Cost-effectiveness of pharmaceutical strategies to prevent respiratory syncytial virus disease in young children: a decision-support model for use in low-income and middle-income countries.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in young children. A number of mathematical models have been used to assess the cost-effectiveness of RSV prevention strategies, but these have not been designed for ease of use by multidisciplinary teams working in low-income and middle-income countries (LMICs). METHODS: We describe the UNIVAC decision-support model (a proportionate outcomes static cohort model) and its approach to exploring the potential cost-effectiveness of two RSV prevention strategies: a single-dose maternal vaccine and a single-dose long-lasting monoclonal antibody (mAb) for infants. We identified model input parameters for 133 LMICs using evidence from the literature and selected national datasets. We calculated the potential cost-effectiveness of each RSV prevention strategy (compared to nothing and to each other) over the lifetimes of all children born in the year 2025 and compared our results to a separate model published by PATH. We ran sensitivity and scenario analyses to identify the inputs with the largest influence on the cost-effectiveness results. RESULTS: Our illustrative results assuming base case input assumptions for maternal vaccination ($3.50 per dose, 69% efficacy, 6 months protection) and infant mAb ($3.50 per dose, 77% efficacy, 5 months protection) showed that both interventions were cost-saving compared to status quo in around one-third of 133 LMICs, and had a cost per DALY averted below 0.5 times the national GDP per capita in the remaining LMICs. UNIVAC generated similar results to a separate model published by PATH. Cost-effectiveness results were most sensitive to changes in the price, efficacy and duration of protection of each strategy, and the rate (and cost) of RSV hospital admissions. CONCLUSIONS: Forthcoming RSV interventions (maternal vaccines and infant mAbs) are worth serious consideration in LMICs, but there is a good deal of uncertainty around several influential inputs, including intervention price, efficacy, and duration of protection. The UNIVAC decision-support model provides a framework for country teams to build consensus on data inputs, explore scenarios, and strengthen the local ownership and policy-relevance of results.

Evaluating the potential economic and health impact of rotavirus vaccination in 63 middle-income countries not eligible for Gavi funding: a modelling study.

BACKGROUND: Middle-income countries (MICs) that are not eligible for funding from Gavi, the Vaccine Alliance, have been slow to adopt rotavirus vaccines. Few studies have evaluated the cost-effectiveness and benefit-risk of rotavirus vaccination in these settings. We aimed to assess the potential economic and health impact of rotavirus vaccination in 63 MICs not eligible for funding from Gavi. METHODS: In this modelling study, we estimated the cost-effectiveness and benefit-risk of rotavirus vaccination in 63 MICs not eligible to Gavi funding. We used an Excel-based proportionate outcomes model with a finely disaggregated age structure to estimate the number of rotavirus gastroenteritis cases, clinic visits, hospitalisations, and deaths averted by vaccination in children younger than 5 years over a 10-year period. We calculated cost-effectiveness ratios (costs per disability-adjusted life-years averted compared with no vaccination) and benefit-risk ratios (number of hospitalisations due to rotavirus gastroenteritis averted per excess hospitalisations due to intussusception). We evaluated three alternative vaccines available globally (Rotarix, Rotavac, and Rotasiil) and used information from vaccine manufacturers regarding anticipated vaccine prices. We ran deterministic and probabilistic uncertainty analyses. FINDINGS: Over the period 2020-29, rotavirus vaccines could avert 77 million (95% uncertainty interval [UI] 51-103) cases of rotavirus gastroenteritis and 21 million (12-36) clinic visits, 3 million (1·4-5·6) hospitalisations, and 37 900 (25 900-55 900) deaths due to rotavirus gastroenteritis in 63 MICs not eligible for Gavi support. From a government perspective, rotavirus vaccination would be cost-effective in 48 (77%) of 62 MICs considered. The benefit-risk ratio for hospitalisations prevented versus those potentially caused by vaccination exceeded 250:1 in all countries. INTERPRETATION: In most MICs not eligible for Gavi funding, rotavirus vaccination has high probability to be cost-effective with a favourable benefit-risk profile. Policy makers should consider this new evidence when making or revisiting decisions on the use of rotavirus vaccines in their respective countries. FUNDING: Bill & Melinda Gates Foundation.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Modeling the cost-effectiveness of maternal acellular pertussis immunization (aP) in different socioeconomic settings: A dynamic transmission model of pertussis in three Brazilian states.

