Sökning: "nonlinear mixed-effects models"

Visar resultat 16 - 20 av 27 avhandlingar innehållade orden nonlinear mixed-effects models.

  1. 16. Improved Methods for Pharmacometric Model-Based Decision-Making in Clinical Drug Development

    Författare :Anne-Gaëlle Dosne; Mats O. Karlsson; Rik Schoemaker; Uppsala universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; pharmacometrics; nonlinear mixed-effects models; confirmatory trials; residual error modeling; parameter uncertainty; sampling importance resampling; model-averaging; Farmaceutisk vetenskap; Pharmaceutical Science;

    Sammanfattning : Pharmacometric model-based analysis using nonlinear mixed-effects models (NLMEM) has to date mainly been applied to learning activities in drug development. However, such analyses can also serve as the primary analysis in confirmatory studies, which is expected to bring higher power than traditional analysis methods, among other advantages. LÄS MER

  2. 17. Data-driven modeling of combination therapy in oncology

    Författare :Tim Cardilin; Göteborgs universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; NATURVETENSKAP; NATURAL SCIENCES; NATURVETENSKAP; NATURAL SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; Oncology; Model-Based Drug Development; Pharmacokinetics Pharmacodynamics; Nonlinear Mixed-Effects Models; Combination Therapy; Mathematical Modeling; Nonlinear Mixed-Effects Models;

    Sammanfattning : This thesis contains two manuscripts: Tumor Static Concentration Curves in Combination Therapy and Extending the Tumor Static Concentration Curve to Exposure - A Combination Therapy Example with Radiation Therapy. There is also an introductory chapter presenting some basic facts necessary to understand the appended manuscripts. LÄS MER

  3. 18. Applied Adaptive Optimal Design and Novel Optimization Algorithms for Practical Use

    Författare :Eric Strömberg; Andrew Hooker; Mats Karlsson; Timothy Waterhouse; Uppsala universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; Nonlinear Mixed Effects Models; Pharmacometrics; Fisher Information Matrix; Approximation; Optimality Criterion; Parallelization; Model Based Adaptive Optimal Design; Pharmaceutical Science; Farmaceutisk vetenskap;

    Sammanfattning : The costs of developing new pharmaceuticals have increased dramatically during the past decades. Contributing to these increased expenses are the increasingly extensive and more complex clinical trials required to generate sufficient evidence regarding the safety and efficacy of the drugs. LÄS MER

  4. 19. Model-Based Optimization of Clinical Trial Designs

    Författare :Camille Vong; Mats O. Karlsson; Andrew C. Hooker; Lena E. Friberg; Marylore Chenel; Oliver Sander; Uppsala universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; nonlinear mixed-effects models; pharmacometrics; likelihood ratio test; NONMEM; power; sample size; study design; proof-of-concept; dose-finding; population optimal design; LOQ; BQL data; neutropenia; docetaxel; myelosuppression; thrombocytopenia; MTD; Bayesian methods; 3 3 algorithm; dose escalation study; Pharmaceutical Science; Farmaceutisk vetenskap;

    Sammanfattning : General attrition rates in drug development pipeline have been recognized as a necessity to shift gears towards new methodologies that allow earlier and correct decisions, and the optimal use of all information accrued throughout the process. The quantitative science of pharmacometrics using pharmacokinetic-pharmacodynamic models was identified as one of the strategies core to this renaissance. LÄS MER

  5. 20. Novel Pharmacometric Methods for Informed Tuberculosis Drug Development

    Författare :Oskar Clewe; Ulrika S.H. Simonsson; Mats O. Karlsson; Piet van der Graaf; Uppsala universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; pharmacokinetics; pharmacodynamics; PKPD; pharmacometric; nonlinear mixed-effects models; multistate tuberculosis pharmacometric model; general pharmacodynamic interaction model; general pulmonary distribution model; tuberculosis; rifampicin; isoniazid; ethambutol; Pharmaceutical Science; Farmaceutisk vetenskap;

    Sammanfattning : With approximately nine million new cases and the attributable cause of death of an estimated two millions people every year there is an urgent need for new and effective drugs and treatment regimens targeting tuberculosis. The tuberculosis drug development pathway is however not ideal, containing non-predictive model systems and unanswered questions that may increase the risk of failure during late-phase drug development. LÄS MER