How POC testing is pushing the envelope

An experience five years ago showed Dr. Campbell’s second law at work, when the VA in Connecticut made plans to do rapid HIV testing in primary care. “We got the tests in, got trained up, and had a full pile of clinicians ready to perform rapid HIV tests, and in the next four months they did exactly one test.”

“Nobody was doing it because these patients were being seen in an environment where followup was not that big a challenge, and it was not easier than checking off one more box on the lab order form and getting the results 20 minutes later with the other results you need anyway.” So while rapid HIV tests have made a substantial difference in diagnosing certain patient populations, “in our health care system they are not particularly useful.”

That’s one reason why he thinks the magical Star Trek tricorder, a science-fiction POC instrument that could theoretically replace the laboratory, is 50 years away or more. “There’s no good intermediate stage between doing one key analyte at point of care and doing everything the laboratory does.”

He points, too, to the constant QC struggle. Thus, his first law of POC testing: “Nobody ever went into nursing because they wanted to do lab tests.” “People do QC because they have to, not because they understand it or are dedicated to doing it,” he says.

When molecular tests are approved for performance at POC, Dr. Campbell says, the typical POC testing problems will be compounded because of the interferences. “Molecular tests are going to have to have internal extraction controls, and many tests can be inhibited by things like blood and excess DNA in the sample. So the internal controls to look at those things are going to be important.”

“Molecular tests are also particularly prone to contamination. If there are lots of patients walking through with the flu, they can be dropping droplets on surfaces, or the collection device, or the port of the instrument can cross-contaminate specimen A with specimen B. I think the current generation of molecular tests has a better handle on that, but it’s something you have to think about with waste disposal and getting rid of cartridges after the test is done.”

Bringing POC tests online involves a tricky metric of cost-effectiveness, Dr. Campbell points out. “The savings don’t come on the testing side; they come on the care side. And it’s really hard to know how much it’s worth to get one lab result 20 minutes sooner. Quantifying those savings is one of my challenges.”

He expects dramatic changes as the FDA starts to expand its authorization of waived tests. “But nothing happens as fast as you think it will.” Antibiotic susceptibility tests will be the very last to be available at POC, he predicts. “They are really, really complicated. At some point we’ll be able to do antibiotic susceptibility by sequencing bacterial genomes, but that’s quite a ways off. Maintaining a sequence database for HIV testing, with a couple dozen drugs and two main genes, is a small industry; it’s about three orders of magnitude harder for bacterial susceptibility testing, with some 50 to 100 antibiotic drugs and thousands of genes.”

National differences in economies, health care systems, and social environment will play a huge role in the future of POC testing, Dr. Campbell believes. For the developed world, it’s a question of choosing between fast and faster on many tests. But where POC testing will really make a difference is in the developing world, where lab order forms, nurses, refrigeration, power, and lights can be in scarce supply.

There, Dr. Campbell’s laws are less relevant and POC diagnostics are desperately needed, he says. “It’s one thing to have a central lab where you can pick up a test today and review it tomorrow. But where you have to put a sample on a truck that goes 50 miles over bad roads and you get the results next week, that’s where POC diagnostics will be extraordinarily important.”

In the regulatory arena, two recent developments indicate that the key federal agencies are planning more flexibility for some point-of-care devices in the area of quality control, but a lot less flexibility for the POC workhorse, the glucose meter.

At the Centers for Medicare and Medicaid Services, new guidelines for Individualized Quality Control Plans (IQCP) promise to ease some of the burden of QC without compromising it. “When CLIA developed, there were really no POC tests beside glucose meters and pregnancy tests, and there’s been an explosion of POC tests since CLIA,” says James H. Nichols, PhD, medical director of clinical chemistry and professor of pathology, microbiology, and immunology at Vanderbilt University School of Medicine.

“Originally, all manufacturers recommended you run daily QC, but with newer point of care, the tests have built-in QC processes,” Dr. Nichols explains. “So how do you balance the right amount of external liquid QC with the built-in QC? If you have a test you run only once a day, you might consume three cartridges for every patient you are testing, and for an expensive test like fetal fibronectin at $100 per test, that becomes very expensive.”

Since 2000, lab directors have had latitude to set their own equivalent, more economical alternatives. But now the CMS IQCP will add new options. “It will allow laboratory directors to dictate the frequency and how QC is going to be run across all the POC devices in their lab. It no longer dictates once a week QC for some tests, but allows you to set frequency based on your risk assessments. So it helps us really find the correct balance, to conduct QC on the key things that could go wrong.” The IQCP was formally adopted this January, starting a two-year education period before it becomes mandatory in January 2016.

Far more controversial is new proposed guidance from the FDA on hospital use of glucose meters. Released in January for a 90-day comment period, the proposal would drastically change current standards by making all glucose meters coming onto the market moderate complexity under CLIA, instead of waived. That means an increased education level for operators to perform the tests plus additional requirements in proficiency testing, training, quality assurance, and other areas.

The FDA’s move stems not from the technology but from complaints the agency has received, Dr. Nichols explains. One high-profile case involving a maltose interference led the FDA to send out warnings. Interferences such as oxygen and hematocrit have been known to affect glucose results, he says. The meters’ long-entrenched use for intensive insulin management in ICU patients has also been a factor in the FDA’s proposal, because the meters have never been tested for insulin protocols.

New York state has already incorporated the FDA proposal into its own regulations and sent a letter warning against off-label uses of glucose meters such as for screening of patients at health fairs. So even before the FDA makes a final decision, the proposal is having a significant effect on POC testing.

