Quality Control, Delta Checks and Predictive Value

CLS 500 Application and Interpretation of Clinical Laboratory Data

Objectives
1. Discuss the use of quality control in ensuring the validity of laboratory test results 2. Define the acceptable range as it relates to quality control and how this range is determined.

Ricki Otten, MT(ASCP)SC uotten@unmc.edu

Objectives
3. Define the terms as they relate to quality control: a. Accuracy b. Precision c. Reliability 4. Explain the use of delta checks to assure accurate patient test results
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Objectives
5. Define the following terms: a. Test sensitivity b. Test specificity c. Predictive value 6. Discuss how sensitivity, specificity and predictive value are used to assess the diagnostic usefulness of a test
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Quality Control (QC)

Who needs it? What is it? Why is it done? How is it used?
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The most basic and fundamental expectation of a laboratory is

CLS 500 Application and Interpretation of Clinical Laboratory Data QC, Delta Check and Predictive Value Lecture

Quality Control (QC)

QC is a statistical tool that is used to assure the reliability of test results Statistical quality control practices are critical for assuring test results are correct

QC: What is it?

The value of the quality control specimen is known and is represented by an acceptable range of values that has been statistically calculated Acceptable range = Mean 2 SD
For each control level for each assay: 1. Control is analyzed repeatedly on separate days 2. Values are collected until 30+ values are obtained 3. Statistics are calculated: mean, SD, %CV 4. Acceptable range is determined

QC: What Does it Do?

QC statistically validates the accuracy (correctness) of Methodology Testing procedure Reagents Entire test system Instruments
Acceptable range = Mean 2SD = 6.8 0.6 = 6.2 7.4 g/dl
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Analytical Run

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QC cannot determine if the sample submitted is from the correct patient!

QC: How is it Used?

The laboratory wants to report the most accurate and precise values
QC samples are analyzed along with the patient samples Evaluation of QC results determines the validity of the analytical run If analytical run is valid, then we are confident the patient results are also valid 12

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CLS 500 Application and Interpretation of Clinical Laboratory Data QC, Delta Check and Predictive Value Lecture

 If QC results are within acceptable limits

then the analytical run is validated as accurate. This means the patient results are valid and can be reported

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If QC results are not within acceptable limits

then the analytical run is not valid. This indicates an analytical error has occurred that jeopardizes the patient results. This means the patient results may not be valid and cannot be reported. After troubleshooting the error, all samples must be reanalyzed and QC must be statistically re-evaluated before patient test results are reported
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What does accuracy and precision mean?

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CLS 500 Application and Interpretation of Clinical Laboratory Data QC, Delta Check and Predictive Value Lecture

 Accuracy refers to the closeness of a measurement to the true value Precision refers to the reproducibility of a measurement Reliability refers to the accuracy and precision of a measurement

Quality Control Exercise

Evaluate the following analytical run in relation to test validity. Should the patient test results be released to the medical record? Why or why not?
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Analytical Run: plasma glucose 1. Level I control 2. Level II control 3. John Smother 4. Gomer Pyle 5. Jayne Sealess

Result (mg/dl) 69 150 43 132 97

Analytical Run: plasma glucose 1. Level I control 2. Level II control 3. John Smother 4. Gomer Pyle 5. Jayne Sealess

Result (mg/dl) 69 150 43 132 97 OK Not OK

Quality Control Acceptable Limits Mean +/- 2SD Level I Level II 70 +/- 4 mg/dl 180 +/- 9 mg/dl Acceptable Range 62 78 mg/dl 162 198 mg/dl

Expected Reference Range and Critical Limits Fasting plasma glucose: 70-99 mg/dl Critical low: Critical high: < 45 mg/dl > 450 mg/dl

Quality Control Acceptable Limits Mean +/- 2SD Level I Level II 70 +/- 4 mg/dl 180 +/- 9 mg/dl Acceptable Range 62 78 mg/dl 162 198 mg/dl

Expected Reference Range and Critical Limits Fasting plasma glucose: 70-99 mg/dl Critical low: Critical high: < 45 mg/dl > 450 mg/dl

Is level I control within acceptable limits? Is level II control within acceptable limits?
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Can patient test results be reported? Why/why not?

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Analytical Run: plasma glucose 1. Level I control 2. Level II control 3. John Smother 4. Gomer Pyle 5. Jayne Sealess
Quality Control Acceptable Limits Mean +/- 2SD Level I Level II 70 +/- 4 mg/dl Acceptable Range 62 78 mg/dl

Result (mg/dl) 69 150 43 132 97 OK Not OK

Delta Check
Another tool used by the laboratory to assure accurate patient test results for specific analytes The most recent test result for a particular patient is compared to the most previous test result for that patient

Expected Reference Range and Critical Limits Fasting plasma glucose: 70-99 mg/dl Critical low: Critical high: < 45 mg/dl > 450 mg/dl

180 +/- 9 mg/dl 162 198 mg/dl

Can patient test results be reported? Why/why not? No; the validity of the analytical run is questioned because control level II is outside of acceptable limits. All testing must be repeated and when all controls are within acceptable limits, 23 the patient test results may be reported.

