NOVEL PATIENT-CENTERED APPROACH TO CLINICAL TRIAL READINESS IN RARE DISEASES
Author(s)
Anjana Sevagamoorthy, MD, MPH1, Francesco Gavazzi, MD, PhD1, Zarrin Tashnim, BA1, Peter Hong, BA1, Vaia Ylenia, MD, PhD2, Min Lee-Kirsch, MD3, Despina Eleftheriou, MD, PhD4, Shanice Beerepoot, MD, PhD5, Marie Hully, MD6, Elizabeth Berry-Kravis, MD, PhD7, Pamela Ventola, PhD8, Melissa Raspa, PhD9, Anne Wheeler, PhD9, Sara DeMauro, MD, MSCE10, Allan Glanzman, PT, DPT, PCS10, Elise Townsend, DPT, PHD, PCS11, Tina Duong, MPT, PhD12, Stacy Cusack, MSOT10, Ann Harrington, PT, DPT, PhD10, Samuel Pierce, PT, PhD, NCS10, Michelle Fitzgerald, MS, OTR/L10, Elisa Fazzi, MD, PhD13, Jessica Galli, MD, PhD13, Simona Orcesi, MD, PhD14, Davide Tonduti, MD, PhD2, Evangeline Wassmer, MD15, Devon Cordova, BA16, Laura Adang, MD, PhD, MSTR10, Cherie Butts, PhD17, Adeline Vanderver, MD10;
1Children's Hospital of Philadelphia, Division of Neurology, Philadelphia, PA, USA, 2V. Buzzi Children's Hospital, Milan, Italy, 3Dresden University of Technology TU Dresden, Dresden, Germany, 4University College London, London, United Kingdom, 5VUmc University, Amsterdam, Netherlands, 6Necker hospital, Paris, France, 7Rush University, Chicago, IL, USA, 8Yale School of Medicine, New Haven, CT, USA, 9RTI International, Durham, NC, USA, 10Children's Hospital of Philadelphia, Philadelphia, PA, USA, 11Massachusetts General Hospital, Boston, MA, USA, 12Stanford Medicine, Stanford, CA, USA, 13ASST Spedali Civili Brescia, Brescia, Italy, 14University of Pavia, Pavia, Italy, 15Birmingham Children’s Hospital, Birmingham, United Kingdom, 16AGSAA, Crested Butte, CO, USA, 17Biogen, Cambridge, MA, USA
1Children's Hospital of Philadelphia, Division of Neurology, Philadelphia, PA, USA, 2V. Buzzi Children's Hospital, Milan, Italy, 3Dresden University of Technology TU Dresden, Dresden, Germany, 4University College London, London, United Kingdom, 5VUmc University, Amsterdam, Netherlands, 6Necker hospital, Paris, France, 7Rush University, Chicago, IL, USA, 8Yale School of Medicine, New Haven, CT, USA, 9RTI International, Durham, NC, USA, 10Children's Hospital of Philadelphia, Philadelphia, PA, USA, 11Massachusetts General Hospital, Boston, MA, USA, 12Stanford Medicine, Stanford, CA, USA, 13ASST Spedali Civili Brescia, Brescia, Italy, 14University of Pavia, Pavia, Italy, 15Birmingham Children’s Hospital, Birmingham, United Kingdom, 16AGSAA, Crested Butte, CO, USA, 17Biogen, Cambridge, MA, USA
OBJECTIVES: Novel disease-modifying therapies for rare diseases are forthcoming, and inclusion of patients’ voices early in drug development is urgently needed. In this study, we propose a novel approach to design a patient-centered COA (Clinical Outcome Assessments) protocol for rare disease clinical trials.
METHODS: We propose a multicomponent and sequential approach to (i) determine patient/caregiver-identified health priorities, (ii) identify COIs (Concepts of Interest), (iii) select COAs capable of measuring the COIs, (iv) assess the feasibility of COA application, and (v) design COA protocol. Health priorities were determined using Health-Related Quality of Life surveys and qualitative interviews. COIs were identified and COAs selected through expert consensus (≥70% agreement), using the modified eDelphi approach, among disease and COA experts, respectively. COA protocol is designed upon incorporating feedback from patient stakeholders on COA feasibility in a clinical trial.
RESULTS: The approach identified caregiver-identified health priorities and revealed a set of fit-for-purpose disease-expert-selected COIs across key functional domains. Consensus-building for COA selection for each identified COI resulted in a paired COI-COA panel for the disease of interest. Patient stakeholder engagement elicited critical information on COA feasibility as well as logistical barriers/facilitators such as high travel and time expense, and the need for COA optimization, including strategic scheduling. Patient feedback was incorporated into the protocol through the design of a single-day protocol using remote assessments, when feasible. Individualized COA protocol based on functional levels and availing accommodative devices as needed during the in-person visit. Finally, scheduling of endurance COAs early in the day with optimal breaks between assessments to avoid patient fatigue.
CONCLUSIONS: The proposed approach marks the first step toward a patient-centered clinical trial design for rare diseases. It establishes a disease-specific paired COI-COA panel, as well as a patient-centered COA protocol, as a toolkit for future clinical trials.
METHODS: We propose a multicomponent and sequential approach to (i) determine patient/caregiver-identified health priorities, (ii) identify COIs (Concepts of Interest), (iii) select COAs capable of measuring the COIs, (iv) assess the feasibility of COA application, and (v) design COA protocol. Health priorities were determined using Health-Related Quality of Life surveys and qualitative interviews. COIs were identified and COAs selected through expert consensus (≥70% agreement), using the modified eDelphi approach, among disease and COA experts, respectively. COA protocol is designed upon incorporating feedback from patient stakeholders on COA feasibility in a clinical trial.
RESULTS: The approach identified caregiver-identified health priorities and revealed a set of fit-for-purpose disease-expert-selected COIs across key functional domains. Consensus-building for COA selection for each identified COI resulted in a paired COI-COA panel for the disease of interest. Patient stakeholder engagement elicited critical information on COA feasibility as well as logistical barriers/facilitators such as high travel and time expense, and the need for COA optimization, including strategic scheduling. Patient feedback was incorporated into the protocol through the design of a single-day protocol using remote assessments, when feasible. Individualized COA protocol based on functional levels and availing accommodative devices as needed during the in-person visit. Finally, scheduling of endurance COAs early in the day with optimal breaks between assessments to avoid patient fatigue.
CONCLUSIONS: The proposed approach marks the first step toward a patient-centered clinical trial design for rare diseases. It establishes a disease-specific paired COI-COA panel, as well as a patient-centered COA protocol, as a toolkit for future clinical trials.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
PCR187
Topic
Patient-Centered Research
Topic Subcategory
Adherence, Persistence, & Compliance, Instrument Development, Validation, & Translation, Patient Engagement
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Neurological Disorders, SDC: Rare & Orphan Diseases, STA: Personalized & Precision Medicine