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PhD Dissertation 2016.pdf (553.51 KB)
ETD Abstract Container
Abstract Header
Dose-Response Analysis for Time-Dependent Efficacy
Author Info
Islam, Mohammad Mafijul
ORCID® Identifier
http://orcid.org/0000-0001-6508-6771
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1467295354
Abstract Details
Year and Degree
2016, Doctor of Philosophy (Ph.D.), Bowling Green State University, Statistics.
Abstract
In dose-response studies, a critical research issue is to estimate the minimum effective dose (MED) and the Maximum Tolerated dose (MTD) of a drug. The problems of identifying the minimum effective dose and the maximum tolerated dose of a drug have been studied by many researchers when the endpoints are continuous and binary, and are measured at a particular time point. However, in recent dose-response related research, the responses are measured over a sequence of time points. In this situation, the previously developed procedures for the continuous and binary outcomes at a single time point are not applicable for the estimations of MED and the MTD of a drug when the longitudinal effect of the drug is taken into consideration. In this dissertation, we developed statistical procedures to find the MED and the MTD of a drug when the responses are observed over a period of time at different dose levels. Since finding the time-dependent MED and MTD of a drug is a multiple comparison problem, we need to control the family-wise error rate, the probability of incorrectly declaring any ineffective doses of a drug as effective for MED (or any unsafe doses as safe for MTD) at a pre-specified level of significance (alpha) for the adjustment of multiplicity. Two types of statistical procedures are developed to address the problem of time dependent MED (and MTD) in this dissertation. One type is with multiplicity adjustment such as the Bonferroni Correction method for MED (and for MTD, respectively). And another is without multiplicity adjustment such as the partitioning method for MTD (and for MTD, respectively). In our study, we assumed that both the efficacy and the toxicity of a drug increase with the dose level over time. The consequence of this assumption is that if a dose is not declared as efficacious, then we stop checking the lower doses when evaluating efficacy (or if a dose is not declared as safe, we do not need to test the higher doses for toxicity investigation). In this dissertation, we used the partitioning principle to propose confidence-set based procedures for estimating the minimum effective dose (MED) and the maximum tolerated dose(MTD) of a drug when the responses are measured over time at different dose levels. The proposed procedures are compared by simulation studies, which cast new lights on the power performance of different innovative procedures proposed in this dissertation. We proved that the simultaneous confidence regions have the correct coverage probability 1 - alpha, and applied these procedures to analyze two real data sets. One is for the beetle killing effect on a plant based insecticide (Pyrethrurm); and another is for the hind-limb grip strength of rats under different levels of toxicity over time. The new confidence procedures proposed in this dissertation reveal new insights on the efficacy for insecticide over time, and neurotoxic effects on nervous system of rats over time. They also enhance the literature on statistical methodologies for time dependent dose-response research.
Committee
John Chen (Advisor)
Hanfeng Chen (Committee Member)
Junfeng Shang (Committee Member)
Vipaporn Phuntumart (Other)
Pages
95 p.
Subject Headings
Statistics
Keywords
Minimum Effective Dose
;
Maximum Tolerated Dose
;
Partitioning Principle
;
Bonferroni Correction
;
Recommended Citations
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Mendeley
Citations
Islam, M. M. (2016).
Dose-Response Analysis for Time-Dependent Efficacy
[Doctoral dissertation, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1467295354
APA Style (7th edition)
Islam, Mohammad .
Dose-Response Analysis for Time-Dependent Efficacy.
2016. Bowling Green State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1467295354.
MLA Style (8th edition)
Islam, Mohammad . "Dose-Response Analysis for Time-Dependent Efficacy." Doctoral dissertation, Bowling Green State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1467295354
Chicago Manual of Style (17th edition)
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Document number:
bgsu1467295354
Download Count:
379
Copyright Info
© 2016, all rights reserved.
This open access ETD is published by Bowling Green State University and OhioLINK.