Clinical Chemistry: Quality Control/Assurance (Exam 2)

What are some preanalytical conditions or situations with patients which could affect the results of laboratory testing?

Diet basal state post prandial state diurnal variations exercise patient position pregnancy smoking stress interfering substances (ie: drugs)

What is semiquantitative testing?

Doesn't give an exact value, but rather a range. Includes using a manufactured positive and negative control

What is quantitative testing?

Done on large instruments. Give an actual value. Manufactured controls are used to check the validity of the laboratory test. Two or three levels of control samples may be necessary to ensure that all levels are being accurately detected.

Negative predictive value

Fraction of negative test results that are true negatives. Identifies individuals who do not have the disease

Positive predictive value

Fraction of positive test results that are true positive. Identifies individuals who are diseased

Analytical Specificity

Freedom from interference and cross reactivity, to determine solely the analyte being measured. Represents what is being measured and nothing else.

Trend

Gradual but steady change in QC results. Moving up or down away from the mean

What is a Levy-Jennings chart?

Graph used to plot the ongoing results of control samples. Plotting daily results helps visualize deviation of results from the mean.

What is qualitative testing?

Have a built in positive control that produces a colored band if working. Validity must be checked by external manufactured positive and negative controls at intervals recommended by the manufacturer

Bias

Observed result minus the assigned value. Difference between results from the reference method (current) and results from a method under investigation (new)

Which test is most affected by hemolysis?

Potassium

Quality Assessment Quality Assurance Quality Management

Process that includes a set of activities that aids in improving the reliability of the laboratory

What is the importance of the Gold Standard Method in comparison to other laboratory methodology?

Provides the best available approximation of a true value. Have been established and reproduced across different measurement systems, laboratories, and over periods of time. Method whose precision and accuracy are well described when the exact procedure is followed.

Falls under quality assurance:

Quality control

Reagent dispensing, sample evaporation, temperature of analyzer, optical system, calibrator reconstitution, environmental conditions, instability of instrument, variation in specimen handling techniques, variation in operators are all examples of what kind of error?

Random Error

Systematic Error

Recurring error that affects all results. Can be identified by a trend in QC measurement.

Describe the process of establishing reference ranges

Reference point to determine whether a disease is present or absent, or if a patient is at risk for future disease states. Normal = concentration of chemical that is measured for 95% of the healthy population

What are the proper specimen handling and storage procedures?

Serum or plasma should be separated within 2 hrs, tested within 3hrs or stored refrigerated/frozen. Avoid air exposure. Protect from light, especially for bilirubin and liver assays

What is diagnostic testing?

Should detect all positives without giving any false positives. High sensitivity AND high specificity

How are QC materials manufactured and used in the lab?

Solution or chemical substance of known concentration that mimics a patient's specimen is collected, processed, and manufactured commercially. A minimum of 2 QC samples must be analyzed at least once per day for each analyte to detect immediate errors.

What is the typical centrifugation speed and time?

Speed: 3,000-5,000rpms Time: 10-15min

What are confidence intervals/limits?

The term used when the reference range is expressed using 2 SD on either side of the mean, with 95% of the values falling above or below the mean. Test point falling outside the confidence interval may be termed error.

Diagnostic Specificity

True negative rate. Likelihood of a negative test result in patients without disease. Measures how well the test excludes disease

What are the four diagnostic categories used for medical decision limits?

True positive False positive True negative False negative

Diagnostic Sensitivity

True positive rate. Likelihood of a positive test result in patients with disease; measures how well the test detects the disease

What are Westgard Rules?

Use a combination of decision criteria or control rules to decide whether a run is in control or out of control. Generally used with 2 or more control levels per run.

What is the purpose of SDI?

Validates individual lab results as compared to peer group QC.

Mode

Value that occurs most commonly in a group of data

What is a 1-2s Westgard rule?

Warning--one control exceeds +-2 standard deviations

How are medical decision limits established?

after consultation between laboratory and medical staff. Determined by quantifying the analyte of interest in a sampling of a patient population with the disease and a sampling of those without the disease

What is plasma and what type of tube is it collected in?

clot has not been formed; contains no clotting factors Green

What is whole blood and what type of tube is it collected in?

contains whole blood that hasn't clotted. Lavender tube

What does true negative mean?

disease not present

What does true positive mean?

disease present

What does false negative mean?

disease present (but shows as - )

What are some common interference substances?

hemoglobin (due to hemolysis), lipids, bilirubin, drugs, anticoagulants

What is screening testing?

initial test that should detect everyone with the disease BEFORE presenting with symptoms. High degree of SENSITIVITY

What is serum and what type of tube is it collected in?

