Evidence map›Paper›PMID 29736890›Full record

ArticleJournal of pharmacokinetics and pharmacodynamics2018

A tutorial on model informed approaches to cardiovascular safety with focus on cardiac repolarisation.

S Y A Cheung, J Parkinson, U Wählby-Hamrén, C D Dota, Å M Kragh, L Bergenholm, T Vik, T Collins, C Arfvidsson, C E Pollard and 2 more

Abstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in Journal of pharmacokinetics and pharmacodynamics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Unveiling the Multifaceted Problems Associated with Dysrhythmia.International journal of molecular sciences · 2023
    Review
  2. Article
  3. Article
  4. KInternational journal of molecular sciences · 2020
    Review
  5. Article
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

12 authors.

S Y A CheungQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Cambridge, UK. Amy.Cheung@astrazeneca.com.ORCID 0000-0001-5138-7688
J ParkinsonQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
U Wählby-HamrénQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
C D DotaQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Å M KraghQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
L BergenholmDMPK CVRM Modelling and Simulation, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
T VikCardiovascular Safety Center of Excellence, Global Medicine Development, Gothenburg, Sweden.
T CollinsSafety and ADME Translational Sciences Department, Drug Safety and Metabolism, IMED Biotech Unit, Cambridge, UK.
C ArfvidssonClinical Operation, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
C E PollardSafety and ADME Translational Sciences Department, Drug Safety and Metabolism, IMED Biotech Unit, Cambridge, UK.
H K TomkinsonQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Cambridge, UK.
B HamrénQuantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.

Funding

Innovative Medicines Initiative (IMI) Joint Undertaking 115156Marie Curie FP7 ITN EID project 316736National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/K001205/1
6 · The paper itself

Abstract

Drugs can affect the cardiovascular (CV) system either as an intended treatment or as an unwanted side effect. In both cases, drug-induced cardiotoxicities such as arrhythmia and unfavourable hemodynamic effects can occur, and be described using mathematical models; such a model informed approach can provide valuable information during drug development and can aid decision-making. However, in order to develop informative models, it is vital to understand CV physiology. The aims of this tutorial are to present (1) key background biological and medical aspects of the CV system, (2) CV electrophysiology, (3) CV safety concepts, (4) practical aspects of development of CV models and (5) regulatory expectations with a focus on using model informed and quantitative approaches to support nonclinical and clinical drug development. In addition, we share several case studies to provide practical information on project strategy (planning, key questions, assumptions setting, and experimental design) and mathematical models development that support decision-making during drug discovery and development.

Indexed as

AnimalsBlood PressureCardiovascular DiseasesCardiovascular SystemDogsDrug DiscoveryDrug Evaluation, PreclinicalDrug-Related Side Effects and Adverse ReactionsGuinea PigsHeart RateHumansMacaca mulattaPharmaceutical PreparationsRabbitsRatsPharmaceutical PreparationsCardiovascular safetyDrug developmentDrug discoveryModel Informed Drug Discovery and DevelopmentQTRegulatoryTranslation

Identifiers

What OpenQuestion holds

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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.