In 1900, speaking about the clinical and ward laboratory, William Osler, physician-in-chief at Johns Hopkins from 1889 to 1905 said, “They [lab tests] are to the physician just as the knife and scalpel are to the surgeon.”1 Since Osler made that observation, the availability of laboratory testing has increased and expanded to all fields of medicine. As diagnostic testing has advanced, so too has the goal of applying diagnostic testing within the context of the patient-physician experience, which in turn has led to the availability of point-of-care testing (POCT).
Over time, many descriptive names have been applied to POCT, including bedside testing, near-patient testing, physician office-based testing, decentralized testing, off-site testing, ancillary/alternative site testing, and testing performed by non-laboratory trained personnel. While debates persist about the best terminology to encompass POCT, there can be little debate about its intent. In order for POCT to provide tangible clinical benefit, its results should be actionable and used to make decisions which lead to improved health outcome.
Why POCT for microbiology?
Access to rapid, reliable POCT for the diagnosis of infectious disease is essential in support of initial diagnoses, defining antimicrobial/antiviral administration, and narrowing evolving clinical differentials. However, POCT for infectious disease is not nearly as well established as laboratory disciplines such as clinical chemistry and hematology, and laboratory techniques customary to microbiology have not found roles in POCT. Point-of-care tests have historically not been able to achieve the versatility of laboratory-based culture diagnostics, and specialized equipment (e.g., polymerase chain reaction, or PCR) used by trained laboratory staff is often required.
Many POC tests have suffered from inferior sensitivity or specificity compared with reference tests, which has made them difficult to interpret, advocate, or adopt in routine clinical practice. Furthermore, because few infectious syndromes are pathognomonic of infection due to a single organism, POCT has struggled compared to culture-based systems, which detect a wide variety of pathogens. This restricts the versatility of POCT; the clinical presentation points are limited to one or a small number of potential pathogens.
Sensitivity and specificity
With the advent of new technologies, clinically robust POC testing for infectious disease now seems like an achievable goal. Next generation lateral flow immunoassays incorporating digital output of results have entered the market, with reports of enhanced sensitivity and specificity for influenza and group A streptococcus.2,3 Isothermal technologies for detection of DNA and RNA targets have also been introduced recently, but in some series they have been less than 80 percent sensitive.4 This has prompted some to ask, “What is the minimum level of sensitivity and specificity required for a point-of-care test?” The value of immediate and actionable results at the POC at acceptable price points is often balanced against the relative sensitivity and specificity of the tests, and the concerns over sensitivity and specificity have often been the barrier to POCT in microbiology.
In fact, many questions regarding POCT in microbiology still exist. What levels of sensitivity and specificity are required for a physician, patient, or laboratory professional to feel confident in overall testing results delivered by POCT? At what point do the increased costs of follow-up testing negate clinical benefit? Is the “clinical price” of performing inexpensive POCT options really less than the cost of missed diagnoses in patients? Proposed FDA guidance designed to reclassify many rapid POC tests to Class II devices should establish a minimum level of analytical performance standards that may foster further adoption of POCT.5
PCR technology at the POC
Ultimately, acceptance of POCT for infectious disease may come from advances in next-generation platforms. Panel-based infectious disease testing has proven to have both clinical and economic benefits to patients and healthcare systems.6,7 However, many clinicians still feel that the challenges associated with operationalizing testing in the patient environment, required quality-control processes, and the 60-90 minute turnaround time still causes this approach to fall well outside a window that can directly impact the patient at the time of admittance.
Another new technology that shows great promise is rapid-cycling PCR, which provides a true cycling PCR reaction within the context of a POC environment (results in 15 to 20 minutes, depending on the assay). The clinical response of a physician to any test result is directly impacted by one’s confidence in the test result, and PCR gold standard testing represents a potential leap forward in the era of POCT.
Recently, my colleagues and I analyzed the impact of rapid influenza testing on a new POC PCR platform that has FDA-cleared assays for influenza A and B and Group A streptococcus, the latter of which is also CLIA-waived. We performed testing in the emergency department (ED) setting and recorded changes in patient management as a result of access to rapid influenza test results. Providers were specifically tasked with documenting and describing the effect of an influenza test result on their subsequent management of suspected influenza patients seen in a busy ED. Based on PCR influenza test results that were available to providers within 25 minutes, the study documented changes to admission/discharge orders, antimicrobial/antiviral prescriptions, changes to procedures (e.g., chest x-ray), or changes to follow-up labs.
