Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases: Third of Three Sets of Expanded Proceedings from the 2020 ISCTM Autumn Conference on Pediatric Drug Development

This article expands on a session, titled "Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases," that was presented as part of a two-day meeting on Pediatric Drug Development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Speakers from various areas of pediatric drug development addressed a variety of implications of including children in drug development programs, including implications for rare/orphan diseases. The speakers have written summaries of their talks. The session's lead Chair was Dr. Joan Busner, who wrote introductory and closing comments. Dr. Simon Day, regulatory consultant, outlined some of the past mistakes that have plagued trials that did not consult with patient groups in the early design phase. Dr. Atul Mahableshwarkar provided an industry perspective of a recent trial that benefited from the inclusion of patient input. Drs. Lucas Kempf and Maria Sheean provided regulatory input from the perspectives of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Dr. Judith Dunn outlined a novel approach for assessing and rank ordering patient and clinician clinical meaningfulness and the disconnect that may occur. Dr. Busner provided closing comments, tied together the presented issues, and provided a synopsis of the lively discussion that followed the session. In addition to the speakers above, the discussion included two representatives from patient advocacy groups, as well as an additional speaker who described the challenges of conducting a pediatric trial in the US and European Union (EU), given the often competing regulatory requirements. This article should serve as an expert-informed reference to those interested and involved in CNS drug development programs that are aimed at children and rare diseases and seek to ensure a patient-centric approach.Copyright © 2023, Matrix Medical Communications. All rights reserved.

Global Regulatory and Public Health Initiatives to Advance Pediatric Drug Development for Rare Diseases.

The literature thoroughly describes the challenges of pediatric drug development for rare diseases. This includes (1) generating interest from sponsors, (2) small numbers of children affected by a particular disease, (3) difficulties with study design, (4) lack of definitive outcome measures and assessment tools, (5) the need for additional safeguards for children as a vulnerable population, and (6) logistical hurdles to completing trials, especially with the need for longer term follow-up to establish safety and efficacy. There has also been an increasing awareness of the need to engage patients and their families in drug development processes and to address inequities in access to pediatric clinical trials. The year 2020 ushered in yet another challenge-the COVID-19 pandemic. The pediatric drug development ecosystem continues to evolve to meet these challenges. This article will focus on several key factors including recent regulatory approaches and public health policies to facilitate pediatric rare disease drug development, emerging trends in product development (biologics, molecularly targeted therapies), innovations in trial design/endpoints and data collection, and current efforts to increase patient engagement and promote equity. Finally, lessons learned from COVID-19 about building adaptable pediatric rare disease drug development processes will be discussed.