Although pneumococcal vaccine is currently recommended for many patients with conditions associated with an increased risk of serious pneumococcal infection, the use of the vaccine remains controversial because of uncertainty about its clinical efficacy. Randomized clinical trials of the vaccine's efficacy cannot resolve the issue because of overwhelming logistical, financial and ethical obstacles to conducting such trials. Unfortunately, both experimental and non-experimental studies with inadequate statistical power continue to be reported and add to the uncertainties about the vaccine's efficacy. The principal investigator initiated a multi-hospital case-control study of the vaccine's efficacy in late 1984. The subjects are hospitalized patients who have recognized indications for pneumococcal vaccine. The cases, patients with systemic pneumococcal infections, are identified through active surveillance of the bacteriology laboratories of all major hospitals in Connecticut. The pneumococci are serotyped to ascertain whether they are a type that is included in the polyvalent vaccine. One control, matched to each case by the indication for the vaccine (e.g. chronic lung disease), age, date of hospitalization and duration that the indication for the vaccine had been recognized, is randomly selected from patients without pneumococcal infection. Antecedent receipt of pneumococcal vaccine is ascertained from the records of all hospitals, physicians' offices, clinics and nursing homes at which the subject had received care. Based on the number of eligible subjects that have been enrolled during the first two years of the study, it can be estimated that at the conclusion of the third year of the study about 450 subjects will be enrolled. Thus far, 8% of the cases and 19% of the controls had received the vaccine. Based on these results, at the end of 3 years the vaccine will be shown to be efficacious but the 95% confidence limits will be wide (42-80%). By continuing the study the precision of the estimate of the vaccine's efficacy will be greatly improved (58-70% based on these rates). In addition, meaningful estimates of the vaccine's efficacy could be made for specific subgroups of patients (e.g. patients with chronic lung disease), and it will be possible both to assess the duration of protection that is afforded by the vaccine and to identify specific serotypes of pneumococci against which the vaccine may have poor efficacy. This information will have a substantial impact on both national and individual health care planning.
|Shapiro, Eugene D (2004) Case-control studies of the effectiveness of vaccines: validity and assessment of potential bias. Pediatr Infect Dis J 23:127-31|
|Shapiro, E D; Berg, A T; Austrian, R et al. (1991) The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 325:1453-60|