[Skip to Content]
Outline
Claim CME
PDF
Neurology

Renewing the Call for Reforms to Medical Device Safety—The Case of Penumbra

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
JAMA Internal Medicine
Published Online: November 29, 2021
Special Communication
Kushal T. Kadakia, MSc1;
Adam L. Beckman, BS1,2;
Joseph S. Ross, MD, MHS3,4,5;
Harlan M. Krumholz, MD, SM4,5,6
Author Affiliations
  • 1Harvard Medical School, Boston, Massachusetts
  • 2Harvard Business School, Boston, Massachusetts
  • 3Section of General Internal Medicine and the National Clinician Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
  • 4Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
  • 5Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut
  • 6Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
Read article on JAMA Network

MOC/CME Information

editorial comment icon
Editorial
Comment
 related articles icon
Related
Articles
 author interview icon
Interviews
 multimedia icon
Multimedia
Abstract

Importance  Strengthening premarket and postmarket surveillance of medical devices has long been an area of focus for health policy makers. The recent class I recall (the most serious of the US Food and Drug Administration [FDA] recalls) of reperfusion catheters manufactured by Penumbra, a US-based medical device company, illustrates issues of device safety and oversight that mandate attention.

Objectives  To review the regulatory history and clinical evidence of the Penumbra JET 7 Reperfusion Catheter with Xtra Flex Technology (JET 7) and use the device recall as a case study of the challenges associated with clinical evaluation, transparency, and oversight of medical devices in the US.

Evidence  Regulatory history and clinical evidence for the Penumbra medical devices were analyzed through a qualitative review of decision letters in the Access FDA database for medical devices and medical device reports in the Manufacturer and User Facility Device Experience database and a review of market data (eg, earnings calls, company communications) and clinical literature.

Findings  The JET 7 device was subjected to a class I recall following more than 200 adverse event reports, 14 of which involved patient deaths. Regulatory analysis indicated that each of the Penumbra reperfusion catheters was cleared under the 510(k) pathway (which allows devices to be authorized with limited to no clinical evidence), with limited submission of either new clinical or animal data. Clinical evidence for Penumbra devices was generated from nonrandomized, single-arm trials with small sample sizes. The regulatory issues raised by JET 7 are reflective of broader challenges for medical device regulation. Opportunities for reform include strengthening premarket evidence requirements, requiring safety reporting with unique device identifiers, and mandating active methods of postmarket surveillance.

Conclusions and Relevance  The case study of JET 7 highlights the long-standing gaps in medical device oversight and renews the impetus to build on the Institute of Medicine recommendations and reform FDA medical device regulation to protect public health.

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Related Articles

  1. FDA Regulation of Medical Devices

  2. Japanese Framework for Access to High-Risk Medical Devices—Reply

  3. Japanese Framework for Access to High-risk Medical Devices

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

See More About

Cerebrovascular Disease Medical Devices and Equipment Neurology Health Care Safety Stroke Regulatory Agencies Health Policy
Article Information

Accepted for Publication: September 9, 2021.

Published Online: November 29, 2021. doi:10.1001/jamainternmed.2021.6626

Corresponding Author: Harlan M. Krumholz, MD, SM, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, 195 Church St, 5th Flr, New Haven, CT 06510 (harlan.krumholz@yale.edu).

Author Contributions: Mr Kadakia and Mr Beckman 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: All authors.

Acquisition, analysis, or interpretation of data: Ross.

Drafting of the manuscript: Kadakia, Beckman.

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

Administrative, technical, or material support: Kadakia, Beckman.

Conflict of Interest Disclosures: Mr Kadakia reported previous employment at Cleveland Clinic London, Blue Cross Blue Shield of North Carolina, and the US Food and Drug Administration (FDA), and has received consulting fees from the National Academy of Medicine, all unrelated to this article. At the time of publication, Mr Beckman is on a leave of absence from Harvard and is serving in the federal government COVID-19 response. However, this article was conceived and drafted while Mr. Beckman was a student at Harvard Medical School and Harvard Business School, and the findings and views in this article do not reflect the official views or policy of the Department of Health and Human Services. Dr Ross reported receiving grants from the FDA, Johnson and Johnson, Medical Devices Innovation Consortium, Association for Healthcare Research and Quality, the National Institutes of Health National Heart, Lung, and Blood Institute, and the Laura and John Arnold Foundation outside the submitted work. In the past 3 years, Dr Krumholz received expenses and/or personal fees from UnitedHealth (consulting), IBM Watson Health (consulting), Element Science (consulting), Aetna (consulting), Facebook (consulting), the Siegfried and Jensen Law Firm (expert testimony on behalf of plaintiffs), Arnold and Porter Law Firm (expert testimony on behalf of Bristol-Myers Squibb), Martin/Baughman Law Firm (expert testimony on behalf of plaintiffs), F-Prime (consulting), and the National Center for Cardiovascular Diseases in Beijing (research collaboration).