OBJECTIVES: Using dynamic transmission models we evaluated the health and cost outcomes of adding acellular pertussis (aP) vaccination of pregnant women to infant vaccination in three Brazilian states that represent different socioeconomic conditions. The primary objective was to determine whether the same model structure could be used to represent pertussis disease dynamics in differing socioeconomic conditions. METHODS: We tested three model structures (SIR, SIRS, SIRSIs) to represent population-level transmission in three socio-demographically distinct Brazilian states: São Paulo, Paraná and Bahia. Two strategies were evaluated: infant wP vaccination alone versus maternal aP immunization plus infant wP vaccination. Model projections for 2014-2029 include outpatient and inpatient pertussis cases, pertussis deaths, years of life lost, disability-adjusted life-years (DALYs) lost, and costs (in 2014 USD) of maternal aP vaccination, infant vaccination, and pertussis medical treatment. Incremental cost per DALY averted is presented from the perspective of the Brazilian National Health System. RESULTS: Based on goodness-of-fit statistics, the SIRSIs model fit best, although it had only a modest improvement in statistical quantitative assessments relative to the SIRS model. For all three Brazilian states, maternal aP immunization led to higher costs but also saved infant lives and averted DALYs. The 2014 USD cost/DALY averted was $3068 in Sao Paulo, $2962 in Parana, and $2022 in Bahia. These results were robust in sensitivity analyses with the incremental cost-effectiveness ratios exceeding per capita gross regional product only when the probability that a pertussis case is reported was assumed higher than base case implying more overt cases and deaths and therefore more medical costs. CONCLUSIONS: The same model structure fit all three states best, supporting the idea that the disease behaves similarly across different socioeconomic conditions. We also found that immunization of pregnant women with aP is cost-effective in diverse Brazilian states.

Cost-effectiveness of maternal pertussis immunization: Implications of a dynamic transmission model for low- and middle-income countries.

OBJECTIVE: This study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model. METHODS: We developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY). RESULTS: The dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90-95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model's time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage. CONCLUSION: A dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90-95%.

Comparison of static and dynamic models of maternal immunization to prevent infant pertussis in Brazil.

BACKGROUND: This paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile. METHODS: We defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models' different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated. RESULTS: The dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90-95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models' estimates over their different time horizons are compared at infant coverage < 90-95%, their projections fall in the same range. CONCLUSIONS: Static models may serve to explore an intervention's cost-effectiveness against infectious disease: the direction and principal drivers of change were the same in both models. When, however, an intervention too small to have significant herd immunity effects itself, such as maternal aP immunization, takes place against a background of vaccination in the rest of the population, a dynamic model is crucial to accurate estimates of cost-effectiveness. This finding is particularly important in the context of widely varying routine infant vaccination rates globally. CLINICAL TRIAL REGISTRY: Clinical Trial registry name and registration number: Not applicable.

Assessment of missed opportunities for vaccination (MOV) in Burkina Faso using the World Health Organization's revised MOV strategy: Findings and strategic considerations to improve routine childhood immunization coverage.

