Using ctDNA for prognosis and monitoring
Volume 8, Issue 8 | August 2, 2023
In This Issue
First DTC blood test for Alzheimer’s is on the market
Big step toward diagnosing dementia before symptoms
Free COVID tests for everyone again? Not yet
How to decrease antibiotic use in Staph infections
New and Noteworthy
Circulating tumor DNA valuable for prognosis and management
A recent review in Nature strongly supports the use of repeated testing for circulating tumor DNA (ctDNA) both for prognosis and when monitoring for the recurrence of solid tumors. The figure shown here exemplifies the test’s value in determining prognosis: It’s the recurrence-free timeline difference for one panel used prior to surgery, covering ~500 cases across four different early-stage tumor types (breast, lung, renal and bladder).
The article is thorough and nuanced, with important implications for both patients and physicians. For this test, sensitivity and specificity vary across a wide variety of parameters: test vendor, tumor type, tumor size, tissue, histological subtype, grade, and lymph-node involvement.
You don’t need to ask your doctor before getting tested for Alzheimer’s
Two powerful trends in diagnostics (direct-to-consumer testing and Alzheimer’s diagnostics) came together this week with the roll-out of the first consumer-initiated blood test for Alzheimer’s disease. Quest’s AD-Detect is a blood-based test to evaluate levels of amyloid beta proteins, and while it’s being marketed to consumers, it’s not an at-home test. Folks who want to get tested must have their blood drawn by a phlebotomist and sent to Quest for analysis and results. (For more on research into biomarkers for even earlier AD detection, see our Food for Thought section below.)
Commentary: As we have discussed throughout this summer, we expect to see an increasing number of AD tests that are increasingly non-invasive as well as increasing use of direct-to-consumer tests.
For Alzheimer’s, there now are and will continue to be tests for use in two different situations. An overly simplistic summary: 1) Early detection of AD for those with few or no symptoms, and 2) Differential diagnosis among other neurodegenerative diseases for those with symptoms.
Free COVID tests for everyone coming back? Don’t hold your breath.
When the federal COVID public health emergency ended on May 11, the government lost its power to require insurers to provide free COVID tests to beneficiaries. The US Preventive Services Task Force is now exploring the possibility of reinstating that requirement under a different source of federal power: the Affordable Care Act.
As STAT News reported, “Under the Affordable Care Act, insurers are required to cover tests, screening, and other preventive medicines like HIV PrEP drugs that the task force strongly recommends.” So in theory, if the group gives COVID tests the strong thumbs-up, COVID tests could be free again. Note that word “preventive,” however - it means that while the task force has the authority to require coverage of screening tests, requiring coverage of diagnostic tests might be a stretch. Most likely, this means that if they make a recommendation, it would be focused on asymptomatic persons.
But that could be the least of the task force’s worries, since a federal judge recently challenged the group’s authority to require anything. Since the task force is made up of volunteers who weren’t officially appointed by the HHS secretary, the judge argues that its existence violates the US Constitution’s appointment clause. That case is currently being considered by an appeals court. So it could be a while before we have an answer about those COVID tests. Cross your fingers.
Rapid testing + algorithm-based stewardship = decreased antibiotic use for Staph bacteremia
In a recent study, use of rapid testing alone wasn’t enough to decrease antibiotic use for Staph bacteremia - but adding algorithm-based antibiotic stewardship recommendations did the trick. The combination of rapid diagnostic testing with the algorithm-based recommendation led to a significant increase both in the percentage of patients who received antibiotics for less than 24 hours (from 33% to 54%) and in the percentage of cases in which patients received no antibiotics at all (from 15% to 28%). Critically, the mortality rate remained the same across interventions.
Commentary: Given the large and growing challenge on antibiotic resistance, any and all interventions that reduce antibiotic use safely are very much welcome.
Food for Thought
A big step toward the goal of diagnosing dementia before symptoms
An exceptional paper in last week’s Science Translational Medicine is a must-read for anyone who works in the field of neurodegenerative disease. The paper is unique in its duration: The longitudinal study tracked 10,981 adults who were recruited back in 1987-89 through the ARIC program. Over the course of 25 years, the authors monitored the levels of 4,877 plasma proteins in these volunteers, searching for those associated with dementia onset.
A handful of proteins were associated with risk of developing dementia up to 25 years later. Proteins involved in two processes were particularly elevated long before symptoms appeared: immune / inflammatory proteins and proteins involved in protecting the brain from excessive protein production (aka maintaining proteostasis). As the authors note, these compounds can now become targets for diagnostics that could finally identify at-risk individuals well before brain damage happens. They can also be used as the starting point in discovering causal pathways that early intervention therapies could interrupt.
Commentary: Although this paper uses its data to find early patterns that are unique to later dementia development, it is much harder to go in the other direction because these processes are invoked for many non-dementia reasons, too. Positive and negative predictive value will be the acid test of diagnostic utility.
Quick Hits
Researchers in Australia have developed models that can predict COVID hospitalization levels up to four weeks in advance, using wastewater data. They used US county-level wastewater surveillance data from June 2021 to January 2023 to develop the model.
The Biden administration has formed a new office dedicated to Long COVID at HHS. The office will coordinate government efforts, including NIH’s $1+ billion RECOVER initiative focused on Long COVID research and practice. (While not strictly diagnostics-related, we wanted to share.)
EUA Update
The FDA issued one new 510(k) premarket notification, two new EUAs, eight amendments to existing EUAs, and one revocation in July. Data is available at TestingCommons.com
510(k) Premarket Notifications (1):
New EUAs (2):
COVID Molecular (1): Alphadera Labs ALPHADx SARS-COV-2 RT-PCR Test
COVID Antigen (1): Immunostics Inc. Swab-N-Go Home Test COVID-19 Ag
Amendments to Existing EUA’s (8):
COVID Molecular: 4
COVID Collection Kits: 0
COVID Antigen: 2
Respiratory multiplex (COVID and Flu): 2
Revocations (1):
Of note - We have received several comments expressing surprise that the FDA is still issuing EUAs for COVID tests given that the federal Public Health Emergency for COVID (PHE) ended on May 11, 2023. Why? An FDA “EUA Declaration” (which is authorized by Section 564 of the Food, Drug and Cosmetics Act and allows FDA to issue EUAs) is separate and distinct from a federal PHE declaration (which is authorized by section 319 of the Public Health Service Act). EUAs can continue to be issued until the relevant EUA declaration is ended. The FDA issued four EUA declarations related to different product categories in 2020. They have since pledged to give 180 days notice before ending these declarations. Once an EUA declaration is ended, product EUAs cease to be in effect. In order to do that, the FDA has already issued guidance for labs and test manufacturers to transition their diagnostics to full FDA marketing approval.