By Allison Proffitt
August 23, 2017 | Over 1,000 diagnostics professionals converged in D.C. last week for a pre-eclipse exploration of diagnostics technologies and challenges including point-of-care diagnostics, clinical NGS, circulating tumor cells, biomarkers, coverage and reimbursement, and companion diagnostics at the Next Generation Dx Summit*. With six content tracks and an exhibit hall full of technologies and news, I wasn’t able to cover nearly all that I wanted to, but here are some of the highlights from my time in the session rooms.
Colleen Kraft, an associate professor of pathology and laboratory medicine at Emory University School of Medicine broke down what a diagnostic test needs to be. The criteria are simple. Tests should be disruptive: they should fundamentally change the way we do something. They should be inexpensive. Next-generation sequencing isn’t yet inexpensive, but it’s certainly getting there, she said. They should be iterative. And tests should be clinically actionable. At the end of the day, Kraft said, she wants a “yes,” “no,” or “maybe” response from a test. Anything more complicated than that, degrades clinical action.
Marilynn Larson from the University of Nebraska Medical Center has been using Oxford Nanopore’s MinION device to track emerging infectious diseases. She’s been doing base calling using the Metrichor software in the cloud, and using the Metrovar software on computers or in the cloud for multiple MinION devices. The platform’s weak link is definitely sample prep, Larson said, but she was positive about the promise in general. She envisioned attaching MinION devices to drones to sample for airborne pathogens.
You Li, a scientific reviewer in the Division of Molecular Genetics and Pathology at FDA, outlined the differences in reviewing NGS tests versus earlier types of tests. Before NGS, most tests were looking for a single biomarker, Li said. NGS tests don’t work that way.
Since December 2016, FDA has approved the first three NGS companion diagnostics: the CDxBRCA Assay from Foundation Medicine; Thermo Fisher’s Oncomine Dx Target Test; and Illumina’s Praxis Extended RAS Panel. The Illumina panel was the first companion diagnostic approval based on a “negative” mutation finding, Li pointed out.
Li didn’t outline the data each company provided during his presentation, instead directing those who were interested to the published Summary of Safety and Effectiveness Data forms for each device approval (SSED, linked above for each test). But he did highlight three points that have proven challenging for NGS test submissions.
In vitro diagnostic developers tend to want a broad claim, he said, but he warned against trying to validate all variants, calling it “impractical.” He also mentioned the limited availability of clinical specimens, unknowingly lending support to the Lung Cancer Consortium and similar efforts. Finally, he noted that for many tests, standard reference material or comparator methods are unavailable, a challenge that test makers must address.
Stop and Shop Healthcare
In a pair of talks from CVS Health, Alex Sbordone and Andrea Vastis presented almost competitive views of point-of-care testing. Sbordone, representing the CVS MinuteClinic, discussed point-of-care testing in a retail setting. Vastis, representing CVS’s retail pharmacies, discussed the pharmacist’s role in point-of-care testing.
CVS MinuteClinics already offer testing and routine healthcare across the country by nurse practitioners or physician assistants. Sbordone, senior advisor, operations, to MinuteClinic, discussed the MinuteClinic’s needs in test platform. The MinuteClinic experience is meant to about wholly contained, Sbordone explained. Test results must be ready during the visit, and patients don’t generally wait around for slow tests. Ideally, Sbordone said, test results would be returned within 10-20 minutes.
Space is another concern. MinuteClinic exam rooms are usually about 10ft by 10ft, he said. Within that space is a work station, an exam table, cabinetry, and a chair or two. Any sort of testing instrument needs to be desktop at least, Sbordone said. Refrigeration space is limited, and much will be dedicated to immunizations, so materials that can be kept at room temperature are preferred.
MinuteClinic has been offering patient care since 2000 within CVS locations, so it may seem that training pharmacists to deliver similar care would be cannibalizing the company’s own business. But while there are 1,100 MinuteClinic locations across 33 states, there are 9,600 CVS pharmacies located in 49 states. There is significant opportunity for pharmacist-delivered care.
CVS believes that pharmacists can and should be a more integral part of the healthcare system, said Andrea Vastis, senior manager of Patient Care Programs. There are a host of tests and services that pharmacists are already trained and equipped to offer: monitor blood pressure and blood sugar, prescribe hormonal birth control, flu and strep tests, immunizations, and prescribing authority for some medications like travel medications or treatments for poison ivy or pink eye.
“We want to establish the pharmacy as a place for medical care, not just as an adjunct facility,” Vastis said.
California has already given pharmacists prescribing authority for hormonal birth control in what Vastis called, “such a win”. CVS invested in pharmacist training and role play to equip the pharmacist to clinically assess birth control needs. The service is an improvement for both patients and the healthcare system, Vastis said. CVS charges a $25 annual consult fee. If you’re prescribed an option that doesn’t work well for you, there’s no fee for any follow up visits to re-evaluate options.
CVS began piloting flu and strep care testing in Michigan this August. To launch the pilot program, CVS invested in 12 hours of online training and 8 hours of live training for all pharmacy staff. In a 24-hour facility, every staff member must be trained, Vastis said. Facilites that offer the testing, will offer it during all business hours. CVS picked Michigan for the pilot because Michigan is moving toward certification for even pharmacy techs, allowing them to participate in some patient intake processes.
The pharmacists partnered with CVS MinuteClinic nurse practitioners for the training. Although PharmD programs are equipping students with clinical skills and a clinical focus, Vastis admitted that testing—throat swabs, nose swabs, palpating lymph nodes—can sometimes take them out of their comfort zones.
Of course Vastis didn’t argue that the pharmacy is the right location for all testing. While flu or strep testing is an easy fit, she said, HIV and hepatitis C testing is more challenging. The retail pharmacy doesn’t typically have the space or time for the counseling needed after a positive result, she said.
Research to Clinical Spectrum
Matthew Lebo, director of bioinformatics at Brigham and Women’s Hospital, reported a large-scale secondary findings project and advocated for gene curation before testing. In otherwise healthy individuals, the goal is to minimize the variants requiring manual review, he said, calling it slow and expensive. We want to maximize the identification of reportable variants, he said.
During Brigham and Women’s BabySeq project, Lebo and the team identified 1,500 genes potentially involved in pediatric conditions. That was far too many to report on, especially when many were of unknown pathogenicity. We wanted things strongly associated with disease, Lebo said. Instead, the team pre-screened the list and came up with their own, curated list of genes on which to gather and return findings.
Returning findings is challenging, Lebo said. There are staff costs, time costs, and privacy issues. Returning research results is fairly straightforward, but any downstream testing moves the patient from research into the clinical realm and comes with clinical costs.
One change the Brigham and Women’s team made was to get CLIA certification for its biobank, which meant the team didn’t need to collect a second sample for further testing, saving time and money.
Lebo’s parting advice had to do with how results are collected. Giving a patient and physician a PDF report of sequencing findings is valuable, he said, but having the data in an EHR in a structured way is much more valuable.
*Next Generation Dx Summit; August 15-18, 2017; Washington D.C. The event was sponsored by Cambridge Healthtech Institute, the parent company of Diagnostics World News.