The immuassay handbook parte47

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The immuassay handbook parte47

  1. 1. 455© 2013 David G. Wild. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/B978-0-08-097037-0.00031-2 The decision to conduct laboratory testing in a formal, main laboratory or to decentralize the testing closer to a patient care unit is a balance between clinical need and patient outcome. With recent economic pressures, decreasing reimbursement for healthcare costs, and the advent of accountable care organizations, the choice of where to conduct laboratory testing will be determined by the cost effectiveness of the delivery model, integration into the overall healthcare system, and ultimately the benefit to the patient. As hospitals and clinics consolidate to form more cost-effective partnerships, some main laboratories are being closed, resulting in the transporta- tion of specimens to regional reference laboratories with delays in the reporting of test results. The clinical need for a rapid turnaround of critical tests has increased the utility of point-of-care testing (POCT) at remote sites in these health systems. POCT promises rapid results and earlier therapeutic intervention. However, the convenience of obtaining a fast result does not necessarily lead to improved patient care, particularly when the technical performance of POCT is not equivalent to that of a main laboratory result. Con- cerns over the quality of the test, incorrect test perfor- mance, and inadequate operator training can cause clinicians to doubt the validity of POCT and lead to dupli- cate and confirmatory testing that actually increases healthcare costs and risk to the patient. In addition, there is a spectrum of delivery options for POCT from bedside testing, portable carts, home care, and even formal satellite laboratories. The optimal delivery model for any given institution will be influenced by a variety of factors. Test menu, test volume, patient population, cost, number of operators, management structure of the institution, regu- latory environment, educational level of the operators, dif- ficulty level of performing the test, and documentation of test results are just some of the complex issues which must be considered before choosing to offer POCT. Delivery Options TERMINOLOGY Point-of-Care Testing (POCT) is defined as laboratory testing conducted close to the site of patient care, typically by clinical personnel whose primary training is not in the clinical laboratory sciences, or by patients (self-testing). POCT refers to any testing conducted outside a main, central, or core laboratory setting. Other common terms for POCT are ancillary, bedside, decentralized, near- patient, patient-focused, peripheral, portable, and satellite testing. Some of the terms may be more general in mean- ing, as ancillary or peripheral testing can describe any testing outside of a main laboratory. Other terms are more specific, like bedside testing that describes testing con- ducted solely at the patient’s bed. The multitude of words used to describe POCT adds confusion. In general, discus- sions of POCT should limit the number of terms and always define the exact meaning whenever changing POCT terminology. SITES POCT will not necessarily be utilized in the same manner in every location, as each testing site will involve different patient populations and clinical applications of the test result. The location determines the types of patients ana- lyzed: the patient population. POCT in the ambulance/ helicopter transport, emergency room, operating room, and intensive care units (ICUs) involves acutely ill patients. These patients present with extremes of hematocrit, blood gases, metabolites, and multiple drug therapies that place added technical demands on POCT performance. Devices calibrated to the average population may demonstrate sig- nificant bias when used on certain hospitalized patients. Chronically ill patients, on the other hand, present with more average profiles. Chronic patients are found in the general medicine, obstetrics/gynecology, psychiatric, dial- ysis, dental, outpatient clinics, and home nursing settings. Other areas for POCT involve the judiciary system, insur- ance industry, and even patient self-management. Although POCT brings laboratory testing closer to the patient, there are many different options for conducting POCT. Testing can be performed at the patient’s bedside on capillary whole blood collected by fingerstick. Another option is to collect a blood specimen from an indwelling line and carry the specimen to a utility closet in the ward where POCT can be conducted. The difference between bedside testing and testing in a spare utility closet down the hall may require anticoagulation of the specimen due to delays in testing, which may be minimal but sufficient to start specimen clotting. Differences in sample type and collection (fingerstick vs. line draws) can further affect the technical performance of a device. Thus, devices manufac- tured for home use on capillary blood may not perform equally well when utilized in a hospital setting on venous or arterial blood. Other delivery options for POCT include portable carts where POCT devices and reagents can be moved from room to room in an institution using a small staff of dedicated operators. POCT has also been per- formed in patients’ bathrooms where urine dipstick analy- sis and occult blood testing is common, but also where POCT reagents may be exposed to water, humidity, and cleaning solutions commonly used in bathrooms. Given the variety of delivery options, immunoassay test- ing, whether conducted as POCT or in a main laboratory, Point-of-Care Testing James H. Nichols (james.h.nichols@vanderbilt.edu) C H A P T E R 6.3
  2. 2. 456 The Immunoassay Handbook must be equivalent throughout an institution or health sys- tem in order to manage clinical therapies. Patients may enter a hospital through the emergency room, have an operation and end up in an ICU, an intermediary care unit, a general medicine unit, and finally be treated as an outpatient through clinic visits and home healthcare. POCT results from each of these locations, performed by different operators on different devices or test kits can be interspersed with main laboratory results. To achieve con- tinuity of care, a test must be site independent and gener- ate equivalent results, otherwise separate reference ranges need to be established for effective clinical interpretation. Maintaining testing equivalency and reliability of results in order to meet clinical needs are the goals of POCT quality assurance and management efforts. OPERATORS The quality of POCT is directly related to the ability of the operator to perform the test. POCT devices are mar- keted to be easy to use so that POCT can be conducted by a variety of individuals with minimal training. Quality, however, requires operators to be trained on the specific POCT method (not just general familiarization) with ongoing, periodic checks of operator competency. Opera- tors can have varied levels of education from support tech- nologists