The use of error and uncertainty methods in the medical laboratory.

Error methods - compared with uncertainty methods - offer simpler, more intuitive and practical procedures for calculating measurement uncertainty and conducting quality assurance in laboratory medicine. However, uncertainty methods are preferred in other fields of science as reflected by the guide to the expression of uncertainty in measurement. When laboratory results are used for supporting medical diagnoses, the total uncertainty consists only partially of analytical variation. Biological variation, pre- and postanalytical variation all need to be included. Furthermore, all components of the measuring procedure need to be taken into account. Performance specifications for diagnostic tests should include the diagnostic uncertainty of the entire testing process. Uncertainty methods may be particularly useful for this purpose but have yet to show their strength in laboratory medicine. The purpose of this paper is to elucidate the pros and cons of error and uncertainty methods as groundwork for future consensus on their use in practical performance specifications. Error and uncertainty methods are complementary when evaluating measurement data.

Repeat patient testing quality control (RPT-QC): Background and theory.

Repeat-patient testing quality control (RPT-QC) is a version of statistical quality control (SQC) in which individual patient samples, rather than commercial control materials, are used. Whereas conventional SQC assumes control material stability and repeatedly measures the same lot of control material over time, RPT-QC uses a unique patient sample for each QC event and exploits the labile nature of patient samples under prescribed storage conditions for QC purposes. Advantages of RPT-QC include commutability, lower cost, and QC at concentrations of medical interest. Challenges include sample procurement and the establishment of control limits. The objective of this review is to compare and contrast the principles and procedures of RPT-QC and conventional SQC and to provide an overview of RPT-QC control limit establishment.

Preferences of clinical pathologists for probability-modifying terms describing cytologic sample evaluations: A survey study.

BACKGROUND: A recent study identified 7 probability ranges used by clinical pathologists and associated qualitative terms used in cytology reports. Clinicians and clinical pathologists agreed that limiting the number of terms could help enhance communication between clinical pathologists and clinicians. However, the preferred terms for each range remain undetermined. OBJECTIVE: We sought to determine a single term for each probability range that could be adopted by the global veterinary clinical pathology community. METHOD: Clinical pathologists responded to a survey invitation distributed via the specialty listserv. Clinical pathologists were asked to rank previously identified terms for each probability range from "most preferred" to "least preferred." An alternative term could be proposed if they preferred a term not included in the question. The preferences were summed by rank. Where first choice ranks were within 20% of each other, the 1st and 2nd choices were added. The term with the highest counts was chosen to represent the probability range. RESULTS: The highest-ranking terms corresponding to the probability ranges of 0%-20%, 20%-50%, 50%-65%, 65%-75%, 75%-85%, 85%-95%, and 95%-100% were "no evidence for," "cannot rule out," "possible," "suspicious for," "most likely," "most consistent with," and no modifier, respectively. CONCLUSIONS: We have sampled clinical pathologists across the globe to rank terms in cytology reports associated with previously identified probability ranges to identify single qualitative terms for which there was the most agreement between clinicians and clinical pathologists. Our study provides the foundation for standardizing and limiting probability-modifying terms to improve communication with clinicians.

Veterinary clinicians prefer template-style reports with personal confidence estimates for cytologic sample evaluations.

OBJECTIVE: To examine preferences of veterinary clinical pathologists, clinicians, and students for cytology report formats. SAMPLE: 24 clinical pathologists, 1,014 veterinarians, and 93 veterinary students who were members of the Veterinary Information Network. METHODS: Members of the Veterinary Information Network responded to an online survey invitation, made available between July 11, 2023, and July 24, 2023. Respondents were randomly directed to 1 of 4 sets of cytology reports, each containing a traditional narrative format, narrative format with terms expressing a degree of confidence and associated numerical ranges, and template format with similar estimates of confidence. Respondents ranked the reports in order of preference and then provided comments about their top-ranked choice. Responses were analyzed mostly with descriptive statistics or comparisons of proportions. RESULTS: 14 of 24 clinical pathologists preferred the traditional narrative format, whereas 449 of 1,042 veterinary clinicians and veterinary students preferred the template format. Respondents (460/1,131) ranked the template format as most preferred, but the narrative format with terms expressing a degree of confidence ranked highest overall. Many respondents appeared to misunderstand the degree of confidence estimates being expressed numerically. Respondents choosing each format often stated that their preferred choice was "easiest to understand" and "most comprehensive." CLINICAL RELEVANCE: Given the preferences of veterinary clinicians and veterinary students for a template format, clinical pathologists should consider modifying the way they report evaluations of cytologic specimens. Template formats should help standardize reporting of cytologic specimens, thereby improving communication between clinical pathologists and clinicians. However, both clinicians and clinical pathologists need to better understand the purpose of terminology expressing degrees of confidence in such reports.

