Commercial Quality Control Materials Research Articles

Abstract 978: Functional characterization and a real-world clinical laboratory pilot of the Foundation for the National Institutes of Health’s (FNIH) circulating tumor DNA (ctDNA) quality control materials (QCMs)

Abstract Background: Analysis of ctDNA now permits assessment of targetable mutations (e.g. EGFR L858R/Ex19del) using noninvasive blood tests. There are several FDA-approved tests using digital PCR (ddPCR) or next-generation sequencing (NGS) and many more laboratory developed tests in use. The FNIH Biomarkers Consortium identified the absence of validated standards to qualify the performance of ctDNA assays as a critical need and set out to aid in the characterization of QCMs. Here we report on a commutability study comparing the performance of three commercial QCMs to clinical samples at or above LoD (limit of detection) and update on a real-world assessment of these QCMs by 11 clinical laboratories spanning 4 continents and 3 assay modalities. Methods: QCMs were provided by Horizon Discovery (H), Thermo Fisher (T) and SeraCare (S). Clinical samples with known EGFR L858R and Ex19del mutations were prepared by diluting specimens at known concentrations into cell-free DNA (cfDNA) from healthy donors. The functional characterization compared detection of the mutations in QCM to clinical samples and consisted of 2 parts: (1) Evaluation of EGFR L858R/Ex19del (range 0.1% to 5% allele frequency [AF]) by ddPCR, amplicon and hybrid-capture NGS; (2) Evaluation near the LoD of the amplicon NGS assay at the assay LoD95 of 0.3% AF. For the clinical pilot, participants were sent QCM pools formulated at 0.5% and 1% AF by ddPCR. Some participants also tested clinical specimens with EGFR L858R and Ex19del at 0.5% and 1% AF by ddPCR. All participants were blinded to AF and identity of the manufacturer. Results: For Part 1, QCM results from hybrid-capture NGS of EGFR L858R were similar to ddPCR; for Ex19del, QCM AF trended lower compared to ddPCR. In contrast, L858R clinical samples showed a strong positive bias compared to ddPCR. For amplicon NGS, QCMs performed similarly to clinical samples, with amplicon NGS AF closest to ddPCR AF for T QCM. For Part 2, the observed hit rates mostly approximated expected values. For H QCM, observed LoD95 (10% for EGFR L858R; 50% for Ex19del) and subsequent dilution hit rates were lower than expected. For the clinical pilot, median Ex19del AF of amplicon NGS were higher than for hybrid-capture NGS for both the 1% QCM formulations and 0.5% QCM formulations. Median QCM L858R AF were similar for amplicon and hybrid-capture NGS, with greatest contributor to variance being inter-lab differences. Conclusions: This project, unprecedented in the number of participants and analytical rigor, revealed unexpected differences in performance of both assays and QCMs. These findings merit consideration by laboratories that rely on QCMs to develop and perform assays for ctDNA testing as diagnostics. Citation Format: Cloud P. Paweletz, Thomas D. Forbes, Grace A. Heavey, Laura M. Yee, Hua-Jun He, Zhiyong He, Dana E. Connors, Daniel Stetson, Susan Keating, Kenneth D. Cole, Gary Kelloff, Robert T. McCormack, Mickey P. Williams, Chris Karlovich. Functional characterization and a real-world clinical laboratory pilot of the Foundation for the National Institutes of Health’s (FNIH) circulating tumor DNA (ctDNA) quality control materials (QCMs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 978.

Repeat patient testing-quality control compared to commercial quality control material for the Sysmex XT-2000iV hematology analyzer in a multi-site veterinary laboratory.

