Interview by Steve Halasey

When most people think of the achievements that are making possible today’s advances in healthcare, the contributions of clinical laboratories and in vitro diagnostic manufacturers are rarely near the top of the list. It’s little wonder, then, that members of the clinical laboratory community have seen President Obama’s creation of a National Cancer Moonshot initiative, to be led by Vice President Biden, as an opportunity to raise the profile of the diagnostic tools and techniques that are essential to advanced cancer care.

In a letter to Biden on March 31, 2016, industry association AdvaMed, Washington, DC, offered its own view, focusing on the important roles that medical technology plays in cancer care and treatment.1 “A wide range of medical diagnostic tests are used in every stage of cancer care, from disease research and drug development, screening, diagnosis, staging, and prognosis, to therapy selection, therapy and disease monitoring, and follow up testing,” wrote the association.

Andrew C. Fish, JD, AdvaMedDx.

Andrew C. Fish, JD, AdvaMedDx.

To find out more about the roles that clinical diagnostics play in cancer care, CLP recently spoke with Andrew C. Fish, JD, executive director of AdvaMedDx, the in vitro diagnostics subsidiary of AdvaMed.

CLP: It is in the early days for the National Cancer Moonshot, but what is your understanding of the scope of activities defined for the task force?

Andrew C. Fish, JD: To my understanding, the primary goal of the task force is to better coordinate various activities across the landscape of the federal government—to ensure that there is maximum collaboration, maximum sharing of information, and ultimately faster progress in the longstanding fight against cancer. The appointment of a blue ribbon panel that will report to the task force suggests an additional goal of identifying how to break down barriers within the research community, so that various players can share data more effectively, and work with the governmental infrastructure, to make faster advances in cancer therapy and care.

CLP: In the general public, there’s a tendency to think of drug therapies first, with less understanding of the roles played by diagnostics. Does the task force share that tendency?

Fish: I can’t speak directly to whether the individuals on the task force have a full appreciation for the critical role of diagnostics, but we have certainly observed that diagnostics play essential roles that are often not appreciated. One of the key reasons for such underappreciation is the fact that the use of diagnostics typically happens out of the sight of both patients and clinicians. Although clinicians use diagnostics all the time to gather the information they need to make decisions, the process of actually conducting testing—and a lot of the fundamental understanding of what goes into diagnostic testing—takes place outside the doctor’s office. More commonly, it takes place in a laboratory either within a hospital setting, or in a third-party laboratory.

As a result, the impact and power of diagnostics to guide all aspects of care are often overlooked by the broader public, as well as by patients and doctors. Even though diagnostics are essential for guiding therapeutic decisions, people tend to see and appreciate therapies much more easily. We spend a relatively small amount of money upfront to get good diagnostic information, which then guides our decisions about spending potentially tens of thousands of dollars on treatment.

Such relationships between diagnostics and treatments underscore how important it is for people to better understand the roles of diagnostics, and how we can even better leverage diagnostics in cancer care.

CLP: What other notions underlie AdvaMed’s recent letter to Vice President Biden regarding the role of medical technologies in cancer care?

Fish: The purpose of our letter to the vice president’s office shortly after he announced the initiation of the National Cancer Moonshot was simply to underscore that AdvaMed member companies are continuing to develop and improve a range of pertinent technologies, and that those technologies are critical to both better diagnoses and better treatment for patients. Molecular diagnostics, in particular, represent a tremendous advance for the healthcare system. And there has been an enormous amount of progress made in oncology, in particular, as a result of advances in diagnostics.

We’re also calling out the ability of a variety of other technologies to contribute to cancer therapy. For example, radiation therapies play a critical role. Most cancer patients receive and benefit from radiation therapy as part of their treatment. We also pointed out that a number of other companies manufacture surgical tools and other pieces of medical equipment that are critical in the overall picture of cancer care. In short, our letter to the vice president stressed the central role of medical technologies in pretty much every stage of cancer diagnosis, therapy, and recovery.

CLP: The letter also requested a meeting with the staff of the task force, in order to provide a more detailed briefing about the cancer-related technologies described in the letter. Have you received a reply to that request?

Fish: We have had follow-up communications with the vice president’s office, and we anticipate having further, more substantive conversations. Yes, they have reached back out to us.