Repeat patient testing-quality control with canine samples shows promise as an alternative to commercial quality control material for a network of four Sysmex XT-2000iV hematology analyzers.

BACKGROUND: Repeat patient testing-quality control (RPT-QC) uses retained patient samples as an alternative to commercial quality control material (QCM). We elected to calculate and validate RPT-QC limits for red blood cell count (RBC), hemoglobin (HBG), hematocrit (HCT), and white blood cell count (WBC). OBJECTIVES: (1) To validate RPT-QC across a network of four harmonized Sysmex XT-2000iV hematology analyzers and determine the total error that can be controlled with RPT-QC. (2) To generate quality control (QC) limits using the standard deviation (SD) of the duplicate measurement differences and determine a suitable simple QC rule with a probability of error detection >0.85 and probability of false rejection <0.05. (3) Monitor RPT-QC using sigma metrics as a performance indicator and (4) to challenge RPT-QC to ensure acceptable sensitivity. METHODS: Fresh adult canine EDTA samples with results within reference intervals were selected and run again on days 2, 3, and 4. QC limits were generated from the SD of the duplicate measurement differences. The QC limits were challenged using interventions designed to promote unstable system performance. The total error detectable by RPT-QC was determined using EZRULES 3 software. RESULTS: In all, 20-40 data points were needed for RPT-QC calculations and validated using 20 additional data points. The calculated limits differed among the network of analyzers. The total error that could be controlled was the same or better than that of the manufacturer's commercially available quality control material using the same analyzer for all measurands except hematocrit, which required a higher total error goal than that proposed by ASVCP guidelines to achieve an acceptable probability of error detection. The challenges designed to mimic unstable system performance were successfully detected as out-of-control QC. CONCLUSIONS: The challenges for RPT-QC resulted in acceptable detection of potential unstable system performance. This initial study demonstrates that RPT-QC limits differ among the network of Sysmex XT-2000iV analyzers, indicating a requirement to customize for the individual analyzer and laboratory conditions. RPT-QC could achieve ASVCP total allowable error goals for RBC, HGB, and WBC, but not for HCT. Sigma metrics were consistently >5.5 for RBC, HGB, and WBC, but not for HCT.

Repeat patient Testing-Quality control: An example of implementation in a network of commercial laboratories.

The theory and calculations underpinning Repeat Patient Testing-Quality Control (RPT-QC) have been presented in prior publications. This paper gives an example of the process used for implementing RPT-QC in a network of veterinary commercial reference laboratories and the stages associated with the transition to the sole use of RPT-QC. To employ RPT-QC in this commercial laboratory network, eight stages of implementation were identified: (1) education, (2) data collection, (3) calculations, (4) QC recording and documentation, (5) running RPT-QC in parallel with a commercially available quality control material (QCM), (6) development of a Standard Operating Procedure (SOP), (7) development of complementary aspects supporting RPT-QC, and (8) sole use of RPT-QC. Advantages of RPT-QC included cost savings for QCM and External Quality Assessment (EQA) participation and the ability to use commutable specimens with a veterinary matrix at a result level that is of clinical significance for the species. A disadvantage of RPT-QC using a single level of control was the inability to demonstrate stable performance over a range of results. Future avenues for investigation include ongoing refinement of control limits using a pooled standard deviation of the duplicates (SDdup), Sdup over time, investigation of blood samples from species other than the dog, and manipulation of specimens to produce "low abnormal" or "high abnormal" RPT-QC specimens.

Analytical performance of feline plasma on current Heska and IDEXX point-of-care biochemistry analyzers compared with a commercial laboratory analyzer.

