FDA is working with hospitals to modernize data collection about medical devices

Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health

By: Jeffrey Shuren, M.D., J.D.

America’s hospitals and their dedicated staff helps us fight disease and suffering by delivering life-saving and life-enhancing care every day in an astounding variety of ways.

From helping set a broken leg or responding to an emerging viral threat, to assisting and performing delicate heart surgeries on tiny newborns, these hospital personnel are the front line of surveillance, vigilance, and intervention.

Throughout their work day, hospital staff use a variety of medical devices: imaging machines, EKGs and in vitro tests to make diagnoses; infusion pumps, ventilators and robotics to provide treatment, and an array of implants to replace diseased joints and organs. And, as the nation’s hubs for real-time health care data, hospitals are uniquely positioned to help identify new safety problems with devices as well as changes in the frequency of already known safety problems because they use these technologies in the real-world setting of clinical practice, outside of the more controlled setting  of a clinical trial.

FDA is looking to improve the way we work with hospitals to modernize and streamline data collection about medical devices.

Jeffrey Shuren

Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health

Given the greater diversity and complexity of medical devices today; the rapid technological advances and iterative nature of medical device product development; the interface between the technology and the user – including the learning curve associated with adopting new technology; and, in some cases, a relatively short product life cycle that can be measured in months, not years; FDA’s evaluation of medical device safety presents unique challenges not seen with drugs and biologics. Therefore, assuring the safety of medical devices depends on many factors and should a problem arise, it could be due to a variety of causes.

At the time of premarket evaluation, however, it is not feasible to identify all possible risks or to have absolute certainty regarding a technology’s benefit-risk profile. Among other reasons, studies required to do so would likely be prohibitively large in order to capture less frequent and more unpredictable effects or consequences. In addition, such larger studies still may not reflect the true benefit-risk profile of the device. Once a device is on the market, for example, doctors may use it beyond the FDA cleared intended use. In addition, subsequent modifications to the device or changes in how the device is used in practice can result in new safety risks or greater frequency of known risks.

FDA has several tools for watching devices once they are on the market, also called postmarket surveillance, all of which have inherent limitations. For one thing, we can require that a manufacturer conduct a post-approval or postmarket surveillance study that focuses on identifying potential longer-term issues noted at the time of clearance or approval or specific safety concerns that may arise after clearance or approval. However, conducting studies on a product after it’s already on the market can be challenging because patients often have little incentive to enroll in a study when the device is already available to them.

Likely the most well-known of FDA’s postmarket surveillance tools is medical device reporting, which FDA requires from certain entities, including device manufacturers and device user facilities, such as hospitals. Federal law requires hospitals and other user facilities to report when they become aware of information reasonably suggesting that a medical device has or may have caused or contributed to a death or serious injury to a patient.  They must report these medical device-related deaths to both FDA and the manufacturer, if known; and device-related serious injuries to the manufacturer, or to FDA, if the manufacturer is not known.  Such passive surveillance has important limitations because it relies on people to identify that a harm occurred or a risk is present, recognize that the harm or risk is associated with the use of a particular device, and take the time to report it.

Congress mandated this reporting by user facilities in 1990 to complement similar adverse event reporting by manufacturers. But then, in 1997, Congress required that FDA establish a reporting program that could limit user facility reporting to a subset of representative user facilities. As part of our efforts to develop this  reporting program, FDA set up a large-scale network of about 300 hospitals, called MedSun (the Medical Product Safety Network), with whom we work interactively to better understand and report on device use in the real-world environment. Even with MedSun, all hospitals were required to continue reporting until FDA implements by regulation a program limiting user facility reporting to a subset of facilities.

Although FDA has recognized that requiring all hospitals and other user facilities to report may provide limited added value and could entail unnecessary costs that take away from patient care, we have not yet established the program limiting reporting to a subset of user facilities. In the past, we have not enforced universal reporting requirements for hospitals and other user facilities.

