Sample size and rejection limits for detecting reagent lot variability: analysis of the applicability of the Clinical and Laboratory Standards Institute (CLSI) EP26-A protocol to real-world clinical chemistry data

2021 ◽  
Vol 59 (1) ◽  
pp. 127-138
Author(s):  
Sollip Kim ◽  
Jeonghyun Chang ◽  
Soo-Kyung Kim ◽  
Sholhui Park ◽  
Jungwon Huh ◽  
...  
Keyword(s):  
Sample Size ◽  
Real World ◽  
Statistical Power ◽  
Clinical Laboratory ◽  
Clinical Chemistry ◽  
Test Results ◽  
Real World Data ◽  
Reference Change Value ◽  
Laboratory Test Results ◽  
Allowable Error

AbstractObjectivesTo maintain the consistency of laboratory test results, between-reagent lot variation should be verified before using new reagent lots in clinical laboratory. Although the Clinical and Laboratory Standards Institute (CLSI) document EP26-A deals with this issue, evaluation of reagent lot-to-lot difference is challenging in reality. We aim to investigate a practical way for determining between-reagent lot variation using real-world data in clinical chemistry.MethodsThe CLSI EP26-A protocol was applied to 83 chemistry tests in three clinical labs. Three criteria were used to define the critical difference (CD) of each test as follows: reference change value and total allowable error, which are based on biological variation, and acceptable limits by external quality assurance agencies. The sample size and rejection limits that could detect CD between-reagent lots were determined.ResultsFor more than half of chemistry tests, reagent lot-to-lot differences could be evaluated using only one patient sample per decision level. In many cases, the rejection limit that could detect reagent lot-to-lot difference with ≥90% probability was 0.6 times CD. However, the sample size and rejection limits vary depending on how the CD is defined. In some cases, impractical sample size or rejection limits were obtained. In some cases, information on sample size and rejection limit that met intended statistical power was not found in EP26-A.ConclusionsThe CLSI EP26-A did not provide all necessary answers. Alternative practical approaches are suggested when CLSI EP26-A does not provide guidance.

scholarly journals refineR: A Novel Algorithm for Reference Interval Estimation from Real-World Data

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tatjana Ammer ◽  
André Schützenmeister ◽  
Hans-Ulrich Prokosch ◽  
Manfred Rauh ◽  
Christopher M. Rank ◽  
...  
Keyword(s):  
Real World ◽  
Direct Method ◽  
Total Error ◽  
Ground Truth ◽  
Reference Intervals ◽  
Percentage Error ◽  
Test Results ◽  
Real World Data ◽  
World Data ◽  
Laboratory Test Results

AbstractReference intervals are essential for the interpretation of laboratory test results in medicine. We propose a novel indirect approach to estimate reference intervals from real-world data as an alternative to direct methods, which require samples from healthy individuals. The presented refineR algorithm separates the non-pathological distribution from the pathological distribution of observed test results using an inverse approach and identifies the model that best explains the non-pathological distribution. To evaluate its performance, we simulated test results from six common laboratory analytes with a varying location and fraction of pathological test results. Estimated reference intervals were compared to the ground truth, an alternative indirect method (kosmic), and the direct method (N = 120 and N = 400 samples). Overall, refineR achieved the lowest mean percentage error of all methods (2.77%). Analyzing the amount of reference intervals within ± 1 total error deviation from the ground truth, refineR (82.5%) was inferior to the direct method with N = 400 samples (90.1%), but outperformed kosmic (70.8%) and the direct method with N = 120 (67.4%). Additionally, reference intervals estimated from pediatric data were comparable to published direct method studies. In conclusion, the refineR algorithm enables precise estimation of reference intervals from real-world data and represents a viable complement to the direct method.

scholarly journals Real-world data suggest antibody positivity to SARS-CoV-2 is associated with a decreased risk of future infection

2020 ◽  
Author(s):  
Raymond A. Harvey ◽  
Jeremy A. Rassen ◽  
Carly A. Kabelac ◽  
Wendy Turenne ◽  
Sandy Leonard ◽  
...  
Keyword(s):  
Real World ◽  
Antibody Test ◽  
The United States ◽  
Test Results ◽  
Real World Data ◽  
World Data ◽  
Positive Antibody ◽  
Laboratory Test Results ◽  
Over Time

