In This Issue
Can worms detect cancer?
Which tests are driving the growth in molecular diagnostics?
The case for adding ApoB to cholesterol panels
New and Noteworthy
Dogs can detect COVID-19, but can worms or ants detect cancer?
Several studies have confirmed that dogs can detect COVID infections with high accuracy. Ok, fine - dogs have an extraordinary sense of smell, and we know how to train them. But worms? Ants?
A Japanese company recently launched a $100 cancer test based on a 2015 study that demonstrated that nematode worms (C. elegans) are attracted to cancer patients’ urine, with 96% sensitivity and 95% specificity. Nature recently reported widespread skepticism and conflicting results among early adopting Japanese oncologists. The company has responded to these criticisms by directing naysayers to an analysis they’ve written, but unfortunately for us, it’s only available in Japanese.
Commentary: As readers of Ed Yong’s prize-winning book on animal senses will know, nearly all animals have at least some capabilities far beyond our own. In addition to worms, ants have also demonstrated the ability to discriminate between healthy and cancer urine. That said, we’re not convinced that either ants or worms are going to be the next big thing in cancer detection.
Molecular diagnostics growth strong - here’s what’s driving it
Concert Genetics (CG) has published its 2023 Genetic Test Price Transparency Report, covering 10.4 million allowed claims made by 44.6 million commercially insured individuals from 2018-22. Molecular (i.e., DNA/RNA-related) diagnostics have been the fastest-growing segment within clinical diagnostics for two decades, and the momentum continues without signs of abating. Overall spending per member per year grew 73% from 2018 to 2022 at a steady annual rate of 14.7%, with nearly all coming from increased usage.
Looking at just the CG top 20 tests:
The most expensive test is whole-exome sequencing (WES; median price is $9,545 but highly variable). It appears that most of these tests are being done in infants and young children.
Of infants tested in the NICU, where use of WES is still rare, an average of 36% had a genetic disorder (this percentage excludes neonates with straightforward diagnoses). Most of those results generated important changes in care (based on 31 studies reviewed here). It is likely that usage will rise and prices come down as these tests become more standard in pediatrics.Tests that determine carrier status for families with a possible history of genetic disorders comprise six of the CG top 20. In aggregate, they still make up the highest area of spending today.
Half of these tests are multi-gene/multi-disease panels (these are growing fastest); the remainder are single-gene tests: BRCA, cystic fibrosis, and Lynch syndrome. Prices range from about $600 for a common heritable disorder panel (sickle cell; cystic fibrosis; fragile X; spinal muscular atrophy) to three times as much for the others.Not surprisingly, the two individual tests that drive the most spending are also among the cheapest: molecular fecal testing (a less-invasive, lower-cost screen for colorectal cancer than colonoscopy) and non-invasive prenatal testing (NIPT). Both tests have become standard of care, with steady spending growth at flat to declining prices (~$500-650).
Molecular testing involving cancer has six separate entries in the CG top 20 - and since this report covers only spending on younger, healthier, commercially insured under-65s, spending on these tests is underestimated. Medicare is not included.
Tissue-specific solid-tumor profiling with high clinical utility drives higher pricing (~$2,500 to $5,000). This includes breast at #5, thyroid at #6, prostate at #14, and melanoma at #16.
Pan-cancer gene testing (51 or more genes) is generally priced lower than tissue-specific tests. When biopsy is available, this type of analysis may identify druggable mutations (#8). If no tissue is available, cell-free circulating tumor DNA from a blood draw can be used for screening healthy patients and/or monitoring for recurrence (#12).
Commentary: We are strong believers that all relevant information is valuable to patients and their physicians even when the clinical consequences are not immediately obvious. However, we still believe that pan-cancer early detection technologies in healthy patients have uncertain clinical benefit.
Food for Thought
Diagnostic errors – why so many, why so persistent?
JAMA Internal Medicine just released a comprehensive report on diagnostic errors “in adult patients who are transferred to the intensive care unit (ICU) or die in the hospital” (i.e., emergency-department and direct-to-ICU admissions were excluded). The study covered 29 academic medical centers and looked at 2,428 cases, randomly selected from the 24,591 that met the criteria for inclusion. It subdivided diagnostic errors into nine stages of the care pathway: Access; History; Physical Exam; Testing; Monitoring; Consultation; Teamwork; Communication; and Assessment.
The results aren’t pretty.
23% of patents suffered a diagnostic error. Of those:
22% caused no harm.
35% caused fixable harms.
12% caused permanent harm.
30% were potentially fatal, and of this group, 77% died.
Of patients transferred to ICU, 38% of those with Dx errors died, versus 31% of the error-free.
#1 Dx error: Recognizing sepsis too late to successfully treat.
#2 Dx error: Recognizing stroke.
Not testing where appropriate, was the largest single driver, comprising 34% of the errors.
Commentary: It is a tragedy that academic centers, who are typically the best at diagnosis and treatment, are failing these patients. We believe that inadequate physician knowledge of, experience with, and education about modern diagnostic techniques is the leading cause of patient-harming medical errors. What to do?
- Medical schools must find space in the curriculum to teach current diagnostic technologies and how they need to be integrated in different pathways of care.
- Diagnostics must also be a larger and more important component of Continuing Medical Education (CME) because diagnostic technologies are more sophisticated and informative every year and practicing physicians need to be up to date.
And, the challenge that these centers face is growing, as admitted patients become more complex. A recent study done in Canada reported that over the past 15 years, average hospital inpatient age has risen from 61 to 64, and these patients had increasing numbers of co-morbidities (2.4, up from 2.0) and more routine meds (4.7, up from 3.8). Managing these patients can be really hard - and it’s getting harder.
Why add ApoB to standard cholesterol panels?
This week the Washington Post summarized the strong argument for adding apolipoprotein B (ApoB100) testing to standard cholesterol panels. The primary reason for the change: The traditional LDL test measures the total amount of “bad” cholesterol in circulation, but risk of disease is higher if any given level of LDL is carried by more, smaller particles. Since each particle has one (and only one) ApoB molecule attached, counting these is a better indicator of disease risk - especially in younger at-risk patients.
Commentary: Decreased cardiovascular mortality has been a major success story, with deaths in 2020 half what they were in 1960 (27% of all-cause deaths versus 54% then). Nevertheless, heart disease is still the number-one cause of death in the US and worldwide. Adding ApoB to the standard cholesterol test would be especially valuable in the under-65 population, where cardiovascular disease drives as many years of life lost as cancer (about 10% each).
Quick Hits
Can your bra or boxers take your blood pressure? Not yet - but an “undergarment” that can monitor your blood pressure did just get FDA approval. It wraps around your torso and goes over one shoulder. Let us know when it comes out in hot pink.
Speaking of undergarments, the FDA also approved the first test to use menstrual blood as a diagnostic specimen. The test, Q-Pad A1c, measures hemoglobin A1c in patients with diabetes. We liked the company’s tagline about menstrual blood: “It still has the ‘ick’ factor. But it's actually a superpower.”