BACKGROUND: Despite the remarkable achievements of the Expanded Programme on Immunization (EPI) in Burkina Faso, numerous challenges remain, including missed opportunities for vaccination (MOV) which occur when people visit a health facility with at least one vaccine due according to the national immunization schedule, are free of contraindications, and leave without receiving all due vaccine doses. In 2016, we used the revised World Health Organization's (WHO) MOV strategy to assess the extent of and reasons for MOV in Burkina Faso. METHODS: We purposively selected 27 primary health facilities (PHFs) from the eight health districts with the highest absolute numbers of children who missed the first dose of measles-rubella (MR1) in 2015. We conducted exit interviews with caregivers of children aged 0-23 months, and requested health workers to complete a self-administered knowledge, attitudes and practices (KAP) questionnaire. RESULTS: A total of 489 caregivers were interviewed, of which 411 were eligible for inclusion in our analysis. Medical consultation (35%) and vaccination (24.5%) were the most frequent reasons for visiting PHFs. Among the 73% of children eligible for vaccination, 76% of vaccination opportunities were missed. Among eligible children, the percentage with MOV was significantly higher in those aged ≥12 months and also in those attending for a reason other than vaccination. A total of 248 health workers completed the KAP questionnaire. Of these, 70% (n = 168/239) considered their knowledge on immunization to be insufficient or outdated; 83% failed to correctly identify valid contraindications to vaccination. CONCLUSION: Addressing MOV offers the potential for substantial increases in vaccine coverage and equity, and ultimately reducing the burden of vaccine-preventable diseases (VPDs). This will require the implementation of a series of interventions aimed at improving community knowledge and practices, raising health workers' awareness, and fostering the integration of immunization with other health services.

Assessment of missed opportunities for vaccination in Kenyan health facilities, 2016.

BACKGROUND: In November 2016, the Kenya National Vaccines and Immunization Programme conducted an assessment of missed opportunities for vaccination (MOV) using the World Health Organization (WHO) MOV methodology. A MOV includes any contact with health services during which an eligible individual does not receive all the vaccine doses for which he or she is eligible. METHODS: The MOV assessment in Kenya was conducted in 10 geographically diverse counties, comprising exit interviews with caregivers and knowledge, attitudes, and practices (KAP) surveys with health workers. On the survey dates, which covered a 4-day period in November 2016, all health workers and caregivers visiting the selected health facilities with children <24 months of age were eligible to participate. Health facilities (n = 4 per county) were purposively selected by size, location, ownership, and performance. We calculated the proportion of MOV among children eligible for vaccination and with documented vaccination histories (i.e., from a home-based record or health facility register), and stratified MOV by age and reason for visit. Timeliness of vaccine doses was also calculated. RESULTS: We conducted 677 age-eligible children exit interviews and 376 health worker KAP surveys. Of the 558 children with documented vaccination histories, 33% were visiting the health facility for a vaccination visit and 67% were for other reasons. A MOV was seen in 75% (244/324) of children eligible for vaccination with documented vaccination histories, with 57% (186/324) receiving no vaccinations. This included 55% of children visiting for a vaccination visit and 93% visiting for non-vaccination visits. Timeliness for multi-dose vaccine series doses decreased with subsequent doses. Among health workers, 25% (74/291) were unable to correctly identify the national vaccination schedule for vaccines administered during the first year of life. Among health workers who reported administering vaccines as part of their daily work, 39% (55/142) reported that they did not always have the materials they needed for patients seeking immunization services, such as vaccines, syringes, and vaccination recording documents. CONCLUSIONS: The MOV assessment in Kenya highlighted areas of improvement that could reduce MOV. The results suggest several interventions including standardizing health worker practices, implementing an orientation package for all health workers, and developing a stock management module to reduce stock-outs of vaccines and vaccination-related supplies. To improve vaccination coverage and equity in all counties in Kenya, interventions to reduce MOV should be considered as part of an overall immunization service improvement plan.

Re-evaluating the potential impact and cost-effectiveness of rotavirus vaccination in 73 Gavi countries: a modelling study.

