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

Abstract

Objective: To compare consistency of adverse drug reaction (ADR) data in publicly available product information documents for brand drugs, between the USA and Europe. To assess the usefulness of information for prescribers and patients.

Design: A comparison review of product information documents for antidepressants and anticonvulsants concurrently marketed by the same pharmaceutical company in the USA and Europe.

Setting: For each drug, data were extracted from the US Product Inserts and the European Summary of Product Characteristics documents between 09/2013 and 01/2015.

Participants: Individuals contributing ADR information to product information documents.

Main outcomes measures: All ADRs reported in product information sections 5 and 6 (USA), and 4·4 and 4·8 (Europe).

Results: Twelve brand drugs--24 paired documents--were included. On average, there were 77 more ADRs reported in the USA compared with in the European product information document, with a median number of 201 ADRs (range: 65-425) and 114 (range: 56-265), respectively. More product information documents in the USA reported information on the source of evidence (10 vs 5) and risk (9 vs 5) for greater than 80% of ADRs included in the document. There was negligible information included regarding duration, severity, reversibility or recurrence of ADRs. On average, only 29% of ADR terms were reported in both paired documents.

Conclusions: Product information documents contained a large number of ADRs, but lacked contextual data and information important to patients and prescribers, such as duration, severity and reversibility. The ADR profile was found to be inconsistently reported between the USA and Europe, for the same drug. Identifying, selecting, summarising and presenting multidimensional harm data should be underpinned by practical evidence-based guidelines. In order for prescribers to provide considered risk-benefit advice across competing drug therapies to patients, they need access to comprehensible and reliable ADR information.

Keywords: Summary of Product Characteristics; United States Product Inserts; adverse drug reactions; anticonvulsants; antidepressent; product infomation.

Figure 1

Overview of issues to address in selection and presentation of harm information from clinical studies. ADRs, adverse drug reaction; AEs, adverse event; QoL, quality of life; RCT, randomised controlled trial; SARs, serious adverse reaction; SUSARs, suspected unexpected serious adverse reactions.