Evidence map›Paper›PMID 39814773›Full record

ArticleNPJ systems biology and applications2025

Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population.

Andrew E Stine, Jignesh Parmar, Amy K Smith, Zachary Cummins, Narasimha Rao Pillalamarri, R Joseph Bender

Abstract read
In one paragraph

Article in NPJ systems biology and applications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Review
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

6 authors.

Andrew E StineUnited Therapeutics Corporation, Silver Spring, MD, USA.
Jignesh ParmarUnited Therapeutics Corporation, Silver Spring, MD, USA.
Amy K SmithUnited Therapeutics Corporation, Silver Spring, MD, USA.
Zachary CumminsUnited Therapeutics Corporation, Silver Spring, MD, USA.
Narasimha Rao PillalamarriUnited Therapeutics Corporation, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0002-7484-0550
R Joseph BenderUnited Therapeutics Corporation, Silver Spring, MD, USA. jbender@unither.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials. We then used this virtual population to predict the results of clinical trials on the basis of disease severity, dosing regimen, time since diagnosis, and co-administered background therapies. The virtual population captured the effect of changes in trial design and patient subpopulation on clinical response. We also demonstrated the virtual trial workflow's potential for enriching populations based on clinical biomarkers to increase likelihood of trial success.

Indexed as

Antihypertensive AgentsClinical Trials as TopicEpoprostenolHypertension, PulmonaryPulmonary Arterial HypertensionAdministration, OralComputer SimulationHumansVascular ResistanceAntihypertensive AgentsEpoprostenoltreprostinil

Identifiers

PMID39814773
PMCPMC11735615

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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.