Do drug‐related safety warnings have the expected impact on drug therapy? A systematic review

Abstract

Purpose The need for drug‐related safety warnings is undisputed, and their impact should also be evaluated. This systematic review investigates and assesses the impact of safety warnings on drug therapy. Methods Studies published in English between January 1998 and December 2018 were searched in EMBASE and MEDLINE, complemented by manual search. Randomised controlled trials, cohort studies with a before/after component, and case‐control studies were included, selected to predefined criteria, and assessed for their reporting and methodological quality. Results Out of 7454 references identified, 72 studies were included. A total of 28/72 (39%) studies described the impact of safety warnings on drug therapy as being effective, whereas 12/72 (17%) studies did not. Further, 26/72 (36%) studies described a partial implementation of the warnings (one part of the warning had an impact on drug therapy and another did not). Unintended effects were investigated in 6/72 (8%) studies. While 34 (47%) studies examined safety warnings on psychotropic drugs using an interrupted time series (ITS) design (53%), a before/after (26%), and a time series design (21%), 38 (53%) studied other substances using an ITS design (34%), a before/after (40%), and a time series design (26%). The proportion of an effective impact on drug therapy was lower in the “psychotropic drugs” group (23%) than in the “others” group (53%). Conclusion Drug‐related safety warnings induce intended and unintended effects. The included studies are of broadly varying methodological quality. To better compare their effectiveness, studies should be conducted using standardised procedures.

Impact of safety warnings for fluoroquinolones on prescribing behaviour. Results of a cohort study with outpatient routine data

“…Written safety warnings on human drugs addressed to health care professionals (e.g., physicians and pharmacists) intend to minimise the risk of drug therapy. The need for drug-related safety warnings is therefore undisputed and three systematic reviews [1][2][3] investigated their impact on prescribing behaviour. Many studies included in these reviews described the impact of safety warnings contradictorily.…”

Regulatory post‐market drug safety advisories on cardiac harm: A comparison of four national regulatory agencies

“…Current research on the effectiveness of advisories is mixed and has mostly focused on individual advisories and regulators. There have been a small number of systematic reviews which have investigated the effects of these advisories on rates of prescribing 38‐42 . These have generally found that the current evidence is mixed, as advisories may have intended or unintended effects, to varying degrees, emphasizing that more research is required to understand why these effects are seen.…”

“…[38][39][40][41][42] These have generally found that the current evidence is mixed, as advisories may have intended or unintended effects, to varying degrees, emphasizing that more research is required to understand why these effects are seen. One review which looked into papers on FDA advisories found that there was a mixed impact depending on the type of advisory 38.…”

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

“…5 Systematic reviews suggest advisories issued by regulators may influence clinical practice. [6][7][8][9] Original research with a recommendation to change practice based on a change or restriction in indication were associated with a 34% change in the rate of prescribing in the intended direction, while risk communications to 'be aware' of new information about a drug's risk were associated with an 11% change in prescribing. 9 These findings suggest prescribing changes may differ in relation to how information about drug risk is communicated in an advisory.…”