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.

Personalized reference intervals – statistical approaches and considerations

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Abdurrahman Coskun ◽  
Sverre Sandberg ◽  
Ibrahim Unsal ◽  
Fulya G. Yavuz ◽  
Coskun Cavusoglu ◽  
...  
Keyword(s):  
Laboratory Test ◽  
Population Based ◽  
Reference Intervals ◽  
Biological Variation ◽  
Test Results ◽  
Data Quality Assessment ◽  
Laboratory Test Results ◽  
Variation Database ◽  
Statistical Approaches

Abstract For many measurands, physicians depend on population-based reference intervals (popRI), when assessing laboratory test results. The availability of personalized reference intervals (prRI) may provide a means to improve the interpretation of laboratory test results for an individual. prRI can be calculated using estimates of biological and analytical variation and previous test results obtained in a steady-state situation. In this study, we aim to outline statistical approaches and considerations required when establishing and implementing prRI in clinical practice. Data quality assessment, including analysis for outliers and trends, is required prior to using previous test results to estimate the homeostatic set point. To calculate the prRI limits, two different statistical models based on ‘prediction intervals’ can be applied. The first model utilizes estimates of ‘within-person biological variation’ which are based on an individual’s own data. This model requires a minimum of five previous test results to generate the prRI. The second model is based on estimates of ‘within-subject biological variation’, which represents an average estimate for a population and can be found, for most measurands, in the EFLM Biological Variation Database. This model can be applied also when there are lower numbers of previous test results available. The prRI offers physicians the opportunity to improve interpretation of individuals’ test results, though studies are required to demonstrate if using prRI leads to better clinical outcomes. We recommend that both popRIs and prRIs are included in laboratory reports to aid in evaluating laboratory test results in the follow-up of patients.

Pediatric reference interval verification for endocrine and fertility hormone assays on the Abbott Alinity system

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Siobhan Wilson ◽  
Alexandra Hall ◽  
Khosrow Adeli
Keyword(s):  
Clinical Decision Making ◽  
De Novo ◽  
Reference Interval ◽  
Clinical Decision ◽  
Reference Intervals ◽  
Healthy Children ◽  
Confidence Limits ◽  
Test Results ◽  
Serum Samples ◽  
Abbott Architect

Abstract Objectives The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed an extensive database of reference intervals (RIs) for several biomarkers on various analytical systems. In this study, pediatric RIs were verified for key immunoassays on the Abbott Alinity system based on the analysis of healthy children samples and comparison to comprehensive RIs previously established for Abbott ARCHITECT assays. Methods Analytical performance of Alinity immunoassays was first assessed. Subsequently, 100 serum samples from healthy children recruited with informed consent were analyzed for 16 Alinity immunoassays. The percentage of test results falling within published CALIPER ARCHITECT reference and confidence limits was determined. If ≥ 90% of test results fell within the confidence limits, they were considered verified based on CLSI guidelines. If <90% of test results fell within the confidence limits, additional samples were analyzed and new Alinity RIs were established. Results Of the 16 immunoassays assessed, 13 met the criteria for verification with test results from ≥ 90% of healthy serum samples falling within the published ARCHITECT confidence limits. New CALIPER RIs were established for free thyroxine and prolactin on the Alinity system. Estradiol required special considerations in early life. Conclusions Our data demonstrate excellent concordance between ARCHITECT and Alinity immunoassays, as well as the robustness of previously established CALIPER RIs for most immunoassays, eliminating the need for de novo RI studies for most parameters. Availability of pediatric RIs for immunoassays on the Alinity system will assist clinical laboratories using this new platform and contribute to improved clinical decision-making.

Annual biological variation and personalized reference intervals of clinical chemistry and hematology analytes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shuo Wang ◽  
Min Zhao ◽  
Zihan Su ◽  
Runqing Mu
Keyword(s):  
Clinical Chemistry ◽  
Population Based ◽  
Reference Intervals ◽  
Biological Variation ◽  
Annual Data ◽  
Healthy Individuals ◽  
Reference Change Value ◽  
Index Of Individuality ◽  
Personalized Diagnosis

Abstract Objectives A large number of people undergo annual health checkup but accurate laboratory criterion for evaluating their health status is limited. The present study determined annual biological variation (BV) and derived parameters of common laboratory analytes in order to accurately evaluate the test results of the annual healthcare population. Methods A total of 43 healthy individuals who had regular healthcare once a year for six consecutive years, were enrolled using physical, electrocardiogram, ultrasonography and laboratory. The annual BV data and derived parameters, such as reference change value (RCV) and index of individuality (II) were calculated and compared with weekly data. We used annual BV and homeostatic set point to calculate personalized reference intervals (RIper) which were compared with population-based reference intervals (RIpop). Results We have established the annual within-subject BV (CVI), RCV, II, RIper of 24 commonly used clinical chemistry and hematology analytes for healthy individuals. Among the 18 comparable measurands, CVI estimates of annual data for 11 measurands were significantly higher than the weekly data. Approximately 50% measurands of II were <0.6, the utility of their RIpop were limited. The distribution range of RIper for most measurands only copied small part of RIpop with reference range index for 8 measurands <0.5. Conclusions Compared with weekly BV, for annual healthcare individuals, annual BV and related parameters can provide more accurate evaluation of laboratory results. RIper based on long-term BV data is very valuable for “personalized” diagnosis on annual health assessments.

