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 Information:
Jennifer Bartsch from RTI Health Solutions contributed to the statistical programming. Abenah Harding from RTI Health Solutions provided quality checks and support for the development of the manuscript and assistance with responding to reviewer comments. Kate Lothman from RTI Health Solutions provided medical writing support. Helle Kieler contributed to the study as a primary investigator in Sweden. Alison McGinnis, a research nurse, toured Scottish hospitals to gather original hospital case records for the purposes of endpoint adjudication. The authors acknowledge the Electronic Data Research and Innovation Service (eDRIS) of ISD Scotland for providing the ISD data. Amy Rogers and Kerr Grieve provided assistance with validation. This study is based in part on data from the CPRD obtained under license from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the National Health Service (NHS) as part of their care and support. The interpretation and conclusions contained in this study are those of the authors alone. Copyright © 2020, re-used with the permission of The Health & Social Care Information Centre. All rights reserved.
Funding Information:
This study was performed under a research contract between RTI Health Solutions and Shire Pharmaceuticals GmbH, now part of the Takeda group of companies. The content of the publication was developed independently from the sponsor. Alicia Gilsenan, Joan Fortuny, Estel Plana, Miguel Cainzos-Achirica, Ryan Ziemiecki, and Elizabeth B. Andrews are or were salaried employees of RTI Health Solutions at the time the study was conducted. Miguel Cainzos-Achirica now works at Houston Methodist DeBakey Heart and Vascular Center and has participated in a research study funded by a non-conditioned research grant from Vifor. Ana Ruigómez and Luis-Alberto Garcia-Rodriguez work at the Spanish Centre for Pharmacoepidemiologic Research (CEIFE Madrid, Spain), which has received research funding from RTI Health Solutions. Luis-Alberto Garcia Rodriguez also received honoraria for serving on advisory boards for Bayer AG. Robert W.V. Flynn is an employee of the University of Dundee and has received research grants from Novartis and GlaxoSmithKline. Professor Thomas M. MacDonald is an employee of the University of Dundee who received financial support under the research contract between RTI Health Solutions and Shire Pharmaceuticals GmbH, now part of the Takeda group of companies, to carry out the study. Thomas M. MacDonald also works with MEMO Research at the University of Dundee and received or has received research funding from Novartis, Amgen, Ipsen, GRK Teijin, and Menarini and has received honoraria for educational lectures from Takeda. He has been the Principal Investigator on trials paid for by Novartis, Ipsen, Teijin, GlaxoSmithKline, and Menarini. In the last 3 years, he has been paid consulting fees by Novartis.
Funding Information:
This study was funded by Shire Pharmaceuticals GmbH, now part of the Takeda group of companies.
Publisher Copyright:
© 2021, The Author(s).
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.
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U2 - 10.1007/s40264-021-01044-4
DO - 10.1007/s40264-021-01044-4
M3 - Article
C2 - 33606202
AN - SCOPUS:85101288201
VL - 44
SP - 541
EP - 551
JO - Drug Safety
JF - Drug Safety
SN - 0114-5916
IS - 5
ER -