BACKGROUND: Point-of-care (POC) biochemistry analyzers are widely used in small animal clinical practice but infrequently independently assessed for performance. OBJECTIVE: To assess the performance of two current model point-of-care biochemistry analyzers (Heska Element DC and IDEXX Catalyst) compared with a commercial laboratory analyzer (Cobas 8000). METHODS: One hundred twenty-one cats from a feline hospital population were sampled with plasma results from a single lithium heparin tube assessed on all three analyzers. Plasma biochemistry results from each POC analyzer were compared with the commercial laboratory analyzer using Bland-Altman difference plots and by determining whether the limits of agreement (LOAs) (95% of differences) fell within various quality goals after correcting for inherent bias. RESULTS: Only 7 of 14 analytes on the Heska analyzer and 2 analytes on the IDEXX analyzer attained the most stringent LOA quality goal, which was being within desirable total error based on biologic variation (TEdes ). The number of analytes achieving quality goals increased with less stringent standards such as American Society of Veterinary Clinical Pathologists allowable total error (ASVCP TEA ) guidelines or if <95% of clinical comparisons reaching these quality goals is considered acceptable. Widespread bias was found between both POC analyzers and the commercial laboratory analyzer. CONCLUSIONS: The performance of both POC biochemistry analyzers was variable compared with a commercial laboratory analyzer. Performance goals were only able to be attained after the bias for each analyzer was accounted for by offsetting the LOAs and quality goals set by the mean bias for each analyte on each analyzer.

Guidelines for resident training in veterinary clinical pathology. IV: Laboratory quality management-Teaching domains, competencies, and suggested learning outcomes.

BACKGROUND: The 2019 ASVCP Education Committee Forum for Discussion, presented at the annual ASVCP/ACVP meeting, identified a need to develop recommendations for teaching laboratory quality management principles in veterinary clinical pathology residency training programs. OBJECTIVES: To present a competency-based framework for teaching laboratory quality management principles in veterinary clinical pathology residency training programs, including entrustable professional activities (EPAs), domains of competence, individual competencies, and learning outcomes. METHODS: A joint subcommittee of the ASVCP Quality Assurance and Laboratory Standards (QALS) and Education Committees executed this project. A draft guideline version was reviewed by the ASVCP membership and shared with selected ACVP committees in early 2022, and a final version was voted upon by the full QALS and Education Committees in late 2022. RESULTS: Eleven domains of competence with relevant individual competencies were identified. In addition, suggested learning outcomes and resource lists were developed. Domains and individual competencies were mapped to six EPAs. CONCLUSIONS: This guideline presents a framework for teaching principles of laboratory quality management in veterinary clinical pathology residency training programs and was designed to be comprehensive yet practical. Guidance on pedagogical terms and possible routes of implementation are included. Recommendations herein aim to improve and support resident training but may require gradual implementation, as programs phase in necessary expertise and resources. Future directions include the development of learning milestones and assessments and consideration of how recommendations intersect with the American College of Veterinary Pathologists training program accreditation and certifying examination.

Clinical pathologists should limit modifier terms used to denote probability of a diagnosis: a survey-based study.

OBJECTIVE: To examine the probability estimates for modifying terms used by clinical pathologists when interpreting cytologic samples and compare these to probability estimates assigned to these terms by clinicians, and to provide restricted, standardizing terms used in cytology reports. SAMPLE: 49 clinical pathologists and 466 Veterinary Information Network members responded to 2 similar surveys. PROCEDURES: Online surveys were distributed to diplomates of the European College of Veterinary Clinical Pathologists and clinician members of the Veterinary Information Network, made available between March 17, 2022, through May 5, 2022. Respondents assigned a range of probabilities to each of 18 modifier terms used by clinical pathologists to denote probability associated with diagnoses; clinicians identified terms that would affect their treatment decisions in cases of canine lymphoma. Respondents then provided thoughts about restricting and standardizing modifying terms and assigning numeric estimates in reports. RESULTS: 49 clinical pathologists and 466 clinicians provided responses. For many terms, probability ranges agreed between the 2 groups. However, differences in estimated probability inferred by a term existed for at least 6 terms. Modifying terms could be restricted to 7 largely nonoverlapping terms that spanned the range of probabilities. Clinicians preferred having numeric estimates of probability, but clinical pathologists resisted providing such estimates in reports. CLINICAL RELEVANCE: Reducing and standardizing the number of modifying terms to reflect specific probability ranges would reduce disagreement between the clinical pathologist's intended probability range and the clinician's interpretation of a modifying term. This could result in fewer errors in interpretation and better patient care.