BACKGROUND: Previous studies have found rotavirus vaccination to be highly cost-effective in low-income countries. However, updated evidence is now available for several inputs (ie, rotavirus disease mortality rates, rotavirus age distributions, vaccine timeliness, and vaccine efficacy by duration of follow-up), new rotavirus vaccines have entered the market, vaccine prices have decreased, and cost-effectiveness thresholds have been re-examined. We aimed to provide updated cost-effectiveness estimates to inform national decisions about the new introduction and current use of rotavirus vaccines in Gavi countries. METHODS: We calculated the potential costs and effects of rotavirus vaccination for ten successive birth cohorts in 73 countries previously and currently eligible for Gavi support, compared with no vaccination. We used a deterministic cohort model to calculate numbers of rotavirus gastroenteritis cases, outpatient visits, hospitalisations, and deaths between birth and 5 years, with and without rotavirus vaccination. We calculated treatment costs from the government and societal perspectives. The primary outcome measure was the incremental cost-effectiveness ratio (discounted US$ per disability-adjusted life-year averted). Country-specific model input parameters were based on the scientific literature, published meta-analyses, and international databases. We ran deterministic and probabilistic uncertainty analyses. FINDINGS: Over the period 2018-27, rotavirus vaccination has the potential to prevent nearly 600 000 deaths in Gavi countries. Averted outpatient visits and hospitalisations could lead to treatment savings of approximately $484·1 million from the government perspective and $878·0 million from the societal perspective. The discounted dollars per disability-adjusted life-year averted has a very high probability (>90%) of being less than 0·5 times the gross domestic product per capita in 54 countries, and less than 1·0 times gross domestic product per capita in 63 countries. INTERPRETATION: Rotavirus vaccination continues to represent good value for money across most Gavi countries despite lower rotavirus mortality estimates and more stringent willingness-to-pay thresholds. FUNDING: Bill & Melinda Gates Foundation.

Opportunities to improve vaccination coverage in a country with a fledgling health system: Findings from an assessment of missed opportunities for vaccination among health center attendees-Timor Leste, 2016.

INTRODUCTION: Since its independence in 2002, Timor Leste has made significant strides in improving childhood vaccination coverage. However, coverage is still below national targets, and children continue to have missed opportunities for vaccination (MOV), when eligible children have contact with the health system but are not vaccinated. Timor Leste implemented the updated World Health Organization methodology for assessing MOV in 2016. METHODS: The MOV data collection included quantitative (caregiver exit interviews and health worker knowledge, attitudes, practices surveys (KAP)) and qualitative arms (focus group discussions (FGDs) with caregivers and health workers and in-depth interviews (IDIs) with health administrators). During a four-day period, health workers and caregivers with children <24 months of age attending the selected eight facilities in Dili Municipality were invited to participate. The researchers calculated the proportion of MOV and timeliness of vaccine doses among children with documented vaccination histories (i.e., from a home-based record or facility register) and thematically analyzed the qualitative data. RESULTS: Researchers conducted 365 caregiver exit interviews, 169 health worker KAP surveys, 4 FGDs with caregivers, 2 FGDs with health workers, and 2 IDIs with health administrators. Among eligible children with documented vaccination histories (n = 199), 41% missed an opportunity for vaccination. One-third of health workers (33%) believed their knowledge of immunization practices to be insufficient. Qualitative results showed vaccines were not available at all selected health facilities, and some facilities reported problems with their cold chain equipment. CONCLUSION: This study demonstrates that many children in Timor Leste miss opportunities for vaccination during health service encounters. Potential interventions to reduce MOV include training of health workers, improving availability of vaccines at more health facilities, and replacing unusable cold chain equipment. Timor Leste should continue to scale up successful MOV interventions beyond Dili Municipality to improve vaccination coverage nationally and strengthen the health system overall.

ProVac Global Initiative: a vision shaped by ten years of supporting evidence-based policy decisions.

