Numbers refer to key questions as follows: (1) Is there direct evidence that screening reduces morbidity and/or mortality? (2) What is the prevalence of disease in the target group? Can a high-risk group be reliably identified? (3) Can the screening test accurately detect the target condition? (a) What are the sensitivity and specificity of the test? (b) Is there significant variation between examiners in how the test is performed? (c) In actual screening programs, how much earlier are patients identified and treated? (4) Does treatment reduce the incidence of the intermediate outcome? (a) Does treatment work under ideal, clinical trial conditions? (b) How do the efficacy and effectiveness of treatments compare in community settings? (5) Does treatment improve health outcomes for people diagnosed clinically? (a) How similar are people diagnosed clinically to those diagnosed by screening? (b) Are there reasons to expect people diagnosed by screening to have even better health outcomes than those diagnosed clinically? (6) Is the intermediate outcome reliably associated with reduced morbidity and/or mortality? (7) Does screening result in adverse effects? (a) Is the test acceptable to patients? (b) What are the potential harms, and how often do they occur? (8) Does treatment result in adverse effects?