Simulation studies of phase III clinical trials to test the efficacy of a candidate HIV-1 vaccine.

One question of particular importance in phase III HIV vaccine trials is the choice of efficacy measure (EM) to validly and precisely estimate the true vaccinal efficacy. Traditional EMs, based on hazard rate ratio (HRR) or cumulative incidence ratio (CIR) are time-sensitive to mode of vaccine action and population heterogeneities. Through Monte-Carlo simulation, the performance of HRR and CIR based EMs are examined across different trial designs and vaccine and population characteristics. A new EM based on log-spline hazard regression (HARE) is proposed. Given that vaccinal properties (mode of action, time-lag, waning) are unknown a priori, appropriate selection of EM is problematic, and HRR and CIR can be unreliable to estimate the true maximum efficacy of candidate products. Non-random sexual mixing can exacerbate biases in HRR and CIR. HARE can offer valid estimation across different modes of vaccine action and in presence of frailty effects, contrary to its traditional counterparts. Our simulation studies highlight the weaknesses of widely used EMs while offering guidelines for trial design and suggesting new avenues for statistical analysis.

The preventive and therapeutic potential of the squalene-containing compound, Roidex, on tumor promotion and regression.

Recent scientific evidence has shown free radicals or reactive oxygen species (ROS) to play an important role in the initiation and progression of cancer. Many radical scavengers have also been found to help reduce the attacks by these ROS. Interestingly, the ROS scavengers that have been investigated are naturally occurring compounds such as vitamins C and E. Roidex is a formulation of squalene, vitamin e, and aloe vera. It was our goal to investigate whether Roidex was able to prevent the development of chemically induced cancer and to cause regression of any tumors already formed in a mouse skin model. In the prevention study, skin tumors were initiated in 50 female CD-1 mice with 7,12-dimethylbenz[a]-anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). The mice were treated with either mineral oil, 5% squalene, or Roidex. At the end of the prevention study, there was a 33.34% incidence to tumors (multiplicity of 1.40) in the mineral oil-treatment group, 26.67% (multiplicity of 0.467) in the 5% squalene and Roidex groups, respectively. The tumor regression study involved the selection of mice with tumors and possible regression of these tumors with Roidex treatment. There was a regression of 33.34% of the tumors in the Roidex-treated group (39 tumors to 26 tumors) compared to the non-treated group whose tumors regressed only 3.44% (29 tumors to 28 tumors).