In light of several high-profile device safety issues occurring in hospitals, FDA, in December 2015, initiated inspections at 17 hospitals, chosen because there were reports of events at these facilities related to the spread of uterine cancer from the use of morcellators or the spread of infections associated with contaminated duodenoscopes. While these events appeared to be the kind that would have fallen under our current medical device reporting requirements, we did not see corresponding adverse event reports in our adverse event (MAUDE) database. From those inspections, we learned three important lessons:

  • First, some hospitals didn’t submit required reports for deaths or serious injuries related to devices used at their facilities, and in some cases, they did not have adequate procedures in place for reporting device-related death or serious injury events to FDA or to the manufacturers.  Based on the number of user facilities in the United States and the number of reports we receive, we believe that these hospitals are not unique in that there is limited to no reporting to FDA or to the manufacturers at some hospitals.  We want to work with all hospitals to address these issues.
  • Second, hospital staff often were not aware of nor trained to comply with all of FDA’s medical device reporting requirements.
  • Third, we feel certain there is a better way to work with hospitals to get the real-world information we need, and we should work with the hospital community to find that right path, especially in light of developments in the creation and evaluation of electronic health information.

In order to effectively address these issues, we will work with the hospital community on what role they should play in assuring the safe use of medical devices. This work will include how they can effectively participate in  the National Evaluation System for health Technology (NEST), and whether or not current reporting requirements should remain, be modified, or eliminated in light of more effective modern tools, such as software tools to conduct active surveillance of electronic health information that contains unique device identifiers.  In many cases, our inspections of these 17 hospitals turned up violations of FDA’s medical device reporting regulation. For some hospitals with significant violations of the regulation, FDA received a response that we determined was not adequate to address those violations, and we engaged with these facilities to facilitate an effective path to compliance. These hospitals indicated their willingness to work with us and address the violations, and at this time, we do not believe any additional action with regard to these hospitals is necessary.  Some hospitals also expressed willingness to work with us on more efficient and effective ways to collect the information we need.

On December 5, FDA will hold a public workshop to solicit input and advice on improving hospital-based surveillance systems and the broader role of using hospitals to evaluate how well devices work in the clinical setting. We encourage all hospital stakeholders—from clinicians to IT system managers—to attend and discuss current hospital-based surveillance efforts, the role of hospitals in evidence generation and future opportunities for hospital-based surveillance. We’d also like their input on the incorporation of unique device identifiers (UDIs) into electronic health records to aid in the future development of evidence generation efforts, including the support of better device development, surveillance and health care delivery.

We are already working directly with the Association of American Medical Colleges and the American Hospital Association to prepare for this workshop and help develop improvements to our systems.

Hospitals are our partners in building the infrastructure for NEST. Together we can build a state-of-the-art system that not only quickly identifies life-threatening problems caused by medical devices but also expedites patient access to crucial life-saving devices. Armed with such information, health care providers can help patients make more informed medical decisions that improve their health.

Jeffrey Shuren, M.D., J.D., is FDA’s Director of the Center for Devices and Radiological Health

FDA Celebrates the 40th Anniversary of the Medical Device Amendments

By: Jeffrey Shuren, M.D., J.D.

In 1976, Steve Jobs and Steve Wozniak founded Apple and a gallon of gas was $.59. And in another action that has had long term impact, President Ford signed the Medical Device Amendments that closed the dangerous gap between what he called FDA’s “horse and buggy authority” and “laser age problems.”

Jeffrey Shuren, M.D., J.D.

Jeffrey Shuren, M.D., J.D., FDA’s Director of the Center for Devices and Radiological Health, speaking at FDA’s Celebration of the 40th Anniversary of the Medical Device Amendments

Unlike the pharmaceutical industry, which was born from large chemical companies that discovered medical uses for the products they made, the device industry sprung to life as a scrappy sibling—mostly mom-and-pop businesses addressing the needs of individual patients and physicians through invention.

Although Congress had first given FDA explicit authority over medical devices in the 1938 Food, Drug, and Cosmetic Act, the focus was on fraudulent products. Efforts to extend FDA’s oversight on medical devices failed in 1962 and again in 1970.