Reference intervals and biological variation for kallikrein 6: influence of age and renal failure

2012 ◽  
Vol 50 (5) ◽  
Author(s):  
Eduardo Martínez-Morillo ◽  
Anastasia Diamandis ◽  
Eleftherios P. Diamandis
Keyword(s):  
Renal Failure ◽  
Significant Positive Correlation ◽  
Reference Interval ◽  
Serum Marker ◽  
Reference Intervals ◽  
Biological Variation ◽  
Serum Samples ◽  
Positive Correlation ◽  
Reference Change Value ◽  
Kallikrein 6

AbstractKallikrein 6 (KLK6) is a serine protease involved in numerous cellular processes, up-regulated in many cancers and associated with some neurodegenerative disorders. The aim of this study was to establish a reference interval and estimate the biological variation of KLK6 in serum samples of adults. Furthermore, levels of this protein in patients with renal failure were also studied.Serum samples from healthy volunteers (n=136) were collected. Between 15 and 18 additional samples from four of these subjects were obtained over a period of 2 months. Samples from individuals (n=1043) who visited the University Health Network for a routine check-up were collected to study the association between KLK6 with age and gender. Samples from patients with renal failure (n=106) were also obtained and KLK6 and creatinine concentrations were analyzed by ELISA and an automated enzymatic method, respectively.The reference interval was established to be 1.04–3.93 ng/mL. The index of individuality was 0.43 and the reference change value was 35%. Only two serum samples would be required to estimate the homeostatic setting point of an individual. There is a weak but highly significant positive correlation between KLK6 and age (p<0.0001). Furthermore, there is a significant positive correlation between serum concentrations of KLK6 and creatinine (p<0.0001), in patients with renal failure.The established reference interval for KLK6 and the estimation of its biological variation will further aid in the clinical use of this protein as a serum marker of malignancy and other diseases.

Reference intervals for 21 clinical chemistry analytes in arterial and venous umbilical cord blood

1993 ◽  
Vol 39 (6) ◽  
pp. 1041-1044 ◽  
Author(s):  
S L Perkins ◽  
J F Livesey ◽  
J Belcher
Keyword(s):  
Alkaline Phosphatase ◽  
Umbilical Cord ◽  
Clinical Chemistry ◽  
Venous Blood ◽  
Reference Interval ◽  
Reference Intervals ◽  
Nonparametric Analysis ◽  
Term Infants ◽  
Male And Female ◽  
Gamma Glutamyltransferase

Abstract Reference intervals were determined for 21 clinical chemistry analytes in umbilical cord arterial and venous blood from healthy term infants. Nonparametric analysis (rank number) was used to determine the central 95% reference interval. No significant differences were observed between male and female infants. Reference intervals for glucose, urea, creatinine, urate, phosphate, calcium, albumin, total protein, cholesterol, triglycerides, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, gamma-glutamyltransferase, and magnesium all were significantly different from adult values.

scholarly journals Partitioning Reference Intervals by Use of Genetic Information

2011 ◽  
Vol 57 (3) ◽  
pp. 475-481 ◽  
Author(s):  
Brian H Shirts ◽  
Andrew R Wilson ◽  
Brian R Jackson
Keyword(s):  
Genetic Information ◽  
Clinical Information ◽  
Reference Interval ◽  
Reference Intervals ◽  
Genetic Effects ◽  
Test Results ◽  
Simple Method ◽  
Asian Populations ◽  
Gilbert Syndrome ◽  
Recessive Effects

BACKGROUND Reference intervals that incorporate genetic information could reduce the misidentification of unusual test results caused by non–disease-associated genetic variation and increase the detection of results indicating underlying pathology. Subdividing reference groups by genetic effects, however, may lead to increased uncertainty around reference interval endpoints (because of the smaller subgroup sample sizes), thus offsetting any benefits. METHODS We evaluated CLSI guidelines to develop a method appropriate for partitioning reference intervals on the basis of genetic variants with dominant or recessive effects. This method uses information available before reference samples are recruited, thus allowing a preliminary decision regarding partitioning to be made before sampling. We used this method to evaluate the example of Gilbert syndrome. RESULTS The decision point for partitioning occurs when the percentage of total variance attributable to a dominant or recessive genetic polymorphism exceeds 4%. Similarly, partitioning decision curves are presented based on difference in means between 2 subgroups, sample SD, and subgroup or allele frequency. Laboratory-specific partitioned reference intervals for Gilbert syndrome appear to be statistically warranted for white and African-American populations, but not for Asian populations. CONCLUSIONS We present a simple method to evaluate whether partitioning based on dominant or recessive genetic effects is statistically justified. Important limitations remain that, in many situations, will preclude integration of genetic, laboratory, and clinical information. As society moves toward personalized medicine, additional research is needed on how to evaluate patient normality while accounting for additive genetic, multigenic, and other multifactorial effects.

