TY - JOUR
T1 - Identification and Validation of Major Cardiovascular Events in the United Kingdom Data Sources Included in a Multi-database Post-authorization Safety Study of Prucalopride
AU - Ruigómez, Ana
AU - Plana, Estel
AU - Gilsenan, Alicia
AU - Fortuny, Joan
AU - Cainzos-Achirica, Miguel
AU - Flynn, Robert W. V.
AU - MacDonald, Thomas M.
AU - Garcia-Rodriguez, Luis
AU - Ziemiecki, Ryan
AU - Andrews, Elizabeth B.
N1 - Funding for this research was provided by:
Shire Pharmaceuticals GmbH, now part of the Takeda group of companies
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101288201&partnerID=8YFLogxK
U2 - 10.1007/s40264-021-01044-4
DO - 10.1007/s40264-021-01044-4
M3 - Article
C2 - 33606202
SN - 0114-5916
VL - 44
SP - 541
EP - 551
JO - Drug Safety
JF - Drug Safety
ER -