In univariate sensitivity analysis, vaccine efficacy (for cervical and non-cervical sites), duration of protection, percent of anogenital warts due to HPV-6/11, proportion of the male population that are men-who-have-sex-with-men Volasertib supplier (MSM), relative risk of disease in MSM vs. heterosexual men, costs and QALY-weights were varied between their minimum and maximum values found in the literature (Supplementary Tables 1 and 2). Finally, favourable scenarios for vaccination of boys were examined in multivariate sensitivity analysis. Variability of model predictions due to natural history parameters is presented
as the median, and first and third quartiles of simulation results, referred to as the interquartile ranges (IQR). Table 1 shows the
potential population-level effectiveness of two- and three-dose schedules assuming different durations of protection Bioactive Compound Library (see Supplementary Fig. 2 for post-vaccination dynamics). Under our base-case (coverage = 80%, vaccine-type efficacy = 95%) and assuming two-dose vaccine duration of protection is 10 years, two-dose girls-only vaccination is predicted to prevent a cumulative 13% of HPV-related cancer cases (12% anogenital warts consultations) over 70 years. Over the same time-horizon, giving a third dose in a girls-only vaccination programme prevents between 13 and 15% extra HPV-related cancer cases, if the duration of protection from three doses is between 25 years and lifelong. The equivalent expanded reductions in anogenital warts consultations are between 54 and 60%. Switching to a two-dose girls & boys strategy would prevent an extra 3% HPV-related cancer cases and 9% anogenital warts consultations compared to a two-dose girls-only vaccination policy. However, when almost assuming the duration
of protection of two doses is 20 or 30 years, the incremental benefits of giving a third dose to girls-only or switching to a two-dose girls & boys strategy are predicted to be relatively small (e.g., between 2 and 6% extra HPV-related cancer cases prevented; Table 1). Of note, the additional benefits provided by a third dose to girls-only are mostly among females whilst the majority of benefits of switching to a two-dose girls & boys strategy are among MSM. Fig. 1 shows the discounted QALYs-gained and cost offsets for girls-only and girls & boys vaccination programmes using two- and three-dose schedules. The incremental QALYs-saved and cost offsets by giving a third dose to girls-only are relatively small when assuming that two-dose protection is 20 years or more, but would increase the overall cost of the programme by almost 30%. Unless two and three doses provide equal duration of protection, switching to a two-dose girls & boys vaccination strategy is predicted to provide similar or lower incremental discounted QALYs-gained and cost-offsets than adding a third dose to girls-only.
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