Veterans and Agent Orange Update 2004 (2005) / Chapter Skim
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2 Evaluating the Evidence
2 Evaluating the Evidence
Pages 20-32
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From page 20... ...
Public Law (PL) 102-4, which led to the committee's work, however, did not specify particular health outcomes of interest.
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From page 21... ...
DMA was long thought to be a biologically inactive metabolite of inorganic arsenic, but recent evidence suggests that one form -- DMAIII -- might be responsible for some of the adverse effects of inorganic arsenic. That evidence, however, is not sufficient to support a conclusion that exposure to cacodylic acid results in the same adverse health effects as does exposure to toxic concentrations of inorganic arsenic.
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From page 22... ...
The committee found that the most relevant evidence came from epidemiologic studies -- investigations in which large groups of people are studied to identify an association between exposure to a chemical of interest and the occurrence of particular health outcomes. Epidemiologists estimate associations between exposure and outcome in a specific population or group by use of such measures as relative risk, standardized mortality ratio, or odds ratio.
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From page 23... ...
The width of the confidence interval is used to quantify the likely variability of the exposure-disease association. Even when a relative risk or standardized mortality ratio exceeds 1, a conclusion regarding increased risk must be qualified when the confidence interval is broad.
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From page 24... ...
Plausible Biologic Mechanisms Chapter 3 details the experimental basis for assessment of biologic plausibility or the extent to which an observed statistical association in epidemiology studies is consistent with biologic or medical knowledge. In other words, would causation of the particular health effect observed make sense based on what is known about how the chemical acts at the tissue, cellular, or molecular level?
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From page 25... ...
EVALUATION OF THE EVIDENCE The associations between exposures to the chemicals of interest and specific health outcomes are determined through an analysis of available epidemiologic studies, informed by an understanding of the toxicology of the chemicals and their exposure pathways. In reaching conclusions, VAO committees consider the nature of the exposures, the nature of the health outcomes, the populations exposed, and the quality of the evidence examined.
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From page 26... ...
Because the effect of Agent Orange in individuals or groups of veterans is evaluated in terms of disease or medical outcome, attention to disease classification was important to the committee in accurately assembling all pertinent data related to a particular endpoint from various investigations prior to integrating the information. The researchers conducting the studies reviewed by the committee faced the same challenge in reliably interpreting the available documentation when assigning a diagnostic label to a given subject and in then grouping those labels for analysis.
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From page 27... ...
Little research has been done to address whether the rate of concurrence is greater than would be expected by chance. Simultaneous analysis of multiple health outcomes could potentially provide more insight into the effect of the chemicals of interest in causing multiple health effects, competing risks between various health outcomes, and the interactive effects of some health endpoints on others.
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From page 28... ...
In such studies, the committee looked for evidence of health effects that are associated with the specific compounds contained in the chemicals used as defoliants in Vietnam, with consideration to and adjustment for other possibly confounding exposures. The quality of exposure information in the scientific literature reviewed by this committee spanned a broad range.
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From page 29... ...
In most cases, the measurement of compounds in blood has taken place many years after exposure. There are numerous difficulties in extrapolating back from contemporaneous TCDD tissue concentrations to estimate TCDD (and indirectly herbicide)
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From page 30... ...
Although studying AhR biology in transformed human cell lines minimizes the inherent error associated with species extrapolations, caution must be exercised because it is still not clear to what extent toxicity is affected by the transformation itself or by the conditions under which cell lines are cultured in vitro. Publication Bias Some studies are more likely to be published than others.
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From page 31... ...
Those aspects of the committee's review required thoughtful consideration of alternative approaches at several points and could not be accomplished by adherence to a narrowly prescribed formula. The realized approach, as described here, was determined to a large extent by the nature of the exposures, of the health outcomes, and of the resultant evidence available for examination; therefore, it has evolved in the course of the work of this and previous VAO committees.
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From page 32... ...
1997. Publication bias: Evidence of delayed publication in a cohort study of clinical research projects.
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