Cohort Profile: The Whitehall II study

Abstract

The Whitehall studies have come to be closely associated with the investigation of socioeconomic differences in physical and mental illness and mortality: the social gradient. 1,2 That was not the initial purpose of the first Whitehall study. Donald Reid and Geoffrey Rose set up Whitehall, in the 1960s, as a kind of British Framingham: 3 ‘Framingham’ insofar as it was a longitudinal study of cardiorespiratory disease and diabetes, looking at individual risk factors for disease; ‘British’ in that it was done on the cheap—a simple screening examination with follow-up limited to deaths identified from the National Health Service Central Registry. Socioeconomic differences were initially not on the agenda. In the 1970s there was a small group of researchers who continued the British tradition that went back to William Farr in the nineteenth century of examining social inequalities in health. 4 For the most part, within epidemiology, ‘social class’ was not an object of study but a control variable: a potential confounder that you got rid of in order to arrive at the ‘correct’ conclusion about the association between risk factor and disease. To the extent that there was a focus on inequalities in health, the general view was that poor people got diseases of material deprivation and rich people got heart disease and peptic ulcers. If this perception had been true,5,6 Whitehall showed that it was no longer so. In a population of middle-aged men, all employed in stable jobs in the British Civil Service, there was an inverse social gradient in mortality: the lower the grade, the higher the risk of death. Ten-year follow-up showed that there was a steep inverse relation between grade of employment and death from all causes, from coronary heart disease (CHD), and from non-coronary causes.7 The relative risk of death owing to CHD was 2.2 in clerical compared with senior administrative staff, and 1.6 for those in the intermediate professional and executive grade. The first Whitehall study made clear that inequalities in health were not limited to the health consequences of poverty. Important as that issue remains, the Whitehall question was why there should be a social gradient in disease in people above the poverty threshold. When conventional risk factors were controlled for, two-thirds of the mortality risk differential between the clerical and administrative grades remained unexplained.7,8 Mortality gradients in the study were in the same direction as national social class mortality data,9 but larger. We hypothesized that psychosocial factors and aspects of nutrition other than those affecting plasma cholesterol (which was higher in high grades in Whitehall) might fill in the unexplained part of the social gradient in mortality.7 We therefore set up the Whitehall II study, a new longitudinal study of British civil servants, with the explicit intention of examining reasons for the social gradient in health and disease in men and extending the research to include women. If research funding were organized in an imaginary world, the way to launch a new cohort study would be to write a proposal setting out the research questions, the long-term aims of the study, the mechanisms for enrolling the cohort, and the system of follow-up. One hopes for approval in the peer review process and a big grant, and off one goes. This bears little resemblance to how Whitehall II was funded. We had our research questions but did not dare to write the big grant application. Instead we funded the recruitment and baseline of the study with a series of small grants, each to fund a piece of the whole—except that without the pieces, there was no whole. The Medical Research Council (MRC) in the UK, the National Heart, Lung, and Blood Institute in the USA, and the UK Health and Safety Executive all provided small project grants. Once the cohort was assembled, we then secured programme support from the MRC, the British Heart Foundation, the National Institute of Aging, the National Heart, Lung, and Blood Institute, the MacArthur Foundation, and a variety of other sponsors (see Acknowledgements). Although this method worked to establish the Whitehall II study, the major drawback is that the writing of grant applications becomes a major extra task. If one needs five grants to fund the next round of data collection and analysis, the burden is large. In our view it has been worth it. We wanted a study that was not done on the cheap. We planned regular contacts with the cohort to track changes in social and economic circumstances, psychological states, health behaviours, and biological pathways to clinical and subclinical disease. The variety of funding sources allowed this rich data collection to continue through seven phases of contact with the cohort, with Phases 8 and 9 planned. The original broad research aim—to investigate social and occupational influences on health and illness—has been much elaborated but remains the central theme almost 20 yea