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Figure.  Kaplan-Meier Time to Highest Recall Class
Kaplan-Meier Time to Highest Recall Class

Time-to-recall analysis of devices approved by priority review compared with standard review (P < .001).

Table.  Types of Devices, Time to Approval, Recalls, and Time to Recall of Class III Devices Approved by US Food and Drug Administration Standard and Priority Premarket Approval Review
Types of Devices, Time to Approval, Recalls, and Time to Recall of Class III Devices Approved by US Food and Drug Administration Standard and Priority Premarket Approval Review
1.
US Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health. Expedited review of premarket submissions for devices. Updated February 2008. Accessed February 20, 2020. https://www.emergobyul.com/sites/default/files/file/expedited_review_for_medical_device_submissions.pdf
2.
Kramer  DB, Xu  S, Kesselheim  AS.  How does medical device regulation perform in the United States and the European union? a systematic review.   PLoS Med. 2012;9(7):e1001276. doi:10.1371/journal.pmed.1001276PubMedGoogle Scholar
3.
US Food and Drug Administration. Premarket approval (PMA). Updated December 16, 2018. Accessed February 17, 2020. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm
4.
US Food and Drug Administration. Breakthrough Devices Program: guidance for industry and Food and Drug Administration staff. Updated December 16, 2018. Accessed February 17, 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/breakthrough-devices-program
5.
Dhruva  SS, Bero  LA, Redberg  RF.  Strength of study evidence examined by the FDA in premarket approval of cardiovascular devices.   JAMA. 2009;302(24):2679-2685. doi:10.1001/jama.2009.1899PubMedGoogle ScholarCrossref
6.
Kesselheim  AS, Wang  B, Franklin  JM, Darrow  JJ.  Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study.   BMJ. 2015;351:h4633. doi:10.1136/bmj.h4633PubMedGoogle ScholarCrossref
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    Research Letter
    March 30, 2020

    Comparison of Priority vs Standard US Food and Drug Administration Premarket Approval Review for High-Risk Medical Devices

    Author Affiliations
    • 1Division of Cardiology, New York University, New York
    • 2UCSF School of Medicine, University of California, San Francisco
    • 3Division of Cardiology, UCSF School of Medicine, University of California, San Francisco
    • 4Editor, JAMA Internal Medicine
    JAMA Intern Med. 2020;180(5):801-803. doi:10.1001/jamainternmed.2020.0297

    The US Food and Drug Administration (FDA) requires that high-risk (class III) medical devices undergo premarket approval (PMA) review, the most stringent path through which devices enter the market. Since 1994, in an effort to enable breakthrough technology to reach market faster, the FDA has also offered priority review.1 There is a paucity of data on the speed and effectiveness of regulatory review in these expedited pathways.2 We compared priority vs standard PMA review with regard to review times, device recalls, and adverse events.

    Methods

    Using publicly accessible FDA databases, we identified new class III devices approved by PMA between January 1, 2005, and December 31, 2015.3 We excluded ex vivo and in vitro devices. Using the PMA order for each approval, we determined device type, review pathway, application submission date, and approval date. We abstracted recalls and adverse events through May 31, 2018, from the FDA’s Medical Device Recall database and Medical Product Safety Network (MedSun), a mandatory adverse event–reporting program administered by the agency. We used χ2 tests to compare the number of recalled devices and Wilcoxon rank sum tests to compare time to approval and rate of adverse events. We used the Kaplan-Meier method to make time-to-event comparisons of time to recall by review pathway. Using logistic regression modeling, we assessed the associations between review pathway, review times, device type, recalls, and adverse events. Two-sided P values less than .05 were considered statistically significant. We used STATA/MP, version 10.0 (StataCorp), for all analyses. The University of California, San Francisco Institutional Review Board considered this study as exempt because we used only publicly available deidentified data.