Then in 1975, reports emerged that thousands of women had been harmed, some even died, from pelvic inflammatory disease, as the result of using the Dalkon Shield, an intrauterine device for contraception. Congress responded the following year by enacting the Medical Device Amendments, which authorized FDA to classify all medical devices based on risk into one of three classifications, to require premarket approval for Class III devices, and for devices to comply with reporting and GMP requirements.

The law ushered in a new era for medical technology innovation, patient access, and patient safety, but also created a tension, contributing to a political environment where the pendulum continues to swing between these objectives, defining and driving the medical device ecosystem ever since.

In signing the legislation, President Ford noted that, when “well designed and well-made and properly used” medical devices “support and lengthen life.” But when medical devices are “poorly designed, poorly made, and improperly used” they can “threaten and impair” life.” His words still ring true today.

The initial Medical Device Program started with about 180 people. Today, FDA’s Center for Devices and Radiological Health (CDRH) is 1,700 strong; a vibrant family of individuals with a wide range of scientific, clinical, engineering, legal, and other expertise, who hail from a variety of backgrounds, and who are ready to tackle the latest scientific advancement.

And the mom and pop industry has transformed into a world of sophisticated software algorithms, miniaturization, combination products, wearable sensors, non-invasive procedures and diagnostics, robotics, and artificial intelligence.

Along the way, CDRH has adapted its expertise and regulatory approaches to meet the needs of such rapidly evolving innovation. While we will continue to adapt, more importantly, we are focusing on proactively anticipating where we need to be so that regulatory innovation is out in front of medical device innovation. We’re doing this now in the digital health space, by designing regulatory frameworks around the type of technology and its unique evidence generation and innovation cycle rather than applying a one-size-fits-all approach.

We are implementing new models for evidence generation. They include the establishment of a National Evaluation System for health Technology, or NEST, that could transform the historical tension between device innovation, patient access and patient safety into an alignment of interests to drive the development and more timely access to life-saving, life-enhancing, and life-advancing devices. This is consistent with our vision: That patients in the U.S. have access to high-quality, safe and effective medical devices of public health importance first in the world.

And we are also going to new places with patients by establishing a foundation for engaging with them as our partners and routinely incorporating their perspectives in our decisions. And that’s fitting because improving the health and the quality of life of patients by assuring they have timely access to medical technologies that will benefit them is at the heart of who we are and what we do.

As we look ahead to the future, it is our work, our care and our dedication that will allow us to reach our vision.

Jeffrey Shuren, M.D., J.D., is FDA’s Director of the Center for Devices and Radiological Health

For more information read: Remarks at FDA’s Celebration of the 40th Anniversary of the Medical Device Amendments, by Jeffrey Shuren, M.D., J.D.

Listening to Patients’ Views on New Treatments for Obesity

By: Kathryn O’Callaghan and Jeffrey Shuren, M.D., J.D.

The world was a very different place in 1976, when the Food and Drug Administration launched its medical device program.

Kathryn O'Callaghan

Kathryn O’Callaghan, Associate Director for Science and Strategic Partnerships (Acting), FDA’s Center for Devices and Radiological Health

Since Steve Jobs and Steve Wozniak were just that year launching a computer company called Apple, doctors weren’t yet able to view X-ray images or look up drug prescribing information on their iPhones. Moreover, patients couldn’t Google treatments for heart disease, nor were they able to instantly find all open U.S. clinical trials for breast cancer. Not only was patients’ access to health care information much more limited, so was their role in making their own health care decisions.

Doctors diagnosed. Doctors made treatment decisions. Patients followed directions.

It’s different now.

Patients are more empowered today. Driven in part by a need to address emerging or neglected illnesses, such as HIV/AIDS and rare disorders, patients over the past three decades have increasingly banded together, creating organizations that advocated for their interests and generated public awareness of their diseases, their needs, and the lack of effective therapies. This activity produced legions of informed and empowered patients, who today urge us to take a more active role in our own health and urge clinicians to engage patients in shared health care decision-making. Patients are now not only partners in their health care but active consumers who make choices about their doctors, treatments, diagnostics, and health care experiences, an empowerment that is affecting the development of innovative therapies and new clinical solutions.

