The LEAP Checklist for Laboratory Evaluation and Analytical Performance Characteristics Reporting of Clinical Measurement Procedures

Loh Tze Ping,Cooke Brian R,Tran Thi Chi Mai,Markus Corey,Zakaria Rosita,Ho Chung Shun,Theodorsson Elvar,Greaves Ronda F 대한진단검사의학회 2024 Annals of Laboratory Medicine Vol.44 No.2

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practi- tioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describ- ing the analytical performance of measurement procedures. These variations also chal- lenge authors, readers, reviewers, and editors in deciding the quality of a submitted manu- script. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recom- mends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the Laboratory Evaluation and Analytical Performance Char- acteristics (LEAP) checklist will improve the standardisation of journal publications describ- ing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners.

An Objective Approach to Deriving the Clinical Performance of Autoverification Limits

Loh Tze Ping,Tan Rui Zhen,Lim Chun Yee,Markus Corey 대한진단검사의학회 2022 Annals of Laboratory Medicine Vol.42 No.5

This study describes an objective approach to deriving the clinical performance of autoverification rules to inform laboratory practice when implementing them. Anonymized historical laboratory data for 12 biochemistry measurands were collected and Box-Cox-transformed to approximate a Gaussian distribution. The historical laboratory data were assumed to be error-free. Using the probability theory, the clinical specificity of a set of autoverification limits can be derived by calculating the percentile values of the overall distribution of a measurand. The 5th and 95th percentile values of the laboratory data were calculated to achieve a 90% clinical specificity. Next, a predefined tolerable total error adopted from the Royal College of Pathologists of Australasia Quality Assurance Program was applied to the extracted data before subjecting to Box-Cox transformation. Using a standard normal distribution, the clinical sensitivity can be derived from the probability of the Z-value to the right of the autoverification limit for a one-tailed probability and multiplied by two for a two-tailed probability. The clinical sensitivity showed an inverse relationship with between-subject biological variation. The laboratory can set and assess the clinical performance of its autoverification rules that conforms to its desired risk profile.

Functional Reference Limits: Describing Physiological Relationships and Determination of Physiological Limits for Enhanced Interpretation of Laboratory Results

Chuah Tyng Yu,Lim Chun Yee,Tan Rui Zhen,Pratumvinit Busadee,Loh Tze Ping,Vasikaran Samuel,Markus Corey 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.5

Functional reference limits describe key changes in the physiological relationship between a pair of physiologically related components. Statistically, this can be represented by a significant change in the curvature of a mathematical function or curve (e.g., an observed plateau). The point at which the statistical relationship changes significantly is the point of curvature inflection and can be mathematically modeled from the relationship between the interrelated biomarkers. Conceptually, they reside between reference intervals, which describe the statistical boundaries of a single biomarker within the reference population, and clinical decision limits that are often linked to the risk of morbidity or mortality and set as thresholds. Functional reference limits provide important physiological and pathophysiological insights that can aid laboratory result interpretation. Laboratory professionals are in a unique position to harness data from laboratory information systems to derive clinically relevant values. Increasing research on and reporting of functional reference limits in the literature will enhance their contribution to laboratory medicine and widen the evidence base used in clinical decision limits, which are currently almost exclusively contributed to by clinical trials. Their inclusion in laboratory reports will enhance the intellectual value of laboratory professionals in clinical care beyond the statistical boundaries of a healthy reference population and pave the way to them being considered in shaping clinical decision limits. This review provides an overview of the concepts related to functional reference limits, clinical examples of their use, and the impetus to include them in laboratory reports.

