The role of POCT and rapid testing

Point-of-care testing (POCT) is defined as medical testing at or near the site of patient care.^1-3 The first reported use of POCT is found in papyrus documents dating back to 1550 B.C., which depict Egyptian physicians using ants to determine glycosuria in patients suspected of having diabetes mellitus. Today, as it was then, the goal of POCT is to provide immediate, convenient, and easy-to-use diagnostic testing that shortens the therapeutic turnaround time when providing care for a patient. The objective is to provide rapid diagnostic information that permits immediate clinical management decisions to be made that will improve patient safety and clinical outcomes, not to mention patient satisfaction.

In the post-Medicare era, centralization of testing in the lab was the norm until the mid-1980s, when new technologies were introduced and some testing, most notably glucose and blood gas testing, migrated from the lab to patient care settings (Figure 1). The market for in vitro diagnostic (IVD) testing is estimated to be $54 billion in 2013, with POCT, according to several market research company reports,^4-9 representing 14% to 15% of the market. With the evolution of blood glucose, blood gas, urinalysis, pregnancy, and coagulation testing in the mid-1990s, the menu of POCTs has expanded from fewer than 10 tests available in 1995 to approximately 110 tests available today (Figure 2).¹⁰

POCT is found in several environments: hospital bedside, ambulatory care settings (clinics or physician offices), alternate care (skilled nursing facilities), and home settings. Today, POCT is used widely in major university medical centers, hospitals, clinics, physician offices, and pharmaceutical clinical trial sites. The use of point-of-care systems in clinical trials offers researchers the ability to conduct double blind studies using encrypted test results. With the advent and expansion of retail clinics, certain POC tests have the benefit of supporting immediate treatment. Beyond home glucose testing, other POCT in the home will become a major growth segment to support management of chronic disease.

As summarized in Figure 3, there are in each of these environments significant differences in what is tested, who can perform the tests, how the data is processed, and how each setting is regulated. POCT labeling (“OTC” versus “For Professional Use”) and device application in the respective environments have become increasingly blurred with respect to waived versus non-waived testing. POCT can be classified as either waived or non-waived testing according to the criteria outlined in CLIA ’88.¹¹ Many POCTs are designated as waived tests, and there appears to be a preference among point-of-care coordinators and laboratory directors for waived testing. The reasons for that may include the decreased regulatory and oversight requirements, particularly for labs performing only waived testing under a Certificate of Waiver or a Certificate for Physician Provided Microscopy and not accredited by either CAP or JCAHO.

Before a POC kit or device can be legally marketed and sold, its labeling must be approved by the FDA. Point-of-care tests fall under the category of in vitro diagnostic products, defined as “those reagents, instruments, and systems intended for the use in the 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.”¹²  Devices intended for use in the home, commonly referred to as over-the-counter (OTC), are sometimes used in the hospital setting as well. Moreover, devices given an OTC designation by the FDA are also categorized as waived tests.

During the past 10 years there has been an increasing concern about the use of OTC devices in the hospital. This is particularly true when devices are used in settings where they have not necessarily been properly validated. An example of this is the use of handheld glucose meters in high acuity settings such as the intensive care unit, where they are frequently utilized in the management of patients on tight glycemic control using intensive insulin therapy. All stakeholders (healthcare professionals, manufacturers, regulators, and standards organizations) are actively participating in discussions about how glucose meters should be evaluated in the future. The outcome of this collaboration will undoubtedly affect all POCT systems and most likely result in new guidelines or standards for evaluation and performance of POCT devices.

Benefits of POCT

The key benefits of point-of-care testing include:

• Positive patient identification;
• Immediate diagnostic test results (reduced test and therapeutic turnaround time);
• Reduction and/or elimination of specimen/sample transport;
• Elimination of blood collection tubes and centrifugation with fresh whole blood specimen;
• Reduced blood specimen volume;
• Room temperature storage of test devices (few require refrigeration);
• Data management and connectivity. Connected POCT system benefits include:
  • Reduction in transcription errors;
  • Immediate data analysis—utilization, QC, compliance, data mining;
  • Development of disease specific algorithms—for example, tight glycemic control.
• New and novel approaches to patient care—for example, patient-centric care.

