Point: Is There a Future for Innovative Epidemiology?

Risk prediction functions for incident coronary heart disease (CHD) were estimated using data from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of CHD in 15,792 persons recruited in 1987-1989 from four U.S. communities, with follow-up through 1998. Predictivity of which individuals had incident CHD was assessed by increase in area under ROC curves resulting from adding nontraditional risk factors and markers of subclinical disease to a basic model containing only traditional risk factors. We also assessed the increase in population attributable risk. The additional factors were body mass index; waist-hip ratio; sport activity index; forced expiratory volume; plasma fibrinogen, factor VIII, von Willebrand factor, and Lp(a); heart rate; Keys score; pack-years smoking; and subclinical disease marker carotid intima-media thickness. These factors substantially improved prediction of future CHD for men, less for women, and also increased attributable risks.

Large prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers. This is the approach used by a large-scale national resource in the United Kingdom known as the “UK Biobank,” which completed recruitment/examination of 503,000 participants between 2007 and 2010 within budget and ahead of schedule. A key lesson from UK Biobank and similar studies is that large studies are not simply small studies made large but, rather, require fundamentally different approaches in which “process” expertise is as important as scientific rigor. Embedding recruitment in a structure that facilitates outcome determination, utilizing comprehensive and flexible information technology, automating biospecimen processing, ensuring broad consent, and establishing essentially autonomous leadership with appropriate oversight are all critical to success. Whether and how these approaches may be transportable to the United States remain to be explored, but their success in studies such as UK Biobank makes a compelling case for such explorations to begin.