Advancing patient-centric care: integrating patient reported outcomes for tolerability assessment in early phase clinical trials - insights from an expert virtual roundtable

Christina Yap; Olalekan Lee Aiyegbusi; Emily Alger; Ethan Basch; Jill Bell; Vishal Bhatnagar; David Cella; Philip Collis; Amylou C Dueck; Alexandra Gilbert; Ari Gnanasakthy; Alastair Greystoke; Aaron R Hansen; Paul Kamudoni; Olga Kholmanskikh; Bellinda L King-Kallimanis; Harlan Krumholz; Anna Minchom; Daniel O'Connor; Joan Petrie; Claire Piccinin; Khadija Rerhou Rantell; Saaeha Rauz; Ameeta Retzer; Steven Rizk; Lynne Wagner; Maxime Sasseville; Lesley K Seymour; Harald A Weber; Roger Wilson; Melanie Calvert; John Devin Peipert

doi:10.1016/j.eclinm.2024.102838

Advancing patient-centric care: integrating patient reported outcomes for tolerability assessment in early phase clinical trials - insights from an expert virtual roundtable

EClinicalMedicine. 2024 Sep 24:76:102838. doi: 10.1016/j.eclinm.2024.102838. eCollection 2024 Oct.

Authors

Christina Yap¹, Olalekan Lee Aiyegbusi^{2

3

4

5

6}, Emily Alger¹, Ethan Basch^{7

8}, Jill Bell⁹, Vishal Bhatnagar¹⁰, David Cella¹¹, Philip Collis², Amylou C Dueck¹², Alexandra Gilbert¹³, Ari Gnanasakthy¹⁴, Alastair Greystoke¹⁵, Aaron R Hansen^{16

17}, Paul Kamudoni¹⁸, Olga Kholmanskikh¹⁹, Bellinda L King-Kallimanis²⁰, Harlan Krumholz²¹, Anna Minchom²², Daniel O'Connor²³, Joan Petrie²⁴, Claire Piccinin²⁵, Khadija Rerhou Rantell²⁶, Saaeha Rauz^{27

28}, Ameeta Retzer^{29

30}, Steven Rizk³¹, Lynne Wagner³², Maxime Sasseville³³, Lesley K Seymour²⁴, Harald A Weber³⁴, Roger Wilson³⁵, Melanie Calvert^{2

3

4

5

6}, John Devin Peipert¹¹

Affiliations

¹ Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK.
² Centre for Patient-Reported Outcomes Research (CPROR), Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
³ National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC), University Hospital Birmingham and University of Birmingham, Birmingham, UK.
⁴ NIHR Applied Research Collaboration West Midlands, University of Birmingham, Birmingham, UK.
⁵ NIHR Blood and Transplant Research Unit in Precision Transplant and Cellular Therapeutics, University of Birmingham, Birmingham, UK.
⁶ Birmingham Health Partners Centre for Regulatory Science and Innovation, University of Birmingham, Birmingham, UK.
⁷ Lineberger Comprehensive Cancer Center, Chapel Hill, NC, 27514, USA.
⁸ Division of Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, 27514, USA.
⁹ AstraZeneca, Oncology Research and Development, Gaithersburg, MD, USA.
¹⁰ Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD, USA.
¹¹ Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹² Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ, USA.
¹³ Leeds Institute for Medical Research, University of Leeds, St James's University Hospital, Leeds, UK.
¹⁴ RTI Health Solutions, Patient Centered Outcomes Research, Research Triangle Park, NC, USA.
¹⁵ NU Cancer, Newcastle University, Newcastle upon Tyne, UK.
¹⁶ Princess Alexandra Hospital, Cancer Services, Brisbane, Queensland, Australia.
¹⁷ University of Queensland, Faculty of Medicine, Australia.
¹⁸ Merck KGaA, Darmstadt, Germany.
¹⁹ Federal Agency for Medicines and Health Products (FAMHP), Brussels, Belgium.
²⁰ LUNGevity Foundation, Bethesda, MD, USA.
²¹ Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA.
²² Drug Development Unit, Royal Marsden/Institute of Cancer Research, Sutton, UK.
²³ The Association of the British Pharmaceutical Industry, UK.
²⁴ Canadian Cancer Trials Group (CCTG), Kingston, Ontario, Canada.
²⁵ Quality of Life Department, European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
²⁶ Medicines and Healthcare Products Regulatory Agency (MHRA), UK.
²⁷ Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, UK.
²⁸ Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK.
²⁹ Centre for Patient Reported Outcomes Research (CPROR), Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
³⁰ National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
³¹ Veloxis Pharmaceuticals, Cary, NC, USA.
³² University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
³³ Health Canada, Ottawa, Ontario, Canada.
³⁴ Pfizer Oncology, Global Medical Affairs/Early-Stage Development, Zug, Switzerland.
³⁵ Cancer Research Advocates Forum UK, Sarcoma Patient Advocacy Global Network, UK.

Abstract

Early phase clinical trials provide an initial evaluation of therapies' risks and benefits to patients, including safety and tolerability, which typically relies on reporting outcomes by investigator and laboratory assessments. Use of patient-reported outcomes (PROs) to inform risks (tolerability) and benefits (improvement in disease symptoms) is more common in later than early phase trials. We convened a two-day expert roundtable covering: (1) the necessity and feasibility of a universal PRO core conceptual model for early phase trials; (2) the practical integration of PROs in early phase trials to inform tolerability assessment, guide dose decisions, or as real-time safety alerts to enhance investigator-reported adverse events. Participants (n = 22) included: patient advocates, regulators, clinicians, statisticians, pharmaceutical representatives, and PRO methodologists working across diverse clinical areas. In this manuscript, we report major recommendations resulting from the roundtable discussions corresponding to each theme. Additionally, we highlight priority areas necessitating further investigation.

Keywords: Dose-finding; Early phase trials; Patient-centred clinical development; Patient-reported outcomes; Phase I; Phase II; Quality of life; Tolerability; Trial designs.

Publication types

Review