References
1.
The Motley Fool. Penumbra Inc (PEN) Q4 2019 earnings call transcript. February 25, 2020. Accessed September 13, 2021. https://www.fool.com/earnings/call-transcripts/2020/02/25/penumbra-inc-pen-q4-2019-earnings-call-transcript.aspx
2.
US Food and Drug Administration. Penumbra’s recall of the JET 7 reperfusion catheter due to distal tip damage. https://www.fda.gov/medical-devices/medical-device-recalls/penumbras-recall-jet-7-reperfusion-catheter-due-distal-tip-damage. Accessed September 13, 2021.
3.
US Food and Drug Administration. Recalls, corrections and removals (devices). January 29, 2021. Accessed September 13, 2021. https://www.fda.gov/medical-devices/postmarket-requirements-devices/recalls-corrections-and-removals-devices
4.
Penumbra, Inc. Urgent voluntary medical device recall notification. Accessed September 13, 2021. https://www.penumbrainc.com/wp-content/uploads/2020/12/JET-7XF-15Dec20.pdf.
5.
Hauser  RG .  Here we go again—another failure of postmarketing device surveillance.   N Engl J Med. 2012;366(10):873-875. doi:10.1056/NEJMp1114695 PubMedGoogle ScholarCrossref
6.
Institute of Medicine. Medical devices and the public’s Health: the FDA 510(k) clearance process at 35 years. Accessed September 13, 2021. https://www.nap.edu/catalog/13150/medical-devices-and-the-publics-health-the-fda-510k-clearance.
7.
US Food and Drug Administration. 510(k) Summary: K072718. September 20, 2007. Accessed September 13, 2021. https://www.accessdata.fda.gov/cdrh_docs/pdf7/K072718.pdf
8.
US Food and Drug Administration. The 510(k) program: evaluating substantial equivalence in premarket notifications. July 28, 2014. Accessed September 13, 2021. https://www.fda.gov/media/82395/download
9.
Penumbra Pivotal Stroke Trial Investigators.  The Penumbra Pivotal Stroke trial: safety and effectiveness of a new generation of mechanical devices for clot removal in intracranial large vessel occlusive disease.   Stroke. 2009;40(8):2761-2768. doi:10.1161/STROKEAHA.108.544957 PubMedGoogle ScholarCrossref
10.
Rathi  VK , Krumholz  HM , Masoudi  FA , Ross  JS .  Characteristics of clinical studies conducted over the total product life cycle of high-risk therapeutic medical devices receiving FDA premarket approval in 2010 and 2011.   JAMA. 2015;314(6):604-612. doi:10.1001/jama.2015.8761 PubMedGoogle ScholarCrossref
11.
Johnston  JL , Dhruva  SS , Ross  JS , Rathi  VK .  Clinical evidence supporting US Food and Drug Administration clearance of novel therapeutic devices via the De Novo Pathway between 2011 and 2019.   JAMA Intern Med. 2020;180(12):1701-1703. doi:10.1001/jamainternmed.2020.3214 PubMedGoogle ScholarCrossref
12.
Smith  WS , Sung  G , Saver  J ,  et al; Multi MERCI Investigators.  Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial.   Stroke. 2008;39(4):1205-1212. doi:10.1161/STROKEAHA.107.497115 PubMedGoogle ScholarCrossref
13.
Tomsick  TA .  Editorial comment—mechanical embolus removal.   Stroke. 2005;36(7):1439-1440. doi:10.1161/str.36.7.1439 PubMedGoogle ScholarCrossref
14.
Tomsick  T , Broderick  J , Carrozella  J ,  et al; Interventional Management of Stroke II Investigators.  Revascularization results in the Interventional Management of Stroke II trial.   AJNR Am J Neuroradiol. 2008;29(3):582-587. doi:10.3174/ajnr.A0843 PubMedGoogle ScholarCrossref
15.
US Food and Drug Administration. Decision Letter Re: K190010. June 16, 2019. Accessed September 13, 2021. https://www.accessdata.fda.gov/cdrh_docs/pdf19/K190010.pdf
16.
Tarr  R , Hsu  D , Kulcsar  Z ,  et al.  The POST trial: initial post-market experience of the Penumbra system: revascularization of large vessel occlusion in acute ischemic stroke in the United States and Europe.   J Neurointerv Surg. 2010;2(4):341-344. doi:10.1136/jnis.2010.002600 PubMedGoogle ScholarCrossref