Total observed error, total allowable error, and QC rules for canine serum and urine cortisol achievable with the Immulite 2000 Xpi cortisol immunoassay.

Determining a simple quality control (QC) rule for daily performance monitoring depends on the desired total allowable error (TEa) for the measurand. When no consensus TEa exists, the classical approach of QC rule validation cannot be used. Using the results of previous canine serum and urine cortisol validation studies on the Immulite 2000 Xpi, we applied a reverse engineering approach to QC rule determination, arbitrarily imposing sigma = 5, and determining the resulting TEa for the QC material (QCM; TEaQCM) and the resulting probability of error detection (Ped) for each QC rule. For the simple QC rule 12.5S with Ped = 0.96 and probability of false rejection (Pfr) = 0.03, the associated TEaQCM were 20% and 35% for serum and 28% and 24% for urine QCM1 and QCM2. If these levels of TEaQCM are acceptable for interpretation of patient sample results, then users can internally validate the 12.5S QC rule, provided that their QCM CVs and biases are similar to ours. Otherwise, more stringent QC rules can be validated by using a lower sigma to lower the TEaQCM. With spiked samples (relevant cortisol concentrations in the veterinary patient matrix) at 38.6 and 552 nmol/L of cortisol, TEaQCM at sigma = 5 were much higher (54% and 40% for serum; 90.3% and 42.8% for urine). Spiked samples generate TEa that is probably too high to be suitable for daily QC monitoring; however, it is crucial to verify spiked sample observed total error (TEo; 26% and 18% for serum, 60% and 30% for urine) < TEaQCM, and to use spiked sample TEo for patient result interpretation. In the absence of consensus TEa for cortisol in dogs, we suggest the use of a 12.5S rule, provided that users accept the associated level of TEaQCM also as clinical TEa for results interpretation.

Quality control validation for a veterinary laboratory network of six Sysmex XT-2000iV hematology analyzers.

BACKGROUND: Quality control (QC) validation is an important step in the laboratory harmonization process. This includes the application of statistical QC requirements, procedures, and control rules to identify and maintain ongoing stable analytical performance. This provides confidence in the production of patient results that are suitable for clinical interpretation across a network of veterinary laboratories. OBJECTIVES: To determine that a higher probability of error detection (Ped ) and lower probability of false rejection (Pfr ) using a simple control rule and one level of quality control material (QCM) could be achieved using observed analytical performance than by using the manufacturer's acceptable ranges for QCM on the Sysmex XT-2000iV hematology analyzers for veterinary use. We also determined whether Westgard Sigma Rules could be sufficient to monitor and maintain a sufficiently high level of analytical performance to support harmonization. METHODS: EZRules3 was used to investigate candidate QC rules and determine the Ped and Pfr of manufacturer's acceptable limits and also analyzer-specific observed analytical performance for each of the six Sysmex analyzers within our laboratory system using the American Society of Veterinary Clinical Pathology (ASVCP)-recommended or internal expert opinion quality goals (expressed as total allowable error, TEa ) as the quality requirement. The internal expert quality goals were generated by consensus of the Quality, Education, Planning, and Implementation (QEPI) group comprised of five clinical pathologists and seven laboratory technicians and managers. Sigma metrics, which are a useful monitoring tool and can be used in conjunction with Westgard Sigma Rules, were also calculated. RESULTS: The QC validation using the manufacturer's acceptable limits for analyzer 1 showed only 3/10 measurands reached acceptable Ped for veterinary laboratories (>0.85). For QC validation based on observed analyzer performance, the Ped was >0.94 using a 1-2.5s QC rule for the majority of observations (57/60) across the group of analyzers at the recommended TEa . We found little variation in Pfr between manufacturer acceptable limits and individual analyzer observed performance as this is a characteristic of the rule used, not the analyzer performance. CONCLUSIONS: An improved probability of error detection and probability of false rejection using a 1-2.5s QC rule for individual analyzer QC was achieved compared with the use of the manufacturers' acceptable limits for hematology in veterinary laboratories. A validated QC rule (1-2.5s) in conjunction with sigma metrics (>5.5), desirable bias, and desirable CV based on biologic variation was successful to evaluate stable analytical performance supporting continued harmonization across the network of analyzers.

