Dose-finding design based on level set estimation in phase I cancer clinical trials Keiichiro Seno 1 a, Kota Matsui 2b, Shogo Iwazaki 3, Yu Inatsu 4, Shion Takeno 5, 6 and Shigeyuki Matsui 2, 7 1 Department of Biostatistics, Nagoya University 2 Department of Biostatistics, Kyoto University 3 MI-6 Ltd. 4 Department of Computer Science, Nagoya Institute of Technology 5 Department of Mechanical Systems Engineering, Nagoya University 6 Center for Advanced Intelligence Project, RIKEN 7 Research Center for Medical and Health Data Science, The Institute of Statistical Mathematics Abstract The primary objective of phase I cancer clinical trials is to evaluate the safety of a new experimental treatment and to find the maximum tolerated dose (MTD). We show that the MTD estimation problem can be regarded as a level set estimation (LSE) problem whose objective is to determine the regions where an unknown function value is above or below a given threshold. Then, we propose a novel ...

The objective of active level set estimation for a black-box function is to precisely identify regions where the function values exceed or fall below a specified threshold by iteratively performing function evaluations to gather more information about the function. This becomes particularly important when function evaluations are costly, drastically limiting our ability to acquire large datasets. A promising way to sample-efficiently model the black-box function is by incorporating prior knowledge from a related function. However, this approach risks slowing down the estimation task if the prior knowledge is irrelevant or misleading. In this paper, we present a novel transfer learning method for active level set estimation that safely integrates a given prior knowledge while constantly adjusting it to guarantee a robust performance of a level set estimation algorithm even when the prior knowledge is irrelevant. We theoretically analyze this algorithm to show that it has a better level set convergence compared to standard transfer learning approaches that do not make any adjustment to the prior. Additionally, extensive experiments across multiple datasets confirm the effectiveness of our method when applied to various different level set estimation algorithms as well as different transfer learning scenarios.

Level set estimation (LSE), the problem of identifying the set of input points where a function takes value above (or below) a given threshold, is important in practical applications. When the function is expensive-to-evaluate and black-box, the \textit{straddle} algorithm, which is a representative heuristic for LSE based on Gaussian process models, and its extensions having theoretical guarantees have been developed. However, many of existing methods include a confidence parameter $\beta^{1/2}_t$ that must be specified by the user, and methods that choose $\beta^{1/2}_t$ heuristically do not provide theoretical guarantees. In contrast, theoretically guaranteed values of $\beta^{1/2}_t$ need to be increased depending on the number of iterations and candidate points, and are conservative and not good for practical performance. In this study, we propose a novel method, the \textit{randomized straddle} algorithm, in which $\beta_t$ in the straddle algorithm is replaced by a random sample from the chi-squared distribution with two degrees of freedom. The confidence parameter in the proposed method has the advantages of not needing adjustment, not depending on the number of iterations and candidate points, and not being conservative. Furthermore, we show that the proposed method has theoretical guarantees that depend on the sample complexity and the number of iterations. Finally, we confirm the usefulness of the proposed method through numerical experiments using synthetic and real data.

A common problem encountered in many real-world applications is level set estimation where the goal is to determine the region in the function domain where the function is above or below a given threshold. When the function is black-box and expensive to evaluate, the level sets need to be found in a minimum set of function evaluations. Existing methods often assume a discrete search space with a finite set of data points for function evaluations and estimating the level sets. When applied to a continuous search space, these methods often need to first discretize the space which leads to poor results while needing high computational time. While some methods cater for the continuous setting, they still lack a proper guarantee for theoretical convergence. To address this problem, we propose a novel algorithm that does not need any discretization and can directly work in continuous search spaces. Our method suggests points by constructing an acquisition function that is defined as a measure of confidence of the function being higher or lower than the given threshold. A theoretical analysis for the convergence of the algorithm to an accurate solution is provided. On multiple synthetic and real-world datasets, our algorithm successfully outperforms state-of-the-art methods.