Safety and Efficacy of Orthopaedic Surgical Devices Under the FDA's Updated Premarket Notification Program.

Author:Griffin, Frank

"The enemy of good is better." (1) TABLE OF CONTENTS ABSTRACT 779 I. INTRODUCTION 781 II. FDA'S RECENT CHANGES TO THE 510(K) PATHWAY 783 A. Increased Premarket Expectations for 510(k) Submissions 783 1. More pages of paperwork 783 2. Incorporation of Benefit/Risk factors 784 B. Refuse-To-Accept Policy 785 C. Improved Consistency and Thoroughness 785 D. Elimination of 510(k) for Class III Devices 786 E. Elimination of More Than 1000 Devices as Legal Predicates 788 III. ORTHOPAEDIC IMPLANTS, 510(K), AND LIKELY EFFECTS OF FDA 788 CHANGES A. 510(k) and Orthopaedic Implants 788 1. The 510(k) facilitated orthopaedic device "races" 788 2. 510(k)'s Facilitation of Outlier Device Approval 793 3. Back to the Future: Orthopaedic Device Predicates Are 795 Often Better Than Their 510(k) Descendants B. Analysis of FDA's Recent 510(k) Changes on Orthopaedic 798 Device Outcomes 1. Things that did not change 798 2. Things that have changed: Numerous Holes in the 800 November 2018 Changes a. Increased Premarket Expectations for 510(k) 800 Submissions b. Refuse-To-Accept Policy 805 c. Improved Consistency and Thoroughness 805 d. Elimination of 510(k) for Class III Devices 806 e. Elimination of More Than 1000 Devices as Legal 807 Predicates IV. ADDITIONAL PROPOSED SOLUTIONS 808 A. Regulatory Changes by the FDA 808 B. Ensuring Fairness in Medical Device-Related Trials 810 1. State Tort Law: Informed Consent 810 2. Ensuring a Fair Trial Under Daubert in Medical Device 813 Cases a. A Balanced Approach to Expert Testimony: Stop 814 Favoring Insider Defendants' Experts with Conflicts of Interest and Disfavoring Plaintiffs' Experts b. Stop Blame-Shifting Liability onto Hospitals and 816 Doctors for Poorly Performing 510(k) Devices C. Congressional Action 817 1. Introduction of a "Medicare 510(k) Payment Reduction 817 Program" 2. Start "" to Give the Public 822 Access to Clearance Pathway Information and Statistics 3. Medicare Should Make Sure Future Doctors Are Trained 823 Preferentially Using Proven Medical Devices V. CONCLUSION 827 APPENDIX A: ESTIMATED NUMBERS OF TKAS PERFORMED IN THE U.S. 828 I. INTRODUCTION

Orthopaedic surgical devices are recalled 11.5 times more commonly when they obtain FDA clearance by Premarket Notification ("510(k)") than when they are cleared via the more vigorous Premarket Approval ("PMA") review. (2) Recall of implanted orthopaedic devices that have been affixed to or implanted within a large bone, like the femur, can be devastating for patients--especially if the device must be removed or revised. For example, Medicare patients undergoing revision total hip replacements are at risk for infection (17.3%), blood clots (i.e., venous thromboembolic disease; 11.1%), dislocation (5.43%), pulmonary embolism (3.24%), and death (2.11%). (3) Due to the significant potential for life-altering consequences of revision of recalled medical devices affixed to or implanted within large bones, recall of orthopaedic devices is unacceptable and the FDA should optimize orthopaedic device clearance pathways to minimize the chances that approved devices will later be recalled.

The FDA clears implantable medical devices using two main pathways: PMA review and 510(k). (4) The PMA pathway is longer, more expensive, and requires clinical trials confirming safety and efficacy. (5) The law presumes that implantable medical devices will undergo PMA review; (6) but 510(k) provides a shortcut for most devices if the manufacturer/marketer ("submitter") can show that the new device is "at least as safe and effective" (i.e., "substantially equivalent") as a device that is already being legally marketed (i.e., a "predicate" device). (7) The 510(k) program is the most common pre-market regulatory review pathway for new medical devices. (8) In 2017, the FDA cleared 82% of its approved or cleared devices via the 510(k) pathway. (9)

In November 2018, the FDA announced changes to 510(k). (10) In response to vociferous criticism of 510(k), the FDA asked the Institute of Medicine ("IOM") to review 510(k) in 2011 and to make recommendations to protect the public health while also protecting legitimate industry interests. (11) The IOM concluded that the 510(k) process was fatally "flawed," (12) that it generally does not evaluate safety and efficacy, and cannot be transformed into such a process. (13) In addition, the IOM noted that 510(k) "lacks the statutory basis to be a reliable premarket screen for safety and effectiveness" of moderate risk devices and recommended that Congress replace the system. (14) However, Congress failed to act.

