Clinical Chemistry

Screening

Detection of subclinical disease with regular periodic testing and no symptom presentation

Diagnosis

Confirmation or ruling out of a disease with symptom presentation

Monitoring

Checking for treatment or disease progression

Prognosis

Long-term outcome of disease state (recovery or relapse)

Specimen factors

Age, sex, ethnicity, pregnancy, posture, exercise, stress, nutrition, time of day, drugs, needs to be in appropriate containers, labels, and transport conditions

Issues with specimen collection

Hemolysis (pink serum/plasma), delayed centrifugation (false low blood sugar because of glycolysis), incorrect anticoagulant, temperature requirement deviation

Organic biochemical markers

Carbohydrates, lipids, proteins, nucleic acids

Inorganic chemical markers

Ions (Na+ and K+), minerals, dissolved gases (arterial blood gas)

Exogenous chemical markers

Taken in: therapeutic drugs (chemotherapy), harmful substances (poisons/toxins)

Quality assessment/assurance

System of creating and following procedures and policies providing most reliable patient laboratory results (includes QC)

Quality control

System designed to ensure individual patient sample measurements are within clinically acceptable limits, monitors quality of lab testing and accuracy and precision of results, routine collection and analysis of data, allows for immediate corrective action

Qualitative testing

Determines presence or absence of substance or analyte, requires + and = control in each run of patient samples

Quantitative testing

measures amount of substance present, at least two levels of controls should be included in each day of patient testing (normal and abnormal ranges determine likelihood of error)

Pre-analytical errors (QC)

Problems with specimen (collection, handling, anticoagulant, contamination) and patient identification

Analytical (QC)

Implementation of QC processes, selection and managing of control materials, analysis and monitoring QC data, staff training, documentation, review

How to choose QC program

Choose high quality QC materials with known analyte concentrations, 2-3 levels of control, values cover medical decision levels, similar to test specimen, available in large amounts

Assayed control material

Mean is calculated by manufacturer and is commercially produced, needs to be verified by lab

Unassayed control materials

Less expensive than assayed (made “in house” with pooled sera or specimen), data analysis is performed, mean is determined by lab

How to establish control ranges

20 data points over 2 weeks or 10 working days, not over 4 weeks or 20 working days, represent procedural variation (different operators and time of day), determine amount of allowable error

Median

Value at center (midpoint) of observation points

Mean

Calculated average of valuesM

Mode

Value that occurs with the greatest frequency

Precision

Degree of fluctuation in measurements indicates precision

Accuracy

Closeness of measurements to true value is accuracy

Between run precision

Reproducibility - closeness of individual results with same method and test material but different conditions, operator, and instruments

Within run precision

Repeatability - closeness of individual results with same method, test material, conditions, operator, instrument, and time intervals

Measures of dispersion of variability

Range, variance, standard deviation, coefficient of variation

Standard deviation

Gaussian distribution with +/= 1, 2, 3, SD result in values falling within range 68.2, 95.4, and 99.7% of the time, respectively

Standard deviation criteria for reference ranges

Usually +/= 2 SD are used to set criteria for acceptable limit (95.4% confidence), values fall outside of criteria 4.5% of time most likely due to error

Coefficient of variation (CV)

SD expressed as percentage of mean (index of precision), ideally less than 5%

CV% = SD/mean x 100

Levey-Jennings Chart

Graphical method of displaying control results and evaluating if a procedure is in or out of control, plotted vs. time

Random error

Error that occurs unpredictably due to poor precision

Systemic error

Error that occurs predictably once a pattern of recognition is established

Shift

Sudden and sustained change in quality control results above or below mean

Trend

Gradual and steady change in QC results moving up or down away from mean