    Results

    Between 2005 and 2015, the FDA granted 230 class III devices premarket approval, including 201 following standard review and 29 following priority review (Table). Review times were longer for priority review than for standard review (median, 21 months, interquartile range [IQR], 10-35 months, vs 14 months, IQR, 9-22 months; P = .04). Devices with priority review were more likely to be recalled than those with standard review (18 of 29 [62%] vs 60 of 201 [29.9%], P = .001) and had shorter time from approval to highest (greatest risk of hazard) recall class (hazard ratio, 2.96; 95% CI, 1.74-5.02; P < .001; Figure). The length of approval time and device type were not associated with the likelihood of recall. Devices subject to a recall were more likely to be associated with a reported adverse event (odds ratio, 1.80; 95% CI, 1.01-3.23; P = .04). With a median follow-up of 7 years (IQR, 4-11 years), there was no difference in the number of adverse events reported for devices approved by either pathway.

    Discussion

    We found that high-risk medical devices that underwent FDA priority review had higher recall rates and shorter time on the market prior to more serious recalls compared with high-risk devices receiving standard review. Moreover, despite the priority designation, priority review took longer than standard review, likely because of the novel and complex nature of the devices in the priority category. We relied on FDA registries and databases for our analysis. Thus, we cannot rule out the possibility that there were additional, unrecorded factors associated with the approval times of the devices under review and in adverse events reported to MedSun. It is reassuring that in a major Government Accountability Office report on the FDA device approval review structure, the Office found that the quality of the FDA databases are of sufficient accuracy for the purposes of tracking and collating device review and approval characteristics.

    The 2016 21st Century Cures Act allows case reports, expert opinion, and registries in lieu of clinical trials to encourage further expedited FDA approval of breakthrough devices. In 2018, the agency released guidelines for a new breakthrough device program based on the existing priority review program.4 This regulatory emphasis on speed of approval over a strong evidence base for safety and effectiveness for high-risk devices is concerning. Safety data are already sparse at time of approval; preapproval device studies are often small, with short follow-up times.5

    Priority review processes for drugs have led to increased applications and approvals under expedited pathways.6 For medical devices, similar increases are likely. The findings of this study demonstrate that higher recall rates despite longer review times for devices approved with priority review raises concerns about the inherent risks of these first-in-class devices. Before premarket approval times are shortened, patient protections should be improved. Initiatives might include identifying appropriate safeguards during the approval process, strengthening postmarket surveillance to allow prompt identification of safety concerns, and increased availability and transparency of adverse event reports.

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    Article Information

    Corresponding Author: Rita F. Redberg, MD, MSc, UCSF Division of Cardiology, 505 Parnassus Ave, Suite M-1180, San Francisco, California 94143-0124 (rita.redberg@ucsf.edu).

    Published Online: March 30, 2020. doi:10.1001/jamainternmed.2020.0297

    Author Contributions: Drs Redberg and Ong had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Ong, Redberg.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Ong, Redberg.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Ong.

    Conflict of Interest Disclosures: None reported.

    Disclaimer: Dr Redberg is the Editor of JAMA Internal Medicine, but she was not involved in any of the decisions regarding review of the manuscript or its acceptance.

    References
    1.
    US Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health. Expedited review of premarket submissions for devices. Updated February 2008. Accessed February 20, 2020. https://www.emergobyul.com/sites/default/files/file/expedited_review_for_medical_device_submissions.pdf
    2.
    Kramer  DB, Xu  S, Kesselheim  AS.  How does medical device regulation perform in the United States and the European union? a systematic review.   PLoS Med. 2012;9(7):e1001276. doi:10.1371/journal.pmed.1001276PubMedGoogle Scholar
    3.
    US Food and Drug Administration. Premarket approval (PMA). Updated December 16, 2018. Accessed February 17, 2020. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm
    4.
    US Food and Drug Administration. Breakthrough Devices Program: guidance for industry and Food and Drug Administration staff. Updated December 16, 2018. Accessed February 17, 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/breakthrough-devices-program
    5.
    Dhruva  SS, Bero  LA, Redberg  RF.  Strength of study evidence examined by the FDA in premarket approval of cardiovascular devices.   JAMA. 2009;302(24):2679-2685. doi:10.1001/jama.2009.1899PubMedGoogle ScholarCrossref
    6.
    Kesselheim  AS, Wang  B, Franklin  JM, Darrow  JJ.  Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study.   BMJ. 2015;351:h4633. doi:10.1136/bmj.h4633PubMedGoogle ScholarCrossref
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