Quality control material (QCM) for hematology in veterinary laboratories is limited, and repeat patient testing quality control (RPT-QC) is an alternative method using excess matrix-specific samples. This study aimed to determine if median differences between RPT-QC analyses for each time interval for RBC, HGB, HCT, and WBC were the same, determine if unified RPT-QC limits can be applied to a network of veterinary laboratories, compare the performance of RPT-QC to commercial QCM for the reference analyzer and evaluate the experience over a 4 month period and design, improve and implement an automated spreadsheet for RPT-QC data management. The potential to unify individual analyzer RPT-QC limits for red blood cells (RBC), hematocrit (HCT), hemoglobin (HGB), and white blood cells (WBC) on multi-site Sysmex XT-2000-iV analyzers was explored by a difference of means test and confidence interval determination for the median difference for each network analyzer in comparison to the network reference analyzer. User experience of an automated RPT-QC data management Excel spreadsheet was collected by user feedback during monthly meetings. Numbers of out-of-control results and the root causes for these for RPT-QC were compared against those of a commercial QCM over a 4-month period. Differences between individual analyzer RPT-QC limits were too large to allow for unification of network limits. The automated spreadsheet successfully highlighted out-of-control events for RPT-QC. Trends or shifts were more frequent for commercial QCM based on observed performance and a 1-2.5 s QC rule than for RPT-QC. Following routine troubleshooting, RPT-QC out-of-control events were resolved with an alternative RPT-QC sample indicating random error associated with excessive deterioration. Use of an automated spreadsheet for recording RPT-QC, documentation and troubleshooting of out-of-control events, and collating monthly summary calculations were considered an asset in laboratory quality management. RPT-QC can be successfully implemented and integrated into a multi-site veterinary laboratory. Individual analyzer RPT-QC limit generation is recommended. The deterioration of commercial QCM caused shifts or trends in QC results, which initiated more repeat analyses and investigations than did RPT-QC.

Use of patient sample for quality control of hematology analyzers: Is it a feasible option in resource-poor setting?

Objectives: The operation of hematology analyzers (HAs) is assured by quality control (QC) procedures. For internal QC, the use of stable hematology control material is recommended; however, its use has various limitations such as prohibitive cost, limited shelf life, and logistics. The aims of this study were to determine the utility and efficacy of patient samples in regular QC and HAs. Material and Methods: The patient’s samples were used for duplicate testing, comparability testing, and replicate testing along with X̅B monitoring to determine the performance of primary HA MEK 1900. Results: Paired t-test and correlation results in duplicate test and Scatter plot, Bland–Altman plot, and Passing– Bablok regression results derived from comparability studies revealed acceptable results as per recommendations. In replicate testing, acceptable coefficients of variation were obtained for hemoglobin (Hb) (1.6%), platelet count (4.9%), red blood cell (RBC) count (1.1%), and white blood cell (WBC) count (1.9%). Discussion: In duplicate sample testing paired t-test revealed P > 0.05. In 97% of samples, the standard deviation (SD) was <±2SD for duplicate testing for Hb, platelet count, RBC count, and WBC count. In comparability testing, for Hb, platelet count, RBC count, and WBC count, the correlation coefficient values were close to 1 and comparable to similar published studies. Results for repeatability studies in our study are within acceptable limits as per recommendations. X̅B monitoring revealed results acceptable within the prescribed limits by the manufacturer. The experiments done and results obtained in our study favor the use of patient samples to perform IQC for HA; however, it does not replace the use of stable commercial quality control material. Conclusion: In small-scale laboratories in resource-poor settings, patient samples can be of some use in QC of HA.

A performance evaluation of sthemO 301 coagulation analyzer and associated reagents.

