Application of Multi-Criteria Decision Analysis (MCDA) to Prioritize Real-World Evidence Studies for Health Technology Management: Outcomes and Lessons Learned by the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

Multi-criteria decision analysis (MCDA) is a value assessment tool designed to help support complex decision-making by incorporating multiple factors and perspectives in a transparent, structured approach. We developed an MCDA rating tool, consisting of seven criteria evaluating the importance and feasibility of conducting potential real-world evidence (RWE) studies aimed at addressing uncertainties stemming from initial cancer drug funding recommendations. In collaboration with the Canadian Agency for Drugs and Technologies in Health's Provincial Advisory Group, a validation exercise was conducted to further evaluate the application of the rating tool using RWE proposals varying in complexity. Through this exercise, we aimed to gain insight into consensus building and deliberation processes and to identify efficiencies in the application of the rating tool. An experienced facilitator led a multidisciplinary committee, consisting of 11 Canadian experts, through consensus building, deliberation, and prioritization. A total of nine RWE proposals were evaluated and prioritized as low (n = 4), medium (n = 3), or high (n = 2) priority. Through an iterative process, efficiencies and recommendations to improve the rating tool and associated procedures were identified. The refined MCDA rating tool can help decision-makers prioritize important and feasible RWE studies for research and can enable the use of RWE for the life-cycle evaluation of cancer drugs.

Institutional Priority-Setting for Novel Drugs and Therapeutics: A Qualitative Systematic Review.

BACKGROUND: There is a lack of guidance on approaches to formulary management and funding for high-cost drugs and therapeutics by individual healthcare institutions. The objective of this review was to assess institutional approaches to resource allocation for such therapeutics, with a particular focus on paediatric and rare disease populations. METHODS: A search of Embase and MEDLINE was conducted for studies relevant to decision-making for off-formulary, high-cost drugs and therapeutics. Abstracts were evaluated for inclusion based on the Simple Multiple-Attribute Rating Techniques (SMART) criteria. A framework of 30 topics across 4 categories was used to guide data extraction and was based on findings from the initial abstract review and previous health technology assessment (HTA) publications. Reflexive thematic analysis was conducted using QSR NVivo 12 software. RESULTS: A total of 168 studies were included for analysis. Only 4 (2%) focused on paediatrics, while 21 (12%) centred on adults and the remainder (85%) did not specify. Thirty-two (19%) studies discussed the importance of high-cost therapeutics and 34 (23%) focused on rare/orphan drugs. Five themes were identified as being relevant to institutional decision-making for high-cost therapeutics: institutional strategy, substantive criteria, procedural considerations, guiding principles and frameworks, and operational activities. Each of these themes encompassed several sub-themes and was complemented by a sixth category specific to paediatrics and rare diseases. CONCLUSION: The rising cost of novel drugs and therapeutics underscores the need for robust, evidence-based, and ethically defensible decision-making processes for health technology funding, particularly at the hospital level. Our study highlights practices and themes to aid decision-makers in thinking critically about institutional, substantive, procedural, and operational considerations in support of legitimate decisions about institutional funding of high-cost drugs and therapeutics, as well as opportunities and challenges that exist for paediatric and rare disease populations.

Priority-setting for hospital funding of high-cost innovative drugs and therapeutics: A qualitative institutional case study.

OBJECTIVES: Rising costs of innovative drugs and therapeutics (D&Ts) have led to resource allocation challenges for healthcare institutions. There is limited evidence to guide priority-setting for institutional funding of high-cost D&Ts. This study sought to identify and elaborate on the substantive principles and procedures that should inform institutional funding decisions for high-cost off-formulary D&Ts through a case study of a quaternary care paediatric hospital. METHODS: Semi-structured, qualitative interviews, both virtual and in-person, were conducted with institutional stakeholders (i.e. staff clinicians, senior leadership, and pharmacists) (n = 23) and two focus groups at The Hospital for Sick Children in Toronto, Canada. Participants involved in, and impacted by, high-cost off-formulary drug funding decisions were recruited through stratified, purposive sampling. Participants were approached for study involvement between July 27, 2020 and June 7, 2022. Data was analysed through reflexive thematic analysis. RESULTS: Institutional resource allocation for high-cost D&Ts was identified as ethically challenging but critical to sustainable access to novel therapies. Important substantive principles included: 1) clinical evidence of safety and efficacy, 2) economic considerations (direct costs, opportunity costs, value for money), 3) ethical principles (social justice, professional/organizational responsibility), and 4) disease-specific considerations. Multidisciplinary deliberation was identified as an essential procedural component of decision-making. Participants identified tension between innovation and the need for evidence-based decision-making; clinician and institutional responsibilities; and value for money and social justice. Participants emphasized the role of health system-level funding allocation in alleviating the financial and moral burden of decision-making by institutions. CONCLUSIONS: This study identifies values and processes to aid in the development and implementation of institutional resource allocation frameworks for high-cost innovative D&Ts.

