Defining the Path Forward: Guidance for Laboratory Medicine Guidelines.

The National Academy of Clinical Biochemistry (NACB) has developed consensus-based guidelines for the laboratory evaluation and monitoring of patients with specified disorders for two decades. In 1997, the NACB recognized the need to standardize the process of guideline development and promulgated its first Standard Operating Procedure (SOP) for this purpose. In 2010, the American Association of Clinical Chemistry (AACC) and NACB created the Evidence-Based Laboratory Medicine Committee (EBLMC). Among other roles, this group was given responsibility to provide oversight of clinical practice guideline development in accordance with SOP guidance and using currently accepted good practices. In 2011, the U.S. Institute of Medicine (IOM) published two reports of relevance: 'Clinical Practice Guidelines We Can Trust' and 'Finding What Works in Health Care - Standards for Systematic Reviews.' These reports were created as part of a response to a legislative mandate from the U.S. Congress requesting that steps be taken to implement recommendations from lOM's report on 'Knowing What Works in Health Care' (2008). The latest revision of the laboratory medicine practice guidelines (LMPG) SOP was in part driven by these reports. NACB continues to develop LMPGs at a rate of roughly one per year through standard processes detailed in its 2014 revision of the SOP. This article describes the NACB and EBLMC experience in developing LMPGs with a focus on the evolution and use of the latest SOP. AACC and NACB have established a solid track record in collaboratively working with many clinical societies and professional organizations on clinical practice guideline development. Presently, three LMPG's are in various stages of development and all with the collaboration of other clinical/professional groups. The practices and tools being used for current LMPGs in progress are also highlighted in the context of the challenges that presently exist for effective clinical practice guideline development in the U.S.

Effectiveness of barcoding for reducing patient specimen and laboratory testing identification errors: a Laboratory Medicine Best Practices systematic review and meta-analysis.

OBJECTIVES: This is the first systematic review of the effectiveness of barcoding practices for reducing patient specimen and laboratory testing identification errors. DESIGN AND METHODS: The CDC-funded Laboratory Medicine Best Practices Initiative systematic review methods for quality improvement practices were used. RESULTS: A total of 17 observational studies reporting on barcoding systems are included in the body of evidence; 10 for patient specimens and 7 for point-of-care testing. All 17 studies favored barcoding, with meta-analysis mean odds ratios for barcoding systems of 4.39 (95% CI: 3.05-6.32) and for point-of-care testing of 5.93 (95% CI: 5.28-6.67). CONCLUSIONS: Barcoding is effective for reducing patient specimen and laboratory testing identification errors in diverse hospital settings and is recommended as an evidence-based "best practice." The overall strength of evidence rating is high and the effect size rating is substantial. Unpublished studies made an important contribution comprising almost half of the body of evidence.

Roadmap for harmonization of clinical laboratory measurement procedures.

Results between different clinical laboratory measurement procedures (CLMP) should be equivalent, within clinically meaningful limits, to enable optimal use of clinical guidelines for disease diagnosis and patient management. When laboratory test results are neither standardized nor harmonized, a different numeric result may be obtained for the same clinical sample. Unfortunately, some guidelines are based on test results from a specific laboratory measurement procedure without consideration of the possibility or likelihood of differences between various procedures. When this happens, aggregation of data from different clinical research investigations and development of appropriate clinical practice guidelines will be flawed. A lack of recognition that results are neither standardized nor harmonized may lead to erroneous clinical, financial, regulatory, or technical decisions. Standardization of CLMPs has been accomplished for several measurands for which primary (pure substance) reference materials exist and/or reference measurement procedures (RMPs) have been developed. However, the harmonization of clinical laboratory procedures for measurands that do not have RMPs has been problematic owing to inadequate definition of the measurand, inadequate analytical specificity for the measurand, inadequate attention to the commutability of reference materials, and lack of a systematic approach for harmonization. To address these problems, an infrastructure must be developed to enable a systematic approach for identification and prioritization of measurands to be harmonized on the basis of clinical importance and technical feasibility, and for management of the technical implementation of a harmonization process for a specific measurand.

Analytic bias among certified methods for the measurement of hemoglobin A1c: a cause for concern?