17.
Faris  O , Shuren  J .  An FDA viewpoint on unique considerations for medical-device clinical trials.   N Engl J Med. 2017;376(14):1350-1357. doi:10.1056/NEJMra1512592 PubMedGoogle ScholarCrossref
18.
Gartenberg  AJ , Peleg  A , Dhruva  SS , Redberg  RF .  Presumed safe no more: lessons from the Wingspan saga on regulation of devices.   BMJ. 2014;348:g93. doi:10.1136/bmj.g93 PubMedGoogle ScholarCrossref
19.
Saver  JL , Goyal  M , Bonafe  A ,  et al; SWIFT PRIME Investigators.  Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.   N Engl J Med. 2015;372(24):2285-2295. doi:10.1056/NEJMoa1415061 PubMedGoogle ScholarCrossref
20.
Bracard  S , Ducrocq  X , Mas  JL ,  et al; THRACE investigators.  Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial.   Lancet Neurol. 2016;15(11):1138-1147. doi:10.1016/S1474-4422(16)30177-6 PubMedGoogle ScholarCrossref
21.
US Food and Drug Administration. MAUDE adverse event report: Penumbra, Inc. Penumbra system JET7 Reperfusion Catheter NRY. October 3, 2019. Accessed October 25, 2021. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/detail.cfm?mdrfoi__id=9151990&pc=NRY
22.
Pearly Ti  J , Yeo  L , Anil  G .  Can a stent retriever damage the JET 7 reperfusion catheter?   AJNR Am J Neuroradiol. 2020;41(12):2317-2319. doi:10.3174/ajnr.A6804 PubMedGoogle ScholarCrossref
23.
Majidi  S , Bageac  DV , Fayed  I , Yim  B , De Leacy  R , Armonda  RA .  JET 7 XTRA Flex reperfusion catheter related complications during endovascular thrombectomy.   J Neurointerv Surg. 2021;13(4):352-356. doi:10.1136/neurintsurg-2020-016826. doi:10.1136/neurintsurg-2020-016826PubMedGoogle ScholarCrossref
24.
Penumbra, Inc. Notification to healthcare providers. July 27, 2020. Accessed September 13, 2021. https://www.penumbrainc.com/wp-content/uploads/2020/07/FINAL-Notification-to-Healthcare-Providers-27Jul20202.pdf
25.
The Motley Fool. Penumbra Inc (PEN) Q3 2020 Earnings call transcript. October 28, 2020. Accessed September 13, 2021. https://www.fool.com/earnings/call-transcripts/2020/10/28/penumbra-inc-pen-q3-2020-earnings-call-transcript/
26.
The Capitol Forum. Penumbra: majority of JET 7 malfunctions unrelated to contrast injections, according to FDA database. September 4, 2020. Accessed September 13, 2021. https://thecapitolforum.com/wp-content/uploads/2020/12/Penumbra-2020.09.04.pdf
27.
Lipschultz  B , Fineman  J. Short Seller QCM Questions Safety of Penumbra Stroke Device. November 10, 2020. Accessed September 13, 2021. https://www.bloomberg.com/news/articles/2020-11-10/short-seller-qcm-questions-safety-of-penumbra-stroke-device
28.
Katsanos  AH , Malhotra  K , Goyal  N ,  et al.  Mortality risk in acute ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy.   J Am Heart Assoc. 2019;8(21):e014425. doi:10.1161/JAHA.119.014425 PubMedGoogle Scholar
29.
Anand  SK , Benjamin  WJ , Adapa  AR ,  et al.  Trends in acute ischemic stroke treatments and mortality in the United States from 2012 to 2018.   Neurosurg Focus. 2021;51(1):E2. doi:10.3171/2021.4.FOCUS21117 PubMedGoogle Scholar
30.
International Consortium of Investigative Journalists. Implant files. Accessed September 13, 2021. https://www.icij.org/investigations/implant-files/
31.
Salazar  JW , Redberg  RF .  Leading the call for reform of medical device safety surveillance.   JAMA Intern Med. 2020;180(2):179-180. doi:10.1001/jamainternmed.2019.5170 PubMedGoogle ScholarCrossref
32.
