Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population
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 predic...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-024-00481-y |
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| _version_ | 1832594616704040960 |
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| author | Andrew E. Stine Jignesh Parmar Amy K. Smith Zachary Cummins Narasimha Rao Pillalamarri R. Joseph Bender |
| author_facet | Andrew E. Stine Jignesh Parmar Amy K. Smith Zachary Cummins Narasimha Rao Pillalamarri R. Joseph Bender |
| author_sort | Andrew E. Stine |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4baf336954274abcbea9eb705ce87a07 |
| institution | Kabale University |
| issn | 2056-7189 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Systems Biology and Applications |
| spelling | doaj-art-4baf336954274abcbea9eb705ce87a072025-01-19T12:28:16ZengNature Portfolionpj Systems Biology and Applications2056-71892025-01-0111111110.1038/s41540-024-00481-ySimulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual populationAndrew E. Stine0Jignesh Parmar1Amy K. Smith2Zachary Cummins3Narasimha Rao Pillalamarri4R. Joseph Bender5United Therapeutics CorporationUnited Therapeutics CorporationUnited Therapeutics CorporationUnited Therapeutics CorporationUnited Therapeutics CorporationUnited Therapeutics CorporationAbstract 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.https://doi.org/10.1038/s41540-024-00481-y |
| spellingShingle | Andrew E. Stine Jignesh Parmar Amy K. Smith Zachary Cummins Narasimha Rao Pillalamarri R. Joseph Bender Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population npj Systems Biology and Applications |
| title | Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population |
| title_full | Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population |
| title_fullStr | Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population |
| title_full_unstemmed | Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population |
| title_short | Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population |
| title_sort | simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population |
| url | https://doi.org/10.1038/s41540-024-00481-y |
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