The Conversation Begins: Recap from Day One of FDA’s LDT Regulatory Meeting

Welcome to Hyattsville, MD, where we have just completed day one of FDA’s two day “Public Meeting on Oversight of Laboratory Developed Tests” (LDTs). The session was civil, well-organized and largely devoid of surprises. It did, however, mark the official kick-off of the FDA’s highly publicized decision to develop a “risk-based application of oversight” for all LDTs.

If you’re interested in the details of what was said and by whom you’ll find links at the bottom to all of the relevant transcripts, video feeds and Twitter coverage. For my part, here are the three key take-away points from day one:

Timing. Last week I wrote that it was unlikely that this meeting, or any of the other myriad regulatory and legislative proposals for LDT regulation, would produce a significant shift in the legal and regulatory landscape any time soon. One day of FDA meetings has done nothing to change that opinion.

In the morning session, Dr. Elizabeth Mansfield, the Director of Personalized Medicine for the FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), repeatedly emphasized the Agency’s intention to “phase in” any LDT regulations. That theme was echoed by other presenting FDA officials, and OIVD Director Dr. Alberto Gutierrez made the same point when I spoke with him after the meeting. Dr. Gutierrez indicated that the next step was likely to be draft regulatory guidance, but that completion of the regulatory process was unlikely to be brief, given the complexity of the issues and the FDA’s commitment to developing reasonable, tailored regulation. (As an aside, the Director of CDRH, Dr. Jeffrey Shuren, in response to an audience question, made it crystal clear that he does not believe the FDA need undertake notice and comment rulemaking in order to implement its new regulatory policy, whatever it may turn out to be.)

Dr. Gutierrez also indicated that any new policy will be developed and delivered in a way that helps provide regulated entities with a clear understanding of what the FDA’s long-term regulatory goals are, even if the details of the regulatory framework require additional time to fully articulate.

Openness. One reason that a fully articulated regulatory policy is unlikely to emerge from the FDA in short order is that the Agency appears strongly committed to gathering stakeholder input and developing regulations that respond to that input. This is a standard talking point for any regulatory agency, and with numerous conflicting opinions over whether and how the FDA should  regulate LDTs, it is obvious that the Agency will not satisfy every stakeholder. Still, I was struck by the Agency’s commitment—in both private and public conversations—to understanding the issues and keeping an open mind about how to proceed. There seemed no reason to doubt Dr. Mansfield when she said that when it comes to LDT regulation, “nothing is set in stone; we have not made any decisions.” This only serves to underscore the importance of participation in the regulatory process which, if attendance at this meeting is any indication, is a strategy that the LDT community has embraced.

Details. As willing as the FDA officials were to listen and to encourage comments from the audience, the Agency’s own comments where characterized by an expected lack of detail about what form regulation might take. One theme Agency officials repeatedly struck was that of a “level playing field.” This echoes Genentech’s 2008 citizen petition (pdf) in which it urged the agency to hold all diagnostic tests, including LDTs, to the same regulatory standards, but it provides no real clue as to how the Agency expects to accomplish this. Similar and familiar talking points from the FDA—including the importance of developing risk-based oversight and ensuring safety and efficacy—did not come with significant new details. Those will be expected to emerge in the coming months, likely beginning with the release of draft regulatory guidance from the Agency.

Debate and Uncertainty. While the FDA’s public comments were light on the details, the stakeholder comments—as well as the panel discussion that followed—contained plenty of discussion about whether and how the FDA should proceed.

Show me the data. One recurring area of disagreement was whether the FDA currently has sufficient data on how LDTs are actually used and the harms, if any, that they produce. Without this information, many argued, it would be impossible for the Agency to develop accurate, tailored regulations, an imperative given the downsides of regulation and the FDA’s scarce regulatory resources. Among many who made this point, Mary Pendergast of Pendergast Consulting agreed that a risk-based approach to regulation was needed but argued that the FDA was in danger of regulating on “opinion and anecdote,” not facts. The ongoing comments about the need for improved data collection and transparency seemed to sway at least one of the afternoon panelists, Colonel Alan J. Magill of the Walter Reed Army Institute of Research, who indicated that over the course of the day he’d come to recognize the probable value of collecting more robust information about which LDT-related risks actually exist and need to be corrected.

