Clinical Chemistry I 0202304 Lecture Notes PDF

Clinical Chemistry I 0202304 Instructor: Mohammad QABAJAH E-mail: [email protected] Week_07 Reference Values 2 Objectives I. State the need for establishing reference intervals for the major clinical tests. II. List conditions that are essential w...

Clinical Chemistry I 0202304 Instructor: Mohammad QABAJAH E-mail: [email protected] Week_07 Reference Values 2 Objectives I. State the need for establishing reference intervals for the major clinical tests. II. List conditions that are essential when a valid comparison of individual laboratory results with reference values is performed III. Understand the exclusion criteria used in the production of health- associated reference values IV. List the partitioning criteria used to subgroup a reference group V. state the parametric and nonparametric statistical methods of determining an interpercentile interval VI. Discuss the issue of transferability of reference values with regard to prerequisites and solutions to the issue. VII. Compare the terms reference value and reference interval Decision Making: Comparison Medical interviews, Clinical examinations, Supplementary investigations ??? Does not resembles resembles that of a that of a typical typical particular particular disease disease Exclude diagnosis Diagnose In laboratory: Decision Making by Comparison Reference values ̵ Healthy Individuals ̵ Patients with Diseases Reference values; Obtained from ̵ single individual (Subject-based reference values) ̵ or group of individuals (Population-based reference values) Corresponding to a stated description, which must be spelled out and made available for use by others Comparing of Observed Data Several collections of reference values - Healthy people - Undifferentiated hospital population Reference Individuals - People with typical diseases Conditions to Ensure Proper Comparison - All groups of reference individuals should be clearly defined - The patient examined should resemble sufficiently - The conditions should be known - All quantities should be of the same type - Standardized methods for all results - The clinical sensitivity, clinical specificity, and prevalence should be known Selection of Reference Individuals Ideally: the whole population Random sampling (as large as possible (120~ Exclusion Criteria - Diseases - Risk Factors - Obesity - Hypertension - Risks from occupation or environment - Genetically determined risks - Intake of Pharmacologically Active Agents - Specific Physiological States - Pregnancy - Stress - Excessive exercise Subgrouping of the Reference Group - Age - Gender - Physiological Factors - Stage in menstrual cycle - Stage in pregnancy - Physical condition Specimen Collection Preanalytical standardization ̵ Preparation of individuals before sample collection ̵ The sample collection ̵ Handling of the sample before analysis Analytical Procedures and Quality Control Components that need to be defined - Analysis method, including information on - Equipment - Reagents - Calibrators - Types of raw data - Calculation method - Quality control - Reliability criteria Statistical Treatment of Reference Values - Partitioning of the reference values into appropriate groups - Inspection of the distribution of each group - Determination of reference limits - Identification of outliers Inspection of Distribution Display the reference distribution graphically (frequency distribution) - Unimodal, Bimodal or polymodal distribution - The shape of the distribution - Highly deviating values (outliers) Determination of Reference Limits Reference interval: ̵ Upper reference limit and a lower reference limit ̵ Representing specified proportion of the reference population 95% Range: (Higher value - Lower value) Clinical decision limits: ̵ Provide optimal separation among clinical categories. (healthy individuals, patients with relevant diseases) Identification of outliers Assumption that the distribution is Gaussian An outlier is defined as being any point of data that lies over 1.5 IQRs below the first quartile (Q1 :25th percentile) or above the third quartile (Q3: 75th percentile) in a data set. 19 Determination of Reference Limits ◦ Reference limit ◦ Clinical decision limit ◦ Reference range vs. Reference interval ◦ Reference interval: Tolerance interval Interpercentile interval Prediction interval Interpercentile Interval ◦Simple to estimate, most used; recommended by IFCC, used for: - Parametric techniques: Calculation based on mean and SD 2.5 Percentile = Mean - 1.96 SD 97.5 Percentile = Mean + 1.96 SD Lower limit = Percentile Limit – 2.81*SD/√n Upper limit = Percentile Limit + 2.81*SD/√n - Non-parametic techniques: Makes no assumption about the data ◦Based on the rank ◦Sort data, compute rank numbers 2.5 and 97.5 ◦Find reference value corresponding to the rank ◦Determine the confidence interval 2.5% 97.5% Clinical Decision Limit_ Example Transferability/Transference of Reference Values The use of reference values generated by other laboratory Major requirements (population wise) ̵ Populations must be comparable ̵ No major ethnic differences ̵ No major social differences ̵ No major environmental differences Transferability/Transference of Reference Values Major requirements (pre analytical wise) ̵ Qualifying reference individuals ̵ Preparing individuals for specimen collection ̵ Performing specimen collection ̵ Using the same analytical method Transferability/Transference of Reference Values Points to be considered (analytical wise) ̵ Standardization of analytical protocols ̵ Common calibration ̵ Design of a sufficiently efficient external quality control scheme ̵ Mathematical transferring if results are not directly comparable Transferability/Transference of Reference Values Verification (CLSI recommendation) ̵ Measure 20 individuals ̵ If no more than 2 outside values, adopt reference values ̵ Multicenter production of reference values: Minimum 120 readings See YOU Next Lecture ☺