analysis is conducted in which there is a quantitative summarization of the data. Such an analysis is not a necessary step and in fact may not be indicated. Only data from valid studies may be included in a meta-analysis, and among valid studies, all studies must contain similar information. In essence, a meta-analysis is a formal rather than an informal summarization of the epidemiologic literature.

A pooled analysis of data from similar studies is not the same procedure as a meta-analysis, but rather a useful extension of basic data analysis. An important tool for obtaining a broad assessment of the evidence from several studies is to conduct combined analyses of data from groups of similar studies. Analyses based on combined data provide tighter confidence limits on risk estimates than analyses based on data from any single study population. To the extent that biases found in individual studies tend to cancel out, combined analyses may help to reduce bias that results from confounding and other potential sources of bias. Such analyses also help to determine if differences in findings among studies are truly inconsistent or are simply the result of chance fluctuations. The application of similar methodology to data from all populations, in addition to the presentation of results in a comparable format, facilitates comparison of results from different studies.

A third step in interpretating epidemiologic data is to compare the results of an individual study with those of similar studies. The goal of such an exercise is to reach a judgment about whether, in general, it may be concluded that under certain conditions, an exposure causes a disease.

The so-called Bradford Hill criteria are the standard criteria used to assess whether the general epidemiologic literature on some exposure or some disease provides sufficient information to judge causality (Hill 1966). These criteria have been expanded, reduced, revised, and reinterpreted by countless authors to meet their special needs, but the core idea remains—use rational operational criteria to judge evidence from observational studies. A revised version of the Hill criteria follows:

  • Consistency—An association is seen in a variety of settings.

  • Specificity—The association is well defined rather than general.

  • Strength—The association is high or low rather than close to 1.0.

  • Dose-response—The higher the exposure, the higher is the rate of disease.

  • Temporal relationship—The exposure occurs before the disease.

  • Coherence—The association is believable based on information from other scientific disciplines.

  • Statistical significance—The association is statistically significant or not.

Each of these criteria should be considered in assessing whether an association between exposure and disease can be judged to be causal. Except for temporal relationship, there need not be evidence for each of these criteria.

With respect to the use of the Hill criteria in assessing the association between exposure to ionizing radiation and health outcome, they are of limited current value for human cancer. Ionizing radiation at high doses is acknowledged to be a cause of most relatively common human cancers (IARC 2000). The presence of a dose-response relationship for many cancers is considered strong evidence for a causal relationship. For less common cancers and for diseases other than cancer, there are not sufficient data to apply the Hill criteria. IARC (2000) notes: “A number of cancers, such as chronic lymphocytic leukaemia, have not been linked to exposure to x or γ rays.”

Assessment of Dose-Response Relationships

As noted above, evaluation of a dose-response relationship is one of the Hill criteria to be applied in assessing whether or not an association is judged to be causal. With respect to providing a risk estimate for low-dose, low-linear energy transfer radiation in human subjects, other information is necessary. Specifically, one needs relatively accurate information for individuals on dose from ionizing radiation, as well as a relatively complete measure of the incidence of or mortality from diseases. To date, the data from the survivors of the atomic bomb in 1945 in Hiroshima and Nagasaki have been the primary source of such information. The Radiation Effects Research Foundation has been responsible for estimating the exposure of individuals and for measuring the incidence and mortality of cancer and other diseases.

One of the primary tasks of this committee has been to evaluate the data that are available from studies of populations exposed to medical radiation, occupational radiation, and environmental radiation so as to assess whether information on dose-response associations from these data sources can be assembled and to evaluate whether such information can be compared to that obtained from the populations exposed to radiation from the atomic bombs. Chapters 7, 8, and 9 address these studies.



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