Back to Search
Start Over
Application of Item Response Theory to Modeling of Expanded Disability Status Scale in Multiple Sclerosis
- Source :
- AAPS JOURNAL, 19, 172
- Publication Year :
- 2016
-
Abstract
- In this study, we report the development of the first item response theory (IRT) model within a pharmacometrics framework to characterize the disease progression in multiple sclerosis (MS), as measured by Expanded Disability Status Score (EDSS). Data were collected quarterly from a 96-week phase III clinical study by a blinder rater, involving 104,206 item-level observations from 1319 patients with relapsing-remitting MS (RRMS), treated with placebo or cladribine. Observed scores for each EDSS item were modeled describing the probability of a given score as a function of patients' (unobserved) disability using a logistic model. Longitudinal data from placebo arms were used to describe the disease progression over time, and the model was then extended to cladribine arms to characterize the drug effect. Sensitivity with respect to patient disability was calculated as Fisher information for each EDSS item, which were ranked according to the amount of information they contained. The IRT model was able to describe baseline and longitudinal EDSS data on item and total level. The final model suggested that cladribine treatment significantly slows disease-progression rate, with a 20% decrease in disease-progression rate compared to placebo, irrespective of exposure, and effects an additional exposure-dependent reduction in disability progression. Four out of eight items contained 80% of information for the given range of disabilities. This study has illustrated that IRT modeling is specifically suitable for accurate quantification of disease status and description and prediction of disease progression in phase 3 studies on RRMS, by integrating EDSS item-level data in a meaningful manner.
- Subjects :
- Disease status
medicine.medical_specialty
Item Response Theory
Pharmaceutical Science
cladribine tablets
Logistic regression
Placebo
multiple sclerosis
Severity of Illness Index
behavioral disciplines and activities
030226 pharmacology & pharmacy
Disability Evaluation
03 medical and health sciences
Pharmaceutical Sciences
Multiple Sclerosis, Relapsing-Remitting
0302 clinical medicine
Item response theory
medicine
Humans
Cladribine
disease progression model
Expanded Disability Status Scale
business.industry
Multiple sclerosis
Models, Theoretical
medicine.disease
Farmaceutiska vetenskaper
Pharmacometrics
Logistic Models
Clinical Trials, Phase III as Topic
Disease Progression
Physical therapy
business
Immunosuppressive Agents
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- AAPS JOURNAL, 19, 172
- Accession number :
- edsair.doi.dedup.....43aefce095d36622ec6b9ac28fbf084c