The current diagnostic laboratory system has been slow to change, and when properly evaluated is in need of change to a more patient-centered system (personalized medicine and companion diagnostics). This model of centralized lab testing was developed in the late 1960s and early 1970s and further refined with development of core laboratories to support laboratory services in Integrated Health Systems in the late 1990s to the present. Instrumentation and new methods have been developed which expand the lab industry’s capabilities, but the demand for more rapid testing with shorter turnaround times is the leverage point for change leading to a significant increase in POCT. Development of new technologies, such as lab on a chip^13,14  and DNA/RNA-based molecular diagnostic tests,^15,16 will expand the POCT test menu and increase POCT utilization.

Several healthcare dynamics are at play that support this shift to a patient-centric care model. These market drivers include the fact that an educated, aging population with the top four chronic diseases (cardiovascular, diabetes, chronic kidney disease, and osteoarthritis) are living longer because medical advancements work; consumer demand; emergence of new technologies; empowerment of primary care providers; reimbursement pressures; an aging healthcare workforce; and insufficient personnel to meet the increasing demand for healthcare.

POCT issues and concerns

The key issue of alignment and concordance of POCT with Central Lab Methods cannot be overlooked by laboratories, regulators, and industry. Lack of alignment with definitive methods remains a potential barrier to further acceptance and growth of POCT. Manufacturers must demonstrate traceability of their methods to definitive methods, e.g., IDMS glucose and creatinine, or properly aligned reference methods. Recent concern over bed side POCT glucose system performance due to exogenous and endogenous interferences has received much attention in the literature (Figure 4).

New guidelines for acceptable performance of POCT glucose systems are in the final stages of review by CAP, CLSI, IFCC, ISO, and the FDA, and two have been published in 2013.^17,18 In terms of creatinine, the global program for standardization of central lab plasma methods was implemented in 2005, and it demonstrated improvement, but there are still significant method biases between enzymatic and non-enzymatic methods as evidenced in external proficiency program data. This poses a unique problem for fresh whole blood specimen POCT methods and alignment of these methods with a specific lab method. As clinical laboratory scientists, we need to keep an open mind about agreement between POCT and central lab plasma chemistry methods and evaluate POCT not only on comparative analytical significance, but also on clinical sensitivity and specificity. Given acceptable analytical and clinical performance, we should ask the question: “Is fresh whole blood the specimen of choice?”

Immunoassay method agreement is equally concerning because of method differences and specimen type (whole blood, urine, saliva, CSF, etc.). With the evolution of molecular diagnostic methods, POCT has expanded into the realm of rapid pathogen detection in various body fluids other than blood and urine, and manufacturers and laboratorians must work together to determine acceptable concordance. With the implementation of the Affordable Care Act in 2013 and the development of Health Information Exchanges (HIEs), it is incumbent upon laboratorians, regulators, and manufacturers to achieve alignment and concordance of all in vitro diagnostic methods. The primary goal in healthcare is to reduce medical errors, and this requires acceptable concordance of all IVD methods. In vitro diagnostic data combined with vitals measurements (weight, BP, pulse, etc.) represent about 72% to 75% of the medical information reviewed by clinicians, and this data should be in agreement no matter where a patient enters a healthcare delivery system.

As we shift emphasis to chronic disease diagnosis and management, it is necessary, based on clinical research, to identify disease-specific test groupings and develop methods that go beyond the walls of the laboratory. These disease groupings can both identify patients at risk or, once diagnosed, patient compliance with therapy or effectiveness of therapy. A disease-specific grouping of biomarkers, e.g., hsCRP, intact pro-insulin, and adiponectin, was recommended for assessment of the underlying inflammation related to cardiovascular disease and/or diabetes.^19-22 These biomarker rapid tests were developed on individual lateral flow immunoassay strip platforms with semi-quantitative interpretation by the healthcare professional while the patient is present in the clinic.

