By Deborah Borfitz
September 21, 2020 | The FDA’s regulatory process for home-use tests, including Emergency Use Authorizations (EUAs), and concerns surrounding in-home sample collection, were the focus of a series of talks at the recent Next Generation Dx Summit. While increasing access to testing, particularly during a pandemic, home-use tests come with significant challenges that include fairly weighing the risks and benefits, points out conference speaker Elliot Cowan, principal and founder of Partners in Diagnostics.
The new reality in the context of a public health emergency is that “as risk goes up the time to clinical use has to go down since time is lives,” says Cowan. The FDA consequently requires less documentation showing benefits outweigh risks today than it did before the COVID-19 outbreak.
EUAs for new or unproven COVID-19 diagnostic tests are “not a back door into indefinite marketing,” he notes, because the products will need to go back through the conventional pathway (premarket approval or notification) once the pandemic is over. The first step is a pre-EUA submission, which prompts an interaction between the FDA and test manufacturer. The agency authorizes use of a product within days or weeks—versus the usual months or year—based on an EUA submission that requires validation testing, per revised COVID-19 policy guidance issued in May.
This was followed on July 29 with publication of a template for molecular- and antigen-based COVID-19 tests for non-lab use that “almost takes you by the hand [through] what is necessary to include in an EUA application,” continues Cowan. “You can cut-and-paste information into the template. It’s ordered, organized and clear.” It also doesn’t apply to serology tests, he adds.
Among the required information are what the test detects, its proposed intended use, a description of the device, how results get interpreted, how the product will be manufactured and distributed, mechanisms for reporting test results, performance evaluations (e.g., limits of detection, inclusivity of circulating subtypes), exclusivity (cross-reactivity and interference studies), and flex studies done to ensure the test’s resilience to human error, Cowan says.
A usability study needs to be done prior to clinical studies to identify any design issues, continues Cowan. The comparator method on clinical studies should be nasal swab or home collection, and a discrepant analysis (providing estimates of sensitivity and specificity) can be done. The studies need to include “all comers,” with at least 10 of the required 30 participants being asymptomatic.
Among his tips for EUA applicants: Be sure the test’s positive percent agreement is at least 90% and its negative percent agreement at least 95%, submit a complete EUA application, follow the FDA’s recommendations for analytical and clinical studies, be sure to meet performance requirements (they’re not being loosened), emphasize the test’s unique features, and “don’t make careless errors.”
Next up was Charlotte Gaydos, professor in the division of infectious diseases at Johns Hopkins University School of Medicine, discussing the I Want The Kit (IWTK) program offering internet-requested kits for the home collection of samples screened for common sexually transmitted infections (STIs). The program, which started in 2004 as an academic research project, is not a public sector collaboration, she says.
Prior to 2013, individuals would order a kit, mail in a sample via a prepaid envelope and get called with the results, she says. Since then, the process has involved logging into a website and selecting a clinic before ordering the kit designating where test results can be sent. Text notifications are sent out when samples are received and when test results are available. Reminders can also be sent if another test is needed. Detailed how-to-collect instructions are provided for each swab type.
To date, the IWTK program has done 9,000 genital swabs, 5,000 penile swabs, and 2,000 rectal and throat swabs, she says. HIV home testing kits (FDA-approved OraQuick, retailing for about $39), were also available free of charge to Baltimore residents until March when COVID-19 arrived.
Requests for STI test kits ballooned by over 500% during the pandemic, peaking at nearly 400 tests for the month of July, and the positivity rate also steadily increased to 5.8%, Gaydos says. HIV kit orders also increased.
An earlier research study found that user acceptability of the HIV kits was very high, based on ease of collection, clarity of instructions, trust in the process and willingness to recommend to others, says Gaydos. “Most people are willing to pay $20 or less.” Similar results emerged from acceptability testing of a point-of-care (POC) test for trichomoniasis, she adds.
Additional research via online acceptability surveys, data analysis and geo mapping has also found high user satisfaction with the IWTK program. “Users prefer genital [swabs] over urine collection and want options for other STIs … [including] dried blood spot testing for syphilis.” A 2016 study found the prevalence of any STI was a bit higher among males (9.5%) than females (8.7%).
The IWTK program includes a “risk quiz” that is now mandatory, Gaydos says. Positive predictive scores for having an STI didn’t reach statistical significance for men when the quiz was optional.
While vast numbers of home STI tests are commercially available, says Gaydos, they’re expensive and the FDA is not regulating their use.
The future for IWTK includes the addition of dried blood spot collection for syphilis and HIV (including viral load) testing, she says. “STIs are commonly detected via internet recruitment [of test-takers].”
Home Collection Concerns
Even before COVID-19, the FDA had started to crack down on tests involving home collection of samples sent to a central lab, says Cowan, who joined Gaydos for a panel session on POC diagnostics. “The lab where specimens are sent has been FDA-cleared but the specimens have to be collected and shipped and can get compromised in between.” The lab might also not be cleared to process a sample type (e.g., saliva) it’s being shipped. “There’s a lot of confusion out there.”
“COVID is why patient home collection is in the forefront,” says Gaydos. “It’s clear it works; it just has to be regulated.” She says the FDA needs to “step up” when clearing a test for home collection and start requiring validation studies where patients are actually doing the sample collection at home. That’s a study no company has ever done, she adds.
Panelist Jeanne Mumford, pathology manager for point-of-care testing for Johns Hopkins Medicine, says her experience with home collection has been mixed and she, too, would favor more regulatory involvement. But it doesn’t necessarily have to be the FDA but possibly the College of American Pathologists or the lab accreditation organization COLA.
Based on conversations with the Centers for Disease Control and Prevention, Cowan says, regulators will be putting greater emphasis on ensuring home use test have appropriate linkages to required care. Telemedicine applications could have a “big role” to play here. Interest is high in COVID-19 home testing as well as home use tests for the flu, especially among parents with children in the house.
Cowan encourages companies to produce an analysis for the FDA that looks at the benefits (e.g., limiting spread of infection) and risks (e.g., false- positive and false-negative results) of their diagnostic test.
In the case of flu, strep and STI home use tests, Gaydos notes, the benefits are likely to outweigh the risks. Flu and STI tests have both been shown to perform well despite temperature changes during shipping and when sample collection happens without a clinic nearby.
With flex testing, says Mumford, “you have to think outside the box. Any way you can imagine [users] will break [a device] they absolutely will.” It’s her preference to see standards across all home testing, at least when it is going to be done completely at home (e.g., pregnancy test), she adds.
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