with only a high school education, to nurses with 2 or 4 years of college, medical students, and practicing physicians with postgraduate education. Research has demonstrated that for simple, one-step devices containing internal controls and not requiring sophisticated volumet- ric pipetting, operators can perform equally well indepen- dent of educational level provided that they have successfully completed a standardized training program on that device. When devices are more complicated, involv- ing multiple steps and technical expertise, training becomes even more important and performance becomes depen- dent on educational level. Thus, training with periodic competency checks is fundamental to obtaining quality POCT results. MENU Many laboratory tests are currently available in a point- of-care format. Critical care whole blood analytes include blood gases, electrolytes, coagulation, glucose, and hemoglobin. Organ-specific tests can be conducted for cardiac enzymes (creatine kinase, myoglobin and tropo- nin), renal function (creatinine and urea nitrogen), pan- creatic enzymes (amylase and lipase), and bone turnover (N-telopeptides). Occult blood is available for gastric and fecal specimens. Neonatal hypoxia can be assessed through scalp pH. Urine tests include pregnancy, specific gravity, urine dipsticks, and drugs of abuse. Rapid micro- biologic screens are available for Streptococcus, Helicobacter pylori, and influenza. Human immunodeficiency virus (HIV-1), infectious mononucleosis, and lyme disease antibody testing can be performed on fingerstick capil- lary blood. Microscopic tests can also be conducted point-of-care by clinicians for wet mounts, pinworm exams, fern tests, semen, postcoital exams of cervical mucous, and urine sediment. The varied menu of tests available in a point-of-care format indicates the potential utility of POCT in many patient care settings. ECONOMICS The cost of POCT is dependent on how the test is deliv- ered and managed at each site. As each site is unique in the delivery of POCT, overall costs will be related to the num- ber of testing devices, number of trained operators, test volume, and percentage of testing dedicated to quality control tests. Each device or test kit requires regular qual- ity control to document stability of performance during storage. As the number of devices, opened test kits, or bot- tles of test reagents increase, there will be additional qual- ity control required. Additional labor and supplies will be dedicated to quality control testing, increasing cost. Limit- ing the number of devices is one way to lower cost. Unless testing volumes at a particular site are high enough to necessitate the use of multiple devices, POCT manage- ment should seek to minimize the number of devices and open test kits at each site. The number of operators at a site also affects the cost of testing. The time involved initially training operators and maintaining skills competency increases with the number of operators in a nursing unit. As the number of staff increases, more labor is required to manage staff compe- tencies. Operators need to perform quality control testing to document skills competency. More quality control leads to higher costs both in reagents and labor. Thus, decreas- ing the number of operators is a further means of minimiz- ing POCT costs. Test volume is another factor affecting POCT cost. POCT differs from testing conducted in a central labora- tory, as there is no dedicated space. For a large, automated analyzer in a main laboratory, there is a considerable initial investment in the instrument as well as ongoing facility overhead, for space, light, water, and electricity. Yet, the variable, unit reagent cost of each test is minimal. POCT is exactly the opposite, the capital and overhead costs for the analyzer are lower (or negligible with test reagents that are read visually) but the unit, variable costs are generally higher. POCT thus has higher variable costs but lower fixed instrument and facility costs when compared to test- ing in a main laboratory (Table 1). The overall effect of these factors will depend on the test volume. The cost per test for main laboratory analysis will drop faster than POCT as test volume increases, since high fixed costs can be distributed among more tests. For POCT, there are minimal fixed costs for instrumentation and facili- ties, but the labor involved in training and supervising operators is greater due to the larger number of POCT operators compared with the limited staff in a main labora- tory. In comparing the two delivery options (POCT vs. main laboratory), fixed instrument costs and facilities in the main laboratory balance the cost of labor for initial POCT training and ongoing program supervision (Table 1). The greatest difference is in variable reagent costs. As testing volume increases for POCT, unit costs increase propor- tionally. Depending on the volume, cost for POCT can approach equivalence with cost of testing in a main labora- tory when POCT sites are performing high volumes of testing compared to lower volume testing in the main
  3. 3. 457CHAPTER 6.3 Point-of-Care Testing laboratory; see 10,000 patients/year main laboratory cost per test compared to cost of POCT for 100,000 patients/ year (Table 1). Quality control testing, however, can significantly affect test cost. Since POCT quality control is performed at higher unit cost, minimizing the amount of quality control significantly reduces the cost of POCT. Table 1 compares the price per test for main laboratory and POCT at 10% and 20% quality control to patient testing ratios. A change that increases the percentage of quality control by only 10% leads to a change of $0.09–$0.17/test, adds 4–8% to the total test cost. As more devices and operators are added to a POCT program, there is more quality control. The cost of testing increases, since the ratio of quality control to patient tests increases. Ultimately, in order to reduce the amount of quality control performed, a balance needs to be achieved at each site between the minimal number of staff required to meet clinical demands, and the amount of quality control required to maintain a sufficient number of patient samples for each operator to maintain competency. Thus, keeping quality control testing to a minimum decreases POCT cost. POCT costs are a summation of site-specific factors. Costs can vary, since each site has a different number of devices, operators, test volume, and frequency of quality control. Cost estimates for one site are, therefore, not entirely applicable to other sites. Published cost savings from one institution should be viewed cautiously when extrapolating to other institutions. Even with comparable methodology and clinical application, differences in POCT delivery and administrative policies can affect the amount and type of documentation and supervision required such that the same cost savings from one institu- tion may not be achievable at other institutions. CLINICAL OUTCOME POCT, as with any laboratory test, should always be uti- lized to answer specific clinical