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Estimation of vaccine efficacy for both susceptibility and reduction in infectiousness for prophylactic HIV vaccines.
Longini IM; Datta S; Halloran E; Biostatistics, Atlanta, GA, USA. Fax:
January 30, 1997
Int Conf AIDS. 1996 Jul 7-12;11(2):34 (abstract no. We.C.210). Unique

Objectives: Current phase III trials are designed to assess only a vaccine candidate's ability to reduce susceptibility to infection or disease, i.e., vaccine efficacy for susceptibility VES). HIV vaccination, however, may reduce infectiousness of vaccines who become infected. This could produce an important indirect reduction in HIV transmission even if the vaccine does not protect well against infection. We propose two approaches for augmenting the information of a classical trial to estimate additionally the vaccine's effect on infectiousness, i.e., vaccine efficacy for infectiousness (VEI). Methods: In the first augmentation, sexual partners of trial participants are recruited, but not randomized to vaccine or placebo. Their infection status is monitored throughout the trial. In the second augmentation, the sexual partners are randomized. Through computer simulations, we demonstrate the gains in precision of the VE estimators, and in power for the three hypothesis tests H0: VES = 0; H0: VEI = 0; and H0: VES = 0, VEI = 0 (no vaccine effect). All tests are two sided. Results: A classical trial which assumes 2,000 subjects per arm, 10% annual infection rate, and VES = 0.2, leads to a 95% confidence interval (CI) on VES of [0.02,0.35] and a power to reject H0: VES = 0 of 0.67, for one year of follow-up. If we add 500 partners per arm under the first augmentation, assume a 50% secondary attack rate within the partnership, and VEI = 0.5, then the 95% CI's on VES and VEI are [0.05,0.32], [0.01,0.95], respectively. The powers to reject H0: VES = 0 is increased to 0.78, the power to reject H0: VEI = 0 is 0.57, and the power to reject H0: VES = 0, VEI = 0 is 0.86. Under the second augmentation, the 95% CI's on VES and VEI are [0.06,0.32], [0.11,0.78], respectively. The power to reject H0: VES = 0 and H0: VEI = 0 are further increased to 0.85 and 0.86, respectively. If we add 1,000 partners per arm under the second augmentation, the 95% CI on VEI is [0.26,0.70] and the power to reject H0: VES = 0, VEI = 0 is increased to 1.00. Conclusions: Current envelope vaccines may not give good protection against infection, but decrease infectiousness during primary infection in infected vaccines. Thus, it will be very important to estimate VEI in phase III vaccine trials. Employment of augmented designs described here would accomplish this goal. Not only do these designs allow estimation of VEI, but they increase the precision of the VES estimator and the power to reject the null hypothesis of no vaccine effect.

*AIDS Vaccines/IMMUNOLOGY *Clinical Trials, Phase III *HIV Infections/IMMUNOLOGY