Objective 1: Early economic evaluation and a pediatric rare disease framework for value of information analysis

• Due to recognized challenges in generating evidence to inform policy decisions about rare disease treatments (e.g., due to small, often heterogenous, and geographically dispersed patient populations), evaluative research through the life cycle of development of rare disease interventions should anticipate the needs of regulatory and coverage decision-makers. This supports an iterative approach to economic evaluation as part of ongoing health technology assessment [1].

• Our team is developing early economic evaluation and value of information analysis frameworks for rare disease therapies to inform next steps in their evaluation. Our framework can help in pointing out the features of an intervention that significantly impact cost-effectiveness or highlight where an intervention should be placed along the treatment pathway [2]. Our approach can also help estimate the value of future research, pinpointing study areas with the greatest potential benefits, and making design and sample size suggestions [3]. We will implement these approaches within the registry-based randomized trials supported by INFORM RARE to both answer specific questions about the pediatric rare disease therapies evaluated and test and refine our framework.

• For example, we are collaborating with the INFORM MPS research theme on a Phase 2 trial of adalimumab to address pain in pediatric mucopolysaccharidosis (MPS). We will use data from the literature, from the new Canadian MPS Registry the team is co-developing, and from the trial to develop an early economic evaluation based on a probabilistic Markov model [4]. We will use our model to estimate the minimum efficacy at which adalimumab would be cost-effective [5], and conduct a value of information analysis to identify the important outcomes, sample size, and follow-up period for a future Phase 3 trial [6]. The findings will contribute to the development of a future trial, inform priorities for collection of outcomes data in the longitudinal registry, and support the refinement of our framework for value of information analysis in a life cycle approach to rare disease technology evaluation.

Objective 2: Routine capture of family spillover effects and measuring child and family quality of life

• Parents and other caregivers of children with rare diseases often experience challenges in coordinating care within the health system as well as accessing and coordinating education and social care services and managing care at home. There is substantial literature showing that caring for pediatric chronic illness impacts many aspects of parents’ and siblings’ lives [7]. The meaningful conceptualization and accurate measurement of these effects, and how they relate to and can be integrated with measures of child well-being, is important in the true determination of the value of rare disease treatments.

• Measuring quality of life in children with chronic illness or disability is itself challenging: there is no consensus on the most relevant dimensions or best measurement instruments, many existing tools lack relevance to the specific needs of children with disabilities, and many were developed without the key partnership of children and their caregivers [8].

• We have begun to review measures of quality of life for children with rare diseases and their family caregivers, in order to establish research priorities and develop approaches to integrating these into the evaluation, including economic evaluation, of therapies. This work will be completed in partnership with patients and their families, health care providers, and policy decision-makers or their advisors.

1. Sculpher M, Drummond M, Buxton M. The iterative use of economic evaluation as part of the process of health technology assessment. J Heal Serv Res Policy. 1997;2(1):26-30.

2. Zheng K, Kumar S, Sarti A, et al. Economic feasibility of a novel tool to assist extubation decision-making: an early health economic modeling. Int J Technol Assess Health Care. 2022;38(1):e66.

3. Thavorn K, van Katwyck S, Krahn M, et al. Value of mesenchymal stem cell therapy for patients with septic shock: an early health economic evaluation. Int J Technol Assess Health Care. 2020;36(5):525-532.

4. Andrew B, Mark S. An Introduction to Markov Modelling for Economic Evaluation. Pharmacoeconomics. 1998;13(4):397-409.

5. Girling A, Lilford R, Cole A, Young T. Headroom approach to device development: Current and future directions. Int J Technol Assess Health Care. 2016;31(5):331-338.

6. Claxton K, Posnett J. An economic approach to clinical trial design and research priority-setting. Health Econ. 1996;5(6):513-524.

7. Prosser LA, Wittenberg E. Advances in Methods and Novel Applications for Measuring Family Spillover Effects of Illness. Pharmacoeconomics. 2019;37(4):447-450.

8. Coleman CL, Morrison M, Perkins SK, Brosco JP, Schor EL. Quality of Life and Well-Being for Children and Youth With Special Health Care Needs and their Families: A Vision for the Future. Pediatrics. 2022 Jun 1;149(Suppl 7):e2021056150G.