Today, there are no health care debates, discussions and decisions without considering the patient perspective.

Jeffrey Shuren

Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health

At FDA’s Center for Devices and Radiological Health (CDRH), we have been systematically involving patients in our regulatory decision making process. Since 1999, CDRH has included a patient representative on each of our advisory panels of outside experts, giving us a better understanding of patient concerns about particular technologies. And in 2012, we began focusing our medical device approval decisions on incorporating the patients’ perspective.

Under this benefit-risk framework for high-risk and innovative, lower-risk medical devices, CDRH’s health care professionals, scientists, and engineers consider the patients’ perspective on both a product’s benefits and their tolerance for any risks when weighing the evidence to determine whether or not to approve a product.

In the past, CDRH experts may have determined that a device should not be approved because its probable risks outweighed its probable benefits. However today, under a patient-centric assessment of risk, if adequate evidence indicates that a subset of well-informed patients with a particular illness or condition would value the product’s benefits more than its risks, CDRH may approve the device for that particular group. However, if we were to approve such a device we may require appropriate product labeling that clearly defines the patient sub-population and their benefit-risk preference. That information would be included in the product’s “Indications for Use” section of the label to ensure that patients and health care practitioners are able to make well-informed decisions.

Better tools are needed to more reliably and scientifically characterize patient preferences about benefit and risks, so we launched our Patient Preferences Initiative, to identify and develop methods for assessing patient valuations of benefit and risk related to specific device types and specific illnesses and conditions.

The goal is to ensure we have sufficient confidence in these methods to rely on them to inform product approval decisions.

Earlier this month, a team of FDA scientists led by Telba Irony, PhD, Chief of General and Surgical Devices Branch in the Division of Biostatistics, published an article in Surgical Endoscopy with leading behavioral economists at RTI Health Solutions, a business unit of RTI International, illustrating how this paradigm can inform medical device approval decisions. The authors successfully tested a new method for capturing patient sentiment and translated it into a decision-making tool for incorporating patient preferences into clinical trial design for obesity treatments. They were able to estimate the tradeoffs in risks that obese patients are willing to accept in exchange for a certain amount of weight loss, and the minimum number of pounds they would have to lose to tolerate the risks of a weight loss device.

Shortly after the study was published, FDA approved a new weight loss device – the Maestro Rechargeable System, an important therapeutic option for obese patients. The decision to approve the device was based in part on the data from Irony’s study that showed a substantial portion of obese patients would accept the risks associated with a surgically implanted device if they lost a sufficient number of pounds. Maestro is the first FDA-approved obesity device since 2007.

Our Patient Preferences Initiative is testing other ways to reach out to patients and capture their views through public workshops, websites, and a new patient-focused advisory committee. CDRH is also participating in related research as a member of the Medical Device Innovation Consortium (MDIC), a non-profit partnership between the FDA, National Institutes of Health, Centers for Medicare & Medicaid Services, and 43 medical device companies, patient groups and other non-profit organizations. MDIC is developing a framework for incorporating patient preferences into the device development and assessment process, and compiling a catalog of methods for collecting patient preference information that can be used to develop, design, and market devices that meet the needs of patients. Simultaneously, CDRH is developing draft guidance outlining how data from patient preference assessment tools can inform device approvals and other regulatory decision making.

As patient groups, industry sponsors, and others conduct more patient preference studies, we will better understand the tradeoffs that patients with medical device-treatable diseases and conditions are willing to make. This research, along with actions taken by CDRH, MDIC and others will drive more patient-centered device development and assessment. As a result, patients will play an influential role in determining which treatments and diagnostics are available in the U.S. market.

It may have taken more than 30 years, but patients are finally having their say.

We should take care to listen.

Kathryn O’Callaghan is Associate Director for Science and Strategic Partnerships (Acting), FDA’s Center for Devices and Radiological Health

Jeffrey Shuren, M.D., J.D., is Director of FDA’s Center for Devices and Radiological Health

Report: CDRH on Track to Improve Device Submission Review Process

By: Jeffrey Shuren, M.D.

