Once such method gaining support is Comparitive Effectiveness Research (CER).  According to Maria Shepherd, Founder and CEO of Data Decision Group the method is already being funded by the current political administration.  Ms. Shepard provided some financial numbers during the Medical Devices Summit, in Boston, Massachusetts.  According to her research, the American Recovery and Reinvestment Act of 2009 provided $1.1 billion for Comparative Effectiveness Research, splitting the funds between two agencies;  The Agency for Healthcare Research and Quality (AHRQ)  Received $700 Million and the National Institutes of Health (NIH) was alloted the remaining $400 Million.  Medical Devices are a high priority group for CER proponents, especially for atrial fibrillation (AF) , endoscopies, prostate cancer and obesity treatments.  FDA and the medical community like CER because it is outcomes based.   The merits of CER were also touted in a recent paper by Alec B. O’Connor, MD, MPH published in the Journal of the American Medical Association (JAMA).  Dr. O’Conner wrote that, “ The current FDA standards for approval fail to assess whether newly approved drugs and devices are less efficacious or less well-tolerated than existing alternatives. This raises the possibility that patients may be harmed by receiving a newly approved treatment instead of an alternative with established efficacy and safety.”  He goes on to suggest that FDA should provide oversight of CER active-comparator trials, designed to prove superiority, equivalence or at the very least, noninferiority.   While this makes sense from an analysis standpoint, the actual practice of designing a CER study can make it difficult to statistically prove superiority or non-inferiority.  Based on the sampling, small differences in outcomes may be hard to detect or rule out.  The FDA has suggested the use of a Beyes study, which was explained in an earlier post.  Still, time and and cost can be a significant issue.  Because of the large sample size and costs that can reach upwards of $15 Million to conduct, a fully designed active control trial for CER will not be economically feasible for Class I & II device makers.  Still some migration from a predicate system to a risk-based system of device approval may be in store.

To give us an idea what the new model might look like we can review the comments of, Craig Coombs, faculty at University of California Berkeley and President of Coombs Medical Device Consulting.  Mr. Coombs made his case during the FDA public meeting about ways to strengthen the 510(k) process.   He suggested a shift from the current precedent justified system to “truly risk-based system” in order to regain consistency in review and increase public confidence in the Agency.  This idea would align with FDA’s renewed focus on test data for regulatory submissions.  Using the system suggested by Mr. Coombs, device approval would be more heavily based on data to substantiate the application of the new device for its intended use.  Rather than focusing on a comparative study against a predicate, the device is truly evaluated on it’s own merits.  As Mr. Coombs said during the meeting,

“ An unless a predicate is considered gold standard my client does not test predicate devices or compare themselves to a predicate when it comes to performance testing. Rather, all devices including 510(k) devices stand on their own testing. This is a requirement of the quality design regulation and been the reality of the 510(k) process for years. “

With all of the continuing debate over possible changes in the FDA’s medical device review process, there are a few emerging points of concensus.  First, most believe that some form of change is needed to strengthen the current 510(k) process.  Second, there is more emphasis being placed on risk and test data.  Many of the ideas discussed in last month’s meeting  are being reivewed at the FDA, and additional time was granted for submitting comments to the official docket.  Anyone with thoughts or ideas on the process should submit their comments before March 19, 2010.

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.

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.

Last time we woke up in this situation, it was 1993.  Punxsutawney Phil had predicted 6 more weeks of winter as then-President Bill Clinton was in his first term with a large agenda.  Health care reform and changes to the FDA were at the top of his list.   Legislation was being pushed by late Sen. Edward Kennedy (D-Mass) to increase regulations under then-Chief, Dr. David Kessler (actually appointed by former-President George Bush).  Dr. Kessler made it his mission to take on medical device companies.  The fear and uncertainty of increased regulations had the industry very concerned by late 1993.    Many companies were forced to delay major product releases, while struggling to comply with FDA regulations.  It seemed that this was to be the future for medical devices in the 90’s…until the 1994 Congressional election.

Once the power of congress was reversed, the newly appointed House Speaker, Newt Gingrich (R-Ga.) moved to streamline the FDA, claiming that slower medical device approvals were “killing jobs–and people”.  The reforms were designed to create a more efficient FDA, and encourage the regulatory agency to work with manufactures of new drugs and devices.  Eventually, Kessler resigned in 1996, and a year later legislation finally passed that benefited the industry, the FDA, and patients.