INTRODUCTION: The Pan American Health Organization (PAHO) created the ProVac Initiative in 2004 with the goal of strengthening national technical capacity to make evidence-based decisions on new vaccine introduction, focusing on economic evaluations. In view of the 10th anniversary of the ProVac Initiative, this article describes its progress and reflects on lessons learned to guide the next phase. METHODS: We quantified the output of the Initiative's capacity-building efforts and critically assess its progress toward achieving the milestones originally proposed in 2004. Additionally, we reviewed how country studies supported by ProVac have directly informed and strengthened the deliberations around new vaccine introduction. RESULTS: Since 2004, ProVac has conducted four regional workshops and supported 24 health economic analyses in 15 Latin American and Caribbean countries. Five Regional Centers of Excellence were funded, resulting in six operational research projects and nine publications. Twenty four decisions on new vaccine introductions were supported with ProVac studies. Enduring products include the TRIVAC and CERVIVAC cost-effectiveness models, the COSTVAC program costing model, methodological guides, workshop training materials and the OLIVES on-line data repository. Ten NITAGs were strengthened through ProVac activities. DISCUSSION: The evidence accumulated suggests that initiatives with emphasis on sustainable training and direct support for countries to generate evidence themselves, can help accelerate the introduction of the most valuable new vaccines. International and Regional Networks of Collaborators are necessary to provide technical support and tools to national teams conducting analyses. Timeliness, integration, quality and country ownership of the process are four necessary guiding principles for national economic evaluations to have an impact on policymaking. It would be an asset to have a model that offers different levels of complexity to choose from depending on the vaccine being evaluated, the availability of data, and the time frame of the decision. CONCLUSION: Decision support for new vaccine introduction in low- and middle-income countries is critical to maximizing the efficiency and impact of vaccination programs. Global technical cooperation will be required. In the future, PAHO and WHO have an opportunity to expand the reach of the ProVac philosophy, models, and methods to additional regions and countries requiring real-time support. The ProVac Global Initiative is proposed as an effective mechanism to do so.

Evaluating the potential risks and benefits of infant rotavirus vaccination in England.

Rotarix(®), a vaccine for the prevention of gastroenteritis in young children, was introduced in England in July 2013. At around this time, an elevated risk of intussusception (a cause of bowel obstruction) was reported among infants vaccinated in Australia and the USA. A risk-benefit analysis compared potential vaccine-related risks (additional intussusception admissions and deaths) with estimated vaccine benefits (prevented rotavirus general practitioner visits, emergency visits, admissions and deaths) in the 2012 birth cohort. Detailed data from England included the incidence of intussusception events aged <2 years by week of age, the coverage of vaccination aged <2 years by week of age, and the incidence of rotavirus gastroenteritis (RVGE) events aged <5 years by week of age. Recent estimates of vaccine-related risk from Australia were applied during the 1-21 day period after the first and second dose of vaccination. Rotarix(®) is estimated to cause one additional intussusception admission in every 18,551 vaccinated English infants (5th and 95th percentiles, 6728-93,952), equivalent to 35 (7-98) additional intussusception admissions each year. The vaccine is estimated to prevent three rotavirus deaths, 13,000 rotavirus admissions, 27,000 rotavirus emergency visits and 74,000 rotavirus GP consultations in children aged <5 years, and lead to annual savings of over £11 million, each year. We estimate 375 (136-1900) fewer RVGE admissions for every additional intussusception admission, and 88 (18-852) fewer RVGE deaths for every additional intussusception death. The estimated benefits of Rotarix(®) vaccination would greatly exceed the potential risk in England.

TRIVAC decision-support model for evaluating the cost-effectiveness of Haemophilus influenzae type b, pneumococcal and rotavirus vaccination.

