Abstract
The accurate determination of exposure to environmental tobacco smoke is notoriously difficult. There have been to date two approaches to determining this exposure in the study of association of passive smoking and lung cancer: the biochemical approach, using cotinine in the main as a marker, and the epidemiological approach. Typically results of the former have yielded much lower relative risk than the latter, and have tended to be ignored in favour of the latter, although there has been considerable debate as to the logical basis for this. We settle this question by showing that, using the epidemiologically based meta-analysis technique of Wald et al. (1986), and misclassification models in the EPA Draft Review (1990), one arrives using all current studies at a result which is virtually identical with the biochemically-based conclusions of Darby and Pike (1988) or Repace and Lowry (1990). The conduct of this meta-analysis itself raises a number of important methodological questions, including the validity of inclusion of studies, the use of estimates adjusted for covariates, and the statistical significance of estimates based on meta-analysis of the epidemiological data. The best estimate of relative risk from spousal smoking is shown to be approximately 1.05-1.10, based on either of these approaches; but it is suggested that considerable extra work is needed to establish whether this is significantly raised.
Highlights
With the epidemiological studies, there has been a second and more direct approach to the problem of estimating levels of ETS exposure
We show that after the now-standard 'Wald adjustment' for differential misclassification, the two methods can be reconciled to provide an estimate of the relative risk of lung cancer associated with exposure to ETS, with a best current estimate of around 1.07
If 6 is the level of cotinine in the supposedly unexposed individuals, if a is the level in supposed non-smokers exposed to ETS, and if RRo is the observed relative risk for exposure to ETS as found from epidemiological studies, one may find the true relative risk RRETS = 1 + a from solving
Summary
Data may be insufficient for accurate estimates of relative risks to be made. There are different techniques for such pooling, but the concept has been used widely in recent assessment of the overall risk of passive smoking The use of this technique for epidemiological data was pioneered in the paper by Wald et al (1986), following its development for clinical studies by Yusuf et al (1985), and the technique has been adopted in the NRC Report (1986) and the EPA Draft Review (1990). Since the NRC Report (1986) and the Wald et al (1986) paper have been published, a number of further studies of the relationship between exposure to ETS and the risk of lung cancer have been published Many of these further studies are included in the EPA Draft Review (1990), Varela (1987) is not included in the EPA Draft Review meta-analysis, and Wu-Williams et al (1990), Sobue et al (1990), Kabat (1990), Kalandidi et al (1990), Liu et al (1991) and Fontham et al (1991) have appeared since the preparation of the EPA Draft Review (1990). The Varela (1987) estimate is itself a combined estimate, using the variance-weighted method of Wald et al (1986), of the estimates in Table II of Varela (1987)
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