Implications of different study designs for the evaluation of acellular pertussis vaccines

Twelve different pertussis vaccines (eight of them acellular) have been evaluated in seven different studies planned to provide absolute or relative efficacy measures. Study designs included trials with randomized unvaccinated (DT) and/or whole-cell vaccine control groups, a cohort study, household contact studies and a case-control study. Although some of the studies were designed only to provide relative measures comparing the efficacy of an acellular versus a whole-cell vaccine, striking variation in the efficacy of the whole-cell vaccines led all studies to emphasize estimates of absolute efficacy. The reliability of the various results is likely to be dependent upon details of the study designs. In particular three randomized, placebo-controlled, double-blind trials (carried out in Italy and Sweden) provide the most convincing results through their avoidance of selection bias in the (unvaccinated) baseline control groups. Problems in differential case ascertainment were inherent in all studies. This paper reviews the design of each of the studies and comments on methodological problems likely to have influenced their findings.