questions. Laboratory test- ing, in general, should reflect the clinical symptoms and assist in moving patients through clinical and diagnostic pathways. Random use of POCT is as dangerous a practice as blindly ordering all available main laboratory tests on every patient in the hopes of finding an abnormality. TABLE 1 Cost Analysis of a Hypothetical POCT ($) Main Laboratory POCT 10,000 pts/yr 100,000 pts/yr 10,000 pts/yr 100,000 pts/yr Fixed costs Instrumentation 10,000 10,000 2000 2000 Facilities 2100 2100 – – Training 1200 1200 2800 2800 Supervision 4160 4160 10,400 10,400 Proficiency 500 500 500 500 Fixed total 17,960 17,960 15,700 15,700 Variable costs Reagent 10% QC 5500 55,000 11,000 110,000 Reagent 20% QC 6000 60,000 12,000 120,000 Labor 10% QC 3667 36,670 7370 73,700 Labor 20% QC 4000 40,000 8040 80,400 QC 10% calibration verification 1200 1200 1500 1500 QC 20% calibration verification 2000 2000 1500 1500 Variable total 10% QC 10,367 92,870 19,870 185,200 20% QC 12,000 102,000 21,540 201,900 Total costs 10% QC 28,327 110,830 35,570 200,900 20% QC 29,960 119,960 37,240 217,600 Cost/test 10% QC 2.83/patient 1.11/patient 3.56/patient 2.01/patient 20% QC 3.00/patient 1.20/patient 3.72/patient 2.18/patient Main laboratory costs based on: two laboratory instruments of $100,000/ea to perform four tests amortized over 5years (2×$100,000/4×5=$10,000/year): facility costs of $2100/year for water, lighting, space rental; training of five technologists for 10h at $20.00 (including benefits) and 10h to write the procedure at $20/h (50×$20+10×$20=$1200); supervision costs of 0.1 full time equivalent (FTE) at $20/h or $41,600/year (0.1×$41,600=$4160); proficiency survey $500; reagent costs $0.50/test (10,000×$0.50+1000×$0.50 for QC=$5500); labor of 1min/test ($20/h/60min=$0.33/test+10 or 20% for QC); quality control and calibration verification based on utilization per year with a discount for higher volumes. POCT costs estimated as: four devices on two patient care units at $500 (4×$500=$2000); training of 100 operators for 1h at $20/h nursing (including benefits) and writing standardized training program 40h at $20 (100×$20+40×$20=$2800); supervision of 0.25 laboratory FTE (0.25×$41,600=$10,400); proficiency survey $500; reagent of cost $1.00/test (10,000×$1.00+1000×$1.00 for QC=$11.000); labor of 2 min/test at $20/h nursing ($20/60 min×2=$0.67/test+10 or 20% for QC); quality control and calibration verification based on fixed price per year for up to 10 devices. Note how the price of POCT/patient is actually lower than the laboratory cost per patient when testing volume is high at the POCT site ($2.01/patient at 100,000 test/year) and low in the laboratory ($2.83/patient at 10,000 tests/year). Cost analysis for POCT is therefore dependent on the organization and individual delivery options at each site.
  4. 4. 458 The Immunoassay Handbook Laboratory testing should be ordered judiciously to answer specific diagnostic questions based on the patient’s pre- senting symptoms and pretest probability/prevalence of disease. POCT is no exception. POCT should compli- ment main laboratory testing by offering the clinician a comparable diagnostic test for specific patient care dilem- mas where a faster result can improve patient outcome. Despite the potential of POCT to enhance patient care, POCT is often used more for convenience than for answering a specific clinical problem. Overutilization and use of POCT for convenience only raises healthcare costs when POCT results do not agree and additional testing is ordered from the main laboratory to confirm a question- able POCT result, duplicating efforts. Important clinical reasons to justify implementation of POCT are: G Turnaround time – faster results and potential for rapid treatment. G Vascular entry – decreased risk for fingerstick com- pared to phlebotomy, especially with oncology patients and others with coagulation disorders. G Blood loss – smaller volumes of specimen required for POCT, which is beneficial for neonates. G Education – required as part of house-staff training in a teaching institution. G Practice trends – the increased acuity of inpatient ill- nesses that require immediate clinical action on results. G Efficiency – clinicians treat other patients while waiting for test results, time must then be spent refamiliarizing the case history when the result becomes available. POCT provides rapid results with immediate treat- ment and eliminates the time wasted in rereading case histories. The common theme sustaining POCT is its ability to resolve a clinical need. POCT blood gases and glucose, for instance, have been implemented in sites that have criti- cally ill patients where the concentration changes so rap- idly that the physiologic state of the patient will be different by the time a test result is available from a main laboratory. Immediate results and faster clinical treatment (like inten- sive insulin management) can move patients through an ICU faster and result in shorter hospitalizations. Coagula- tion testing has been utilized to adjust clotting times after cardiac bypass surgery. By providing faster coagulation results, POCT allows immediate titration of protamine doses, saving time spent in expensive postoperative recov- ery areas waiting for laboratory results. Use of pregnancy tests in the same day surgery area, reduces patient wait times for those women who show up for outpatient sur- gery without a recent pregnancy test. By offering onsite pregnancy testing, POCT eliminates patient waiting, rescheduling surgery, and the loss of expensive surgeon and operating room time. Use of hemoglobin testing in postsurgical recovery rooms has further allowed quicker assessment of postsurgical bleeding and limits the need for blood transfusions. Implementation of bedside blood gases in the ICU has decreased the frequency of testing and the amount of blood drawn for each test, resulting in signifi- cantly less blood loss over an entire ICU stay. POCT can therefore offer beneficial patient outcomes when utilized to meet specific clinical needs. Outcomes can be measured in real units like time and money or in subjective units like patient satisfaction. In this manner, the cost of performing the test at the point-of-care can be balanced with the clini- cal effect, both justifying the need for POCT and docu- menting improvements in clinical service. Although POCT may benefit some patient populations, these outcomes do not imply that the same test can be per- formed universally on all patients with the same effect. Pub- lications touting the tremendous cost savings and significant advances in patient care provided by POCT need to be viewed critically for the administrative structure of the test- ing practices at that site, particularly with respect to the patient population, volume of testing, number of trained operators, quality control practices, and management over- sight. Given the spectrum of possible situations, cost- effective POCT at one site on a specific patient population may not be cost-effective at another site on a different patient population. Each site needs to