Evidence map›Paper›PMID 21327538›Full record

Trial reportJournal of pharmacokinetics and pharmacodynamics2011

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.

Chuanpu Hu, Philippe O Szapary, Newman Yeilding, Honghui Zhou

Abstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Journal of pharmacokinetics and pharmacodynamics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
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  6. Trial
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  10. Bounded outcome score modeling: application to treating psoriasis with ustekinumab.Journal of pharmacokinetics and pharmacodynamics · 2011
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  13. Visual predictive check of longitudinal models and dropout.Journal of pharmacokinetics and pharmacodynamics · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Chuanpu HuPharmacokinetics and Pharmacometrics, Biologics Clinical Pharmacology, Centocor Research and Development, Inc., 200 Great Valley Parkway, Malvern, PA 19355, USA. chu25@its.jnj.com
Philippe O Szapary
Newman Yeilding
Honghui Zhou

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The physician's global assessment (PGA) score is a 6-point measure of psoriasis severity that is widely used in clinical trials to assess response to psoriasis treatment. The objective of this study was to perform exposure-response modeling using the PGA score as a pharmacodynamic endpoint following treatment with ustekinumab in patients with moderate-to-severe psoriasis who participated in two Phase 3 studies (PHOENIX 1 and PHOENIX 2). Patients were randomly assigned to receive ustekinumab 45 or 90 mg or placebo, followed by active treatment or placebo crossover to ustekinumab, dose intensification or randomized withdrawal and long-term extension periods. A novel joint longitudinal-dropout model was developed from serum ustekinumab concentrations, PGA scores, and patient dropout information. The exposure-response component employed a semi-mechanistic drug model, integrated with disease progression and placebo effect under the mixed-effect logistic regression framework. This allowed potential tolerance to be investigated with a mechanistic approach. The dropout component of the joint model allowed the examination of its potential influence on the exposure-response relationship. The flexible Weibull dropout hazard function was used. Visual predictive check of the joint longitudinal-dropout model required special handling, and a conditional approach was proposed. The conditional approach was extended to external model validation. Finally, appropriate interpretation of model validation is discussed. This longitudinal-dropout model can serve as a basis to support future alternative dosing regimens for ustekinumab in patients with moderate-to-severe plaque psoriasis.

Indexed as

Models, StatisticalPatient DropoutsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedDisease ProgressionDouble-Blind MethodHumansLongitudinal StudiesPhysiciansPsoriasisUstekinumabAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedUstekinumab

Identifiers

PMID21327538

What OpenQuestion holds

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Registered trials

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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.