Trends in patient-reported outcome use in early phase dose-finding oncology trials - an analysis of ClinicalTrials.gov

Patient-reported adverse events (AEs) may be a useful adjunct to clinician-assessed AEs for assessing tolerability in early phase, dose-finding oncology trials (DFOTs). We reviewed DFOTs on ClinicalTrials.gov to describe trends in patient-reported outcome (PRO) use.

DFOTs commencing 01 January 2007 - 20 January 2020 with 'PROs' or 'quality of life' as an outcome were extracted and inclusion criteria confirmed. Study and PRO characteristics were extracted. Completed trials that reported PRO outcomes and published manuscripts on ClinicalTrials.gov were identified, and PRO reporting details were extracted.

5.3% (548/10 372) DFOTs included PROs as an outcome. 231 (42.2%) were eligible: adult (224, 97%), solid tumour (175, 75.8%), and seamless phase 1/2 (108, 46.8%). PRO endpoints were identified in more trials (2.3 increase/year, 95% CI: 1.6-2.9) from an increasing variety of countries (0.7/year) (95% CI: 0.4-0.9) over time. PROs were typically secondary endpoints (207, 89.6%). 15/77 (19.5%) completed trials reported results on the ClinicalTrials.gov results database, and of those eight included their PRO results. Eighteen trials had published manuscripts available on ClinicalTrials.gov. Three (16.7%) used PROs to confirm the maximum tolerated dose. No trials identified who completed the PROs or how PROs were collected.

PRO use in DFOT has increased but remains limited. Future work should explore the role of PROs in DFOT and determine what guidelines are needed to standardise PRO use.