Epidemiology 503 Screening: Multiple Testing How do multiple tests improve screening programs? Carrie Karvonen-Gutierrez, PhD, MPH Learning Objectives & Key Concepts Describe the two types of multiple testing screening protocols Calculate net sensitivity and net specificity when using sequential testing Key Terms: Sequential testing Simultaneous testing Evaluate the usefulness of multiple screening tests on net sensitivity & net specificity 2 Using Multiple Tests Sequential Tests (2-stage): Simultaneous Tests (parallel): Less expensive, less invasive, less uncomfortable test first If positive on first test, then follow-up with additional testing Conduct multiple screening tests at the same time To be considered positive, the person can test positive on either test. To be considered negative, the person must test negative on all tests Each test has own sensitivity and specificity, so must calculate net sensitivity and net specificity 3 Sequential Cervical Cancer Screening Visual Examination and Pap Smear (Denny et al. Am J Obstet Gynecol 183;383-8, 2000.) Prevalence 0.5% (500/100,000 women) 1: Visual Exam Sensitivity=75% Specificity=81% Cervical Cancer No Cervical Cancer TOTAL TOTAL 500 99,500 100,000 2: Pap Smear Sensitivity=82% Specificity=93% Cervical Cancer No Cervical Cancer TOTAL 375 18,905 19,280 Positive Negative Positive Negative TOTAL 4 Sequential Cervical Cancer Screening 1: Visual Exam 2: Pap Smear Cervical Cancer No Cervical Cancer Cervical Cancer No Cervical Cancer Positive 375 18,905 308 1,323 Negative 125 80,595 67 17,582 TOTAL 500 99,500 375 18,905 NET Sensitivity = # diseased who screen positive / # with disease NET Specificity = # nondiseased who screen negative / # without disease Sequential testing: ↓ net sensitivity ↑ net specificity Sensitivity Specificity Visual Exam 75% 81% Pap Smear 82% 93% Net 62% 99% 5 Simultaneous Screening Screen using more than 1 test at same time Each test has its own sensitivity and specificity To be positive, can screen + on either test To be negative, must screen – on ALL tests Examples: Clinical “work-up” Urine screening for doping agents Simultaneous testing: ↑ net sensitivity ↓ net specificity 6 Sequential vs. Simultaneous Testing Sequential Testing Test 1 + Test 2 + Clinically Positive Clinically Negative ↓ net sensitivity ↑ net specificity - Simultaneous Testing Test 1 + - Clinically Positive Clinically Negative Clinically Negative Test 2 + Clinically Positive ↑ net sensitivity ↓ net specificity 7 Summary Sequential testing is when an initial screening test is done, and those individuals that screen positive are screened again using a second test Simultaneous testing is when multiple screening tests are undertaken at the same time, on the same samples Utilization of multiple testing can improve net sensitivity (simultaneous testing) or net specificity (sequential testing) 8