The Use of Bone-Turnover Markers in Asia-Pacific Populations

Vasikaran Samuel,Thambiah Subashini C.,Tan Rui Zhen,Loh Tze Ping 대한진단검사의학회 2024 Annals of Laboratory Medicine Vol.44 No.2

Bone-turnover marker (BTM) measurements in the blood or urine reflect the bone-remod- eling rate and may be useful for studying and clinically managing metabolic bone diseases. Substantial evidence supporting the diagnostic use of BTMs has accumulated in recent years, together with the publication of several guidelines. Most clinical trials and observa- tional and reference-interval studies have been performed in the Northern Hemisphere and have mainly involved Caucasian populations. This review focuses on the available data for populations from the Asia-Pacific region and offers guidance for using BTMs as di- agnostic biomarkers in these populations. The procollagen I N-terminal propeptide and β-isomerized C-terminal telopeptide of type-I collagen (measured in plasma) are reference BTMs used for investigating osteoporosis in clinical settings. Premenopausal reference in- tervals (established for use with Asia-Pacific populations) and reference change values and treatment targets (used to monitor osteoporosis treatment) help guide the manage- ment of osteoporosis. Measuring BTMs that are not affected by renal failure, such as the bone-specific isoenzyme alkaline phosphatase and tartrate-resistant acid phosphatase 5b, may be advantageous for patients with advanced chronic kidney disease. Further stud- ies of the use of BTMs in individuals with metabolic bone disease, coupled with the har- monization of commercial assays to provide equivalent results, will further enhance their clinical applications.

Hemoglobin A1c Levels Are Slightly but Significantly Lower in Normoglycemic Subjects With the Hemoglobin E Phenotype

Busadee Pratumvinit,Kanit Reesukumal,,Sithikan Hanyongyuth,,Sujitra Wangchaijaroenkit,,Julaporn Pooliam,,Gerald J. Kost,,Panumas Kamkang,,Tze Ping Loh, 대한진단검사의학회 2019 Annals of Laboratory Medicine Vol.39 No.2

Hb mutations can alter the structure, behavior, stability, or quantity of the globin chain produced. Some Hb variants shorten the erythrocyte life span, resulting in physiologically lower hemoglobin A1c (HbA1c) levels. The hemoglobin E (HbE) phenotype involves a single-nucleotide polymorphism that reduces β-globin chain synthesis. We compared the HbA1c levels of subjects with normal Hb (HbAA; N=131) and HbE (N=148) phenotypes, examining potential hematological and biochemical factors contributing to differences in HbA1c levels. All had normal fasting plasma glucose (<5.6 mmol/L), AST, ALT, and creatinine levels. Mean±SD HbA1c levels differed between HbAA and HbE subjects: 5.5±0.3% and 5.3±0.3% (P<0.001) according to an immunoassay, and 5.5±0.3% and 5.3±0.3% (P<0.001) according to cation-exchange HPLC, respectively. In multiple logistic regression, only mean corpuscular volume (P<0.001) contributed to the difference in HbA1c levels between groups. Although a 0.2% difference in HbA1c is relatively small and unlikely to alter clinical decisions, epidemiologically, this can lead to misclassification of a significant proportion of the population, especially since the threshold of non-diabetes HbA1c (≤5.6%) falls very close to the HbA1c median of the general population.

Calibration Practices in Clinical Mass Spectrometry: Review and Recommendations

Cheng Wan Ling,Markus Corey,Lim Chun Yee,Tan Rui Zhen,Sethi Sunil Kumar,Loh Tze Ping 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.1

Background: Calibration is a critical component for the reliability, accuracy, and precision of mass spectrometry measurements. Optimal practice in the construction, evaluation, and implementation of a new calibration curve is often underappreciated. This systematic review examined how calibration practices are applied to liquid chromatography-tandem mass spectrometry measurement procedures. Methods: The electronic database PubMed was searched from the date of database inception to April 1, 2022. The search terms used were “calibration,” “mass spectrometry,” and “regression.” Twenty-one articles were identified and included in this review, following evaluation of the titles, abstracts, full text, and reference lists of the search results. Results: The use of matrix-matched calibrators and stable isotope-labeled internal standards helps to mitigate the impact of matrix effects. A higher number of calibration standards or replicate measurements improves the mapping of the detector response and hence the accuracy and precision of the regression model. Constructing a calibration curve with each analytical batch recharacterizes the instrument detector but does not reduce the actual variability. The analytical response and measurand concentrations should be considered when constructing a calibration curve, along with subsequent use of quality controls to confirm assay performance. It is important to assess the linearity of the calibration curve by using actual experimental data and appropriate statistics. The heteroscedasticity of the calibration data should be investigated, and appropriate weighting should be applied during regression modeling. Conclusions: This review provides an outline and guidance for optimal calibration practices in clinical mass spectrometry laboratories.

