In recent decades, cancer screening programmes (screening that is publicly organised and includes invitation procedures for eligible people of the average risk population in the screening area) have been established in many countries. While cancer screening in the context of clinical trials is innovative and investigative, cancer screening programmes themselves are largely static and not designed to generate new, evidence based knowledge. However, screening programmes themselves affect health and healthcare, which may in turn substantially affect the effectiveness of the programmes. Many screening programmes today can be regarded as supertankers; once under way, they are difficult to halt or alter in direction or content. In mammography, increasing concern about the benefits and harms of screening programmes has led to the announcement of an independent review of mammography screening in the United Kingdom.1 Here, we outline new approaches that aim to overcome this obstacle, using the principles of comparative effectiveness research.