Interventions for Tuberculosis Control and Elimination 2002

the number of person-years of observation. The measures are incidence
rates among the exposed and unexposed and the summary measure is the
relative risk (the risk among the exposed divided by the risk among the
unexposed). Vaccine efficacy (in per cent) is calculated as (1 – relative
risk) × 100. 732 The 95% confidence intervals were calculated (or recalculated,
where appropriate) using the formula proposed by Orenstein in his
review on assessment of vaccine efficacy, 732 unless adjusted or stratified
summary estimates were provided by the authors.
To defray the costs incurred in clinical trials and to obtain results more
quickly, it was proposed to ascertain the effectiveness of BCG vaccination
by means of (retrospective) case-control studies. 733 Briefly, case-control
studies start with looking at the outcome (tuberculosis) and then ascertain
exposure (BCG vaccination given or not) in a group of patients with the
outcome, compared to an appropriately selected control group of persons
without the outcome (table 10). 734 A relative risk cannot be calculated as
this measurement is confined to population-based studies. The measurement
of risk in a case-control study is the odds ratio (or relative odds). For
rare diseases the odds ratio approximates the relative risk in a clinical trial.
The advantages and disadvantages in the use of the case-control approach
are linked to its being observational, having subjects selected on the basis
of disease status, and using controls from the population from which the
cases emanated. 735 The advantages of case-control studies include avoidance
of ethical problems arising in situations where there is already evidence
that the vaccine is better than placebo; allowing much faster conduct than
randomized trials; and requiring a much smaller number of subjects. They
are thus substantially cheaper to conduct than randomized clinical trials. 735
The most challenging difficulty in the design of case-control studies
is the selection of appropriate controls in that they have to be selected in
such a way that they are comparable to cases in every respect except for
the outcome. Selection bias resulting from a failure to ensure this comparability
may thus invalidate any findings.
The results of some of these case-control studies are summarized
below. Vaccine effectiveness (in per cent) from a case-control study is
estimated as (1 – odds ratio) × 100. 732 For unmatched case-control studies,
the 95% confidence intervals were calculated (or recalculated where
appropriate) using Woolf’s method. 734 For matched and adjusted analyses,
the confidence interval published by the authors of the study was chosen.
If not stated for matched studies, the confidence interval around the crude
odds ratio was calculated as above.
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