The CONSORT (CONsolidated Standards Of Reporting Trials) 2010 statement is the standard guideline for reporting completed randomised trials. The CONSORT Dose-finding Extension (DEFINE) extends the guidance (with 21 new items and 19 modified items) to early phase dose-finding trials with interim dose escalation or de-escalation strategies. Such trials generally focus on safety, tolerability, activity, and recommending dosing and scheduling regimens for further clinical development. These trials are often inadequately reported, hampering their informativeness and making evidence informed decisions difficult. The CONSORT-DEFINE guidance aims to develop an international, consensus driven guideline for reporting early phase dose-finding trials to promote transparency, completeness, reproducibility, and facilitate the interpretation of the results. The CONSORT-DEFINE guidance provides recommendations for essential items that should be reported in early phase dose-finding trials to promote greater clarity, reproducibility, informativeness, and usefulness of results.
Early phase dose-finding (EPDF) or dose escalation or de-escalation trials, commonly known as phase 1 or phase 1 or 2 trials, are an integral part of clinical development. EPDF trials typically evaluate new interventions that can be given in different doses and can be pharmacological (chemical or biological—eg, drugs, vaccines, cell therapies, gene therapies), non-pharmacological (eg, radiotherapy, rehabilitation, devices, digital therapies), or a combination of both. These trials require interim decisions on dosing changes of an intervention and generate data on safety and other information such as pharmacokinetics, pharmacodynamics, biomarker, or clinical activity to guide dosing selection and future clinical development.1234 In this article, a broad definition of “dose” is applied, because terms such as “dose finding,” “dose escalation,” “dose de-escalation,” “dose expansion,” and “dose level” are widely used. Here, dose might refer not only to the amount but also to the frequency, intensity, or duration of an intervention.5 The term could therefore be regarded as synonymous and used interchangeably …