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Drug side-effect warnings differ by up to 86% between US and EU, study finds

A new study has found warnings for drug side-effects, called adverse drug reactions, can differ by up to 86% between US and European documents for the same drug. The study, led by researchers from King’s College London, suggests more consistent, evidence-based reporting of side-effects is needed so doctors prescribing drugs can make informed risk-benefit decisions.

The authors also found the majority of the drugs they investigated reported more than 150 adverse reactions, with one US drug document listing 425 possible adverse reactions.

The study, published in BMJ Open, compared product information documents for 12 antidepressant and anticonvulsant drugs marketed in the US and Europe by the same pharmaceutical companies. Drug manufacturers are required to report adverse drug reactions in a product information document, which informs prescribers - medical doctors and pharmacists - how to use the medication safely and appropriately.

When the researchers compared the adverse reactions listed in the US and European versions of the drug information document, they found the percent of adverse reactions that did not match ranged from 40% to 86%. On average, 71% of the side-effect terms listed in the US drug information document was not in its European counterpart, or vice versa.

The study also found the documents lacked information useful to prescribers and patients, such as the likelihood, severity or duration of adverse reactions. The study authors observe: “a patient may be willing to risk the occurrence of, for example, tinnitus or peripheral vision loss if the condition resolves, but not if the duration is excessive and recurring”.

Dr Victoria Cornelius, lead author of the study from the King’s Division of Health and Social Care Research (and now based at ICL), said: “We found that the information about side-effects contained in these drug documents is inconsistently presented and the volume of adverse drug reactions included is often overwhelming, as a result it’s hard to see how this can be useful for prescribers and patients. Drug documents often don’t include information of central importance to patients and prescribers, such as likely seriousness or reversibility of an adverse reaction.”

“As a research community committed to evidence-based medicine, we should not accept inadequate synthesis and unclear reporting of drug harm as an unsolvable problem. Improving the quality of harm reporting may require better adherence to best practice guidance for clinical trials and action by drug regulators.”

Better ways to prioritise and present harm data are required to enable patients and prescribers to undertake informed risk-benefit decisions, the study concludes.

The study found US drug documents contained more information on methodology, such as the data source and clinical indications, which are needed to interpret harm events. However, on average the US documents reported 77 more adverse reactions, making the overall harm profile harder to absorb than information in European documents.

The authors suggest the unexpected inconsistency between European and US documents could be due to data being from different clinical trials, use of different medical dictionaries to code the adverse drug reactions, fear of litigation, or different regulatory regimes. In the US drugs are regulated by the Food and Drug Agency (FDA) and in Europe by the European Medicines Agency (EMA).

Notes to editors

For more information, please contact Hilary Jones, communications officer for the Division of Health and Social Care Research at King’s College London:, tel: +44 (0)20 7848 6684; or the KCL press office on tel: +44 (0) 20 7848 3202

‘Variation in adverse drug reactions listed in product information for antidepressants and anticonvulsants between the USA and Europe: a comparison review of paired regulatory documents’ by Cornelius et al is published in BMJ Open and accessible here.