In 57 percent of cases, ED providers documented a change in the initial work-up of suspected influenza patients because of positive or negative influenza test results. Not surprisingly, 61 percent of the time, changes in patient management occurred in cases where influenza results were negative, providing further evidence that negative test results also influence patient care in the POC setting. Overall sensitivity and specificity of the influenza assay, compared to another PCR method, were 97.6 percent and 98.5 percent, respectively, for 314 cases analyzed.
POCT for microbiology: a new perspective
Initiation of the diagnostic process typically begins with the patient and the doctor having a question that requires an answer. Increasingly, there is a new emphasis on an overall patient-centered experience, and that can conflict with the realities of delivering healthcare in clinically and financially responsible environments. It is clear that a major change in healthcare will involve shifting our focus to patient demands and the way in which healthcare is delivered.
The role that POC may play in this emerging paradigm is self-evident. So, too, is an immediate concern: that POCT is usually seen as more expensive when viewed strictly in the light of cost per test. In many cases, however, it yields cost benefits in reduced utilization of resources (e.g., blood products, antimicrobial consumption, use of staff, costs of follow-up testing for tests with poor sensitivity). For this reason, broader adoption of POCT in microbiology requires not only meeting acceptable thresholds of sensitivity and specificity but also a recognized system for transfer of resources between cost centers.
Accurate and rapid diagnostics have the potential to affect healthcare decisions to a degree that is well out of proportion to their cost. Most laboratorians are familiar with the oft-cited statistic: It has been estimated that diagnostics account for only two percent of the cost of healthcare, but affect 60 percent to 70 percent of treatment decisions. Studies of POCT have tended to focus on relativity straightforward comparisons of the sensitivity and specificity of tests against reference culture rather than examining the impact of POCT on clinical outcomes, and very few studies have examined the cost-effective role of POCT for microbiology tests that aren’t considered lifesaving.8 Perhaps POCT for microbiology would benefit from a broader approach to examining the cost of testing involved per patient episode. If the importance of rapid, reliable testing could be acknowledged by Sir William Olser more than a century ago, there is hope that we can improve patient access to important testing, change the way POCT is perceived, and capitalize on advances in POCT today to realize a pathway to better patient care.
References
- Osler W. Discussion. JAMA 1900;35:230.
- Lewandrowski K, Tamerius J, Menegus M, Olivo PD, Lollar R, Lee-Lewandrowski E. Detection of influenza A and B viruses with the Sofia analyzer. Am J Clin Pathol. 2013;139(5):684–689.
- Dunn J, Obuekwe J, Baun T, Rogers J, Patel T, Snow L. Prompt detection of influenza A and B viruses using the BD Veritor System Flu A_B, Quidel, Sofia, Influenza A_B FIA, and Alere BinaxNOW Influenza A&B compared to real-time reverse transcription-polymerase chain reaction (RT-PCR). Diagn Microbiol Infect Dis. 2014;79(1):10–13.
- Hazelton B, Gray T, Ho J, Ratnamohan M, Dwyer DE, Kok J, Detection of influenza A and B with the Alere i Influenza A & B: a novel isothermal nucleic acid amplification assay. Influenza Other Respir Viruses. 2015;9(3):151-4.
- US Department of Health and Human Services. 2014. Microbiology devices; reclassification of influenza virus antigen detection test systems intended for use directly with clinical specimens. 21 CFR Part 866. http://www.gpo.gov/fdsys/pkg/FR-2014-05-22/html/2014-11635.htm?source=govdelivery. Accessed June 29, 2015.
- Sango A, McCarter YS, Johnson D, Ferreira J, Guzman N, Jankowski CA. Stewardship approach for optimizing antimicrobial therapy through use of a rapid microarray assay on blood cultures positive for Enterococcus species. J Clin Microbiol. 2013;51(12):4008-4011.
- Dundas NE, Ziadie MS, Ravell PA, et al. A lean laboratory: operational simplicity and cost effectiveness of the Luminex xTAG respiratory viral panel. J Mol Diagn. 2011;13(2):175-179.
- Price CP. Point of care testing. BMJ. 2001;322:1285. http://www.bmj.com/content/322/7297/1285
