When you're the boss, people tend to pay more attention to what you say. Unless of course you're the parent of a teenager. But I digress...
Recently, Alberto Gutierrez from FDA gave a presentation at the annual AACC meeting in Chicago during a session on the need for standardization. I was in attendance, and I can say that it was very similar in tone and substance to talks he and others from OIVD have given during the last couple of months. The difference this time was that Dr. Gutierrez is now the head of OIVD, and thus his talk carried more weight, which explains some of the buzz it generated at the meeting.
It shouldn't come as a surprise that the each word he spoke was carefully scrutinized. One widely-circulated story gave the impression that the FDA is taking a tough new stance on enforcement. Uh, maybe. But faithful readers of MyRAQA blogs would have found the talk to be very familiar, with the themes we've discussed here before. For those that missed it, or would like another perspective on what they've read or heard, here are the highlights.
- Dr. Gutierrez reiterated FDA's concern regarding LDTs. As in previous talks, he emphasized the talking points that the agency has hit on in the past: LDTs are impacting patient care, there is no real oversight, and FDA has the legal authority to regulate these tests. The one slight variation was the tie-in to the theme of the session, specifically the need for greater standardization and traceability, and how LDTs only further muddy the waters.
- He took IVD manufacturers to task for the variation seen in tests from lab to lab, while at the same time acknowledging FDA's role in not pressing for greater standardization. He was quick to point out the flaws in the 510(k) process, which often allows manufacturers to tenuously tie their product to a predicate device, thus exacerbating the situation. And he also hinted that how predicate devices were used in the past won't necessarily be allowed in the future.
- One area that Dr. Gutierrez really emphasized was the liberal definitions of performance that some manufacturers have used in labeling. In particular, he cited how some have used sensitivity (rate of true positives) and specificity (rate of true negatives) in more relative terms, rather than the rigorous statistical definitions. This is an area that clearly FDA wants to address in future submissions, as they see it as a way to improve the accuracy and reliability of the test results.
- Clinical utility / validation is definitely on the minds of those at FDA. Dr. Gutierrez suggested that kit manufacturers looking for clearance will need to do a better job of demonstrating this in the future. This has always been a keystone of the IVD MIA guidance strategy as well. In his talk Dr. Gutierrez mentioned how LDTs often have only analytical performance (CLIA validation) and limited clinical data on which to base their claims for the test. This coupled with a lack of pre-market review and few post-market controls leads to an overall concern by the FDA about the quality of the LDTs.
- Dr. Gutierrez was very candid about some of the shortcomings of the 510(k) process in particular. That said, don't expect any major reforms anytime soon. A risk-based approach is still seen as the best method for evaluating new tests. Instead, he suggested that FDA will bolster the existing program, leading one to believe that more rigor will be applied to future applications. He acknowledged that some manufacturers have found LDTs launched in a CLIA lab to be a faster route to market than the traditional 510(k) path, and stated that the agency was trying to deal with the issues. But he stopped short of offering any specifics.
So what are the take home messages from his talk? First, the days of "black box" LDTs are likely drawing to a close (and this shouldn't be a surprise). Second, FDA is aware of the issues of traceability and standardization, and though they acknowledge that they don't have any specific regulatory authority to force manufacturers to tie their results to some gold standard, they can (and will) hold them more accountable for the analytical performance and clinical utility of their tests. And finally, if you have the sense that FDA is probably strengthening enforcement, you're probably right. It's just a question of when and how much.