CLP: It is believed and often repeated that in vitro diagnostic testing accounts for 2% to 5% of healthcare costs but influences 60% to 70% of medical decisionmaking. Do those numbers hold up when it comes to cancer care?

Fish: The numbers are probably even more dramatic when it comes to cancer care. Over a long period of time, our understanding of cancer has dramatically shifted from viewing cancer as a disease that occurs in a particular part of the body, to understanding that cancer is many different kinds of diseases, generally characterized by abnormal cell growth. A particular kind of cancer can occur in multiple places around the body, and many cancers are driven by changes in our genome—in our genetic makeup—that cause cells to develop abnormally, leading to tumors and the spread of various kinds of cancer around the body.

This understanding has led to the development of tests that can help patients understand what kind of cancer they have, at a molecular level. And it has also led to the development of drugs that specifically target the underlying, genetically driven molecular problems that lead to a specific cancer.

What all of this means is that it is now essential that cancer patients understand what genetic variations and mutations may be driving their cancer, because that will lead them to a much better understanding of their overall cancer care, including which drugs may work for them, and which drugs may not work for them.

Cancer offers a good illustration of the role of diagnostics, because a small investment in getting the diagnostic information needed to fully understand an individual patient’s cancer upfront can drive far better decisionmaking about how to spend tens of thousands of dollars in cancer care. It can steer a patient away from extremely expensive drugs that will not work, or that may lead to undesirable side effects, and instead point to alternatives that will work better for that specific patient.

CLP: The term “in vitro diagnostics” obscures some of the functions that are performed by these tools. AdvaMed’s letter calls out the importance of diagnostics “in every stage of cancer care from disease research and drug development, screening, diagnosis, staging, and prognosis, to therapy selection, therapy and disease monitoring, and follow-up testing.” Beyond the diagnostic function of such tests, can you comment about the importance of these other tasks?

Fish: There is much more to diagnostics than merely the ability to provide a diagnosis. Even before a diagnostic is ever used on a patient specimen, diagnostic testing can be used in early-stage research, including research for drug development.

Diagnostics also provide actionable insights at virtually every stage of care. When used for screening, diagnostics can reveal whether someone is at risk for acquiring a condition down the road, or even developing cancer as a result of a particular genetic mutation. It can also be used to screen patients to find out if they have cancer now, thereby identifying cancer earlier, when it’s more treatable at less cost. Diagnostic information can also be used to determine how far a cancer has spread in the body, what stage it’s at, and the likelihood that it is an aggressive cancer requiring equally aggressive treatment.

After a patient has been given a particular drug, diagnostics can measure how the cancer responds to the drug, and perhaps inform the patient that they need to move to a different therapy. And after a patient is in remission, regular testing can help determine whether cancer has recurred. These tests are critical at virtually every stage of the cancer story, in basic research and therapy development, as well as at every stage of cancer care.

CLP: When it comes to making commitments of funding and resources, the development of in vitro diagnostics often takes a back seat to other pursuits. How would you recommend that the task force address the need to support the development of advanced diagnostic technologies for cancer?

Fish: With regard to funding, there are a couple of areas to which the task force might pay attention. One is to ensure a robust, regular funding stream for basic research in the life sciences. The development process for diagnostics relies upon and leverages our steadily increasing understanding of biomarkers relevant to various health conditions, disease conditions, and diseases. Certainly, that’s true in cancer. Our knowledge base about the various underlying mechanisms of cancer is growing all the time. The more that basic research dollars can be spent on discovering and developing pertinent biomarkers, the faster we can develop tests that can be used in patient care. So, funding of basic research is a very important first step.

Second, there could be additional funding for various activities that FDA is undertaking to collect broad sets of information about biomarkers and genomics, which may be leveraged by a wide variety of entities that develop additional tests. Coordinating the funding of these activities with the funding streams for basic research could be a very important goal for the task force.

CLP: There have been some recent breakthroughs in diagnostic technologies for cancer, including a study demonstrating the viability of the liquid biopsy technique in breast cancer and the first FDA approval of a liquid biopsy test, for colorectal cancer. What will it take to advance these breakthroughs so that they become part of the first-line protocols in cancer care?

