title: Comparison of rates of safety issues and reporting of trial outcomes for medical devices approved in the European Union and United States: cohort study.
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.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Novel cardiovascular, orthopedic, and neurologic devices approved in the EU through Conformité Européenne marking between 2005 and 2010.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Faculty of Arts and Sciences, Harvard University, Cambridge, MA, USA Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hwang
authors.affiliation: Department of Neurology and Neurophysiology, King's College London, London, UK.
authors.forename: Elisaveta
authors.initials: E
authors.lastname: Sokolov
authors.affiliation: Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Franklin
authors.affiliation: Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Kesselheim
mesh_terms: D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003257:Consumer Product Safety / Q000592:standards*; D016208:Databases, Factual; D018795:Device Approval; D004864:Equipment and Supplies / Q000145:classification / Q000592:standards / Q000706:statistics & numerical data; D005062:European Union; D006801:Humans; D057052:Medical Device Recalls; D035703:Therapies, Investigational / Q000295:instrumentation; D014481:United States