vaccine and control groups, all of whom would be issued standard military chemoprophylaxis. Although subjects would be recommended to take chemoprophylaxis, there would be no systematic direct supervision of subjects taking their daily medication. Rather this would be left to the discretion of the individual subject, recognizing that in real-life conditions, a variable proportion of military personnel deployed to sites of known malaria risk do not take chemoprophylaxis in a reliable way. Accordingly, in a conservative assumption, 10 percent of the study subjects would fail to take chemoprophylaxis for sufficiently extended periods so that these subjects would be equivalent in risk to the nonprophylaxed subjects of the preceding two efficacy trials.

Thus, if 2,000 enrolled subjects were randomly allocated to receive the maturing candidate vaccine and 2,000 others to the control group, by the end of the study, despite some expected dropouts and loss to follow-up, approximately 1,640 analyzable subjects would be available in each group. Of these, because of random allocation, one would expect about 164 “nonchemoprophylaxed” subjects to be available for analysis in each group. Among the 1,640 analyzable control subjects, one would expect to detect around 115 cases of P. falciparum malaria (70 percent attack rate among the 164 controls who did not adhere strictly to chemoprophylaxis). One would also expect to detect 46 cases of P. falciparum malaria in the vaccine recipients (60 percent proportionate reduction); this constitutes a total of 161 cases between the two groups. The limits of the 95 percent CI around the 60 percent point estimate of vaccine efficacy, as in the previous example, would be 43 percent (lower limit) and 72 percent (upper limit) around the point estimate of efficacy.



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