to compare products made by different manufacturers and to studyvaccine efficacy, lot-specific differences in vaccines, reactionsthat occur following the simultaneous administration of more thanone vaccine, and the incidence of age-appropriate administrationof vaccines.
The exposures of interest are all childhood vaccines. The outcomesof particular and current interest are a number of adverse eventsthat have been reported to occur after vaccination. The literaturewas carefully reviewed in 1990, and 34 adverse events were thoughtto be biologically plausible. The determination of which outcomesto study, however, is envisioned as a long-term dynamic process,and the IOM reports published since work began on designing the LLDB(Institute of Medicine, 1991, 1994a,b) are being used to reevaluatethe list to see whether other events can and should be included.The study is evolving, and data collection plans can be changed asthe study proceeds.
Hospital discharge records are not sufficient as a basis for gatheringinformation about vaccine-related adverse events, partly becausesome of the serious reactions of interest are treated or evaluatedin clinics and urgent care facilities. Thus, case ascertainment isaccomplished directly from diagnoses upon hospital discharge, treatmentrecords at clinics and urgent care centers, and death certificatesand autopsy reports and indirectly from records of laboratory culturesand tests, specialist referrals, diagnostic procedures, and drugprescriptions; all of these data exist in the computerized data systemsof the HMOs. Even the use of a system that includes records of alltreatments for putatively vaccine-related adverse reactions doesnot guarantee that all relevant information will be obtained, becausediagnoses are not always made, medical attention is not always sought,and the disposition to resolve medical problems and to be vaccinatedmay be related. Associations that emerge consistently from site tosite and year to year by either path will be subjected to furtherepidemiologic studies to confirm the association based on a thoroughreview of conventional medical reports.
Study statisticians have calculated the statistical power of thetechnique, that is, the probability of being able to detect particularvaccine-adverse event associations during the time allotted to thestudy, taking into account the timing of vaccine exposures, misclassificationof adverse events, compliance with recommended vaccination schedules,and the like. Investigators have recommended that the study continuebeyond the allotted 4 years because some rarely occurring adverseevent-vaccine relations will not be detectable statistically overthat period of time, if they do in fact occur. However, it is notclear how long of a follow-up would be required.
Most of the first 2 years of the project were spent on creating casedefinitions and standardization among the HMOs and their databases.Some existing databases, for example, serve only administrative purposes,and attempts are being made to increase the quality of the recordsfrom those databases for scientific study. Much heterogeneity remains.