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 innovative therapies in pediatric oncology: Report of the nationwide experience in Canada.

BACKGROUND: The need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to "out-of-trial" use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020. METHODS: Innovative therapies were defined as cancer-directed drugs used (a) off-label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics. We excluded cytotoxic chemotherapy, cellular products, and cytokines. RESULTS: We retrieved data on 352 innovative therapy drug requests. Underlying diagnosis was primary CNS tumor 31%; extracranial solid tumor 37%, leukemia/lymphoma 22%, LCH 2%, and plexiform neurofibroma 6%. RAS/MAP kinase pathway inhibitors were the most frequently requested innovative therapies in 28% of all requests followed by multi-targeted tyrosine kinase inhibitors (17%), inhibitors of the PIK3CA-mTOR-AKT pathway (8%), immune checkpoints inhibitors (8%), and antibody drug conjugates (8%). In 112 out of 352 requests, innovative therapies were used in combination with another anticancer agent. 48% of requests were motivated by the presence of an actionable molecular target. Compassionate access accounted for 52% of all requests while public insurance was used in 27%. Mechanisms of funding varied between provinces. CONCLUSION: This real-world data collection illustrates an increasing use of "out-of-trial" innovative therapies in pediatric oncology. This new field of practice warrants further studies to understand the impact on patient trajectory and equity in access to innovative therapies.

Physical late effects of treatment among survivors of childhood cancer in low- and middle-income countries: a systematic review.

PURPOSE: Physical late effects of treatment are well-documented among childhood cancer survivors in high-income countries, but whether prevalence and risk factors are comparable in low- and middle-income countries (LMICs) is unclear. We conducted a systematic review to assess physical late effect outcomes among childhood cancer survivors in LMICs. METHODS: Five health sciences databases were searched from inception to November 2022 in all languages. We included observational studies conducted in LMICs that evaluated physical late effects of treatment in childhood cancer survivors. Mean or median cohort follow-up must have been ≥ 5 years from original cancer diagnosis. RESULTS: Sixteen full articles and five conference abstracts were included. Studies were conducted in lower-middle (n = 12, 57%) or upper-middle income (n = 9, 43%) countries; nearly half (n = 9, 43%) were conducted in India. Five cohorts (24%) were comprised entirely of 5-year survivors. Subsequent malignant neoplasms were reported in 0-11% of survivors (n = 10 studies). Hypothyroidism and metabolic syndrome prevalence ranged from 2-49% (n = 4 studies) and 4-17% (n = 5 studies), respectively. Gonadal dysfunction ranged from 3-47% (n = 4 studies). Cardiac dysfunction ranged from 1-16% (n = 3 studies). Late effects of the musculoskeletal and urinary systems were least investigated. CONCLUSIONS: Substantial knowledge gaps exist in LMIC childhood cancer survivorship. No low-income country data were found. In middle-income countries, late effects were defined and assessed variably and limited by selection bias and small sample sizes. IMPLICATIONS FOR CANCER SURVIVORS: Survivors in LMICs can experience physical late effects of treatment, though additionally systematically collected data from survivor cohorts are needed to fill knowledge gaps.

The promise of POSIT: Real-world application of the Paediatric Oncology System Integration Tool.

