Intention-to-Treat

(ITT) cohorts, also designated Total Vaccine Cohort (TVC), are the most inclusive, including all individuals that are randomized and participate in the trial. For vaccine trials “participation” is usually defined as receiving at least Akt activity one dose of the vaccine. These cohorts include women with evidence of prior HPV exposure and hence current infection/lesions by vaccine-targeted as well as other HPV types. ITT analyses can be viewed as an approximation of the effectiveness of the vaccine in general use, at least for individuals with similar demographic and risk characteristics as the subjects in the trial. The most restrictive cohorts are According to Protocol (ATP), also designated Per Protocol Efficacy (PPE). ATP analyses

are restricted to individuals who adhere to all aspects of the study protocol: for example, they received the three vaccine doses within specified intervals, and events are not counted until after receiving all three doses. Importantly, individuals included in ATP cohorts have no evidence of exposure to the vaccine-targeted type under analysis. Thus ATP analyses can be viewed as the best-case scenario for the effectiveness of a prophylactic vaccine. Modified buy BKM120 Intention-To-Treat (MITT) analyses fall somewhere in between ITT and ATP, allowing for some deviation from the ideal protocol. One interesting MITT cohort is designated TVC-naïve or ITT-naïve. These cohorts include all participating individuals with no evidence at baseline of cervical

cytology abnormalities, prevalent infection by any of the genital HPV types evaluated (up to 14 types) or serological evidence of past exposure to the vaccine-targeted types. These cohorts are currently the best approximation for the primary target group for the vaccines, pre- and early-adolescent why girls who have not yet become sexually active. Finally, it is always import to note whether the efficacy against lesion development is restricted to those specifically related to vaccine-targeted types or irrespective of HPV type. As discussed below, protection from infection by the L1 VLP vaccines is type restricted and so efficacy is generally higher in the analyses restricted to the vaccine-targeted types. Most publications have concentrated on reporting vaccine efficacy, which can be thought of as the percent reduction in an individual’s probability of acquiring a given endpoint if s/he received the experimental vaccine versus the control. However, analyses of rate reductions in disease or treatment, generally reported using the denominator of per 100 subject-years, have also been reported in some of the more recent publications. Rate reductions can sometimes be more useful indicators of the potential for health impact of an intervention.