Dubin  JR , Simon  SD , Norrell  K , Perera  J , Gowen  J , Cil  A .  Risk of recall among medical devices undergoing US Food and Drug Administration 510(k) clearance and premarket approval, 2008-2017.   JAMA Netw Open. 2021;4(5):e217274. doi:10.1001/jamanetworkopen.2021.7274 PubMedGoogle Scholar
33.
US Food and Drug Administration. Decision letter: K173200. June 11, 2018. Accessed September 13, 2021. https://www.accessdata.fda.gov/cdrh_docs/pdf17/K173200.pdf
34.
Rathi  VK , Ross  JS .  Modernizing the FDA’s 510(k) Pathway.   N Engl J Med. 2019;381(20):1891-1893. doi:10.1056/NEJMp1908654 PubMedGoogle ScholarCrossref
35.
US Food and Drug Administration. Recommended content and format of non-clinical bench performance testing information in premarket submissions. December 20, 2019. Accessed September 13, 2021. https://www.fda.gov/media/113230/download
36.
US Food and Drug Administration. Safety and Performance Based Pathway. Guidance for industry and Food and Drug Administration. September 20, 2019. Accessed September 13, 2021. https://www.fda.gov/media/112691/download
37.
Redberg  RF , Dhruva  SS .  Moving from substantial equivalence to substantial improvement for 510(k) devices.   JAMA. 2019;322(10):927-928. doi:10.1001/jama.2019.10191 PubMedGoogle ScholarCrossref
38.
US Food and Drug Administration. Class I device recall Penumbra 3D Revascularization Device. June 22, 2017. Accessed September 13, 2021.https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfres/res.cfm?id=156554
39.
US Food and Drug Administration. Class 1 device recall MINDFRAME CAPTURE(TM) LP revascularization Device. May 16, 2018. Accessed September 13, 2021. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRES/res.cfm?id=162387
40.
US Food and Drug Administration. Class 1 Device Recall Trevo XP ProVue Retriever. October 21, 2020. Accessed September 13, 2021.https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRES/res.cfm?id=184096
41.
US Food and Drug Administration. Learn if a Medical Device Has Been Cleared by FDA for Marketing. December 29, 2017. Accessed September 13, 2021. https://www.fda.gov/medical-devices/consumers-medical-devices/learn-if-medical-device-has-been-cleared-fda-marketing
42.
Office of the Inspector General. FDA’s clearance of medical devices through the 510(k) process. Accessed September 2013. September 13, 2021. https://oig.hhs.gov/oei/reports/oei-04-10-00480.pdf
43.
US Food and Drug Administration. Medical device product classification codes: guidance for industry and Food and Drug Administration Staff. April 11, 2013. Accessed September 13, 2021. https://www.fda.gov/media/82781/download
44.
Loftus  CM , Hoffmann  M , Heetderks  W , Zheng  X , Peña  C .  Regulation of neurological devices and neurointerventional endovascular approaches for acute ischemic stroke.   Front Neurol. 2018;9:320. doi:10.3389/fneur.2018.00320 PubMedGoogle ScholarCrossref
45.
Ardaugh  BM , Graves  SE , Redberg  RF .  The 510(k) ancestry of a metal-on-metal hip implant.   N Engl J Med. 2013;368(2):97-100. doi:10.1056/NEJMp1211581 PubMedGoogle ScholarCrossref
46.
Resnic  FS , Normand  SL .  Postmarketing surveillance of medical devices—filling in the gaps.   N Engl J Med. 2012;366(10):875-877. doi:10.1056/NEJMp1114865 PubMedGoogle ScholarCrossref
47.
Tau  N , Shepshelovich  D .  Assessment of data sources that support US Food and Drug Administration medical devices safety communications.   JAMA Intern Med. 2020;180(11):1420-1426. doi:10.1001/jamainternmed.2020.3514 PubMedGoogle ScholarCrossref
48.
Department of Health and Human Services. Office of Inspector General. Adverse event reporting for medical devices. October 2009. Accessed September 13, 2021. https://oig.hhs.gov/oei/reports/oei-01-08-00110.pdf
49.