The TRIVAC decision support model has been used widely in Latin America and other regions to help national teams evaluate the cost-effectiveness of Haemophilus influenzae type b (Hib) vaccine, pneumococcal conjugate vaccine (PCV) and rotavirus vaccine (RV). We describe the structure and functioning of this model, and identify the parameters with the greatest influence on the results. The TRIVAC model is a spreadsheet software program that calculates incremental cost-effectiveness ratios (ICERs) and other indicators for three childhood vaccines (Hib, PCV and RV) utilising parameters such as demography, disease burden, vaccine costs, vaccine coverage, vaccine efficacy, health service utilisation and costs. There is a good deal of uncertainty about the local values of many of the parameters that have most influence on the cost-effectiveness of these new vaccines. Cost-effectiveness models can be used to explore the implications of different values of these parameters. However, for such models to be seen as relevant and helpful by decision-makers, they need to be transparent, flexible, easy to use, and embedded in a process which is owned and led by national teams. In this paper the key drivers of cost-effectiveness in the model are identified by one-way sensitivity analyses, run for each vaccine in 147 countries. The data used are mainly from standard international sources and the published literature. The primary indicator was the discounted cost per Disability Adjusted Life-Year (DALY) averted, from a government perspective, over a 20-year period (2013-2032). For all three vaccines, the ICER was most sensitive to changes in relative coverage (the coverage of the children who would have become diseased or, more importantly, died if the population had not been vaccinated, as a % of overall national coverage) and the herd effect multiplier. Other influential parameters for all three vaccines were: the incidence and case fatality of disease, the baseline trend in disease mortality in the absence of vaccination, vaccine efficacy, vaccine price and the % decline in vaccine price per year. Important vaccine-specific parameters included the cost of Hib meningitis sequelae, PCV serotype coverage and the rotavirus gastro-enteritis (RVGE) admission rate. While vaccine efficacy, herd effects, disease mortality and vaccine price are commonly cited as important drivers of cost-effectiveness, this analysis highlights the potentially important influence of relative coverage, a parameter rarely considered in models of vaccine impact and cost-effectiveness.

Impact and cost-effectiveness of Haemophilus influenzae type b conjugate vaccination in India.

OBJECTIVE: To estimate the potential health impact and cost-effectiveness of nationwide Haemophilus influenzae type b (Hib) vaccination in India. STUDY DESIGN: A decision support model was used, bringing together estimates of demography, epidemiology, Hib vaccine effectiveness, Hib vaccine costs, and health care costs. Scenarios favorable and unfavorable to the vaccine were evaluated. State-level analyses indicate where the vaccine might have the greatest impact and value. RESULTS: Between 2012 and 2031, Hib conjugate vaccination is estimated to prevent over 200 000 child deaths (∼1% of deaths in children <5 years of age) in India at an incremental cost of US$127 million per year. From a government perspective, state-level cost-effectiveness ranged from US$192 to US$1033 per discounted disability adjusted life years averted. With the inclusion of household health care costs, cost-effectiveness ranged from US$155-US$939 per discounted disability adjusted life year averted. These values are below the World Health Organization thresholds for cost effectiveness of public health interventions. CONCLUSIONS: Hib conjugate vaccination is a cost-effective intervention in all States of India. This conclusion does not alter with plausible changes in key parameters. Although investment in Hib conjugate vaccination would significantly increase the cost of the Universal Immunization Program, about 15% of the incremental cost would be offset by health care cost savings. Efforts should be made to expedite the nationwide introduction of Hib conjugate vaccination in India.

Potential intussusception risk versus health benefits from rotavirus vaccination in Latin America.

