Development of a Value Assessment Framework for Pediatric Health Technologies Using Multicriteria Decision Analysis: Expanding the Value Lens for Funding Decision Making.

OBJECTIVES: A health technology assessment (HTA) does not systematically account for the circumstances and needs of children and youth. To supplement HTA processes, we aimed to develop a child-tailored value assessment framework using a multicriteria decision analysis approach. METHODS: We constructed a multicriteria-decision-analysis-based model in multiple phases to create the Comprehensive Assessment of Technologies for Child Health (CATCH) framework. Using a modified Delphi process with stakeholders having broad disciplinary and geographic variation (N = 23), we refined previously generated criteria and developed rank-based weights. We established a criterion-pertinent scoring rubric for assessing incremental benefits of new drugs. Three clinicians independently assessed comprehension by pilotscoring 9 drugs. We then validated CATCH for 2 childhood cancer therapies through structured deliberation with an expert panel (N = 10), obtaining individual scores, consensus scores, and verbal feedback. Analyses included descriptive statistics, thematic analysis, exploratory disagreement indices, and sensitivity analysis. RESULTS: The modified Delphi process yielded 10 criteria, based on absolute importance/relevance and agreed importance (median disagreement indices = 0.34): Effectiveness, Child-specific Health-related Quality of Life, Disease Severity, Unmet Need, Therapeutic Safety, Equity, Family Impacts, Life-course Development, Rarity, and Fair Share of Life. Pilot scoring resulted in adjusted criteria definitions and more precise score-scaling guidelines. Validation panelists endorsed the framework's key modifiers of value. Modes of their individual prescores aligned closely with deliberative consensus scores. CONCLUSIONS: We iteratively developed a value assessment framework that captures dimensions of child-specific health and nonhealth gains. CATCH could improve the richness and relevance of HTA decision making for children in Canada and comparable health systems.

Access to novel drugs and therapeutics for children and youth: Eliciting citizens' values to inform public funding decisions.

INTRODUCTION: The unique evidentiary, economic and ethical challenges associated with health technology assessment (HTA) of precision therapies limit access to novel drugs and therapeutics for children and youth, for whom such challenges are amplified. We elicited citizens' perspectives about values-based criteria relevant to the assessment of paediatric precision therapies to inform the development of a child-tailored HTA framework. METHODS: We held four citizen panels virtually in May-June 2021, informed by a plain-language citizen brief summarizing global and local evidence about the challenges, policy and programmatic options and implementation strategies related to enhancing access to precision therapies for Canadian children and youth. Panellists were recruited through a nationally representative database, medical/patient networks and social media. We inductively coded and thematically analysed panel transcripts to generate themes and identify priority values. RESULTS: The perspectives of panellists (n = 45) coalesced into four overlapping themes, with attendant subthemes, relevant to a child-tailored HTA framework: (1) Childhood Distinctions: vulnerability, 'fair innings', future potential, family impacts; (2) Voice: agency of children and youth; lived versus no lived experience; (3) One versus Many: disease severity, rarity, equity, unmet need and (4) Health System Governance: funding, implementation inequities, effectiveness and safety. Participants broadly agreed that childhood distinctions, particularly family impacts, justify child-tailored HTA. Dissent arose over whose voice should inform HTA and how such perspectives are best incorporated. CONCLUSIONS: Citizens can offer unique insights into criteria relevant to the development or revision of HTA frameworks to capture holistic, societally responsive dimensions of value attached to unique contexts or populations, including children. Balancing the hopes and expectations of patients and caregivers for access to expensive but potential life-altering therapies against the opportunity costs borne by encompassing health systems is a fundamental challenge that will require rigorous methods to elicit, weigh and reconcile varied views. PATIENT OR PUBLIC CONTRIBUTION: A patient advocate served on the steering committee of this study and co-authored this article. Key informants for the Citizen Brief included patient advocates and caregivers; a separate patient advocate reviewed the Brief before dissemination. Qualitative and quantitative data were collected from the general public and caregivers of children, with written consent.

