Senate Special Committee on Aging: FDA and the Reform of the Medical Device Approval Process

Continuing the ongoing scrutiny surrounding the regulatory environment for medical devices in America, the Senate Aging Committee recently held a hearing entitled, “A Delicate Balance: FDA and the Reform of the Medical Device Approval Process.”

In his opening remarks, Chairman Herb Kohl (D-WI) recognized that “innovative technology has provided valuable, life‐saving medical devices that have prolonged life and reduced suffering.”  He also emphasized the importance of ensuring that “these new medical products get to the market quickly and safely.”  However, Mr. Kohl noted that the “FDA must constantly strive to maintain a delicate balance between safety and innovation,” which can be extremely “difficult.”

Consequently, the Chairman also noted how the medical device industry has “understandable concerns that significant changes in the medical device approval process contemplated by FDA could slow the rapid progress of new medical technologies to hospitals, patients, and the marketplace.”  Accordingly, below is a summary of the individuals who gave testimony during the hearing, including:

• Katie Korgaokar, Patient, Denver, CO
• Marcia Crosse, Health Care, Government Accountability Office, Washington, DC
• Diana Zuckerman President, National Research Center for Women and Families, Cancer Prevention and Treatment Fund, Washington, DC
• Frederic Resnic, Assistant Professor of Medicine, Harvard Medical School and Director of the Cardiac Catheterization Laboratory, Brigham and Women’s Hospital, Boston, MA 
• Ralph Hall Distinguished Professor, University of Minnesota Law School, Minneapolis, MN
• David Nexon, Senior Executive Vice President, Advanced Medical Technology Association (AdvaMed), Washington, DC
•  William Maisel, Deputy Center Director for Science and the Chief Scientist, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD

Katie Korgaokar

Ms. Krogaokar, a patient, gave testimony about how she was unfortunately one of the  96,000 unlucky people who received the DePuy ASR prosthetic hip that was recently recalled in August 2010.  Her heartfelt testimony explained how she was unaware that devices could be “fastracked” by the FDA with little or no testing (i.e. 510(k)).  She also expressed her concern that the doctors who use such devices are receiving “consulting income” from companies who make the devices.  Accordingly, her testimony was largely centered on ensuring that FDA has systems in place to monitor medical devices for potential defects and to promote more safety in medical device approval.

Marcia Crosse

Speaking on behalf of the Government Accountability Office (GAO), Ms. Crosse’s testimony focused on the results a report the GAO conducted on medical devices and FDA’s Premarket Review and Postmarket Safety Efforts.  Ms. Crosse first noted how GAO has identified a “wide variety of concerns related to FDA’s ability to fulfill its mission of protecting the public health, including weaknesses in FDA’s premarket review and postmarket surveillance activities related to medical devices

The GAO report discussed how the FDA has been unable to adopt recommendations from a 2009 GAO report about high-risk devices that are allowed to enter the US market through the 510(k) process.  Specifically, GAO noted that FDA’s action on 26 types of high-risk devices is incomplete.  GAO also asserted that FDA has not been routinely analyzing recall data that would explain trends in recall over time, thus missing an opportunity to proactively identify and address risks presented by unsafe devices. 

The report also indicated that FDA lacks clear guidance for overseeing recalls, which has led to inconsistencies in FDA’s assessments of whether individual recalls were implemented effectively.  In fact, GAO noted that FDA officials examining similar situations sometimes reached opposite conclusions regarding whether recalls were effective.  GAO also determined that FDA did not document its justification for terminating recalls.  As a result, GAO concluded that the gaps at FDA in device regulation may increase the risk that unsafe medical devices could remain on the market.

Diana Zuckerman, PhD

Dr. Zuckerman presented her recent study of medical device recalls, published in the

Archives of Internal Medicine.  The study looked at recalls between 2005 and 2009 that the FDA designated as the highest risk because they could cause “serious health problems or death.”  Using the FDA’s public databases, the study found that more than 3 out of 4 of those high-risk recalls were not approved by the FDA’s PMA process, but rather were cleared through the 510(k) process or were exempt from any review because they were considered so low-risk. 