“Everyone nationwide at this point is holding their breath and waiting to see what the final guidance will be like,” Dr. Nichols says. “Speaking for myself, I fully understand why the FDA is looking at this, and I agree there are definitely some patients where fingerstick glucose is inappropriate.” Although some major manufacturers like LifeScan had already exited the hospital glucose meter market, he does not believe the FDA action will mean less POC glucose testing, because the test has become indispensable to managing patients’ glucose levels.

As much convenience as point-of-care testing has to offer, it also entails more expense and more complex management in the hospital setting than tests on automated central laboratory platforms, says Gyorgy Abel, MD, PhD, medical director of clinical chemistry, molecular diagnostics, immunology, and POC testing at Lahey Hospital & Medical Center. Lahey Health is a system of community hospitals and physician groups in northeastern Massachusetts and southern New Hampshire anchored by the 320-bed Lahey Hospital & Medical Center in Burlington, Mass.

“In the hospital setting, the main advantage of POC testing would be speed—but that’s not always significantly better,” Dr. Abel notes. “If the core laboratory and the stat laboratory are set up correctly, and you have a pneumatic tube system from the ER or OR, then sometimes you see the advantages of POC tests kind of melting away.”

He supports the use of good economic and observational models and clinical trials to measure the cost-effectiveness of POC testing. For example, researchers could take the outcome of a particular disease that makes use of POC testing versus a hospital-lab–based test and find if there are differences in life expectancy or quality-adjusted life years. “These are quite complicated analyses which have not been thoroughly done.”

Over the years, there has been a strong perception that POC testing quality was inferior to central lab testing. “And there were very significant differences between central lab and POC INR and HbA1c,” Dr. Abel says. “But now, with the use of microfluidics, micro-electronics, and nanotechnology, we see less and less difference in the actual analytical performance of POC when compared to central lab testing.” With INR, for example, since his hospital switched to a different POC system, the reproducibility has improved substantially.

Lahey does have certain blood gas testing at POC in the cardiac cath lab. “There is certain testing you don’t want to send to the lab, but most blood gas testing can be done there if it is placed very close to the pneumatic tube reception area and there is somebody always there waiting for the specimens,” Dr. Abel says. Another example is HbA1c. Pricing can be eight to 10 times as much as comparable lab tests, and it remains a sticking point when the hospital considers taking on new POC tests. “We can perform the testing in the lab for a fraction of what the POC test costs. But that said, POC testing for HbA1c could provide immediate results, resulting in therapeutic decisions without delay and fewer patient visits.”

At Lahey, clinicians have requested POC HbA1c, and the hospital is considering offering it at point of care in its satellite locations. But one procedural change in the chemistry lab has made a big difference in the hospital. “We set up a system where the patient comes in one hour before the doctor’s appointment. They get their blood drawn, sit down in the doctor’s office for 45 minutes, and by the time the endocrinologist sees the patient, the HbA1c result is there.” The process requires extensive synchronization of laboratory work and patient appointments, Dr. Abel says, but it has answered a need by providing results to patients in the same visit.
He is eager to see POC molecular diagnostics, not necessarily in the hospital lab, which has well-developed molecular and microbiology capability, but in long-term facilities, community group practices, and other primary care settings where these tests will be useful. The cartridge-based molecular tests require only loading, placement, and pushing a start button. “I call these ‘POC-type’ tests. Currently they aren’t true POC because they must be run with a CLIA license under the direction of a CLIA director.” But some of the tests are so simple they probably will become CLIA-waived, he predicts.

“I hope the FDA will eventually approve these molecular diagnostics, because a number of ID tests such as C. difficile and other hospital-acquired infection tests could possibly come online. But there’s a mystique about nucleic acid testing, and we know studies show that even simple POC tests are usually performed better if done by a medical technologist than by other personnel. So many things can go wrong.”

Unlike the central laboratory molecular systems, most of which require batch processing and can be run once or twice a week, the POC-type systems could take a specimen sent to the lab from the ER by pneumatic tube, and have a result in 20 minutes. “So literally in 30 minutes, you’d have a definitive answer. That can be very important if a patient has influenza or other severe respiratory infection, meningitis, or a hospital-acquired infection and you can do the test without a delay.”

Such a test would tend to cost at least twice as much as the same kind of test on a larger automated lab instrument—about $40 to $80 as opposed to about $20—“but that’s still a lot less than eight or 10 times as much, and the clinical benefit is very easy to demonstrate.”

Dr. Abel thinks that the systemic change to be wrought by health care reform under the Affordable Care Act will affect POC testing, but it’s not clear how. “These huge health systems that have been formed in the Midwest, in Pennsylvania, Texas, and recently in Massachusetts—they are everywhere I go, with new names, new logos, new branding. It’s a very big movement, and they will mean more patients remaining within the same system for the entire spectrum of care.”

“This will lead to systemwide unification and standardization of the EHRs and the LISs, and eventually the laboratory tests and procedures used on patients. I don’t have a clear vision of how this will affect POC, but I can imagine that we’ll see a lot more POC testing in home settings, on smart phones that can monitor certain key parameters, and in primary care settings.” Inside the hospital, whether the central laboratory or POC testing is more efficient in delivering results depends on the infrastructure and laboratory configuration of the particular hospital, he adds.

Weighing both the proven and speculative benefits of shifting more testing to point of care, Dr. Abel believes that evidence-based POC testing should be the goal. “By no means am I against POC testing, but I try to take a balanced view. Before we get carried away completely by enthusiasm for the exciting new technologies in POC testing, we should think it over. We need to study where exactly are the efficiencies going to be realized and the costs going to be saved. I think we will see more POC testing. But it needs to be adopted on the basis of the evidence, and often the evidence isn’t there yet.”

[hr]

Anne Paxton is a writer in Seattle.