On the Interval-Based Dose-Finding Designs

TL;DR

This paper reviews and compares recent interval-based dose-finding designs for phase I clinical trials, highlighting their differences, similarities, and performance through extensive simulations to guide better decision-making.

Contribution

It provides the most comprehensive simulation-based comparison of interval-based dose-finding designs, clarifying their characteristics and practical implementation insights.

Findings

Interval-based designs outperform traditional methods in certain scenarios.

Decision tables offer valuable transparency for non-statisticians.

Simulation results guide optimal design selection for phase I trials.

Abstract

The landscape of dose-finding designs for phase I clinical trials is rapidly shifting in the recent years, noticeably marked by the emergence of interval-based designs. We categorize them as the iDesigns and the IB-Designs. The iDesigns are originated by the toxicity probability inter- val (TPI) designs and its two modifications, the mTPI and mTPI-2 designs. The IB-Designs started as the cumulative cohort design (CCD) and is recently extended by the BOIN design. We discuss the differences and similarities between these two classes of interval-based designs, and compare their simulation performance with popular non-interval designs, such as the CRM and 3+3 designs. We also show that in addition to the population-level operating characteristics from simulated trials, investigators should also assess the dose-finding decision tables from the implemented designs to better understand the per-trial and per-patient behavior. This is particularly important for nonstatisticians to assess the designs with transparency. We pro- vide, to our knowledge, the most comprehensive simulation-based comparative study on various interval-based dose-finding designs.