Her testimony then went on to explain the differences between the PMA and 510(k) processes, and she compared her study’s results to that of the other presenters (listed below).  Dr. Zuckerman also noted that there is an inconsistency in the FDA’s policies regarding the classifications of risk for review compared to recall criteria, since 71 % of high-risk recalls were cleared through the 510(k) process and an additional 7% were never even subject to FDA review indicates. 

Accordingly, she asserted that the detrimental impact of these defective medical devices on patients and the public health is substantial and could be reduced with

relatively small changes in the 510(k) process and how it is implemented.  She noted that the risk is substantial because from 2005 through 2009, the 113 highest-risk device recalls involved 112.6 million recalled products. In the first six months of 2010, the FDA recalled more than 437 million additional products because of high risks, including death. That means that in just six months there were 1.4 medical devices recalled for every person living in the U.S. 

She explained how the 510(k) process has several major differences from the PMA process, all of which reduce safeguards for patients, including: 

1.      No clinical trials

2.      No pre-market inspections

3.      No post-market studies required as a condition of approval 

The 510(k) process relies on bioengineering testing and other tests, rather than clinical trials. Although clinical data such as subjective reports are sometimes included, well designed clinical trials are almost never part of the 510(k) criteria. 

Dr. Zuckerman noted that if clinical trials were conducted, they would often catch errors of design or manufacturing before the product was sold. Even if a defective product were cleared for market without either clinical trials or pre-market inspections, requiring post-market studies as a condition of approval would allow problems to be caught more quickly than through non-scientific passive reporting of adverse events. 

As a result, she recommended that Class III devices always be subjected to, the PMA process and that devices subject to the PMA process should be defined to include all devices that can cause death when they fail.  

Frederic S. Resnic, MD MSc

The focus of Dr. Resnic’s comments were on:

 

• Understanding the infrequent but very severe impact of medical device failures
• Identifying existing barriers to effective post-market surveillance of medical device failures and safety risks.
• Proposing a new paradigm, based on continuous automated surveillance to monitor clinical registries, to provide timely and meaningful information to regulators, the public and medical device manufacturers to substantially improve the safety of medical devices. 

His testimony offered ways the U.S. could greatly improve the nation’s medical device safety system to assure that patients are treated with technologies and approaches

that are as safe as possible; recognizing that no device can be absolutely free of risk of failure.  Consquently, although Dr. Resnic praised CDRH, and specifically their epidemiology and post-market surveillance divisions for their great progress over the past several years in addressing gaps in the safety net for medical devices, he noted that much is still needed to “adequately protect the public against infrequent, but potentially dangerous complications or failure of such devices.”

Dr. Resnic also noted how the medical device manufacturer industry has recognized, over the past several years, the critical importance of comprehensive safety surveillance both for improving their products and also to reduce the significant business risk of any delay in recognizing and addressing a safety concern for one of their products.

Nevertheless, Dr. Resnic acknowledged several key challenges to the existing medical device safety surveillance, including: 

1.      Current systems are passive & depend on voluntary reporting of adverse events

2.      GAO estimates that only 0.5% of all device adverse events are reported to FDA

3.      Medical devices do not yet have a unique identifier in administrative or claims data complicating efforts to systematically study their use and safety

4.      Other challenges such as learning curve effects, and rapid product lifecycle are unique to medical devices and will challenge current plans such as the FDA Sentinel Initiative. 

Consequently, Dr. Resnic noted that a better approach would be Automated Continuous Safety Surveillance, which recent studies have demonstrated can effectively detect low frequency safety signals not discovered through other means.  He noted that this approach could greatly reduce the time to discover safety risks thereby sparing additional patients the exposure to the device. 