The FDA's recent 510(k) changes (15) appear to be an attempt to address some of the concerns and offset Congress' lack of action. The FDA's November 2018 report outlined changes to strengthen the program, including: (1) increasing premarket expectations for device submissions, (2) implementing a "Refuse-to-Accept" policy for incomplete applications, (3) improving the consistency and thoroughness of device review, (4) eliminating the use of 510(k) for devices considered to be of higher risk (i.e., Class III devices), and (5) eliminating over 1000 devices as 510(k) legal predicates. (16)

First, this Article explores the recent changes to 510(k) outlined by the FDA in 2018. Then, it evaluates their likely effects on the outcomes of orthopaedic devices. Finally, this Article proposes solutions to improve those outcomes.


    Late in 2018, the FDA announced changes to the 510k pathway to "strengthen" the path and highlighted some of the changes that have been occurring over the past several years. (17) These changes include that the FDA has (1) "increased its premarket expectations for 510(k) submissions," (2) "implemented a Refuse-To-Accept policy to improve the quality of 510(k) submissions," (3) "improved consistency and thoroughness of 510(k) review," (4) "taken steps to eliminate the use of 510(k) for Class III devices," and (5) "eliminated the use of more than 1000 510(k)s as legal predicates." (18)

    1. Increased Premarket Expectations for 510(k) Submissions

      According to the FDA's report, the increased premarket expectations are primarily (1) the completion of more pages of paperwork and (2) the incorporation of benefit/risk factors into the paperwork analysis. (19)

      1. More pages of paperwork

        In 2017, the FDA updated its 510(k) Modifications Guidance for companies making changes to existing devices, (20) including how to incorporate Benefit-Risk Factors. (21) The FDA's Center for Devices and Radiological Health ("CDRH") published over 50 guidance documents since 2009 "to help improve predictability, consistency, and transparency of submission content while clarifying expectations, policies[,] and procedures surrounding review of the submission." (22) The "average number of pages for each 510(k) has increased 150% since 2009" such that the average number of pages was 1,185 for each 510(k) submission in 2017. (23)

      2. Incorporation of Benefit/Risk factors

        The FDA encourages inclusion of benefit and risk factors in the 510(k) application and notes that benefit and risk factors are considered during assessment of devices; the FDA provides examples of benefits and risks that should be included. (24)

        Possible device benefits may include (among others): (1) "Reduction in treatment time to achieve same effect"; (2) "Improvement of mechanical properties to reduce probable likelihood of adverse events or to improve handling"; (3) "Reduction of variability in device output"; and (4) "Improvements in clinical management, probability of survival, other aspects of patient health status (e.g., effect on patient management and quality of life, improvement of patient function, prevention of loss of function, relief from symptoms), and patient satisfaction in the target population, which may be measured with the use of PROs." (25) In considering benefits, the FDA assesses information provided in the 510(k) by comparing potential benefits to the predicate device. (26)

        Possible device risks are likewise considered. In assessing risks, the FDA considers "among others, the following factors individually and in the aggregate as compared to the predicate device: (1) Severity, Types, Number, and Rates of Harmful events; (2) Probability of a Harmful Event; (3) Probability of the Patient Experiencing One or More Harmful Events; and (4) Duration of Harmful Events." (27) Risk assessment is discussed further below in relation to orthopaedic devices.

        Additional factors considered in the benefit/risk assessment include (1) uncertainty, (2) characterization of the disease/condition, (3) innovative technology, (4) patient tolerance for risk and perspective on benefit, (5) benefit for the health care professional or caregiver, (6) risk mitigation, and (7) postmarket data. (28)

    2. Refuse-To-Accept Policy

      To determine whether an application is administratively complete, the FDA does a review within 15 days of receipt. (29) The FDA updated its "Refuse-to-Accept" policy in January 2018; procedures were implemented, including criteria to assess "whether a 510(k) submission meets a quality threshold of acceptability for review" by evaluating submissions for completeness related to 52 elements--including biocompatibility, shelf life, performance data, and others. (30) If any one of the 52 elements is missing, the submitter is notified that the submission is not accepted for review; roughly 30% fall into this category initially. (31) This is not a substantive review, just an initial checklist review for completeness of the application. (32)

    3. Improved Consistency and Thoroughness

      To improve consistency and thoroughness, the FDA created the 510(k) SMART memo template for use by FDA reviewers for guidance during the 510(k) premarket process. (33) The FDA instituted the SMART memo template for mandatory use beginning in October 2015, and it guides the FDA'S review staff "by...

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