Originally Published IVD Technology April 2005
Anniversary Essays
6. Point-of-care testing
Overcoming laboratory traditionalists, slow-responding regulatory authorities,
and interconnectivity obstacles, POCT technology now shows bright promise
for enhancing patient care.
Michael Groves
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Michael Groves is vice president of sales and marketing at Response Biomedical Corp. (Burnaby, BC, Canada). He can be reached at mgroves@ |
Point-of-care testing (POCT) developed out of the need for clinicians to have more rapid-test results to improve the patient care process. It is estimated that in 2005, the U.S. market for POCT products will total $8.3 billion: $5.4 billion from self-testing of whole-blood glucose, $1.8 billion from professional POC testing, and the remainder from home pregnancy kits and similar products.1
Whole-blood glucose testing continues to grow at 10% per year, and some of the professional POCT market is expanding at more-dramatic rates, driven by the need for faster clinical decision making as well as economic conditions such as reimbursement, labor shortages, and the cost of hospital services (length of stay, time in the emergency department, etc.). With POCT, the clinician can in many cases simultaneously diagnose, triage, and treat patients.
POCT was once viewed by laboratory personnel as suitable only for rapid test results in extreme situations, not as a substitute for results generated within the laboratory. Today, many POCT systems perform as well as, if not better than, laboratory-based systems. Technological advances also continue to improve the robustness of these devices in the hands of nonlaboratory users. This ability of
nonprofessionals to get valid results has eased somewhat the central laboratory’s resistance to relinquishing the tests in question.
For example, glucose strips are largely based on electrochemical measurement techniques, and are far less sensitive to variations in hemoglobin levels and other optical interferents, which occurred with previous generations using colorimetric optical measurements. They are also much more precise and use smaller volumes of blood. Most require less than 10 µl of whole blood, and some less than 1 µl, thereby improving sample application to the test strip and testing compliance (the smaller samples are less painful to collect). Several platforms are moving into the realm of the minimally invasive and noninvasive. Tight glycemic control, more achievable with such minimally invasive continual monitoring of glucose, improves outcomes for diabetics undergoing cardiovascular procedures.2 This case exemplifies the therapeutic potential of further developments in POCT technology.
An Evolving Technology
In the 1980s, many of the POCT systems were essentially downsized chemistry analyzers for use in physician offices or critical-care settings. The term near-patient testing (NPT) was coined to describe such systems, which were definitely benchtop in design but nevertheless could be used closer to the patient. This term suggests a useful distinction from the adjective point-of-care, which is better reserved for more-portable systems that can be used wherever a patient is encountered, or even by patients themselves. POCT systems effectively bring the lab to the patient’s side.
Numerous systems have come onto the market during the past 15 years that have been specifically designed for use by nonlaboratory personnel. The miniaturization of electrochemical sensors into disposable formats and advances in immunological solid-phase technology have resulted in an explosion of qualitative and quantitative POCT systems for a wide range of analytes ranging from blood gases, coagulation, and general chemistry to immunoassays.
The introduction of quantitative POCT immunoassays may yield the greatest impact on current and future POCT practices. Advances made in detection techniques and antibodies have brought about tremendous improvements in POC immunoassay systems, with results comparable to those run on central laboratory systems.
Key Assays for Growth
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The RAMP system by Response Biomedical Corp. (Burnaby, BC, Canada). |
Cardiac markers appear to be one of the major growth areas for POCT, with annual increases estimated close to 20%, contributing substantially to growth in POCT sales. New quantitative systems on the market include a troponin I electrochemical immunoassay by Abbott Point-of-Care (Abbott Park, IL), and the Ramp troponin I, creatine kinase-MB (CKMB), and myoglobin system by Response Biomedical Corp. (Burnaby, BC, Canada), which is based on an immunofluorescence lateral-flow technology. While POCT immunoassay systems for some or all of these markers have been available for several years, they have been either qualitative, such as the Cardiac Status by Spectral Diagnostics Inc. (Toronto), or semiquantitative, such as the Triage system by Biosite Inc. (San Diego).
As these quantitative products start to penetrate the market, patients with chest pain will get lab-quality, sensitive cardiac markers performed in the emergency room, or in the ambulance during transport. Interestingly, the B-type natriuretic peptide (BNP) test, targeted for patients with shortness of breath or congestive heart failure, was first introduced on a POCT platform. Despite being introduced only a few years ago, POCT sales of BNP now amount to more than $160 million, representing close to 10% of the total POCT market. Other POCT immunoassays with a focus on acute coronary syndromes such as ischemia markers, pulmonary embolism (d-dimer), and stroke are entering the market or are being developed.