In other parts of the world, such as South Africa, the National Health System is very interested in POCT for management of HIV-positive patients diagnosed with AIDS.^23,24 The need in South Africa is to assess patients in their villages who are on anti-viral therapy for lactate, CD4, HIV mRNA viral load, and drug resistant TB strains. In this setting, it is very challenging to collect and transport specimens for central lab analysis and provide timely data for disease management.

These examples demonstrate the need for integrated POCT systems which may combine several analytical methods on a single platform. The next phase of POCT is the use of micro-fluidic and nano-technologies which combine several analytical methods on a single platform such as a lab-on-a-chip. It will be possible to identify many test combinations for inclusion in novel POCT technologies, as more clinical diagnostic and therapeutic data is collected and analyzed through connected devices.

POCT methods

POCT technologies include meters and strips; urine chemistry strips; occult blood slides; lateral flow immunoassay devices; photometric methods; DNA/RNA-based molecular methods; and several non-laboratory methods. Lab-on-a -chip (LOAC) and nano-technologies are in the feasibility stages of development, and these devices use a variety of analytical methods for measurement of a specific analyte such as a routine chemistry, biomarker (protein or peptide), DNA/RNA, or a pathogen. POCT is accomplished through the use of transportable, portable, and handheld instruments (e.g., blood glucose meter, nerve conduction study device) and test kits (e.g., CRP, HbA1c, homocysteine, HIV salivary assay, etc.). Small, mobile bench top analyzers or fixed equipment can also be used when handheld devices are not available.

As previously stated, the goal is to collect the specimen, test, and obtain test results rapidly at or near the location of the patient so that the treatment plan can be adjusted as necessary before the patient leaves.³ Smaller, easier to use, faster, smarter, and connected POCT devices have increased the use of POCT because it is now cost-effective for diagnosis and management of many diseases, such as diabetes, carpal tunnel syndrome,²⁵ and acute coronary syndrome, while with the patient.

In diabetes care, continuous glucose monitoring systems are in routine use. These subcutaneous devices monitor glucose in real time and communicate with an insulin pump wirelessly. Insulin dose is then adjusted based on pre-programmed patient specific algorithms. Due to the differences between blood and interstitial fluid glucose, these devices have not been implemented in the hospital setting. There are several patient-connected devices under review at the FDA which continuously measure glucose ex vivo in a patient-connected monitor. These devices represent a new class of in vitro POCT technology for acute patient monitoring. Unlike pulse oximeters or patient-connected hemoglobin monitors, this new class of continuous glucose monitors will
require routine calibration and excellent agreement to a
definitive method.

Connectivity and information technologies are beyond the scope of this review. That is a topic unto itself. The value of POCT connectivity has been previously addressed.^26-28 The value of connected and smart POCT devices is foundational to the growth of POCT in all patient care environments. These new devices should enable seamless, real-time capture of patient data not only for immediate patient assessment and treatment but also for data collation, analysis, and evaluation to determine new approaches to improving patient safety (reduction in medical errors) and improved patient outcomes. POCT and real-time assessment of patient data represent a new frontier in the application of medical technology and a new opportunity for laboratory scientists.