Comparison of Luminex NxTAG Respiratory Pathogen Panel and xTAG Respiratory Viral Panel FAST Version 2 for the Detection of Respiratory Viruses

Chun Kiat Lee,Hong Kai Lee,Christopher Wei Siong Ng,Lily Chiu,Julian Wei-Tze Tang,Tze Ping Loh,Evelyn Siew-Chuan Koay 대한진단검사의학회 2017 Annals of Laboratory Medicine Vol.37 No.3

Owing to advancements in molecular diagnostics, recent years have seen an increasing number of laboratories adopting respiratory viral panels to detect respiratory pathogens. In December 2015, the NxTAG respiratory pathogen panel (NxTAG RPP) was approved by the United States Food and Drug Administration. We compared the clinical performance of this new assay with that of the xTAG respiratory viral panel (xTAG RVP) FAST v2 using 142 clinical samples and 12 external quality assessment samples. Discordant results were resolved by using a laboratory-developed respiratory viral panel. The NxTAG RPP achieved 100% concordant negative results and 86.6% concordant positive results. It detected one coronavirus 229E and eight influenza A/H3N2 viruses that were missed by the xTAG RVP FAST v2. On the other hand, the NxTAG RPP missed one enterovirus/rhinovirus and one metapneumovirus that were detected by FAST v2. Both panels correctly identified all the pathogens in the 12 external quality assessment samples. Overall, the NxTAG RPP demonstrated good diagnostic performance. Of note, it was better able to subtype the influenza A/H3N2 viruses compared with the xTAG RVP FAST v2.

Evaluation of the Luminex ARIES HSV 1&2 Assay and Comparison with the FTD Neuro 9 and In-house Real-Time PCR Assays for Detecting Herpes Simplex Viruses

Chun Kiat Lee,Chean Nee Chai,Sharah Mae Capinpin,Alynn Ang,Sau Yoke Ng,Peak Ling Lee,Christopher Wai Siong Ng,Gabriel Yan,Hong Kai Lee,Lily-Lily Chiu,Roland Jureen,Benedict Yan,Tze Ping Loh 대한진단검사의학회 2018 Annals of Laboratory Medicine Vol.38 No.5

Background: Human herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are responsible for a plethora of human diseases, of which cutaneous and mucocutaneous infections are the most prevalent. In its most severe form, HSV infection can cause meningitis/encephalitis. We compared the Luminex ARIES HSV 1&2 assay (Luminex Corp., Austin, TX, USA), an automated sample-to-result molecular solution, to two non-automated HSV DNA assays. Methods: A total of 116 artificial controls were used to determine the analytical performance of the ARIES assay. Controls were prepared by spiking universal transport medium (UTM) and cerebrospinal fluid (CSF) samples from patients who tested negative for HSV by an in-house HSV-1 and -2 DNA assay with reference materials (SeraCare Life Sciences, MA, USA; ZeptoMetrix Corp., MA, USA). Another 117 clinical samples were then used to compare the clinical performance of the ARIES assay with those of an in-house assay and the FTD Neuro 9 assay (Fast Track Diagnostics, Junglinster, Luxembourg). Results: The analytical sensitivity (95% limit of detection) of the ARIES assay was 318 copies/mL (UTM samples) and 935 copies/mL (CSF samples) for HSV-1 strain 96 and 253 copies/mL (UTM samples) and 821 copies/mL (CSF samples) for HSV-2 strain 09. No cross-reactivity was observed in samples spiked with 14 non-HSV microorganisms. Compared with the reference result (agreement between the in-house and FTD Neuro 9 results), the ARIES assay had overall concordance rates of 98.2% (111/113) and 100% (113/113) for HSV-1 and HSV-2, respectively. Conclusions: The ARIES assay appears to be an excellent alternative for rapid detection and differentiation of HSV in skin and genital infections, meningitis, and encephalitis.