left over at blood clots, does not contain clotting factors. Red, gold, red/gray

What are the advantages of using a gel type collection tube for specimen collection?

less manipulation of specimen hemolysis minimized less chemical interaction of blood to serum enhanced recovery of serum decreased staff time lower frequency of testing error storage time

Would recent calibrations, a new shipment of control, or a new lot of calibrator be more likely to cause a shift or trend in data?

shift

What items need to be included in the Standard Operating Procedure

specimen requirements specimen handling and processing requirements test methodology/procedures linearity (reportable range) reference range information (normal ranges) dilution information interferences/limitations

Would aging controls or reagents, needed maintenance, or a fading light source be more likely to cause a shift or trend in data?

trend

Mean

x with a line over it. A mathematical average, calculated by dividing the sum of all individual values by the number of values

Type II QC Error

Accepting a control when it should be rejected

Coefficient of Variation (CV)

Used to compare the

What is confirmatory testing?

Used to verify the results of an initial test. High degree of SPECIFICITY

What does false positive mean?

disease not present (but shows as + )

What are some examples of pre-analytical activities?

--Physician order/requisition --Patient ID --Patient instructions or compliance --Collection of specimen --Processing of specimen --Storage of specimen --Transportation of specimen Avoiding contamination

What are some examples of post analytical activities?

--Positively identifying the test report with the pt. sample --Reporting pt results in a timely manner --Using a reporting format that can be understood and correctly interpreted by health care providers, complete with reference ranges --System for alerting health care providers with critically significant results --Notifying health care providers when results arrive from outside reference labs --Patient notification --Proper disposal of laboratory specimens and other biohazards -Disinfection/decontamination of work areas where testing takes place

What are some examples of analytical activities?

--Specimen or reagent preparation --Instrument maintenance and calibration --Quality control and proficiency testing --Producing the laboratory report

What is a 10x Westgard rule?

10 consecutive controls fall on one side of the mean

Relevancy

A connection or correlation with an associated disease or condition based on interpretive guidelines. Criteria for these interpretive guidelines are often expressed as reference ranges

A minimum of ________ QC samples must be analyzed at least ___________ per day for each analyte to detect immediate errors.

A minimum of TWO QC samples must be analyzed at least ONCE per day

Analytical Sensitivity

Ability to detect small concentrations of the measured analyte. The more sensitive the test, the smaller the amount of assayed substance that can be measured

What are the advantages and disadvantages of assayed controls?

Advantages: arrive with target ranges, helpful for tests that are performed infrequently, specific for instrumentation and reagents Disadvantages: more expensive, may not be available for certain test systems

What are the advantages and disadvantages of unassayed controls?

Advantages: cheaper, not instrument dependent Disadvantages: target values must be determined by lab which can be time consuming

Allowable Error

Amount of error that can be tolerated without invalidating the medical usefulness of the analytical result

What are the requirements for the competency evaluation of laboratory personnel?

Appropriate education, training, experience Documentation required Always have someone in the lab at all times that can perform every single test Competency activities: reading standard operating procedures perform procedure with supervision perform procedure without supervision and achieve expected results supervisor verification of test results until personnel feel comfortable with all steps involved participation in internal QC among lab personnel participation in proficiency testing activities participation in internal and external lab continuing education activities annual laboratory training

What is the difference between assayed and unassayed controls?

Assayed: controls come WITH value ranges for tests being conducted Unassayed: control values must be calculated

Why is a first morning specimen optimal for urine collection?

Because it's the most concentrated, so it's most representative of what's going on with the patient

Standard Deviation Index

Describes the number of standard deviations away from the mean that a result is

What are the four reasons for ordering a laboratory test?

1. Diagnosis 2. Monitoring 3. Screening 4. Research

What is the CV and what is its purpose?

Coefficient of Variation. Describes SD as a percentage of the mean. Makes it easier to compare precision over the analytical range of the assay. Reflects a ration of the SD to the concentration being measured, t/f it often provides a better estimate of method performance over a range of concentrations

What is a delta check?

Computerized check performed to detect changes from earlier individual patient test results.

How are quality control ranges established in the lab?

Control material is tested as a patient specimen--minimum of 20 data values required, each in a separate run. Acceptable limit or variation from the mean can then be calculated based on the SD from the mean. Most labs use 2 SD's above and below the mean as the allowable range for the analyte.

Accuracy

Correctness How closely a measured value agrees with a true or expected value. Occurs when control results consistently fall within 1 SD of the mean. Concerned with sensitivity and specificity

What is the comparison method of studies?

Correlation of a new method. Differences are interpreted as systematic analytical errors, which are referred to as the bias of a method--can be positive or negative

What are medical decision limits?