The study objective was to evaluate the performance of sthemO 301 system and to compare it with the analyzer used in our university hospital laboratory (STA R Max® 2), for a selection of hemostasis parameters. Method comparison (according to CLSI EP09-A3), carryover (according to CLSI H57-A), APTT sensitivity to heparin (according to CLSI H47-A2), HIL level assessment, and productivity were performed using leftover samples from our laboratory (n > 1000). Commercial quality control materials were used to evaluate precision (according to CLSI EP15-A3) and accuracy. The assays tested on sthemO 301 were: PT, APTT (silica and kaolin activators), fibrinogen (Fib), thrombin time (TT), chromogenic and clotting protein C (PC) activity, and von Willebrand factor antigen (VWF:Ag) levels. All intra-assay and inter-assay precision CVs were below the maximal precision limit proposed by the French Group for Hemostasis and Thrombosis (GFHT). Accuracy was verified with bias below GFHT criteria and most Z-scores were between -2 and +2. No clinically relevant carryover was detected. Silica APTT reagent sensitivity to unfractionated heparin was moderate, as expected. Productivity results were consistent over the 10 repeats performed. The overall agreement between the two systems was excellent for all assays, with Spearman rank correlation coefficient all above 0.9 and slopes of Passing-Bablok correlation near 1 and intercepts close to 0. For the methods tested, sthemO 301 system met all the criteria to implement a novel coagulation analyzer in the laboratory and result comparability with STA R Max® 2 was good.

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.

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). (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. 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. 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. 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.

The VES-Matic 5 system: performance of a novel instrument for measuring erythrocyte sedimentation rate.

The VES-Matic 5 is an automated analyzer that assesses erythrocyte sedimentation rate based on a modified Westergren sedimentation technique. Instrument performance was established by addressing the recommendations of the International Council for Standardization in Haematology. Comparison against the reference Westergren method was performed for all samples, and further for the low, middle, and upper third of the analytical range. Intra-run precision, inter-run precision, and interference studies were further assessed. This study included the evaluation of reference ranges. The comparison of methods by Passing-Bablok analysis has shown a good agreement without systematic or proportional differences. The regression equation was y=-0.646+0.979x. The mean bias of-0.542 was obtained by Bland-Altman analysis and the upper limit of 8.03 withthe lower limit of-9.11 can be considered clinically acceptable. Intra-run and inter-run precision were good for each parameter and interference studies did not show any significant bias with exception of anemia samples, which showed a proportional difference when comparing high erythrocyte sedimentation rate values. Using the local adult reference population, we verified the reference ranges in comparison to those available in the literature, and according to the Clinical Laboratory Standards Institute (CLSI) EP28-A3C document. We determined the upper limit partitioned by gender and the following age groups: from 18 to 50, from 50 to 70, and over 70. The VES-Matic 5 analyzer presented good comparability with the reference method. As there are commercial quality control and suitable external quality assessment (EQA) material and programs, the VES-Matic 5 can be employed appropriately for routine purposes.

Evaluation and operationalization of commercial serum indices quality control material in the clinical laboratory

BackgroundEvaluation of specimen suitability for downstream analytical testing and identification of potential interferents in the clinical laboratory is critical for the generation of actionable clinical results. Within the clinical laboratory, hemolysis, icterus, and lipemia are commonly assessed spectrophotometrically. While clinical laboratories rely on analyte-specific quality control (QC) materials to monitor test or instrument performance, QC materials evaluating specimen integrity checks are infrequently implemented. MethodsUsing commercially available specimen integrity materials, we evaluated the Bio-Rad Liquichek™ Serum Indices product on Roche cobas® c701 analyzers at a large academic medical center. Target arbitrary values for the hemolysis, icterus, and lipemia QC materials were 200, 20, and 500, respectively. Means, standard deviations (SD), and coefficients of variation (%CV) were established for hemolysis, icterus, lipemia, and non-interfered QCs, and performance was monitored over a 60-day period. ResultsAcross four c701 instruments, all QC materials performed well, with %CVs ≤ 1.76%, 4.51%, and 3.46% for hemolysis, icterus, and lipemia QC, respectively. ConclusionsThe Bio-Rad Liquichek Serum Indices product can serve as an effective means of monitoring specimen integrity checks in a manner congruous with existing QC programs.

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

Repeat patient testing-based quality control (RPT-QC) is a form of statistical QC and an alternative to commercial quality control materials (QCM). 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. 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. Refrigerated storage of canine plasma for 7days 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. This study provides evidence that RPT-QC using canine heparinized plasma refrigerated for 7days 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.

