Screening and Diagnostic Tests - PDF

Presenter- DR. BHARAT PAUL  Introduction  Need for screening  Lead time  Uses of screening  Types of screening  Screening and diagnostic tests  Use of multiple tests  Bias in screening  Evaluation of screening programmes  Examples  References Types of prevention ...

Presenter- DR. BHARAT PAUL  Introduction  Need for screening  Lead time  Uses of screening  Types of screening  Screening and diagnostic tests  Use of multiple tests  Bias in screening  Evaluation of screening programmes  Examples  References Types of prevention  Primordial prevention - prevention of development of risk factors.  Primary prevention - health promotion , specific protection  Secondary prevention - early diagnosis and treatment  Tertiary prevention - disability limitation, rehabilitation  Screening-  Search for unrecognized disease or defect by means of rapidly applied tests, examinations or other procedures in apparently healthy individuals.  For example –breast cancer screening using mammography Case finding-  Use of a clinical and/or laboratory test to detect disease in individuals seeking health care for other reasons.  For example- VDRL to detect syphilis in pregnant women  Diagnostic tests-  Use of clinical and/or laboratory procedures to confirm or refute the existence of disease or true abnormality in patients with signs & symptoms presumed to be caused by the disease.  Example: VDRL testing of patients with lesions suggestive of secondary syphilis.  Gold standard test is the best test available. It is often invasive or expensive.  Example: Breast biopsy for breast cancer. The iceberg phenomena of disease  Quarantine of cases of an infectious disease.  In an immunization programme, it might be necessary to screen out those already infected.  Detect disease at a phase in its development in which there is successful treatment.  Advantage gained by screening i.e the period between diagnosis by early detection and diagnosis by other means.  Apparently Healthy (Screening tests) Apparently Normal Apparently Abnormal (Periodic re-screening) a. Normal – periodic – re- screening b. Intermediate - surveillance c. Abnormal - treatment 1. Case detection  Prescriptive screening.  Presumptive identification of unrecognized disease.  Does not arise from patient’s request.  People screened for their own benefit.  For example- neonatal screening.  Bacteriuria in pregnancy ,breast cancer, diabetes mellitus, iron deficiency anemia, etc. 2. Control of diseases  Prospective screening.  People examined for benefit of others.  For example –screening of immigrants for syphilis. 3. Research purposes  For example – screening to know the natural history of a disease(cancer). 4. Educational opportunities  Mass screening: Screening of a large population or a sub group, eg. all adults.  High risk or selective screening: Applied selectively to high risk groups, the groups defined on the basis of epidemiological research, e.g., screening of cancer cervix in lower social groups.  Multiphasic screening: Application of two or more screening tests in combination to a large number of people at one time. It is very expensive.  Screening tests Diagnostic tests Done on apparently healthy Done on those with indications for disease Applied to groups Applied to single patient Results arbitrary and final Diagnosis is not final Based on one criteria or cut off point Based on a number of findings Less accurate More accurate Less expensive More expensive Not a basis for treatment Used as a basis for treatment Initiation comes from the investigator Initiation comes from a patient 1. Disease  Important health problem.  Recognizable latent or early symptomatic stage.  Natural history should be known.  Presence of a test that can detect the disease prior to onset of signs and symptoms.  Facilities for confirmation of diagnosis.  Effective treatment.  Policy on whom to treat as patients.  Reduction in morbidity and mortality with early treatment.  Expected benefits exceed the risks and costs. 2. Screening test  Acceptability  Repeatability/ Reliability/ Precision/ Reproducibility  Validity (accuracy)  Yield  Simplicity, safety, rapidity and cost  The test should be acceptable to the people at whom it is aimed.  It should not be painful, discomforting, or embarrassing.  For example – in prostate cancer, per rectal examination is not/less acceptable. But PSA(prostate specific antigen) levels is acceptable.  Reliability/precision/reproducibility.  Test must give consistent results when repeated more than once on same individual or material, under same conditions. 3 MAJOR FACTORS  Observer variation  Biological variation  Errors related to technical methods A. Observer variation  Intra-observer variation- Variation between repeated observations by the same observer on the same subject at the same time.  Inter-observation variation- Variation between different observers on the same subject. B. Biological variation May be due to -  Changes in the parameters observed Example: Cervical smears from a woman on different days.  Patient’s perception of symptoms. C. Errors related to technical methods  Erroneous calibration ,defective instruments  To what extent the test accurately measures which it purports to measure.  Expresses ability of test to separate or distinguish those who have the disease from who do not.  Closeness with which measured values agree with true values.  SENSITIVITY  Ability of test to identify correctly all those who have the disease, i.e., true positives.  