AbstractImportanceThere is limited evidence regarding whether the presence of serum antibodies to SARS-CoV-2 is associated with a decreased risk of future infection. Understanding susceptibility to infection and the role of immune memory is important for identifying at-risk populations and could have implications for vaccine deployment.ObjectiveThe purpose of this study was to evaluate subsequent evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among individuals who are antibody-positive compared with those who are antibody-negative, using real-world data.DesignThis was an observational descriptive cohort study.ParticipantsThe study utilized a national sample to create cohorts from a de-identified dataset composed of commercial laboratory test results, open and closed medical and pharmacy claims, electronic health records, hospital billing (chargemaster) data, and payer enrollment files from the United States. Patients were indexed as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test recorded in the database. Patients with more than 1 antibody test on the index date where results were discordant were excluded.Main Outcomes/MeasuresPrimary endpoints were index antibody test results and post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, as measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, such as recorded signs and symptoms or prior evidence of COVID-19 (diagnoses or NAAT+) and recorded comorbidities.ResultsWe included 3,257,478 unique patients with an index antibody test. Of these, 2,876,773 (88.3%) had a negative index antibody result, 378,606 (11.6%) had a positive index antibody result, and 2,099 (0.1%) had an inconclusive index antibody result. Patients with a negative antibody test were somewhat older at index than those with a positive result (mean of 48 versus 44 years). A fraction (18.4%) of individuals who were initially seropositive converted to seronegative over the follow up period. During the follow-up periods, the ratio (CI) of positive NAAT results among individuals who had a positive antibody test at index versus those with a negative antibody test at index was 2.85 (2.73 - 2.97) at 0-30 days, 0.67 (0.6 - 0.74) at 31-60 days, 0.29 (0.24 - 0.35) at 61-90 days), and 0.10 (0.05 - 0.19) at >90 days.ConclusionsPatients who display positive antibody tests are initially more likely to have a positive NAAT, consistent with prolonged RNA shedding, but over time become markedly less likely to have a positive NAAT. This result suggests seropositivity using commercially available assays is associated with protection from infection. The duration of protection is unknown and may wane over time; this parameter will need to be addressed in a study with extended duration of follow up.Key PointsQuestionCan real-world data be used to evaluate the comparative risk of SARS-CoV-2 infection for individuals who are antibody-positive versus antibody-negative?FindingOf patients indexed on a positive antibody test, 10 of 3,226 with a NAAT (0.3%) had evidence of a positive NAAT > 90 days after index, compared with 491 of 16,157 (3.0%) indexed on a negative antibody test.MeaningIndividuals who are seropositive for SARS-CoV-2 based on commercial assays may be at decreased future risk of SARS-CoV-2 infection.

Herbal Remedies: Effects on Clinical Laboratory Tests

2006 ◽  
Vol 130 (4) ◽  
pp. 521-528 ◽  
Author(s):  
Amitava Dasgupta ◽  
David W. Bernard
Keyword(s):  
Chinese Medicine ◽  
Laboratory Test ◽  
Alternative Medicine ◽  
Clinical Laboratory ◽  
Herbal Remedies ◽  
Test Results ◽  
Abnormal Laboratory ◽  
St John's Wort ◽  
Laboratory Test Results ◽  
Laboratory Results

AbstractContext.—Complementary and alternative medicine (herbal medicines) can affect laboratory test results by several mechanisms.Objective.—In this review, published reports on effects of herbal remedies on abnormal laboratory test results are summarized and commented on.Data Sources.—All published reports between 1980 and 2005 with the key words herbal remedies or alternative medicine and clinical laboratory test, clinical chemistry test, or drug-herb interaction were searched through Medline. The authors' own publications were also included. Important results were then synthesized.Data Synthesis.—Falsely elevated or falsely lowered digoxin levels may be encountered in a patient taking digoxin and the Chinese medicine Chan Su or Dan Shen, owing to direct interference of a component of Chinese medicine with the antibody used in an immunoassay. St John's wort, a popular herbal antidepressant, increases clearance of many drugs, and abnormally low cyclosporine, digoxin, theophylline, or protease inhibitor concentrations may be observed in a patient taking any of these drugs in combination with St John's wort. Abnormal laboratory results may also be encountered owing to altered pathophysiology. Kava-kava, chaparral, and germander cause liver toxicity, and elevated alanine aminotransferase, aspartate aminotransferase, and bilirubin concentrations may be observed in a healthy individual taking such herbal products. An herbal product may be contaminated with a Western drug, and an unexpected drug level (such as phenytoin in a patient who never took phenytoin but took a Chinese herb) may confuse the laboratory staff and the clinician.Conclusions.—Use of alternative medicines may significantly alter laboratory results, and communication among pathologists, clinical laboratory scientists, and physicians providing care to the patient is important in interpreting these results.

scholarly journals Personalized Reference Intervals in Laboratory Medicine: A New Model Based on Within-Subject Biological Variation

2020 ◽  
Author(s):  
Abdurrahman Coşkun ◽  
Sverre Sandberg ◽  
Ibrahim Unsal ◽  
Coskun Cavusoglu ◽  
Mustafa Serteser ◽  
...  
Keyword(s):  
Steady State ◽  
Personalized Medicine ◽  
Clinical Chemistry ◽  
Reference Interval ◽  
Reference Intervals ◽  
Biological Variation ◽  
Test Results ◽  
Steady State Condition ◽  
Laboratory Test Results ◽  
Measurement Results