Childhood cancer presents significant acute and long-term challenges for patients,families, communities, and health systems. Although meaningful strides have been made in research and treatment, severe outcome disparities prevail between low- and middle-income countries (LMICs) and high-income countries (HICs), with childhood cancer survival rates lower than 20% in LMICs, as compared with over 80% across many HICs. In recent years, greater emphasis has been placed on health system strengthening as a means to develop domestic policy and capacity for sustainable improvements in childhood cancer outcomes in LMICs. In pursuit of a systems approach to childhood cancer in LMICs, our research team developed the Paediatric Oncology System Integration Tool (POSIT)-the first comprehensive framework for the design and evaluation of childhood cancer systems. Since its development, POSIT has been applied in an exploration of key determinants of access to essential childhood cancer medicines across two separate multi-site studies. In this commentary, we explore the value of the POSIT framework and toolkit as a constructive systems-level guide for examining interactions between childhood cancer-specific programs and encompassing health system. socio-political, and economic contexts.

"I just wanted more": Hereditary cancer syndromes patients' perspectives on the utility of circulating tumour DNA testing for cancer screening.

Hereditary cancer syndromes (HCS) predispose individuals to a higher risk of developing multiple cancers. However, current screening strategies have limited ability to screen for all cancer risks. Circulating tumour DNA (ctDNA) detects DNA fragments shed by tumour cells in the bloodstream and can potentially detect cancers early. This study aimed to explore patients' perspectives on ctDNA's utility to help inform its clinical adoption and implementation. We conducted a qualitative interpretive description study using semi-structured phone interviews. Participants were purposively sampled adult HCS patients recruited from a Canadian HCS research consortium. Thirty HCS patients were interviewed (n = 19 women, age range 20s-70s, n = 25 were white). Participants were highly concerned about developing cancers, particularly those without reliable screening options for early detection. They "just wanted more" than their current screening strategies. Participants were enthusiastic about ctDNA's potential to be comprehensive (detect multiple cancers), predictive (detect cancers early) and tailored (lead to personalized clinical management). Participants also acknowledged ctDNA's potential limitations, including false positives/negatives risks and experiencing additional anxiety. However, they saw ctDNA's potential benefits outweighing its limitations. In conclusion, participants' belief in ctDNA's potential to improve their care overshadowed its limitations, indicating patients' support for using ctDNA in HCS care.

Advances in the Global Initiative for Childhood Cancer: implementation in Latin America and the Caribbean.

This report describes the status of childhood cancer control initiatives in Latin America and the Caribbean (LAC). Progress between 2017 and 2023 is measured using the outcome indicators from the Pan American Health Organization (PAHO) childhood cancer logic model aligned with the World Health Organization Global Initiative for Childhood Cancer (GICC). This report also describes the advances, barriers, and facilitators for the implementation of the GICC at the Regional level. Methods used in this report encompassed a comprehensive approach, incorporating a literature review, interviews, surveys, and a Delphi study developed by the technical team of the PAHO Non-Communicable Diseases and Mental Health Department and by the GICC LAC working group. Since 2017, there has been a substantial increase in the number of countries that have included childhood cancer in their national regulations. Currently, 21 LAC countries are involved in the GICC implementation, activities, and dialogues. However, the objectives for 2030 will only be achieved if Member States overcome the barriers to accelerating the pace of initiative implementation. There is an urgent need to increase the efforts in childhood cancer control in LAC, especially regarding the prioritization of timely detection, essential diagnostics, access to cancer treatment, palliative care, and close follow-up of children and adolescents with cancer.

En este artículo se describe la situación de las iniciativas para el control del cáncer infantil en América Latina y el Caribe. Para medir los progresos entre el 2017 y el 2023, se utilizan los indicadores de resultados del modelo lógico del cáncer infantil de la Organización Panamericana de la Salud (OPS) que es coherente con la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud. También se describen los avances, los obstáculos y los elementos que han facilitado la aplicación de esa iniciativa en la Región Los métodos utilizados en este trabajo incluyeron un enfoque integral que incorporó una revisión bibliográfica, entrevistas, encuestas y un estudio de tipo Delfos llevado a cabo por el equipo técnico del Departamento de Enfermedades No Transmisibles y Salud Mental de la OPS y por el grupo de trabajo de América Latina y el Caribe de la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud.Desde el 2017 ha habido un incremento considerable en el número de países que incorporan el cáncer infantil en sus regulaciones nacionales. En la actualidad, 21 países de América Latina y el Caribe participan en la puesta en práctica, las actividades y las deliberaciones de la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud. No obstante, los objetivos para el 2030 solo podrán alcanzarse si los Estados Miembros son capaces de superar los obstáculos que dificultan la aceleración del ritmo de aplicación de esta iniciativa. Existe una necesidad urgente de aumentar las actividades dirigidas al control del cáncer infantil en América Latina y el Caribe, en especial en lo que respecta a priorizar la detección temprana, los medios de diagnóstico esenciales, el acceso a los tratamientos oncológicos, los cuidados paliativos y el seguimiento estricto de la población infantil y adolescente con cáncer.

