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Comparative Study
. 2016 Jun 28:353:i3323.
doi: 10.1136/bmj.i3323.

Comparison of rates of safety issues and reporting of trial outcomes for medical devices approved in the European Union and United States: cohort study

Thomas J Hwang  1 , Elisaveta Sokolov  2 , Jessica M Franklin  3 , Aaron S Kesselheim  3
Affiliations
Comparative Study

Comparison of rates of safety issues and reporting of trial outcomes for medical devices approved in the European Union and United States: cohort study

Thomas J Hwang et al. BMJ. .

Abstract

Objective: To evaluate safety alerts and recalls, publication of key trial outcomes, and subsequent US approval of high profile medical devices introduced in the European Union.

Design: Cohort study.

Setting: Novel cardiovascular, orthopedic, and neurologic devices approved in the EU through Conformité Européenne marking between 2005 and 2010.

Data sources: Public and commercial databases searched up to January 2016 for press releases and announcements of approvals; public Food and Drug Administration and European regulatory authority databases for US approvals and safety alerts and recalls; and Medline, Embase, and Web of Science for peer reviewed publications.

Main outcome measures: We categorized the novelty of the devices in the study sample as a "major innovation" or an "other change," and extracted descriptive data about the devices and information on any safety alerts and withdrawals. Linear regression models examined factors associated with differential EU and US approvals. Cox proportional hazards regression models were used to evaluate factors associated with safety alerts and recalls and the publication of trial outcomes for devices categorized as major innovations. Models controlled for time, therapeutic category, regulatory pathway, size of sponsoring company, and indicator variables for devices approved first in the EU and devices approved only in the EU.

Results: 67% (206/309) of devices identified were approved in both the US and the EU, of which 63% (129/206) were approved first in the EU. The unadjusted rate of safety alerts and recalls for devices approved first in the EU was 27% (62/232) compared with 14% (11/77) for devices approved first in the US. The adjusted hazard ratio for safety alerts and recalls was 2.9 (95% confidence interval 1.4 to 6.2) for devices approved first in the EU. The results of pivotal trials were published for 49% (37/75) of devices categorized as major innovations, with an overall publication rate of 37% five years after approval.

Conclusions: Devices approved first in the EU are associated with an increased risk of post-marketing safety alerts and recalls. Poor trial publication rates mean that patients and clinicians need greater regulatory transparency to make informed decisions about treatment.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare that (within the past three years): TJH has received funding from Harvard University and the Interfaculty Initiative in Health Policy and was employed by Blackstone and Bain Capital; JMF has received funding from the Patient-Centered Outcomes Research Institute and Merck, and has consulted for Aetion, a software company; and ASK is a Greenwall faculty scholar and has received funding from the Harvard program in therapeutic science, the Laura and John Arnold Foundation, and the FDA Office of Generic Drugs and Division of Health Communication.

Figures

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Fig 1 Study flowchart. FDA=Food and Drug Administration
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Fig 2 Median time between Conformité Européenne (CE) marking and approval of Food and Drug Administration (FDA). Approval refers to CE marking in European Union (EU) and clearance or approval by FDA in United States. IQR=interquartile range
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Fig 3 (A) Cumulative incidence of safety alerts and recalls. (B) Cumulative incidence of recalls only. Approval refers to Conformité Européenne (CE) marking in the European Union and clearance or approval by the Food and Drug Administration
See this image and copyright information in PMC

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