Weak associations in epidemiological research: some examples and their interpretation

The study of the epidemiology of chronic non-infectious diseases grew rapidly after the Second World War. In the early 1950s strong associations were found in studies based on hypotheses derived from clinical, demographic and animal observations. The associations between smoking and lung cancer, physical exercise and myocardial infarction, and air pollution and mortality all led to more than three decades of epidemiological endeavour to refine our understanding of the initial observations. As the large effects were discovered, new associations were perforce of smaller magnitude. The benefits of milk supplements to the diet of school-age children was elegantly shown in an MRC trial in 1920s using small numbers of deprived children, whereas in the 1970s, when the population's nutrition was vastly improved, many thousands of children were needed to give an answer. The impact of passive smoking on cancer incidence, on children's health and on pregnancy is a current debate because of the vanishingly small effects. Studies of the relation between alcohol consumption during pregnancy and the outcome of pregnancy has given rise to conflicting findings so that clear cut scientifically based recommendations cannot be given to social drinkers. The demands of governments for epidemiological evidence on which to base standards for pollutants in the air, water and ground, has resulted in the need for multiple studies using different techniques to suggest whether or not an association between health and exposure exists. These examples are used to illustrate the difficulties of interpretation of epidemiological studies when the effects of suspected risk factors are small.