- Christina Yap, professor of clinical trials biostatistics
- Clinical Trials and Statistics Unit, Institute of Cancer Research, London, UK
In 2017, I was drafting the first manuscript for a phase I clinical trial. I was familiar with the consolidated standards of reporting trials (Consort) for randomised parallel group trials, so I was surprised by the absence of Consort reporting guidance tailored for early phase dose finding trials.
After searching top medical journals for published dose finding trials to assess how they had been reported, I found huge variation in what was being reported and their quality. This presented some big problems for medical research—poor reporting in clinical trials jeopardises patient safety, erodes public trust, wastes vital resources, and hinders medical progress. Despite the pivotal role of these trials in shaping future clinical development, the importance of quality reporting had arguably been overlooked. It’s undeniable: we need robust reporting guidelines to enhance transparency and ensure reproducibility.
Serendipitously, in 2018 I had the privilege of speaking to the late Doug Altman, a pioneer of the Consort guidance, during the Adaptive Design Consort extension consensus meeting. His enthusiasm for the idea and our subsequent email exchanges inspired me to venture further down this path. And so, the Consort-Define (dose finding committee) guidance was conceived.
The establishment of the Define executive committee was driven by broad recognition by clinicians, trialists, methodologists, and patients of the need to enhance early clinical trial reporting quality. Everyone I approached expressed a willingness to collaborate in tackling this unmet need.
Our journey wasn’t without obstacles. While our first funding application didn’t get the green light, perseverance led to the UK Medical Research Council and National Institute for Health and Care Research funding the study in 2020. While developing Consort-Define, it became increasingly evident that there was also a pressing need to enhance protocols for early phase dose finding trials, linking protocol guidance (Spirit-Define) seamlessly with its reporting counterpart for trial reports (Consort-Define). But roadblocks persisted. Our Spirit-Define application, despite a commendable score of 8 out of 10 and outstanding peer reviews, went unfunded. This situation underlines the often overlooked significance of funding methodology research, the very backbone of rigorous scientific endeavours. Resolute, we leveraged internal resources, and engaged additional external partners to propel the Spirit-Define and Consort-Define vision.
Another challenge was our ambitious goal to encompass early phase dose finding trials across diverse interventions (both pharmacological and non-pharmacological) and disease areas. Given the variations in terminologies and trial designs in areas such as first-in-human trials, oncology, and non-oncology trials, it was imperative for the Define executive committee to precisely define the scope of the guidelines.1
While we anticipated various modifications and additions to the standard Spirit and Consort checklists, what took us by surprise was the sheer number of items that emerged as critically important. Furthermore, while we initially expected participation from around 100 people in the Delphi survey, we were astounded to have 206 participants from 24 different countries contribute to shaping the guidelines2.
The development of these checklists published in The BMJ is just the beginning;34 their consideration and thoughtful implementation is now urgently required. Early phase dose finding trials play a vital role in establishing the foundation for future clinical development. To genuinely enhance their transparency and reporting quality, implementation is the key. Given the recent Reproducibility and Research Integrity 2023 initiative by the UK government5 and similar efforts worldwide, we anticipate the Define guidelines will improve reporting quality and ultimately reduce research inefficiencies and inconsistencies, driving pivotal advances in clinical care.
High quality early clinical trial reporting is not optional—it is our commitment to the patients we serve and a fundamental aspect of conducting high quality research. Together, we can make a difference in the reporting of early phase dose finding trials, improve clinical care, and reap the societal benefits of transformative clinical research.
Define executive committee; Consort-Define is funded by the MRC-NIHR Methodology Research Programme (Grant: MR/T044934/1). The Institute of Cancer Research Clinical Trials and Statistics Unit receives programmatic infrastructure funding from Cancer Research UK (C1491/A25351) which has contributed to accelerating the advancement and successful completion of this work.
Competing interests: none declared.
Provenance and peer review: commissioned, not peer reviewed.