US Food and Drug Administration. Unique device identification system. October 13, 2021. Accessed May 6, 2021. https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system
50.
Kinard  M , McGiffert  L .  Medical device tracking—how it is and how it should be.   JAMA Intern Med. 2021;181(3):305-306. doi:10.1001/jamainternmed.2020.7797 PubMedGoogle ScholarCrossref
51.
Dhruva  SS , Ross  JS , Schulz  WL , Krumholz  HM .  Fulfilling the promise of unique device identifiers.   Ann Intern Med. 2018;169(3):183-185. doi:10.7326/M18-0526 PubMedGoogle ScholarCrossref
52.
Krupka  DC , Wilson  NA , Reich  AJ ,  et al. The post-market surveillance system for implanted devices is broken. Here’s how CMS And the FDA can act now to fix it. Health Affairs blog. April 23, 2021. https://www.healthaffairs.org/do/10.1377/hblog20210420.717948/full/
53.
Office of the Inspector General. OIG’s top unimplemented recommendations: solutions to reduce fraud, waste, and abuse in HHS programs. August 2020. Accessed September 13, 2021. https://oig.hhs.gov/reports-and-publications/compendium/files/compendium2020.pdf
54.
US Government Accountability Office. FDA ordered postmarket studies to better understand safety issues, and many studies are ongoing. September 2015. Accessed September 13, 2021. https://www.gao.gov/assets/680/672860.pdf
55.
Reynolds  IS , Rising  JP , Coukell  AJ , Paulson  KH , Redberg  RF .  Assessing the safety and effectiveness of devices after US Food and Drug Administration approval: FDA-mandated postapproval studies.   JAMA Intern Med. 2014;174(11):1773-1779. doi:10.1001/jamainternmed.2014.4194 PubMedGoogle ScholarCrossref
56.
Zuckerman  DM , Brown  P , Nissen  SE .  Medical device recalls and the FDA approval process.   Arch Intern Med. 2011;171(11):1006-1011. doi:10.1001/archinternmed.2011.30 PubMedGoogle Scholar
57.
Regulation  EUR-LEX. (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices. Accessed September 13, 2021. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:02017R0745-20200424
58.
Davidsson  GA , Jonsdottir  GM , Oddsson  H , Lund  SH , Arnar  DO .  Long-term outcome of implantable cardioverter/defibrillator lead failure.   JAMA Intern Med. 2020;180(2):322-324. doi:10.1001/jamainternmed.2019.4717 PubMedGoogle ScholarCrossref
59.
Tseng  ZH , Hayward  RM , Clark  NM ,  et al.  Sudden death in patients with cardiac implantable electronic devices.   JAMA Intern Med. 2015;175(8):1342-1350. doi:10.1001/jamainternmed.2015.2641 PubMedGoogle ScholarCrossref
60.
Resnic  FS , Majithia  A , Marinac-Dabic  D ,  et al.  Registry-based prospective, active surveillance of medical-device safety.   N Engl J Med. 2017;376(6):526-535. doi:10.1056/NEJMoa1516333 PubMedGoogle ScholarCrossref
61.
Fleurence  RL , Shuren  J .  Advances in the use of real-world evidence for medical devices: an update from the National Evaluation System for Health Technology.   Clin Pharmacol Ther. 2019;106(1):30-33. doi:10.1002/cpt.1380 PubMedGoogle ScholarCrossref
62.
US Food and Drug Administration. Narrative by activity: devices and radiological health. Accessed September 13, 2021. https://www.fda.gov/media/132800/download
63.
US Food and Drug Administration. Medical Device Recall Report FY 2003-FY 2012. Accessed September 13, 2021. http://fmdic.org/wp-content/uploads/2014/04/Medical-Device-Recall-Report-amf-2.pdf
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Close
Want full access to the AMA Ed Hub?
Become an AMA member now
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
Become an AMA member now
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close
Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue