Impact of medicines regulatory risk communications in the UK on prescribing and clinical outcomes: Systematic review, time series analysis and meta‐analysis

Abstract

Aims Regulatory risk communications are important to ensure medication safety, but their impact is poorly understood. The aim was to quantify the impact of UK risk communications on medication use and other outcomes. Methods We conducted a systematic review of studies reporting prescribing/health outcome data relevant to UK regulatory risk communication. Data were reanalysed using interrupted time series regression 12 months after each regulatory intervention. Mean changes were pooled using random‐effects generic inverse variance examining the following subgroups: drug withdrawals; restrictions/changes in indications; be aware messages without specific recommendations for action; communication via direct healthcare practitioner communications; communication via drug bulletins. Results Of 11 466 articles screened, 40 studies examining 25 UK regulatory risk communications were included. Product withdrawals, restriction in indications and be aware communications were associated with relative mean changes of −78% (95% confidence interval [CI] −60 to −96%), −34% (95% confidence interval [CI] −12 to −55%) and −11% (95%CI −8 to −15%) in targeted drug prescribing respectively. Direct healthcare professional communications were associated with relative mean changes of −47% (95%CI −27 to −68%) compared to −13% (95%CI −6 to −20%) for drug bulletins. Of 7 studies examining unique health outcomes related to the safety concern, risk communications were associated with a mean −10% (95%CI −3 to −16%) decrease in intended and a 7% (95%CI 4 to 10%) increase in unintended health outcomes. Discussion UK regulatory risk communications were associated with significant changes in targeted prescribing and potential changes in clinical outcomes. Further research is needed to systematically study the impact of regulatory interventions.

Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands

“…Heterogeneity in impact may also relate to features such as the type of warning, method of dissemination, clinical context, media coverage, changes in guidelines, and public and professional perceptions that risks are serious . For example, the 2004 UK risk communication on the use of antipsychotics in dementia containing clear recommendations led to greater changes in prescribing in Scotland compared with the 2009 less specific communication in a drug bulletin .…”

“…Further information examining what impact the regulatory action had on targeted populations in whom diclofenac was contraindicated or cautioned would support those decisions. The effective implementation of regulatory actions is complex and requires input from multiple stakeholders, but there is some evidence demonstrating which types of dissemination and communication methods are most effective . It seems imperative that evaluating the impact of regulatory actions should routinely account for both intended and unintended consequences on either prescribing health outcomes or both.…”

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

“…[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.…”

Correction

“…In column 2 of page 635, the reference Weatherburn et al (2019) 1 is to be inserted at the end of the sentence “The Achilles heel of regulatory pharmacovigilance remains the ability to change behaviour. Examples of effective action are included in the paper by Weatherburn et al”…”