A high performance liquid chromatography fluorescence method for the analysis of both pyridoxal-5-phosphate and thiamine pyrophosphate in whole blood

Background and aimsThe active coenzymes of the water soluble vitamins B1 and B6 (thiamine pyrophosphate (TPP) and pyridoxal-5-phosphate (P5P) respectively) play an important role in numerous bodily functions. The simultaneous analysis of both these analytes is limited to either mass spectrometry based methods or commercial kit suppliers. In this study we developed a novel method for analysis of both TPP and P5P by fluorescence detection. MethodsBriefly, whole blood samples are precipitated by trichloroacetic acid, and P5P and TPP are both derivatised before separation on a C18-PFP column. The new assay’s performance was compared against a recent cycle from an external quality assurance program (RCPAQAP) and the current only existing commercial kit (n = 76). ResultsLinearity for both analytes was above 0.99 (r2) up to a concentration range of: 4000 nmol/L (P5P) and 2000 nmol/L (TPP). Precision of the method (intra-day and inter-day) compared against commercial quality control material was below 6% (coefficient of variation). Recovery of both compounds exceeded 90%. Accuracy of the protocol displayed satisfactory results in proficiency testing and had an acceptable level of agreement with the existing current kit method. ConclusionsOverall, this method provides an economical alternative in routine clinical diagnostic laboratories wishing to perform P5P and TPP analysis.

An automated workflow approach for the analysis of flavin adenine dinucleotide by HPLC with internal standard

Flavin adenine dinucleotide (FAD) is an active coenzyme of vitamin B2 involved in oxidation and reduction reactions. In this study we have developed a fully automated method for the analysis of FAD by fluorescence detection. FAD is extracted from whole blood samples by trichloroacetic acid, with diethyl ribityl isoalloxazine used as an internal standard. Linearity for FAD was above 0.99 (r2) up to a concentration range of 1000 nmol/L. Precision of the method (intra-day and inter-day) compared against commercial quality control material was below 8% (coefficient of variation) with recovery of FAD exceeding 90%. Accuracy of the protocol was compared against a previous cycle from an external quality assurance program (RCPAQAP) (n = 12) with satisfactory agreement. Overall, this method has increased laboratory workflow and reduced manual labour required in performing FAD analysis.

Atellica UAS 800 urine sediment analyzer compatibility with commercial quality control materials and urine preservative tubes

Atellica UAS 800 urine sediment analyzer compatibility with commercial quality control materials and urine preservative tubes

Verification of the Heska Element Point‐of‐Care blood gas instrument for use with venous blood from alpacas and llamas, with determination of reference intervals

The Heska Element POC ("EPOC") is a blood gas instrument intended for use with canine, feline, and equine whole blood; no verification for use with camelid specimens has been reported. Using camelid specimens and commercial quality control materials (QCM), we investigatee EPOC analytical performance and establish EPOC camelid reference intervals (RIs). Camelid blood (n=124) was analyzed using the EPOC (pH, pCO2 , pO2 , HCO3 , base excess, SO2 , sodium, potassium, chloride, ionized calcium, TCO2 , anion gap, HCT, HGB, glucose, lactate, and creatinine); plasma was analyzed using a Roche Cobas c501 (sodium, potassium, chloride, TCO2 , anion gap, glucose, and creatinine). Method comparison data were assessed using Pearson's correlation, Passing-Bablok regression, and Bland-Altman plots. EPOC precision was evaluated using QCM and camelid blood. For all measurands except anion gap, the EPOC vs Cobas instrument correlation was r>.85. Except for pO2 and pCO2 , EPOC precision (QCM and blood) ranged from a repeatability CV <1%-6.3%. Mild constant bias for chloride, glucose, TCO2 , anion gap, and creatinine, and mild proportional bias for chloride, glucose, and anion gap were present. The total error (QCM data) for the EPOC instrument was below the ASVCP-recommended allowable total error. Alpacas had higher potassium and lactate, while llamas had higher creatinine, sodium, chloride, ionized calcium, pO2 , and SO2 . Statistical RIs based on alpaca (n=74-96) and llama data (n=12-17) are reported descriptively. The EPOC analyzer shows good performance with camelid blood. A lack of complete agreement with automated chemistry analyzers highlights the importance of interpreting patient data using instrument-specific RIs.

