By Tom Hubbard, Vice President of Policy Research, NEHI
An emerging class of blood-based screening tests known as multi-cancer early detection (MCED) tests may transform cancer care profoundly in the years ahead. MCED screening tests are intended to detect indications of cancer from DNA and other analytes shed by tumors into the bloodstream. MCED analysis enables preliminary identification of multiple types of cancers, including cancers such as breast, colon and lung cancer - where the MCED is a complement to the current standard of care screening (mammography, colonoscopy, and lung cancer CT scanning) - and the dozens of cancer types that are not routinely screened among patients today. In both scenarios, MCED tests may enable detection of cancers that often are not diagnosed, and therefore treated, until they reach later stages of progression.
At present the two leading products in this new category of cancer tests are from two NEHI member organizations, Thrive (now a unit of Exact Sciences, Inc.), and Grail LLC. Other multi-cancer early detection tests are expected to arrive in the years ahead, as these and other companies leverage innovations in assay technology, and artificial intelligence to develop and refine MCED tests.
The oncoming availability of blood tests for cancer screening raise important questions for patients, clinicians, and health care payers alike.
- Cancer screening is intended for asymptomatic patients (i.e., patients who present with no apparent signs of cancer.) How will patients who are apparently cancer-free react to findings from MCED tests?
- How will MCED findings influence the way physicians counsel patients on their risks of cancer, and how will it influence their use of other cancer diagnostic tests, including diagnostic imaging and intrusive methods such as surgical biopsies?
- How will payers evaluate the impact of MCED screening on patient outcomes and the cost of follow-up diagnostic testing needed to confirm that a positive MCED test result is true (a true positive) or not true (a false positive)?
In February Grail and Point32Health, a NEHI member organization, announced an important step towards finding answers to these questions.
Point32Health is the recently formed health insurance company that combines Tufts Health Plan and Harvard Pilgrim Health Care to serve subscribers in New England. In collaboration with Grail, Point32Health will launch a two-phase pilot project with Grail’s Galleri MCED test. In the first phase, Point32Health will offer Galleri to its employees, subject to certain eligibility criteria, including age and family history of cancer. In a second phase, Point32Health will collaborate with a provider group that serves Point32Health commercial members by offering subscribers access to the Galleri test. Real world evidence will be collected to assess the impact of the test on health care utilization and on patient-reported outcomes.
Point32Health is the first commercial health plan in the U.S. to collaborate on a demonstration of MCED technology, a technology that Point32Health CEO Cain Hayes noted could be “game changing” in its impact on detection of cancers at early stages when the odds of successful treatment are highest. In subsequent comments to members of the NEHI board of directors, Dr. Michael Sherman, Chief Medical Officer of Point32Health (and a NEHI director himself) explained the significance of the Point32Health-Grail collaboration: the pilot project will generate critically needed findings on the real-world impact of a technology that produces information never available to patients and clinicians before now. Real world evidence from sound studies and innovative clinical trials will be especially important in demonstrating the effectiveness of MCED tests, since MCED tests currently in development are designed to detect dozens of low-prevalence cancers. Traditional clinical trials to demonstrate the effectiveness of screening for these low prevalence cancers would require extremely large recruitment of asymptomatic patients, prolonged trials, or both, resulting in significant delays in the launch of MCED tests for use by patients and clinicians.
Grail markets Galleri as a laboratory-developed test (LDT) in compliance with the Clinical Laboratory Improvement Amendments (CLIA) of 1988. Test developers also expect to seek review and approval of MCED tests as devices regulated by the U.S. Food and Drug Administration, a step that could lead eventually to widespread adoption of MCED screening as an essential preventive health measure.
Up to now, all cancer screening tests submitted to the FDA for review have been tests to detect single forms of cancer. The advent of multi-cancer screening poses a new challenge for the FDA, which is responsible for approving the safe and effective use of medical devices based on an assessment of benefits and risks to patients. A NEHI white paper on MCED screening tests, also released in February, underscores the need for adapting the current FDA framework for assessing medical devices to accommodate the complexity and unprecedented capabilities of MCED tests designed for use in cancer screening.
The NEHI paper (“Multi-Cancer Early Detection Tests for Cancer Screening: A Call for Consensus on Benefit-Risk Assessment”) is based on consultation with an expert panel that met over a period of months in 2020 and 2021. The paper recommends assessment of MCED tests across several categories of patient benefit and risk, including the impact of MCED testing on diagnosis of low-prevalence cancers that typically are not detected among individual patients until late stages, and the impact on detection of all cancers among adults screened with the tests, (a change in the overall cancer detection rate, or CDR).
The paper also calls for an expedited effort to develop consensus in the oncology and regulatory communities on how MCED benefits and risks should be weighed against each other when benefits and risks are defined by the potential detection of one of many cancer types, including cancers which have never been screened in the past. A few over-arching principles of assessment seem clear, such as demonstration in clinical trials and in other forms of evidence that MCED tests perform at a high level of test specificity (that is, a low rate of false positive findings), a principle that test developers have embraced.
Consensus is still needed to address other issues of benefit and risk. For example: how will MCED testing influence patient compliance with existing, recommended non-MCED forms of cancer screening? MCED tests now in development are tests that can be completed with a blood sample that most patients give while visiting a doctor for an annual physical. Will the convenience of the MCED make patients more likely or less likely to follow through with appointments for other recommended cancer screenings, such as mammography and colonoscopy?
The Point32Health collaboration with Grail is a pioneering approach to demonstrating results from a highly innovative use of technology that also poses complex issues for resolution by clinicians, payers, and patients. Equally innovative approaches are needed for FDA assessment so that MCED tests will be adopted at scale and, like advances in molecular diagnostics and targeted cancer therapies, will create more personalized and effective cancer care in coming years. We encourage NEHI members and friends to alert us to other highly innovative collaborations that NEHI members are devising to address cancer and other complex issues in U.S. health care.
