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. 2019 Oct;42(10):1167-1177.
doi: 10.1007/s40264-019-00836-z.

Study Design and Cohort Comparability in a Study of Major Cardiovascular Events in New Users of Prucalopride Versus Polyethylene Glycol 3350

Joan Fortuny  1 , Alicia Gilsenan  2 , Miguel Cainzos-Achirica  1   3 , Oscar F Cantero  4 , Robert W V Flynn  5 , Luis Garcia-Rodriguez  4 , Bianca Kollhorst  6 , Pär Karlsson  7 , Love Linnér  7 , Thomas M MacDonald  5 , Estel Plana  1 , Ana Ruigómez  4 , Tania Schink  6 , Ryan Ziemiecki  8 , Elizabeth B Andrews  8
Affiliations

Study Design and Cohort Comparability in a Study of Major Cardiovascular Events in New Users of Prucalopride Versus Polyethylene Glycol 3350

Joan Fortuny et al. Drug Saf. 2019 Oct.

Abstract

Introduction: Given prior safety experience with other 5-HT4 agonists for chronic constipation, an observational, population-based cohort study in five data sources from Germany, Sweden, and the UK was conducted to evaluate the cardiovascular safety of prucalopride.

Objectives: Our objective is to describe the methods and resulting comparability of cohorts in a multi-database, multinational study of prucalopride initiators and polyethylene glycol 3350 (PEG) initiators following a harmonized protocol.

Methods: Prucalopride initiators were matched on age, sex, and index date to PEG initiators (1:5 ratio). Study exposures, cardiovascular risk factors, and other covariates were identified from healthcare utilization codes harmonized across databases. Cardiovascular outcomes were identified using database-specific algorithms based on diagnosis codes. The propensity score (PS) in each database was estimated using logistic regression, with prucalopride versus PEG as the outcome and including clinically relevant variables associated with major adverse cardiovascular events.

Results: In total, 12,030 prucalopride initiators and 59,985 PEG initiators were identified. After matching and trimming, cohorts from the UK and Sweden were well-balanced for cardiovascular risk factors and cancer. However, in Germany, PEG initiators remained older and sicker than prucalopride initiators. The prevalence of these characteristics also differed from those in the UK and Sweden. The pooled analyses included only data from the UK and Sweden.

Conclusions: Matching, trimming, and PS stratification yielded comparable cohorts in four of five data sources. Use of these methods could not achieve balance for key covariates within the German cohort, likely due to reimbursement differences in Germany.

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Conflict of interest statement

This study was performed under a research contract between RTI Health Solutions and Shire, now part of the Takeda group of companies, and was funded by Shire. The research contract granted independent publication rights to the research team, and the content of the publications was developed independently from the study sponsor. Alicia Gilsenan, Joan Fortuny, Estel Plana, Ryan Ziemiecki, and Elizabeth B. Andrews are salaried employees of RTI Health Solutions. Miguel Cainzos-Achirica was a salaried employee of RTI Health Solutions when this research was conducted and is currently affiliated with the Hospital Universitari de Bellvitge Department of Cardiology, Feixa Llarga, Hospitalet de Llobregat, Barcelona, Spain. Luis Garcia-Rodriguez, Oscar F. Cantero, and Ana Ruigómez are employed at the Spanish Centre for Pharmacoepidemiologic Research (CEIFE Madrid, Spain). Robert W. V. Flynn and Professor Thomas M. MacDonald are employees of the University of Dundee, an academic organization that received financial support under the research contract between RTI Health Solutions and Shire, now part of the Takeda group of companies, to carry out the study. Robert W. V. Flynn has received research grants from Novartis and GlaxoSmithKline. Professor Thomas M. MacDonald is the director of MEMO Research at the University of Dundee, an organization that has received research funding from Pfizer, Novartis, Amgen, Ipsen, GlaxoSmithKline, Teijin, and Menarini, mostly for post-licensing studies requested by regulatory authorities, and has personally received honoraria for educational lectures from Takeda. He has been the principal investigator on trials paid for by Pfizer, Novartis, Ipsen, Teijin, GlaxoSmithKline, and Menarini (mostly post-licensing regulatory requested studies). In the last 3 years, he has received consulting fees from Novartis. Pär Karlsson and Love Linnér are employed at the Centre for Pharmacoepidemiology, Karolinska Institutet, which receives grants from several entities (pharmaceutical companies, regulatory authorities and contract research organizations) for performance of drug safety and drug utilization studies. These entities had no role in the data collection and analysis and were not involved in the interpretation of results, writing, revision, and approval of the manuscript. Miguel Cainzos-Achirica has participated in a research study funded by a non-conditioned research grant from Vifor. Tania Schink and Bianca Kollhorst are working at an independent, non-profit research institute, the Leibniz Institute for Prevention Research and Epidemiology – BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. Almost exclusively, these are post-authorization safety studies requested by health authorities. The design and conduct of these studies as well as the interpretation and publication are not influenced by the pharmaceutical industry.

Figures

Fig. 1
Fig. 1
Study design and implementation of analyses
Fig. 2
Fig. 2
Cohort attrition. GePaRD German Pharmacoepidemiological Research Database, PEG polyethylene glycol 3350, SNR Swedish National Registers
See this image and copyright information in PMC

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