Este relatório descreve a situação das iniciativas de controle do câncer infantil na Região da América Latina e do Caribe (ALC). O progresso alcançado entre 2017 e 2023 foi medido usando os indicadores de resultados intermediários do modelo lógico de câncer infantil da Organização Pan-Americana da Saúde (OPAS), em linha com a Iniciativa Global para o Câncer Infantil (GICC) da Organização Mundial da Saúde. O relatório também descreve os avanços, as barreiras e os facilitadores para a implementação da iniciativa em nível regional. Os métodos utilizados neste relatório aplicaram uma abordagem abrangente que incluiu revisão da literatura, entrevistas, levantamentos e um estudo Delphi desenvolvido pela equipe técnica do Departamento de Doenças Não Transmissíveis e Saúde Mental da OPAS e pelo grupo de trabalho da GICC para a ALC.Desde 2017, houve um aumento significativo no número de países que passaram a incluir o câncer infantil em regulamentações nacionais. Atualmente, 21 países da América Latina e do Caribe estão envolvidos na implementação da GICC, bem como em atividades e diálogos relacionados. No entanto, os objetivos para 2030 só serão alcançados se os Estados Membros superarem as barreiras ao aceleramento do ritmo de implementação da iniciativa. Existe uma necessidade urgente de intensificar os esforços de controle do câncer infantil na ALC, especialmente no tocante à priorização da detecção em tempo hábil, diagnósticos essenciais, acesso a tratamentos oncológicos, cuidados paliativos e acompanhamento cuidadoso de crianças e adolescentes com câncer.

Developing a partnership to improve health care delivery to children <18 years with cancer and blood disorders in the English-speaking Caribbean: lessons from the SickKids-Caribbean Initiative (SCI).

In 2013, the SickKids-Caribbean Initiative (SCI) was formalised among The Hospital for Sick Children in Toronto, Canada, the University of the West Indies, and Ministries of Health in six Caribbean countries (Barbados, The Bahamas, Jamaica, St. Lucia, St. Vincent and the Grenadines, and Trinidad and Tobago). The aim was to improve the outcomes and quality of life of children (<18 years) with cancer and blood disorders in the partner countries. Core activities included filling a human resource gap by training paediatric haematologists/oncologists and specialised registered nurses; improving capacity to diagnose and treat diverse haematology/oncology cases; developing and maintaining paediatric oncology databases; creating ongoing advocacy activities with international agencies, decision makers, and civil society; and establishing an integrated administration, management, and funding structure. We describe core program components, successes, and challenges to inform others seeking to improve health service delivery in a multidisciplinary and complex partnership.

Advances in the Global Initiative for Childhood Cancer: implementation in Latin America and the Caribbean / Adelantos en la Iniciativa Mundial contra el Cáncer Infantil: aplicación en América Latina y el Caribe / Avanços na Iniciativa Global para o Câncer Infantil da OMS: implementação na América Latina e no Caribe