FDA’s Center for Devices and Radiological Health (CDRH) is committed to speeding innovative new medical devices to market and to improving the efficiency of our device submission review process. That’s critical for patients getting access to medical devices that treat often life-threatening conditions. It’s also important for industry’s ability to continue developing new products.

Jeffrey ShurenWhile recent data suggest we’re making solid progress in bringing down total review times for both 510(k) submissions and our higher risk premarket approval applications, it’s always useful to get a reality check.

That’s why, as part of the 2012 Medical Device User Fee Amendments (MDUFA III), FDA agreed with the medical device industry to participate in an independent and comprehensive assessment of our review process.

A third party consulting firm assessed CDRH’s review process, management systems, IT infrastructure, workload management tools, reviewer training programs and staff turnover. Key findings were released in December 2013, along with a list of high-priority recommendations for improvements.

Their Final Report on Findings and Recommendations, released today, affirms that CDRH is on a path to meeting many of the challenges that were flagged in the months leading up to the enactment of MDUFA III, including such topics as sponsor communication, IT infrastructure, reviewer training, reviewer attrition, and submission quality.

Initially, the contractor identified 31 unique issues related to the device submission review process. They concluded that CDRH had taken steps to address 21 of those 31 issues – either through the development and implementation of new MDUFA III provisions, updated systems, and/or processes for review staff – and that we had at least begun to address another nine of the issues. Only one issue – creating the tools and metrics to assess the consistency of decision-making across the program – remained. It was the driver for one of the contractor’s high-priority recommendations.

After the December report came out, we put together our own plan of action to implement the high-priority recommendations. These recommendations call for:

  • Developing criteria and establishing mechanisms to improve consistency in decision-making throughout the review process.
  • Providing mandatory full staff training for the three primary IT systems that support MDUFA III reviews.
  • Identifying metrics and incorporating methods to better assess review process training satisfaction, learning and staff behavior changes.
  • Adopting a holistic, multi-pronged approach to address five quality component areas to standardize process lifecycle management activities and improve consistency of reviews. This approach addresses such topics as corrective and preventive action and continuous process improvement, resource management, document management and system evaluation.

This action plan, also out today, has been divided into two stages. The first stage includes those actions needed to address specific recommendations identified in the December report, most of which will be implemented by 2016. The second stage covers longer-term actions to further enhance the efficiency of our processes beyond what the contractor recommended. We will now begin to execute this action plan. In addition, as we committed to do under MDUFA III, we will now develop an implementation plan for the new recommendations in this final report.

I encourage you to take a close look at the report and our plan of action. I think you’ll agree with me that sustained focus on these various management improvements will translate to more consistent and efficient reviews, advanced innovation and ultimately improved patient health.

Jeffrey Shuren, M.D., is Director of FDA’s Center for Devices and Radiological Health

Considering Women’s Needs in Developing Medical Devices: Here’s ‘HoW’

By: Michelle McMurry-Heath, MD, Ph.D. 

Women differ from men in anatomy, physiology, risk factors and disease symptoms. They are also likely to use more medical devices over the course of their lives than men do.

That is why FDA is actively trying to learn more about how medical devices uniquely affect women, and how women can be better served by them.

This month we published a snapshot of how FDA is doing with such efforts. A congressionally-required report (Section 907 of the Food and Drug Administration Safety and Innovation Act) looked at the inclusion and analysis of women and other demographic subgroups in clinical studies supporting the approval of medical devices and other FDA-regulated medical products. After reviewing 2011 product applications, including 37 premarket approval applications, or PMAs, for devices, we found that in the majority of cases, sponsors provide information about women, conduct subset analyses and share information with the public in a variety of ways.

One specific activity highlighted in the report was a workshop sponsored earlier this summer by the Center for Devices and Radiological Health (CDRH) to formally launch a new program designed to more closely look at medical device use and the health of women (HoW). The three main goals of HoW are to:

  • Improve the availability, consistency and communication of information to patients and providers that is specific to women’s needs for the safe and effective use of medical devices.
  • Address identified gaps and unmet needs through targeted resources.
  • Foster the development of innovative strategies, technology and clinical study models.

