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		Protective Effects of Exposures Professor John Kaldor, RMA Member Paper prepared from edited transcripts of the RMA Forum March 2004 Protective Effects of Exposures In the course of reviewing the medical scientific literature for a SOP, most factors that emerge as potentially causally related to the disease that is the subject of the SOP show a positive association; in other words, exposure to the factor is associated with an increased likelihood that the disease will occur. Nevertheless, we are increasingly faced with data on factors that show an inverse association with the disease, in that exposure is associated with a lower risk. As with positive associations, we need to exclude chance, bias and confounding as alternative explanations, before we can translate an inverse association into a claim that the exposure is protective, in that it is causally related to reducing the likelihood of disease occurrence. At first glance, it might seem that protective factors would not need to be considered in a SOP on causal factors, given that the purpose of the SOP is to describe causes of disease. In fact, if exposure to a factor can reduce the risk of disease, it is reasonable to conclude that a reduction in the exposure level may actually increase the likelihood of the disease occurring. The absence of any factor that is established as being protective can therefore be transformed into a causal factor if a person is unable to maintain exposure to the normal or beneficial level of the factor. For example, a number of studies have now shown that exercise protects against colorectal cancer. Therefore, the circumstance of being unable to exercise could be interpreted as being a causal factor for colorectal cancer. For a causal factor, we would generally expect to see consistent estimates of the relative risk that were above about 1.25, such that exposure to the factor gives a 25 per cent increase in the chance of getting the disease, compared to people not exposed to the factor. Similarly, it would be appropriate to define a factor based on inability to maintain protective levels of exposure, provided the estimated relative risk associated with the absence of exposure was consistently observed to be greater than about 1.25. For factors in the RH instrument, the RMA has accepted relative risks as low as 1.1, in circumstances where the combined evidence from epidemiological studies provides particularly strong evidence for causality. While the RMA is encouraged to be generous in its interpretation of the evidence for causation, it clearly cannot go beyond the limits of scientific credibility. When a person develops a disease that is covered by a SOP, the relevance of any factor included in the SOP depends on the threshold level of exposure specified in the SOP. This level is determined from the available published literature, as being associated with a measurable increment in risk. For some factors, the increase in risk associated with exposure is calculated in published studies by making comparisons with people who were considered to have little or no exposure. For example, in studies of exposure to herbicide, it is generally assumed that comparison groups were unexposed, and that any increment in risk associated with exposure is with reference to this background. On the other hand, there are factors for which exposure is ubiquitous in human populations, and the calculation of risk increments in published studies must be made with reference to people whose exposure was below a specified level, rather than being zero. Consider fat consumption, or sunlight exposure as examples. In these situations, the true relative risk associated with the threshold level of exposure specified in the SOP will vary from person to person, depending on the individual levels of exposure arising from sources other than service. To illustrate this point, think of two individuals, one of whom had been exposed to 90% of the specified threshold level of a factor prior to the start of qualifying service, and another who had been exposed to 10%. If each of these individuals then has service related exposure that takes the cumulative level exactly to the threshold specified in the SOP, they will both qualify for acceptance of the factor. However, the service-related exposure will clearly have been associated with a much smaller increment in risk for the first individual than the second. To illustrate the point in another way, take the hypothetical circumstance that our SOP system covered not just Australia but a number of countries of our region, and consider a SOP for malaria. If a person lives predominantly in Australia and develops malaria following deployment to a malaria endemic area, the relative risk associated with the deployment would be very high. On the other hand, for a person who lives in an endemic area, and is then deployed in an endemic area, the increment in risk associated with service may be quite small. Thus the background risk of an individual can substantially influence a person's real relative risk. The current system is effectively based on averages, in that it makes acceptance of a factor more difficult for people who have a very low background, while it advantages people who actually have a very high background. Formally, the legislation governing the SOPs does not make provision for taking account of the levels of exposure experienced by an individual outside service, although there is one major factor for which such considerations have been built into the operation of the corresponding SOPs. Exposures that become SOP factors through their absence or the inability to maintain protective levels would be of this second kind. Clearly if removal of the exposure is to be judged to cause an increase in disease risk, there must be widespread exposure to the factor under normal circumstances. Consider exercise levels or fruit and vegetable consumptions as illustrations. Thus individuals who qualify under factors for which it is the absence that increases risk are doing so at a variety of relative risks, because of the variation in their background levels of exposure. The incorporation of protective factors (or at least their absence or reduction) in SOPs is thus an evolving area of interest for the RMA. It has encouraged us to look more closely at some key methodological issues underpinning the calculation of threshold levels for exposure, and will certainly provide a wider range of factors for consideration in SOPs. Previous | Contents | Next This page last updated 22 March 2005.

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