Patient-reported adverse events may be a useful adjunct for assessing a drug’s tolerability in DFOT. However, PRO use is limited and the reasons for this are unknown. We conducted a global online stakeholder survey and a survey at the NCRI Consumer Forum to understand attitudes to PROs in DFOT.
A 35-question survey of clinicians, trial managers, statisticians, funders and regulators of DFOT from hospitals, academia or industry was distributed via professional bodies. Questions examined prior experience of using PROs, benefits/ barriers to PRO use and their potential role in defining tolerable doses. An 8-question survey of the NCRI Consumer Forum explored similar themes with patients and carers.
Global survey: 112 responses from 15 September-30 November 2020; 103 trialists [48 clinicians (42.9%), 38 statisticians (34.0%), 17 trial managers (15.2%)], 7 regulators (6.3%), 2 funders (1.8%). Most trialists had no prior experience designing (73, 70.9%), conducting (52, 50.5%) or reporting (88, 85.4%) PROs in DFOT. Most agreed PROs could identify new toxicities (75, 67.0%) and provide data on frequency (86, 76.8%) and duration (81, 72.3%) of toxicities. The top 3 barriers were lack of guidance regarding PRO selection (73/103, 70.9%), missing PRO data (79/112, 70.5%), and overburdening staff (68/103, 66.0%). NCRI survey: 57 responses on 21 March 2021. 27 (48.2%) were willing to spend ≤15 minutes/day completing PROs. Most (55, 96.4%) preferred to complete PROs online. There was broad support for using PROs to inform selection of tolerable doses (table). Table: 520MO
|Strongly agreed/ agreed (n, %)|
|Global survey (n=112)||NCRI Consumer forum survey (n=57)|
|PROs should be communicated in real-time to investigators||62 (55.3%)||54 (94.7%)|
|PROs on adverse events (in conjunction with clinician- assessed CTCAE data) should be used to inform dose escalation decisions||61 (54.5%)||57 (100%)|
|PROs on adverse events (in conjunction with clinician- assessed CTCAE data) should be used to inform the maximum tolerated dose||63 (56.3%)||Not assessed|
|PROs on adverse events (in conjunction with clinician- assessed CTCAE data) should be used to inform the recommended phase 2 dose||76 (67.9%)||54 (94.7%)|
Trialists and consumers reported minimal prior experience using PROs in DFOT but broadly supported their use in defining tolerable doses. Collaboration between key stakeholders and consumers should inform the research agenda in this area. Guidelines are needed to standardise PRO selection, analysis and reporting in DFOT.
Clinical trial identification
Legal entity responsible for the study
All authors are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The authors also acknowledge funding from Cancer Research UK and the Experimental Cancer Centre Initiative.
A. Minchom: Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Advisory Board: FARON; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: Janssen. C. Yap: Financial Interests, Institutional, Funding: FARON; Financial Interests, Institutional, Funding: Celgene. All other authors have declared no conflicts of interest.