Validation study of canine urine cortisol measurement with the Immulite 2000 Xpi cortisol immunoassay.

We report here validation of the Immulite 2000 Xpi cortisol immunoassay (Siemens; with kit lot numbers <550) for measurement of urine cortisol in dogs, with characterization of the precision (CV), accuracy (spiking-recovery [SR] bias), and observed total error (TEo = bias + 2CV) across the reportable range. Linearity assessed by simple linear regression was excellent. Imprecision, SR bias, and TEo increased markedly with decreasing urine cortisol concentration. Interlaboratory comparison studies determined range-based (RB) bias and average bias (AB). The 3 biases (SR, RB, and AB) and resulting TEo differed markedly. At 38.6 and 552 nmol/L (1.4 and 20 µg/dL), between-run CVs were 10% and 4.5%, respectively, and TEoRB were ~30% and 20%, respectively, similar to observations in serum in another validation study. These analytical performance parameters should be considered for urine cortisol:creatinine ratio (UCCR) result interpretation, given that, for any hypothetical errorless urine creatinine measurement, the error % on UCCR mirrors the error % on urine cortisol. Importantly, there is no commonly used interpretation threshold for UCCR, given that UCCR varies greatly depending on measurement methods and threshold computation. To date, there is no manufacturer-provided quality control material (QCM) with target values for urine cortisol with an Immulite; for Liquicheck QCM (Bio-Rad), between-run imprecision was ~5% for both QCM levels. Acceptable QC rules are heavily dependent on the desired total allowable error (TEa) for the QCM system, itself limited by the desired clinical TEa.

Validation study of canine serum cortisol measurement with the Immulite 2000 Xpi cortisol immunoassay.

We report the results of validation of canine serum cortisol determination with the Immulite 2000 Xpi cortisol immunoassay (Siemens), with characterization of precision (CV), accuracy (spiking-recovery [SR] bias), and observed total error (TEo = bias + 2CV) across the reportable range, specifically at the most common interpretation thresholds for dynamic testing. Imprecision increased at increasing rate with decreasing serum cortisol concentration and bias was low, resulting in increasing TEo with decreasing serum cortisol concentration. Inter-laboratory comparison study allowed for determination of range-based bias (RB) and average bias (AB). At 38.6 and 552 nmol/L (1.4 and 20 µg/dL), between-run CV was 10% and 7.5%, respectively, and TEo ~30% and ~20%, respectively (TEo remained similar regardless of the considered bias: SR, RB, or AB). These analytical performance parameters should be considered in the interpretation of results and for future expert consensus discussions to determine recommendations for allowable total error (TEa). Importantly, the commonly used thresholds for interpretation of results were determined ~40 y ago with different methods of measurements and computation, hence updating is desirable. Quality control material (QCM) had between-run imprecision of 4% for QCM1 and 7% for QCM2; the bias was minimal for both levels. Acceptable QC rules are heavily dependent on the desired TEa for the QCM system (TEaQCM), itself limited by the desired clinical TEa. At low TEaQCM (20-33%), almost no rules were acceptable, whereas at high TEaQCM (50%), almost all rules were acceptable; further investigation is needed to determine which TEaQCM can be guaranteed by simple QC rules.

Comparison of serum and plasma SDMA measured with point-of-care and reference laboratory analysers: implications for interpretation of SDMA in cats.

OBJECTIVES: Symmetric dimethylarginine (SDMA) reflects the glomerular filtration rate (GFR) in people, dogs and cats. Initial assays used a liquid chromatography-mass spectroscopy (LC-MS) technique. A veterinary immunoassay has been developed for use in commercial laboratories and point-of-care (POC) laboratory equipment. This study sought to: determine POC and commercial laboratory (CL) SDMA assay imprecision; determine any bias of the POC assay compared with the CL assay; calculate observed total error of the POC assay and compare with analytical performance goals; and calculate dispersion and sigma metrics (σ) for POC and CL SDMA methods. METHODS: Two separate studies were performed that assessed: (1) imprecision, determined by evaluation of pooled feline plasma or serum; and (2) bias, assessed by comparing pooled plasma and serum results, as well as paired analyses of clinical samples from a single venepuncture measured using both analysers. Results were assessed in relation to performance goals. Dispersion and σ were calculated for both analysers. RESULTS: Bias between CL and POC analysers was consistent and high numbers of clinical results were outside performance goals across both studies. Imprecision was poor for both analysers for study 1 and improved to within quality goals for the CL analyser for study 2. Dispersion was at least 40%, meaning a measured result of 14 µg/dl represents a range of possible results from 8 µg/dl to 20 µg/dl. CONCLUSIONS AND RELEVANCE: Clinicians should be careful ascribing medical significance to small changes in SDMA concentration, as these may reflect analytical and biological variability. Analyser-specific reference intervals are likely required.