Performance characteristics of the Beckman Coulter UniCel DxI 800 TSH (3rd IS) assay

IntroductionBeckman Coulter recently reformulated their commercial TSH assay with primary calibration to the World Health Organization 3rd TSH international standard. An extensive evaluation of the performance characteristics for this assay was completed. MethodsIntra-day and inter-day precision was evaluated using 3 concentrations of commercial quality control material. Linearity, reportable range, stability, sensitivity and susceptibility to common inferences were determined using pooled patient specimens. Inter-assay variability was assessed across 5 different platforms (n=47 patient specimens). ResultsIntra-day and inter-day CVs were <10% at all concentrations evaluated. The LOQ, LOD and LOB were 0.0047μIU/ml (10% CV), 0.0012μIU/ml and 0.0005μIU/ml, respectively. Variable bias was observed for the TSH3 assay when evaluated against the previous generation assay and other platforms, but overall TSH3 gave comparable results. ConclusionsThe TSH3 assay for UniCel DxI 800, is precise, highly sensitive and comparable to the previous generation assay. The assay is acceptable for clinical testing.

Analytic and quality control validation and assessment of field performance of a point‐of‐care chemistry analyzer for use in the White rhinoceros

A chemistry point-of-care analyzer would be useful for evaluating injured wildlife, particularly White rhinoceros (Ceratotherium simum) that survive poaching attempts. The IDEXX VetTest could be suitable, but species-specific validation, development of a statistical quality control (QC) strategy, and evaluation under field conditions are necessary. The objectives were to (1) validate the VetTest for the White rhinoceros, (2) perform QC validation on the VetTest and generate a statistical QC strategy, and (3) apply this QC strategy to monitor performance under typical field conditions. Differences between White rhinoceros heparin plasma and serum, short-term imprecision, and reportable range using rhinoceros plasma and long-term imprecision using commercial quality control material (QCM) were assessed against prescribed total allowable error (TEa ) for up to 15 analytes. Quality control validation was performed using data from the long-term imprecision study and TEa . A QC strategy using QCM was developed and used to monitor performance under field conditions. Imprecision was acceptable for all analytes except for ALP, ALT, and AST at low activities. The reportable range for AST and LDH differed from the manufacturer's specifications. Eleven analytes were suitable for statistical QC using the 13s rule, 3 using the 2s rule; ALP was not suitable. In the field, observed error was < TEa for all 15 analytes and the sigma metric was > 3.0 for 12 analytes. The VetTest is suitable for use in the White rhinoceros. Statistical QC is possible for most analytes and useful for evaluation of field performance.

Commutability and interchangeability of commercial quality control materials with feline plasma for common biochemical analytes.

Species-specific plasma or serum pools are considered the ideal standard material for quality control materials (QCM) instead of commercially available human QCM. However, using plasma or serum pools is limited by volume restrictions, degradation over time, and a narrow range of analyte concentrations. Concentrations of QCM analytes should be consistent or commutable with those from species-specific plasma/serum samples, and the precision from plasma pools should be comparable or interchangeable with commercial human QCM. The aims of this study were to determine the commutability and interchangeability of 2 levels of commercial QCM (MAS chemTRAK-H [CT]) with feline plasma pools (PP) from normal and renal disease cats measured using a commercial laboratory analyzer and a veterinary in-house analyzer. Agreement between the 2 analyzers was assessed for 16 analytes by correlation and Passing-Bablok regression analyses of feline plasma samples. The difference between each CT data point and the regression line (residuals) was determined and standardized, and CT were considered 'commutable' with PP if the standardized residual was within a range of -3 to 3. Coefficients of variation (CVs) for CT and PP for 16 analytes on 2 analyzers were compared by bootstrap analysis to determine interchangeability. Most CT analytes were within the range of patient plasma sample analytes, thus commutable. Only 2 analytes had equivalent precision for both levels of CT and both levels of PP, and 5 additional analytes had similar precision for at least one level of CT compared to at least one level of PP. The QCM assessed is commutable to feline PP within the tested ranges for 2 particular analyzers. Commutability does not grant interchangeability.

