Joint TITE-CRM: A Design for Dose Finding Studies for Therapies with Late-Onset Safety and Activity Outcomes.

In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and shows sufficient activity that maximizes some optimality criterion based on safety and activity. In cancer, treatment is typically given over several cycles, complicating the identification of the OBD as both toxicity and activity outcomes may occur at any point throughout the follow up of multiple cycles. In this work we present and assess the Joint TITE-CRM, a model-based design for late onset toxicities and activity based on the well-known TITE-CRM.

SPIRIT-DEFINE explanation and elaboration: recommendations for enhancing quality and impact of early phase dose-finding clinical trials protocols.

Unlabelled: Transparent and accurate reporting in early phase dose-finding (EPDF) clinical trials is crucial for informing subsequent larger trials. The SPIRIT statement, designed for trial protocol content, does not adequately cover the distinctive features of EPDF trials. Recent findings indicate that the protocol contents in past EPDF trials frequently lacked completeness and clarity.

CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.

Unlabelled: Early phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical development phases and providing valuable insights for reverse translation. Comprehensive and transparent reporting of these studies is critical for their accurate and critical interpretation, which may improve and expedite therapeutic development. However, quality of reporting of design characteristics and results from EPDF trials is often variable and incomplete.

A Preplanned Multi-Stage Platform Trial for Discovering Multiple Superior Treatments With Control of FWER and Power.

There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed superiority. In such trials, it can be important to ensure that error rates are controlled. This paper introduces a multi-stage design that enables the addition of new treatment arms, at any point, in a preplanned manner within a platform trial, while still maintaining control over the family-wise error rate.

Adaptive enrichment trial designs using joint modelling of longitudinal and time-to-event data.

Adaptive enrichment allows for pre-defined patient subgroups of interest to be investigated throughout the course of a clinical trial. These designs have gained attention in recent years because of their potential to shorten the trial's duration and identify effective therapies tailored to specific patient groups. We describe enrichment trials which consider long-term time-to-event outcomes but also incorporate additional short-term information from routinely collected longitudinal biomarkers.