Understanding integrated HPV testing and treatment of pre-cancerous cervical cancer in Burkina Faso, Cote d'Ivoire, Guatemala and Philippines: study protocol.

BACKGROUND: Many low- and-middle-income countries are disproportionately burdened by cervical cancer, resulting in high morbidity and mortality. HPV-DNA testing coupled with treatment with thermal ablation is a recommended screening and precancer treatment strategy, but not enough is known about how this can be effectively implemented in the context of integrated services. The (Scale Up Cervical Cancer Elimination by Secondary prevention Strategy, (SUCCESS) project is conducting a study to understand this approach, integrated into existing women's health services in Burkina Faso, Cote d'Ivoire, Guatemala, and the Philippines (2020-2024). METHODS: A hybrid effectiveness-implementation type III mixed-methods observational study design is used to assess feasibility, acceptability, and costs of integrated service delivery in 10 sites per country, selected considering urban/rural location, facility level, onsite/offsite laboratories, and health services type. In each country, a sample size of 2227 women aged 25-49 years will be enrolled with about 20% being women living with HIV. The primary outcome is proportion of HPV positive women completing precancer treatment, if eligible, within three months of screening. Data collection and analysis includes; facility and client exit surveys, key informant and client interviews, registries and project records extractions, and costing data analysis. Analysis includes descriptive statistics, context description, thematic analysis, and document analysis. Quantitative analyses will be stratified by participant's HIV status. DISCUSSION: Recruitment of study participants started in April 2022 (Burkina Faso and Côte d'Ivoire) and August 2022 (Guatemala and the Philippines). Enrolment targets for women screened, client exit, in-depth and key informant interviews conducted were reached in Burkina Faso and Cote d'Ivoire in November 2022. Guatemala and Philippines are expected to complete enrolment by June 2023. Follow-up of study Participants 12-months post-treatment is ongoing and is expected to be completed for all countries by August 2024. In LMICs, integrating cervical cancer secondary prevention services into other health services will likely require specific rather than incidental recruitment of women for screening. Reconfiguration of laboratory infrastructure and planning for sample management must be made well in advance to meet induced demand for screening. Trail Registration ClinicalTrials.Gov ID: NCT05133661 (24/11/2021).

Comprehensive approach to costing cervical cancer prevention and control: a case study in the United Republic of Tanzania using the Cervical Cancer Prevention and Control Costing (C4P) tool.

BACKGROUND: The World Health Organization (WHO) has developed a costing tool, the Cervical Cancer Prevention and Control Costing (C4P) tool, to estimate the comprehensive cost of cervical cancer primary, secondary and tertiary prevention in low- and middle-income countries. The tool was piloted in the United Republic of Tanzania, a country with a high incidence of cervical cancer with 62.5 cases per 100,000 women in 2020. This paper presents the costing tool methods as well as the results from the pilot in Tanzania. METHODS: The C4P tool estimates the incremental costs of cervical cancer prevention and control programmes. It estimates the financial (monetary costs to the government) and economic costs (opportunity costs). For the pilot, the study team collected data on costs and programme assumptions for human papillomavirus (HPV) vaccination of 14-year-old girls and scaling up of cervical cancer screening (visual inspection with acetic acid and HPV-DNA testing) and treatment for women for 2020-2024. Assumptions were made on how vaccination coverage would increase over the 5 years as well as developing additional screening and treatment capacity through health personnel training and infrastructure strengthening. RESULTS: The total financial and economic costs of the comprehensive programme during 2020-2024 are projected to be US$68 million and US$124 million, respectively. The financial and economic costs of a fully immunized girl with HPV vaccine are estimated to be US$6.68 and US$17.31, respectively, while the costs per woman screened for cervical cancer are, on average, US$4.02 and US$5.83, respectively; US$6.44 and US$9.37 for pre-cancer treatment, respectively; and US$101 and US$107 for diagnosis of invasive cancer, respectively. The cost of treating and managing invasive cancer range from US$7.05 and US$7.83 for outpatient palliative care to US$800.21 and US$893.80 for radiotherapy, respectively. CONCLUSIONS: The C4P costing tool can assist national cervical cancer programmes to estimate monetary resources needed as well as opportunity costs of reducing national cervical cancer incidence through primary, secondary and tertiary prevention.