Quality assurance of clinical biochemistry testing: a mualti-center study based reference interval for clinical chemistry tests in the Chinese population

Objective To verify and monitor the performance of accuracy, precision and comparability of 26 clinical biochemical analytes (29 methods) in the six centers involved in multi-centers reference intervals research, and to ensure the reliability of theirmeasurement results. Methods During the period of the systems evaluating, two levels of commercial quality control materials and fresh frozen human serum reference materials were applied to verify the performance of inter-laboratory precision and accuracy of analysis systems. During the period of samples testing, the commercial quality control materials were measured whenever samples were analysed, the fresh frozen serum reference materials were measured once a month. The coefficient of variations (CVs), bias and total errors were calculated to assess the precision, accuracy and comparability. Results Verification of precision and accuracy: (1) the ranges of CVs of 29 methods in the six laboratory laboratories were 0.4%-6.0%, the CVs of all 29 methods met the criterion .(2) The overall average bias of the analysis systems of 21 analytes (24 methods) ranged from -5.15% (ALT) to 4.46% (Ur). Among 24 methods the overall average bias of TP, Glu-GOD, Ur, Cl, Ca exceeded the acceptable range. The quality assessment during the period of samples testing: (1) The overall average bias ranged from -1.95%(Ca) to 2.92%(Ur), median 1.26%, they all met the requirements of relevant standards.(2)When commercial control materials were tested, the requirements of CVs were fulfilled for most methods in the six laboratories, and the CVs of TP, Alb, Cl, Ca exceeded the acceptable range.The overall average TE of all methods met the quality specification for the C-N controls material. For the C-P control material, only the overall average TE of TP (5.05%) exceeded thearceptable range while the other methods met the requirement in criterion. Conclusions The performance of precision and accuracy of the analysis systems used in the six laboratories passed the verification. During the period of sample testing, the performance of precision and accuracy of the most methods in the 6 laboratories met the requirements of quality specifications, and the overall performance was good. Because of the limitation of current technology the performance of some methods didn't fulfill the requirement of specifications, and need to be improved.(Chin J Lab Med, 2015, 38: 301-305) Key words: Reference values; Quality assurance, health care; Clinical chemistry tests; Laboratory proficiency testing

Performance characteristics of the Beckman Coulter total βhCG (5th IS) assay

BackgroundBeckman Coulter recently released the first commercially available hCG reagent calibrated against the 5th International Standard (IS) for hCG (total βhCG (5th IS)). We performed a comprehensive analytical validation of this reagent. MethodsPrecision experiments were completed using 3 concentrations of commercial quality control material. Linearity, sample stability, and analytical sensitivity were evaluated using pools of human serum. Reportable range was assessed by comparing manual dilutions to those performed by the instrument. Male and female reference intervals were established using residual serum specimens submitted for routine testing. Inter-lot variability of hCG assay reagent was assessed by analyzing serum specimens with detectable hCG using 2 different reagent lots. Inter-assay variability was established using 203 serum specimens analyzed for hCG on 6 different reagent platforms. ResultsInter-day precision showed a CV of <6.0% for all concentrations of QC material. LOB, LOD, and LOQ were determined to be 0.3, 0.4, and 0.6U/l, respectively. The Access (5th IS) reagent has an average positive bias of approximately 20% when compared to most platforms and the previous generation Beckman hCG assay. Results were consistent between lots. Female reference intervals varied by age: <1.0U/l (<41y), <6.0U/l (41–50y), and <8.0U/l (>50y). Male reference intervals were <2.0U/l. ConclusionsThe analytical performance of the total βhCG (5th IS) was established. Care should be taken to re-baseline patients needing serial monitoring and/or notify physicians when transitioning to the total βhCG (5th IS) reagent.