Nearly 200 representatives from industry, academia, health care, federal agencies, patient and advocacy groups, gathered to discuss the issues related to medical devices and health in women and to brainstorm about effective strategies to address clinical research needs in this population.

This work builds on a December 2011 draft guidance, also highlighted in this month’s 907 report. That guidance outlined CDRH’s proposed expectations regarding sex-specific enrollment in clinical studies, data analysis, and reporting of study information. Ideally, the final guidance will provide a clear decision-making framework for when and how to analyze and communicate data involving women in device clinical studies.

The CDRH HoW program also plans to complement this by developing, in partnership with other stakeholders, strategies for communicating information about differences to the people who most need to know: health care professionals, clinical investigators, the medical device industry, and most importantly, patients.

With these activities, we are laying the groundwork for making sure the unique health needs of women are considered in research agendas and device innovation. The goal is to strengthen the focus of FDA, industry and the clinical community in developing medical devices designed to meet the unique clinical needs of women, and to communicate new information as we learn more about how differences affect treatment options and outcomes.

Now, with the issuance of the 907 report, and an accompanying docket to receive comments from the public, we hope to gain an even more in-depth understanding about demographic subgroups. The input we receive will become the starting point for developing an Action Plan, to be released next year.

These are all important steps towards ensuring that medical devices developed will take into account the unique needs of women.

Michelle McMurry-Heath, M.D., Ph.D., is the Associate Director for Science at the FDA’s Center for Devices and Radiological Health

Resolving Disputes Concerning FDA and Medical Devices

By: David S. Buckles, PhD, FACC, and Lawrence “Jake” Romanell 

Disagreements are inevitable in science, medicine – and even life. As part of a regulatory agency committed to public health, the FDA’s medical devices center occasionally confronts scientific and policy disagreements among our staff and with the various stakeholders we strive to serve. 

Disputes can occur at any stage of a particular interaction, from an initial inquiry or pre-submission review to a final regulatory decision on an application or submission.

David S. Buckles, PhD, FACC

As Ombudsmen for FDA’s medical devices center, our office investigates complaints from outside the FDA and facilitates the resolution of disputes between FDA’s medical devices center and the industry we regulate. Since part of our job is maintaining impartiality and neutrality, we are a good starting point if you have a complaint, question, or dispute of a scientific, regulatory, or procedural nature. Given the inevitably of disputes, what we find important is how we deal with those disagreements. 

Legislation passed last year by Congress introduced the term “significant decision” to our regulatory lexicon and included certain expectations of how we are to deal with disagreements over such decisions. FDA has proposed its interpretation of what constitutes a “significant decision” in a question and answer draft guidance document, entitled, “Center for Devices and Radiological Health Appeals Processes: Questions and Answers about 517A.” This draft guidance is available for public comment. We believe that when it comes to disputes, all stakeholders play an important role in resolution. Therefore, we strongly encourage interested parties to provide comments and suggestions to improve our appeals process to help us meet our goal of providing a fair, equitable, predictable and transparent means for seeking resolution of disputes. 

In our current experience, differences of opinion that arise before a final decision is reached can usually be resolved through discussion, or even, occasionally, mediation. If interactive discussion with a lead reviewer, team leader or Consumer Safety Officer does not move the ball forward, we have found that outreach by the stakeholder to engage Branch and Division management in the discussion usually has a good chance of success. We have never yet had a senior manager turn us down when we’ve asked them to take a look at a situation, and we strongly encourage stakeholders to make a good faith effort to connect with management at least through the Division level before considering more formal approaches. 

Lawrence "Jake" Romanell

When discussion and interaction through the Division level fails to resolve a dispute, stakeholders usually have several options. By far the most common approach is to request internal agency supervisory review as provided in the Code of Federal Regulations, at 21 CFR 10.75. When a request is made for internal agency review of a decision of an FDA employee, the decision is subject to review by the FDA employee’s supervisor. Generally, such a request for internal agency review is filed with the manager at the next organizational level above the level that either signed the document in dispute or was substantively involved in the decision. 

