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Simultaneous estimation of parameters in the bivariate Emax model
Stockholms universitet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
Stockholms universitet, Samhällsvetenskapliga fakulteten, Statistiska institutionen.
Antal upphovsmän: 22015 (Engelska)Ingår i: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 34, nr 28, s. 3714-3723Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

In this paper, we explore inference in multi-response, nonlinear models. By multi-response, we mean models with m > 1 response variables and accordingly m relations. Each parameter/explanatory variable may appear in one or more of the relations. We study a system estimation approach for simultaneous computation and inference of the model and (co)variance parameters. For illustration, we fit a bivariate Emax model to diabetes dose-response data. Further, the bivariate Emax model is used in a simulation study that compares the system estimation approach to equation-by-equation estimation. We conclude that overall, the system estimation approach performs better for the bivariate Emax model when there are dependencies among relations. The stronger the dependencies, the more we gain in precision by using system estimation rather than equation-by-equation estimation.

Ort, förlag, år, upplaga, sidor
2015. Vol. 34, nr 28, s. 3714-3723
Nyckelord [en]
multi-response nonlinear models, system estimation, clinical trials, Emax model
Nationell ämneskategori
Sannolikhetsteori och statistik
Forskningsämne
statistik
Identifikatorer
URN: urn:nbn:se:su:diva-176165DOI: 10.1002/sim.6585ISI: 000363940700006PubMedID: 26190048OAI: oai:DiVA.org:su-176165DiVA, id: diva2:1375834
Tillgänglig från: 2019-12-06 Skapad: 2019-12-06 Senast uppdaterad: 2019-12-06Bibliografiskt granskad
Ingår i avhandling
1. Estimation and optimal designs for multi-response Emax models
Öppna denna publikation i ny flik eller fönster >>Estimation and optimal designs for multi-response Emax models
2014 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

This thesis concerns optimal designs and estimation approaches for a class of nonlinear dose response models, namely multi-response Emax models. These models describe the relationship between the dose of a drug and two or more efficacy and/or safety variables. In order to obtain precise parameter estimates it is important to choose efficient estimation approaches and to use optimal designs to control the level of the doses administered to the patients in the study.

We provide some optimal designs that are efficient for estimating the parameters, a subset of the parameters, and a function of the parameters in multi-response Emax models. The function of interest is an estimate of the best dose to administer to a group of patients. More specifically the dose that maximizes the Clinical Utility Index (CUI) which assesses the net benefit of a drug taking both effects and side-effects into account. The designs derived in this thesis are locally optimal, that is they depend upon the true parameter values. An important part of this thesis is to study how sensitive the optimal designs are to misspecification of prior parameter values.

For multi-response Emax models it is possible to derive maximum likelihood (ML) estimates separately for the parameters in each dose response relation. However, ML estimation can also be carried out simultaneously for all response profiles by making use of dependencies between the profiles (system estimation). In this thesis we compare the performance of these two approaches by using a simulation study where a bivariate Emax model is fitted and by fitting a four dimensional Emax model to real dose response data. The results are that system estimation can substantially increase the precision of parameter estimates, especially when the correlation between response profiles is strong or when the study has not been designed in an efficient way.

Ort, förlag, år, upplaga, sidor
Stockholm: Department of Statistics, Stockholm University, 2014. s. 38
Nyckelord
multi-response Emax models, Clinical Utility Index (CUI), optimal designs, system estimation, dose-response studies.
Nationell ämneskategori
Sannolikhetsteori och statistik
Forskningsämne
statistik
Identifikatorer
urn:nbn:se:su:diva-102888 (URN)978-91-7447-909-6 (ISBN)
Disputation
2014-05-30, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 13:00 (Engelska)
Opponent
Handledare
Anmärkning

At the time of the doctoral defence the following papers were unpublished and had a status as follows: Paper 1: Manuscript; Paper 2: Manuscript; Paper 3: Manuscript; Paper 4: Manuscript.

Tillgänglig från: 2014-05-08 Skapad: 2014-04-24 Senast uppdaterad: 2019-12-06Bibliografiskt granskad

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Magnúsdóttir, Bergrún TinnaNyquist, Hans
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