[ABSTRACT]. This report describes the status of childhood cancer control initiatives in Latin America and the Caribbean (LAC). Progress between 2017 and 2023 is measured using the outcome indicators from the Pan American Health Organization (PAHO) childhood cancer logic model aligned with the World Health Organization Global Initiative for Childhood Cancer (GICC). This report also describes the advances, barriers, and facilitators for the implementation of the GICC at the Regional level. Methods used in this report encompassed a comprehensive approach, incorporating a literature review, interviews, surveys, and a Delphi study developed by the technical team of the PAHO Non-Communicable Diseases and Mental Health Department and by the GICC LAC working group. Since 2017, there has been a substantial increase in the number of countries that have included childhood cancer in their national regulations. Currently, 21 LAC countries are involved in the GICC implementation, activities, and dialogues. However, the objectives for 2030 will only be achieved if Member States overcome the barriers to accelerating the pace of initiative implementation. There is an urgent need to increase the efforts in childhood cancer control in LAC, especially regarding the prioritization of timely detection, essential diagnostics, access to cancer treatment, palliative care, and close follow-up of children and adolescents with cancer.

[RESUMEN]. En este artículo se describe la situación de las iniciativas para el control del cáncer infantil en América Latina y el Caribe. Para medir los progresos entre el 2017 y el 2023, se utilizan los indicadores de resultados del modelo lógico del cáncer infantil de la Organización Panamericana de la Salud (OPS) que es coherente con la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud. También se describen los avances, los obstáculos y los elementos que han facilitado la aplicación de esa iniciativa en la Región Los métodos utilizados en este trabajo incluyeron un enfoque integral que incorporó una revisión bibliográfica, entrevistas, encuestas y un estudio de tipo Delfos llevado a cabo por el equipo técnico del Departamento de Enfermedades No Transmisibles y Salud Mental de la OPS y por el grupo de trabajo de América Latina y el Caribe de la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud. Desde el 2017 ha habido un incremento considerable en el número de países que incorporan el cáncer infantil en sus regulaciones nacionales. En la actualidad, 21 países de América Latina y el Caribe participan en la puesta en práctica, las actividades y las deliberaciones de la Iniciativa Mundial contra el Cáncer Infantil de la Organización Mundial de la Salud. No obstante, los objetivos para el 2030 solo podrán alcanzarse si los Estados Miembros son capaces de superar los obstáculos que dificultan la aceleración del ritmo de aplicación de esta iniciativa. Existe una necesidad urgente de aumentar las actividades dirigidas al control del cáncer infantil en América Latina y el Caribe, en especial en lo que respecta a priorizar la detección temprana, los medios de diagnóstico esenciales, el acceso a los tratamientos oncológicos, los cuidados paliativos y el seguimiento estricto de la población infantil y adolescente con cáncer.

[RESUMO]. Este relatório descreve a situação das iniciativas de controle do câncer infantil na Região da América Latina e do Caribe (ALC). O progresso alcançado entre 2017 e 2023 foi medido usando os indicadores de resultados intermediários do modelo lógico de câncer infantil da Organização Pan-Americana da Saúde (OPAS), em linha com a Iniciativa Global para o Câncer Infantil (GICC) da Organização Mundial da Saúde. O relatório também descreve os avanços, as barreiras e os facilitadores para a implementação da iniciativa em nível regional. Os métodos utilizados neste relatório aplicaram uma abordagem abrangente que incluiu revisão da literatura, entrevistas, levantamentos e um estudo Delphi desenvolvido pela equipe técnica do Departamento de Doenças Não Transmissíveis e Saúde Mental da OPAS e pelo grupo de trabalho da GICC para a ALC. Desde 2017, houve um aumento significativo no número de países que passaram a incluir o câncer infantil em regulamentações nacionais. Atualmente, 21 países da América Latina e do Caribe estão envolvidos na imple- mentação da GICC, bem como em atividades e diálogos relacionados. No entanto, os objetivos para 2030 só serão alcançados se os Estados Membros superarem as barreiras ao aceleramento do ritmo de implementação da iniciativa. Existe uma necessidade urgente de intensificar os esforços de controle do câncer infantil na ALC, especialmente no tocante à priorização da detecção em tempo hábil, diagnósticos essenciais, acesso a tratamentos oncológicos, cuidados paliativos e acompanhamento cuidadoso de crianças e adoles- centes com câncer.

Precision oncology for children: A primer for paediatricians.

