Need for large-scale observational epidemiology
Previous observational epidemiologic studies have helped to identify a number of causative factors for the main chronic diseases of middle age and there is, perhaps, the perception that little more can be learnt from further such studies, particularly for established risk factors (such as smoking and blood lipids). But, the effects of such factors can vary enormously from one population to another, and there is still substantial uncertainty as to how important these are in different settings, and as to how their importance is changing with time. For example, over the past few years there has been an increasingly clear realisation, in large part due to the work of CTSU, of approximately how great the future epidemic of deaths due to tobacco will be in developing countries: if current smoking patterns persist, worldwide deaths from tobacco will increase from about 3 million/year at present to about 10 million/year by 2025 [18-21].
Meta-analyses of observational studies
Small prospective case-control studies, involving just a few hundred patients with the outcome of interest, may suffice to identify a risk factor, but (due to their inherent statistical uncertainties) do not generally suffice to assess the age-specific quantitative importance of such factors or any "interactions" with other risk factors. So, for example, CTSU established a collaborative meta-analysis of data on over one million individuals in prospective observational studies of blood pressure and cholesterol conducted throughout the world [22-24], and this is providing -- for the first time -- appropriately reliable and unbiased estimates of the age-specific relevance of those risk factors to particular causes of death.
Current research
- (PSC) Prospective Studies Collaboration
- Homocysteine, inflammation and blood rheology in CHD
- Meta-analysis of case-control studies of residential radon and lung cancer
Large observational studies
More recently proposed risk factors have not, however, been studied nearly as extensively as blood pressure and cholesterol, so appropriately reliable estimates of their importance cannot yet be obtained even if all relevant studies are combined. Further large prospective studies (involving at least a few hundred thousand people and a few thousand events of interest) and large case-control studies (with thousands of "cases") would reduce the quantitative uncertainties about known risk factors, and would help identify new causative factors. By involving populations that have not previously been studied extensively (for example, women, the elderly, and various very different developed and developing populations), such studies would allow more reliable assessments of the real importance of various causes of death. The range of hypotheses to be studied could be substantially widened if blood samples were stored for future analyses, which could involve not only factors already of interest but also factors that will in the future become of interest.
Current research
- ISIS case-control study of the determinants of MI
- Chinese ecological studies (monograph)
- Large-scale retrospective studies of smoking and death in China
- Large-scale retrospective studies of smoking and death in India
- Other large retrospective studies in developing populations
- Prospective blood-based study of 200,000 individuals in Mexico
- Re-survey and follow-up of 1970 Whitehall Study (7000 elderly individuals)
- Prospective study in 250,000 middle-aged Chinese individuals
- Kadoorie Study of Chronic Disease in China (KSCDC)
- Other large prospective studies in developing populations
- ISIS and PROCARDIS sibling-pair studies of genetic determinants of MI
- Mortality from smoking in developed countries 1950-2000
- UKHCDO Study of the Impact of HIV on Mortality
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