Transcript Document 7546470

Lecture 3
Validity of screening and
diagnostic tests
• Reliability: kappa coefficient
• Criterion validity:
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“Gold” or criterion/reference standard
Sensitivity, specificity, predictive value
Relationship to prevalence
Likelihood ratio
ROC curve
Diagnostic odds ratio
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Clinical/public health
applications
• screening:
– for asymptomatic disease (e.g., Pap test,
mammography)
• for risk (e.g., family history of breast cancer
• case-finding: testing of patients for diseases
unrelated to their complaint
• diagnostic: to help make diagnosis in
symptomatic disease or to follow-up on
screening test
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Evaluation of screening and
diagnostic tests
• Performance characteristics
– test alone
• Effectiveness (on outcomes of disease):
– test + intervention
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Criteria for test selection
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Reliability
Validity
Feasibility
Simplicity
Cost
Acceptability
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Measures of inter- and intra-rater
reliability: categorical data
• Percent agreement
– limitation: value is affected by prevalence higher if very low or very high prevalence
• Kappa statistic
– takes chance agreement into account
– defined as fraction of observed agreement not
due to chance
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Kappa statistic
Kappa = p(obs) - p(exp)
1 - p(exp)
p(obs): proportion of observed agreement
p(exp): proportion of agreement expected by chance
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Example of Computation of Kappa
Agreement between the First and the Second Readings to Identify Atherosclerosis Plaque
in the Left Carotid Bifurcation by B-Mode Ultrasound Examination in the
Atherosclerosis Risk in Communities (ARIC) Study
Second reading
Plaque
Normal
Total
Plaque
140
69
209
First Reading
Normal
Total
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192
725
794
777
986
Observed agreement = 140 +725/986 = 0.877
Chance agreement for plaque – plaque cell = (209 x 192)/986 = 40.7
Chance agreement for normal- normal cell = 777 x 794/986 = 625.7
Total chance agreement = 40.7 + 625.7/986 = 0.676
Kappa = 0.877 – 0.676 = 0.62
1 – 0.676
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Interpretation of kappa
• Various suggested interpretations
• Example: Lanis & Koch, Fleiss
excellent:
over 0.75
fair to good: 0.40 - 0.75
poor:
less than 0.40
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Validity (accuracy) of
screening/diagnostic tests
• Face validity, content validity: judgement of the
appropriateness of content of measurement
• Criterion validity
– concurrent
– predictive
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Normal vs abnormal
• Statistical definition
– “Gaussian” or “normal” distribution
• Clinical definition
– using criterion
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Selection of criterion
(“gold” or criterion standard)
• Concurrent
– salivary screening test for HIV
– history of cough more than 2 weeks (for TB)
• Predictive
– APACHE (acute physiology and chronic
disease evaluation) instrument for ICU patients
– blood lipid level
– maternal height
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Sensitivity and specificity
Assess correct classification of:
• People with the disease (sensitivity)
• People without the disease (specificity)
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"True" Disease Status
Present
Absent
Screening
test results
Positive
"True positives"
A
"False positives"
B
Negative
"False negatives"
C
"True negatives"
D
Sensitivity of screening test =
A
A+C
Specificity of screening test =
D
B+D
Predictive value of positive test =
A
A+B
Predictive value of negative test =
D
C+D
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Predictive value
• More relevant to clinicians and patients
• Affected by prevalence
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Choice of cut-point
If higher score increases probability of disease
• Lower cut-point:
– increases sensitivity, reduces specificity
• Higher cut-point:
– reduces sensitivity, increases specificity
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Considerations in selection of
cut-point
Implications of false positive results
• burden on follow-up services
• labelling effect
Implications of false negative results
• Failure to intervene
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Receiver operating characteristic
(ROC) curve
• Evaluates test over range of cut-points
• Plot of sensitivity against 1-specificity
• Area under curve (AUC) summarizes
performance:
– AUC of 0.5 = no better than chance
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Likelihood ratio
• Likelihood ratio (LR) = sensitivity
1-specificity
• Used to compute post-test odds of disease
from pre-test odds:
post-test odds = pre-test odds x LR
• pre-test odds derived from prevalence
• post-test odds can be converted to
predictive value of positive test
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Example of LR
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prevalence of disease in a population is 25%
sensitivity is 80%
specificity is 90%,
pre-test odds = 0.25 = 1/3
1 - 0.25
• likelihood ratio = 0.80 = 8
1-0.90
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Example of LR (cont)
• If prevalence of disease in a population is
25%
• pre-test odds = 0.25 = 1/3
1 - 0.25
• post-test odds = 1/3 x 8 = 8/3
• predictive value of positive result = 8/3+8
= 8/11 = 73%
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Diagnostic odds ratio
• Ratio of odds of positive test in diseased vs
odds of negative test in non-diseased:
a.d
b.c
• From previous example:
OR = 8 x 27 = 36
2x3
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Summary: LR and DPR
• Values:
– 1 indicates that test performs no better than
chance
– >1 indicates better than chance
– <1 indicates worse than chance
• Relationship to prevalence?
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Applications of LR and DOR
• Likelihood ratio: Primarily in clinical
context, when interest is in how much the
likelihood of disease is increased by use of
a particular test
• Diagnostic odds ratio Primarily in research,
when interest is in factors that are
associated with test performance (e.g., using
logistic regression)
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