80MO - Optimising participant flow diagrams for phase I clinical trials

Background

CONSORT 2010 recommends the use of flow diagrams within Randomised Control Trials (RCTs). Phase I trial designs have dose-finding features not captured by flow diagrams for RCTs, yet there are currently no recommendations on diagrams for these trials. This project aims to: (1) assess the completeness of information in flow diagrams of phase I published 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 phase I papers across all diseases, published from 2011-2020 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 attendees at the 7th Early Phase Adaptive Workshop held in October 2022 and 11 members of the Drug Development Unit (DDU) team at the Institute of Cancer Research in December 2022.

Results

98 (38%) papers included a flow diagram. Flow diagrams best reported the number of patients allocated to intervention (95%) and received allocated intervention (55%). 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 dose-decision stages. Non-cancer trials presented more flow diagrams in their publications than cancer trials (56%, 20.9% respectively), with better quality of reporting (46.9%, 34.3%). Of the voting workshop attendees, 33/38 (87%) agreed or strongly agreed that for patients recruited in cohorts, presenting the (de-)escalation steps in the flow diagram is a useful feature, also expressed by the DDU team. Most workshop attendees (35/39, 90%) preferred a larger dose to be displayed higher up within the flow diagram than a smaller dose.

Conclusions

Most published trials do not provide a flow diagram, and for those that do, essential information is often omitted. Phase I 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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.