Patient-reported adverse events may be a useful adjunct for assessing a drug’s tolerability in DPOT. A review of DPOT registered on clinicaltrials.gov showed increasing use of PROs over time, but overall use remained limited. Little is known about the reasons for limited PRO use. We conducted a global online survey of key stakeholders to understand attitudes towards PROs in DPOT.
A 35-question survey of clinicians, trial managers, statisticians, funders and regulators involved in DPOT in hospitals, academia or industry distributed via professional bodies. Questions focussed on prior experience of designing, conducting and reporting DPOT with PROs, attitudes towards benefits and barriers to PRO use and their potential role in defining tolerable doses. Adaptive questioning was used. No identifiable data was collected.
112 responses from 15 September to 30 November 2020; 103 trialists [48 clinicians (42.9%), 38 statisticians (34.0%), 17 trial managers (15.2%)], 7 regulators (6.3%) and 2 funders (1.8%). Most had worked in DPOT for 6-10 years (35, 31.3%). Most worked in the United Kingdom (65, 58.0%) or United States (22, 19.6%). Most trialists had no prior experience designing (73, 70.9%), conducting (52, 50.5%) or reporting (88, 85.4%) PROs in DPOT. Respondents strongly agreed/ agreed that PROs could identify new toxicities (75, 67.0%), provide data regarding frequency (86, 76.8%) and duration (81, 72.3%) of toxicities, especially in agents with moderate, chronic or delayed toxicities (77, 68.8%). Respondents agreed that PROs should be reviewed when making dose-escalation decisions (61, 54.5%), when determining the maximum tolerated dose (63, 56.3%) and recommended phase II dose (76, 67.9%). Top 5 concerns were: lack of guidance regarding PRO selection (73/103, 70.9%), missing PRO data (79/112, 70.5%), overburdening staff (68/103, 66.0%) or patients (57/103, 55.3%), and analysis and publication (58/112, 51.8%).
Key stakeholders reported minimal experience collecting and analysing PROs in DPOT. However, there was broad support for using PROs to inform selection of tolerable doses. Guidelines are needed to standardise selection, analysis and reporting, and increase efficiency of PRO collection in DPOT.
Christina Yap.
Has not received any funding.
A. Minchom: Honoraria (institution), Advisory/Consultancy: Merck; Honoraria (institution), Advisory/Consultancy: Faron; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Janssen. All other authors have declared no conflicts of interest.