Adverse Effects of Vaccines Evidence and Causality (2012) / Chapter Skim
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2 Approach
2 Approach
Pages 39-56
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From page 39... ...
Drawing from both lines of evidence to support causal inference is well established in the literature. When confronted with epidemiologic and mechanistic evidence suggesting -- however 1 Asdescribed in a subsequent section, previous IOM committees described the strongest evidence as establishing a causal relationship; this committee uses the term convincingly supports.
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From page 40... ...
Titles and abstracts, where available, were reviewed to screen out articles that did not address one of the potential vaccine adverse events to be reviewed or that were not primary research articles. See Figure 2-1.
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From page 41... ...
CAUSALITY CONCLUSION 41 FIGURE 2-1 Epidemiologic and mechanistic evidence reviewed by the committee.
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From page 42... ...
A brief description of major study designs and methodological considerations can be found in Appendix A Surveillance studies were reviewed, but the absence of a control group limited their contribution to the weight of epidemiologic evidence; studies that included individual case descriptions were reviewed for their contribution to the evaluation of mechanistic evidence (discussed in subsequent sections)
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From page 43... ...
The committee was rigorous in assessing the strengths and weaknesses of each epidemiologic study. For many of the conditions and adverse events considered by the committee, the expected incidence and prevalence rates in the general unvaccinated population as well as in unvaccinated but potentially susceptible subgroups may be very low.
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From page 44... ...
The reader will see in the summary paragraphs for the epidemiologic studies and, in some circumstances, the causality conclusion the committee's interpretation of the evidence more fully than can be captured with the formal and consistent wording of the conclusions used in this report. Evaluation of the Body of Studies The committee reviewed methodological approaches of other systematic review efforts, but it was unable to identify one approach that incorporated all of the committee's needs and could be adopted for immediate use.
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From page 45... ...
Assessments of limited or insufficient include no direction of effect. The committee does not consider a single study -- regardless of how well it is designed, the size of the estimated effect, or the narrowness of the confidence interval -- sufficient to merit a weight of "high" or, in the absence of strong or intermediate mechanistic evidence, sufficient to support a causality conclusion other than "inadequate to accept or reject a causal relationship." This requirement might seem overly rigorous to some readers.
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From page 46... ...
Some authors of older case reports use a diagnosis appropriate for the time, but by today's understanding of clinical disease and pathophysiology, the committee offers a different diagnosis and the case report is described within that committee-directed assessment. 4 What constitutes reasonable latency will vary across vaccines and across adverse events.
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From page 47... ...
This is consistent with previous IOM committees tasked with reviewing evidence of causality for vaccine safety. Evidence consisting only of parallels with the natural infections is never sufficient to merit a conclusion other than the evidence is inadequate to accept or reject a causal relationship.
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From page 48... ...
• Lacking evidence of a biologic mechanism: No clinical, diagnos tic, or experimental evidence consistent with relevant biological response to vaccine,6 regardless of the presence of individual cases in the literature. CAUSALITY ASSESSMENT The committee adopted the categories of causation developed by previous IOM committees.
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From page 49... ...
influence the final causality conclusion. It is important to note that mechanistic evidence can only support causation.
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From page 50... ...
The focus of this particular committee is only on the question of what particular vaccines can cause particular adverse effects. In general, the framework shown in Figure 2-2 illustrates how causality conclusions can be based primarily on epidemiologic evidence, primarily on mechanistic evidence, or on a combination of the two, and that on occasion expert judgment, such as that provided by the complement of expertise represented on the committee, is needed to weigh uncertain or competing evidence.
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From page 51... ...
* Causality conclusion is favors rejection only if mechanistic assessment is not strong or intermediate.
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From page 52... ...
See Chapter 13 for a discussion of this issue. Evidence Favors Acceptance of a Causal Relationship A conclusion of "favors acceptance of a causal relationship" must be supported by either epidemiologic evidence of "moderate" certainty of an increased risk or by mechanistic evidence of intermediate weight.
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From page 53... ...
A weight of mechanistic evidence of low-intermediate was not sufficient, without concurring epidemiologic evidence, to support a conclusion favoring acceptance of a causal relationship. As will be described in subsequent chapters of the report, the committee concluded the evidence favors acceptance of four specific vaccine–adverse event relationships.
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From page 54... ...
For example, the risk of invasive disease following varicella vaccine, a live virus vaccine, is likely much higher in immunocompromised persons than in persons who are immunocompetent. Other subpopulation analyses in the report include age and sex for some specific adverse events.
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From page 55... ...
2001. Causality assessment of adverse events following immunization.
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