Costs and Cost-Effectiveness of 9-Valent Human Papillomavirus (HPV) Vaccination in Two East African Countries

Background: Current prophylactic vaccines against human papillomavirus (HPV) target two of the most oncogenic types, HPV-16 and -18, which contribute to roughly 70% of cervical cancers worldwide. Second-generation HPV vaccines include a 9-valent vaccine, which targets five additional oncogenic HPV types (i.e., 31, 33, 45, 52, and 58) that contribute to another 15–30% of cervical cancer cases. The objective of this study was to determine a range of vaccine costs for which the 9-valent vaccine would be cost-effective in comparison to the current vaccines in two less developed countries (i.e., Kenya and Uganda). Methods and Findings: The analysis was performed using a natural history disease simulation model of HPV and cervical cancer. The mathematical model simulates individual women from an early age and tracks health events and resource use as they transition through clinically-relevant health states over their lifetime. Epidemiological data on HPV prevalence and cancer incidence were used to adapt the model to Kenya and Uganda. Health benefit, or effectiveness, from HPV vaccination was measured in terms of life expectancy, and costs were measured in international dollars (I$). The incremental cost of the 9-valent vaccine included the added cost of the vaccine counterbalanced by costs averted from additional cancer cases prevented. All future costs and health benefits were discounted at an annual rate of 3$9.7 per vaccinated girl. To be considered very cost-effective, the added cost per vaccinated girl could go up to I$5.2 and I$16.2 in the worst-case and best-case scenarios, respectively. At a willingness-to-pay threshold of three times per-capita GDP where the 9-valent vaccine would be considered cost-effective, the thresholds of added costs associated with the 9-valent vaccine were I$27.3, I$14.5 and I$45.3 per vaccinated girl for the base case, worst-case and best-case scenarios, respectively. In Uganda, vaccination with the 9-valent vaccine was very cost-effective when the added cost of the 9-valent vaccine did not exceed I$8.3 per vaccinated girl. To be considered very cost-effective, the added cost per vaccinated girl could go up to I$4.5 and I$13.7 in the worst-case and best-case scenarios, respectively. At a willingness-to-pay threshold of three times per-capita GDP, the thresholds of added costs associated with the 9-valent vaccine were I$23.4, I$12.6 and I$38.4 per vaccinated girl for the base case, worst-case and best-case scenarios, respectively. Conclusions: This study provides a threshold range of incremental costs associated with the 9-valent HPV vaccine that would make it a cost-effective intervention in comparison to currently available HPV vaccines in Kenya and Uganda. These prices represent a 71$5 per dose) for the currently available 2- and 4-valent vaccines in Kenya and Uganda, respectively. Despite evidence of cost-effectiveness, critical challenges around affordability and feasibility of HPV vaccination and other competing needs in low-resource settings such as Kenya and Uganda remain

How Much (More) Should CEOs Make? A Universal Desire for More Equal Pay

Do people from different countries and different backgrounds have similar preferences for how much more the rich should earn than the poor? Using survey data from 40 countries (N = 55,238), we compare respondents’ estimates of the wages of people in different occupations—chief executive officers, cabinet ministers, and unskilled workers—to their ideals for what those wages should be. We show that ideal pay gaps between skilled and unskilled workers are significantly smaller than estimated pay gaps, and that there is consensus across countries, socioeconomic status, and political beliefs for ideal pay ratios. Moreover, data from 16 countries reveals that people dramatically underestimate actual pay inequality. In the United States—where underestimation was particularly pronounced—the actual pay ratio of CEOs to unskilled workers (354:1) far exceeded the estimated ratio (30:1), which in turn far exceeded the ideal ratio (7:1). In sum, respondents underestimate actual pay gaps, and their ideal pay gaps are even further from reality than those underestimates

Potential Benefits of Second-Generation Human Papillomavirus Vaccines

Background: Current prophylactic vaccines against human papillomavirus (HPV) target two oncogenic types (16 and 18) that contribute to 70% of cervical cancer cases worldwide. Our objective was to quantify the range of additional benefits conferred by second-generation HPV prophylactic vaccines that are expected to expand protection to five additional oncogenic types (31, 33, 45, 52 and 58). Methods: A microsimulation model of HPV and cervical cancer calibrated to epidemiological data from two countries (Kenya and Uganda) was used to estimate reductions in lifetime risk of cervical cancer from the second-generation HPV vaccines. We explored the independent and joint impact of uncertain factors (i.e., distribution of HPV types, co-infection with multiple HPV types, and unidentifiable HPV types in cancer) and vaccine properties (i.e., cross-protection against non-targeted HPV types), compared against currently-available vaccines. Results: Assuming complete uptake of the second-generation vaccine, reductions in lifetime cancer risk were 86.3% in Kenya and 91.8% in Uganda, representing an absolute increase in cervical cancer reduction of 26.1% in Kenya and 17.9% in Uganda, compared with complete uptake of current vaccines. The range of added benefits was 19.6% to 29.1% in Kenya and 14.0% to 19.5% in Uganda, depending on assumptions of cancers attributable to multiple HPV infections and unidentifiable HPV types. These effects were blunted in both countries when assuming vaccine cross-protection with both the current and second-generation vaccines. Conclusion: Second-generation HPV vaccines that protect against additional oncogenic HPV types have the potential to improve cervical cancer prevention. Co-infection with multiple HPV infections and unidentifiable HPV types can influence vaccine effectiveness, but the magnitude of effect may be moderated by vaccine cross-protective effects. These benefits must be weighed against the cost of the vaccines in future analyses

Who decides: me or we? family involvement in medical decision making in eastern and western countries

