Friends of Cancer Research 7th Annual Blueprint for Breakthrough Forum

(Remarks as Prepared for Delivery)

Good morning and thank you for having me here today.

One of the most critical points on a patient’s journey is the moment of diagnosis.  The moment when you find out what’s wrong.  What the options are.  The uncertainty of the unknown can be the hardest part of a grave diagnosis. And the emotional health that comes with more confidence and more certainty is inextricably linked to physical health and outcomes.

Narrowing this information gap is a key to making sure patients get the right treatment and timely care. It’s also key to helping resolve some of the irksome ambiguities of serious illness. This is especially true for patients diagnosed with cancer. Learning information early, and with the level of precision that allows for certainty amid of all the doubts, can improve care and sow confidence.

Having experienced that moment myself, I know how important it is to have confidence in that diagnosis -- to know that the information you’re getting is accurate and actionable. While the treatment – for instance chemotherapy, which can be very hard on a patients physical and emotional wellbeing – follows a predictable course in the best of cases, it’s the uncertainty of outcome that can be the hardest part of the journey. Not being sure of a diagnosis, or of how the drugs will attack a tumor, or of your odds of success.

Advances in our ability to define and treat cancer make that moment of diagnosis even more critical. We now have the ability to understand the genetic alterations that drive a tumor forward.  This insight is more frequently married to identifying drugs targeted to these underlying mutations.

Additionally, we have even more opportunities today to predict who among us might be at the highest risk of facing a diagnosis of cancer, and how a person at risk can take steps to mitigate that outcome.

At FDA, we want to take every chance we have to foster and maximize the kinds of innovations that will make these opportunities available to patients.

That means, in part, taking steps to advance effective diagnostics that help reduce uncertainty and target effective care.

As clinical testing gets more and more sophisticated, we need to make certain that we have the right regulatory framework in place to ensure that these new clinical tests—including ones that we cannot even envision today—are accurate, reliable, and safe. And that these tests are made accessible to patients as soon as possible. 

If we have the right framework, we can give doctors and patients more of the information they need to pursue the right treatment, at the right time, and for the right patient. And in constructing that framework, we recognize that many diagnostic tests are already well-understood. They’ve become a part of the standard delivery of healthcare. These established tests may not need the same level of oversight as other newer and less well-understood tests.

The right framework must also recognize that for certain serious conditions there can also be significant benefits to a diagnostic test that can provide potentially helpful information to patients early on, even while clinicians are still working hard to more fully understand a particular disease or condition.

This framework needs to work well across the spectrum of tests and the patients who need them. It needs to work for the regular cholesterol check that helps us maintain a healthy lifestyle. It needs to work for the newborn screening that could identify an early intervention to change the trajectory of a baby’s life. It needs to work for the hospitalized patient suffering from a serious infection who needs the right antibiotics. And it needs to work for healthy person with well-founded concerns about their health -- perhaps because of a family history of Alzheimer’s or breast cancer. The person who wants to know as much as possible, as soon as possible, about their risks so that they can take steps to reduce their odds of a bad outcome.

Such a framework is readily achievable and it’s something we should all expect.  And FDA is working closely with our partners to make this framework a reality and has taken new steps to bring it about.
       
In pursuing a new framework for the appropriate regulation of diagnostics, there will be difficult policy decisions to make and tradeoffs on any path to legislation. We know that the FDA must be flexible and open minded to new approaches that best meet the needs of patients so that patients can have confidence in the results and the treatment that comes from it. That’s the spirit of our proposed reforms.

FDA’s Center for Devices and Radiological Health has taken exactly this approach in providing feedback to Congress on proposed diagnostics legislation.  We have embraced a more modern, flexible approach to promote the extraordinary innovation that’s already well underway in this space, while ensuring patient protections.

In providing the contours for such a pathway to Congress, we’ve proposed new regulatory concepts that reflect some of the core principles we believe are fundamental to efforts to modernize diagnostics oversight.

First, we should have a consistent approach for all in vitro clinical tests. Our approach needs to be the same whether the test developer is a traditional manufacturer or a clinical laboratory.

Second, in general, FDA should focus its premarket review on evaluating the analytical and clinical validity of a subset of tests that are higher risk, or highly novel and used in circumstances where they can present greater uncertainties that can impact patients. A new framework could result in most tests being exempt from individual premarket review. But any approach that reallocates FDA’s premarket review resources must also include robust post-market authorities to protect patients from potential risks.

We know that many developers seek to continuously improve their tests. We shouldn’t stifle the natural iteration that characterizes the cycle of innovation in this space with overly burdensome pre-market review requirements. Moreover, we need to foster a streamlined pathway for truly breakthrough technologies that have the potential to significantly improve patient care. We need to make the route to market more efficient for technologies that can transform healthcare. But we also need to provide transparency around a test’s characteristics and performance, and make sure that the information is accurate and easily accessible to doctors, patients, and payors.

And finally, we need an efficient approach that leverages -- rather than duplicates -- the current framework that’s in place, including the requirements that apply to clinical laboratories under the Clinical Laboratory Improvement Amendments, and leverages the laboratory test expertise of third-party organizations.

These core principals are reflected in technical assistance that the FDA provided to Congress.  Let me tell you a bit more specifically how this approach would work, and how it could advance these goals.

First, the approach we proposed would grandfather most laboratory-developed tests currently being offered to patients. Under this framework, all in vitro clinical tests would fall under a unified set of requirements that would also exempt from pre-market review many categories of new or subsequently-modified tests. This would include manual tests, tests for rare disease, and low-risk and low-volume diagnostics.

