The United Kingdom has successfully used LLDBs in a three-step processof signal detection, causality assessment, and risk calculation.In the incident related to the Urabe-strain mumps vaccine mentionedearlier, for example, 5 public health laboratories participated initially;the number has since been expanded to 20. Each of the laboratoriessearched its database for mention of any child who had undergonea lumbar puncture (and thus might have been treated for suspectedmeningitis). This information was then cross-checked with districthealth databases to determine the vaccination history of each suchchild. The success of this project was attributed in part to thesmall, manageable size of the individual component (a public healthlaboratory).

Discussion

Strengths and Weaknesses of LLDBs

The LLDB was thought to be a powerful tool for vaccine safety studies.Two valuable contributions of LLDBs noted by participants were theability to compare children receiving different formulations of thesame vaccine and the ability to compare new vaccines with standardvaccines. It is possible, for example, to compare vaccinated andunvaccinated children at age 3 months or to compare the same childbefore and after vaccination. Comparisons between children who receivedvaccines according to different schedules could be made as well.Because the cohort is being followed for several years, it mightbe possible to study long-term outcomes and chronic conditions aswell.

The LLDB was characterized by one participant as a framework in whichthe data for most of the key elements of a good epidemiologic studyare already in place. It then should be possible not only to generatehypotheses but to begin to test those hypotheses as well. Passivesurveillance reporting systems are not amenable to answering questionsin a timely manner. Well-designed LLDBs should avoid that pitfall.

It was suggested that, in addition to safety concerns, issues aboutthe persistence of vaccine efficacy over the time frame of the studycould also be addressed by LLDBs. It might be possible to look atthe occurrence of vaccine-preventable diseases in vaccinated children,for example. A PHS representative indicated that LLDBs have indeedbeen used to look at one particular efficacy issue. Recently, resultsfrom a clinical research study led a manufacturer to question thepotency of a lot of a particular vaccine. An LLDB was used to identifywhich children had been given that vaccine. It was then possibleto test a sample of those children for antibody levels and to identifywhich vaccine lots produced lower antibody levels than others.

Several participants stressed that some questions will not be answerableby the LLDB method and that this should be acknowledged from thestart. The



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