Useful to whom? There was also considerable disagreement among commentators on the role of clinical utility in the FDA’s review process. Some, like panelist Dr. Steve Gutman of Blue Cross and Blue Shield, argued that “clinical utility is in the eye of the beholder,” suggesting that the demonstration of clinical utility as a condition of a diagnostic test’s clearance or approval might be, at a minimum, extremely difficult for the FDA to evaluate. Others, including panelist Cara Tenenbaum of the Ovarian Cancer National Alliance, saw clinical utility evaluation as a means of directing limited development and regulatory resources to those tests which provide end users with information they will actually use.

What about tomorrow? Another area of considerable confusion, if not necessarily disagreement, was what to do with the coming wave of multiplex diagnostic tests including, ultimately, a proliferation of whole-genome sequence data and corresponding interpretive tools. This was not an issue that the FDA tackled directly, but it was clear in the afternoon question and answer session that many of the panelists, at least, were unsure how the next generation of diagnostic tests would fit into the current (or contemplated) regulatory model. The challenges posed by the next generation of sequencing and bioinformatics tools are hardly new, but designing a regulatory framework equipped to survive the next decade will be one of the FDA’s greatest challenges.

Everything is connected. Another point raised in several side conversations—less so in the public discussions—was the importance of determining how changes in the FDA’s regulatory policy will impact other aspects of personalized medicine development and commercialization. From encouraging changes in coverage and reimbursement decisions to influencing which types of tests are developed and where, one of the FDA’s toughest tasks will be to think through how its decisions will change not only the regulation of LDTs, but also the broader personalized medicine landscape. It’s not always easy for regulatory agencies to work together, but in this instance close collaboration between the FDA, CMS, NIH and other relevant government stakeholders will be essential. After all, what ultimately matters is not whether and how LDTs are approved, but whether and how they reach the marketplace and improve the lives of patients and consumers.

Potpourri. There was relatively little discussion about the unique issues associated with direct-to-consumer (DTC) genetic testing, which might be seen as surprising given that a DTC announcement from Pathway Genomics was so instrumental in producing the meeting. However, DTC’s limited role was probably appropriate given that (a) it represents a relatively small segment of the LDT marketplace and (b) tomorrow there is an entire panel devoted to DTC issues. Also, while the NIH’s Genetic Testing Registry was mentioned several times, both by FDA officials and other commentators, there was no clear indication whether the FDA believes that NIH’s effort is either sufficient, useful as a model for the FDA, or something that the FDA plans to participate in (or even co-opt). One reason this matters, as Kirell Lahkman has pointed out in the past, is the real possibility of developing multiple, overlapping test registries.

Counting the Votes. With so many details yet to be determined, and with most stakeholders acutely focused on those particular aspects of a potential regulatory framework that most seriously impact their own interests, the overall mood was sometimes difficult to judge. Not surprisingly, one common (although not especially helpful) conclusion was that some form of regulation was probably advisable, provided that it was the right regulation. My unofficial tally from the 18 public comments presented today found 8 generally in favor of FDA regulation at this time, 5 generally opposed and 5 who managed not to express a discernable opinion on the topic. That split seemed largely to correspond with the informal conversations I had throughout the day although, again, almost everyone was withholding judgment pending the release of additional details from the FDA.

Logistics. Finally, a few logistical details for anyone who missed the meeting (or those who would like to relive it):

In a somewhat surprising display of government efficiency, today’s meeting wrapped up a full 90 minutes earlier than expected. If tomorrow’s sessions are similarly expedited, I will try to run a similar summary covering any new themes or unexpected developments. Until then, let the speculation begin continue.

Filed under: Bioinformatics/IT, Direct-to-Consumer Services, FDA LDT Regulation, General Interest, Genetic Testing/Screening, Genomic Policymaking, Genomic Sequencing, Genomics & Society, Industry News, Legal & Regulatory, Pending Regulation
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