Costs, affordability, and feasibility of an essential package of cancer control interventions in low-income and middle-income countries: key messages from Disease Control Priorities, 3rd edition.

Investments in cancer control--prevention, detection, diagnosis, surgery, other treatment, and palliative care--are increasingly needed in low-income and particularly in middle-income countries, where most of the world's cancer deaths occur without treatment or palliation. To help countries expand locally appropriate services, Cancer (the third volume of nine in Disease Control Priorities, 3rd edition) developed an essential package of potentially cost-effective measures for countries to consider and adapt. Interventions included in the package are: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioids. These interventions would cost an additional US$20 billion per year worldwide, constituting 3% of total public spending on health in low-income and middle-income countries. With implementation of an appropriately tailored package, most countries could substantially reduce suffering and premature death from cancer before 2030, with even greater improvements in later decades.

Characterizing measles transmission in India: a dynamic modeling study using verbal autopsy data.

BACKGROUND: Decreasing trends in measles mortality have been reported in recent years. However, such estimates of measles mortality have depended heavily on assumed regional measles case fatality risks (CFRs) and made little use of mortality data from low- and middle-income countries in general and India, the country with the highest measles burden globally, in particular. METHODS: We constructed a dynamic model of measles transmission in India with parameters that were empirically inferred using spectral analysis from a time series of measles mortality extracted from the Million Death Study, an ongoing longitudinal study recording deaths across 2.4 million Indian households and attributing causes of death using verbal autopsy. The model was then used to estimate the measles CFR, the number of measles deaths, and the impact of vaccination in 2000-2015 among under-five children in India and in the states of Bihar and Uttar Pradesh (UP), two states with large populations and the highest numbers of measles deaths in India. RESULTS: We obtained the following estimated CFRs among under-five children for the year 2005: 0.63% (95% confidence interval (CI): 0.40-1.00%) for India as a whole, 0.62% (0.38-1.00%) for Bihar, and 1.19% (0.80-1.75%) for UP. During 2000-2015, we estimated that 607,000 (95% CI: 383,000-958,000) under-five deaths attributed to measles occurred in India as a whole. If no routine vaccination or supplemental immunization activities had occurred from 2000 to 2015, an additional 1.6 (1.0-2.6) million deaths for under-five children would have occurred across India. CONCLUSIONS: We developed a data- and model-driven estimation of the historical measles dynamics, CFR, and vaccination impact in India, extracting the periodicity of epidemics using spectral and coherence analysis, which allowed us to infer key parameters driving measles transmission dynamics and mortality.

Adding interventions to mass measles vaccinations in India.

OBJECTIVE: To quantify the impact on mortality of offering a hypothetical set of technically feasible, high-impact interventions for maternal and child survival during India's 2010-2013 measles supplementary immunization activity. METHODS: We developed Lives Saved Tool models for 12 Indian states participating in the supplementary immunization, based on state- and sex-specific data on mortality from India's Million Deaths Study and on health services coverage from Indian household surveys. Potential add-on interventions were identified through a literature review and expert consultations. We quantified the number of lives saved for a campaign offering measles vaccine alone versus a campaign offering measles vaccine with six add-on interventions (nutritional screening and complementary feeding for children, vitamin A and zinc supplementation for children, multiple micronutrient and calcium supplementation in pregnancy, and free distribution of insecticide-treated bednets). FINDINGS: The measles vaccination campaign saved an estimated 19 016 lives of children younger than 5 years. A hypothetical campaign including measles vaccine with add-on interventions was projected to save around 73 900 lives (range: 70 200-79 300), preventing 73 700 child deaths (range: 70 000-79 000) and 300 maternal deaths (range: 200-400). The most effective interventions in the whole package were insecticide-treated bednets, measles vaccine and preventive zinc supplementation. Girls accounted for 66% of expected lives saved (12 712/19 346) for the measles vaccine campaign, and 62% of lives saved (45 721/74 367) for the hypothetical campaign including add-on interventions. CONCLUSION: In India, a measles vaccination campaign including feasible, high-impact interventions could substantially increase the number of lives saved and mitigate gender-related inequities in child mortality.

