A. The Past, Present, and Future of POCT
|“Everything old is new again” by Peter Allen (1944 – 1992),
Australian songwriter and entertainer.
Bedside → Central laboratories → POCT
- In the beginning, all testing was performed near the patient.
- As early as 1500 BC urine was noted in relation to diabetic symptoms in Egypt since ants were attracted to the sweetness of urine from diabetics. One of the earliest diagnostic practices was uroscopy, in which urine was visually examined and assessed for sweetness by tasting.
- Testing moved to central laboratories as hospitals were built (1800-1900’s) and testing technologies were developed.
- The development of hospitals and specialized care fostered the creation of laboratories, which required the transport of specimens from the patient to a central testing site. The introduction of advanced and automated technologies also encouraged centralization of laboratory testing. Economies of scale, regulations, and specialized technical staff were further incentives to consolidate testing.
- Shifts from the central laboratory to POCT and steady growth in the type and number of POC tests performed (late 1900’s to date) have been stimulated by:
- Technological advancements:
- Method and operation simplification
- Lockouts and failsafe mechanisms
- Electronic quality control
- Interconnectivity with laboratory and hospital information systems
- Demand for faster turnaround times and testing platforms to facilitate patient care (e.g. ICUs, POLs)
- Waived testing designation under CLIA88. See below.
- Creation of specialty clinics
- Desire for self-testing and patient control
- Mergers and reorganizations of healthcare systems, resulting in decreased numbers of central laboratories in the US
- Need for simple, robust testing tools in developing countries and other sites, e.g. military or disaster, underserved populations. See previous “Definition of POCT” with the multiple sites using POCT
- CLIA88 provided a tremendous impetus for growth in POCT. The history of that important legislation is summarized below
B. The Clinical Laboratory Improvement Amendments of 1988 (CLIA88)
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- Soon after Medicare and Medicaid went into effect in 1965, the United States government became aware of the programs’ vulnerability to fraud and abuse. To assure that money was not being siphoned off through overcharging for services and that the quality of services financed with tax dollars was adequate, the federal government established minimum quality requirements for those clinical laboratories that wished to participate in Medicare. These requirements, collectively known as the Clinical Laboratory Improvement Act of 1967 (CLIA67), officially covered only those laboratories doing business across state lines, which accounted for only a fraction of all US clinical laboratories. Soon, the need to regulate all laboratories performing tests on human specimens became apparent to lawmakers and, throughout the 1970s, amendments to CLIA67 were proposed--to stiffen personnel requirements and to mandate inspections to certify that laboratory facilities meet minimum standards for accuracy and quality control. CLIA67 took longer than many expected to revise. Eventually, the Clinical Laboratory Improvement Amendments were enacted in 1988 (CLIA88).
- In the meantime, to implement CLIA67, section 5(a) Part F of title III of the Public Health Service Act (42 U.S.C. 262-3) was amended by changing the title to read: “Licensing — Biological Products and Clinical Laboratories” and by adding the requirement (section 353) that any laboratory engaged in interstate commerce (i.e., soliciting or accepting, directly or indirectly, any specimen for laboratory examination or other laboratory procedures) must be CLIA67 licensed. Laboratories were given a full, partial, or exempt CLIA67 license, depending on the scope of the laboratory testing performed. CLIA67 regulations included applicability, license application and renewal, general provisions, quality control, personnel standards, proficiency testing, accreditation and sanctions.
- By 1972, 100 new amendments to the Social Security Act were made, including changes to the Medicare law. These new amendments established professional standards review organizations (PSROs), groups assembled by the Department of Health, Education and Welfare (HEW) that reviewed medical necessity, and the appropriateness and quality of services paid for with Medicare and Medicaid funds. Only independent and hospital laboratories seeking Medicare/Medicaid reimbursement were regulated under the Social Security Act and each facility type had its own regulations to follow. Later, the Omnibus Budget Reconciliation Act of 1987 was amended to require physician offices that performed more than 5000 tests per year to meet the laboratory regulations. At that time, laboratory testing in both physician office laboratories (POLs) and rural health clinics that did not accept and perform tests on referral specimens were not subject to those revisions because both the Medicare and CLIA67 statutes precluded the regulation of POLs and rural health clinics that performed tests only for their own patients.
