Bringing the Laboratory Test to the Patient with Point-of-Contact Tests

Oct. 8, 2018

Pharmacies are rapidly moving forward with innovative health care options for patients. CVS has opened over 1,100 MinuteClinics staffed by nurse practitioners and physician assistants in 33 U.S. states. Only a few infectious diseases diagnostic tests are available at these pharmacy clinics. However, the future looks bright for widespread adoption of infectious disease point-of-care testing (POCT) in pharmacies and other alternative testing sites in the future.

Point-of-care testing goes by many names—point-of-impact, near-patient, bedside, off-site, physician office-based or decentralized testing. By definition, POCT is testing that is not performed in a centralized laboratory. In the U.S., there are two types of POCT: tests that are run with a Clinical Laboratory Improvement Amendments (CLIA) waiver, and tests that are moderately complex but are performed in POC settings by clinically licensed personnel. Under CLIA 1988, U.S. facilities or laboratory sites that test human specimens for diagnosis, prevention or treatment of disease must follow quality standards for testing. The U.S. Food and Drug Administration (FDA) assigns a level of complexity to each test based on several criteria determined through CLIA. Tests may be waived or nonwaived. Nonwaived testing refers collectively to moderate- and high-complexity testing performed in a laboratory or at a site that holds a CLIA certificate and where tests are run by trained personnel. In essence, the site of testing determines point-of-care status, while the FDA determines the complexity status of a test—waived or not.

Designation of a CLIA waiver for an assay means that the test is simple to perform and difficult to mess up; in fact, incorrect results would be hard to achieve. Of course, tests must also be accurate. If a CLIA waiver is granted for an assay, the site performing the assay does not need to document personnel qualifications and training, perform quality control (unless specified that quality control is required in the test instructions), participate in proficiency testing or assess routine quality assessment related to that assay. Most CLIA-waived tests are either antigen-based, antibody-based, or molecular-based.

Some terms may be confused with POCT and CLIA-waived testing. “CLIA-exempt” sounds similar but refers to the state of a laboratory being exempt from CLIA rules, and is not related to a specific test or assay. CLIA-exempt laboratories are licensed or approved in states in which Centers for Medicare and Medicaid Services (CMS) decided that the state has laws which are at least as stringent as the CLIA requirements. Another term, FDA-clearance, refers to a situation in which a test has been reviewed by the FDA and is equivalent to a test system already marketed. FDA-clearance applies to waived, moderate or high-complexity systems. In the U.S., tests that are intended for use in diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae, must be cleared by the FDA prior to being marketed to customers.

Patient-centered testing has been a popular term lately. The draw of such testing is convenience and rapidity, with an informative and actionable result. The World Health Organization (WHO) has developed criteria for POCTs, the ASSURED criteria.  According to these criteria the test must be:
  • Affordable.
  • Sensitive.
  • Specific.
  • User-friendly.
  • Rapid/robust.
  • Equipment-free.
  • Deliverable to end users.
POCT has in fact been used for decades. Some of the earliest applications were home pregnancy tests based on antigen testing by lateral flow immunoassays (LFIA). Such assays were based on capillary migration of fluid and the ability to couple antibodies to gold or latex particles for detection and visualization of antigen. Many POCTs are based on the LFIA principle, but, more recently, POCTs have been developed based on nucleic acid amplification testings (NAATs) through real-time PCR that targets DNA or RNA sequences. Another popular approach to molecular POCT is the loop-mediated isothermal amplification (LAMP) technique which eliminates the need for an expensive thermocycler. Pathogens targeted by FDA-cleared, CLIA-waived assays include influenza, respiratory syncytial virus, and other respiratory viruses, as well as Group A Streptococcus, respiratory bacterial pathogens, agents of bacterial vaginosis, Trichomonas and Helicobacter pylori (the latter performed directly on gastric biopsies or stool).

Why Use Point-of-Contact Tests?

Accessibility is the most attractive feature of POCT to consumers. Understandably, patients may wish to avoid potentially unnecessary contact with the larger health care system, the long waits at central laboratories, or perhaps other reasons. POCT laboratories have been set up in various creative settings, such as aboard cruise ships, within barber shops,  inside churches, and alongside Hajj pilgrims on their way to Mecca. POCT has also been implemented with much success in resource-limited settings such as some African countries and elsewhere.

Rapidity is the second attraction of POCT, but how rapid must a POCT be? How long would you be willing to wait in the doctor’s office, or in the pharmacy, for an answer? For me, the answer differs according to location. In a pharmacy, I’d give it 15 minutes—to browse the greeting card aisle a bit…perhaps a little loitering in the candy aisle…and then I’d be up at the counter waiting for my result. In the doctor’s office, I’d give it a little longer, but only up to an hour, in particular if the test was done by a physician assistant before I saw the doctor. Preferences for turnaround times of various POC assays differ widely in the literature—from 5 minutes to 2 hours.

However, it is likely an assay’s performance which most concerns the laboratorians. Even with a simple assay, errors may occur in any step of the process, especially if the manufacturer’s instructions are not followed. For instance, a 2015 Morbidity and Mortality Weekly Report (MMWR) from the CDC noted misdiagnosis of Group A streptococcal pharyngitis in people attending a rural clinic at which staff members were interpreting test results later than the incubation time recommended by the manufacturer, resulting in false positives with this assay. The issue of training and careful adherence to the manufacturer’s instructions is compounded when considering the adoption of highly sensitive molecular amplification assays and the potential for contamination. However, results must also be actionable. The response of a clinician to a test result is dependent upon the confidence the provider has in the assay. With some exceptions, molecular assay results are almost always more highly trusted than results from an antigen assay. Some studies have shown positive clinical impact of performance of molecular POCT in emergency departments, measured by shorter length of stay, fewer ordered tests and more appropriate use of antimicrobials.

Other issues beyond the assay’s diagnostic performance become relevant specifically for POCT. Results may not be electronically interfaced with the patient’s medical chart. How and where are results recorded? Proper documentation of results is especially important for the busy clinician who is receiving many different test results on various patients and may not be able to rely on memory for the test results of a particular patient. There are also privacy concerns related to obtaining test results―how are the data transferred to the patient’s central health care record, and by whom?

Furthermore, public health laboratories track laboratory results of certain viruses and other organisms which can cause epidemics. How would POCT results be transmitted to the public health centers?  Molecular POCT is also expensive, and, although more sensitive and specific than many antigen-based POC testing, it can be hard to justify the cost of such testing. Such issues were discussed during the 2016 colloquium of the American Academy of Microbiology which explored the impact of POCT on patient outcomes, health care delivery models, public health and health care costs.

Running the test closer to the patient and the patient’s provider will give providers results more quickly and POC infectious disease testing is rapidly gaining ground in this consumer-driven environment. POC testing allows clinical management decisions to be made immediately and may be critical for proper infection control and antimicrobial stewardship practices. In our increasingly data-driven world, we want answers faster. However, it is critical to maintain the integrity of our tests so that the results are meaningful―whether the results are obtained in a pharmacy or in a hospital bed. As larger numbers of POCTs are pushed to the market, it will be increasingly important to continue to explore the utility of these tests, especially through use of outcome-focused studies.