Background: Research suggests that desired family involvement (FI) in medical decision making may depend on cultural values. Unfortunately, the field lacks cross-cultural studies that test this assumption. As a result, providers may be guided by incomplete information or cultural biases rather than patient preferences. Methods: Researchers developed 6 culturally relevant disease scenarios varying from low to high medical seriousness. Quota samples of approximately 290 middle-aged urban residents in Australia, China, Malaysia, India, South Korea, Thailand, and the USA completed an online survey that examined desired levels of FI and identified individual difference predictors in each country. All reliability coefficients were acceptable. Regression models met standard assumptions. Results: The strongest finding across all 7 countries was that those who desired higher self-involvement (SI) in medical decision making also wanted lower FI. On the other hand, respondents who valued relational-interdependence tended to want their families involved – a key finding in 5 of 7 countries. In addition, in 4 of 7 countries, respondents who valued social hierarchy desired higher FI. Other antecedents were less consistent. Conclusion: These results suggest that it is important for health providers to avoid East–West cultural stereotypes. There are meaningful numbers of patients in all 7 countries who want to be individually involved and those individuals tend to prefer lower FI. On the other hand, more interdependent patients are likely to want families involved in many of the countries studied. Thus, individual differences within culture appear to be important in predicting whether a patient desires FI. For this reason, avoiding culture-based assumptions about desired FI during medical decision making is central to providing more effective patient centered care

Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer

BACKGROUND: The aim of this study was to evaluate epigenetic status of cyclin A1 in human papillomavirus-associated cervical cancer. Y. Tokumaru et al., Cancer Res 64, 5982-7 (Sep 1, 2004)demonstrated in head and neck squamous-cell cancer an inverse correlation between cyclin A1 promoter hypermethylation and TP53 mutation. Human papillomavirus-associated cervical cancer, however, is deprived of TP53 function by a different mechanism. Therefore, it was of interest to investigate the epigenetic alterations during multistep cervical cancer development. METHODS: In this study, we performed duplex methylation-specific PCR and reverse transcriptase PCR on several cervical cancer cell lines and microdissected cervical cancers. Furthermore, the incidence of cyclin A1 methylation was studied in 43 samples of white blood cells, 25 normal cervices, and 24, 5 and 30 human papillomavirus-associated premalignant, microinvasive and invasive cervical lesions, respectively. RESULTS: We demonstrated cyclin A1 methylation to be commonly found in cervical cancer, both in vitro and in vivo, with its physiological role being to decrease gene expression. More important, this study demonstrated that not only is cyclin A1 promoter hypermethylation strikingly common in cervical cancer, but is also specific to the invasive phenotype in comparison with other histopathological stages during multistep carcinogenesis. None of the normal cells and low-grade squamous intraepithelial lesions exhibited methylation. In contrast, 36.6%, 60% and 93.3% of high-grade squamous intraepithelial lesions, microinvasive and invasive cancers, respectively, showed methylation. CONCLUSION: This methylation study indicated that cyclin A1 is a potential tumor marker for early diagnosis of invasive cervical cancer

Decision Making for Medical Innovations

The objective of this dissertation is to evaluate decision making related to medical innovations

Replication data for: A reassessment of India's Janani Suraksha Yojana conditional cash transfer program: State-level effects matter

There have been few formal assessments of India's Janani Suraksha Yojana (JSY), a national-level conditional cash transfer program to incentivize women to deliver in health facilities in order to reduce maternal and neonatal mortality. Using data from India's 2007-2008 District-Level Household Survey (DLHS-3), we undertake a reassessment of JSY based on a recent impact evaluation (Lim 2010). The impact of JSY and the characteristics of women reporting receipt of nancial assistance from JSY were previo usly reported at the national level (Lim 2010). We demonstrate that there was great heterogeneity in JSY uptake across the Indian states. Further, our results show that the impact of JSY on increasing antenatal care, in-facility birth, and skilled birth attendance also varies widely across states. Assessments of the uptake and impact of JSY should be carefully contextualized to the appropriate setting to allow for more informed policy insight in order to improve program implementation at the state and national level

Impact of discount rate on thresholds of incremental cost (I$) per vaccinated girl associated with the 9-valent vaccine^*.

<p>* GDP  =  gross domestic product; I$=  international dollars. Values represent the added cost of the 9-valent HPV vaccine at which the incremental cost-effectiveness ratio (compared to current 2- or 4-valent vaccines) would be equal to 1x per capita GDP in each country.</p>†<p> Base case scenario  =  some benefits to prevent cervical cancer with unidentifiable types and multiple infections, defined as a function of the prevalence of the five targeted HPV types relative to the prevalence of all non-16/18 types, with 37.4$) per vaccinated girl associated with the 9-valent vaccine^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106836#nt103" target="_blank">*</a>}.</p

Potential benefits of the 9-valent vaccine by HPV type distribution, multiple HPV infections and unidentifiable types in Kenya.

<p>The whole pie chart represents all cervical cancer cases in Kenya. The slice of the blue pie on the right depicts those cases that caused by non-16/18 types. The bar graph adjacent to the blue pie slice shows the proportion of the non-16/18 cases that are associated with multiple infections and unidentifiable types. The remaining non-16/18 cases were estimated to be the 9-valent vaccine target and non-target by their HPV prevalence. In the bar chart adjacent to the pie, blue shading depicts the cases that could be prevented by the 9-valent vaccine. In Scenario A, the 9-valent vaccine could not offer any benefit to prevent cervical cancer with unidentifiable type and multiple infections. In Scenario B, the 9-valent vaccine could prevent some cases with unidentifiable type and multiple infections and the proportion of cases that it can offer benefit was estimated by the prevalence of the five targeted HPV type relative to the prevalence of all non-16/18 types. In Scenario C, the 9-valent vaccine could offer full protective benefits in cases with unidentifiable types and multiple infections.</p