1、Predictive ValuesBob L.Larson,DVM,PhD University of MissouriCommercial Agriculture,Beef Focus TeamUse and Interpretation of Diagnostic Tests Help to make a diagnosis(does not stand alone)Judge severity of disease Predict subsequent clinical course of disease Estimate likely responsiveness to therapy
2、 Determine response to therapy(post therapy)1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic Tests Must be tested against a“gold standard”Although no perfect test exists,a gold standard is an accepted,reliable test Properties of diagnostic tes
3、ts Sensitivity=proportion of true positives that test positiveHow effective is the test at identifying animals with the condition?Specificity=proportion of true negatives that test negativeHow effective is the test at identifying animals without the condition?1.Measurement of disease events2.Infecti
4、ous disease epidemiology3.Interpreting diagnostic testsDiagnostic TestsDisease StatusPresentAbsentTest PositiveTest Negative1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic TestsDisease StatusPresentAbsentTest PositiveTrue PositiveTest Negativ
5、e1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic TestsDisease StatusPresentAbsentTest PositiveTest NegativeTrue Negative1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic TestsDisease Sta
6、tusPresentAbsentTest PositiveFalse PositiveTest Negative1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic TestsDisease StatusPresentAbsentTest PositiveTest NegativeFalse Negative1.Measurement of disease events2.Infectious disease epidemiology3.
7、Interpreting diagnostic testsDiagnostic TestsDisease StatusPresentAbsentTest Positiveaba+bTest Negativecdc+da+cb+da+b+c+dSensitivity =a/(a+c)1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic TestsDisease StatusPresentAbsentTest Positiveaba+bTes
8、t Negativecdc+da+cb+da+b+c+dSensitivity =a/(a+c)Specificity=d/(b+d)1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic TestsDisease StatusPresentAbsentTest Positiveaba+bTest Negativecdc+da+cb+da+b+c+dSensitivity =a/(a+c)Specificity=d/(b+d)False n
9、egative=c/(a+c)1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic TestsDisease StatusPresentAbsentTest Positiveaba+bTest Negativecdc+da+cb+da+b+c+dSensitivity =a/(a+c)Specificity=d/(b+d)False negative=c/(a+c)False positive=b/(b+d)1.Measurement o
10、f disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsNumber of animalsMeasurementDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abnormal)Population APopulation B1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting
11、diagnostic testsNumber of animalsMeasurementDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abnormal)Population APopulation B1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsNumber of animalsMeasurementDiagnostic tests use
12、 an arbitrary cut-off to separate two populations(normal vs.abnormal)Population APopulation B1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsNumber of animalsMeasurementDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abno
13、rmal)Population APopulation B1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsNumber of animalsMeasurementDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abnormal)Population APopulation B1.Measurement of disease events2.In
14、fectious disease epidemiology3.Interpreting diagnostic testsDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abnormal)NumberMeasurementWhere cut-off is placed determines sensitivity and specificity1.Measurement of disease events2.Infectious disease epidemiology3.Interp
15、reting diagnostic testsDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abnormal)NumberMeasurementWhere cut-off is placed determines sensitivity and specificityNormalAbnormalFew False NegativesHigh Sensitivity-result+result1.Measurement of disease events2.Infectious di
16、sease epidemiology3.Interpreting diagnostic testsDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abnormal)NumberMeasurementWhere cut-off is placed determines sensitivity and specificityNormalAbnormalFew False PositivesHigh Specificity-result+result1.Measurement of dis
17、ease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abnormal)NumberMeasurementWhere cut-off is placed determines sensitivity and specificityNormalAbnormalTrade off between False and False+-result+r
18、esult1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abnormal)NumberMeasurementTest with High SensitivityNormalAbnormalA negative result allows you to rule-out whatever you
19、are testing-result+resultSnNout1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic tests use an arbitrary cut-off to separate two populations(normal vs.abnormal)NumberMeasurementTest with High SpecificityNormalAbnormalA positive result allows you
20、 to rule-in whatever you are testing-result+resultSpPin1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsDiagnostic Tests Sensitivity and specificity are inversely related Sensitivity and specificity are properties of the diagnostic test and tell us if th
21、e test is valid Test sensitivity and specificity have little effect on the confidence a veterinarian has in an individual result.1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsBecause NumberMeasurementMy illustration is not consistent with true disease
22、 dynamics in a population(the real world)1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsNumberMeasurementBecause My illustration is not consistent with true disease dynamics in a population(the real world)1.Measurement of disease events2.Infectious dis
23、ease epidemiology3.Interpreting diagnostic testsPredictive ValueWhat we are really interested in Predictive values tell us if a test is useful Positive Predictive Value(PPV)The probability that an animal with a positive test result is truly positive Negative Predictive Value(NPV)The probability that
24、 an animal with a negative test result is truly negative Dependent on disease prevalence and test sensitivity and specificity1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60%sensitive and 90%specific On e
25、xamination of a 5 year old dairy cow,with typical history,clinical signs and positive herd-matesWe assume 90%of cows with this description are positive(prevalence=90%)Dz+Dz-Test Positive54010550Test Negative360904509001001,000Prevalence is 90%(900/1000=90%)1.Measurement of disease events2.Infectious
26、 disease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60%sensitive and 90%specific On examination of a 5 year old dairy cow,with typical history,clinical signs and positive herd-matesWe assume 90%of cows with this description are positive(prevalence=90%)D
