Resolving the pneumococcal vaccine controversy: are there alternatives to randomized clinical trials?

It has been more than five years since the relicensure of pneumococcal vaccine. There are few data, however, with which to evaluate the efficacy of pneumococcal vaccine for the conditions constituting current vaccine indications. As a result, recommendations for the use of pneumococcal vaccine remain controversial, and it is widely agreed that further clinical studies should be undertaken. Recommendations for future studies have emphasized the need for randomized clinical trials, which offer the best opportunity to assure scientifically valid results. Generally not considered are the substantial ethical and logistic problems that may impede the conduct of randomized clinical trials capable of resolving the current uncertainty. Observational studies, which include cohort, quasi-cohort, and case-control studies, are alternative approaches for evaluating pneumococcal vaccine. Although lacking the scientific strength of randomized clinical trials, certain observational designs, particularly case-control studies, pose no ethical difficulties and offer logistic advantages that will permit the rapid acquisition of statistically meaningful estimates of the efficacy of the vaccine for patients with current indications. When conducted with careful attention to measures for minimizing bias, observational designs offer attractive alternative strategies for resolving the pneumococcal vaccine controversy.