To help the FDA use its resources most efficiently, while protecting patients and maintaining an appropriate level of oversight over all tests, our feedback to Congress includes a proposed precertification pathway. This builds on an approach we recently applied to direct-to-consumer genetic health risk tests. For developers that qualify for this path, pre-certification would allow for review of a single test, and the validation procedures associated with that test, to serve as an umbrella for clearance of a suite of related tests.

These accommodations would enable the FDA to take a risk- based approach that would focus our resources and expertise on the individual premarket review of certain categories of tests where it’s most needed, including tests that are higher-risk and novel, and many companion diagnostics and home-use tests.

Overall, the pathway that we’ve described also would allow for earlier patient access to breakthrough technologies -- those that are analytically valid and can demonstrate probable clinical validity and have the potential to change the way we identify and treat some of the most challenging conditions to diagnose. We’d work to make these technologies available to patients who might benefit, while taking steps to make sure that these tests meet the standard for full approval to stay on the market.

To balance the change in premarket review, it’s critical the agency be able to protect patient safety with strong post-market oversight and enforcement authorities.  FDA would require post-approval data as needed and would efficiently monitor the market for adverse events that can identify problematic tests.

And in what I hope will be a compelling new paradigm for the cancer research community, the FDA would seek to establish collaborative communities of scientists, clinicians, test developers, and patients to help support the agency’s decision making.  For example, FDA would hope to work on an on-going basis with leading oncologists, pathologists, and other outside experts in real time to develop standards for analytical validity for different types of tests.  We’d also seek to work with the right experts to evaluate emerging clinical evidence to support the clinical validity of newly identified variants. Part of this approach would build off the steps we’ve taken for the regulation of next generation sequencing (NGS) tests. The FDA would leverage public databases, the expertise of academic medical centers, and work with the community of researchers, in oncology and broadly across other medical specialties, to develop agile regulatory expectations for the most novel technologies, like NGS.

An example of the work that’s already underway is the device center’s engagement with the Medical Device Innovation Consortium. This is a public-private partnership to develop reference samples of tumor and normal tissue to help evaluate the various components of a next generation sequencing test and ensure confidence in the results being provided to patients. 
Our device center is also working with the National Institute of Standards and Technology to advance reference materials that can be used to evaluate the analytical performance of NGS tests.

The device center already has introduced a fluid approach to allow the reporting of additional oncogenes or gene variants of the same type without an additional submission to FDA, as long as they meet criteria established in the original submission.  This allows for rapid updates of NGS platforms to detect these new biomarkers as they’re identified by researchers.

And as evidence about the clinical significance of a gene mutations grows within the clinical community, there’s an efficient pathway for NGS tests to obtain FDA review.

Think about what all of this could mean. We could reduce patient screening time and the need for additional biopsies with more widespread use of these methods. And we could accelerate cancer drug development and improve clinical outcomes by pursuing these novel regulatory approaches. This is the path we should be on for our most advanced technologies that have the greatest potential to help us treat and cure disease.

Efforts like these demonstrate how the FDA is working to keep pace with advances in diagnostics, like new blood biopsies that measure circulating tumor DNA or panels of protein biomarkers.

But currently, our device program is constrained by a framework that’s existed since 1976, which hasn’t been enforced consistently with respect to all in vitro clinical tests and isn’t well suited to the modern challenges presented by the new technologies we’re seeing.

The decision to exercise enforcement discretion over laboratory developed tests was made in a different time and under different circumstances. We must ask whether that approach still makes sense? Or whether we should be enforcing the same standards for analytical and clinical validity across the range of diagnostics that patients rely on to make decisions about their health, but do so under a modern, flexible framework that allows us to adjust our oversight based on risk and how these tests are being used by providers and relied on by patients.

If the opportunity exists to modernize our approach to diagnostics regulation through legislation, FDA is a willing partner in those efforts. We’ve already made clear we’ll embrace it and offer new ideas.  We know there’s a lot of work to be done.  And we know that stakeholder feedback is critical.

In developing this approach, our device center remains committed to working with all stakeholders — the patient groups, professional societies, academic medical centers, large commercial laboratories, small specialty laboratories, in vitro diagnostic manufacturers, and many more. We look forward to following Congress’s lead on continuing to engage with stakeholders to refine these concepts throughout this process.

Through this modernized approach, we envision a world in which, eventually, fewer than 10 percent of all tests would require individual premarket review. About 40 percent of tests would be eligible for a precertification pathway. And more than 50 percent of tests would be exempt from premarket review.

In addition, we can foresee a market in which only about one-half of the test modifications that are currently subject to FDA premarket review would still be reviewed premarket. So, the process we envision can be far more efficient and even more robust than our current efforts. That’s because the FDA’s resources would be better leveraged by carefully focusing them where they are most needed. 

Under this framework, patients would have better information to direct their own healthcare. Tests for serious conditions that could offer large advances in patient care would reach patients more quickly. And the FDA would have better tools to protect patients from tests that could cause harm.

Diagnostics play a critical role in all aspects of healthcare. They can identify the right therapy for the right patient at the right time. They can help patients with chronic conditions monitor their individual health. And enable patients to more easily adjust necessary medicines as their health changes. Advanced diagnostics can empower consumers to take charge of their healthcare and make decisions to maintain a healthy lifestyle. They can reassure worried patients of a clean bill of health.

The FDA has an obligation to regulate diagnostics, and I believe we should do so in a way that advances opportunities for innovation, while maximizing protections for patients. We must be flexible and risk-based about where we focus our resources and expertise.  We must modernize our approach to keep pace with the technological change that’s underway.  I want to assure you that the FDA is committed to working with Congress to move forward on all these goals. 

Thank you.