Details

Autor(en) / Beteiligte

• Takeda, Kentaro
• Morita, Satoshi
• Taguri, Masataka

Titel

TITE‐BOIN‐ET: Time‐to‐event Bayesian optimal interval design to accelerate dose‐finding based on both efficacy and toxicity outcomes

Ist Teil von

• Pharmaceutical statistics : the journal of the pharmaceutical industry, 2020-05, Vol.19 (3), p.335-349

Ort / Verlag

Chichester, UK: John Wiley & Sons, Inc

Erscheinungsjahr

2020

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Summary One of the primary purposes of an oncology dose‐finding trial is to identify an optimal dose (OD) that is both tolerable and has an indication of therapeutic benefit for subjects in subsequent clinical trials. In addition, it is quite important to accelerate early stage trials to shorten the entire period of drug development. However, it is often challenging to make adaptive decisions of dose escalation and de‐escalation in a timely manner because of the fast accrual rate, the difference of outcome evaluation periods for efficacy and toxicity and the late‐onset outcomes. To solve these issues, we propose the time‐to‐event Bayesian optimal interval design to accelerate dose‐finding based on cumulative and pending data of both efficacy and toxicity. The new design, named “TITE‐BOIN‐ET” design, is nonparametric and a model‐assisted design. Thus, it is robust, much simpler, and easier to implement in actual oncology dose‐finding trials compared with the model‐based approaches. These characteristics are quite useful from a practical point of view. A simulation study shows that the TITE‐BOIN‐ET design has advantages compared with the model‐based approaches in both the percentage of correct OD selection and the average number of patients allocated to the ODs across a variety of realistic settings. In addition, the TITE‐BOIN‐ET design significantly shortens the trial duration compared with the designs without sequential enrollment and therefore has the potential to accelerate early stage dose‐finding trials.