Penalized spline modeling of the ex-vivo assays dose-response curves and the HIV-infected patients' bodyweight change
dc.contributor.advisor | Harezlak, Jaroslaw | |
dc.contributor.author | Sarwat, Samiha | |
dc.contributor.other | Yiannoutsos, Constantin T. | |
dc.contributor.other | Li, Xiaochun | |
dc.contributor.other | Wools-Kaloustian, Kara K. | |
dc.date.accessioned | 2016-01-08T16:51:36Z | |
dc.date.available | 2017-10-05T09:30:15Z | |
dc.date.issued | 2015-06-05 | |
dc.degree.date | 2015 | |
dc.degree.discipline | Biostatistics | |
dc.degree.grantor | Indiana University | |
dc.degree.level | Ph.D. | |
dc.description | Indiana University-Purdue University Indianapolis (IUPUI) | en_US |
dc.description.abstract | A semi-parametric approach incorporates parametric and nonparametric functions in the model and is very useful in situations when a fully parametric model is inadequate. The objective of this dissertation is to extend statistical methodology employing the semi-parametric modeling approach to analyze data in health science research areas. This dissertation has three parts. The first part discusses the modeling of the dose-response relationship with correlated data by introducing overall drug effects in addition to the deviation of each subject-specific curve from the population average. Here, a penalized spline regression method that allows modeling of the smooth dose-response relationship is applied to data in studies monitoring malaria drug resistance through the ex-vivo assays.The second part of the dissertation extends the SiZer map, which is an exploratory and a powerful visualization tool, to detect underlying significant features (increase, decrease, or no change) of the curve at various smoothing levels. Here, Penalized Spline Significant Zero Crossings of Derivatives (PS-SiZer), using a penalized spline regression, is introduced to investigate significant features in correlated data arising from longitudinal settings. The third part of the dissertation applies the proposed PS-SiZer methodology to analyze HIV data. The durability of significant weight change over a period is explored from the PS-SiZer visualization. PS-SiZer is a graphical tool for exploring structures in curves by mapping areas where rate of change is significantly increasing, decreasing, or does not change. PS-SiZer maps provide information about the significant rate of weigh change that occurs in two ART regimens at various level of smoothing. A penalized spline regression model at an optimum smoothing level is applied to obtain an estimated first-time point where weight no longer increases for different treatment regimens. | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/8010 | |
dc.identifier.uri | http://dx.doi.org/10.7912/C2/2779 | |
dc.language.iso | en_US | en_US |
dc.subject | Dose response | en_US |
dc.subject | Penalized spline regression | en_US |
dc.subject | Semi-parametric | en_US |
dc.subject | SiZer | en_US |
dc.subject.lcsh | Social sciences -- Research -- Statistical methods | en_US |
dc.subject.lcsh | Biometry | en_US |
dc.subject.lcsh | Quantitative research | en_US |
dc.title | Penalized spline modeling of the ex-vivo assays dose-response curves and the HIV-infected patients' bodyweight change | en_US |