Cancer is the leading cause of disease-related death in children, adolescents, and young adults beyond the newborn period in North America. Improving survival rates for patients with hard-to-cure cancer remains a challenge. One approach that has gained particular traction is 'precision oncology', whereby next-generation sequencing is used to identify genomic or transcriptomic changes that can help clarify the diagnosis, refine prognosis, define an underlying genetic cause, or identify a unique treatment target for a patient's cancer. In this primer, we provide a brief overview of the evolution of precision paediatric oncology, its current application to clinical oncology practice, and its future potential as a foundational approach to paediatric oncology care in Canada and around the world. We also address the many challenges and limitations inherent to the implementation of precision oncology as the standard of care, including ethical and economic considerations.

Translating Precision Health for Pediatrics: A Scoping Review.

Precision health aims to personalize treatment and prevention strategies based on individual genetic differences. While it has significantly improved healthcare for specific patient groups, broader translation faces challenges with evidence development, evidence appraisal, and implementation. These challenges are compounded in child health as existing methods fail to incorporate the physiology and socio-biology unique to childhood. This scoping review synthesizes the existing literature on evidence development, appraisal, prioritization, and implementation of precision child health. PubMed, Scopus, Web of Science, and Embase were searched. The included articles were related to pediatrics, precision health, and the translational pathway. Articles were excluded if they were too narrow in scope. In total, 74 articles identified challenges and solutions for putting pediatric precision health interventions into practice. The literature reinforced the unique attributes of children and their implications for study design and identified major themes for the value assessment of precision health interventions for children, including clinical benefit, cost-effectiveness, stakeholder values and preferences, and ethics and equity. Tackling these identified challenges will require developing international data networks and guidelines, re-thinking methods for value assessment, and broadening stakeholder support for the effective implementation of precision health within healthcare organizations. This research was funded by the SickKids Precision Child Health Catalyst Grant.

Development of a Multi-Criteria Decision Analysis Rating Tool to Prioritize Real-World Evidence Questions for the Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration.

The Canadian Real-world Evidence for Value of Cancer Drugs (CanREValue) collaboration developed an MCDA rating tool to assess and prioritize potential post-market real-world evidence (RWE) questions/uncertainties emerging from public drug funding decisions in Canada. In collaboration with a group of multidisciplinary stakeholders from across Canada, the rating tool was developed following a three-step process: (1) selection of criteria to assess the importance and feasibility of an RWE question; (2) development of rating scales, application of weights and calculating aggregate scores; and (3) validation testing. An initial MCDA rating tool was developed, composed of seven criteria, divided into two groups. Group A criteria assess the importance of an RWE question by examining the (1) drug's perceived clinical benefit, (2) magnitude of uncertainty identified, and (3) relevance of the uncertainty to decision-makers. Group B criteria assess the feasibility of conducting an RWE analysis including the (1) feasibility of identifying a comparator, (2) ability to identify cases, (3) availability of comprehensive data, and (4) availability of necessary expertise and methodology. Future directions include partnering with the Canadian Agency for Drugs and Technology in Health's Provincial Advisory Group for further tool refinement and to gain insight into incorporating the tool into drug funding deliberations.

Evidence of clinical benefit of WHO essential anticancer medicines for children, 2011-2021.

Background: Access to essential cancer medicines is a key determinant of childhood cancer survival. WHO published the Model List of Essential Medicine for Children (EMLc) and updated it every two years since 2007 to promote better access to medicines for children. This study aimed to assess whether the inclusion of essential anticancer medicines for respective indications for children was based on evidence of significant clinical benefit between 2011 and 2021. Methods: We identified all anticancer medicine indications added to the WHO EMLc Section 8 since 2011 and extracted evidence of benefit documented in the corresponding technical reports. Evidence in children was defined as evidence that included participants under 12, and graded into five levels, according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. We analyzed whether each anticancer medicine indication was listed with documented OS benefit or improvements in surrogate measures based on the highest level of documented evidence in children. Findings: A total of 115 anticancer medicine indications were added to the EMLc from 2011 to 2021, of which 101 (87.8%) had some clinical evidence in children and 4 (3.5%) were added without any clinical evidence. Among the 101 medicine indications, none were added with level-1 evidence in children, and 43 (42.6%), 11 (10.9%), 41 (40.6%), and 6 (5.9%) were listed with level-2, level-3, level-4, and level-5 evidence in children, respectively. Only eight (7.9%) medicine indications were reported to have OS benefit, another 12 (11.9%) were reported to have improvements on surrogate measures, and 81 (80.2%) were listed in the EMLc without documented improvements in either OS or surrogate measures. Interpretation: Most anticancer medicine indications of the WHO EMLc were added based on limited evidence of statistically significant clinical benefit in children. Our results suggest that WHO should refine requirements for clinical benefit criteria and permissible forms, quality, and reporting of evidence of essential anticancer medicines for children, specify whether anticancer medicine indications have required evidence of clinical benefit in children, and provide further details in its technical reports that summarise the available evidence. Funding: Not applicable.

