Person:

Hwang, Thomas

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 Conformite Europeenne 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.RESULTS67% (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.

BACKGROUND: Medical devices can be useful in a variety of diseases, but few devices have been specifically approved for use in children. The 2007 Pediatric Medical Device Safety and Improvement Act was passed to stimulate pediatric device development. The current state of trial evidence underpinning the approval of pediatric devices remains poorly described.

METHODS: We identified all high-risk (ie, class III) devices approved through the premarket approval or humanitarian device exemption pathways for therapeutic use in children between 2008 and 2011. We collected key information on clinical trial design (randomization, blinding, controls, and types of end points) as well as age distribution of trial participants. We also identified US Food and Drug Administration (FDA)–mandated postmarketing trials.

RESULTS: Twenty-two devices were approved for use in children via the premarket approval pathway and 3 via the humanitarian device exemption pathway. Twenty-two (88%) qualified as pediatric despite minimum approval ages of ≥18 years (the FDA Center for Devices and Radiologic Health considers patients 18–21 years old as pediatric). Most devices were approved on the basis of nonrandomized (59%), open-label (68%) studies with surrogate effectiveness end points (86%). Overall, 21 (84%) devices were not studied in any patients <18 years of age. Postmarketing studies were mandated by the FDA for 19 (76%) devices, although only 3 (18%) required enrollment of pediatric patients.

CONCLUSIONS: Most high-risk pediatric devices are approved on the basis of trials in patients ≥18 years old, with few pediatric patients exposed to the devices before market availability. Few postmarketing studies require additional study in pediatric patients.