In addition, he emphasized his belief in a path to achieve an organized, coordinated and rational approach to post-market medical device safety surveillance that would not stifle innovation nor delay the release of important healthcare advances to the public. This strategy would be based on the use of available and emerging computerized tools to support continuous surveillance of health information registries to detect unexpected safety signals in a timely manner. 

He noted that such a strategy could be sustainably funded through the use of existing fees assessed during the medical device approval process without incurring additional costs to the medical device manufacturer industry.  Dr. Resnic also touched on how emerging standards for electronic health records including the “meaningful use” regulations being implemented over the next several years will provide unprecedented opportunities for securely mapping clinical information to distributed clinical registries.  He asserted that, this health care information revolution “will dramatically increase the ability to extract the necessary information, and should greatly reduce the cost of collecting detailed medical device safety information to permit surveillance from hospital-based and clinical practice based health information systems.” 

Ultimately, Dr. Resnic concluded that the post-approval monitoring of medical devices in the United States “requires significant enhancement to avoid preventable injury and death to patients treated with high risk medical devices that ultimately fail.”  He noted that , “unique and specific challenges for studying medical devices, such as the lack of unique device identifiers, intrinsic learning curve effects, and interactions between devices, medications and medical conditions may challenge current advanced monitoring strategies such as the Sentinel initiative.”  Accordingly, he asked the committee to consider the following recommendations:

1.      FDA, in collaboration with CMS, should mandate that detailed information regarding high-risk medical device use and clinical outcomes be universally submitted to selected national clinical registries.

2.      The registries should be operated by independent academic or professional society organizations as part of public-private partnerships, informed and guided by MDEpiNet and the Sentinel Initiative and other federal stakeholders.

3.      FDA should redirect resources currently spent by the medical device industry on condition of approval studies to support the national medical device safety registries.     

4.      Automated safety surveillance tools should be uniformly applied to the device registries to continuously and prospectively monitor each registry for the most severe as well as most common complications and failures of each high risk medical device.

5.      The results of the automated surveillance should be provided, in real time, to both the FDA, to complement existing event reporting systems, as well as to manufacturers to support refinements in product design.  

Ralph Hall – University of Minnesota Law School

Mr. Hall’s testimony focused on the study he conducted, which assessed the overall safety profile of medical devices approved or cleared by FDA from 2005-2009 by using Class I safety recall data.  The study evaluated Class I (or high risk) recalls of all medical devices, regardless of whether they were approved through the PMA system, cleared through the 510(k) process or were otherwise exempt.  He then discussed a number of the key conclusions from his study, including:

• Over 99.5% of 510(k) submissions assessed during this study period did not result in a Class I safety recall. 
• Over 99.7% of 510(k) submissions did not result in a Class I recall for any reason relevant to the 510(k) premarket system.
• Greater than 99.5% of PMA or sPMA submissions do not result in a Class I safety recall during the study period.
• Very few (less than 9%), Class I recalls during the study period involve possible undiscovered clinical risks.  As such, increased preapproval clinical testing would not have any meaningful impact on reducing the number of Class I recalls. 
• The majority (approximately 55%) of all Class I recalls involve problems or issues that arose after market release and could not be affected by premarket approval systems or requirements. 

Ultimately, he concluded that the study shows that FDA has a very positive safety record in its 510(k) clearance decisions.

David Nexon – AdvaMed

Mr. Nexon discussed the positive impact the medical technology industry has on the American economy and job market.  He noted how the industry employs more than 400,000 workers nationwide and the industry ranks eleventh among all manufacturing industries in gross exports.  He also emphasized how the medical device industry has improved patient care.  For example, he noted that between 1980 and 2000, medical progress added more than three years to life expectancy.  Moreover, the death rate from heart disease was cut in half; the death rate from stroke was cut by one-third, and the death rate from breast cancer was cut 20%

Accordingly, Mr. Nexon recognized that the 510(k) process is “critical to a vibrant and successful device industry and to the process of medical innovation that provides better products for patients to address unmet clinical needs. In a typical year, 3,800-4,000 new products will be cleared for marketing through the 510(k) process.  This compares to 30-40 products annually approved through the PMA process.”  

