BACKGROUND: A post-authorization safety study (PASS) was conducted to assess the cardiovascular safety of prucalopride, comparing the occurrence of major adverse cardiovascular events (MACE, a composite of hospitalization for acute myocardial infarction [AMI], hospitalization for stroke, and in-hospital cardiovascular death) among initiators of prucalopride and among a matched comparator cohort. The study was conducted in five data sources from three European member states: the United Kingdom (UK), Germany and Sweden.
OBJECTIVES: To report the validation process of MACE endpoints conducted for the prucalopride multi-database PASS in the UK data sources: Clinical Practice Research Datalink (CPRD), the Health Improvement Network (THIN), and the Information Services Division (ISD) Scotland.
METHODS: Potential MACE events were identified using an automated algorithm based on previous studies. Validation was conducted per the common validation plan, which included (1) direct confirmation via linkage to hospital records (CPRD only); (2) requests for additional clinical information through questionnaires (CPRD), free text (THIN), or original hospital case records (ISD); (3) patient profile review by study investigators (CPRD/THIN) to rule out non-cases; and (4) event adjudication by three clinicians, all blinded to exposure, for all potential endpoints not previously confirmed or determined as non-case. Cases were assigned final status of definite, probable, possible, or non-cases.
RESULTS: The electronic algorithms identified 260 potential MACE events, of which 38 cases were considered confirmed via linkage to hospital records (CPRD only), 91 were considered non- cases after profile review (CPRD and THIN), and 13 were not available for adjudication (THIN and ISD). Of the remaining 118 potential cases, 62 were adjudicated as definite, 10 adjudicated as probable, 13 as possible, and 33 as non-cases. The general practitioner questionnaire response rate in CPRD was 79%, free text was available for all potential cases from THIN, and all but three requested hospital case records from ISD were retrieved. This was the first observational study in Scotland in which access to hospital case records was granted.
CONCLUSION: A common validation protocol, with local adaptations based on the types of clinical information available in each data source, allowed for the validation of MACE endpoints in the prucalopride multi-database PASS in three UK data sources.
