April 2014—It can be hard to remember a time when GPS was not available in cars, the Web didn’t exist, and only eight diagnostic tests were classified as waived and able to be performed at the point of care. But after CLIA’s enactment in 1988, those were some basic realities of location and speed.
Today, whether for blood gas and electrolytes, glucose, coagulation, cardiac markers, drugs of abuse, food pathogens, hemoglobin, or infectious diseases, hundreds of tests once considered too complex for point of care are routinely performed outside the laboratory. But some of the nation’s experts in point-of-care testing say that developments on the near horizon could make previous advances in POC testing look tame.
“A number of tests are on the cusp of being available at point of care, from the realm of infectious disease biomarkers, all the way up to PCR and molecular testing right at the bedside,” says Timothy R. Hamill, MD, vice chair of the CAP Point-of-Care Testing Committee. Wearable biosensors and lab tests on a chip are no longer just the stuff of science fiction, says Dr. Hamill, who is director of clinical laboratories at the University of California, San Francisco. “It’s amazing technology and it’s going to bring a real revolution.”
“Ten years ago, people would have said, yeah, maybe when we’re flying around in spaceships that’ll happen. But it’s here. And where it will go will be really interesting to see.”
It’s not only technology that’s pushing POC testing in new directions. Research findings, new regulatory scrutiny, and economic and business imperatives are powering point-of-care testing to carve out a new niche within the health care system. In conversations with CAP TODAY, pathologists and others all agree that it will continue to diversify and mushroom. From differing perspectives, they report on how government and industry initiatives are combining with research and clinical practice to steer POC testing into its next era.
“We’ve got competing pressure points on POC testing,” Dr. Hamill says. “One is a desire to get a quick, reliable answer immediately so a provider can make a treatment decision on a patient. Second, that laboratory test is probably more expensive than what we can do in the clinical lab. Everyone’s looking at cost containment these days, so the cost of testing in the inpatient arena is being scrutinized. In the outpatient setting, the question is: Can we get reimbursed for a POC test? And is a lack of reimbursement sufficient to say we shouldn’t use it?”
“Third, there is the ever increasing level of regulatory scrutiny on POC testing, particularly when it comes to provider-performed tests. It used to be the doctor could run any kind of test. Now pretty much everything has regulations wrapped around it—competency evaluations are an example. I think it is appropriate, but all of this weighs against the potential benefits of having rapid POC testing at the bedside.”
Quick answers on possible infectious diseases are a chronic need, but there are always tradeoffs to take into account. For instance, a POC test for methicillin-resistant Staphylococcus aureus is in the regulatory pipeline and will be a significant step forward in identifying infections with these organisms, but Dr. Hamill does not believe it would change the way patients are screened for MRSA carriage. “Although potentially quicker, the cost will likely be an issue,” he says, and the MRSA culture his hospital can do in the clinical lab probably has a fast enough turnaround already.
“Other things like rapid tests for viral pathogens and/or diagnosing ventilator-associated pneumonia may be viewed as more important to clinicians than screening for MRSA carriers. Similarly, in the case of a patient with possible sepsis, being able to do a quick test to find out if it looks like gram-positive or gram-negative bacteria would let clinicians start an empiric therapy right away while they’re waiting for a test to be done in the lab on a MALDI-TOF or one of the other newer bacterial identification systems.”
More POC testing that helps reduce antimicrobial resistance would be a boon, Dr. Hamill believes. With the right POC device, “You could test at the bedside, find out the nature of the causative bacteria, and perhaps learn something about its susceptibility patterns based on the test result. Then you would know how to structure your antibiotic therapy right from the get-go, and not expose it to that heavyweight drug that we really need to reserve for that organism that’s really resistant.” Such a device isn’t available at the point of care yet, but with MALDI-TOF mass spectrometry in the central laboratory, answers that used to take 24 to 36 hours can now get out in a few hours, helping hospitals with antibiotic stewardship.
Molecular testing at the point of care is promising, Dr. Hamill says, but it will take some time. “I think when the FDA approves molecular tests at point of care, they will initially be either moderate or high complexity, and at least from the institutions I’ve reviewed as a CAP inspector, no one is going to do high-complexity tests at point of care. For example, here in California, because of our regulations regarding who can perform high-complexity testing, if I tried to roll out a POC test that only licensed clinical laboratory scientists or physicians could perform, it would be very hard. Certainly in inpatient care and probably the physician office, it’s eventually going to happen, but I don’t know when.”