Mr. Nexon then discussed the studies presented by the other witnesses and emphasized how each study came to the same conclusion – that FDA’s 510(k) process has a strong safety record.  While AdvaMed recognized that product recalls do occur and that one patient harmed is one too many, he noted that “companies are striving – everyday – to make their products safer for patients, and we know that FDA shares this same goal.” 

Nevertheless, Mr. Nexon pointed to troubling trends that have emerged at the FDA that risk unduly delaying patient access to  safe and effective products.  These trends also increase uncertainty for companies and are negatively impacting investment in new treatments and diagnostics.  For example:

• Average approval times for original PMAs have risen 75% just since 2007, to more than two years
•  Companies report that the time to get an Investigational Device Exemption (IDE) – the prerequisite to beginning the clinical trials that must be completed before a PMA application and some more complex 510(k) applications – have lengthened dramatically – to times that are often measured in years rather than months.  And the time just to get a meeting to discuss an IDE can be six months or more.
• The average 510(k) decision time has risen 20% (97 days (2002) vs. 116 days (2008))
• The number of days 510(k) submitters spend answering FDA requests for more data has nearly tripled (19 days in 2002 vs. 51 days in 2008)
• The number of review cycles (the number of times FDA “stops the clock” on its review because it has decided to ask the manufacturer for more information) per 510(k) submission increased by one-third between 2002 and 2008 (1.4 per application in 2002 vs. 1.9 in 2008)

Mr. Nexon also pointed out that the percentage of 510(k)s “withdrawn by sponsors has skyrocketed 89 percent from 2004 to 2009 (nine percent to 17 percent), indicating a lack of clarity and consistency in FDA’s review standards.”  Additionally, he pointed to recent studies showing that America is falling behind other countries in medical device innovation and Americans are waiting longer for medical devices. 

William Maisel, MD, MPH – FDA, CDRH

On behalf of the FDA and Center for Devices and Radiological Health, Dr. Maisel discussed how his Center took a hard look at how they conduct their business, how they utilize scientific information and make decisions, and how they can improve the health of American patients.  

His testimony mainly focused on how the Center and FDA have taken strategic steps to strengthen the premarket evaluation and post-market surveillance of medical devices, while simultaneously promoting opportunities for medical device innovation.  He asserted that these steps will improve predictability, consistency, and transparency in the premarket and post-market programs and strengthen our scientific decision-making.  However, we cannot do this alone.  

He did recognize however that “industry also shares a responsibility for the success of the review process and safety of medical devices,” and that “some companies submit poor quality applications, ask to meet with us but then ignore our feedback, or conduct poor quality clinical studies.”  He noted that this “leads to unnecessary delays, wastes time and money for both industry and FDA, and exposes patients to unnecessary risks.”

Dr. Maisel also provided the committee with a brief overview of FDA’s regulatory authorities for medical devices and the different classifications of devices.  Then, he explained how there are “a limited number of areas in which FDA is not meeting the goals agreed to with the industry.”  He noted that goals are not met because of several factors, including “increasing workload, turnover of key staff, growing device complexity, and poor-quality submissions.  The number of applications for premarket approval and panel-track supplements (for “breakthrough” devices) has increased by 48 percent over the past two years.” 

In addition, he noted how “medical devices are becoming more technologically complex, as reflected by the growing number and variety of technical experts that FDA must consult during the review process.  Finally, a significant number of submissions received by the Agency are incomplete or fail to address basic elements, such as the device’s description or proposed indications for use.” 

Accordingly, Dr. Maisel pointed out that although FDA is meeting its performance goals for 510(k)s, submissions with quality problems “delay the completion of the marketing clearance process and unnecessarily divert resources from more productive activities in the review process.”  Finally, Dr. Maisel concluded by noting FDA’s recent 510(k) proposed changes and the Innovation Pathway.