How do we delay disease progress once it has started? Epidemiology matters: a new introduction to methodological foundations Chapter 13

Epidemiology Matters – Chapter 13 What is screening? When should we screen? How do we evaluate a screening test? PPV, NPV, and prevalence Summary Epidemiology Matters – Chapter 13

Epidemiology Matters – Chapter 13 What is screening? When should we screen? How do we evaluate a screening test? PPV, NPV, and prevalence Summary Epidemiology Matters – Chapter 13

Epidemiology Matters – Chapter 13 Screening Screening is the process in which we use a test to determine whether an individual likely has a particular health indicator or not or is likely to develop a particular health indicator or not Screening is not the same as diagnosis; screening tests give us information about whether the disease is likely to be present A screening test assesses the presence of an underlying marker that is associated with outcome of interest Epidemiology Matters – Chapter 13

Epidemiology Matters – Chapter 13 Screening, examples Women receive regular screening tests beginning in young adulthood for cervical cancer (Pap smear) Physicians assess blood pressure and cholesterol as screening tools for the development of cardiovascular disease Women use home pregnancy tests to screen for presence of an embryo or fetus Epidemiology Matters – Chapter 13

Epidemiology Matters – Chapter 13 What is screening? When should we screen? How do we evaluate a screening test? How do we decide on a cut-off? PPV, NPV, and prevalence From screening test to screening program Summary Epidemiology Matters – Chapter 13

Epidemiology Matters – Chapter 13 When to screen We screen for disease when we have the opportunity to reduce costs and risk associated with diagnoses on large proportions of at-risk individuals We screen for health indicators that affect population health principally, not for rare diseases (although there are exceptions for rare diseases screen in utero) There should be sufficient time between biological onset of disease and appearance of signs and symptoms of the disease exist so that screening could detect the presence of the disease earlier than it would come to clinical attention There should be available treatment for the disease so that early detection improves the lives of affected Screening tests should be cheaper and less invasive than best available diagnostic tool Epidemiology Matters – Chapter 13

Epidemiology Matters – Chapter 13 What is screening? When should we screen? How do we evaluate a screening test? How do we decide on a cut-off? PPV, NPV, and prevalence From screening test to screening program Summary Epidemiology Matters – Chapter 13

Screening test evaluation Sensitivity Specificity Positive predictive value Negative predictive value https://www.youtube.com/watch?v=FnJ3L-63Cf8 Epidemiology Matters – Chapter 13

Screening test evaluation sensitivity and specificity To assess the validity of a screening tool in establishing the presence of disease we compare with a gold standard Sensitivity: Whether individuals with disease are correctly identified by the screening test as having the disease Specificity: Whether individuals without the disease are correctly identified by the screening test as not having the disease Epidemiology Matters – Chapter 13

Screening test evaluation cut-off False Positives  Screens Negative Screens  Positive D+ Screening Cut-Off D- Antigen Lowest value on the antigen distribution of men with prostate cancer = 38 ng/mL. Cut-off score = 38 ng/mL Epidemiology Matters – Chapter 13

Screening test evaluation Epidemiology Matters – Chapter 13

Screening test evaluation sensitivity Among those with disease, what proportion does the screening test detect? Interpretation: With a cut-off of 38 ng/mL, we have a test with 100% sensitivity. Among those with prostate cancer, the test captures all cases. There are no false negatives. Epidemiology Matters – Chapter 13

Screening test evaluation specificity Among those without disease, what proportion does the screening test correctly identify as disease free? Interpretation: With a cut-off of 38 ng/mL, screening test classifies 61.2% of men without prostate cancer as not having prostate cancer, remaining 38.8% are false positive cases. Epidemiology Matters – Chapter 13

Screening test evaluation sensitivity and specificity tradeoffs Test cut-off is very sensitive: All those who have the disease will be captured by the test Test cut-off is very specific: Individuals who do not have the disease are will not screen positive High sensitivity/low specificity tests are common in practice; i.e., we will not miss many individuals with disease but we also will screen positive those who do not have disease Epidemiology Matters – Chapter 13

Screening test evaluation sensitivity and specificity, example Primary care physicians query patients about whether they engaged in at least one episode of heavy drinking in the past year as a screening tool for identifying individuals with an alcohol disorder Almost all individuals with an alcohol disorder will have engaged in at least one episode of heavy drinking in the past year, but many individuals without an alcohol disorder may have engaged in one or more heavy drinking episodes as well. The test is sensitive, but not specific Epidemiology Matters – Chapter 13

Screening test evaluation PPV, NPV, and prevalence How well does our screening test predict who is diseased and who is not? Epidemiology Matters – Chapter 13

Screening test evaluation positive predictive value Among those who screen positive, what proportion actually has the disease? Interpretation: With a cut-off of 38 ng/mL, one fifth of the men who screen positive on test have prostate cancer, leaving about 80% of men screening positive falsely. Epidemiology Matters – Chapter 13

Screening test evaluation negative predictive value Among those who screen negative, what proportion actually do not have the disease? PPV = 1529 = 1.0 or 100% 1529 + 0 Interpretation: With a cut-off of 38 ng/mL, the test has perfect negative predictive value. Among those who are negative on the screening test, we can be perfectly confident that none of those individuals actually have the disease. Epidemiology Matters – Chapter 13

Screening test evaluation Assess sensitivity and specificity to understand the proportion of diseased and non-diseased individuals correctly categorized as diseased and non-diseased Assess PPV and NPV to understand the proportion of positively screened and negatively screened individuals that have disease or are disease-free Epidemiology Matters – Chapter 13

Ramifications of false positives vs. false negatives Low rate of false negatives preferred Infectious diseases critical to maintain low rate of false negative When disease can be readily remediated if caught early but devastating if not Low rate of false positivity preferred When subsequent diagnostic test is invasive and expensive procedures Screening is done routinely on low burden diseases Epidemiology Matters – Chapter 13

Epidemiology Matters – Chapter 13 What is screening? When should we screen? How do we evaluate a screening test? How do we decide on a cut-off? PPV, NPV, and prevalence From screening test to screening program Summary Epidemiology Matters – Chapter 13

Epidemiology Matters – Chapter 13 Summary Screening for health indicators is integral part of improving population health Screening predicts who will develop a specific disease and detects disease among those in early stages Screening tests need to be studied for validity (sensitivity and specificity) We often have a trade-off between sensitivity and specificity Predictive value of screening test is maximized in populations with high prevalence of health indicator of interest Value of screening program will depend on cost-effectiveness, minimal invasiveness, availability of effective treatment Epidemiology Matters – Chapter 13

Epidemiology Matters – Chapter 1 epidemiologymatters.org Epidemiology Matters – Chapter 1