- Beginning in 1987, a series of newspaper and magazine articles were published on the quality of laboratory testing. Simultaneously, television programs were aired concerning the number of laboratories that were not subject to either federal or state regulations. Congress held hearings in 1988 and heard testimony from “victims” of faulty laboratory testing. Specific concerns were raised about the validity of cholesterol screening and the accuracy of Pap smear results.
- On October 31, 1988, in response to the congressional hearings, Congress enacted Public Law 100-578, the Clinical Laboratory Improvement Amendments of 1988 or CLIA88, which greatly revised the authority for the regulation of laboratories. It was enacted as a means for the Secretary of Health and Human Services to develop comprehensive quality standards for all laboratory testing. Based on the concept of “site neutrality”, CLIA88 was to ensure the accuracy, reliability and timeliness of patient test results regardless of where the test was performed. CLIA88 defines a laboratory as any facility that performs laboratory testing on specimens derived from humans for the purpose of providing information for the diagnosis, prevention and treatment of disease, or for assessment of health. Facilities that do not accept Medicare or Medicaid or accept only cash must also be certified under CLIA88. It is the act of performing a laboratory test that defines the requirement of certification and not if or how the test is paid for. The definition of “laboratory” was also expanded to include any site where clinical laboratory testing occurs. Therefore, sites performing POCT, such as the patient’s bedside, a POL, or clinic, also assumed “laboratory” designation, a concept that was not fully appreciated by some clinical providers.
- CLIA88 is a user fee-funded government program; therefore, all costs of administering the program must be covered by the regulated facilities. The final CLIA88 regulations were published on February 28, 1992 after more than 70,000 comments and widespread public debate.
- CLIA88 also introduced the complexity model for test methods. Three categories of tests were established: waived, moderate complexity (including the subcategory of provider-performed microscopy), and high complexity. The more complicated the test, the more stringent the requirements. While CLIA88 specifies quality standards for personnel, patient test management, proficiency testing (PT), quality control, and quality assurance for moderate and high complexity tests, waived testing requirements are minimal.
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- Waived Testing
- Waived tests were defined under CLIA as “…simple laboratory examinations and procedures that are cleared by the Food and Drug Administration (FDA) for home use; employ methodologies that are so simple and accurate as to render the likelihood of erroneous results negligible; or pose no reasonable risk of harm to the patient if the test is performed incorrectly.”
- According to CLIA88, to perform waived tests, a laboratory must simply:
- Enroll in the CLIA program
- Pay applicable certificate fees biennially
- Follow manufacturers’ test instructions for tests that are FDA-approved for waived testing
- Be inspected if complaints or issues arise
- The original list of waived tests was limited to:
- Urine dipstick or tablet testing (bilirubin, glucose, hemoglobin, ketones, leukocytes, nitrites, protein, pH, specific gravity)
- Fecal occult blood testing
- Ovulation tests for luteinizing hormone (LH)
- Urine pregnancy testing
- Erythrocyte sedimentation sate (ESR), non automated
- Hemoglobin by copper sulfate
- Blood glucose testing by meters
- Microhematocrit, spun
- (Hemoglobin by a single test device was soon added)
- The concept of waived testing caused a great deal of controversy. Many organizations and groups felt that the proposed amendments to CLIA67 were too strict for all sites to comply with and patients would be denied access to testing so a simpler category of testing was needed. It was felt by other groups that the waived testing category created a dual standard for testing, with some laboratories having higher standards than others. Conceptually, many believed it was not really possible for a procedure to be so simple that the chance for error is negligible, or for a clinically useful test to have a negligible possibility of causing harm. For that reason, accrediting agencies other than the US government, such as the CAP and some states, have imposed stricter requirements on waived testing than are mandated by CLIA88.