Also likely in time, he says: Glucose, sodium, serum chemistry, and chloride testing will be done by biosensor or new POC technology, and samples for such testing will no longer be sent to the clinical lab. That means the laboratory will be moving on to testing more esoteric biomolecules, hormones, drugs, and other analytes that still aren’t available as a POC-type test, Dr. Hamill predicts. “With point-of-care testing, I think we’ll be amazed by what happens in five years. And we’ll be stupefied at what we’ll be able to do in 10 years.”
One factor that has kept POC testing on the leading edge technologically is that it has drawn major investment from the Pentagon through DARPA, the Defense Advanced Research Projects Agency, which is funding companies like Ceres Nanosciences, Tasso, and Biomatrica to work on biospecimen collection and preservation. Tasso, for example, has a DARPA grant to develop a wearable blood draw device that collects a 200-µL blood draw with a microfluidic platform, while Ceres has invented Nanotrap technology to better capture low-abundance protein biomarkers and protect them from degradation.
Under a contract with DARPA’s Autonomous Diagnostics to Enable Prevention and Therapeutics (ADEPT): Diagnostics on Demand program, Biomatrica is developing technology to solve biostability problems. DARPA describes ADEPT as seeking to “provide Soldiers, Sailors, Airmen, and Marines actionable information about their health, on demand, by developing…diagnostics that can be carried on-person and self-administered, coupled with formats suitable for preservation of self-collected biospecimens for later expanded testing.”
“We are funding both chemistries that you add to a specimen to preserve it without culturing, and materials that blood would bind to or be absorbed in to protect it from degradation,” says Lt Col Daniel Wattendorf, MD, program manager at DARPA. “On top of that, we have two strategies: one where you draw a specimen into the preservation device for immediate analyses, and the second where samples may be archived for future analyses.” The specimen preservation formats for immediate analyses allow the sample to be shipped to the lab and used directly in instruments in the reference lab with few changes. Processes similar to a filter paper card are useful in archival settings such as newborn screening, he explains.
“The Department of Defense is interested in these technologies because it has more than 9 million beneficiaries, with most of our practice either on home soil or in clinics throughout the world,” Dr. Wattendorf says. “We care about emerging threats, such as an influenza pandemic, as well as engineered threats, such as someone engineering a biological organism in a purposeful way to cause harm, and antimicrobial resistance. These are all major challenges to DOD and national security. We think that existing infectious diseases that are highly transmissible need rapid testing performed as locally as possible. But we want to ensure that when they’re performed, wherever they are globally, they are performed within the health care infrastructure.”
The traditional concept has been that the battlefield is a proving ground for what later often become domestic uses. But DOD’s strategy with POC testing is in some ways the reverse of that. “We want to develop diagnostic systems that work for unmet needs in the U.S. health care system; otherwise they will not be adopted and used when there is an engineered threat,” Dr. Wattendorf says. “If we do not have PCR systems in doctors’ offices, how are we ever going to be able to perform a local test for a new threat that develops? We need to get these platforms out and used in more distributed ways before we can think about assays for new threats on the horizon.”
The major challenge is showing the utility of a diagnostic test performed in a distributed place—meaning outside the clinical lab, in a home or office—where the test is linked back to the reference lab. “What we need is the ‘killer app’ for that. For most of the diagnostics industry, it’s not within their business model to sell instruments to the doctors’ office. We’re trying out a model where the reference lab would lease these devices to doctors’ offices, and if the doctor orders a respiratory pathogen panel, the test then gets sent with CPT codes into the laboratory system. The device would still be part of the reference lab; it just won’t be located within the brick and mortar of the reference lab.”
This DOD strategy could aptly be called a hybrid between POC and central lab testing. “To me, POC testing means a standalone test where the result is often outside of a qualified lab setting and doesn’t really enter into the laboratory information management system.” But when instruments are in different settings, Dr. Wattendorf points out, “you have no way of tracking the analytics of the device and its performance in a continuous fashion.” The DOD has in mind not just connectivity of results but also quality assurance of the instruments that can perform complex testing, including high-performance molecular diagnostics, he says.
“We’d like a future diagnostics business where a centralized lab performs most tests. But when turnaround time is a necessity for clinical action—for example, to test a respiratory pathogen for an infectious disease—you want the ability to perform that test as locally as possible. We are hoping that many tests, for everything from serology to proteomic assays to molecular diagnostics, could be performed this way if you are able to assure the quality of the test.”