be viewed independently. POCT devices also do not demonstrate the same accu- racy and precision as core laboratory instrumentation. Greater imprecision and biases between glucose meters, preclude their use in diagnosis of diabetes and limit their usefulness in screening for diabetes. Most POCT creati- nine methods do not have the capability of reporting to two significant decimal places and POCT methods show significant biases when compared to isotope dilution–mass spectrometry calibrated methods in a main laboratory. Current professional guidelines recommend the reporting of creatinine values to two significant decimal places to reduce the variability of estimated glomerular filtration rates from those values. POCT creatinine is increasingly needed to deliver fast estimates of patient renal function in radiology for the determination of a patient’s ability to clear radiopaque dyes and in hematology/oncology for dosing chemotherapy. Differences between various POCT and core laboratory methods are thus an important consid- eration when physicians are ordering and interpreting a test. Yet, the adoption of electronic medical records has sought to maximize the display of information to the clini- cian by overlaying POCT with main laboratory results, despite differences in method performance, interferences, and biases. The clinical situation should dictate the type of method that is appropriate for that point in a patient’s care based on the method’s limitations, and the display of test results should be clearly defined in the patient’s medical record to prevent confusion over the testing method and location where the test was performed. Once the decision to implement POCT has been made, clinicians must be made aware of the available test meth- ods, advantages, and limitations, and educated on how to order the appropriate test. The criteria determined from outcomes assessment should assist clinicians in choosing whether to order a test as POCT, send a sample to a local stat laboratory, or transport the specimen to a more dis- tant main laboratory based on the method’s overall per- formance in the specific patient care setting. The required turnaround time of results, clinical need, and when the result will be acknowledged and therapeutic action insti- tuted by the clinician should be part of the decision of where to perform the test. Staff rushing to perform POCT that sits in a patient’s chart for hours before acknowledg- ment and action by the physician is a poor use of clinical resources. Optimal decision trees for the type of tests and
  5. 5. 459CHAPTER 6.3 Point-of-Care Testing where to send those tests for different patient decisions form the basis for current research in critical pathways and decision support. These pathways seek to optimize patient outcome and minimize healthcare costs by indicat- ing which practices lead to the most beneficial outcome. Initial pathways of care tend to be general and only indi- cate the tests ordered for particular diseases. Later refine- ments of clinical pathways focus on specific outcomes from different tests available, POCT vs. main laboratory and which test is recommended at specific points in the patient’s treatment based on outcomes or evidence-based research. Quality Assurance COMPONENTS OF GOOD LABORATORY PRACTICE Quality assurance of POCT, like other laboratory testing, requires control over the entire testing process, from phy- sician order, patient preparation, and specimen collection, to transportation, analysis of the specimen, result report- ing, clinical interpretation, and therapeutic intervention. Each step must be analyzed for potential sources of error, and control monitors instituted to determine when the testing process is successful and intervene when it fails. POCT shares similar quality issues with main laboratory testing, and POCT only eliminates the specimen transpor- tation and processing steps. Problems with inappropriate testing, improper collection of specimens from unpre- pared patients, transposition of numbers in the test result, and incorrect clinical interpretation of the result are all areas for mishaps. Technical problems with the analysis must also be examined for instrument interferences and operator errors. Historically, quality assurance of laboratory testing has focused on instrument errors. Systematic and random errors occur most frequently from the laboratory instrument and reagent interaction on the instrument. Performance of lab- oratory instrumentation is relatively independent of opera- tor effects. Operators are only required to maintain reagent supplies, load samples, push a button to start the analyzer, and troubleshoot when problems happen. Quality assurance of laboratory testing is more manageable than POCT given the limited number of instruments and technologists in a main laboratory. Each operator has narrow focus and con- siderable experience from repeated operation of the same instrumentation. The performance of POCT devices, on the other hand, is more dependent on the operator. Results can change with differences in specimen loading, test timing, washing steps, and lighting conditions for manual, visually inter- preted tests like pregnancy, drug, and urine dipsticks. Variations in color discrimination between operators can affect POCT results. Newer generations of devices have sought to make devices independent of operator effects by automating the test timing and detection steps. Yet, qual- ity assurance of POCT is more difficult to manage than core laboratory testing, as there can be hundreds of POCT devices and thousands of operators distributed throughout a health system. The primary focus of these operators is patient care. Nurses, physicians, and other clinical staff are not attuned to laboratory practice, and POCT is only a minor part of their daily responsibilities. Staff may only infrequently perform POCT. Quality assurance programs for POCT must therefore ensure consistent test perfor- mance by controlling operators, reagents, and devices. Experience from institutions with POCT programs has linked several components of these programs to high ini- tial quality of testing and consistent improvements in qual- ity over time. These programs: G Involve laboratory personnel in the initial training of operators. G Include standardized training tools, like video/DVDs, as part of the training. G Repeat training and review performance and compe- tency at scheduled intervals. G Regularly compare POCT results to the main laboratory. G Utilize computerized data capture of POCT devices when available to store quality control and patient data. Operator training, with ongoing checks of competency, is important for obtaining good POCT results. Training specific to the particular POCT device guarantees correct initial performance, but periodic comparison of POCT results to the main laboratory with operator retraining guarantees high levels of continued performance. Auto- mated capture of quality control and patient data assists the management of POCT quality by reducing the amount of labor required to document results, verify operator