- The numerous comments received about the waived testing category generated concerns both that the criteria were too subjective or too strict. Thus, in February 1993, the US Department of Health and Human Services (HHS) consulted with the Clinical Laboratory Improvement Advisory Committee (CLIAC) and Centers for Disease Control and Prevention (CDC) and it was agreed that the criteria for giving a test waived status needed “clarification”. A moratorium on granting further waived test approvals was instituted until December 1994. In September 1995 proposed clarification criteria were issued by HHS through the Healthcare Financing Administration (HCFA) and Public Health Services (PHS). These were formally adopted in 1997. Any test already approved by the FDA for home use was considered to be simple and have insignificant risk of error and therefore granted waived status. Tests that were substantially similar to already waived tests were given an expedited review process. New applications for waiver status needed to show performance characteristics that demonstrated the test was simple, easy to perform, and essentially error free. Standard protocols for test evaluation were used to remove the subjectivity in deciding that a test met waived criteria. These new criteria included:
- Specimens must be direct, not processed or manipulated
- Quantitative tests must be fully automated
- Qualitative tests are limited to single reagent impregnated devices giving positive or negative results
- Failsafe mechanisms must allow no results outside of the reportable range or when the system malfunctions
- No invasive trouble-shooting can be necessary. Electronic or mechanical maintenance must not be required.
- Instructions must be written at a 7th grade level, clearly defining all steps of the process and actions to be taken if quality control or calibrators were out of range
- Operators must follow manufacturers’ instructions; if they do not, the system immediately is classified as highly complex with all the strict requirements governing high complexity tests.
- Operators must have access to manufacturer contact information to report problems
- Detailed procedures for manufacturer field studies were established to prove the system could perform to expectations with appropriate specimens in non laboratory environments and by the lowest level of operators required
- These new clarified criteria were also meant to ensure that the operator skills required to perform and interpret waived tests were minimized so that non-laboratory personnel could not disrupt the procedure or introduce error. Since waived testing had no personnel requirements, HHS wanted to ensure that POC tests have minimal chance of producing an erroneous result. One consideration that could not be guaranteed by these new criteria was whether the operators could interpret results properly or recognize the context of a result, even if accurate.
- Because the requirements for waived testing are significantly less stringent than those for non-waived testing (moderate and high complexity testing), implementation of waived tests became attractive to many facilities. Facilities did not need to comply with the detailed CLIA88 requirements that include sections on accreditation, proficiency testing, administration, facilities, quality systems (covering all phases of testing and encompassing test verification, competency assessment, result reporting, etc), personnel standards, inspections, and enforcement. The manufacturing community also saw waived test development as a great opportunity for expanded markets, inside and outside of traditional healthcare facilities, since they could promote waived tests as having less regulatory oversight and easier bring and cheaper to use. In fact, HHS in its proposed clarification criteria anticipated that:
- Manufacturers would benefit from increased sales and distribution of waived tests.
- Laboratories would benefit from having more waived tests to offer with reduced regulatory burden and decreased costs, especially in underserved or rural areas.
- Consumers would benefit from having an increased range of laboratory services that were safe and accessible.
- The rules would drive technology to simpler more widely available laboratory tests.
- The “universe of waived tests” would expand to the benefit of patients, laboratories, manufacturers, and producers. HHS also acknowledged that the degree of growth of waived testing could not be accurately forecasted, but would depend on market decisions and technologic changes that could not be predicted.
- While POCT is not synonymous with waived testing, in practice most POCT is waived testing. Therefore, the growth of waived testing has resulted in the expansion and development of POCT, in ways not fully anticipated by HHS.
- Initially, most POCT/waived tests were simple ones that had been performed in the central laboratory or in home or self testing (e.g., urine dipsticks, fingerstick glucose monitoring, pregnancy testing) and were then redeployed as POCT. Soon, however, manufacturers responded to the growing demand for waived tests by developing new test methods, many designed specifically to be used outside of the traditional laboratory setting by non-laboratory personnel (e.g., hemoglobin A1c in diabetes clinics, prothrombin time and INR in coagulation clinics). As the technical expertise needed to perform some of these new test methods decreased, physicians in specialty areas (e.g., coagulation clinics, HIV clinics, dialysis centers) became interested in assuming responsibility (and revenue) for such tests, rather than sending them to a central laboratory. Similarly, simple POCT devices (e.g., INR) allowed patients who desired more responsibility for managing their health to perform self-testing.
- There are currently nearly 100 different waived analytes with over 1000 waived test systems and the list is constantly changing. The FDA provides an on-line list of waived tests (analytes and manufacturers), as well as a searchable database of all FDA approved tests that includes the testing category for each.