Evaluation of Sysmex XT-2000iV analyzer performance across a network of five veterinary laboratories using a commercially available quality control material.

BACKGROUND: Laboratory and instrument harmonization is seldom reported in the veterinary literature despite its advantages to clinical interpretation, including the use of interchangeable results and common reference intervals within a system of laboratories. OBJECTIVES: A three-step process was employed to evaluate and optimize performance and then assess the appropriateness of common reference intervals across a network of six Sysmex XT-2000iV hematology analyzers at 5 commercial veterinary laboratory sites. The aims were to discover if harmonization was feasible in veterinary hematology and which quality parameters would best identify performance deviations to ensure a harmonized status could be maintained. METHODS: The performance of 10 measurands of a commercially available quality control material (Level 2-Normal e-CHECK (XE)-Hematology Control) was evaluated during three 1-month time periods. Precision and bias were assessed with Six Sigma, American Society of Veterinary Clinical Pathology (ASVCP) total error quality goals and biologic variation (BV)-based quality goal approaches to performance measurement. RESULTS: Instrument adjustments were made to 1 analyzer twice and 3 analyzers once between evaluations to improve performance and achieve harmonization. Sigma metrics improved from 37/50 > 6 to 58/60 > 6 and to all >5 over the course of the harmonization project. BV-based quality goals for desirable bias and for laboratory systems of 0.33 × CVI (within-subject biologic variation) were more sensitive and useful for assessing performance than the ASVCP total error goals. CONCLUSIONS: Optimization and harmonization were achieved, and because BV-derived bias goals were achieved, common reference intervals could be implemented across the network of analyzers.

Analytical quality performance goals for symmetric dimethylarginine in cats.

BACKGROUND: Symmetric dimethylarginine (SDMA) reflects the glomerular filtration rate (GFR) in people, dogs, and cats. Initial assays used a liquid chromatography-mass spectroscopy (LC) technique. A veterinary immunoassay has been developed for use in commercial laboratories and point-of-care (POC) laboratory equipment. There have been no independent assessments of these assays, and analytical performance goals for SDMA testing have not been defined. OBJECTIVES: This study sought to establish analytical performance goals for SDMA in cats from (a) biological variation (BV) data and (b) expert opinion. METHODS: Analytical performance goals were determined from a prior BV study of SDMA in cats and a survey of veterinary internists who have used SDMA in practice. RESULTS: Biological variation-based performance goals included an imprecision of ±10% (immunoassay and LC), bias of ±8% (immunoassay and LC), and total error of ±24% (immunoassay and LC). Expert opinion performance goals were ±0.10 µmol/L (±2 µg/dL), or ±0.15 µmol/L (±3 µg/dL), varying with starting SDMA concentrations. CONCLUSIONS: This study recommends analytical performance goals for SDMA based on BV and expert opinion. Wide dispersion of SDMA results using currently available assays implies that clinicians risk attaching medical significance to small SDMA changes that actually reflect analytical variability.

Repeat patient testing-based quality control shows promise for use in veterinary biochemistry testing.

