Laboratory Medicine: Basic QC Concepts

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Laboratory Medicine Basic QC Concepts

• M. Desmond Burke, MD

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Laboratory Error, Normal Ranges, Predictive
Values

• M. Desmond Burke, M.D.
• Weill Cornell Medical Center
• New York, New York

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Laboratory Diagnosis

• laboratory error - preanalytical -
  analytical accuracy precision
• normal or reference values
• sensitivity, specificity prevalence
• predictive value
• pretest posttest probabilities
• thresholds test strategy

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CLINICAL CLUES
TEST STRATEGIES
HYPOTHESIS ACTIVATION
HYPOTHESIS REVISION
ROUTINE TESTS
PATIENT MANAGEMENT
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CLINICAL VALUE
DIAGNOSTIC VALUE
TECHNICAL RELIABILITY
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Action
Test selection
Interpretation
Question
Reporting
Ordering
Analysis
Identification
Preparation
Collection
Transportation
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Laboratory Error Preanalytical

• patient preparation - diet, activity
• specimen collection - wrong name, wrong tube,
  wrong time wrong technique
• specimen transport storage - delays, wrong
  temperature

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Accuracy Precision

• Accuracy closeness to truth - maintained
  routinely by calibrators - checked by
  inter-laboratory surveys
• Precision reproducibility - estimated by
  Standard Deviation (SD) or Coefficient of
  Variation (CV) - monitored by quality control
  sera

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Precise Inaccurate
Precise Accurate
Inaccurate Imprecise
o
o
o
o

o
o
o
oo
o
o
o
o
o
o
o
Accurate Imprecise
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Importance of Quality Control to the Physician

• QUESTIONwhen is the difference between two
  successive test results within the limits of
  analytical imprecision?
• ANSWERwhen the results differ by more than 3 x
  SD of the laboratory method

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Normal or Reference

• referenceis the appropriate word - central 95
  percent of the range of values in an
  apparently healthy population
• normal could mean - free of neurosis, usual,
  ideal, free of disease, or including the
  central 95 percent of a normal or
  gaussian distribution

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95
68

?
Mg/dL
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Relationship of Expected Abnormal Results to
Number of Measured Constituents
Number of Measured Constituents Expected of one or more abnormal Results
1 5
2 10
4 19
6 26
10 40
15 54
20 64
Probability of abnormal result 1 0.95n n
equals test number
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CLINICAL VALUE
DIAGNOSTIC VALUE
TECHNICAL RELIABILITY
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POST-TEST PROBABILITIES
POST-TEST PROBABILITY, GIVEN A POSITIVE TEST
RESULT PV
POST-TEST PROBABILITY, GIVEN A NEGATIVE TEST
RESULT 100 PV-
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TEST
TREAT DO NOT TEST
DO NOT TEST DO NOT TREAT
1.0
0.0
RULE-IN THRESHOLD
RULE-OUT THRESHOLD
PROBABILITY OF DISEASE
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PRETEST (P)
POSTTEST NEG (P)
POSTTEST POS (P)
50
10
90
TEST
1.0
0.0
RULE-IN THRESHOLD
RULE-OUT THRESHOLD
PROBABILITY OF DISEASE
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Sensitivity Specificity

• SENSITIVITY - the percentage of diseased
  individuals with abnormal test results
• SPECIFICITY - the percentage of healthy
  individuals with normal results

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False Negatives False Positives

• FALSE NEGATIVE RATE - 100 minus SENSITIVITY
• FALSE POSITIVE ATE - 100 minus SPECIFICITY

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Predictive Values

• POSITIVE PREDICTIVE VALUE (PV) - the percentage
  of true positive test results among all
  positive test results
• NEGATIVE PREDICTIVE VALUE (PV-) - the percentage
  of true negative test results among all
  negative test results