1. Kost GJ. Goals, guidelines and principles for point of care testing. In: Kost GJ, ed. Principles and practice of point of care testing. Philadelphia, PA: Lippincott Williams and Wilkins; 2002.
2. Nichols J. Point of Care Testing – Performance Improvement and Evidence Based Outcomes. New York, NY: Marcel Decker, Inc.; 2003.
3. Point of Care Testing Toolkit. Available from www.cap.org.
4. GlobalData, Point of care diagnostics – global pipeline analysis, competitive landscape and market forecast to 2018. 2012.
5. Group, V.P., Point-of-care testing markets: innovative technologies and emerging business opportunities. 2012.
6. Insights, S.B., Point of Care Testing: Evaluating the return to evidence based medicine, novel technologies and the competitive landscape. 2010.
7. Intelligence, E.H., Point of care diagnostics – players, products, and future market prospects.
8. Markets, R.a., Point of Care Diagnostic Testing Sector Trends. 2012.
9. Publications, T., Point of Care Diagnostic Testing World Markets. 2008: TriMark Publications.
10. Point of Care Search. Available from www.pointofcaresearch.com.
11. Clinical Laboratory Improvement Amendments (CLIA). 1988.
12. Code of Federal Regulations, Title 21, Section 809.3.
13. Sauer-Budge AF, Mirer P, Chatterjee A, Klapperich CM, Chargin D, Sharon A. Low cost and manufacturable complete microTAS for detecting bacteria. Lab Chip. 2009;9(19):2803-2810.
14. Malima A, et al. Highly sensitive microscale in vivo sensor enabled by electrophoretic assembly of nanoparticles for multiple biomarker detection. Lab Chip. 2012;12(22):4748-4754.
15. Bhattacharyya A, Klapperich CM. Microfluidics-Based Extraction of Viral RNA for Disposable Molecular Diagnostics. Sensors and Actuators B: Chemical. 2008;129.
16. Mahalanabis M, Al-Muayad H, Kulinski MD, Altman D, Klapperich CM. Cell lysis and DNA extraction of gram-positive and gram-negative bacteria from whole blood in a disposable microfluidic chip. Lab Chip. 2009;9:2811-2817.
17. Clinical and Laboratory Standards Institute. Point of care blood glucose testing in acute and chronic care facilities; approved guideline—Third Edition. Wayne, PAP: Clinical and Laboratory Standards Insistute. 2013. CLSI document POCT12-A3.
18. ISO 15197:2013. In vitro diagnostic test systems—requirements for blood-glucose monitoring systems for self-testing in managing diabetes mellitus.
19. Hohberg C, et al. Successful switch from insulin therapy to treatment with pioglitazone in type 2 diabetes patients with residual beta-cell function: results from the PioSwitch study. Diabetes Obes Metab. 2009;11(5):464-471.
20. Pfutzner A, et al. Intact and total proinsulin: new aspects for diagnosis and treatment of type 2 diabetes mellitus and insulin resistance. Clin Lab. 2004;50(9-10):567-573.
21. Pfutzner A, et al. Association of high-sensitive C-reactive protein with advanced stage beta-cell dysfunction and insulin resistance in patients with type 2 diabetes mellitus. Clin Chem Lab Med. 2006;44(5):556-560.
22. Pfutzner A, Weber MM, Forst T. A biomarker concept for assessment of insulin resistance, beta-cell function and chronic systemic inflammation in type 2 diabetes mellitus. Clin Lab. 2008;54(11-12):485-490.
23. African Society For Laboratory Medicine Holds First International Conference In Cape Town; 2012. Available from www.nhls.ac.za.
24. Stevens W. Point of care technology: Perspectives from South Africa. Presented at: The 4th INTEREST Workshop; 2010; Maputo, Mozambique. http://regist2.virology-education.com/4thINTEREST/docs/27_Stevens.pdf. Accessed July 18, 2013.
25. Tolonen U, Kallio M, Ryhanen J, Raatikainen T, Honkala V, Lesonen V. A handheld nerve conduction measuring device in carpal tunnel syndrome. Acta Neurol Scand. 2007;115(6):390-397.
26. DuBois JA. Point of care testing recognized as a distinct domain. Point of Care. 2004;3(2):85.
27. DuBois JA. POC Connectivity Concepts, Formation of the NCCLS Area Committee for POCT. Advance. 2004.
28. Dubois JA. Point-of-care testing connectivity: past, present and future. Point of Care. 2010;9(4):196-198.

Jeffrey A. DuBois, PhD, FACB, C(ASCP)SC, is Vice President Medical and Scientific Affairs, Nova Biomedical Corporation.