Access to essential cancer medicines for children: a comparative mixed-methods analysis of availability, price, and health-system determinants in east Africa.

BACKGROUND: Access to essential childhood cancer medicines is a core determinant of childhood cancer outcomes. Available evidence, although scarce, suggests that access to these medicines is highly variable across countries, particularly in low-income and middle-income countries, where the burden of childhood cancer is greatest. To support evidence-informed national and regional policies for improved childhood cancer outcomes, we aimed to analyse access to essential childhood cancer medicines in four east African countries-Kenya, Rwanda, Tanzania, and Uganda-by determining the availability and price of these medicines and the health system determinants of access. METHODS: In this comparative analysis, we used prospective mixed-method analyses to track and analyse the availability and price of essential childhood cancer medicines, investigate contextual determinants of access to childhood cancer medicines within and across included countries, and assess the potential effects of medicine stockouts on treatment. Eight tertiary care hospitals were included, seven were public sites (Kenyatta National Hospital [KNH; Nairobi, Kenya], Jaramogi Oginga Odinga Referral and Teaching Hospital [JOORTH; Kisumu, Kenya], Moi University Teaching and Referral Hospital [MTRH; Eldoret, Kenya], Bugando Medical Centre [BMC; Mwanza, Tanzania], Muhimbili National Hospital [MNH; Dar es Salaam, Tanzania], Butaro Cancer Centre of Excellence [BCCE; Butaro Sector, Rwanda], and Uganda Cancer Institute [UCI; Kampala, Uganda]) and one was a private site (Aga Khan University Hospital [AKU; Nairobi, Kenya]). We catalogued prices and stockouts for 37 essential drugs from each of the eight study siteson the basis of 52 weeks of prospective data that was collected across sites from May 1, 2020, to Jan 31, 2022. We analysed determinants of medicine access using thematic analysis of academic literature, policy documents, and semi-structured interviews from a purposive sample of health system stakeholders. FINDINGS: Recurrent stockouts of a wide range of cytotoxic and supportive care medicines were observed across sites, with highest mean unavailability in Kenya (JOORTH; 48·5%), Rwanda (BCCE; 39·0%), and Tanzania (BMC; 32·2%). Drugs that had frequent stockouts across at least four sites included methotrexate, bleomycin, etoposide, ifosfamide, oral morphine, and allopurinol. Average median price ratio of medicines at each site was within WHO's internationally accepted threshold for efficient procurement (median price ratio ≤1·5). The effect of stockouts on treatment was noted across most sites, with the greatest potential for treatment interruptions in patients with Hodgkin lymphoma, retinoblastoma, and acute lymphocytic leukaemia. Policy prioritisation of childhood cancers, health financing and coverage, medicine procurement and supply chain management, and health system infrastructure emerged as four prominent determinants of access when the stratified purposive sample of key informants (n=64) across all four countries (Kenya n=19, Rwanda n=15, Tanzania n=13, and Uganda n=17) was interviewed. INTERPRETATION: Access to childhood cancer medicines across east Africa is marked by gaps in availability that have implications for effective treatment delivery for a range of childhood cancers. Our findings provide detailed evidence of barriers to access to childhood cancer medicine at multiple points in the pharmaceutical value chain. These data could inform national and regional policy makers to optimise cancer medicine availability and affordability as part of efforts to improve childhood cancer outcomes specific regions and internationally. FUNDING: American Childhood Cancer Organization, Childhood Cancer International, and the Friends of Cancer Patients Ameera Fund.

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.