If you want to know what changes may be in store for medical device approvals, look no further.  Change is coming, and it looks like it will start with “substantial equivalence”.  Since the Premarket Notification (510k) has been established, medical device approvals have centered around the idea of substantial equivalence to a predicate device.  Substantial equivalence means that the new device has the same intended use as the predicate, and is at least as safe and effective.  As this paradigm has recently been called into question, a few common ideas have emerged regarding possible changes to the process.  These suggested changes place more emphasis on risk analysis and test data, however they approach it by very different means.

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.