The public health value of vaccines beyond efficacy: methods, measures and outcomes.

BACKGROUND: Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages. DISCUSSION: Pre-licensure: Regulatory concerns dictate an individually randomised clinical trial. However, some circumstances (such as the West African Ebola epidemic) may require novel designs that could be considered valid for licensure by regulatory agencies. In addition, protocol-defined analytic plans for these studies should include clinical as well as etiologically confirmed endpoints (e.g. all cause hospitalisations, pneumonias, acute gastroenteritis and others as appropriate to the vaccine target), and should include vaccine-preventable disease incidence and 'number needed to vaccinate' as outcomes. Post-licensure: There is a central role for phase IV cluster randomised clinical trials that allows for estimation of population-level vaccine impact, including indirect, total and overall effects. Dynamic models should be prioritised over static models as the constant force of infection assumed in static models will usually underestimate the effectiveness and cost-effectiveness of the immunisation programme by underestimating indirect effects. The economic impact of vaccinations should incorporate health and non-health benefits of vaccination in both the vaccinated and unvaccinated populations, thus allowing for estimation of the net social value of vaccination. CONCLUSIONS: The full benefits of vaccination reach beyond direct prevention of etiologically confirmed disease and often extend across the life course of a vaccinated person, prevent outcomes in the wider community, stabilise health systems, promote health equity, and benefit local and national economies. The degree to which vaccinations provide broad public health benefits is stronger than for other preventive and curative interventions

Human Papillomavirus prevalence and associated risk factors in women with cervical pre-cancer and cancer in Switzerland at the beginning of the cantonal vaccination programmes: The CIN3+plus study

Background / Objectives The Swiss Federal Office of Public Health has recommended vaccination against human papillomavirus (HPV) to prevent cervical cancer since 2007. To monitor the future public health impact of vaccination, baseline population-based data are required. The objectives of this study were to determine the prevalence of HPV and examine associated risk factors in women with cervical intraepithelial neoplasia stage 3 or more severe lesions (CIN3+) in Switzerland. Methods We conducted a cross-sectional study with women diagnosed with CIN3+ in Switzerland. Ten pathology institutes from six cantons and three language regions participated. We conducted HPV typing on formaldehyde fixed-paraffin embedded specimens from 2014 and 2015. Women enrolled in 2015 were asked to complete a questionnaire. We described frequencies of HPV types. We also compared demographic characteristics and socioeconomic status (according to the Swiss neighbourhood index of socioeconomic position, Swiss-SEP) in the CIN3+plus group with the Swiss National Cohort (SNC) in 2014 and compared risk factors for HPV infection with the Swiss Health Survey (SHS) in 2012. Results We included 768 biopsies from 767 women aged 17-81 years with CIN3+ in 2014 and 2015. Of these, 745 (97.0%) were positive for any HPV type, 5 (0.7%) were negative and 18 (2.3%) were not evaluable. Overall, 475/768 (61.8%) biopsies contained HPV 16 and/or 18 and 687 (89.5%) contained an oncogenic HPV type covered by the nonavalent HPV vaccine (16, 18, 31, 33, 45, 52, 58). In 2015, 273 women completed a questionnaire. Compared with the SNC, fewer women with CIN3+ were born in Switzerland (49.0 vs. 63.4%; p<0.001) and more were single (48.9 vs. 28.1%; p<0.001), but mean Swiss-Sep index was similar (64.6±10.8 vs. 65.2±10.9; p=0.135). Amongst women with CIN3+, higher proportions reported ≥2 sexual partners in the last 12 months (15.4% vs. 4.1%), smoking (38.5% vs. 22.0%) and hormonal contraception use in the last 12 months (35.5% vs. 22.4%) than women in the SHS. Conclusion This is the first study of HPV in women with CIN3+ covering all three language regions in Switzerland. Women with CIN3+ have levels of socioeconomic position that are similar to the Swiss general population but higher levels of some risk factors for HPV. Surveillance of HPV types in CIN3+ lesions is feasible and can be used to measure the future impact of HPV vaccination on clinical outcomes

P36-05 HPV prevalence and associated risk factors in women with cervical pre-cancer and cancer in Switzerland at the beginning of the cantonal vaccination programmes: The CIN3+plus study

Background / Objectives The Swiss Federal Office of Public Health has recommended vaccination against human papillomavirus (HPV) to prevent cervical cancer since 2007. To monitor the future public health impact of vaccination, baseline population-based data are required. The objectives of this study were to determine the prevalence of HPV and examine associated risk factors in women with cervical intraepithelial neoplasia stage 3 or more severe lesions (CIN3+) in Switzerland. Methods We conducted a cross-sectional study with women diagnosed with CIN3+ in Switzerland. Ten pathology institutes from six cantons and three language regions participated. We conducted HPV typing on formaldehyde fixed-paraffin embedded specimens from 2014 and 2015. Women enrolled in 2015 were asked to complete a questionnaire. We described frequencies of HPV types. We also compared demographic characteristics and socioeconomic status (according to the Swiss neighbourhood index of socioeconomic position, Swiss-SEP) in the CIN3+plus group with the Swiss National Cohort (SNC) in 2014 and compared risk factors for HPV infection with the Swiss Health Survey (SHS) in 2012. Results We included 768 biopsies from 767 women aged 17-81 years with CIN3+ in 2014 and 2015. Of these, 745 (97.0%) were positive for any HPV type, 5 (0.7%) were negative and 18 (2.3%) were not evaluable. Overall, 475/768 (61.8%) biopsies contained HPV 16 and/or 18 and 687 (89.5%) contained an oncogenic HPV type covered by the nonavalent HPV vaccine (16, 18, 31, 33, 45, 52, 58). In 2015, 273 women completed a questionnaire. Compared with the SNC, fewer women with CIN3+ were born in Switzerland (49.0 vs. 63.4%; p<0.001) and more were single (48.9 vs. 28.1%; p<0.001), but mean Swiss-Sep index was similar (64.6±10.8 vs. 65.2±10.9; p=0.135). Amongst women with CIN3+, higher proportions reported ≥2 sexual partners in the last 12 months (15.4% vs. 4.1%), smoking (38.5% vs. 22.0%) and hormonal contraception use in the last 12 months (35.5% vs. 22.4%) than women in the SHS. Conclusion This is the first study of HPV in women with CIN3+ covering all three language regions in Switzerland. Women with CIN3+ have levels of socioeconomic position that are similar to the Swiss general population but higher levels of some risk factors for HPV. Surveillance of HPV types in CIN3+ lesions is feasible and can be used to measure the future impact of HPV vaccination on clinical outcomes

Perspectives WHO criteria for measles elimination: a critique with reference to criteria for polio elimination 33

Quantifying the risk of pandemic influenza in pregnancy and Indigenous people in Australia in 2009