P550: Assessing the value of rare disease research: A qualitative study of investigators’ perspectives

Introduction:The Undiagnosed Diseases Network (UDN) is a collaborative research network funded by the National Institutes of Health since 2013 that has dual clinical and research goals: to diagnose individuals with unknown conditions and to advance the science of rare disease diagnosis.UDN participants undergo extensive clinical evaluation and diagnostic workup that includes state of the art genomic sequencing and analysis.Through spring 2024, the network has successfully diagnosed 826 participants of 2,656 evaluated, submitted 765 variants to ClinVar, and used model organisms to evaluate mechanisms of genetic disruption encoded by previously unrecognized pathogenic variants.However, the UDN has not pursued harmonized efforts to measure the value of its diagnostic process to patients and families or in terms of health care utilization and cost.We aimed to understand the perspectives of UDN investigators regarding key aspects of the value of the UDN process.Methods: We conducted key informant interviews with UDN investigators.To identify potential participants, we used purposive sampling to ensure representation across UDN project roles and sites.We developed a semi-structured interview guide with the goal of eliciting lessons learned from previous efforts to collect and analyze patient surveys, health care utilization, and billing data, as well as ways in which the network generates value to patients and families, the health care system, and society.Interviews were conducted virtually, audio recorded, and professionally transcribed.We analyzed the data using thematic analysis, applying a coding structure developed by two coders that included both deductive and inductive codes.Results: We conducted 18 interviews (mean duration 41 minutes) in February and March 2024 with participants from 11 UDN clinical sites and the UDN coordinating center.Interviewees included site principal investigators (n= 7), site coordinators (n= 6), research genetic counselors (n = 1), directors (n= 2), and clinical co-investigators (n = 2).We developed three themes related to barriers to value demonstration of the UDN process: 1) varied conceptions of network purpose and definitions of success which have impeded development of a clear value proposition from any given perspective; 2) value that is difficult to quantify, including intangible benefits to patients and families, value of protected time for investigators to review and collectively discuss cases, and value of model organism use; and, 3) lack of a network-wide outcomes research component associated with the historical emphasis on basic and clinical science and absence of network expertise in health economics and outcomes research to spearhead development of research protocols for outcomes and billing data.We also developed two themes related to recommendations for network sustainability: 1) development of a value proposition and associated outcomes measurement approach which can be articulated to demonstrate outcomes from the perspectives of multiple interested groups; and 2) quantification of outcomes that have relevance to interested groups, including the dollar value of ending the diagnostic odyssey and advancing basic research.Conclusion: Our qualitative analysis suggests that UDN investigators perceive multiple, varied components of value in this rare disease research network, yet no consensus approach best suited for demonstrating the value of the UDN process has been developed.While a clear articulation of the overall purpose and value proposition of the network is crucial, analyses must be conducted from the perspective of various interested groups, requiring tailored approaches to presentation of outcomes that are important to patients and families, health care payers, academic medical centers, philanthropists, and research funders.Our findings will inform a harmonized approach to data collection and evaluation across UDN clinical sites and provide important information to the rare and undiagnosed disease field regarding the value of the UDN's strategies for diagnostic evaluation.