Fish: Advances in cancer diagnostics are extremely exciting because they’re leveraging newfound and more-effective abilities to get information from patients, and they are doing so earlier in the disease state and in a way that’s less invasive for the patient. For example, liquid biopsy techniques are being developed using a variety of technologies, in order to increase our ability to detect cancer in blood samples and other patient specimens. Using this strategy, it may be possible to detect cancers at a very early stage, when cancer cells are moving around the body, but before a tumor has grown enough to be detectable by other means.

The question of how to bring such breakthroughs into first-line use goes to an ongoing problem in cancer care, which is how to build a deeper understanding of the current knowledge base and the current tools in community care settings. Those of us who are focused on the latest advances sometimes mistakenly assume that every new idea immediately becomes the standard of care. But very often such advances are being developed or used only in a small set of prominent academic research centers, and the lag time between FDA approval of a breakthrough technology and its widespread use in community cancer centers can be many years.

That problem needs to be addressed in at least two ways. First, we need to encourage Medicare and private payors to more quickly assess and pay appropriately for new technologies, so that lack of coverage or appropriate payment doesn’t slow down their adoption for all patients. Second, the community of cancer clinicians needs to be as aggressive as possible about sharing best practices and informing themselves about what technologies are available and how best to use them.

CLP: What other advances in in vitro diagnostic testing are on the horizon and what will it take to bring them into use?

Fish: We’re continuing to see advances in next-generation sequencing (NGS), which is essentially a collection of technologies that allow for more rapid, more accurate, and less expensive sequencing of the human genome, whether the whole genome or portions of the genome. The ability to generate and analyze huge amounts of genomic data, at costs that are continuing to fall, will remain a huge driver of advances in cancer care. It will help advance basic knowledge as well as novel therapies.

Work to develop liquid biopsy techniques has also identified other places within the bodywhere cancer biomarkers can be identified. Some very interesting work is exploring the diagnostic utility of exosomes, which are essentially vesicles that occur naturally in biological fluids, and function to transmit messages among cells throughout the body. These vesicles contain fragments of DNA and other genetic materials. By locating such vesicles and analyzing the biochemical messages they are carrying, one can determine what’s going on in other places in the body. They can help to identify a very early stage cancer, for example, or to monitor the way a patient is responding to a drug therapy. This is another example of fantastically interesting advances in our basic understanding from a life sciences perspective, which are also rapidly being translated into new diagnostic technologies.

Bringing these new techniques into use will require us to deal with the same set of drivers and constraints as apply to other diagnostics. Health systems and payors should be seeking out technologies that have the potential to bring the best care to patients. Payors need to seek out value, and assess candidate technologies aggressively. And then, payors need to reimburse proven tests appropriately.

Cost should not be a barrier to advancing diagnostics, because the cost of these kinds of tests relative to the cost of the decisions they influence is very, very modest. Diagnostics actually help to ensure that the rest of the healthcare dollars are allocated effectively.

CLP: Overall, how important do you consider in vitro diagnostics for advancing the goals of the National Cancer Moonshot? Is there a need to address a seeming underemphasis on diagnostics in this effort?

Fish: Although there is an inherent tendency for diagnostics to be overlooked, we certainly hope that in the end the National Cancer Moonshot will not suffer from an underemphasis on diagnostics. It’s understandable that when people think about cancer care, their first thoughts are about treatments and cures. But such an approach obscures the fact that there is no cure without an understanding of the disease, and it is diagnostic tests that provide that understanding for any given patient.

Diagnostic tests are also essential for developing new therapies. You can’t run a clinical trial on a drug therapy without having an appropriate diagnostic to determine which patients are appropriate for the drug being tested. Diagnostics are an essential cornerstone of everything that’s going to be happening under the National Cancer Moonshot. We’re simply looking for that to be appreciated and to be advanced as quickly as possible.

CLP: The National Cancer Moonshot is not the only such initiative that’s been announced. NantWorks’ founder, Patrick Soon-Shiong, MD, has announced a similar initiative, and Napster’s Sean Parker recently announced a $250 million donation to support immunotherapy research to fight cancer. How do you see these and similar initiatives relating to the national effort?