So now, here we are again.  Punxsutawney Phil gave us the same weather outlook, and it would seem we have the same regulatory forecast as well.  Previous posts on the Five-Ten Blog have discussed the current industry climate at-length; suffice to say we are still looking at proposals of increased regulations and slower device approvals via the 510(k) process.

What does this mean?  It may mean that the upcoming meetings to discuss reforms will only be part of the story.  We as an industry certainly need to make our case to the FDA.  However, we have an important mid-term election coming as well, and President Obama needs Congress to approve his FDA budget.  If the pendulum swings back to a more balanced Congress, it will affect the scope of any proposed reforms.  Hopefully, we see a balance that allows safe and effective medical devices to have more timely reviews, and ultimately an industry that continues to innovate and improve the health outcomes of our patients.

Happy Groundhog Day!

First, since this is a blog we should mention the public hearings that took place just last November regarding how manufactures of FDA Regulated products use the internet and particularly social media.  Most of the discussion that took place over the 2-day hearing covered topics ranging for marketing claims and messages online, to post-market surveillance on social media websites.  Complete coverage of the events and industry reaction can be found on the FDASM website.  Many differing viewpoints still are being considered, and the FDA has yet to enact any formal polices or guidance as a result of these hearings.

Also, most recently the FDA has announced that it will hold a public meeting on Feb. 18 to review the premarket approval, or 510(k) process, used to review and clear medical devices for sale in the United States market.  The goal of the meeting will be to hear comments and questions regarding any pending actions that the Center for Devices and Radiological Health (CDRH) may consider taking to tighten the 510(k) process.  Those wishing to attend  the meeting in person will need to register by 5 p.m. on Feb. 12, 2010. The agency is also accepting written or electronic comments by March 5, 2010.  Other meetings and committee hearings on various topics are posted on the FDA website throughout the year.  Though it remains to be seen how much of the public and industry feedback will find its way into policy, opportunities to have a voice are available.

As a final thought, this newly founded blog and soon to launch social network will be taking comments and feedback to submit to the FDA on the 510(k) process.  In an upcoming panel discussion at the Medical Device Summit there will be an opportunity to give some feedback and suggestions to Heather Rosecrans, Director, 510(k) Staff, CDRH, FDA.  We are collecting these suggestions from the industry in many forms including direct messages on Twitter to @my510k, posts to the Beta my510k.com network site, and comments in this blog.  All feedback will be collated and submitted to FDA on behalf of the community.  Start today and take action to defend our industry.  Change is inevitable, but you can make a difference…just don’t miss the chance to have your voice heard.

Case and point with the proposed Medical Device Tax, that the Obama Administration has repeatedly outlined in the healthcare reform plans.  The interesting thing with this hidden tax is that its effects are being felt already, before it has even been enacted.  The mere discussion of the concept has made companies divert hiring plans, reconsider projects, and even caused entrepreneurs and VCs to reconsider further investment in the industry.

The Chronical Telegram reported that just this past week, Invacare CEO, A. Malachi Mixon III tried to get an appointment with President Obama to tour his facility in Elyria, OH and discuss the ramifications of a medical device tax on his company and the industry.  According to the report, Mr. Mixon made the following plea, “Please tell the medical device industry there will be no medical device excise tax in your health care bill so we can get back to business as usual…They are killing small businesses.”  Clearly the sting can be felt in local areas that depend on these companies for jobs and tax revenues.

Even more concerning is when an entire state economy is at stake, as it seems to be in Minnesota.  Device Industry news leader, MedCity News reports that the VC market for Medical Device startups is running dry to the tune of 40% investment reduction from 2009 in Minnesota.  The economy in the state of Minnesota is built on the Medical Device industry in much the way Silicon Valley depends on the Technology sector.  The combination of a down economy, a more active FDA, and the proposed medical device tax have created the “perfect storm” which is keeping Venture Capital locked in it’s proverbial shelter.

In the end, it’s the health care consumer who is paying the proposed tax.  In an industry where price competition is already fierce, the only way for companies to survive these new threats is to limit or delay product releases.  Many companies are being conservative with their project budgets, and may not include potentially cutting-edge products that would have a longer road to FDA approval.  As for the hidden cost of this proposed tax…Potentially live-saving therapy and life-enhancing treatments will not make it to the patients that desperately need them.