We studied the magnitude, significance, and origin of an analytic bias that emerged between our point-of-care (POC) and our central laboratory (CL) methods for the measurement of hemoglobin A1c (HbA1c) and evaluated the analytic accuracy of 7 commonly used HbA1c methods relative to the National Glycohemoglobin Standardization Program (NGSP) reference method. The POC and CL methods were compared by split-sample analysis of clinical specimens and time series analyses of the HbA1c results reported for a 33-month period. The relative accuracies of 7 HbA1c methods were evaluated using College of American Pathologists proficiency survey results. Long-term drifts in the CL- and POC-analyzed test results caused the median intermethod bias [(POC result)-(CL result)] to increase from -0.4% to -0.9% HbA1c. Systematic biases, drifts in analytic performance over time, and intermethod variability were frequently observed among the 7 NGSP-certified HbA1c methods. Intermethod variability is a potential source of inaccuracy whenever HbA1c results are interpreted relative to universal, fixed, clinical decision thresholds.

Toward standardization of cardiac troponin I measurements part II: assessing commutability of candidate reference materials and harmonization of cardiac troponin I assays.

BACKGROUND: Cardiac tropoin I (cTnI) measurements show an approximately 20- to 40-fold difference between assays, and better standardization and harmonization are needed. Toward this goal, the AACC cTnI Standardization Committee collaborated with the National Institute of Standards and Technology (NIST) in an earlier study to select 2 candidate reference materials (cRMs). METHODS: Two troponin cRMs, a troponin C-troponin I-troponin T (CIT) complex from human heart tissue and a CIT complex from recombinant technology, were supplied to NIST for assessment of composition and purity, and cTnI value assignment. These cRMs and 6 cTnI-positive human serum pools were shipped to manufacturers of 15 cTnI assays. Commutability of the materials was examined by determining the numerical relationship for the cRM preparations between each manufacturer-specified field method and each of the other 14 field methods. These relationships were then compared with the corresponding numerical relationships for the human serum pools. Harmonization of methods was accomplished by determining regression parameters relative to the analytical system yielding values closest to the median for each serum pool. These regression parameters were used to recalculate pool values to harmonize the assays. Interassay CVs before and after harmonization were determined. RESULTS: Characterization of the CIT and CI cRMs showed that these materials were of specified composition. The proportion of cTnI methods that demonstrated commutability for the CIT cRM was 45%; for the CI cRM, 39% of methods demonstrated commutability. Interassay cTnI variability for the field methods ranged from 82% to 97%, median 88%. After harmonization, variability of the serum pools for the cTnI methods was decreased to between 9.0% and 23%, median 15.5%. CONCLUSIONS: The proportion of methods demonstrating commutability was too low for use as a common calibrator for the cTnI field methods. However a simple strategy using serum pools can improve harmonization of field cTnI methods by more than 5-fold. The CIT cRM was selected by the AACC cTnI standardization committee, and a new lot has been classified as the cTnI certified reference material Standard Reference Material 2921 by NIST.

Association of mild transient elevation of troponin I levels with increased mortality and major cardiovascular events in the general patient population.

CONTEXT: The prognostic value of mild elevation of cardiac-specific troponin I (cTnI) levels is poorly defined, which can make interpretation of such an elevation difficult. OBJECTIVE: To study the prognostic value of transient mild elevation of cTnI levels in the hospitalized patient population. DESIGN: We performed a case-control study that compared the outcome of patients hospitalized for any cause with at least 2 subsequent transient cTnI measurements of 0.1 ng/mL or higher and less than 1.5 ng/mL with matched controls with cTnI levels less than 0.1 ng/mL. A cohort of 118 patients (mean +/- SD age, 67.4 +/- 14.0 years; 35.6% men) was followed up for an average +/- SD of 11.9 +/- 7.9 months. Seventy-one cases were matched with 37 controls in terms of demographics, coronary artery disease risk factors, and reason for admission. End points were all-cause mortality and major cardiovascular end points, including cardiovascular mortality, myocardial infarction, and revascularization. RESULTS: The total event rate was significantly increased in the case group compared with the control group at 12, 6, and 3 months (62.0% vs 24.3%, 59.2% vs 16.2%, and 47.9% vs 5.4%, respectively; P < .001). At 12, 6, and 3 months, the cases had a significant increase in all-cause mortality (43.7% vs 16.2%, 40.8% vs 8.1%, and 33.8% vs 0.0%, respectively; P = .005) and major cardiovascular end points (26.8% vs 8.1%, 26.8% vs 8.1%, and 21.1% vs 5.4%, respectively; P = .02) compared with controls. CONCLUSION: Transient mild elevation of cTnI levels in hospitalized patients is associated with an increase in all-cause mortality and major cardiovascular complications. Such elevations of cTnI levels can be considered a marker for both all-cause and cardiovascular morbidity and mortality.