Laboratory Training for Field Epidemiologists Sensitivity and specificity Predictive values positive and negative Interpretation of results Sep 2007

Laboratory Training for Field EpidemiologistsOutline Intrinsic characteristics of a test – Sensitivity – Specificity Performance of a test in a population – Predictive value of a positive test – Predictive value of a negative test

Laboratory Training for Field EpidemiologistsSensitivity Sensitivity = True positives / Affected persons Estimate the 95% confidence interval The sensitivity of a test in the ability of the test to identify correctly affected individuals Proportion of persons testing positive among affected individuals

Laboratory Training for Field Epidemiologists Estimating the sensitivity of a test Identify affected individuals with a gold standard Obtain a wide panel of samples that are representative of the population of affected individuals – Recent and old cases – Severe and mild cases – Various ages and sexes Test the affected individuals Estimate the proportion of affected individuals that are positive with the test

Laboratory Training for Field Epidemiologists Estimating the sensitivity of a rapid test for leishmaniasis Identify persons with leishmaniasis with a gold standard – Parasitologically proven infection Obtain a wide panel of samples that are representative of the population of individuals with leishmaniasis – Recent and old cases – Severe and asymptomatic cases – Various ages and sexes Test the persons with leishmaniasis Estimate the proportion of persons with leishmaniasis that are positive with the rapid test

Laboratory Training for Field Epidemiologists Sensitivity of a rapid test for leishmaniasis Patients with leishmaniasis Rapid test True positive148 False negative2 150 Sensitivity = 148 / (150) = 98% 95% confidence interval: 94%-99%

Laboratory Training for Field Epidemiologists What factors influence the sensitivity of a test? Characteristics of the affected persons? YES: Antigenic characteristics of the pathogen in the area (e.g., if the test was not prepared with antigens reflecting the population of pathogens in the area, it will not pick up infected persons in the area) Characteristics of the non-affected persons?  NO: The sensitivity is estimated on a population of affected persons Prevalence of the disease?  NO: The sensitivity is estimated on a population of affected persons Sensitivity is an INTRINSIC characteristic of the test

Laboratory Training for Field EpidemiologistsSpecificity Specificity = True negatives / Non-affected persons Estimate the 95% confidence interval The specificity of a test in the ability of the test to identify correctly non-affected individuals Proportion of person testing negative among non affected individuals

Laboratory Training for Field Epidemiologists Estimating the specificity of a test Identify non affected individuals – Negative with a gold standard – Unlikely to be infected Obtain a wide panel of samples that are representative of the population of non-affected individuals – Diverse unaffected population: Difficult to find. Ideally, those individuals that would need to be tested but not infected Test the non-affected individuals Estimate the proportion of non-affected individuals that are negative with the test

Laboratory Training for Field Epidemiologists Estimating the specificity of a rapid test for leishmaniasis Identify persons without leishmaniasis – Persons without sign and symptoms of the infection – Persons at low risk of infection, negative with gold standard Obtain a wide panel of samples that are representative of the population of individuals without leishmaniasis – Persons from neighbouring villages having similar characteristics but with no transmission and no infections Test the persons without leishmaniasis Estimate the proportion of persons without leishmaniasis that are negative with the rapid test

Laboratory Training for Field Epidemiologists Specificity of a rapid test for leishmaniasis Individuals without leishmaniasis Test False positive12 True negative Specificity = 188 / 200 = 94% 95% confidence interval: 90%-96%

Laboratory Training for Field Epidemiologists What factors influence the specificity of a test? Characteristics of the affected persons?  NO: The specificity is estimated on a population of non affected Characteristics of the non-affected persons? YES: The diversity of antibodies to various other antigens in the population may affect cross reactivity (e.g., If malaria is endemic, polyclonal hyper gammaglobulinemia may increase the proportion of false positives) Prevalence of the disease?  NO: The specificity is estimated on a population of non affected Specificity is an INTRINSIC characteristic of the test

Laboratory Training for Field Epidemiologists Identifying the cut-off to use with a test on the basis of panel analysis: Ideal case Cut-off Possible values of the test Number of tests Sick Well

Laboratory Training for Field Epidemiologists Identifying the cut-off to use with a test on the basis of panel analysis: Real case Cut-off Possible values of the test Number of tests Sick Well True negatives False negatives True positives False positives

Laboratory Training for Field Epidemiologists To whom sensitivity and specificity matters most? Look at denominators! – Panels of affected individuals – Panels of negative individuals To laboratory specialists!

