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.
High‐dose chemotherapy with autologous stem cell transplant (ASCT) has been a mainstay of high‐risk neuroblastoma treatment for several decades, demonstrating improvements in event‐free survival but ...with risks of serious or even life‐threatening acute toxicities, severe long‐term adverse health effects for survivors, and ongoing contention regarding overall survival benefit. The merits of ASCT in the modern era of immunotherapy are a source of debate among parents, advocates, and some physicians. Here we examine evidence for and against ASCT, explore parent attitudes and their turmoil over decision‐making, and strongly encourage international research consortia to develop a coordinated strategy to accelerate progress toward a future that avoids the routine use of ASCT in high‐risk neuroblastoma.
The need for post-secondary institutions to think strategically about the application of learning technologies has been well documented. The strategy must plan to effect change in faculty approaches ...to teaching and learning, not just to 'add technology and stir'. An effective strategy will also address both content - the particular applications with the most leverage for institutional goals - and the process of obtaining commitment and moving forward (Daniel, 1996).DOI: 10.1080/0968776990070203
e23195 Background: Pediatric patients with relapsed or refractory malignancy have few options. The quality of life (QoL) impact for enrolling in a phase I or II trial compared to those not ...participating is unknown. This information is invaluable to the consenting process as well as to clinical trial design. The primary aim was to determine if those enrolled on a phase I or II trial had lower scores on the Symptom Screening in Pediatrics Tool (SSPedi) total score compared to those not enrolled on a trial. Methods: This Canadian multi-site study had nine sites open for accrual. SSPedi was calculated based on patient reports for 8-18 years and parent-proxy reports for all children. The total score is the sum of 15 items’ 4 Likert scale scores, score ranges from 0 to 60 (worst possible). Scores from baseline, 4 weeks and 8 weeks of those enrolled on an early phase trial were compared to those who did not enroll in such trials. Results: Of the 54 49 patients, 21 (43%) patients were enrolled on an early phase trial and 28 (57%) patients were not enrolled in a study. For those enrolled on the study at enrollment time, 4 weeks and 8 weeks time points, the total SSPedi score for the participant mean was 11.1 (SD 8.1), 9.2 (SD 6.3) and 10.1 (8.3) respectively compared to those not enrolled on a study with mean scores at the same time points of 13.8 (SD 8.6), 13.5 (SD 9.4), and 15.4 (SD 12.6). Conclusions: These results suggest that it is feasible to evaluate patients enrolled and not enrolled on early phase trials, and to compare their symptom experience. Further efforts will focus on more recruitment and using the PedsQL 3.0 Acute Cancer Module to further define differences in QoL. The results suggest that those enrolled in an early phase trial had an improved quality of life compared to those non-enrolled. This research is supported through granting from the C17 Council and Kindred Foundation. Table: see text
Abstract
Background: Cancer advocates and researchers share the same goal of driving science forward to create new therapies to cure more patients. The power of combining researchers and advocates ...has become of increased importance due to their complementary expertise. Therefore, advocacy is a critical component of grants and has become embedded into the Stand Up 2 Cancer (SU2C) applications. The optimal way to combine these skillsets and experiences to benefit the cancer community is currently unknown.
Methods: The Saint Baldrick's Foundation (SBF)-SU2C pediatric dream team is comprised of a highly collaborative network across nine institutions in the United States and Canada. Since SU2C encourages incorporating advocacy into the team structure, we have assembled a diverse team of advocates and scientists by nominating a young investigator (YI) and advocate from each site. During the yearly in person team meeting, a day is dedicated to fostering the advocacy and scientist interaction including discussions with an AACR guest speaker and ending with a night of inspiration to share our stories. Monthly, the advocates have calls that include a young investigator to present their research in lay terms, moderated by the senior investigator team leaders. In order to further bridge this interaction, we developed a questionnaire and conducted interviews. The questionnaire is focused on understanding each member's experience at the intersection between science/advocacy, comparing to previous experiences, providing advice on incorporating advocacy into science and discussing how we can build on our work.
Results: Questionnaire results show that both advocates and YI's see this structure to be valuable and beneficial by improving their science communication, designing patient-friendly clinical trials and sharing experience across institutions. YI's have the opportunity to communicate their research to a non-scientific audience, learn advocate's experience which motivates them to focus on patient priorities and learn skills for career development. For most YI's, this was their first advocacy experience. Advocates learn more about the research being conducted so they can share with patients to provide hope. They can also use this knowledge to help with fundraising, publicity and lobbying. To maintain momentum between yearly in person meetings and bridge interactions between sites, we will add monthly meetings focused on topics including science communication, legislation/government, regulatory science, central IRB protocols, and fundraising.
Conclusion: Through creating a YI and advocate infrastructure, we have cultivated a supportive environment for meaningful conversation that impacts the entire research team. We see this as a model for team science by combining expertise to drive innovation forward and positively impact pediatric cancer patients, and perhaps those with adult malignancies.
Citation Format: Amber K. Weiner, Gavin Lindberg, Melanie Moll, Antonia Palmer, Kevin Reidy, Sharon J. Diskin, Crystal L. Mackall, John M. Maris, Patrick J. Sullivan. Advancing childhood cancer research through young investigator and advocate collaboration abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2633.