BACKGROUND: With the recent postlicensure identification of an increased risk of intussusception with rotavirus vaccine, the 14 Latin American countries currently using rotavirus vaccine must now weigh the health benefits versus risks to assess whether to continue vaccination. To inform policy considerations, we estimated excess intussusception cases and mortality potentially caused by rotavirus vaccine for each of the 14 countries and compared these estimates to hospitalizations and deaths expected to be averted through vaccination. METHODS: We used regional rotavirus disease burden and rotavirus vaccine efficacy data, global natural intussusception and regional rotavirus vaccine-related risk estimates, and country-specific diphtheria, tetanus, and pertussus vaccination coverage rates to estimate rotavirus vaccine coverage rates. We performed a probabilistic sensitivity analysis to account for uncertainty in these parameters. RESULTS: For an aggregate hypothetical birth cohort of 9.5 million infants in these 14 countries, rotavirus vaccine would annually prevent 144 746 (90% confidence interval [CI], 128 821-156 707) hospitalizations and 4124 deaths (90% CI, 3740-4239) due to rotavirus in their first 5 years of life but could cause an additional 172 hospitalizations (90% CI, 126-293) and 10 deaths (90% CI, 6-17) due to intussusception, yielding benefit-risk ratios for hospitalization and death of 841:1 (90% CI, 479:1 to 1142:1) and 395:1 (90% CI, 207:1 to 526:1), respectively. In an uncertainty analysis using 10 000 simulations of our probabilistic parameters, in comparing rotavirus disease averted to intussusception events caused, the hospitalization ratio was never below 100:1, and our death ratio fell below 100:1 only once. CONCLUSIONS: The health benefits of vaccination far outweigh the short-term risks and support continued rotavirus vaccination in Latin America.

A person based formula for allocating commissioning funds to general practices in England: development of a statistical model.

OBJECTIVES: To develop a formula for allocating resources for commissioning hospital care to all general practices in England based on the health needs of the people registered in each practice DESIGN: Multivariate prospective statistical models were developed in which routinely collected electronic information from 2005-6 and 2006-7 on individuals and the areas in which they lived was used to predict their costs of hospital care in the next year, 2007-8. Data on individuals included all diagnoses recorded at any inpatient admission. Models were developed on a random sample of 5 million people and validated on a second random sample of 5 million people and a third sample of 5 million people drawn from a random sample of practices. SETTING: All general practices in England as of 1 April 2007. All NHS inpatient admissions and outpatient attendances for individuals registered with a general practice on that date. SUBJECTS: All individuals registered with a general practice in England at 1 April 2007. MAIN OUTCOME MEASURES: Power of the statistical models to predict the costs of the individual patient or each practice's registered population for 2007-8 tested with a range of metrics (R(2) reported here). Comparisons of predicted costs in 2007-8 with actual costs incurred in the same year were calculated by individual and by practice. RESULTS: Models including person level information (age, sex, and ICD-10 codes diagnostic recorded) and a range of area level information (such as socioeconomic deprivation and supply of health facilities) were most predictive of costs. After accounting for person level variables, area level variables added little explanatory power. The best models for resource allocation could predict upwards of 77% of the variation in costs at practice level, and about 12% at the person level. With these models, the predicted costs of about a third of practices would exceed or undershoot the actual costs by 10% or more. Smaller practices were more likely to be in these groups. CONCLUSIONS: A model was developed that performed well by international standards, and could be used for allocations to practices for commissioning. The best formulas, however, could predict only about 12% of the variation in next year's costs of most inpatient and outpatient NHS care for each individual. Person-based diagnostic data significantly added to the predictive power of the models.

Development of paediatric quality of inpatient care indicators for low-income countries - A Delphi study.

