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The design of cross-over studies subject to dropout

The design of cross-over studies subject to dropout
The design of cross-over studies subject to dropout
A cross-over study is a comparitive experiment in which subjects receive a sequence of two or more treatments, one in each of a series of successive time periods, and the response of each subject is measured at the end of every period. A common problem, particularly in medicine, is that subjects fail to complete a study through dropping out during the later stages of the trial for reasons unrelated to the treatments received! Current practice is to select a design for a study on the basis of its performance under the assumption that no subjects drop out, using a criterion such as A-optimality. This is an unrealistic assumption for many medical applications. This thesis investigates how studies should be designed when it is unrealistic to assume that subjects will not drop out.

A method of assessing cross-over designs is presented which judges how accurately all the pairwise treatment comparisons are estimated under the assumption that each subject has a fixed probability of dropping out during the final period, independent of treatment received and the other subjects. The method of design assessment is computationally intensive even for studies involving a relatively small number of subjects. Ways of reducing the amount of computation required are presented through establishing the link between implemented designs and a colouring problem in combinatorial theory. The reductions achieved make feasible investigations of currently used designs for cross-over studies.

The results of investigations are presented for designs for the cases of particular practical importance, namely four treatment, four period and three treatment, three period studies, in which a simple carry-over model is assumed for the observations. Designs which are more robust to final period dropout than the currently favoured designs are identified
University of Southampton
Low, Janice Lorraine
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Low, Janice Lorraine
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Lewis, S.M
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Prescott, Philip
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Low, Janice Lorraine (1995) The design of cross-over studies subject to dropout. University of Southampton, Department of Mathematics, Doctoral Thesis, 273pp.

Record type: Thesis (Doctoral)

Abstract

A cross-over study is a comparitive experiment in which subjects receive a sequence of two or more treatments, one in each of a series of successive time periods, and the response of each subject is measured at the end of every period. A common problem, particularly in medicine, is that subjects fail to complete a study through dropping out during the later stages of the trial for reasons unrelated to the treatments received! Current practice is to select a design for a study on the basis of its performance under the assumption that no subjects drop out, using a criterion such as A-optimality. This is an unrealistic assumption for many medical applications. This thesis investigates how studies should be designed when it is unrealistic to assume that subjects will not drop out.

A method of assessing cross-over designs is presented which judges how accurately all the pairwise treatment comparisons are estimated under the assumption that each subject has a fixed probability of dropping out during the final period, independent of treatment received and the other subjects. The method of design assessment is computationally intensive even for studies involving a relatively small number of subjects. Ways of reducing the amount of computation required are presented through establishing the link between implemented designs and a colouring problem in combinatorial theory. The reductions achieved make feasible investigations of currently used designs for cross-over studies.

The results of investigations are presented for designs for the cases of particular practical importance, namely four treatment, four period and three treatment, three period studies, in which a simple carry-over model is assumed for the observations. Designs which are more robust to final period dropout than the currently favoured designs are identified

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Published date: 1995
Organisations: University of Southampton

Identifiers

Local EPrints ID: 381795
URI: http://eprints.soton.ac.uk/id/eprint/381795
PURE UUID: 88a65e4e-29ff-4ed2-838d-7e63a4f9534e

Catalogue record

Date deposited: 23 Sep 2015 15:46
Last modified: 06 Jun 2019 16:31

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Contributors

Author: Janice Lorraine Low
Thesis advisor: S.M Lewis
Thesis advisor: Philip Prescott

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