Microbiology is another area in which rapid-testing capability is advancing. Almost exclusively dominated by incubation chambers and petri dishes for decades, immunoassay systems have already started to penetrate this market for rapid rule-in or rule-out screening tests. Sensitivities of many of the POCT influenza tests are still only at or below the 80% mark. However, with the advent of increased-sensitivity techniques, POCT systems will take over more of microbiology, with equivocal results being clarified by assays based on highly sensitive molecular methods.
In the foreseeable future, improvements in the ease of use and sensitivity of immunoassays and protein tests will make obsolete the need for cultures for many tests, enabling these tests to be performed in any part of the laboratory, and, if rapid enough, at the point of care.
For coagulation testing, miniaturized and unitized testing systems have allowed testing to move to the point of care. The activated-clotting-time test for measuring the effect of heparin on the coagulation pathway has been used since the 1970s and is performed next to patients in order to monitor and adjust heparin dosing frequently. In the late 1990s, i-STAT (now Abbott Point-of-Care) introduced an electrochemical thrombin detection system that leaps beyond simply detecting changes in the viscosity of blood, a method that is influenced by sample temperature, hemodilution, and human error. Additional capabilities for POCT coagulation will evolve as manufacturers continue to refine their methods and add these needed assays to their existing platforms.
Standardizing POCT
During the past five years, POCT platforms have begun to emerge with two distinct approaches. One effort has been to integrate disparate technologies onto a single reader, creating a highly functional data accumulator. One example is the i-STAT 1 by Abbott Point-of-Care, which integrates the Medisense glucose strip reader into the handheld reader used to run the i-STAT cartridges.
The other approach has been based on technology expansion in which many different types of tests are integrated onto a single platform. Abbott Point-of-Care has taken the lead integrating immunoassay capabilities with other traditional electrochemical tests such as blood gases and electrolytes. While this integration places a substantial design burden on the manufacturer, it simplifies life for end-users by reducing the number of different systems they have to be familiar with.
However, running tests that range in duration from 2 to 10 minutes on one platform may complicate the care process in some areas, requiring multiple readers to be available in each location where the full menu of tests needs to be run.
Biosite’s plan to integrate many of its tests, including a new d-dimer assay, onto one cartridge may present additional challenges for some users. While presenting a logistical advantage for end-users, it poses a significant problem for hospitals that do not want to perform all of the tests on a panel, as some may not be medically necessary and therefore not reimbursable or reportable. Further advances in technology are necessary to remove these logistical bottlenecks.
Connectivity and Informatics
The tools needed for the laboratory to use informatics in its role of overseeing POCT programs have developed significantly during the past 10 years, mainly because good informatics translates into higher profit by capturing vital information for reimbursement and monitoring compliance. Oversight tools include system quality checking, training and compliance of users, data capture, and integrating the data into usable databases and presentation formats.
One of the first connectivity systems was the i-STAT Central Data Station, introduced in 1992. Its original function was to capture data and integrate it into the laboratory information system (LIS). At that time, LIS vendors were used to writing interfaces only for large laboratory instruments. POCT data collected on dozens of readers throughout an institution yet connected though one data portal was a new model that LIS vendors had little interest in pursuing. As a work-around, POCT manufacturers resorted to writing scripted interfaces that captured and interpreted the script from the LIS using a screen-scrape approach, thereby sending data to the LIS as though it were being sent manually through a dumb terminal.
Today’s POCT data management systems integrate many of the tools necessary for laboratory oversight, including such features as inventory management, reader performance, and identification of noncompliant users. In addition, customers require LIS vendors to have drivers available for the POCT data management systems, and scripted interfaces of the early 1990s are being replaced by ASTM or HL7 interfaces, with much greater participation of the LIS vendors.
A lack of standards and varying characteristics among available systems prompted the development of guidelines, the POCT 1-A document by the Clinical and Laboratory Standards Institute (Wayne, PA).3 A POCT connectivity consortium was later established to help manufacturers achieve greater standardization between management systems.4
By identifying the opportunity to consolidate the number of POCT data management systems into one workstation, several companies have developed a vendor-independent, open POCT connectivity solution. In the United States, at least two vendors have addressed this need: Medical Automation Systems Inc. (MAS; Charlottesville, VA) and Telcor (Lincoln, NE). Conworx (Wildau, Germany) is pursuing the European market. These systems allow each vendor’s data management and reader control software to be integrated into one connectivity platform, thereby creating a consistent user interface. It is estimated that MAS and Telcor cover about 30% of the U.S. hospital POCT market. This rapid advance reflects the maturing of the POCT market, with POCT data management being another essential service of the laboratory.
