Reporting quality of CONSORT flow diagrams in published early phase dose-finding clinical trial reports: Improvement is needed

Abstract

Background: This project aims to: (1) assess the completeness of information in flow diagrams of published early phase dose-finding (EPDF) trials based on CONSORT recommendations, and if additional features on dose (de-)escalation were presented; (2) propose new flow diagrams presenting how doses were (de-)escalated throughout the trial.

Methods: Flow diagrams were extracted from a random sample of 259 EPDF trials, published from 2011 to 2020 indexed in PubMed. Diagrams were scored out of 15 following CONSORT recommendations with an additional score for presence of (de-)escalation. New templates were proposed for features that were deficient and presented to 39 methodologists and 11 clinical trialists in October and December 2022.

Results: 98 (38%) papers included a flow diagram. Flow diagrams were most deficient in the reporting of reasons for lost to follow up (2%) and reasons for not receiving allocated intervention (14%). Few (39%) presented sequential dose-decision stages. Of voting methodologists, 33/38 (87%) agreed or strongly agreed that for participants recruited in cohorts, presenting the (de-)escalation steps in the flow diagram is a useful feature, also expressed by the trial investigators. Most workshop attendees (35/39, 90%) preferred a larger dose to be displayed higher up within the flow diagram than a smaller dose.

Conclusion: Most published trials do not provide a flow diagram, and for those that do, essential information is often omitted. EPDF flow diagrams capturing information on participant flow in the trial's journey, encapsulated within one figure, are highly recommended to promote transparency and interpretability of trial results.

Keywords: CONSORT; Dose-finding; Flow diagrams; Methodological review; Phase I trial; Publication.