Clare E King1, Nicole L Pratt2, Nichole Craig3, Loc Thai3, Margaret Wilson4, Neillan Nandapalan4, Lisa Kalisch Ellet2, Eirene C Behm4. 1. Therapeutic Goods Administration, Australian Government Department of Health, GPO Box 9848, Canberra, ACT, Australia. clare.king@health.gov.au. 2. Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia. 3. Australian Government Department of Health, GPO Box 9848, Canberra, ACT, Australia. 4. Therapeutic Goods Administration, Australian Government Department of Health, GPO Box 9848, Canberra, ACT, Australia.
Abstract
INTRODUCTION: Medicine safety signal detection methods employed by the medicine regulator in Australia (Therapeutic Goods Administration [TGA], Department of Health) rely predominantly on analysis of spontaneous adverse event (AE) reports, sponsor notifications or information shared by international agencies. The limitations of these methods and the availability of large administrative health data sets has given rise to greater interest in the use of administrative health data to support pharmacovigilance (PV). OBJECTIVE: We explored whether prescription sequence symmetry analysis (PSSA) of Pharmaceutical Benefits Scheme (PBS) data can enhance signal detection by the TGA, using the AE, heart failure (HF) as a case study. METHODS: We applied the PSSA method to all single-ingredient medicines dispensed under the PBS between 2012 and 2016, using furosemide initiation as a proxy for new-onset HF. A signal was considered present if the lower limit of the 95% confidence interval for the adjusted sequence ratio was > 1. We excluded medicines known to cause HF, indicated for HF treatment or indicated for diseases that may contribute to HF. RESULTS: Of the 654 tested medicines, 26 potential new HF signals were detected by PSSA. Five signals had additional support for the possible association provided by biological plausibility, consistency and disproportionate reporting of cases of HF to the TGA and the World Health Organization; and clinical impact. CONCLUSION: PSSA was able to identify potential signals for further evaluation. With the increasing availability of different administrative health data sources, the strengths and weaknesses of methods used to analyse these data for the purpose of regulatory PV should be evaluated.
INTRODUCTION: Medicine safety signal detection methods employed by the medicine regulator in Australia (Therapeutic Goods Administration [TGA], Department of Health) rely predominantly on analysis of spontaneous adverse event (AE) reports, sponsor notifications or information shared by international agencies. The limitations of these methods and the availability of large administrative health data sets has given rise to greater interest in the use of administrative health data to support pharmacovigilance (PV). OBJECTIVE: We explored whether prescription sequence symmetry analysis (PSSA) of Pharmaceutical Benefits Scheme (PBS) data can enhance signal detection by the TGA, using the AE, heart failure (HF) as a case study. METHODS: We applied the PSSA method to all single-ingredient medicines dispensed under the PBS between 2012 and 2016, using furosemide initiation as a proxy for new-onset HF. A signal was considered present if the lower limit of the 95% confidence interval for the adjusted sequence ratio was > 1. We excluded medicines known to cause HF, indicated for HF treatment or indicated for diseases that may contribute to HF. RESULTS: Of the 654 tested medicines, 26 potential new HF signals were detected by PSSA. Five signals had additional support for the possible association provided by biological plausibility, consistency and disproportionate reporting of cases of HF to the TGA and the World Health Organization; and clinical impact. CONCLUSION: PSSA was able to identify potential signals for further evaluation. With the increasing availability of different administrative health data sources, the strengths and weaknesses of methods used to analyse these data for the purpose of regulatory PV should be evaluated.
Authors: Ann S Doherty; Faiza Shahid; Frank Moriarty; Fiona Boland; Barbara Clyne; Tobias Dreischulte; Tom Fahey; Seán P Kennelly; Emma Wallace Journal: Pharmacol Res Perspect Date: 2022-10