Advancing personalized medicine through molecular diagnostics

With the mapping of the human genome and the revolution in molecular biology technologies, we are increasingly capable of monitoring human biology and disease in very sophisticated ways. Our ability to measure biological processes and indicators is now essentially "turning on the lights" on our ability to understand how life works. But tests using molecular methods, including molecular diagnostics, are the rate-limiting step for the full promise of personalized medicine to be realized. Challenges include the development of viable business models and the lack of reimbursement policies that recognize the value of companion diagnostics. In addition, laboratory-developed tests are being used extensively, but not always with proper validation, and the Food and Drug Administration (FDA) is struggling to provide regulatory guidelines that address this issue without stifling innovation.

A panel of diverse experts, moderated by Wendy Selig of the Melanoma Research Alliance, came together at Partnering for Cures to discuss the realities and opportunities in the world of molecular diagnostics. Several themes emerged during the discussion, including:

• Regulatory gaps – for example, laboratory developed tests – are creating uncertainty, particularly when it comes to reimbursement.
• Managing next-generation data in a productive way will be key to optimizing the potential of molecular diagnostics.
• Payers are fundamentally optimistic about personalized medicine but cynical because of experience.
• Though we have a lot of information, we don’t always know what it means.

David Parkinson of New Enterprise Associates, who spoke from the perspective of a clinician turned drug developer turned investor, pointed out that there are major disconnects in the world of molecular diagnostics – from regulatory expectations to payment incentives – that impede our ability to take advantage of the technology. “Until these disconnects are brought into equipoise, the question remains: who is going to develop these highly predictive tests, these biological characterizations of patients that allow clinicians to make personalized treatment decisions based on an individual patient’s tumor?”

Michael Pellini of Foundation Medicine underscored this point by highlighting the practical challenges that need to be addressed. “If we continue to think about each molecular test for a targeted therapy as a single test in which the clinician needs to be brilliant enough to single out the markers that he or she will test for in that patient and be right, that is challenge number one,” he explained. Pellini also pointed to other practical challenges, including the question of whether there will be enough tissue from a biopsy to conduct each test and how push-back from payers on reimbursement could impact use.

Jeffrey Trent of The Translational Genomics Research Institute (TGen) added that although technology has led us to a place where we can make informed treatment decisions based on molecular genetics, it is important that we do not overlook patients who do not have genetic alterations that can be specifically targeted by drugs. This is a challenge that TGen is addressing by conducting clinical trials in patient populations who cannot be stratified and treated based on genetic lesions.

Alberto Gutierrez of the FDA discussed some of the challenges with respect to the regulatory environment. He explained that the regulatory environment in this area is not clear and that a lot of the molecular testing that goes into diagnostics are laboratory-developed tests, which are not regulated by the FDA. Despite this gap, Gutierrez said that the FDA is more interested in clinical validity than clinical utility when it comes to molecular diagnostics. He explained the importance of ensuring that these tests provide physicians with meaningful data that they can understand and use confidently when making treatment decisions.

Sean Tunis of the Center for Medical Technology Policy provided the payer perspective. “Payers are fundamentally optimistic about personalized medicine, but cynical by experience because they know that they aren’t going to get exactly what they were promised in terms of savings,” he said. Tunis explained that payers are most concerned that the smaller populations of patients as a result of stratification by genetic subtype will lead to higher cost due to low demand for each individual test. He also said that payers are worried that in cases where risk outcome is low, clinicians may decide to continue with a more aggressive treatment path. In these cases, not only is the test reimbursed, but payers are also paying for a therapy that may not be necessary for the patient.

In conclusion, Selig asked the panelists what they think is the most important change that we need to pursue right away. Everyone agreed that first and foremost, we need not become overly engulfed in exploratory technology, and instead continue to make sure that we can treat the patients that need treatment today. Parkinson and Tunis highlighted that important changes need to be made with respect to reimbursement for diagnostic tests. As Tunis put it, “Whenever we get the regulatory framework figured out, we then need to tie it to reimbursement.”