Sensitivity is a fixed characteristic of the test. SPECIFICITY  Ability of a test to identify correctly those who do not have the disease, i.e., true negatives.  Specificity is also a fixed characteristic of the test. Specificity = Sensitivity= If cut-off point is set at level of C, test will be highly sensitive, but will yield many False Positives If cut-off is set at D, it will increase specificity of the test  If the diagnostic (confirmatory) test is expensive or invasive  Minimize false positives.  Use a cut-point with high specificity.  If the penalty for missing a case is high (e.g., the disease is fatal and treatment exists, or disease easily spreads)  Maximize true positives.  That is, use a cut-point with high sensitivity.  An ideal screening test would be 100% sensitive and 100% specific - that is there would be no false positives and no false negatives.  In practice, these are usually inversely related.  It is possible to vary the sensitivity and specificity by varying the level at which the test is considered positive. Positive predictive value-  The proportion of patients who test positive who actually have the disease. Negative predictive value-  The proportion of patients who test negative who are actually free of the disease. Note: PPV and NPV are not fixed characteristics of the test  Prevalence PPV (%) Se (%) Sp (%) (%) 0.1 1.4 70 95 1.0 12.3 70 95 5.0 42.4 70 95 50.0 93.3 70 95 Amount of previously unrecognized disease that is diagnosed as a result of screening effort. Depends on Sensitivity Specificity Prevalence Participation of individuals Calculated by Prevalence of disease Positive predictive value  Receiver operating characteristic curves.  Ina ROC curve the true positive rate (Sensitivity) is plotted in function of the false positive rate (1- Specificity) for different cut-off points. The overall performance of Test A is better than Test B as well as test C  A testwith perfect discrimination (no overlap in the two distributions) has a ROC plot that passes through the upper left corner (100% sensitivity, 100% specificity).  Therefore the closer the ROC plot is to the upper left corner, the higher the overall accuracy of the test.  For comparing two or more diagnostic tests.  For selecting cut-off levels for a test.  Commonly done in medical practice.  Choice depends on cost, invasiveness, volume of test, presence and capability of lab infrastructure, urgency, etc.  Can be done sequentially or simultaneously.  After the first (screening) test , those who test positive are subjected to the second test to further reduce false positives.  The overall process will increase specificity but with reduced sensitivity.  Diagnosis requires all tests to be positive  When two (or more) tests are conducted in parallel.  The goal is to maximize the probability that subjects with the disease (true positives) are identified (increase sensitivity)  Consequently, more false positives are also identified (decrease specificity)  Used to rule-out serious but treatable conditions (example, breast cancer screening frequently employs a combination of mammography and breast physical examination. Any positive is considered positive) Lead time bias- Overestimation of survival duration among screen detected cases when survival is measured from diagnosis. Length time bias-  Overestimation of survival duration among screen- detected cases due to the relative excess of slowly progressing cases.  These are disproportionally identified by screening because the probability of detection is directly proportional to the length of time during which they are detectable. Over diagnosis bias –  Over diagnosis occurs when all of these people with harmless abnormalities are counted as "lives saved" by the screening, rather than as “healthy people needlessly harmed by over diagnosis”  Screening may identify abnormalities that would never cause a problem in a person's lifetime. For example, prostate cancer screening; it has been said that “more men die with prostate cancer than of it”. Selection bias-  There are factors that differ between those willing to get tested and those who are not.  For example , women with a family history of breast cancer are more likely than other women to join a mammography program.  The tests used in screening are not perfect, so there are false positives and false negatives.  Screening involves cost and use of medical resources on a majority of people who do not need treatment.  Adverse effects of screening procedure (e.g. stress and anxiety, discomfort, radiation & chemical exposure).  Unnecessary investigations and treatment of false positive results.  Stress and anxiety caused by prolonging knowledge of an illness without any improvement in outcome.  A false sense of security caused by false negatives, which may delay final diagnosis.  Randomized control trials  Uncontrolled trials  Other methods: like case control studies  Pap smear for cervical dysplasia or cervical cancer  Fasting blood cholesterol for heart disease  Fasting blood sugar for diabetes  Blood pressure for hypertension  Mammography for breast cancer  PSA test for prostate cancer  Fecal occult blood for colon cancer  Ocular pressure for glaucoma  PKU test for phenolketonuria in newborns  TSH for hypothyroid and hyperthyroid  Parks textbook of preventive and social medicine- 22nd edition.  Leon Gordis Epidemiology – 4th edition  John Hopkins Bloomberg School of Public Health – Open courseware A normal individual is a person who has not been sufficiently