Influence of drug safety advisories on drug utilisation: an international interrupted time series and meta-analysis

Richard L Morrow; Barbara Mintzes; Patrick C Souverein; Marie L De Bruin; Elizabeth Ellen Roughead; Joel Lexchin; Anna Kemp-Casey; Lorri Puil; Ingrid Sketris; Dee Mangin; Christine E Hallgreen; Sallie-Anne Pearson; Ruth Lopert; Lisa Bero; Richard Ofori-Asenso; Danijela Gnjidic; Ameet Sarpatwari; Lucy T Perry; Colin R Dormuth

doi:10.1136/bmjqs-2021-013910

Influence of drug safety advisories on drug utilisation: an international interrupted time series and meta-analysis

BMJ Qual Saf. 2022 Mar;31(3):179-190. doi: 10.1136/bmjqs-2021-013910. Epub 2022 Jan 20.

Authors

Richard L Morrow¹, Barbara Mintzes², Patrick C Souverein³, Marie L De Bruin³, Elizabeth Ellen Roughead⁴, Joel Lexchin⁵, Anna Kemp-Casey⁴, Lorri Puil⁶, Ingrid Sketris⁷, Dee Mangin⁸, Christine E Hallgreen⁹, Sallie-Anne Pearson¹⁰, Ruth Lopert¹¹, Lisa Bero¹², Richard Ofori-Asenso⁹, Danijela Gnjidic², Ameet Sarpatwari¹³, Lucy T Perry², Colin R Dormuth¹⁴

Affiliations

¹ Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada richard.morrow@ubc.ca.
² School of Pharmacy, Faculty of Medicine and Health, and Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
³ Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University Faculty of Science, Utrecht, The Netherlands.
⁴ Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
⁵ School of Health Policy & Management, York University, Toronto, Ontario, Canada.
⁶ School of Population and Public Health, The University of British Columbia Faculty of Medicine, Vancouver, British Columbia, Canada.
⁷ Dalhousie University, College of Pharmacy, Halifax, Nova Scotia, Canada.
⁸ Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada.
⁹ Copenhagen Centre for Regulatory Science, Department of Pharmacy, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark.
¹⁰ Centre for Big Data Research in Health, UNSW Sydney, Sydney, New South Wales, Australia.
¹¹ Department of Health Policy and Management, George Washington University, Washington, District of Columbia, USA.
¹² School of Medicine and Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
¹³ Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁴ Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Objective: To evaluate the association between regulatory drug safety advisories and changes in drug utilisation.

Design: We conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories.

Study population: We included advisories issued in Canada, Denmark, the UK and the USA during 2009-2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months.

Main outcome measures: Change in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population.

Results: Among advisories without dose-related advice (n=20), the average change in drug utilisation was -5.83% (95% CI -10.93 to -0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (-1.93%; 95% CI -17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice.

Conclusions: Among safety advisories issued on a wide range of drugs during 2009-2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest.

Keywords: health policy; health services research; medication safety; pharmacoepidemiology.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Canada / epidemiology
Drug Prescriptions*
Drug Utilization*
Humans
Interrupted Time Series Analysis

Grants and funding

PJT-153275/CIHR/Canada