Clinical Chemistry I - Week 07 Quiz

Clinical Chemistry I - 0202304

• Course instructor: Mohammad QABAJAH
• Email: [email protected]
• Course code: 0202304

Week 07 - Reference Values

• Objectives:
  • State the need for establishing reference intervals for major clinical tests.
  • List conditions essential when comparing individual laboratory results to reference values.
  • Understand exclusion criteria used in producing health-associated reference values.
  • List partitioning criteria used to subgroup a reference group.
  • State parametric and non-parametric statistical methods for determining an interpercentile interval.
  • Discuss the issue of reference value transferability with prerequisites and solutions.
  • Compare the terms "reference value" and "reference interval".

Decision Making: Comparison

• Medical interviews, clinical examinations, supplementary investigations are used to make decisions.
• Results are compared to identify possible diagnoses.
• Diagnoses can be excluded or confirmed based on comparisons with typical disease patterns.

In Laboratory: Decision Making by Comparison

• Reference values
  • Derived from healthy individuals and patients with diseases.
  • Can be based on a single individual (subject-based) or a group of individuals (population-based).
  • Accompanied by a detailed description for clarity and use by others.

Comparing Observed Data

• Reference values are collected from various sources:
  • Healthy individuals.
  • Undifferentiated hospital population.
  • Individuals with typical diseases.

Conditions to Ensure Proper Comparison

• Reference groups should be clearly defined.
• Characteristics of the patient examined should resemble those of the reference group.
• Conditions need to be documented.
• Measurements must be from the same type.
• Standardised methods must be used for all results.
• Clinical sensitivity, specificity, and prevalence need to be considered.

Selection of Reference Individuals

• Ideally, the entire population.
• Random sampling (as large as possible; at least 120-).

Exclusion Criteria

• Diseases.
• Risk factors (obesity, hypertension, occupational or environmental risks, 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

• Pre-analytical standardization, which involves:
  • Preparing individuals before sample collection.
  • Sample collection procedures.
  • Sample handling before analysis.

Analytical Procedures and Quality Control

• Define the following:
  • Analysis method (including details on equipment).
  • Reagents.
  • Calibrators.
  • Types of raw data.
  • Calculation methods.
  • Quality control.
  • Reliability criteria.

Statistical Treatment of Reference Values

• Partition reference values into appropriate groups.
• Assess the distribution of each group.
• Determine reference limits.
• Identify outliers.

Inspection of Distribution

• Graphically display reference distributions (e.g., frequency distributions, histograms).
• Identify distribution patterns (unimodal, bimodal, polymodal).
• Detect highly deviating values (outliers).

Determination of Reference Limits

• Reference interval:
  • Upper and lower reference limits, representing a specified proportion (e.g., 95%) of the reference population.
  • Range: Higher value minus Lower value.
• Clinical decision limits:
  • Provide optimal separations among clinical categories (healthy individuals, patients with diseases).

Identification of Outliers

• Assume Gaussian distribution.
• Define outliers as data points more than 1.5 times the interquartile range (IQR) above the third quartile (Q3) or below the first quartile (Q1).

Quartile Formula

• Formulas to calculate lower quartile (Q1), middle quartile (Q2), and upper quartile (Q3) are provided.

Interquartile Range Formula

• Explain the calculation of the interquartile range (IQR).

Outliers Formula

• Formulas for calculating lower and higher outliers using the interquartile range (IQR).

Sample Data Calculation Example

• Illustrative example to show how to calculate the median and IQR based on a small sample data set.

Determination of Reference Limits

• Differentiate between reference limits and clinical decision limits.
• Explain the factors involved in determining reference intervals.

Interpercentile Interval

• Simple and widely used method, recommended by IFCC.
  • Parametric techniques based on mean and standard deviation (SD).
    • Calculate 2.5th and 97.5th percentiles.
    • Calculate lower and upper limits, using SD and the respective percentile.
  • Nonparametric techniques, not reliant on assumptions about the distribution.
    • Based on ranks.
    • Determine reference values from the sorted ranks.
    • Assess confidence intervals.

Transferability/Transfer of Reference Values

• The usage of reference values established by other laboratories is discussed.
  • Major population-wise requirements involve comparable populations and no major differences in ethnicity, social, or environmental factors.
  • Pre-analytical and analytical-wise requirements are detailed (e.g., similar methodologies, preparation of individuals, measurements, standardisation of analytical protocols, common calibration etc.).
  • CLSI verification recommendations for reference value selection (at least 20 individuals, adjusting limits if needed).
• Note about minimum individual measurements for multicenter production of reference values (minimum 120 readings).

This quiz covers essential concepts from Week 07 of the Clinical Chemistry I course, focusing on the establishment of reference values for clinical tests. Students will explore statistical methods, comparison criteria, and the health implications of reference intervals. Test your knowledge on the importance and applications of reference values in clinical decision-making.