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The i-STAT 1 analyzer by i-STAT Corp. (East Windsor, NJ). |
Health networks that offer patient services from several locations will demand even further data integration. There is still a large disparity in data capture between patients seen within hospitals and those in outlying facilities. This often results in more testing being performed than is necessary and creates delays in results availability. Considerable savings in time and costs would be realized if POCT data were integrated electronically throughout related facilities.
The future of point-of-care information technology is huge, from contextualization of POCT data in terms of previous test results to integrating the management of therapeutic delivery with up-to-date results that can help reduce mistakes and identify opportunities to change therapeutic regimens. For example, National Hospital in Tokyo, Japan, has apparently reached the point where the real-time capture and monitoring of all therapeutic decisions and diagnostic results (including radiological) are transmitted to a centralized patient management system by nurses using personal digital assistants (PDAs). The next step will be to integrate this information and identify changes or contraindications of medications in real time to aid the clinical staff in decision making. Other efforts under way in the United States and the United Kingdom will one day connect the clinician with patient home testing in what some term the “virtual hospital.”
Regulatory Challenges
When designed for nonlaboratory end-users, POCT devices pose significant challenges to regulations written for traditional laboratory instrumentation. Some of the most significant problems have been quality control (QC) and oversight regulations. In some states, oversight required medical technologists to physically observe all POCT being performed.
In the early 1990s, QC regulations were written for devices requiring significant end-user maintenance and repair (i.e., traditional laboratory and NPT instrumentation). On the other hand, POCT devices are designed so that users cannot repair or modify the system’s performance. Controls or calibration checks are built into disposable devices and the associated readers with no opportunity for users to affect the outcome of the results, other than the complete failure of the test, which is appropriately reported. The blind application of QC rules for many modern POCT systems is completely inappropriate.
Manufacturers have come out with tools for users to evaluate the system’s performance (e.g., electronic QC modules).
Clinical Outcomes Research
With the advent of the growing POCT market, assessing the impact of various assays on clinical decision making and patient outcomes will need to be addressed. Many laboratory tests have been used without a great deal of focus on the effect of the results in the care process, as doctors have to make therapeutic decisions well before test results are available. POCT allows clinicians to have relevant information at the time they make therapeutic decisions, which should affect decision making and care.
One of the reasons that BNP testing has been successful is the ability to demonstrate the test’s value in triaging shortness-of-breath patients in the emergency room and monitoring the therapy of congestive heart failure patients.
Clinical outcomes research associated with POCT is high on most clinical laboratory meeting agendas, and manufacturers will need to spend more of their marketing dollars in this area. Activity in this area is increasing, with the topic being high on most clinical laboratory meeting agendas.
Conclusion
Immediate response time is a basic fundamental requirement in many case settings. However, to meet that requirement, the tools required for rapid and accurate diagnosis and treatment need to be accessible and capable of performing at the speed of care. During the last decade, POCT has met this challenge and is now acknowledged by the medical profession as the standard of care in many areas. As one of the fast-growing segments of the diagnostics market, new technological advances will provide even wider usage as broader platforms integrate protein markers with infectious-disease testing, immunoassays, chemistry, and hematology testing. There are currently more than 50 companies involved in POCT, and some consolidation has already started as the larger diagnostic companies recognize the importance of adding POCT capabilities to their portfolio of testing systems.
The market for POCT is expected to grow by more than 10% annually, with specific areas such as cardiac markers and new tests for the critically and chronically ill in the 20–30% range. The future of blood analysis is at the patient’s side, and what was once thought of as a passing fad has become nothing short of a revolution in patient care.
References
1. Clinica, Complete Guide to the Diagnostic Market 2004–2009 (London: PJB Publications, 2003).
2. HL Lazar et al., “Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events,” Circulation 109, no. 12 (2004): 1497–1502.
3. “Point-of-Care Connectivity,” Doc. POCT 1-A (Wayne, PA: National Committee for Clinical Laboratory Standards, 2001).
4. A Reder, “Regulating the Point of Care: The IVD Connectivity Industry Consortium,” Medical Device & Diagnostic Industry 23, no. 4 (2001): 63–73.
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