Cutoff values to associate with specific diseases

Random Error

Error that occurs unpredictably due to poor precision. Identified by a sudden fluctuation in the QC measurement, either above or below the mean.

Analytical

Every step involved in the actual analysis of a laboratory specimen

Preanalytical

Everything that affects a patient specimen before it is tested for the analyte

Post analytical

Everything that affects patient results in the reporting stage

Variance

Factors or fluctuations that affect the measurement of the substance in question. The ERROR of a procedure

Quality Control

Falls under quality assurance. Monitors analytical aspects of a method, verifying that results from a given method are precise and accurate. Monitors performance of lab instruments, reagents, other testing products and equipment, technical error by personnel

What are recovery studies?

Indicator of the accuracy of a particular measurement. A measured amount of a known standard (pure substance) is added to a patient specimen and compared to another patient specimen minus the standard. The difference between the two is calculated and expressed as a %. Ideally the exact amount of standard added should be recovered at the end of the measurement if the method is an accurate one.

What is the difference between internal and external quality control for test systems and personnel?

Internal QC: performed within the lab on internal samples (patient or control) External QC: Proficiency Testing and periodic inspections by accrediting agencies

Why is it important to centrifuge for the appropriate speed and time?

Necessary to remove cells, less than that will lead to fibrin clots, less serum, and a messy specimen

Median

Middle value of a body of data. If all variables are arranged in order of increasing magnitude, the median is that variable which falls halfway between the highest and the lowest

What is the purpose of QC in the lab?

Monitors performance of lab instruments, reagents, other testing products and equipment, and technical error by personnel

What is quality control?

Monitors the analytical aspects of a method; verifying that results from a given method are precise and accurate

Reference Range

Reference point to determine whether a disease is present or absent, or if a patient is at risk for future disease states. Range of values for a given analyte in a defined population. Derived from a group of "normal and healthy" individuals. Measurements will statistically follow the normal Gaussian distribution of data. Includes 95% of test results

What is a 4-1s Westgard rule?

Reject--four consecutive controls exceed the same + or -1 standard deviation

What is a 1-3s Westgard rule?

Reject--one control exceeds +-3 standard deviations

What is a R4s Westgard rule?

Reject--one control exceeds +2 standard deviations and another exceeds the mean -2 standard deviations

What is a 2-2s Westgard rule?

Reject--two consecutive controls exceed +-2 standard deviations

Type I QC Error

Rejecting a control when it should be accepted

Linear Range Reportable Range Analytical Measurement Range

Reportable Range. Range of specimen concentration that can be accurately measured by a test method. The lower limit is the minimum detection level that can be distinguished from zero. The upper limit is the level that can be measured accurately without dilution

What is the purpose of CV?

Represents precision of a test (reproducibility) Used to compare test results from one day to another or one lab to another Helps identify sampling errors and procedural factors

Precision

Reproducibility of a test system. Ability to produce the same test result each time. Detects random error of the method. Used to define the acceptable range.

Describe the actions to be taken when Quality Control fails

Rerun QC sample--can only repeat once according to CLIA Troubleshoot Identify possible sources of error Service call

What is interference studies?

Samples are checked against analytical methods known to be free of interference. The difference or bias can be judged against the allowable bias or the total allowable error

What is an SDI and what is the purpose

Standard Deviation Index. Aka: Z statistic or Z score. Computed values that compare your lab with other labs using the same instruments/methodology Calculated value that tells the number of standard deviations a PT result is from the group mean value expected for that material. SDI= difference between an individual value subtracted from the group mean, divided by the SD of the group

What is the purpose of SOP and what information does it need to contain?

Standard Operating Procedure. Defines the requirements of each test.

What is a Gaussian curve?

Statistic analysis of control samples based on the assumption that a set of measurements will typically follow the normal Gaussian distribution. Bell shaped curve. 68% will be within 1 SD of the mean, 95% will be within 2 SD of the mean, and 99.7% will be within 3 SD of the mean.

Standard Deviation

Statistic that describes the distribution of all values around the mean for a particular group. Used to test precision

Shift

Sudden and sustained change in quality control results above or below the mean, then continues at the same level

Aging reagents or calibrators, instrument components, optical changes, fluctuations in voltage, wear and tear of instrument, reagent lot variability, calibration differences, technologist interactions are all examples of what kind of error?

Systematic Error

What are the disadvantages of using a gel type collection tube for specimen collection?

TDM--therapeutic drug monitoring RBC enzymes lead, trace metals hormones, renin, catecholamines

T or F: Interpretation of control results is based on using specific rules for acceptance and rejection of QC results, documenting results and decisions, and having a process for resolving problems.

TRUE

Reliability

The result when BOTH accuracy and precision are accomplished