Up-and-Down Designs | Wikipedia audio article
Channel: wikipedia tts
Date: 06/10/2019

This is an audio version of the Wikipedia Article:
https://en.wikipedia.org/wiki/Up-and-Down_Designs


00:00:14 1 Mathematical Description
00:00:22 1.1 Definition
00:00:59 1.2 The Transition Probability Matrix
00:01:44 1.3 The Balance Point
00:01:59 1.4 The Stationary Distribution of Dose Allocations
00:02:13 2 Common Up-and-Down Designs
00:02:21 2.1 The Original ("Simple" or "Classical") UDD
00:02:36 2.2 Durham and Flournoy's Biased Coin Design
00:02:58 2.3 Group (Cohort) UDDs
00:03:35 3 Estimating the Target Dose
00:04:35 4 References



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SUMMARY
=======
Up-and-Down Designs (UDDs) are a family of statistical experiment designs used in dose-finding experiments in science, engineering, and medical research. Dose-finding experiments have binary responses: each individual outcome can be described as one of two possible values, such as success vs. failure or toxic vs. non-toxic. Mathematically the binary responses are coded as 1 and 0. The goal of dose-finding experiments is to estimate the strength of treatment (i.e., the 'dose') that would trigger the "1" response a pre-specified proportion of the time. This dose can be envisioned as a percentile of the distribution of response thresholds. An example where dose-finding is used: an experiment to estimate the LD50 of some toxic chemical with respect to mice.

Dose-finding designs are sequential and response-adaptive: the dose at a given point in the experiment depends upon previous outcomes, rather than be fixed a priori. Dose-finding designs are generally more efficient for this task than fixed designs, but their properties are harder to analyze, and some require specialized design software. UDDs use a discrete set of doses rather than vary the dose continuously. They are relatively simple to implement, and are also among the best understood dose-finding designs. Despite this simplicity, UDDs generate random walks with intricate properties. The original UDD aimed to find the median threshold by increasing the dose one level after a "0" response, and decreasing it one level after a "1" response. Hence the name "Up-and-Down". Other UDDs break this symmetry in order to estimate percentiles other than the median, or are able to treat groups of subjects rather than one at a time.
UDDs were developed in the 1940s by several research groups independently. The 1950s and 1960s saw rapid diversification with UDDs targeting percentiles other then the median, and expanding into numerous applied fields. The 1970s to early 1990s saw little UDD methods research, even as the design continued to be used extensively. A revival of UDD research since the 1990s has provided deeper understanding of UDDs and their properties, and new and better estimation methods.UDDs are still used extensively in the two applications for which they were originally developed: psychophysics where they are used to estimate sensory thresholds and are often known as fixed forced-choice staircase procedures, and explosive sensitivity testing, where the median-targeting UDD is often known as the Bruceton test. UDDs are also very popular in toxicity and anesthesiology research. They are also considered a viable choice for Phase I clinical trials.