Implementation factors of non-communicable disease policies and programmes for children and youth in low-income and middle-income countries: a systematic review.

INTRODUCTION: Despite declared life-course principles in non-communicable disease (NCD) prevention and management, worldwide focus has been on older rather than younger populations. However, the burden from childhood NCDs has mounted; particularly in low-income and middle-income countries (LMICs). There is limited knowledge regarding the implementation of paediatric NCD policies and programmes in LMICs, despite their disproportionate burden of morbidity and mortality. We aimed to understand the barriers to and facilitators of paediatric NCD policy and programme implementation in LMICs. METHODS: We systematically searched medical databases, Web of Science and WHOLIS for studies on paediatric NCD policy and programme implementation in LMICs. Screening and quality assessment were performed independently by researchers, using consensus to resolve differences. Data extraction was conducted within the WHO health system building-blocks framework. Narrative thematic synthesis was conducted. RESULTS: 93 studies (1992-2020) were included, spanning 86 LMICs. Most were of moderate or high quality. 78% reported on paediatric NCDs outside the four major NCD categories contributing to the adult burden. Across the framework, more barriers than facilitators were identified. The most prevalently reported factors were related to health service delivery, with system fragmentation impeding the continuity of age-specific NCD care. A significant facilitator was intersectoral collaborations between health and education actors to deliver care in trusted community settings. Non-health factors were also important to paediatric NCD policies and programmes, such as community stakeholders, sociocultural support to caregivers and school disruptions. CONCLUSIONS: Multiple barriers prevent the optimal implementation of paediatric NCD policies and programmes in LMIC health systems. The low sociopolitical visibility of paediatric NCDs limits their prioritisation, resulting in fragmented service delivery and constraining the integration of programmes across key sectors impacting children, including health, education and social services. Implementation research is needed to understand specific contextual solutions to improve access to paediatric NCD services in diverse LMIC settings.

Benefits and harms of cervical screening, triage and treatment strategies in women living with HIV.

To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform ('Policy1-Cervix-HIV') to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7-33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3-5 years.

Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population.

In 2020, the World Health Organization (WHO) launched a strategy to eliminate cervical cancer as a public health problem. To support the strategy, the WHO published updated cervical screening guidelines in 2021. To inform this update, we used an established modeling platform, Policy1-Cervix, to evaluate the impact of seven primary screening scenarios across 78 low- and lower-middle-income countries (LMICs) for the general population of women. Assuming 70% coverage, we found that primary human papillomavirus (HPV) screening approaches were the most effective and cost-effective, reducing cervical cancer age-standardized mortality rates by 63-67% when offered every 5 years. Strategies involving triaging women before treatment (with 16/18 genotyping, cytology, visual inspection with acetic acid (VIA) or colposcopy) had close-to-similar effectiveness to HPV screening without triage and fewer pre-cancer treatments. Screening with VIA or cytology every 3 years was less effective and less cost-effective than HPV screening every 5 years. Furthermore, VIA generated more than double the number of pre-cancer treatments compared to HPV. In conclusion, primary HPV screening is the most effective, cost-effective and efficient cervical screening option in LMICs. These findings have directly informed WHO's updated cervical screening guidelines for the general population of women, which recommend primary HPV screening in a screen-and-treat or screen-triage-and-treat approach, starting from age 30 years with screening every 5 years or 10 years.

The use of cost-effectiveness analysis for pediatric immunization in developing countries.