competencies, and review laboratory comparisons. REGULATIONS Regulation of POCT seeks to ensure that it is conducted under the direction of a structured quality assurance pro- gram. Currently, the United States of America has feder- ally mandated POCT quality regulations with monetary penalties for institutions that fail to meet the guidelines. Other countries are adopting quality regulations regarding POCT, and professional society guidelines have appeared with recommendations for quality assurance practices for POCT devices. In the US, POCT is subject to multiple regulations with varying levels of stringency. Home testing by patients on their own devices requires FDA approval of the device for “home use” prior to marketing. Hospital and healthcare use of POCT must meet both federal and individual state regulations where the test is conducted. State regulations for POCT vary, and some are more or less stringent than the federal regulations. Institutions are advised to consult their own local states for specific guidelines. All healthcare use of POCT, however, is subject to the Department of Health and Human Services, Clinical Lab- oratory Improvement Amendments of 1988 (CLIA ’88). CLIA divides laboratory testing into three levels of com- plexity: waived, moderate, and high complexity, depend- ing on the difficulty of the testing process. These regulations are enforced through the threat of losing fed- eral Medicare reimbursement for laboratory testing which can result in a significant loss of income to the institution
  6. 6. 460 The Immunoassay Handbook as well as additional legal penalties. CLIA focuses on con- trolling the entire testing process, from preanalytic sample collection, device operation, and analyst competency to result reporting and interpretation. The CLIA regulations track the path that a specimen follows through the labora- tory. Updates to CLIA interpretation include the required frequency of quality control for certain tests, and establish- ing one set of quality control standards for all laboratories performing nonwaived complexity testing (i.e. moderate and high complexity tests). Three accreditation agencies inspect and certify health- care laboratories for CLIA compliance: the Joint Commis- sion on the Accreditation of Healthcare Organizations (the Joint Commission), College of American Pathologists (CAP), which accredit hospitals, and the Commission on Office Laboratory Accreditation (COLA), which accredits private physicians’ office laboratories (POLs). Since the CAP guidelines are stricter than the Joint Commission and some state regulations, inspection and accreditation by CAP does not necessarily require reinspection by these other agencies because CAP has “deemed status” with that agency. Other agencies and some states have similar equiv- alencies and “deemed status” to the federal guidelines. Laboratories may, therefore, have multiple certifications but only require a single inspection by the strictest of the accreditation agencies. POCT under CLIA generally falls into waived and moderate complexity categories. Waived POCT includes simple test kits approved by the FDA for home use: glu- cose, urine dipsticks, hemoglobin, and pregnancy, and those tests that have been found by the FDA to be simple in operation, including drugs of abuse tests, HIV testing, and some chemistry analyzers. All other POCT not on the federal waived category list are considered moderate complexity. The Joint Commission has a separate set of guidelines for waived complexity tests. Waived POCT, under the Joint Commission, must comply with six guidelines: G The organization must define how the POCT is to be used; i.e. for diagnosis or patient management. G A list of all personnel involved in POCT (director, supervisors, and operators) must be maintained. G There must be documentation of initial training spe- cific to the POCT device for all operators and demon- stration of ongoing competency. G Written policies covering all aspects of the testing pro- cess – patient preparation, sample collection, analysis, reporting results, and interpretation – must be readily available to each operator. G Quality control must be performed according to manu- facturer’s specifications and at the recommended frequency. G POCT results must be recorded so that there is an audit trail available between patient specimen, quality con- trol performance records, operator competency, and training documentation. The Joint Commission guidelines are general recommen- dations, and the specifics of meeting the guidelines are left to each organization. For instance the following can all demonstrate operator competency. G Routine performance of quality control. G Analysis of a blind specimen of known value (profi- ciency sample). G Visual inspection of the operator. For waived tests, an institution only needs to document that it has a means of demonstrating operator competency and that the institution follows its own policy in order to satisfy the Joint Commission guidelines. Moderate complexity POCT under the Joint Commis- sion, COLA, and CAP is considered comparable to main laboratory testing and is judged by the same standards. POCT must be conducted under the direction of the main laboratory. Moderate complexity testing requires a technical director, a supervisor, and a clinical consultant, and there are specific recommendations regarding the educational level of operators. Patient results must be verified on a regular basis (daily) by the laboratory supervisor. In addition, there are recommendations for method and reagent validation, stor- age, maintenance, laboratory environment, result documen- tation, and operator competency. At a minimum, two levels of quality control must be performed daily and calibration must be verified semiannually or with each shipment of reagent lots. POCT should further be part of an external proficiency testing program to compare POCT perfor- mance to other peer institutions. Oversight of POCT should involve a multidisciplinary team with nursing, clinician, and laboratory membership. Overall, the testing process should be part of a continuous quality improvement scheme that can document baseline performance, target areas for improvement, and indicate the result of systematic program changes to POCT quality. CAP distinguishes between waived and nonwaived categories of testing for some aspects of a testing program including quality control and calibra- tion verification. But, CAP requires that all POCT subscribe to a proficiency testing program and be conducted under the supervision of a laboratory-trained medical director regard- less of the complexity of testing. Operator competency for moderate complexity tests must document all six elements of competency for each operator, annually: 1. Direct observations of routine patient test perfor- mance, including, as applicable, patient identifica- tion and preparation, and specimen collection, handling, processing, and testing; 2. Monitoring the recording and reporting of test results, including, as applicable, reporting critical results; 3. Review of intermediate test results or worksheets, quality control records, proficiency testing results, and preventive maintenance records; 4. Direct observation of performance of instrument maintenance and function checks; 5. Assessment of test performance through testing pre- viously analyzed specimens, internal blind testing samples or external proficiency testing samples; and 6. Evaluation of problem-solving skills. In summary, the US regulations mandate laboratory involve- ment in the POCT process to ensure that testing is con- ducted under a defined quality assurance program. Although some of the regulations may seem trite by requiring exces- sive paperwork and oversight, the final consequence of these
