Proactive Postmarket Safety Surveillance in Scrutinized World

Medical device companies face an expanding set of legal and regulatory requirements to address risks and concerns around product safety. Scrutiny from the public and regulators increasingly focuses on safety concerns, as demonstrated by FDA’s recent changes to the 510(k) process and draft guidance for postmarket safety.^1,2 As product safety requirements increase, device companies must expand their approach to both postmarket safety surveillance and managing product risks.

A proactive system, in contrast, will be necessary moving forward as the device industry continues to advance. An effective and proactive medical device safety surveillance framework in today’s device market requires constant feedback throughout the lifecycle. It ensures that manufacturers are asking the right questions at the right time, that relevant medical input is incorporated from early product development through postmarket surveillance, and that companies have the infrastructure and processes in place to support a corporate culture focused on product safety.

Current Trends

Medical device product recalls and adverse events have increased steadily over the past decade.³ The number of adverse events associated with medical devices reported to FDA doubled from 2003 to 2007.4 Medical device reporting (MDRs) increased from about 77,000 in 2000 to about 320,000 in 2006. FDA indicates that nearly 2,500 medical devices were recalled for potential safety problems in fiscal 2008, nearly double the number reported in 2007, and a 164% increase since 2000. In fact, more than 1,000 recall notices were sent out in the first seven months of 2009, 100 of which were ranked as Class 1 recalls. During the past several years, critics have repeatedly pointed to the urgent need for FDA to strengthen the approval process for medical devices, particularly the 510(k) process, and to increase and improve safety surveillance requirements.

In the past, FDA has considered passive postmarket safety surveillance reports sufficient to identify safety concerns. The agency has been empowered to require postmarket studies as a condition of approval for a Class II or III device, but it has historically lacked both the authority to enforce study completion and the resources to conduct its own studies.⁵ In light of increasing public scrutiny around product safety issues, FDA is responding in a number of ways that indicate this approach is no longer sufficient:

FDA isn’t finished making changes. Device companies should expect demands for product safety and surveillance to continue to increase. In a report released in August 2011, the Institute of Medicine (IOM) specifically cited postmarket safety (as it relates to the 510(k) clearance process) and identified several areas of concern. The report found that FDA is too reliant on manufacturers and healthcare facilities to collect and provide information on devices. Many technical issues exist, limiting the effectiveness of current surveillance efforts. Additionally, FDA’s process for implementing postmarket studies for devices is only used sparingly. While the focus of the IOM’s report was on the 510(k) process, it’s worth noting that the criticisms of FDA’s postmarket safety efforts were less controversial than the study’s primary recommendation— to scrap the 510(k) process altogether—and thus more likely to be part of FDA’s ongoing efforts to improve device safety.

Metal-on-metal hip implants represent a timely example of why concerns about device safety have increased. The metal-on-metal design was supposedly more durable than metal-on-plastic hips, which have a tendency to wear over time. Companies marketed these products based on the success of engineering-focused tests, and surgeons and patients clamored to use the next big thing. After the products were launched, registry data from Australia and the UK reported observations of cobalt entering patients’ bloodstream as a result of metal shavings, leading to complications and a high rate of revision. These reports were largely ignored, and the hips remained on the market for another 18 months in Australia and even longer in the United States, before huge recalls, and lawsuits, made headlines around the world.⁶ 

Such catastrophes could potentially be avoided with more effective postmarket surveillance. The problems in this case stemmed not from a lack of postmarket data, but rather from the lack of a consistent approach to collecting and analyzing data with sufficient medical input. The evidence that the metal-on-metal implant could potentially result in some metal debris in the bloodstream existed, but was discounted as “noise” by engineering-focused assessments of the product’s safety. There is general agreement that had there been a more established process—one designed to include medical input into the signal analysis and decision escalation process—these issues would have been recognized and addressed earlier.

Integrated Approach to Managing Product Safety

Device companies face significant challenges to improve postmarket safety surveillance capabilities. Most devices currently on the market are not supported by sufficient premarket clinical data to detect the potential for life-threatening events once the device is widely used. The impracticality of conducting large-scale clinical trials before approval places a major burden on postmarket surveillance. In addition, some devices have a short product lifecycle, so signals must be reviewed quickly to ensure that they are addressed before one product is replaced by the next.