BACKGROUND: Repeat patient testing-based quality control (RPT-QC) is a form of statistical QC and an alternative to commercial quality control materials (QCM). OBJECTIVE: This study investigated the suitability of canine heparinized plasma for use in RPT-QC and assessed the predicted performance of RPT-QC for the detection of analytical error in chemistry testing. METHODS: The stability of canine plasma for RPT-QC was investigated via storage at two temperatures for three or six time points. Storage data were analyzed using repeated measures ANOVA and by comparing results for stored specimens to baseline data using predetermined criteria. To generate RPT-QC limit-setting and -validation data, leftover plasma was prospectively measured. Once control limits were established, these were challenged by measuring specimens for which the repeat aliquot had been manipulated to mimic analytical error. Finally, the predicted performance of RPT-QC and QCM-QC with four control rules was investigated using Westgard's EZ Rules 3. RESULTS: Refrigerated storage of canine plasma for 7 days allowed mild changes facilitating RPT-QC. RPT-QC limits for 12 of 17 common measurands were validated. Validated limits successfully flagged differences from manipulated specimen pairs as "error." The predicted performance of RPT-QC for analytical error detection (represented by smallest achievable allowable total error, given a probability of error detection ≥ 85% and a probability of false rejection ≤ 5%) for four common control rules is comparable to that of QCM-QC. CONCLUSIONS: This study provides evidence that RPT-QC using canine heparinized plasma refrigerated for 7 days can be used with simple control rules and low numbers of control materials, suggesting RPT-QC is applicable to both reference and in-clinic laboratory settings.

Current and emerging concepts in biological and analytical variation applied in clinical practice.

A single laboratory result actually represents a range of possible values, and a given laboratory result is impacted not just by the presence or absence of disease, but also by biological variation of the measurand in question and analytical variation of the equipment used to make the measurement. Biological variation refers to variability in measurand concentration or activity around a homeostatic set point. Knowledge of biological and analytical variation can be used to facilitate interpretation of patient clinicopathologic data and is particularly useful for interpreting serial patient data and data at or near reference limits or clinical decision thresholds. Understanding how biological and analytical variation impact laboratory results is of increasing importance, because veterinarians evaluate serial data from individual patients, interpret data from multiple testing sites, and use expert consensus guidelines that include decision thresholds for clinicopathologic data interpretation. The purpose of our report is to review current and emerging concepts in biological and analytical variation and discuss how biological and analytical variation data can be used to facilitate clinicopathologic data interpretation. Inclusion of veterinary clinical pathologists having expertise in laboratory quality management and biological variation on research teams and veterinary practice guideline development teams is recommended, to ensure that various considerations for clinicopathologic data interpretation are addressed.

Quality control validation, application of sigma metrics, and performance comparison between two biochemistry analyzers in a commercial veterinary laboratory.

A review of the literature pertinent to interpretation of biochemistry data and quality control (QC) and proficiency testing data from 2 biochemistry analyzers was used to determine clinical quality requirements for biochemistry assays, characterize the performance of and calculate sigma metrics for the analytes run on the 2 analyzers, and perform QC validation in order to determine the needs for statistical QC for each analyzer. Quality requirements suitable for the analytes based on the needs of the authors' laboratory are presented. These requirements may or may not be appropriate for other laboratories, depending on the needs of the clients, species, and equipment performance capability. The majority of the analytes were easily controlled using the 1(3s) control rule, with a sigma metric approaching or exceeding 6 and with a high probability of error detection and a low probability of false rejection. Some analytes could not be controlled using the 1(3s) rule, and additional control rules with a greater number of control data points were required. There were differences between performances of the 2 analyzers. The findings in the present study emphasize the need for QC specific for the analyte and the clinical decision level and the need for separate QC validation on every instrument.

Quality documentation challenges for veterinary clinical pathology laboratories.

An increasing number of veterinary laboratories worldwide have obtained or are seeking certification based on international standards, such as the International Organization for Standardization/International Electrotechnical Commission 17025. Compliance with any certification standard or quality management system requires quality documentation, an activity that may present several unique challenges in the case of veterinary laboratories. Research specifically addressing quality documentation is conspicuously absent in the veterinary literature. This article provides an overview of the quality system documentation needed to comply with a quality management system with an emphasis on preparing written standard operating procedures specific for veterinary laboratories. In addition, the quality documentation challenges that are unique to veterinary clinical pathology laboratories are critically evaluated against the existing quality standards and discussed with respect to possible solutions and/or recommended courses of action. Documentation challenges include the establishment of quality requirements for veterinary tests, the use or modification of human analytic methods for animal samples, the limited availability of quality control materials satisfactory for veterinary clinical pathology laboratories, the limited availability of veterinary proficiency programs, and the complications in establishing species-specific reference intervals.