- Mergers and reorganizations of hospitals and healthcare systems have resulted in fewer full service laboratories. This has also played a role in the growth of POCT, as a means of maintaining access to commonly ordered laboratory tests. In developing countries, the need to be able to perform tests outside of traditional laboratories, without infrastructure such as refrigeration and power, and using less highly trained personnel is now frequently met by POC tests. For example, the Bill and Melinda Gates Foundation initiatives to accelerate the eradication of common infectious diseases in developing countries provides millions of dollars in grants each year to develop innovative, affordable ways to diagnose infectious diseases. Such technology will inevitably find its way into the market in developed countries as well.
- In the US, recognizing the need for testing outside the traditional laboratory, especially in underserved areas, the National Institutes of Health (NIH) through its National Heart, Lung, and Blood Institute, the National Institute for Biomedical Imaging and Bioengineering (NBIB), and the National Science Foundation (NSF) jointly fund POCT development (e.g., Partnerships for Point of Care Diagnostic Technologies for Nontraditional Health Care Settings and Point of Care Technologies Research Network). This funding supports four national centers researching and developing technologies for different aspects of POCT.
- Different regulatory requirements, (e.g., CMS, CDC,) International Organization for Standardization (ISO), World Health Organization (WHO), apply to different testing locales, driving the call for international standards in POCT.
- All these factors have contributed to the steady growth in the type and number of POCT tests performed. In 2010, it was estimated that one billion POCT tests would be performed in US hospitals, and that volume of testing would grow by 12.5% per annum.
C. Drivers of POCT
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- For the foreseeable future, it is anticipated that the trends described above will continue, driving robust growth in POCT. Specific drivers for adoption of POCT will include changes in the testing itself, and in the clinical, regulatory, and commercial environments.
- Changes in POCT methodology
- Technical advances will make POCT testing more attractive by making it:
- More accurate
- More robust
- Better interfaced to computerized patient records
- More inclusive of quality assurance and documentation features
- Changes in the clinical environment
- Demand for POCT will increase due to:
- Economic needs of hospitals for shorter stays and rapid patient turnaround.
Test results are needed rapidly not only for reasons of clinical urgency but to ease patient backlog in the emergency department, post anesthesia care unit, or other areas.
- Innovative therapies requiring rapid laboratory feedback
- The critical shortage of qualified medical technologists, which is likely to worsen
- Increasing demand for medical support at diverse sites (e.g., sporting events such as marathons, resorts, cruise ships, schools, camps)
- Increasing demand for rapid testing in outpatient settings
(e.g., cancer centers for outpatient chemotherapy)
- Increasing demand for self testing in patients’ homes
- Disaster preparedness
- Underserved populations and underdeveloped regions without the infrastructure or manpower for central laboratory testing and to promote access to care
- Changes in commercial environment
- Attracted by the very large growth rates in POCT compared to traditional central laboratory testing, and relatively favorable profit margins, industry will heavily promote POCT.
- Changes in regulatory environment
- Continued trend to promote POCT for all the reasons noted above and to foster “personalized” healthcare
- However, drivers are offset by the potential impact of the 2008 FDA guidance directives that have slowed the introduction of new waived tests.
- In 2008, in response to the growing numbers of waived tests and concerns regarding testing quality and patient safety, HHS issued more detailed and rigorous guidelines for manufacturers of products intended for waived testing. These guidelines made it more difficult for a product to achieve the waived designation and effectively decreased the numbers of submitted waived test requests, as well as the number of new waived testing products introduced to the market place. The impact of these and future regulations remains to be seen, but concerns have been raised about the potential complexity of some of the analytes on waived devices, (e.g., blood gases and metabolites). A growing concern, as evidenced by recent FDA focus, is the use of similar devices for both patient self-monitoring and intensive care monitoring. A prime example of this is glucose meters used on unstable acutely ill patients in ICUs, where many patient variables affect results and life-threatening treatment may be instituted, (e.g. insulin injection with the potential for hypoglycemia and death).
- Questions arise about whether there should be different standards for devices or tests used in different care environments, (e.g., pregnancy tests for home use versus used in healthcare settings before radiologic studies).
- Military applications
- The US military system is comprehensively organized into echelons of care, ranging from Echelon 1, the most basic care on the battlefield, to Echelon 5, representing tertiary care at an Army hospital. The system is intended to provide access to the highest quality care to soldiers, in return for their service, but also to maximize combat effectiveness. At the lowest echelons of care, POCT may be the only type of laboratory support possible, or the most desirable type, especially for combat or transport settings.