A Pharmacoepidemiology Database System for Monitoring Risk Due to the Use of Medicines by New Zealand Primary Care Patients
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The use of large record-linked healthcare databases for drug safety research and surveillance is now accepted practice. New Zealand’s standardized national healthcare datasets provide the potential to automate the conduct of pharmacoepidemiological studies to provide rapid validation of medicine safety signals.
Our objectives were to describe the methodology undertaken by a semi-automated computer system developed to rapidly assess risk due to drug exposure in New Zealand’s population of primary care patients and to compare results from three studies with previously published findings.
Data from three national databases were linked at the patient level in the automated studies. A retrospective nested case–control design was used to evaluate risk for upper gastrointestinal bleeding (UGIB), acute kidney failure (AKF), and serious arrhythmia associated with individual medicines, therapeutic classes of medicines, and concurrent use of medicines from multiple therapeutic classes.
The patient cohort available for each study included 5,194,256 patients registered between 2007 and 2014, with a total of 34,630,673 patient-years at risk. An increased risk for UGIB was associated with non-steroidal anti-inflammatory drugs (NSAIDs) (adjusted odds ratio [AOR] 4.16, 95% confidence interval [CI] 3.90–4.43, p < 0.001) and selective serotonin reuptake inhibitors (AOR 1.39, 95% CI 1.20–1.62, p < 0.001); an increased risk for AKF was associated with NSAIDs (AOR 1.78, 95% CI 1.73–1.83, p < 0.001) and proton pump inhibitors (AOR 1.78, 95% CI 1.72–1.83, p < 0.001); and an increased risk for serious arrhythmia was associated with fluoroquinolones (AOR 1.38, 95% CI 1.26–151, p < 0.001) and penicillins (AOR 1.69, 95% CI 1.61–1.77, p < 0.001).
Automated case–control studies using New Zealand’s healthcare datasets can replicate associations of risk with drug exposure consistent with previous findings. Their speed of conduct enables systematic monitoring of risk for adverse events associated with a wide range of medicines.
Compliance with Ethical Standards
In New Zealand, ethics committee review is not required for secondary use of data for the purpose of quality assurance or outcome analysis where the researchers are bound by a professional or an employment obligation to preserve confidentiality and the patient information is not identifiable. Ethical guidelines for observational studies: National Ethics Advisory Committee. http://www.neac.health.govt.nz/.
Conflicts of interest
David Reith is chair of the Medicines Adverse Reactions Committee of Medsafe, the New Zealand medicines and medical devices safety authority. Murray Tilyard is CEO and Hywel Lloyd is Director of Informatics at BPAC Clinical Solutions: findings from this study could be utilized in the electronic decision support tools that it markets. Andrew Tomlin, David Woods, Alesha Smith, and John Fountain have no conflicts of interest that are directly relevant to the content of this study.
No sources of funding were used to assist in the preparation of this study. The research was conducted as a component of the usual employment of the authors by BPACnz and the University of Otago. BPACnz is a registered charity co-owned by the University of Otago, ProCare Health Limited, South Link Health, General Practice New Zealand, Pegasus Health, and the Royal New Zealand College of General Practitioners.
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