Trial reportJournal of pharmacokinetics and pharmacodynamics2010
A latent variable approach for modeling categorical endpoints among patients with rheumatoid arthritis treated with golimumab plus methotrexate.
Trial report in Journal of pharmacokinetics and pharmacodynamics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed.
- Joint longitudinal model development: application to exposure-response modeling of ACR and DAS scores in rheumatoid arthritis patients treated with sirukumab.Journal of pharmacokinetics and pharmacodynamics · 2018Trial
- Dose/Exposure-Response Modeling to Support Dosing Recommendation for Phase III Development of Baricitinib in Patients with Rheumatoid Arthritis.CPT: pharmacometrics & systems pharmacology · 2017Trial
- Comparative assessment of clinical response in patients with rheumatoid arthritis between PF-05280586, a proposed rituximab biosimilar, and rituximab.British journal of clinical pharmacology · 2016Trial
- Latent variable indirect response modeling of categorical endpoints representing change from baseline.Journal of pharmacokinetics and pharmacodynamics · 2013Trial
- Informative dropout modeling of longitudinal ordered categorical data and model validation: application to exposure-response modeling of physician's global assessment score for ustekinumab in patients with psoriasis.Journal of pharmacokinetics and pharmacodynamics · 2011Trial
- Role of Disease Progression Models in Drug Development.Pharmaceutical research · 2022Review
- Improving categorical endpoint longitudinal exposure-response modeling through the joint modeling with a related endpoint.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Review
- Improvement in latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint in rheumatoid arthritis.Journal of pharmacokinetics and pharmacodynamics · 2016Article
- Simultaneous Exposure-Response Modeling of ACR20, ACR50, and ACR70 Improvement Scores in Rheumatoid Arthritis Patients Treated With Certolizumab Pegol.CPT: pharmacometrics & systems pharmacology · 2014Article
- Latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint.Journal of pharmacokinetics and pharmacodynamics · 2014Article
- Exposure-response modeling of clinical end points using latent variable indirect response models.CPT: pharmacometrics & systems pharmacology · 2014Article
- Bridging Clinical Outcomes of Canakinumab Treatment in Patients With Rheumatoid Arthritis With a Population Model of IL-1β Kinetics.CPT: pharmacometrics & systems pharmacology · 2012Article
- Pharmacokinetic/pharmacodynamic modeling in inflammation.Critical reviews in biomedical engineering · 2012Review
- Extending the latent variable model for extra correlated longitudinal dichotomous responses.Journal of pharmacokinetics and pharmacodynamics · 2011Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The need for accurate exposure-response modeling is critical in the drug development process. Few methods are available for linking discrete endpoints, especially ordered categorical variables, to mechanistic (e.g., indirect response) models. Here we describe a latent-variable approach that is proposed in conjunction with an inhibitory indirect response model to link the placebo/comedication effect and drug exposure to the endpoints. The model is parsimonious, with desirable characteristics at initial timepoints, and allows simultaneous modeling of multiple endpoints that are categorically ordered. Application of the model is demonstrated with data from a phase 3 clinical trial of golimumab, a human IgG1kappa monoclonal antibody that binds with high affinity and specificity to tumor necrosis factor (TNF)-alpha, in patients with rheumatoid arthritis. The efficacy endpoints were 20, 50, and 70% improvement in the American College of Rheumatology criteria (ACR20, ACR50, and ACR70, respectively) as measures of improvement in disease severity. The modeling results were shown to be consistent by using either a sequential or simultaneous pharmacokinetic/pharmacodynamic modeling approach. The suitability of likelihood profiling and proper use of bootstrap methods in assessing parameter estimation precision are also presented. More accurate, parsimonious models with appropriately quantified uncertainty can facilitate better drug development decisions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.