Fish: It is a good thing to have more interest and more investment. One of the emphases of the National Cancer Moonshot is to make the best use of our dollars, whether they’re public or private, by ensuring collaboration and datasharing. The relations of other initiatives to the national effort will probably come mostly through datasharing.

The research community has not traditionally shared data as much as it might, because research data is the stock in trade of researchers. But significant efforts are being undertaken to encourage researchers to share data earlier and more readily for the benefit of all. Such an emphasis on sharing the information that’s being generated is one of the common threads among all of these recent cancer initiatives. So this really is an increasingly collective effort to advance cancer care.

CLP: Datasharing is one of seven areas for which the National Cancer Moonshot’s blue ribbon panel has asked for public input and guidance. The other six areas did not include any with a direct relation to cancer diagnostics. Are you surprised at that?

Fish: I’m not surprised because of the longstanding challenges that diagnostics have had to be recognized as being in the forefront of the cancer fight. Our efforts will certainly continue to be focused on ensuring that diagnostics are fully leveraged.

CLP: Do you think there is a need for an initiative focused exclusively on in vitro diagnostics for cancer?

Fish: I’m not sure there needs to be a standalone initiative. It’s more important that current initiatives, including the National Cancer Moonshot, simply include diagnostics appropriately and fully leverage diagnostics in the work that’s being undertaken.

CLP: Whatever their respective regulatory requirements may turn out to be, what do you see as the distinctive roles of laboratory-developed tests and commercial diagnostics for advancing the task force’s objectives?

Fish: There has been a longstanding debate about possible FDA regulation of laboratory-developed tests (LDTs), and it seems likely that this debate will continue for some time. As a trade association representing manufacturers of commercial diagnostics, we have argued that all tests should be handled under a unified regulatory approach that will ensure patient safety.

But we have also recognized, as has FDA, that LDTs do have an important role. They’re particularly important in academic medical research settings, where patients, doctors, and laboratorians in a single institution can coordinate their use of LDTs to gather information that might not be available yet from tests that have received FDA approval.

But since the quality of information generated by such tests can be uncertain, and since it may be necessary to place limitations on how that information might be used, it’s important that LDTs be utilized only in settings where patient risks can be controlled. Those risks can be reduced in academic medical research settings, where healthcare is taking place in a very coordinated fashion in a single institution.

There will no doubt be some ongoing concerns about LDTs. Patient groups have expressed concern about the use of LDTs to provide information about patients who are somewhere other than the laboratory that is performing the test. And laboratories that are marketing tests without FDA approval to a national audience will continue to raise concerns.

CLP: What are the expectations and prospects for success of the National Cancer Moonshot, and what do you see as the timeframe for its efforts?

Fish: We’re in the late days of the second Obama administration. All of us who want to see the National Cancer Moonshot succeed would like to see some kind of institutional framework put in place so that the effort can be carried over into the administration of the incoming president.

With regard to the prospects for success, I’m not sure that the National Cancer Moonshot has identified concrete measures or timeframes in which it would measure its success. However, I think we can look for directional success through closer collaboration, additional funding, and the acceleration of basic research into diagnostic development, drug development, and appropriate care.

CLP: Does FDA have a role to play in advancing new diagnostic technologies in support of the National Cancer Moonshot?

Fish: Historically, it has been something of a challenge for FDA to put into place efficient regulatory reviews for fast-developing and new technologies. However, we’re very pleased that FDA is working to be flexible in the way that it thinks about new diagnostic technologies, particularly in the molecular diagnostics area.

For example, the agency has been focusing on how to provide effective review of NGS technologies. It has signaled that it will offer a lot of flexibility in the approval of various NGS platforms for diagnostic applications, without requiring simultaneous approval of a specific test to be used on those platforms.

We’re heartened by that approach. We hope FDA will extend that kind of flexibility to other diagnostic platform technologies, allowing those technologies to be more widely distributed with an FDA assurance of analytical quality. We’re looking forward to continued work with FDA to make these kinds of improvements.

Steve Halasey is chief editor of CLP.


  1. Letter to Vice President Joe Biden on the National Cancer Moonshot and the role of technology in cancer care. Washington, DC: AdvaMed, 2016. Available at: documents/the gray sheet/42/14/advamed final cancer moonshot letter 33116.pdf. Accessed May 6, 2016.