Screening Tests: A Review

Learning Objectives: 1.Understand the role of screening in the secondary prevention of disease. 2.Recognize the characteristics of diseases appropriate for screening. 3.Understand the impact of implementing screening on prevalence and incidence of disease. 4.Calculate and interpret measures of the validity of a screening test: -Sensitivity -Specificity

Learning Objectives (cont.): 5.Understand the relationship between sensitivity and specificity. 6.Calculate and interpret measures of the performance (yield) of a screening test: -Predictive value positive (PV+) -Predictive value negative (PV-) 7.Understand factors that influence PV+ and PV- 8.Recognize issues and sources of bias in evaluating screening programs.

Screening for Disease Control Screening: The application of a disease-detection test to people who are as yet asymptomatic. Purpose: To classify individuals with respect to their likelihood of having a particular disease. A screening procedure itself does NOT formally diagnose illness.

Screening for Disease Control Examination of asymptomatic people likely Classification as unlikely ….. to have a disease

Screening for Disease Control “Unlikely”referred to next screening cycle “Likely” further testing for diagnosis yes no referred to next treatment screening cycle

Screening for Disease Control Screening Objective: To lower morbidity and mortality of the disease in a population (the control, rather than the elimination of disease). Screening provides access to the medical care system which is not an actual goal of screening, but is a benefit.

Screening for Disease Control Screening is important because: 1) Diagnostic and therapeutic advances are often slow, but screening may be a “direct solution” to modify history of a disease in a population. 2)It provides a model for studying disease mechanisms and the natural history of a disease.

Screening for Disease Control (4) Primary requirements for screening: 1) Early detection of disease leads to a more favorable prognosis due to early treatment, as compared to delayed treatment. 2)Pre-clinical disease left untreated typically progresses to clinically-evident disease (e.g. no spontaneous regression). 3) The disease should be serious (relates to cost effectiveness, ethics, and prognosis). 4)Prevalence of pre-clinical disease should be relatively high among those screened.

Screening for Disease Control “COSTS” OF SCREENING: 1) Financial - may be very costly if screening is spread out over an entire population. 2) Anxiety - Individuals may have to be screened more often. 3) Some morbidity occurs - both in terms of the initial screening procedure, and subsequent procedures. 4) Creation of “lead time” morbidity.

Natural History of Disease BirthExposure CellsScreened Symptom Death Neoplasia ExfoliateDiagnosis Diagnosis Age of Individual

BirthExposure CellsScreened Symptom Death Neoplasia ExfoliateDiagnosis Diagnosis Age of Individual Natural History of Disease TPCP: Begins at the initiation of disease (exposure); ends when the disease is clinically manifested (25 years in this example) Total Pre-Clinical Phase (TPCP)

Age of Individual Natural History of Disease Detectable Pre-Clinical Phase (DPCP) DPCP: Begins when screening test is able to detect disease; ends when disease is clinically evident (10 years) BirthExposure CellsScreened Symptom Death Neoplasia ExfoliateDiagnosis Diagnosis

Impact of Screening on Epidemiological Measures Screening Time Steady state Prevalence of clinical disease (found by either symptoms or screening)

4 Critical characteristics of a screening test: Validity – the extent to which the test distinguishes between persons with and without the disease High validity requires: High Sensitivity High Specificity Reliability (High) Low cost, minimally invasive, and minimally uncomfortable Performance (Yield)

Validity of Screening Tests The test will actually classify a diseased person as likely to have the condition (“sensitivity”). The test will actually classify a non-diseased person as unlikely to have the condition (“specificity”). Addresses the question: How good is the screening test compared with the confirmatory diagnostic test?

Validity of Screening Tests a d c b True Disease Status + - Results of Screening Test + - a = true positive b = false positive c = false negative d = true negative

Validity of Screening Tests a d c b True Disease Status + - Results of Screening Test + - Sensitivity: The probability of testing positive if the disease is truly present Sensitivity = a / (a + c)

Validity of Screening Tests a d c b True Disease Status + - Results of Screening Test + - Specificity: The probability of screening negative if the disease is truly absent Specificity = d / (b + d)

Ex: Validity of Screening Tests Breast Cancer + - Physical Exam and Mammo- graphy + - Sensitivity: a / (a + c) Sensitivity = Specificity: d / (b + d) Specificity =

Validity of Screening Tests Breast Cancer + - Physical Exam and Mammo- graphy + - Sensitivity:a / (a + c) Sensitivity = 132 / ( ) = 74.6% Specificity: d / (b + d) Specificity = / ( ) = 98.5%

Interpretation Sensitivity:a / (a + c) Sensitivity = 132 / ( ) = 74.6% Specificity: d / (b + d) Specificity = / ( ) = 98.5% Sensitivity: Screening by physical exam and mammography will identify 75% of all true breast cancer cases. Specificity: Screening by physical exam and mammography will correctly classify 98.5% of all non-breast cancer patients as being disease free.

Validity of Screening Tests: Closing comments 1. Lowering the criterion of positivity results in increased sensitivity, but at the expense of decreased specificity. 2. Making the criterion of positivity more stringent increases the specificity, but at the expense of decreased sensitivity.

Validity of Screening Tests 3. The goal is to have both high sensitivity and high specificity, but this is often not possible or feasible. 4. The decision for the cutpoint involves weighing the consequences of leaving cases undetected (false negatives) against erroneously classifying healthy persons as diseased (false positives). 5. In general, specificity must be at least 98% to be effective (because misclassifying 2% of the population will create as many false positives as the sensitivity of the test will actually detect).

Validity of Screening Tests 6.Sensitivity should be increased when: a. the penalty associated with missing a case is high (e.g. minimize false negatives) b. when the disease can be spread c. when subsequent diagnostic evaluations are associated with minimal cost and risk 7. Specificity should be increased when the costs or risks associated with further diagnostic techniques are substantial (minimize false positives – e.g. positive screen requires that a biopsy be performed).