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TEST RESULT
DISEASE PRESENT
DISEASE ABSENT
POSITIVE
TP
FP
POSTTEST PROBABILITY GIVEN A POSITIVE RESULT
TP/TPFP
NEGATIVE
FN
TN
POSTTEST PROBABILITY GIVEN A NEGATIVE RESULT
FN/TNFN
TOTALS
TN FP
TP FN
SENSITIVITY TP/TPFN
SPECIFICITY TN/FPTN
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POSTTEST PROBABILITY OF DISEASE WHEN PRETEST
PROBABILITY IS 50
TEST RESULT
DISEASE PRESENT
DISEASE ABSENT
POSITIVE
90
10
POSTTEST PROBABILITY GIVEN A POSITIVE RESULT
90/100
(90)
NEGATIVE
10
90
POSTTEST PROBABILITY GIVEN A NEGATIVE RESULT
10/100 (10)
TOTALS
100
100
SENSITIVITY 90
SPECIFICITY 90
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PRETEST (P)
POSTTEST NEG (P)
POSTTEST POS (P)
50
10
90
TEST
1.0
0.0
RULE-IN THRESHOLD
RULE-OUT THRESHOLD
PROBABILITY OF DISEASE
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POSTTEST PROBABILITY OF DISEASE WHEN PRETEST
PROBABILITY IS 90
TEST RESULT
DISEASE PRESENT
DISEASE ABSENT
POSITIVE
810
10
POSTTEST PROBABILITY GIVEN A POSITIVE RESULT
810/820 (99)
NEGATIVE
90
90
POSTTEST PROBABILITY GIVEN A NEGATIVE RESULT
90/180 (50)
TOTALS
900
100
SENSITIVITY 90
SPECIFICITY 90
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POSTTEST PROBABILITY OF DISEASE WHEN PRETEST
PROBABILITY IS 10
TEST RESULT
DISEASE PRESENT
DISEASE ABSENT
POSITIVE
90
90
POSTTEST PROBABILITY GIVEN A POSITIVE RESULT
90/180
(50)
NEGATIVE
10
810
POSTTEST PROBABILITY GIVEN A NEGATIVE RESULT
10/820 (1)
TOTALS
100
900
SENSITIVITY 90
SPECIFICITY 90
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Effects of Prevalence

• DECREASING PREVALENCE - decreases (PV)
  increases (PV-)
• INCREASING PREVALENCE - increases (PV)
  decreases (PV-)

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F
D
D
X
Xc
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5
10
12
15
D
D
X
Xc
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RECEIVER-OPERATOR CHARACTERISTIC (ROC) CURVES
100
BEST
BETTER
50
TP
USELESS
100
0
50
FP
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• DETERMINANTS OF SENSITIVITY - choice of cutoff
  or reference limit - severity of disease in
  patients chosen to determine
  sensitivity - increased by multiple testing in
  parallel
• DETERMINANTS OF SPECIFICITY - choice of cutoff
  or reference limit - type of nondiseased persons
  chosen to determine specificity -
  increased by multiple testing in series

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WHICH TEST TO ORDER?
WHAT IS THE PRETEST PROBABILITY OF THE PROBLEM?
WHAT ARE THE RULE IN RULE OUT THRESHOLDS
TO RULE IN
TO RULE OUT
KEY IS SPECIFICITY
KEY IS SENSITIVITY
POSTTEST PROBABILITY () SHOULD BE HIGHER THAN
RULE IN THRESHOLD
POSTEST PROBABILITY (-) SHOULD BE LOWER THAN
THE RULE OUT THRESHOLD
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POSTTEST PROBABILITY OF CHD WHEN PRETEST
PROBABILITY IS 10
TEST RESULT
DISEASE PRESENT
DISEASE ABSENT
POSITIVE
86
207
POSTTEST PROBABILITY GIVEN A POSITIVE RESULT
86/293
(29)
NEGATIVE
14
693
POSTTEST PROBABILITY GIVEN A NEGATIVE RESULT
14/707 (2)
TOTALS
100
900
SENSITIVITY 86
SPECIFICITY 77
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POSTTEST PROBABILITY OF CHD WHEN PRETEST
PROBABILITY IS 90
TEST RESULT
DISEASE PRESENT
DISEASE ABSENT
POSITIVE
774
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POSTTEST PROBABILITY GIVEN A POSITIVE RESULT
774/797
(97)
NEGATIVE
126
77
POSTTEST PROBABILITY GIVEN A NEGATIVE RESULT
126/203 (62)
TOTALS
900
100
SENSITIVITY 86
SPECIFICITY 77
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PRETEST (P)
POSTTEST NEG (P)
POSTTEST POS (P)
90
62
97
TEST
1.0
0.0
RULE-IN THRESHOLD
RULE-OUT THRESHOLD
PROBABILITY OF DISEASE
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PRETEST (P)
POSTTEST NEG (P)
POSTTEST POS (P)
50
1
10
TEST
1.0
0.0
RULE-IN THRESHOLD
RULE-OUT THRESHOLD
PROBABILITY OF DISEASE