In the past several years FDA’s Center for Devices and Radiological Health has come a long way in standardizing the appeal process and setting consistent expectations, both internally and externally, to ensure that stakeholders with a legitimate dispute receive a fair and impartial hearing by senior management. Our updated guidance documents will make our process even more clear—and clarity helps make for smoother decisions. 

Wasn’t it Gandhi who said that honest disagreement is often a good sign of progress? 

David S. Buckles, PhD, FACC, and Lawrence “Jake” Romanell, are in FDA’s Center for Devices and Radiological Health, Office of the Ombudsman

When Conduct Becomes a Crime

By: John Roth 

In my last post, I explained how FDA’s Office of Criminal Investigation (OCI) works when a small portion of the industry fails to adequately respond to regulatory action. For Abbott Laboratories and Amgen, the price for regulatory malfeasance was high:  $1.4 billion – yes, billion — paid in criminal and civil penalties to the United States. 

Sometimes, however, the conduct of entities evinces such a complete disregard for the health and safety of the public that a criminal response is necessary. 

A case that still resonates with the FDA and law enforcement community involves the OCI investigation of the conduct of Synthes, a medical device maker, in the marketing of a bone cement product called Norian XR. The product was cleared by FDA for use in certain instances, but was specifically rejected for the use Synthes wanted: injection into the spine as part of a mixture. 

In fact, the FDA-approved label specifically warned against such use. Rather than attempt to get FDA approval through scientifically-validated clinical trials (at a cost of about $1 million, and taking about three years), Synthes decided to convince doctors to perform the procedure and then publish the results, notwithstanding the risks. And certainly, Synthes had reasons to understand the risks. Before the marketing program began, pilot studies showed that the bone cement reacted chemically with human blood in a test tube to cause blood clots. The research also showed, in a pig, that such cement-caused clots became lodged in the lungs.  

Nevertheless, Synthes executives plunged forward with a plan to conduct what amounted to an unauthorized clinical trial of the use of Norian to treat vertebral compression fractures of the spine. Equally appalling, the company marketed uses of the product in contravention of a “Black Box” warning — the most serious warning the FDA can require. 

The ensuing tragedy was inevitable. Three patients injected with the medication died on the operating table. 

Despite this, the company did not recall the product from the market, an action which would have required them to disclose details of the three deaths to the FDA. Equally egregious, Synthes officials deliberately misled the FDA during an official inspection in May and June 2004. 

After painstaking and complex work by OCI investigators, working with their colleagues in FDA’s Office of Regulatory Affairs and the scientists and public health experts in FDA’s Center for Devices and Radiologic Health, in 2010, Synthes pled guilty and paid the maximum fine allowable by law — in excess of $23 million for the company and its corporate parent. In 2011, four executives were convicted and sentenced to prison terms. 

Another similarly tragic case of reckless conduct involved ApotheCure, a compounding pharmacy in Dallas that shipped colchicine injectable solution to a medical center in Portland, Oregon. Colchicine is used to prevent gout attacks and relieve the pain of gout attacks when they occur. In 2007, three patients, within hours of receiving the drug, died. 

FDA testing of vials selected from the shipment revealed some vials as super potent — containing over 640 percent of the level of the drug that was declared on the label. Others were sub potent, containing less than 63% of the declared strength. After an OCI investigation, the pharmacy and its owners pled guilty to criminal charges in 2012. 

The penalties imposed on these two firms, Synthes and ApotheCure, and the responsible individuals cannot bring back the lives of those six innocent individuals. But OCI’s determined work produces results, and as I noted in my first post, “gives the FDA unique fact-finding tools and provides for strong, industry-wide deterrence.” We trust our forceful actions, then and now, continue to deter other companies and individuals from such reprehensible conduct. 

John Roth is Director of FDA’s Office of Criminal Investigations