The contribution of the case-control approach to vaccine evaluation: Pneumococcal and Haemophilus influenzae type b PRP vaccines

Case control studies have had an increasing role in the postlicensure evaluation of vaccine efficacy. We review the contribution of case control studies to the evaluation of vaccines for Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) and compare these studies with clinical trials of these vaccines. We located one clinical trial and eight case-control studies of Hib PRP vaccine efficacy and three clinical trials and four case control studies of pneumococcal vaccine efficacy. The pooled estimate of Hib PRP vaccine efficacy based on the case-control studies (0.38, 95% CL = 0.15-0.55) was lower than the efficacy of the clinical trial conducted in Finland (0.8, 95% CL = 0.57-0.98). The pooled estimate of pneumococcal vaccine efficacy based on the case-control studies (0.56, 95% CL = 0.44-0.66) was also lower than the pooled efficacy of the South African clinical trials (0.79, 95% CL = 0.69-0.86). Although the clinical trials provided crucial evidence that these vaccines worked in selected international settings, the direct evidence of efficacy in the United States rests largely on the case control results. The utility of the case control approach is supported.