Deficiencies in the reporting of early phase dose-finding oncology trials: findings from a rapid scoping review


Session type:

Christina Yap1, Olga Solovyeva1, Jonathan Martin2, Thubeena Manickavasagar2, Christopher Weir3, Shing Lee4, Munyaradzi Dimairo5, Rong Liu6, Andrew Kightley1, Johann de Bono2
1Institute of Cancer Research (ICR), 2Other, 3University of Edinburgh, 4Columbia University, 5University of Sheffield, 6Bristol-Myers Squibb Pharmaceuticals Ltd



Incomplete, unclear, or inaccurate reporting of the design, conduct and analysis of early phase dose-finding trials can hinder interpretability, reproducibility and impact on timely clinical development and lead to erroneous conclusions on tolerability and efficacy. There currently exists no work that comprehensively assesses the reporting quality in this setting - this scoping review addresses this gap by investigating the quality of published trials using broadly the CONSORT 2010 checklist with added items unique to dose-finding trials.


MEDLINE via PubMed was searched for articles published in English, from 2011 to 2020. Phase I or I/II trials, where interim dosing-decisions have to be undertaken using accumulating data to either escalate, de-escalate, stay at the current level or stop a trial early, with the aim of identifying a recommended dosing regimen(s) for further testing, were included. Trials that did not include interim dosing-decisions were excluded. Results were screened for inclusion and data extracted for 238 randomly selected oncology trials over three stages, with a sample validated by independent reviewers.


As of June 2021, preliminary data based on 48 trials suggest that the key items that are often omitted include:


·         Method of recruitment;

·         Definition of analysis population sets for key outcomes;

·         Planned/maximum sample size, with justification;

·         Oversight committees (role and reporting structure);

·         Who makes the dosing decisions;


·         Baseline demographic and clinical characteristics by each dose level;

·         Participant flow; with ordering of the outcomes (that inform interim dosing decisions) and capturing dose allocation;

·         Losses and exclusions (together with reasons) for each dose level

Notably, very few trials provided accessible protocols. Full results from all 238 trials will be presented.


Reports of dose-finding trials frequently omit important methodological features in design, conduct and analysis. This scoping review further confirmed the need for a robust and comprehensive consensus-driven reporting guidance for authors and journals reporting dose-finding trials, to enhance transparency, completeness, reproducibility, and interpretation to reduce research waste.  

Impact statement

Our findings highlight the gaps in the reporting of dose-finding oncology trials and will lay the foundation for the ongoing development of the CONSORT Extension for early phase dose-finding trials.