Aberrant lamellar body counts noted on the Beckman Coulter Unicel DxH 800

The lamellar body count (LBC) plays a crucial role in fetal lung maturity testing. Lamellar bodies are often counted in the platelet channel of routine hematology analyzers, resulting in a rapid and inexpensive assay for fetal lung maturity. Recently, significant imprecision was noted during LBC validation on the Beckman Coulter Unicel DxH 800. The results of two Beckman Coulter Unicel DxH 800 instruments were compared to those of a Coulter LH 750 and Coulter LH 500. Three pools of amniotic fluid, commercial quality control materials, and proficiency test specimens were analyzed on all four instruments. Fifty patient specimens were also analyzed using the Coulter LH 500 and the Unicel DxH 800. The mean values and precision obtained from commercial quality control materials and proficiency test samples were comparable on all four instruments. However, many erroneously low LBC results were produced from amniotic fluid pools using both DxH 800 instruments. The erroneous values were approximately 50% lower than respective target values, occurred randomly, and affected the low, medium, and high LBC results. Inter-assay precision of the three pools ranged from 24.7 to 39.0 CV% on the DxH 800 instruments. The source of LBC errors likely involves the exclusion of smaller lamellar bodies from the counts. The DxH 800 combines new data fusion technology and mathematical algorithms to produce increased accuracy and flagging efficiency. Laboratorians should be aware that the improved specificity of the DxH 800 may preclude its use for this laboratory-developed test.

Performance Characteristics of Six Intact Parathyroid Hormone Assays

The aim of this study was to evaluate the performance characteristics of 6 intact parathyroid hormone assays: Access 2 (Beckman Coulter, Fullerton, CA), ARCHITECT i2000(SR) (Abbott Diagnostics, Abbott Park, IL), ADVIA Centaur (Siemens Healthcare Diagnostics, Deerfield, IL), Modular E170 (Roche Diagnostics, Indianapolis, IN), IMMULITE 2000 (Siemens Healthcare Diagnostics), and LIAISON (DiaSorin, Stillwater, MN). Sample collection tubes and storage conditions were compared. Imprecision studies were performed using commercial quality control materials. Linearity was assessed using pools prepared from samples. For method comparison, serum and EDTA plasma samples were tested by all methods, and the ARCHITECT was used as the comparison method. Reference intervals were determined using various vitamin D cutoffs. The types of collection tubes and storage conditions are more important for some methods than others. Total coefficients of variation were 10.9% or less. The maximum deviation from the target recovery for linearity ranged from 5.0% to 82.2%. Bland-Altman plots demonstrated percentage biases ranging from -36.3% to 24.4%. The lower limit of the reference interval was not influenced by vitamin D status, whereas the upper reference limit was affected.

Implementing the Stockholm Conference hierarchy of objective quality criteria in a routine laboratory

Analytical performance of clinical laboratory testing should be evaluated against objective quality specifications. The Stockholm Conference consensus recommendation states that from a hierarchy of quality models, the highest-ranking model should be used. This study reports the performance of a routine clinical laboratory using these quality recommendations. Quality standards recommended for use in manufacturers' package inserts are also compared against the objective criteria. Imprecision of 22 analytes was monitored by analyzing three levels of commercial quality control (QC) material daily over a 6-month period. The performance for each analyte was evaluated against defined quality specifications based on biological variation and the National Cholesterol Education Panel (NCEP) criteria. Overall, objective quality specifications were met by the laboratory for 18/22 (82%) analytes. The performance for analytes not meeting the criteria was assessed against quality targets based on a model lower in the hierarchy, i.e., interlaboratory imprecision data derived from an accredited EQA program. All analytes met these quality targets. When quality targets set by the manufacturer were applied to biological variation and NCEP criteria, results for only 8/22 (36%) analytes met the targets. Objective quality specifications can be consistently achieved in a routine laboratory. The hierarchy model of the Stockholm Conference should be promoted for global adoption.