scholarly journals European views on patients directly obtaining their laboratory test results

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
Ian D. Watson ◽  
Joanna Siodmiak ◽  
Wytze P. Oosterhuis ◽  
Joel Corberand ◽  
Per E. Jorgensen ◽  
...  
Keyword(s):  
Information Technologies ◽  
Clinical Chemistry ◽  
Information Age ◽  
Negative Attitude ◽  
Laboratory Medicine ◽  
European Federation ◽  
Test Results ◽  
Laboratory Test Results ◽  
Laboratory Results ◽  
Changing Practices

AbstractMedicine is a highly professionalized endeavour, by tradition centred on the authority of physicians. Better education and the advent of the information age cater for increased demands on society in general and on health care in particular to enable people to make informed decisions regarding themselves. Participation in medical decisions requires informed knowledge which is hard to obtain without substantial and time consuming professional help.We performed a survey amongst the member organizations of European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) in order to investigate the recognition and preparedness of providing help to patients in interpreting their laboratory results.Out of 40 EFLM Member Societies, 27 sent their responses to the survey. In most cases the first line delivery of laboratory results to physicians is by computer link (63%). Patients receive their laboratory results on demand from their physician in 60% of cases. However, 34% of laboratory specialists showed a negative attitude for delivering laboratory results to patients. Yet, in 48% of countries 1–5 patients per day ask a laboratory specialist about the significance of laboratory results outside the reference range. When patients are informed about the purpose of laboratory testing, they seek information primarily from their physician, followed by the internet and the Specialist in Laboratory Medicine.Changing practices increasingly enabling patient access to their records are on the increase facilitated by recent innovations in information technologies. Successful transfer of some of the responsibilities of physicians, demands a mutual triangular dialogue between the patient, their physician and laboratory medicine.

Optimizing the use of the “state-of-the-art” performance criteria

2015 ◽  
Vol 53 (6) ◽  
Author(s):  
Rainer Haeckel ◽  
Werner Wosniok ◽  
Thomas Streichert
Keyword(s):  
State Of The Art ◽  
Clinical Chemistry ◽  
Reference Interval ◽  
German Society ◽  
Laboratory Medicine ◽  
Biological Variation ◽  
The State ◽  
Analytical Performance ◽  
Performance Criteria ◽  
Performance Goals

AbstractThe organizers of the first EFLM Strategic Conference “Defining analytical performance goals” identified three models for defining analytical performance goals in laboratory medicine. Whereas the highest level of model 1 (outcome studies) is difficult to implement, the other levels are more or less based on subjective opinions of experts, with models 2 (based on biological variation) and 3 (defined by the state-of-the-art) being more objective. A working group of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL) proposes a combination of models 2 and 3 to overcome some disadvantages inherent to both models. In the new model, the permissible imprecision is not defined as a constant proportion of biological variation but by a non-linear relationship between permissible analytical and biological variation. Furthermore, the permissible imprecision is referred to the target quantity value. The biological variation is derived from the reference interval, if appropriate, after logarithmic transformation of the reference limits.

scholarly journals Data mining of pediatric reference intervals

2021 ◽  
Vol 45 (6) ◽  
pp. 311-317
Author(s):  
Jakob Zierk ◽  
Markus Metzler ◽  
Manfred Rauh
Keyword(s):  
Data Mining ◽  
Information Systems ◽  
Statistical Methods ◽  
Clinical Decision Making ◽  
Reference Intervals ◽  
Healthy Children ◽  
Test Results ◽  
Young Infants ◽  
Age Related ◽  
Laboratory Test Results

Abstract Laboratory tests are essential to assess the health status and to guide patient care in individuals of all ages. The interpretation of quantitative test results requires availability of appropriate reference intervals, and reference intervals in children have to account for the extensive physiological dynamics with age in many biomarkers. Creation of reference intervals using conventional approaches requires the sampling of healthy individuals, which is opposed by ethical and practical considerations in children, due to the need for a large number of blood samples from healthy children of all ages, including neonates and young infants. This limits the availability and quality of pediatric reference intervals, and ultimately negatively impacts pediatric clinical decision-making. Data mining approaches use laboratory test results and clinical information from hospital information systems to create reference intervals. The extensive number of available test results from laboratory information systems and advanced statistical methods enable the creation of pediatric reference intervals with an unprecedented age-related accuracy for children of all ages. Ongoing developments regarding the availability and standardization of electronic medical records and of indirect statistical methods will further improve the benefit of data mining for pediatric reference intervals.

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