Much has changed in the FDA over the past year, and it appears more change is to come.  Issues surrounding device approvals under the 510(k) process were front-and-center in a public meeting this past Thursday. The meeting was titled by the FDA, “Strengthening the Center for Devices and Radiological Health’s 510(k) Review Process” and the agenda included a full day of discussion.  FDA invited 30 speakers including industry executives, physicians, and policy advocates. Preceding the speakers, FDA did make some presentations citing its challenges under the current system. This was followed by a round-table discussion, along with some open Q&A sessions.  From this meeting, it seemed two clearly differing agendas will shape policy changes over the coming months.

The FDA was clearly laying out the case for why it wants to make changes, while trying to broaden its powers beyond the current 510(k) process. When Dr. Donna-Bea Tillman, Director for CDRH Office of Device Evaluation made her presentation, she seemed to be open minded, stating that, “Trying to find the right balance between a regulatory process that enables us to foster innovation and at the same time ensures reasonable assurance of safety and effectiveness is the challenge we are here to talk about today.”  Christy Foreman, CDRH Deputy Director for Engineering and Science Review was a bit more wary of industry, particularly in areas where FDA does not have as much authority. She contended, “Submission for [510(k) ] modifications are based on firm’s determination regarding the effect on safety and effectiveness. ” Ms. Foreman seemed to be hinting that this was an area she and FDA wanted to see addressed.  Their concern is that documentation for incremental device changes is currently only kept in a firm’s internal files rather than defaulting to an FDA evaluation. Many other suggestions by FDA speakers indicated that The Agency wants increased oversight into clinical trials and labeling regulation. Further, the Director of 510(k) staff, Heather Rosecrans suggested that FDA needs broader powers to more easily rescind a 510(k) clearance if necessary.  Many more comments and side issues emerged during the presentations, and these comments did not go unanswered by the industry representatives in attendance.

Most of the participants from the medical device industry advocated for the continuation of the 510(k) process, with a focus on consistency and transparency.  Medtronic’s Chief Regulatory Officer,  Susan Alpert highlighted the result of a cumbersome 510(k) process citing,  “Our products go more quickly into other markets under other schemes than under this scheme”.   She and her counterparts at the round-table discussion offered several suggestions to help the program evolve, while stressing that the current process works well for the majority of devices. Putting it another way, Craig Coombs, Head of Coombs Medical Device Consulting argued,  “It’s not the 510(k) process.  It’s what our interpretations are… predictability is really what needs to be there in order for us to comply.”  These messages were echoed by many of the other industry speakers, and it is clear that this topic will continue to receive much further discussion.

FDA will continue to hear comments on the 510(k) process, and a Working Group is scheduled to submit its report to CDRH Director, Jeff Shuren, by the end of May 2010.  The docket for comments on 510(k) process will remain open until Mar. 19, 2010.   Comments are also being compiled by the community at my510k.com and on Twitter.  While suggestions are being taken by FDA, their position seems clear that “Strengthening the 510(k) Review Process” means getting tougher on industry.

While the games are underway, bringing stories both great and tragic from the mountains of Vancouver, there is an unsung chronicle of the technology supporting these athletes in their quest for Olympic Gold. The Vancouver Olympic Committee estimates $5 million in medical equipment/supplies have been donated for the Games in 2010. In fact, many athletes would not be able to maintain top form or in some cases even compete without the great Medical Devices advancing sports medicine at the Olympics. Three examples of such products come from three very different companies.

Kris Freeman may not have won a medal in yesterday’s 15k, but he is still regarded as one of the country’s most elite cross-country skiers. As a member of US Ski Team he has won many international races, and all while battling Type I diabetes. Freeman is able to compete even with his condition thanks in part to Insulet’s OmniPod® System, the only tubing-free insulin pump. With its durable design, Freeman can actually can use the pump to manage his diabetes during the race. Freeman hopes to continue the games injury-free and perhaps medal in his 2 remaining events.

Injuries are an unfortunate part of the Olympics. In severe cases, athletes can lose a significant amount of blood from a sustained injury. Belmont Instrument Corp’s Rapid Infuser is being used at the Mobile Medical Unit (MMU), which acts as a mobile ER. In addition to hospital use, the Rapid Infuser is actually “battle-tested” at the US Army stations in both Iraq and Afghanistan. Olympic athletes in need of care can benefit from such devices and facilities. These facilities also need to connect with each other in order to be most effective.

Providing the IT infrastructure, GE is probably the most prominent at the games, with their $80 million “Healthymagination” campaign. Once an athlete in need of care is receiving medical treatment, GE’s Centricity® solution is used to connect medical staff to real-time information about their patients. In its debut at the Olympic Winter Games, GE Healthcare’s technology allows doctors to quickly access the latest information and images needed to treat an injured athlete. The solution has been installed at the MMU, linking it to both the main Vancouver Polyclinic, and the Whistler Polyclinic. The athletes at these stations count on the medical equipment and technology, but surprisingly so do the spectators and staff.

