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

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

Richard L Morrow  1 , Barbara Mintzes  2 , Patrick C Souverein  3 , Marie L De Bruin  3 , Elizabeth Ellen Roughead  4 , Joel Lexchin  5 , Anna Kemp-Casey  4 , Lorri Puil  6 , Ingrid Sketris  7 , Dee Mangin  8 , Christine E Hallgreen  9 , Sallie-Anne Pearson  10 , Ruth Lopert  11 , Lisa Bero  12 , Richard Ofori-Asenso  9 , Danijela Gnjidic  2 , Ameet Sarpatwari  13 , Lucy T Perry  2 , Colin R Dormuth  14
Affiliations
Meta-Analysis

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

Richard L Morrow et al. BMJ Qual Saf. 2022 Mar.

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.

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Conflict of interest statement

Competing interests: MLDB declares PhD grants from Novo Nordisk, Lundbeck, Ferring Pharmaceuticals and LEO Pharma to the Copenhagen Centre for Regulatory Science; CH declares grants or contracts from Novo Nordisk A/S and H. Lundbeck A/S paid to her institution; BM is acting as an expert witness for Health Canada on a legal case and anticipates future payment for doing so; S-AP declares the Centre for Big Data Research in Health received funding for postmarket surveillance research, unrelated to the current study; LP has received a Michael Smith Foundation for Health Research Reach Grant; AS declares grants or contracts from Arnold Ventures and the FDA paid to his institution, consulting fees from West Health and payment for expert testimony from the ACLU; IS has received a CIHR Canadian Network for Observational Drug Effect Studies grant and a Drug Evaluation Alliance of Nova Scotia grant, and payment for serving as a member of the Patented Medicine Prices Review Board.

Figures

Figure 1
Figure 1
Selection of drug safety advisories for inclusion. *Excluding advisories relating to all-clear statements, drugs available over-the-counter in ≥1 country, drug-drug interactions, drugs marketed in only one of the countries and vaccines. Multiple advisories on the same topic were counted only once. Danish advisories were included in analysis, but not in the process of selection of advisories to include. †Based on data from US IBM MarketScan Research Databases. ‡Advisory for fingolimod and progressive multifocal leucoencephalopathy. Created by the authors.
Figure 2
Figure 2
Actual versus predicted percentage change in the rate of prescriptions following drug safety advisories without dose-related advice,* adjusted by change in controls without an advisory. *Actual versus predicted percentage change in the number of prescriptions written or dispensed per 100 000 population during an 11-month period following the month a drug advisory was issued. Created by the authors. IV, inverse variance; PML, progressive multifocal leucoencephalopathy.
Figure 3
Figure 3
Actual versus predicted percentage change in the rate of defined daily doses following dose-related drug safety advisories,* adjusted by change in controls without an advisory. *Actual versus predicted percentage change in the number of defined daily doses prescribed or dispensed per 100 000 population during an 11-month period following the month a drug advisory was issued. Dose-related advisories are those with dose-related advice. Created by the authors. IV, inverse variance.
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