The Advisory Committee Meetings are a good and necessary practice in principle.  The FDA uses these committees to seek independent, expert advice on newly discovered matters of scientific significance.  Dialogue is meant to be open, candid, and free-flowing on all sides.  However, many times in practice these meetings start as a civil debate over scientific matters, only to deteriorate into a mix political and personal agendas.  Negative bias can be especially expected if a sponsor did not follow FDA’s advice on clinical assessments or the overall development program.  The process works best when all stakeholders are well prepared, and send clear, consistent messages.

When devices are reviewed in committee, CDRH tends to look at how the product will fit into actual clinical practice, and more recently, off-label use is being considered.  Sponsors will need to be sure to address these issues early in the process.  In addition, all pertinent information regarding product risks should be fully disclosed right upfront.  Considering the average reviewer only has a limited number of hours to prepare, the Briefing Book and the presentation should be scripted such that the FDA committee members can quickly focus on the most critical and compelling factors during the review.  The meeting should be approached as forum to gain consensus about the science behind the device being submitted.   The degree to which sponsors are sucessful at this process depends on how well they are able to:

1. Understand the Committee (audience)
2. Maintain clear messages througout the presentation
3. Prepare for meeting (Practice, Practice, Practice)
4. Learn from those with past Committee experience

If you have not had to face an Advisory Committee yet in your career, chances are you will soon.  If you have already been in this arena once before, please feel free to add some “lessons learned” in the comments section.  We need to work together as an industry to ensure that all stakeholders in the Advisory Committee process can work towards a meaningful and transparent discussion that protects the health and safety of patients, while providing a pathway to delivering the therapies they so greatly need.

While this measure will hopefully shed more light on the agency’s operations to the public, it does not ease the mind of Medical Device makers, who still see a very unclear approval process.    The new charge to overhaul the 510(k) along with the turnover at FDA have both led to longer review times and general frustration among the manufacturers.  Further compounding the problem, is the seeming lack of a consistent standard by which a device gets cleared.  It often happens that when a reviewer changes just prior to market approval, the new reviewer demands additional testing and data.

Under the current 510(k) review process, device makers must literally “guess” what is necessary to prove their product’s safety and efficacy.  Further, the FDA has been making major changes to the Special 510(k) even in the middle of a device review, denying eligibility and increasing the requirements for test data to show substantial equivalence.

The agency will tell you substantial equivalence does not indicate safety and/or efficacy, but often it is difficult to tell which measure the FDA is emphasizing.   Most manufactures would be very willing to comply with a consistent measure, rather than endure months or longer for a process that is billed as a “90-day review”.

As an industry, we need to share our experiences with each other regarding the FDA’s review process.  Further as an industry we must demand more consistancy and transparency in the approval process.  Now, more than ever is the chance to collaborate towards our shared goals of innovation and public health.

These reports sent the agency’s CDRH (Center for Devices and Radiological Health) acting chief, Jeffrey Shuren into damage control mode with the New York Times, citing alleged “inaccuracies” in the studies.  Shuren did actually agree, however, that FDA’s current process is not acceptable, and stated that they are already making changes in the program.

The Massachusetts Medical Devices Journal, MassDevice.com did an outstanding interview that gives a full account of the fallout from Redberg and Dhruva’s prospectives.

While one can argue either point, the ultimate question is how does this really affect safety and efficacy…and what should be done (if anything) to address it?  Any reaction by FDA is more likely to be overkill than rational measured reform.  At present, several  510(k) applications have ground to a halt, while examiners demand more data than ever before in recent memory.  Even the fast-track Special 510(k) process is being cutback, slowing the release of devices to the US market.  Many of these devices are already being distributed overseas in South America, EU, and Asia by compliant, law-biding companies.  In general, most medical device companies exist to serve their patients by delivering life-saving and life-enhancing therapies.  These firms use all available resource to produce high-quality, reliable devices.  To say that FDA is too swift in it’s approval process is almost to suggest that device makers are taking a slipshod approach to clinical trials and design validation.  If this is the case, where is the surge in MDRs per # of devices in the market?  The exact measures taken by the agency remain to be seen, but don’t be surprised if innovation slows while we in the industry wait to satisfy FDA’s growing glut for more data.