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.
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.
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.
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.
•Health technology assessment (HTA) methods for child health technologies are challenged by evidentiary limitations and incomplete consideration of the unique biological and social circumstances and needs of children and youth. Multicriteria decision analysis has emerged as an HTA tool for explicitly considering nonconventional values.•This article presents novel child-specific value assessment criteria based in societal preferences, which reflect the importance of family impacts and long-term flourishing of children beyond immediate health gains obtained through treatment.•A child-tailored multicriteria decision analysis approach facilitating HTA deliberations may broaden the normative lens through which child health technologies are evaluated, contributing to more comprehensive and relevant decision making.
Abstract
Innovative therapeutic approaches are needed to alleviate the burden of life-limiting, rare, and chronic conditions affecting children, adolescents, and young adults (CAYA). This includes a ...need for improved access to both clinical research and to non-approved or off-label therapies, together with, ultimately, more therapies achieving regulatory approval in Canada. The single patient study (SPS), also known as an open label individual patient (OLIP) study, was introduced by Health Canada to open access to non-marketed drugs where a clinical trial is not readily available, but the drug is considered too investigational to be managed on a standard Special Access Program. SPS is designed for patients who have a serious or life-threatening condition and have exhausted available treatment options. Our report summarizes this relatively new development in the Canadian regulatory environment and highlights the opportunities and challenges as identified by regulators, pharmaceutical representatives, academic researchers, and patient/parent advocates.
Abstract
Background: Over 4,300 children, adolescents, and young adults (CAYA) are diagnosed with cancer each year in Canada, 1/3 of whom have refractory/metastatic disease or will relapse. The ...PRecision Oncology For Young peopLE (PROFYLE) national, collaborative program, was created to provide equitable access to molecular profiling to identify novel targeted treatment options in a clinically relevant timeframe for all CAYA with hard-to-cure cancers in Canada.
Design: Building upon 3 pre-existing regional precision oncology programs, PROFYLE now includes >20 institutions and has united an interdisciplinary team of experts, leaders, research teams, end-users and advocates from across Canada. The program has 14 domain specific nodes that are unified by a shared governance structure, and has harmonized biobanking, genomics, bioinformatics and reporting procedures. PROFYLE includes genomic and transcriptomic sequencing of paired germline and cancer fresh/frozen samples, proteomic analysis, and cancer modelling. Inclusion criteria: ≤29y; treatment at a Canadian center; diagnosis of a hard-to-cure cancer. Profiling results are reviewed by multidisciplinary Molecular Tumor Boards. A report including a results/recommendations summary of actionable findings (therapeutic, diagnostic, prognostic, cancer predisposition), potential targeted therapy options including available clinical trials, clarification of diagnosis, and genetic counseling recommendations is provided to the treating oncologist.
Results: >1,000 CAYA are included from all of the provinces. Cancer diagnoses: 34% sarcoma, 16% leukemia/lymphoma, 16% CNS tumor, 11% neuroblastoma, 23% other. 17% of participants had a cancer-predisposing pathogenic/likely pathogenic germline variant, 45% had ≥1 potentially actionable somatic alteration, 22.6% had a therapeutically targetable somatic alteration. The most frequent classes of therapeutic alterations were RAS/MAPK (15%), cell cycle (14%), epigenetic (13%), RTK (12%), PI3K/AKT/mTOR (11%), DNA repair (9%), immune checkpoint (8%). Of clinicians who reported the utility of results, 55% indicated the findings were useful for clinical management.
Future Directions: Collaborations with other national and international initiatives and data from this interdisciplinary, multi-institutional research program will inform the development of a framework to innovatively link research, clinical and system considerations with Canadian values relevant to multi-omic profiling and drug access for CAYA. In addition, we believe that with a comprehensive molecular view of cancer, PROFYLE will transform our understanding of underlying disease mechanisms, facilitate and improve diagnostic and prognostic indicators, and identify new therapeutic strategies and targets for CAYA patients with cancer.
Citation Format: Stephanie A. Grover, Lesleigh Abbott, Jason N. Berman, Guillaume Bourque, Jennifer A. Chan, Avram E. Denburg, Rebecca J. Deyell, Conrad V. Fernandez, Cynthia Hawkins, Jan-Willem Henning, Meredith S. Irwin, Nada Jabado, Steven J. Jones, Philipp F. Lange, Paul Moorehead, Michael F. Moran, Daniel A. Morgenstern, Sapna Oberoi, Antonia Palmer, Shahrad R. Rassekh, Donna L. Senger, Adam Shlien, Daniel Sinnett, Caron Strahlendorf, Patrick J. Sullivan, Michael D. Taylor, Suzanne Vercauteren, Anita Villani, Stephanie Villeneuve, James A. Whitlock, David Malkin, on behalf of the PROFYLE Consortium. A pan-Canadian precision oncology program for children, adolescents and young adults with hard-to-cure cancer: The PRecision Oncology For Young peopLE (PROFYLE) Program. abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4509.
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