randomized evidence.[3,4] Observational analyses in routinely collected health care (ie, real-world) data are increasingly used to make inferences about the safety and efficacy of interventions, but such nonrandomized analyses cannot fully account for confounding and are unreliable.[5,6] More appropriately, routinely collected data could be used to streamline trial follow-up conduct and design by offering a cost-efficient method to ascertain outcomes.[7,8]The National Health Service (NHS) in the UK has long-established, routinely collected national level mortality and hospital admission records, including Hospital Episode Statistics[9] in England, with equivalents in Wales[10] and Scotland.[11]. These records cover all NHS hospitals and have been collected since the 1990s using standardized clinical coding practices,[12,13,14] but have rarely been adopted into trial designs.[15,16,17,18] This is perhaps owing to the limited evidence of their accuracy and completeness for specific outcomes and delays in receiving the data.[19]

Methods

Results

Discussion

Conclusion