administration on the occurrence of the adverse outcomes under review contribute not to the biological mechanisms argument but to the causality argument.

Beginning with this report, the committee will summarize the biological mechanisms as theoretical only, or as having derived from either experimental evidence or mechanism-related evidence in humans. If there is evidence in experimental models or humans for a mechanism, we will designate it as weak, moderate, or strong. Though the committee tends to judge evidence in humans to be “stronger” than experimental evidence from animals or in vitro systems, the strength of the evidence also depends on other factors, such as the experimental design and sample size. Obviously, the conclusions drawn from this review will depend both on evidence and scientific judgment. To ensure that its own summary judgment is defensible, the committee intends to be as explicit as possible regarding the strengths and limitations of the biological data.

Published and Unpublished Data

Published reports that have been subjected to a rigorous peer review process carry the most weight in the committee’s assessment. Unpublished data and other reports that have not undergone peer review do have value, and they are often considered by the committee; they could be used, for example, in support of a body of published literature with similar findings. If the committee concluded that the unpublished data were well described, had been obtained using sound methodology, and presented very clear results, the committee could report, with sufficient caveats in the discussion, how those data fit with the entire body of published literature. But only in extraordinary circumstances could an unpublished study refute a body of published literature. In general, the committee cannot rely heavily on unpublished data in making its scientific assessments (regarding either causality or biological mechanisms) because they have not been subjected to a rigorous peer review process, and therefore must be interpreted with caution.

The committee acknowledges that its approach differs from the state of the art for evidence-based reviews of clinical practices in medicine, which does not include consideration of unpublished or non-peer-reviewed information or of studies with flawed experimental designs (U.S. Preventive Services Task Force, 1996). However, the Immunization Safety Review Committee was convened specifically to assess topics that are often of immediate and intense concern. In some cases, the committee’s review will take place as data are only beginning to emerge. Thus, given the unique nature of this project, the committee thought it was important to review and consider as much information as possible, including unpublished information. The committee did not perform primary or secondary analyses of unpublished data, however. In reviewing unpublished material, the committee applied generally accepted standards for assessing the quality of scientific evidence, as described above. (All unpublished data reviewed by the

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