  7. 7. 461CHAPTER 6.3 Point-of-Care Testing regulations emphasizes the assessment of clinical need for POCT within a healthcare organization. POCT cannot be viewed as mere convenience. By forcing institutions to real- ize that quality POCT has labor and supervision costs with regulatory impact, unnecessary redundant testing can be limited. Only through complementary use of POCT and testing in the main laboratory with assessment of clinical outcomes can overall healthcare be optimized. DATA MANAGEMENT Quality assurance of POCT generates volumes of data. Records of instrumentation include initial validation, main- tenance, troubleshooting, quality control, and patient test- ing results. Operator records contain training and competency. Finally, reagent records document validation of shipments, utilization, and storage. Managing this data becomes more difficult as the number of devices, operators, and reagent lots increase. Methods that automate the man- agement of POCT data provide an advantage by improving documentation compliance and saving labor in data review. POCT data management is a threefold process involv- ing capture of data by the device at the time of testing, transfer of data to a central information system, and statis- tical reduction to obtain quantitative parameters for review. Computerized POCT devices are capable of auto- mating data management. In terms of testing volume, this includes about half of the current POCT: glucose, electro- lytes, blood gas, hemoglobin, and coagulation testing. The other half is manual POCT: urine dipsticks, pregnancy, occult blood, and drug testing. Management of manual testing continues to pose a challenge. When available, computerized data management can assist the laboratory in supervising the POCT program. POCT devices with data management prompt the operator for required information. Operator and patient identifica- tion can be entered manually or by barcode reader. Test results are stored with the date, time, reagent lot, reagent expiration date, quality control lots, control expiration dates, control ranges, and operator and patient identifica- tion to provide a complete audit trail for quality assurance. Computerized POCT devices also have lockouts, which only allow trained, certified operators to perform testing, remind the operators when to perform quality control and prevent reporting of patient results if controls fail. These features ensure that the device only releases results within institutionally defined parameters. As POCT results have the potential to be utilized immediately in patient care, the POCT device lockouts are invaluable in checking that con- trol criteria are met before patient testing, since laboratory review after analysis would add to the result turnaround time and may not be practical with each result. POCT devices, however, are limited in the amount of data that can be stored and they require periodic down- loading. Data can be transferred directly to a computer with larger memory capacity. Laptop computers are por- table and provide a convenient means of collecting data from remote POCT devices. Yet, laptops require a person to manually connect the computer to each device, physi- cally requiring someone to carry the laptop to the device or to periodically bring the device to the laptop. Telephone connections via modem are also available for downloading POCT data from remote sites, but the internet provides a ready means of collecting data where internet connections are available. Recent developments are exploring the abil- ity to utilize wireless technologies to transfer data from remote sites to a central computer. Wireless provides a real-time means of obtaining data. The amount of labor for a technologist to manually download POCT devices can be significant, particularly for POCT programs with hundreds of devices. Automating the transfer of data thus provides an opportunity for considerable labor savings and improved review of data. Unfortunately, connecting POCT devices can be costly. Each manufacturer has developed their interfaces indepen- dently with proprietary hardware and unique communica- tion protocols. For users, the custom nature of each POCT device translates into separate data manager computer sys- tems for each device with the added expense of separate wir- ing and separate interfaces. This added expense discourages the implementation and conversion to new POCT. Efforts to standardize the communication protocols have led to a collaborative consortium of POCT users, organizations, and manufacturers, and the development of a POCT1-A2 standard for connectivity, now maintained by the Clinical and Laboratory Standards Institute (CLSI). This standard promotes seamless information exchange between POCT devices, electronic medical records, and laboratory informa- tion systems, and meets the key user requirements for bidi- rectional communication, standard device connections, use of existing hospital infrastructure, interoperability with commercial software, and data security. Once POCT data is collected in a central database, the data can be statistically reduced and reviewed. Quality control can be tracked for trends, and problems identified, for targeting future program improvements. Operator performance can be monitored and compared. Patient data can be verified, trend reports printed for clinical man- agement, and billing statements generated for reimburse- ment. Unfortunately, this type of analysis is only available for data stored on a computer. For manual POCT, compa- rable statistical review is only available if results are manu- ally entered into a computer. Given the volume of manual testing, this is a laborious task that can generate other errors involved in numeric transposition and key entry mistakes. Compliance with manual data entry is also impractical on a busy patient care unit. Only a check on test utilization can indicate if all POCT manual testing is accurately being captured. Some computerized POCT devices, like glucose meters, allow entry of test results from manual POCT at the bedside, leveraging the porta- bility of POCT devices and connectivity to capture and transfer results from manual dipsticks and tests. Practical Management TECHNICAL VALIDATION Ensuring that POCT gives accurate results that are com- parable to a main laboratory, in all the situations likely to be encountered in an institution, requires knowledge of the technical limitations of the test. Prior to use on patients,
