How do safety warnings on medicines affect prescribing?

ABSTRACT

Introduction

Many adverse effects of medicines only become known after approval, prompting regulatory agencies to issue post-market safety advisories to support safer care. Our team evaluated advisories issued by national regulators in Australia, Canada, Denmark, the United Kingdom, and the United States from 2007 to 2016 inclusive, comparing regulators’ decisions to warn, effects on prescribing, doctors’ awareness and responses to warnings, relevant regulatory policies, and specific case studies.

Areas Covered

Based mainly on our research program and a narrative review, this commentary describes how often regulators issue safety advisories and effects on clinical practice. We found extensive differences in decisions to warn, timing and content of warnings. Monitoring advice is often inadequate. The most systematic estimate suggests an average reduction in prescribing of around 6% compared with settings with no advisory. Interviews with doctors suggest limited awareness, uptake, and at times belief in these warnings.

Expert Opinion

Post-market safety advisories are an important intervention aiming to improve prescribing and use of medicines. However, differing warnings mean that some patients may be exposed to riskier prescribing than others. Better integration of safety information into clinical practice is needed, as well as improved transparency, independence, and public engagement in regulatory decision-making.

KEYWORDS:

• Drug safety
• pharmacovigilance
• risk communication
• regulatory policy

Article highlights

• Regulatory safety advisories are a commonly used intervention aiming to inform clinicians and the public of emerging post-market evidence on serious harmful effects of medicines and support safer prescribing and associated clinical care.

• Research on advisories issued in Australia, Canada, the United Kingdom and United States from 2007 to 2016 highlights large differences in the decision to warn: of 573 identified safety concerns for medicines available in all four countries, 40 (7%) led to warnings in all included countries.

• Differences in regulatory governance of post-market risk communication, including resource allocation, transparency and accountability of decision-making, may explain many differences.

• A systematic population-based assessment of effects of advisories on medicine use found a modest 6% reduction in use over 11 months, with large variation around this average effect.

• Interview studies suggest that doctors may see regulators as outside of their usual sphere of clinical information sources, leading to underuse of key safety advice.

• Better integration of new safety information into clinical practice is needed, as well as improved transparency, independence, and public engagement in regulatory decision-making.

Declaration of interests

Barbara Mintzes is an expert witness for Health Canada on a legal case involving marketing of an unapproved drug product. Priya Bahri is an employee of the European Medicines Agency (EMA). Lucy Perry was previously employed at George Clinical, a contract research organisation conducting research on behalf of the pharmaceutical industry. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Disclaimer

The views expressed in this article are P Bahri’s personal views and may not be understood or quoted as being made on behalf of or reflect the position of the EMA or one of its committees or working parties.

Additional information

Funding

This paper was funded by the Canadian Institutes of Health Research, Grant/Award Number: ID#153275 and National Health and Medical Research Council, Grant/Award Number: ID#1122332.