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Research Strategies for Assessing Adverse Events Associated withVaccines:: A Workshop Summary
mechanisms of adverse reactions to vaccines has not yet advancedto the point that it is always evident what studies should be undertaken.
Use of Case Reports in Causality Assessment
One participant stressed that individual case reports from passivesystems may in some specific cases, be able to answer causation questionsthat population-based studies never could. For example, the questionof whether the Urabe-strain mumps vaccine can cause meningitis orwhether OPV can cause polio can be answered by a single persuasivecase in which virus is isolated and is typed by molecular biologictechniques as the vaccine strain, rather than the wild-type strain,and there is no other etiologic factor that could cause the disease.The absence of an alternative etiologic factor makes the isolationof the vaccine strain of the virus more compelling, because the presenceof vaccine strain virus does not always prove that the virus causeddisease; it is not known how often vaccine-strain virus might bepresent in asymptomatic individuals.
Several participants agreed that evaluation of case reports of fullyevaluated events should not be minimized as an important method ofexamining very rarely occurring adverse events. Even LLDBs do nothave access to data on populations in the millions, such as mightbe necessary to have enough power to make conclusions about rarelyoccurring adverse events in a population. When a suspected rarelyoccurring adverse event is reported following vaccination, intenseand targeted clinical evaluations and research might help in assessingcausality. As discussed above, this could be costly, and currentlythere is no mechanism to fund these investigations.
Some shortcomings of passive surveillance systems are common to otherstrategies for evaluating adverse events; for example, no data-gatheringsystem, including LLDBs, can easily assess causation when multiplevaccines are administered simultaneously. As another example, becauseof the emphasis on events temporally associated with vaccination,events that occur long after vaccination may not be detected.
Because causation may not be the most fruitful focus for a discussionof VAERS and other passive surveillance systems, one participantsuggested that two additional questions be asked.
Do preexisting conditions play a role in the occurrence or reportingof adverse events?
Are particular lots associated with higher reporting rates of particularadverse events?
Passive surveillance systems such as VAERS could be helpful in addressingboth of these questions. However, as with questions of causality,without complete information in each report, these questions areunanswerable by a passive surveillance system.