  8. 8. 462 The Immunoassay Handbook POCT should be validated to determine that results match manufacturer’s specifications. Testing the devices under conditions in which they are planned to be used is impor- tant to accurately predict POCT performance once imple- mented. Hospitals, physicians’ offices, and home nursing are different practices from the patient self-testing for which many POCT devices were intended. Hospitalized and acutely ill patients can have different physiologic parameters when compared to home patients (e.g. hema- tocrit). Differences in patient population can lead to POCT biases. These effects should be considered when selecting a possible POCT method. Determination of acceptable performance, however, will depend on the clinical application. More variability may be acceptable in some situations and unacceptable in others. A consensus of clinical tolerance needs to be established prior to selecting and validating a POCT method. Published standards can assist in setting tolerance limits for POCT, but ultimately institutions must determine the criteria for acceptable performance within their own clinical practice. Method selection should consider the variables within the institution that can affect POCT. This will involve determining how individual POCT will be utilized at every testing site. Important variables to consider are: G Vibration – is the device sensitive to vibrations that could occur in mobile transport vehicles like ambulances? G Humidity – is the environment controlled or can sea- sonal variations occur? G Temperature – will the device reagents be exposed to ambient temperature extremes of summer heat or win- ter cold during storage, transportation, or analysis? G Lighting – will the POCT be exposed to direct sunlight during storage or analysis? Does indoor fluorescent lighting affect the color development of dipsticks and tests? G Hematocrit – what are the acceptable tolerance limits of the POCT? What are the extremes of hematocrit in the intended patient population? Do these match the device limits? G Altitude – is there an expected bias at different altitudes due to either barometric pressure or oxygen effects that could affect testing at high altitudes, on an airplane, or in a medical rescue helicopter? G Storage – is refrigeration required for any component of the POCT system? How will the temperature of refrigerators be monitored and documented? G Samples – can POCT be used on all types of samples like venous and arterial blood if the device was intended for home use with capillary fingerstick? G Specimen additives – do anticoagulants or glycolysis inhibitors affect the test? Is fresh urine required or should urine preservatives be utilized? The possible combinations of variables are considerable and each practice will need to assess their unique situa- tion. For instance, validation experiments, which utilize stored specimens with anticoagulants, may yield different results from fresh capillary specimens. Additionally, some POCT have narrow temperature ranges, particularly those containing protein enzymes and antibodies, like pregnancy, infectious disease, or drugs of abuse tests. Special attention must be given to home nursing practices where POCT may be transported in cars and exposed to extremes of summer heat and winter cold. Validation of POCT should seek to mimic the actual conditions to which the POCT will be subjected during routine use. In many situations, this may require concurrent use of POCT and main laboratory testing for a limited period of time from the same patients to correlate results. Ultimately, decisions about POCT methodology should seek to meet the prime objective of standardizing results for a given analyte across an institution. As the number of different methods and manufacturers for any given test increases, there will be more problems encountered with test biases. POCT quality assurance programs are thus more easily managed when the numbers of different meth- ods for a laboratory test are kept to a minimum. Minimiz- ing the number of methods also simplifies the need for multiple policies and training programs. With the implementation of electronic medical records, consideration must be given to separation of POCT from main laboratory results for the same test in the patient’s record. POCT is a different methodology from instrumentation in a main laboratory with unique interferences, biases, and test limitations. Overlay of results for the same analyte in a patient’s medical record from different methodologies can lead to clinical confu- sion. CLIA regulations further require an audit trail to the CLIA license responsible for each test result. In a health system with hospital POCT, clinic POCT, nurs- ing home testing, ambulances, and other affiliate sites, POCT may be conducted under multiple CLIA licenses. Overlay of all glucose results in an electronic medical record may cross multiple CLIA certificates and confuse which laboratory directors are technically responsible for specific test results. So, electronic medical records should seek to separate POCT results from other methodologies in the patient’s medical record. QUALITY CONTROL All laboratory testing requires a means of documenting that the method is stable and has not changed over time. This is often achieved through the analysis of liquid con- trols with known target values that can be analyzed like patients. The control results can then be monitored and tracked over time to determine if changes have occurred in the test system that would affect patient results. This use of quality control has been perfected to monitor the system- atic performance of laboratory instruments with large batches of reagent. However, standard quality control practices developed in the main laboratory do a poor job of assessing random, test errors from unit-use POCT devices. POCT is generally manufactured in small batches or as single test cartridges or kits. Routine quality control prac- tice must therefore be modified to measure not only sys- tematic errors in the lot of tests, but also to detect random failures that could occur with single tests. Manufacturers have begun to engineer internal controls in some POCT devices in order to provide a means of monitoring errors with every test. For manual tests, these internal controls can indicate problems with kit storage, sample application, and operator technique by including a second antibody–antigen
