Evidence map›Paper›PMID 28634654›Full record

Trial reportJournal of pharmacokinetics and pharmacodynamics2017

Improvement in latent variable indirect response modeling of multiple categorical clinical endpoints: application to modeling of guselkumab treatment effects in psoriatic patients.

Chuanpu Hu, Bruce Randazzo, Amarnath Sharma, Honghui Zhou

Abstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Journal of pharmacokinetics and pharmacodynamics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 19% of its field
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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

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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 at 1 institution in 1 country.

Chuanpu HuGlobal Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, PO Box 776, Spring House, PA, 19477, USA. CHu25@its.jnj.com.
Bruce RandazzoClinical Immunology, Janssen Research & Development, LLC, 1400 McKean Road, PO Box 776, Spring House, PA, 19477, USA.
Amarnath SharmaGlobal Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, PO Box 776, Spring House, PA, 19477, USA.
Honghui ZhouGlobal Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, PO Box 776, Spring House, PA, 19477, USA.
Janssen (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23. A Phase 2b study was conducted in 238 patients with psoriasis for which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) scores. A latent variable Type I IDR model was developed to evaluate the therapeutic effect of guselkumab dosing on 75, 90 and 100% improvement of PASI scores from baseline and PGA scores, with placebo effect empirically modeled. The results showed that the joint model is able to describe the observed data better with fewer parameters compared with the common approach of separately modeling the endpoints.

Indexed as

Models, BiologicalAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedClinical Trials, Phase II as TopicDose-Response Relationship, DrugDouble-Blind MethodEndpoint DeterminationHumansPsoriasisTreatment OutcomeAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedguselkumabClinical drug developmentNONMEMPopulation pharmacokinetic/pharmacodynamic modeling

Identifiers

PMID28634654
OpenAlexW2682870454

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.