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Concept and application of the probability of pharmacological success (PoPS) as a decision tool in drug development: a position paper

BACKGROUND: In drug development, few molecules from a large pool of early candidates become successful medicines after demonstrating a favourable benefit-risk ratio. Many decisions are made along the way to continue or stop the development of a molecule. The probability of pharmacological success, o...

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Autores principales: Chen, Chao, Zhou, Xuan, Lavezzi, Silvia Maria, Arshad, Usman, Sharma, Raman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832631/
https://www.ncbi.nlm.nih.gov/pubmed/36631827
http://dx.doi.org/10.1186/s12967-022-03849-y
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author Chen, Chao
Zhou, Xuan
Lavezzi, Silvia Maria
Arshad, Usman
Sharma, Raman
author_facet Chen, Chao
Zhou, Xuan
Lavezzi, Silvia Maria
Arshad, Usman
Sharma, Raman
author_sort Chen, Chao
collection PubMed
description BACKGROUND: In drug development, few molecules from a large pool of early candidates become successful medicines after demonstrating a favourable benefit-risk ratio. Many decisions are made along the way to continue or stop the development of a molecule. The probability of pharmacological success, or PoPS, is a tool for informing early-stage decisions based on benefit and risk data available at the time. RESULTS: The PoPS is the probability that most patients can achieve adequate pharmacology for the intended indication while minimising the number of subjects exposed to safety risk. This probability is usually a function of dose; hence its computation typically requires exposure–response models for pharmacology and safety. The levels of adequate pharmacology and acceptable risk must be specified. The uncertainties in these levels, in the exposure–response relationships, and in relevant translation all need to be identified. Several examples of different indications are used to illustrate how this approach can facilitate molecule progression decisions for preclinical and early clinical development. The examples show that PoPS assessment is an effective mechanism for integrating multi-source data, identifying knowledge gaps, and forcing transparency of assumptions. With its application, translational modelling becomes more meaningful and dose prediction more rigorous. Its successful implementation calls for early planning, sound understanding of the disease-drug system, and cross-discipline collaboration. Furthermore, the PoPS evolves as relevant knowledge grows. CONCLUSION: The PoPS is a powerful evidence-based framework to formally capture multiple uncertainties into a single probability term for assessing benefit-risk ratio. In GSK, it is now expected for governance review at all early-phase decision gates.
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spelling pubmed-98326312023-01-12 Concept and application of the probability of pharmacological success (PoPS) as a decision tool in drug development: a position paper Chen, Chao Zhou, Xuan Lavezzi, Silvia Maria Arshad, Usman Sharma, Raman J Transl Med Methodology BACKGROUND: In drug development, few molecules from a large pool of early candidates become successful medicines after demonstrating a favourable benefit-risk ratio. Many decisions are made along the way to continue or stop the development of a molecule. The probability of pharmacological success, or PoPS, is a tool for informing early-stage decisions based on benefit and risk data available at the time. RESULTS: The PoPS is the probability that most patients can achieve adequate pharmacology for the intended indication while minimising the number of subjects exposed to safety risk. This probability is usually a function of dose; hence its computation typically requires exposure–response models for pharmacology and safety. The levels of adequate pharmacology and acceptable risk must be specified. The uncertainties in these levels, in the exposure–response relationships, and in relevant translation all need to be identified. Several examples of different indications are used to illustrate how this approach can facilitate molecule progression decisions for preclinical and early clinical development. The examples show that PoPS assessment is an effective mechanism for integrating multi-source data, identifying knowledge gaps, and forcing transparency of assumptions. With its application, translational modelling becomes more meaningful and dose prediction more rigorous. Its successful implementation calls for early planning, sound understanding of the disease-drug system, and cross-discipline collaboration. Furthermore, the PoPS evolves as relevant knowledge grows. CONCLUSION: The PoPS is a powerful evidence-based framework to formally capture multiple uncertainties into a single probability term for assessing benefit-risk ratio. In GSK, it is now expected for governance review at all early-phase decision gates. BioMed Central 2023-01-11 /pmc/articles/PMC9832631/ /pubmed/36631827 http://dx.doi.org/10.1186/s12967-022-03849-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Methodology
Chen, Chao
Zhou, Xuan
Lavezzi, Silvia Maria
Arshad, Usman
Sharma, Raman
Concept and application of the probability of pharmacological success (PoPS) as a decision tool in drug development: a position paper
title Concept and application of the probability of pharmacological success (PoPS) as a decision tool in drug development: a position paper
title_full Concept and application of the probability of pharmacological success (PoPS) as a decision tool in drug development: a position paper
title_fullStr Concept and application of the probability of pharmacological success (PoPS) as a decision tool in drug development: a position paper
title_full_unstemmed Concept and application of the probability of pharmacological success (PoPS) as a decision tool in drug development: a position paper
title_short Concept and application of the probability of pharmacological success (PoPS) as a decision tool in drug development: a position paper
title_sort concept and application of the probability of pharmacological success (pops) as a decision tool in drug development: a position paper
topic Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832631/
https://www.ncbi.nlm.nih.gov/pubmed/36631827
http://dx.doi.org/10.1186/s12967-022-03849-y
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