  9. 9. 463CHAPTER 6.3 Point-of-Care Testing reaction for immunoassay-based tests. Internal controls can also signal appropriate timing for reading results. Activity of a separate area on guaiac occult blood tests can deter- mine the potency of peroxide developing solutions. For POCT devices, spectrophotometric and electronic controls can detect the integrity of the device, especially if dropped or damaged, as well as the manufacturing consistency of biosensor test cartridges. Electronic controls are beneficial, since there is no utilization of reagents or added cost associ- ated with performance of the control. Yet, electronic con- trols do not assess the chemistry of the test reagents and operator technique like liquid controls can. Recent regula- tory changes by the Joint Commission and CAP allow internal control processes to substitute for liquid controls provided that the institution can document that internal controls detect the same type and frequency of errors as liquid controls on the POCT device. The latest update to CLIA interpretation takes a more global view of POCT quality assurance. This update allows the use of alternative control practices provided that labs also control the other components of the testing process, including areas that may not be covered by an internal control. ADMINISTRATION POCT requires a defined administrative structure within an organization. The laboratory plays a key role in this structure, with a director and supervisory personnel assigned to review data generated by POCT and to oversee the testing practices on the patient care units. Clinical staff also need to be involved in the administrative structure by liaisons with the nursing unit who can address POCT problems as they arise. Educators need to be appointed to guarantee standardized training and competency of staff and to handle the training of new staff as turnover occurs. Oversight of the POCT program should be directed by a multidisciplinary committee that has the power to advise on policy issues and make recommendations regarding management issues as they arise. Membership of this com- mittee should include representation from all parties involved in the POCT process. Laboratory and clinical staff are mandatory. Administrators should be included to handle budgeting and to ensure the support of the organi- zation’s trustees and medical staff. Purchasing representa- tion is also recommended to address inventory issues. Inventory control is particularly problematic given the variety of ways that POCT can enter an organization: pharmacy, physicians carrying in kits from other practices, patient devices and corporate sales representatives leaving samples, to name a few of the ways. Overall, the multidis- ciplinary committee should provide guidance to the labo- ratory in selecting POCT methodologies and standardizing testing throughout the organization. The multidisciplinary committee thus provides the administrative power to allow testing to occur at a given site or to discontinue testing when problems occur and policies are not being followed. Summary POCT is an alternate means of delivering laboratory test- ing closer to the patient that promises faster turnaround of results and improved clinical outcomes. Whether POCT actually delivers beneficial outcomes is determined by how the test is utilized at an individual site. Sites performing few tests with many POCT devices and operators may incur higher costs than other sites. Inefficient testing practices that result in redundant testing and values that sit in a medi- cal record without clinical action do not necessarily lead to improved outcome. The effectiveness of POCT is thus intricately dependent on the clinical practices at a given site. Moreover, quality POCT requires deliberate efforts and a defined administrative structure to implement and maintain high standards of testing. Each testing site must be viewed as a unique situation where all practice variables come together to determine the most appropriate test delivery options for that particular patient population. POCT that is effective at one site may be very ineffective at another. Only through realization that POCT is an extension of the main laboratory with comparable quality assurance problems, and similar training and supervision requirements, will POCT find its optimal role within an institution. References and Further Reading CLSI. EP18-A2 Risk Management Techniques to Identify and Control Laboratory Error Sources; Approved Guideline 2nd edn (Clinical and Laboratory Standards Institute, Wayne, PA, 2009). CLSI. POCT1-A2 Point-of-Care Connectivity; Approved Standard 2nd edn (Clinical and Laboratory Standards Institute, Wayne, PA, 2006). CLSI. POCT2-A Implementation Guide of POCT-1 for Health Care Providers; Approved Standard. (Clinical and Laboratory Standards Institute, Wayne, PA, 2008). CLSI. POCT7-A Quality Management: Approaches to Reducing Errors at the Point of Care; Approved Standard. (Clinical and Laboratory Standards Institute, Wayne, PA, 2010). CLSI. POCT8-A Quality Practices in Noninstrumented Point-of-Care Testing: An Instructional Manual and Resources for Health Care Workers; Approved Standard. (Clinical and Laboratory Standards Institute, Wayne, PA, 2010). CLSI. POCT9-A Selection Criteria for Point-of-Care Testing Devices; Approved Standard. (Clinical and Laboratory Standards Institute, Wayne, PA, 2010). College of American Pathologists Commission on Laboratory Accreditation. Point- of-Care Testing Checklist. (College of American Pathologists, Northfield, IL, 2011). Department of Health and Human Services Centers for Medicare & Medicaid Services Centers for Disease Control and Prevention 42 CFR Part 493; Medicare, Medicaid, and CLIA Programs; Laboratory Requirements Relating to Quality Systems and Certain Personnel Qualifications. Fed. Regist. 68, 3640–3714 (January 24, 2003). Department of Health and Human Services Health Care Financing Administration Public Health Service 42 CFR; Final Rule; Medicare, Medicaid and CLIA Programs; Regulations implementing Clinical Laboratories Improvement Amendments of 1988 (CLIA). Fed. Regist. 57, 7001–7288 (Feb 28, 1992). International Organization for Standardization. ISO15189 Medical Laboratories: Particular Requirements for Quality and Competence. (ISO, Geneva, Switzerland, 2003). International Organization for Standardization. ISO22870 Quality Management of Point-of-Care Testing (POCT). (ISO, Geneva, Switzerland, 2006). Joint Commission. 2011 Comprehensive Accreditation Manual for Hospitals (CAMH): The Official Handbook. (Joint Commission, Oakbrook Terrace, IL, 2011). Joint Commission 2011 Comprehensive Accreditation Manual for Laboratory and Point- of-Care Testing (CAMLAB). (Joint Commission, Oakbrook Terrace, IL, 2011). Jones, B.A. and Howanitz, P.J. Bedside glucose monitoring quality control prac- tices: a College of American Pathologists Q-PROBES study of program quality control documentation, program characteristics, and accuracy performance in 544 institutions. Arch. Pathol. Lab. Med. 120, 339–345 (1996). Kost, G.J. Principles & Practice of Point-of-Care Testing. (Lippincott, Williams & Wilkins, Philadelphia, PA, 2002). Nichols, J.H. Cost analysis of point-of-care testing. In: Advances in Pathology and Laboratory Medicine, vol. 9, (ed Weinstein, R.S.), 121–133 (Mosby-Year Book, Inc. St. Louis, MO, 1996). Nichols J.H. (ed), National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Evidence-Based Practice for Point of Care Testing. (AACC Press, Washington, DC, 2007). Nichols, J.H. (ed), Point-of-Care Testing: Performance Improvement and Evidence- Based Outcomes. (Marcel Dekker, Inc. New York, NY, 2003).

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