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Identifying the right dose is one of the most important decisions in drug development. Adaptive designs are promoted to conduct dose-finding clinical trials as they are more efficient and ethical compared with static designs. However, current techniques in response-adaptive designs for dose allocation are complex and need significant computational effort, which is a major impediment for implementation in practice. This study proposes a Bayesian nonparametric framework for estimating the dose-response curve, which uses a piecewise linear approximation to the curve by consecutively connecting the expected mean response at each dose. Our extensive numerical results reveal that a first-order Bayesian nonparametric model with a known correlation structure in prior for the expected mean response performs competitively when compared with the standard approach and other more complex models in terms of several relevant metrics and enjoys computational efficiency. Furthermore, structural properties for the optimal learning problem, which seeks to minimize the variance of the target dose, are established under this simple model. Summary of Contribution: In this work, we propose a methodology to derive efficient patient allocation rules in response-adaptive dose-finding clinical trials, where computational issues are the main concern. We show that our methodologies are competitive with the state-of-the-art methodology in terms of solution quality, are significantly more computationally efficient, and are more robust in terms of the shape of the dose-response curve, among other parameter changes. This research fits in “the intersection of computing and operations research” as it adapts operations research techniques to produce computationally attractive solutions to patient allocation problems in dose-finding clinical trials.
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Quantal Risk Assessment Database: A Database for Exploring Patterns in Quantal Dose‐Response Data in Risk Assessment and its Application to Develop Priors for Bayesian Dose‐Response Analysis
Abstract Quantitative risk assessments for physical, chemical, biological, occupational, or environmental agents rely on scientific studies to support their conclusions. These studies often include relatively few observations, and, as a result, models used to characterize the risk may include large amounts of uncertainty. The motivation, development, and assessment of new methods for risk assessment is facilitated by the availability of a set of experimental studies that span a range of dose‐response patterns that are observed in practice. We describe construction of such a historical database focusing on quantal data in chemical risk assessment, and we employ this database to develop priors in Bayesian analyses. The database is assembled from a variety of existing toxicological data sources and contains 733 separate quantal dose‐response data sets. As an illustration of the database's use, prior distributions for individual model parameters in Bayesian dose‐response analysis are constructed. Results indicate that including prior information based on curated historical data in quantitative risk assessments may help stabilize eventual point estimates, producing dose‐response functions that are more stable and precisely estimated. These in turn produce potency estimates that share the same benefit. We are confident that quantitative risk analysts will find many other applications and issues to explore using this database.
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- Award ID(s):
- 1740858
- PAR ID:
- 10078351
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Risk Analysis
- Volume:
- 39
- Issue:
- 3
- ISSN:
- 0272-4332
- Page Range / eLocation ID:
- p. 616-629
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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