Identification and Validation of Major Cardiovascular Events in the United Kingdom Data Sources Included in a Multi-database Post-authorization Safety Study of Prucalopride

Ana Ruigómez, Estel Plana, Alicia Gilsenan, Joan Fortuny, Miguel Cainzos-Achirica, Robert W.V. Flynn, Thomas M. MacDonald, Luis Garcia-Rodriguez, Ryan Ziemiecki, Elizabeth B. Andrews

Research output: Contribution to journalArticle

Abstract

Introduction: A multinational post-authorization safety study assessed cardiovascular safety in initiators of prucalopride for chronic constipation compared with a matched cohort of polyethylene glycol 3350 initiators. The primary safety outcome was major adverse cardiovascular events (MACE), a composite of hospitalization for acute myocardial infarction, stroke, or in-hospital cardiovascular death. We report the validation process for MACE endpoints in United Kingdom (UK) data sources: Clinical Practice Research Datalink (CPRD GOLD), The Health Improvement Network (THIN), and the Information Services Division (ISD) Scotland. Methods: Modified electronic algorithms from prior research identified potential MACE cases. Validation followed a common protocol, adapted for each database, with all information anonymized: (1) direct confirmation via linkage to hospital records (CPRD GOLD); (2) requests for additional clinical information through questionnaires (CPRD GOLD), free-text (THIN), or abstraction of hospital records (ISD); (3) manual review of electronic records of potential events retrieved by the algorithm (CPRD GOLD/THIN); and (4) event adjudication by three clinicians, blinded to exposure, for all remaining events. Results: Electronic algorithms identified 260 potential MACE cases: 38 confirmed via linkage to hospital records (CPRD GOLD), 56 ruled out as non-cardiovascular death cases (THIN), and three unavailable for review (ISD), leaving 163 potential cases. After manual review with additional information (steps 2 and 3), 45 were considered noncases (CPRD GOLD/THIN). Upon final adjudication (step 4), remaining potential events were adjudicated as definite (n = 62), probable (n = 10), possible (n = 13), or noncases (n = 33). Conclusions: Given the limitations of relying solely on computer algorithms to identify cardiovascular outcomes, validation with clinical review is essential to guide interpretation.

Original languageEnglish (US)
JournalDrug Safety
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Pharmacology (medical)

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