CONTEXT: Developing countries face critical choices for introducing needed, effective, but expensive new vaccines, especially given the accelerated need to decrease the mortality of children under age five and the increased immunization resources available from international donors. Cost-effectiveness analysis (CEA) is a tool that decision makers can use for efficiently allocating expanding resources. Its use in developing countries, however, lags behind that in industrialized countries. METHODS: We explored how CEA could be made more relevant to immunization policymaking in developing countries by identifying the limitations for using CEA in developing countries and the impact of donor funding on the CEA estimation. We conducted a comprehensive literature search using formal search protocols and hand searching indexed and gray literature sources. We then systematically summarized the application of CEA in industrialized and developing countries through thematic analysis, focusing on pediatric immunization and methodological and contextual issues relevant to developing countries. FINDINGS: Industrialized and developing countries use CEA differently. The use of the Disability-Adjusted Life Year (DALY) outcome measure and an alternative generalized cost-effectiveness analysis approach is restricted to developing countries. In pediatric CEAs, the paucity of evaluations and the lack of attention to overcoming the methodological limitations pertinent to children's cognitive and development distinctiveness, such as discounting and preference characterization, means that pediatric interventions may be systematically understudied and undervalued. The ability to generate high-quality CEA evidence in child health is further threatened by an inadequate consideration of the impact of donor funding (such as GAVI immunization funding) on measurement uncertainty and the determination of opportunity cost. CONCLUSIONS: Greater attention to pediatric interventions and donor funding in the conduct of CEA could lead to better policies and thus more worthwhile and good-value programs to benefit children's health in developing countries.

Clinical impact and cost-effectiveness of integrating smoking cessation into lung cancer screening: a microsimulation model.

BACKGROUND: Low-dose computed tomography (CT) screening can reduce lung cancer mortality in people at high risk; adding a smoking cessation intervention to screening could further improve screening program outcomes. This study aimed to assess the impact of adding a smoking cessation intervention to lung cancer screening on clinical outcomes, costs and cost-effectiveness. METHODS: Using the OncoSim-Lung mathematical microsimulation model, we compared the projected lifetime impact of a smoking cessation intervention (nicotine replacement therapy, varenicline and 12 wk of counselling) in the context of annual low-dose CT screening for lung cancer in people at high risk to lung cancer screening without a cessation intervention in Canada. The simulated population consisted of Canadians born in 1940-1974; lung cancer screening was offered to eligible people in 2020. In the base-case scenario, we assumed that the intervention would be offered to smokers up to 10 times; each intervention would achieve a 2.5% permanent quit rate. Sensitivity analyses varied key model inputs. We calculated incremental cost-effectiveness ratios with a lifetime horizon from the health system's perspective, discounted at 1.5% per year. Costs are in 2019 Canadian dollars. RESULTS: Offering a smoking cessation intervention in the context of lung cancer screening could lead to an additional 13% of smokers quitting smoking. It could potentially prevent 12 more lung cancers and save 200 more life-years for every 1000 smokers screened, at a cost of $22 000 per quality-adjusted life-year (QALY) gained. The results were most sensitive to quit rate. The intervention would cost over $50 000 per QALY gained with a permanent quit rate of less than 1.25% per attempt. INTERPRETATION: Adding a smoking cessation intervention to lung cancer screening is likely cost-effective. To optimize the benefits of lung cancer screening, health care providers should encourage participants who still smoke to quit smoking.

Distributional benefits of tobacco tax and smoke-free workplaces in China: A modeling study.