More than 250,000 people are attending or supporting the venues at Vancouver and Whistler for the 2010 Olympics. Judging from the Winter Games held in Salt Lake City, UT more of them will need medical attention than will the athletes. Back in 2002, 11,575 medical cases were recorded, with Olympic athletes accounting for only 1,377. These number include officials, media, contractors, volunteers and staff in addition to the spectators in need of medical attention.

As the games continue, we will no doubt look to the headlines for the medal counts and stories of Olympic glory. Still, “below the fold”, there is a less-read but equally great story. This is the story of the scientists, engineers, marketers, manufacturers, and regulatory specialists who are creating the medical equipment that supports these athletes in their quest to become Olympic champions.

Before all this talk of “Snowmaggedon”, a beaming headline posted late last week stating that, “FDA Issues Guidance to Help Streamline Medical Device Clinical Trials”.  If you were hoping to learn how it works, you were in for a statistics lesson on Bayesian methods for designing studies and analyzing clinical data.  (Wait, don’t leave!)  Good news is you don’t need a statistics lesson, to simplify the main point. FDA is now advocating the use of prior clinical data and even post-market data from a prior device to justify shorter clinical studies and/or smaller sample sizes. This is a huge change from the same Agency that has demanded more data and more time to review device approval applications.  How can this be?  Why does Bayesian probability allow us to do this? The answer is not rocket science.

Beyes’ Law basically views probability as just “degree of belief” that an event will occur today, given knowledge of prior events.  Think of it this way…Have you ever “tried” to flip heads on a coin, or roll an 8 with dice?  How is this possible, if the probability of coins and dice are already known?  Since we know the physical act of flipping the coin can affect its outcome, it may not be a simple 50-50 probability.   The Bayesian idea of prior beliefs, allow us to set constraints and make conclusions beyond the actual data.  Humans are quite good at intuitively making predictions on very little information.  Bayes just put this into mathematical notation. (not to diminish the significance of Bayes’ Law in any way.)

Now, before this starts to sound like a “free pass” to shorter clinicals, be sure to finish reading the FDA guidance.   Once again for the sake of time, we can summarize… It makes sense that statistical theory cannot replace sound clinical science.  The FDA is quick to caution that patient data from prior studies rarely are 1-to-1 exchangeable with the patients in the current study. Instead, a test can be applied to find their  “borrow strength” from the previous studies.  Also, FDA will require that you still submit to their reviewers, your rationale for considering such prior clinical data. All of the same requirements apply when filing for an Investigational Device Exemption (IDE), and all methods and assumptions will need to be reviewed before the study can begin.

That said, the fact that good prior information on clinical device use exists, and that a Bayesian approach may enable smaller-sized or shorter-duration trials is welcome news to the industry.  In the official press release, FDA Commissioner, Dr. Margaret Hamburg says, “This is a terrific example of regulatory science in practice at FDA.”  We at my510k.com hope to see these kinds of developments continue, balancing regulation enforcement with sound scientific practices.

“How many should I take?”  “What level should I set my device to?”  “How long should I use the therapy?”  Many of these questions are answered in product labeling.  Labeling is all about specifying the “intended use” of the product.  The FDA has always enforced limits on labeling in all of its forms.  As the agency seeks to increase its budget and staffing, companies will need to continue being mindful of  how they promote their devices, especially online.

Companies have to watch the messages they send on their website and in social media channels.  In a recent letter to Bracco Diagnostics, the FDA alleged the company made unfounded claims about its diagnostic agent Isovue, and even minimized or outright omitted its risks on their website.  The FDA’s letter contends that the claims were based on a clinical study, as opposed full-blown prospective trial for Isovue.  According to the company, those web pages were taken down, but it remains to be seen if any legal action will be filed.

Lawsuits and fines did not escape Kimberly Clark’s I-Flow division, which allegedly encouraged doctors to use its OnQ Pain Buster infusion pumps following arthroscopic surgery.  This intra-articular use of the pump was not approved by the FDA, and so far the case has cost Kimberly Clark $4.75 million. These are not isolated events.  In fact, other manufacturers face similar lawsuits and impending action by the FDA as it seeks to devote more time and money towards enforcement of regulations.

According to the latest public documents, the FDA is looking to raise its budget for the medical device division (CDRH) to $1.4 billion, an increase of over $100 million.  With the request for over 1,000 new employees, the FDA may soon have the capacity for monitoring labeling much more closely.

Most device makers are careful not to promote off-label use, but FDA may soon want them to be more of when it is occurring.  This includes monitoring social media sites for information being exchanged between users promoting off-label use.   The FDA has stated in recent communications and at its public meeting on the topic, that they are monitoring social media sites for issues like off-label use and patient harm.  That information is being fed right back into the inspection process as part of the criteria for judging a company’s regulatory compliance.

Even companies that are doing all they can to comply, need to be aware and active in online social networks.  If companies want to avoid enforcement actions and costly legal disputes, they will need to remain vigilant in the digital social world.