BACKGROUND: Indicators of quality of care for children in hospitals in low-income countries have been proposed, but information on their perceived validity and acceptability is lacking. METHODS: Potential indicators representing structural and process aspects of care for six common conditions were selected from existing, largely qualitative WHO assessment tools and guidelines. We employed the Delphi technique, which combines expert opinion and existing scientific information, to assess their perceived validity and acceptability. Panels of experts, one representing an international panel and one a national (Kenyan) panel, were asked to rate the indicators over 3 rounds and 2 rounds respectively according to a variety of attributes. RESULTS: Based on a pre-specified consensus criteria most of the indicators presented to the experts were accepted: 112/137(82%) and 94/133(71%) for the international and local panels respectively. For the other indicators there was no consensus; none were rejected. Most indicators were rated highly on link to outcomes, reliability, relevance, actionability and priority but rated more poorly on feasibility of data collection under routine conditions. There was moderate to substantial agreement between the two panels of experts. CONCLUSIONS: This Delphi study provided evidence for the perceived usefulness of most of a set of measures of quality of hospital care for children proposed for use in low-income countries. However, both international and local experts expressed concerns that data for many process-based indicators may not currently be available. The feasibility of widespread quality assessment and responsiveness of indicators to intervention should be examined as part of continued efforts to improve approaches to informative hospital quality assessment.

Cost-effectiveness of rotavirus vaccination in peru.

BACKGROUND: There are plans to introduce the oral rotavirus vaccine Rotarix (GlaxoSmithKline), 1 of 2 recently developed vaccines against rotavirus, in Peru. METHODS: We modeled the cost-effectiveness of adding a rotavirus vaccine to the Peruvian immunization program under 3 scenarios for the timing of vaccination: (1) strictly according to schedule, at 2 and 4 months of age (on time); (2) distributed around the target ages in the same way as the actual timings in the program (flexible); and (3) flexible but assuming vaccination is not initiated for infants >12 weeks of age (restricted). We assumed an introductory price of US $7.50 per dose, and varied the annual rate of price decrease in sensitivity analyses. RESULTS: The discounted cost per disability-adjusted life-year averted for restricted, flexible, and on-time schedules was $621, $615, and $581, respectively. For each of the 3 scenarios, the percentage reduction in deaths due to rotavirus infection was 53%, 66%, and 69%, respectively. The cost per disability-adjusted life-year averted for alternative "what-if" scenarios ranged from $229 (assuming a 1-dose schedule, administered on time) to $1491 (assuming a 2-dose schedule, with half the baseline vaccine efficacy rates and a restricted timing policy). CONCLUSIONS: On the basis of current World Health Organization guidelines, rotavirus vaccination represents a highly cost-effective intervention in Peru. Withholding the vaccine from children who present for their first dose after 12 weeks of age would reduce the number of deaths averted by approximately 20%. A single dose may be more cost-effective than 2 doses, but more evidence on the protection conferred by a single dose is required.

A new measure of acute physiological derangement for patients with exacerbations of obstructive airways disease: the COPD and Asthma Physiology Score.

BACKGROUND: Decisions about how to treat patients with acute exacerbations of obstructive airways disease-chronic obstructive pulmonary disease (COPD), asthma or mixed diagnoses-often require an understanding of prognosis. This depends on the severity of the acute deterioration and the patient's functional reserve. There are currently no validated disease-specific scores that measure the severity of the acute exacerbation. OBJECTIVE: To develop an acute physiology score for exacerbations of obstructive airways disease. DESIGN: Secondary analysis of a high-quality clinical database, the Case Mix Programme Database. SETTING: One hundred and sixty-eight adult, general critical care units in England, Wales and Northern Ireland. RESULTS: A total of 8527 patients with obstructive airways disease were identified with a mean (SD) age of 65.9 (9.7) years and hospital mortality of 35.5%. The COPD and Asthma Physiology Score (CAPS) was developed using logistic regression. The CAPS included eight variables: heart rate, mean arterial blood pressure, pH, sodium, urea, creatinine, albumin and white blood cell count. The score had fair discrimination with an area under the receiver operating characteristic curve of 0.718. This performance was reproduced in a further validation dataset of 7957 patients. The discrimination of the CAPS in these validation data exceeded that of the acute physiology scores from APACHE II and III and the physiological components of SAPS II. CONCLUSION: The CAPS can be used to estimate the prognostic impact of physiological derangements accompanying an acute exacerbation of obstructive airways disease and has the potential for even greater predictive performance when combined with measures of a patient's functional reserve.