Beyond these challenges, the complex interplay between the device, the surgeon, and the patient must be considered. Often, it is easy to dismiss a possible signal as a user error (as a problem with the surgery) rather than the device. For this reason, it is essential that the postmarket safety surveillance framework include mechanisms to ensure that signals are not discounted in this fashion and that someone with medical experience or expertise can evaluate complaints that are considered a user error.

To address these challenges, it is key to develop a risk profile that is based on product use and characteristics such as novelty of design and materials, clinical use, and variability in patient and tissue interface to guide postmarket safety surveillance. The profile should be a living document, created during product development and periodically reviewed to incorporate additional data throughout the product lifecycle. This profile requires engineering, quality, and medical input, and will inform decision making about postmarket safety surveillance, including what types of information sources should be examined, what signal assessment methods should be used, how signals should be escalated, and how frequently the plan should be reviewed.

As demands for proactive surveillance increase, device companies will need to consider expanding the use of registries, using new data sources and medical claims data, developing new analytical capabilities, and experimenting with other kinds of surveillance activities such as social networks and clinical practice observations. These practices present an opportunity for device companies as well. They can feed the additional information they gather into planning and product development, identifying unmet needs and possible product innovations that can be considered in the next generation of device.  

Throughout the product lifecycle, incorporating medical input is essential to ensure product safety. Specifically, physicians and other medical personnel can advise on training, signal identification, and reviewing other data sources (i.e. additional literature review, database scans and automated surveillance, and enhanced analytics). Medical staff will help identify if a signal can be discounted or if it needs to be escalated, based on the nature of a complaint or the possible effect on the human body. While it may be impractical to have someone with a medical degree reviewing every product complaint, medical staff (including allied health professionals) can assist in reviewing trends and unusual signals. Medical professionals also may serve as consultants to help train call center staff, and identify issues or potential signals.

An integrated approach to safety requires a consistent, risk-based framework that allows for appropriate flexibility based on product characteristics. Developing this approach to postmarket safety, rather than managing each product separately, will allow device companies to ensure a consistent approach while maintaining the local flexibility to support numerous products.

Implementation Challenges

Developing a safety culture may require organizations to change their structure and capabilities. Within many device companies, the various functions (e.g., quality, medical, R&D ) have traditionally been siloed. An integrated approach to managing product safety necessitates a greater degree of cooperation between these groups.

In addition, to manage the growing complexity of devices and their potential for greater human health risk, there likely will be a need for an independent (medical) voice for safety at a management level. What this means in practical terms will depend on company culture, the portfolio of products, and their associated risks. Increasing medical involvement and input throughout the product lifecycle will require well-defined processes and accountability.

Conclusion

Medical device companies preparing to proactively address increasing demands for product safety face significant challenges as well as significant opportunities. By adapting an integrated, risk-based approach to product safety, device companies can not only meet demands handed down from FDA, but also decrease exposure to potential safety issues like recalls and develop an even stronger portfolio and pipeline of products based on the data acquired postmarket.

References

1. FDA, “CDRH Plan of Action for 510(k) and Science - Implementation of Recommendations from the 510(k) and Science Reports,” (Rockville, MD: CDRH, 2011); available from Internet: www.fda.gov/downloads/AboutFDA/CentersOffices/CDRH/CDRHReports/UCM276316.pdf.

2. FDA, “Draft Guidance for Industry and Food and Drug Administration Staff–Procedures for Handling Section 522 Postmarket Surveillance Studies,” (Rockville, MD: FDA, 2011); available from Internet: www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM268141.pdf.

3. D Zuckerman, P Brown, and S Nissen.“Medical Device Recalls and the FDA Approval Process,” Archives of Internal Medicine 171, no. 11 (2011).

4. S Brownlee and J Lenzer,“Why the FDA Can’t Protect the Public,” British Medical Journal 341(2010).

5. “Medical Devices and the Public’s Health: The FDA 510(k) Clearance Process at 35 Years,” Institute of Medicine (2011) 99-115; available from Internet: http://iom.edu/Reports/2011/Medical-Devices-and-the-Publics-Health-The-FDA-510k-Clearance-Process-at-35-Years.aspx.

6.D Cohen, “Out of Joint: The Story of the ASR,” British Medical Journal 342 (2011).

Stephen Rothenberg, JD, is a consultant at Numerof & Associates Inc. (St. Louis). Matt Levy JD is a business analyst at the firm. They can be reached at [email protected].