27、z+Dz-Test Positive54010550Test Negative360904509001001,000Test Sensitivity=540/900=60%1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60%sensitive and 90%specific On examination of a 5 year old dairy cow,wi
28、th typical history,clinical signs and positive herd-matesWe assume 90%of cows with this description are positive(prevalence=90%)Dz+Dz-Test Positive54010550Test Negative360904509001001,000Test Sensitivity=60%NPV=90/450=20%1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting
29、diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60%sensitive and 90%specific On examination of a 5 year old dairy cow,with typical history,clinical signs and positive herd-matesWe assume 90%of cows with this description are positive(prevalence=90%)Dz+Dz-Test Positive54010550Test Negat
30、ive360904509001001,000Test Sensitivity=60%NPV=90/450=20%Test Specificity=90/100=90%1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60%sensitive and 90%specific On examination of a 5 year old dairy cow,with
31、typical history,clinical signs and positive herd-matesWe assume 90%of cows with this description are positive(prevalence=90%)Dz+Dz-Test Positive54010550Test Negative360904509001001,000Test Sensitivity=60%NPV=90/450=20%Test Specificity=90%PPV=540/550=98%1.Measurement of disease events2.Infectious dis
32、ease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60%sensitive and 90%specific On examination of a 5 year old dairy cow,with typical history,clinical signs and positive herd-matesWe assume 90%of cows with this description are positive(prevalence=90%)Dz+Dz
33、-Test Positive54010550Test Negative360904509001001,000PPV=540/550=98%NPV=90/450=20%With positive test we are 98%sure she is a true positiveWith negative test we are 20%sure she is a true negative1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NP
34、V Assume a test for bovine Johnes is 60%sensitive and 90%specific On examination of a 5 year old beef cow,with typical history,clinical signs and unknown herd statusWe assume 50%of cows with this description are positive(prevalence=50%)Dz+Dz-Test Positive30050350Test Negative2004506505005001,000Prev
35、alence is 50%(500/1000=50%)1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60%sensitive and 90%specific On examination of a 5 year old beef cow,with typical history,clinical signs and unknown herd statusWe
36、assume 50%of cows with this description are positive(prevalence=50%)Dz+Dz-Test Positive30050350Test Negative2004506505005001,000Test Sensitivity=300/500=60%1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60
37、%sensitive and 90%specific On examination of a 5 year old beef cow,with typical history,clinical signs and unknown herd statusWe assume 50%of cows with this description are positive(prevalence=50%)Dz+Dz-Test Positive30050350Test Negative2004506505005001,000Test Sensitivity=60%NPV=450/650=69%1.Measur
38、ement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60%sensitive and 90%specific On examination of a 5 year old beef cow,with typical history,clinical signs and unknown herd statusWe assume 50%of cows with this descrip
39、tion are positive(prevalence=50%)Dz+Dz-Test Positive30050350Test Negative2004506505005001,000Test Sensitivity=60%NPV=450/650=69%Test Specificity=450/500=90%1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60
40、%sensitive and 90%specific On examination of a 5 year old beef cow,with typical history,clinical signs and unknown herd statusWe assume 50%of cows with this description are positive(prevalence=50%)Dz+Dz-Test Positive30050350Test Negative2004506505005001,000Test Sensitivity=60%NPV=450/650=69%Test Spe
41、cificity=90%PPV=300/350=86%1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV Assume a test for bovine Johnes is 60%sensitive and 90%specific On examination of a 5 year old beef cow,with typical history,clinical signs and unknown herd statusWe
42、assume 50%of cows with this description are positive(prevalence=50%)Dz+Dz-Test Positive30050350Test Negative2004506505005001,000PPV=300/350=86%NPV=450/650=69%With positive test we are 86%sure she is a true positiveWith negative test we are 69%sure she is a true negative1.Measurement of disease event
43、s2.Infectious disease epidemiology3.Interpreting diagnostic testsPredictive Value of a Diagnostic TestPPV and NPV PPV and NPV are greatly influenced by pre-test likelihood of diseasePublished prevalence dataYour clinical skills and judgmentPositive%Negative%PrePostPrePostExample 190981020Example 250
44、8650691.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV The immunohistochemistry test for persistently infected BVD animals is very good:96%sensitive and 99%specific However,the prevalence of PI animals in the general calf population is low(0.
45、3%)So,how does a very good test perform in a population with low prevalence?1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV The immunohistochemistry test for persistently infected BVD animals is very good:96%sensitive and 99%specific However
46、,the prevalence of PI animals in the general calf population is low(0.3%)So,how does a very good test perform in a population with low prevalence?BVD PIDz+Dz-Test Positive2889971,285Test Negative1298,70398,71530099,700100,000Test Sensitivity=96%Test Specificity=99%1.Measurement of disease events2.In
47、fectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV The immunohistochemistry test for persistently infected BVD animals is very good:96%sensitive and 99%specific However,the prevalence of PI animals in the general calf population is low(0.3%)So,how does a very good test perform i
48、n a population with low prevalence?BVD PIDz+Dz-Test Positive2889971,285Test Negative1298,70398,71530099,700100,000Test Sensitivity=96%NPV=98,703/98,715=99.9%Test Specificity=99%1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV The immunohistoc
49、hemistry test for persistently infected BVD animals is very good:96%sensitive and 99%specific However,the prevalence of PI animals in the general calf population is low(0.3%)So,how does a very good test perform in a population with low prevalence?BVD PIDz+Dz-Test Positive288True+997False+1,285Test N
50、egative1298,70398,71530099,700100,000Test Sensitivity=96%NPV=98,703/98,715=99.9%Test Specificity=99%PPV=288/1,285=22%1.Measurement of disease events2.Infectious disease epidemiology3.Interpreting diagnostic testsPPV and NPV The immunohistochemistry test for persistently infected BVD animals is very