BACKGROUND: Tobacco taxation and smoke-free workplaces reduce smoking, tobacco-related premature deaths and associated out-of-pocket health care expenditures. We examine the distributional consequences of a price increase in tobacco products through an excise tax hike, and of an implementation of smoke-free workplaces, in China. METHODS: We use extended cost-effectiveness analysis (ECEA) to evaluate, across income quintiles of the male population (the large majority of Chinese smokers), the premature deaths averted, the change in tax revenues generated, and the financial risk protection procured (eg, poverty cases averted, defined as the number of individuals no longer facing tobacco-related out-of-pocket expenditures for disease treatment, that would otherwise impoverish them), that would follow a 75% increase in cigarette prices through substantial increments in excise tax fully passed onto consumers, and a nationwide total implementation of workplace smoking bans. RESULTS: A 75% increase in cigarette prices would avert about 24 million premature deaths among the current Chinese male population, with a third among the bottom income quintile, increase additional tax revenues by US$ 46 billion annually, and prevent around 9 million poverty cases, 19% of which among the bottom income quintile. Implementation of smoking bans in workplaces would avert about 12 million premature deaths, with a fifth among the bottom income quintile, decrease tax revenues by US$ 7 billion annually, and prevent around 4 million poverty cases, 12% of which among the bottom income quintile. CONCLUSIONS: Increased excise taxes on tobacco products and workplace smoking bans can procure large health and economic benefits to the Chinese population, especially among the poor.

Controlling measles using supplemental immunization activities: a mathematical model to inform optimal policy.

BACKGROUND: The Measles & Rubella Initiative, a broad consortium of global health agencies, has provided support to measles-burdened countries, focusing on sustaining high coverage of routine immunization of children and supplementing it with a second dose opportunity for measles vaccine through supplemental immunization activities (SIAs). We estimate optimal scheduling of SIAs in countries with the highest measles burden. METHODS: We develop an age-stratified dynamic compartmental model of measles transmission. We explore the frequency of SIAs in order to achieve measles control in selected countries and two Indian states with high measles burden. Specifically, we compute the maximum allowable time period between two consecutive SIAs to achieve measles control. RESULTS: Our analysis indicates that a single SIA will not control measles transmission in any of the countries with high measles burden. However, regular SIAs at high coverage levels are a viable strategy to prevent measles outbreaks. The periodicity of SIAs differs between countries and even within a single country, and is determined by population demographics and existing routine immunization coverage. CONCLUSIONS: Our analysis can guide country policymakers deciding on the optimal scheduling of SIA campaigns and the best combination of routine and SIA vaccination to control measles.

The consequences of tobacco tax on household health and finances in rich and poor smokers in China: an extended cost-effectiveness analysis.

BACKGROUND: In China, there are more than 300 million male smokers. Tobacco taxation reduces smoking-related premature deaths and increases government revenues, but has been criticised for disproportionately affecting poorer people. We assess the distributional consequences (across different wealth quintiles) of a specific excise tax on cigarettes in China in terms of both financial and health outcomes. METHODS: We use extended cost-effectiveness analysis methods to estimate, across income quintiles, the health benefits (years of life gained), the additional tax revenues raised, the net financial consequences for households, and the financial risk protection provided to households, that would be caused by a 50% increase in tobacco price through excise tax fully passed onto tobacco consumers. For our modelling analysis, we used plausible values for key parameters, including an average price elasticity of demand for tobacco of -0·38, which is assumed to vary from -0·64 in the poorest quintile to -0·12 in the richest, and we considered only the male population, which constitutes the overwhelming majority of smokers in China. FINDINGS: Our modelling analysis showed that a 50% increase in tobacco price through excise tax would lead to 231 million years of life gained (95% uncertainty range 194-268 million) over 50 years (a third of which would be gained in the lowest income quintile), a gain of US$703 billion ($616-781 billion) of additional tax revenues from the excise tax (14% of which would come from the lowest income quintile, compared with 24% from the highest income quintile). The excise tax would increase overall household expenditures on tobacco by $376 billion ($232-505 billion), but decrease these expenditures by $21 billion (-$83 to $5 billion) in the lowest income quintile, and would reduce expenditures on tobacco-related disease by $24·0 billion ($17·3-26·3 billion, 28% of which would benefit the lowest income quintile). Finally, it would provide financial risk protection worth $1·8 billion ($1·2-2·3 billion), mainly concentrated (74%) in the lowest income quintile. INTERPRETATION: Increased tobacco taxation can be a pro-poor policy instrument that brings substantial health and financial benefits to households in China. FUNDING: Bill & Melinda Gates Foundation and Dalla Lana School of Public Health.