Document Detail


Latent variable indirect response modeling of categorical endpoints representing change from baseline.
MedLine Citation:
PMID:  23275019     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Accurate exposure-response modeling is important in drug development. Methods are still evolving in the use of mechanistic, e.g., indirect response (IDR) models to relate discrete endpoints, mostly of the ordered categorical form, to placebo/co-medication effect and drug exposure. When the discrete endpoint is derived using change-from-baseline measurements, a mechanistic exposure-response modeling approach requires adjustment to maintain appropriate interpretation. This manuscript describes a new modeling method that integrates a latent-variable representation of IDR models with standard logistic regression. The new method also extends to general link functions that cover probit regression or continuous clinical endpoint modeling. Compared to an earlier latent variable approach that constrained the baseline probability of response to be 0, placebo effect parameters in the new model formulation are more readily interpretable and can be separately estimated from placebo data, thus allowing convenient and robust model estimation. A general inherent connection of some latent variable representations with baseline-normalized standard IDR models is derived. For describing clinical response endpoints, Type I and Type III IDR models are shown to be equivalent, therefore there are only three identifiable IDR models. This approach was applied to data from two phase III clinical trials of intravenously administered golimumab for the treatment of rheumatoid arthritis, where 20, 50, and 70 % improvement in the American College of Rheumatology disease severity criteria were used as efficacy endpoints. Likelihood profiling and visual predictive checks showed reasonable parameter estimation precision and model performance.
Authors:
Chuanpu Hu; Zhenhua Xu; Alan M Mendelsohn; Honghui Zhou
Related Documents :
19398319 - Review of recycling performance indicators: a study on collection rate in taiwan.
22444609 - Carbohydrate quantitative digestion and absorption in ruminants: from feed starch and f...
12362439 - Statistical data validation methods for large cheese plant database.
19327859 - Quantitative risk assessment of listeria monocytogenes in ready-to-eat meats in australia.
18062479 - Feasibility assessment of electrocoagulation towards a new sustainable wastewater treat...
18044539 - What gets recycled: an information theory based model for product recycling.
21466549 - White blood cell count and psychomotor cognitive performance in the elderly.
21395779 - Methods for evaluating genotype-environment interactions illustrated by laying hens.
15857049 - Identification of ultrasound contrast agent dilution systems for ejection fraction meas...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-30
Journal Detail:
Title:  Journal of pharmacokinetics and pharmacodynamics     Volume:  -     ISSN:  1573-8744     ISO Abbreviation:  J Pharmacokinet Pharmacodyn     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101096520     Medline TA:  J Pharmacokinet Pharmacodyn     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Pharmacokinetics and Pharmacometrics, Biologics Clinical Pharmacology, Janssen Research & Development, LLC, PO Box 776, 1400 McKean Road, Spring House, PA, 19477, USA, CHu25@its.jnj.com.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Variability and singularity arising from poor compliance in a pharmacokinetic model I: the multi-IV ...
Next Document:  Maternal and pregnancy-related death: causes and frequencies in an autopsy study population.