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Cited by 43Statistical Methods in Clinical TrialsPharmaceutical studies and practicesPharmacovigilance and Adverse Drug Reactions

A Mechanistic, Model‐Based Approach to Safety Assessment in Clinical Development

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Lippert, J, Brosch, M, von Kampen, O, Meyer, M, Siegmund, H.‐U, Schafmayer, C, Becker, T, Laffert, B +6 more·2012·CPT: Pharmacometrics & Systems Pharmacology
DOI 10.1038/psp.2012.14PMC PMC3600730
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Abstract

Assessing the safety of pharmacotherapies is a primary goal of clinical trials in drug development. The low frequency of relevant side effects, however, often poses a significant challenge for risk assessment. Methodologies allowing robust extrapolation of safety statistics based on preclinical data and information from clinical trials with limited numbers of patients are hence needed to further improve safety and efficacy in the drug development process. Here, we present a generic systems pharmacology approach integrating prior physiological and pharmacological knowledge, preclinical data, and clinical trial results, which allows predicting adverse event rates related to drug exposure. Possible fields of application involve high‐risk populations, novel drug candidates, and different dosing scenarios. As an example, the approach is applied to simvastatin and pravastatin and the prediction of myopathy rates in a population with a genotype leading to a significantly increased myopathy risk. CPT: Pharmacometrics & Systems Pharmacology(2012) 1, e13; doi:10.1038/psp.2012.14; advance online publication 7 November 2012

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Authors
Lippert, J., Brosch, M., von Kampen, O., Meyer, M., Siegmund, H. ‐., Schafmayer, C., Becker, T., Laffert, B., Görlitz, L., Schreiber, S., Neuvonen, P., Niemi, M., Hampe, J., & Kuepfer, L.
Affiliations
  • Bayer (Germany) (DE)
  • Christian-Albrechts-Universität zu Kiel (DE)
  • Department of Internal Medicine I University Hospital Schleswig‐Holstein, Campus Kiel, Christian‐Albrechts‐University Kiel Germany
  • Cell Culture Service Hamburg Germany
  • Department of Clinical Pharmacology University of Helsinki Helsinki Finland
  • University of Helsinki (FI)
Corresponding author
Kuepfer, L
ORCID
Venue
CPT: Pharmacometrics & Systems Pharmacology
Publisher
Wiley
Published
2012-11
Volume
1
Issue
11
Pages
1-8
ISSN
2163-8306 (ISSN-L)
DOI
10.1038/psp.2012.14
PMC
PMC3600730
OpenAlex
W2079342143
Cited by
43
References
3
Citations by year
2026: 1 · 2025: 4 · 2024: 2 · 2022: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 7 · 2013: 5
FWCI
5.19
Type
journal article
Language
en
Open access
Licence
Locations
  • CPT Pharmacometrics & Systems Pharmacology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion, cc-by-nc-nd)
Funders
Bundesministerium für Bildung und Forschung
Topics
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Keywords
drug safety assessment, systems pharmacology, adverse event prediction, simvastatin, pravastatin, statin-induced myopathy, statin-induced rhabdomyolysis, drug exposure, risk assessment, vulnerable populations

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