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CLS 500 Application and Interpretation of Clinical Laboratory Data QC, Delta Check and Predictive Value Lecture

Delta Check
If the test result has changed significantly from the last time the test was done, a delta check failure occurs The delta check failure means the change in test results is not physiologically possible The allowable difference is predetermined by various investigators and clinicians

Delta Check
The technologist is now responsible to determine the cause of the delta check failure before releasing test results
Test sample may have been compromised
Test interference: hemolyzed, lipemic, icteric Sample not handled properly Drawn at incorrect time: trough, peak, tolerance Drawn in incorrect sample tube: B-R-G-P-G Treatment?

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Is this the correct patient? Redraw the specimen?

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Jan.1 BUN (mg/dl) 88

Jan.8 95

Jan.12 105

Jan. 13 22*

Jan.1 K+ 3.9 (mmol/L)

Jan.2 3.6

Jan.3 4.1

Jan.4 6.9*

*Delta check failure What is a likely cause for this failure? Should test results be reported?
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*Delta check failure What is a likely cause for this failure? Should test results be reported?
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Diagnostic Efficacy
Diagnostic sensitivity Diagnostic specificity Positive predictive value Negative predictive value

Ideal
All persons with disease will test positive (referred to as diagnostic sensitivity) All persons without disease will test negative (referred to as diagnostic specificity) Test results would be: 100% sensitive 100% specific
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CLS 500 Application and Interpretation of Clinical Laboratory Data QC, Delta Check and Predictive Value Lecture

Reality
All methods have an inherent amount of error that will affect test results No method is able to detect all persons with disease accurately -andNo method is able to detect all persons without disease accurately
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Possible Test Outcomes

Patients with disease Positive test result Negative test result + (TP) - (FN) Patients without disease + (FP) - (TN)

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Patients with disease Positive test result Negative test result Test sensitivity: Test specificity: + (TP) - (FN)

Patients without disease + (FP) - (TN)

Hypothetical Example
A total of 3000 patients were assessed for acute myocardial infarction (AMI) with Troponin I (cTnI) measurements: 1000 patients tested positive for cTnI and of those, 980 had diagnostic AMI; 2000 patients tested negative for cTnI and of those, 30 had diagnostic AMI 34

TP/(TP + FN) x 100 TN/(TN + FP) x 100

Pos predictive value: TP/(TP + FP) x 100 Neg predictive value: TN/(TN + FN) x 100

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Construct 2x2 Table

Determine the sensitivity, specificity, positive predictive value (+PV) and negative predictive value (-PV) of the test used for assessment of AMI
Patients with AMI Pos test result Neg test result Patients without AMI

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CLS 500 Application and Interpretation of Clinical Laboratory Data QC, Delta Check and Predictive Value Lecture

Calculate Test Sensitivity

Test sensitivity: TP/(TP + FN) x 100

Calculate Test Specificity

Test specificity: TN/(TN + FP) x 100

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Calculate Pos Predictive Value

Pos predictive value: TP/(TP + FP) x 100

Calculate Neg Predictive Value

Neg predictive value: TN/(TN + FN) x 100

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PSA values >4.0 ng/ml

Patients with Patients without prostate cancer prostate cancer Pos test result (>4.0 ng/ml) Neg test result (<4.0 ng/ml)
Sensitivity = 79% +PV = 33%

High Cut-off Value

If a high cutoff value is used, then the specificity of the test can reach 100% However, the sensitivity will decrease

151 (TP) 41 (FN)

Specificity = 46% -PV = 87%

313 (FP) 265 (TN)

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CLS 500 Application and Interpretation of Clinical Laboratory Data QC, Delta Check and Predictive Value Lecture

Low Cut-off Value

If a low cutoff value is used, then the sensitivity of the test can reach 100% However, the specificity will decrease

Disease Prevalence
Using PSA cut off value of 4.0 ng/ml: Sensitivity = 79%; Specificity = 46%; +PV = 33%; -PV = 87%)

Prevalence of disease 0.001 (0.1% of population) 0.01 (1% of pop) 0.1 (10% of pop) 0.2 (20% of pop) 0.5 (50% of pop)
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Pos Predictive Value 0.1% 1.5% 14.0% 26.8% 59.4%

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CLS 500 Application and Interpretation of Clinical Laboratory Data QC, Delta Check and Predictive Value Lecture