Abstract Background The concept of personalized medicine has received widespread attention in the last decade. However, personalized medicine depends on correct diagnosis and monitoring of patients, for which personalized reference intervals for laboratory tests may be beneficial. In this study, we propose a simple model to generate personalized reference intervals based on historical, previously analyzed results, and data on analytical and within-subject biological variation. Methods A model using estimates of analytical and within-subject biological variation and previous test results was developed. We modeled the effect of adding an increasing number of measurement results on the estimation of the personal reference interval. We then used laboratory test results from 784 adult patients (>18 years) considered to be in a steady-state condition to calculate personalized reference intervals for 27 commonly requested clinical chemistry and hematology measurands. Results Increasing the number of measurements had little impact on the total variation around the true homeostatic set point and using ≥3 previous measurement results delivered robust personalized reference intervals. The personalized reference intervals of the study participants were different from one another and, as expected, located within the common reference interval. However, in general they made up only a small proportion of the population-based reference interval. Conclusions Our study shows that, if using results from patients in steady state, only a few previous test results and reliable estimates of within-subject biological variation are required to calculate personalized reference intervals. This may be highly valuable for diagnosing patients as well as for follow-up and treatment.

scholarly journals 1782. Real-World HIV Diagnostic Testing Patterns in the United States

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S656-S656
Author(s):  
James Karichu ◽  
Mindy Cheng ◽  
Pedro Rodriguez ◽  
Nicole Robinson ◽  
Chakkarin Burudpakdee ◽  
...  
Keyword(s):  
Real World ◽  
Index Date ◽  
Clinical Laboratory ◽  
The United States ◽  
Fourth Generation ◽  
Test Results ◽  
Confirmatory Testing ◽  
Confirmatory Tests ◽  
Testing Patterns ◽  
Hiv 1

Abstract Background Current HIV diagnostic laboratory testing guidelines from the US Centers for Disease Control and Prevention (CDC) recommend a sequence of tests for detection, differentiation, and confirmation of HIV-1 and HIV-2 diagnosis. There is a gap in knowledge about real-world implementation of the testing algorithm. The aim of this study was to characterize the population that underwent HIV antibody differentiation and confirmatory testing and to describe subsequent testing patterns from a large US clinical laboratory database. Methods Patients who received one or more HIV-1/2 antibody differentiation test (BioRad Geenius™ HIV 1/2 Supplemental Assay [Geenius]) in the Quest Diagnostics laboratory database between January 1, 2017 and December 31, 2017 were selected into the study; earliest test date was index date. Geenius tests, HIV-1 qualitative RNA (Aptima HIV-1 RNA Qualitative Assay [Aptima]), and HIV-2 DNA/RNA confirmatory tests subsequent to index date were captured. Study measures included pt demographic characteristics, testing frequency and sequencing, and test results. For patients with >1 Geenius test in 2017, concordance between index and subsequent test results was assessed. Results There were 26,319 unique patients identified who received ≥1 HIV antibody differentiation result from the Geenius assay. Mean age was 40.7 ± 14.3 years, 66.4% were male, and 42.5% were from southern states. Among the study population, there were 28,954 Geenius, 7,234 Aptima, and 298 HIV-2 DNA/RNA confirmatory tests. 26.4% of Geenius test results were discordant with the initial positive fourth-generation HIV screening results and required subsequent confirmatory testing. In terms of sequencing, the CDC-recommended HIV diagnostic algorithm was followed 74% of the time after screening. 8.5% of patients had >1 Geenius test in 2017; 11.2% of the retests returned different results compared with the first test. Conclusion The CDC recommended algorithm for HIV diagnosis is complex for laboratories to implement and currently available assays do not support testing efficiency. To mitigate observed inefficiencies and reduce the laboratory burden of HIV testing, a more accurate and reliable approach for HIV differentiation and confirmatory testing is needed. Disclosures All authors: No reported disclosures.

Terminology of cardiac troponin assays and data censoring

2017 ◽  
Vol 55 (11) ◽  
Author(s):  
Petr Jarolim
Keyword(s):  
Laboratory Test ◽  
Cardiac Troponin ◽  
Clinical Laboratory ◽  
Clinical Information ◽  
Reference Population ◽  
Test Results ◽  
Clinical Laboratory Test ◽  
Laboratory Test Results ◽  
Data Censoring ◽  
Selection Of

AbstractWe discuss the sensitivity terminology of cardiac troponin assays and its dependence on the selection of the reference population. In addition, the need for reasonable censoring of clinical laboratory test results is contrasted with potential loss of valuable clinical information.

scholarly journals Roadmap for Harmonization of Clinical Laboratory Measurement Procedures

2011 ◽  
Vol 57 (8) ◽  
pp. 1108-1117 ◽  
Author(s):  
W Greg Miller ◽  
Gary L Myers ◽  
Mary Lou Gantzer ◽  
Stephen E Kahn ◽  
E Ralf Schönbrunner ◽  
...  
Keyword(s):  
Reference Materials ◽  
Systematic Approach ◽  
Clinical Laboratory ◽  
Clinical Sample ◽  
Clinical Importance ◽  
Disease Diagnosis ◽  
Laboratory Measurement ◽  
Pure Substance ◽  
Test Results ◽  
Laboratory Test Results

Abstract 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.

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