Laboratory Training for Field EpidemiologistsOutline Intrinsic characteristics of a test – Sensitivity – Specificity Performance of a test in a population – Predictive value of a positive test – Predictive value of a negative test

Laboratory Training for Field Epidemiologists How is the test doing in a real population? Status of persons AffectedNon-affected Test PositiveTrue +False +A+B NegativeFalse -True -C+D A + CB+DA+C+B+D The test is now used in a real population This population is made of – Affected individuals – Non-affected individuals The proportion of affected individuals is the prevalence

Laboratory Training for Field Epidemiologists Predictive value of a positive test Predictive value of a positive test = True positives / Persons testing positive Estimate the 95% confidence interval The predictive value of a positive test is the probability that an individual testing positive is truly affected Proportion of affected persons among those testing positive

Laboratory Training for Field Epidemiologists Predictive value of a positive test Status of persons AffectedNon-affected Test PositiveABA+B NegativeCDC+D A + CB+DA+C+B+D PVP = A / (A+B) This is only valid for the sample of specimens tested

Laboratory Training for Field Epidemiologists What factors influence the predictive value positive of a test? Sensitivity? YES: To some extend. Specificity? YES: The more the test is specific, the more it will be negative for non affected persons. Thus, when the test is positive, it is probably truly positive (All non affected were correctly identified as testing negative). Prevalence of the disease? YES: Low prevalence: The test will pick up more false positives YES: High prevalence: The test will pick up more true positives

Laboratory Training for Field Epidemiologists Predictive value positive of a test according to prevalence and specificity Specificity

Laboratory Training for Field Epidemiologists Predictive value of a negative test Predictive value of a negative test = True negatives / Persons testing negative Estimate the 95% confidence interval The predictive value of a negative test is the probability that an individual testing negative is truly non-affected Proportion of non-affected persons among those testing negative

Laboratory Training for Field Epidemiologists Predictive value of a negative test Status of persons AffectedNon-affected Test PositiveABA+B NegativeCDC+D A + CB+DA+C+B+D PVN = D / (C+D) This is only valid for the sample of specimens tested

Laboratory Training for Field Epidemiologists What factors influence the predictive value negative of a test? Sensitivity? YES: The more the test is sensitive, the more it captures affected persons. Thus, when the test is negative, it is probably truly negative (all affected were captured among the positive). Specificity? YES: But to a lesser extend. Prevalence of the disease? YES: Low prevalence: The test will pick up more true negatives YES: High prevalence: The test will pick up more false negatives

Laboratory Training for Field Epidemiologists Predictive value negative of a test according to prevalence and sensitivity Sensitivity

Laboratory Training for Field Epidemiologists Relation between predictive values and (1) sensitivity and (2) specificity

Laboratory Training for Field Epidemiologists Positive (PPV) and negative (NPV) predictive values of a test according to the prevalence (95% sensitivity and specificity) PVP PVN

Laboratory Training for Field Epidemiologists To whom predictive values matters most? Look at denominators! – Persons testing positive – Persons testing negative To clinicians and epidemiologists!

Laboratory Training for Field EpidemiologistsSummary Sensitivity and specificity matter to laboratory specialists – Studied on panels of positives and negatives – Look into the intrinsic characteristics of the test: Capacity to pick affected Capacity to pick non affected Predictive values matter to clinicians and epidemiologists – Studied on homogeneous populations – Look into the performance of the test in real life: What to make of a positive test What to make of a negative test

Laboratory Training for Field Epidemiologists Developed by: The Department of Epidemic and Pandemic Alert and Response of the World Health Organization with the assistance of: European Program for Field Epidemiology Training Canadian Field Epidemiology Programme Thailand Ministry of Health Institut Pasteur Interpretation of results