Alternative strategies in cardiac preclinical research and new clinical trial formats

Abstract An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and life-span of our patients. Despite technological advances in the past decade, successful launches of drug candidates per year remain low. We here...

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Published inCardiovascular research Vol. 118; no. 3; pp. 746 - 762
Main Authors Kreutzer, Fabian Philipp, Meinecke, Anna, Schmidt, Kevin, Fiedler, Jan, Thum, Thomas
Format Journal Article
LanguageEnglish
Published England Oxford University Press 21.02.2022
Subjects
Animals
Clinical Trials as Topic
Drug Evaluation, Preclinical
Heart
Humans
Lab-On-A-Chip Devices
Organoids
Quality of Life
Reviews
Adaptive design
Alternatives to animal models
Pandemic trials
Clinical trials
3D cell culture
Organ-on-a-chip
Preclinical research
Master protocols N-of-1 trials
Online AccessGet full text

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Abstract Abstract An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and life-span of our patients. Despite technological advances in the past decade, successful launches of drug candidates per year remain low. We here give an overview about some of these advances and suggest improvements for implementation to boost preclinical and clinical drug development with a focus on the cardiovascular field. We highlight advantages and disadvantages of animal experimentation and thoroughly review alternatives in the field of three-dimensional cell culture as well as preclinical use of spheroids and organoids. Microfluidic devices and their potential as organ-on-a-chip systems, as well as the use of living animal and human cardiac tissues are additionally introduced. In the second part, we examine recent gold standard randomized clinical trials and present possible modifications to increase lead candidate throughput: adaptive designs, master protocols, and drug repurposing. In silico and N-of-1 trials have the potential to redefine clinical drug candidate evaluation. Finally, we briefly discuss clinical trial designs during pandemic times. Graphical Abstract
AbstractList Abstract An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and life-span of our patients. Despite technological advances in the past decade, successful launches of drug candidates per year remain low. We here give an overview about some of these advances and suggest improvements for implementation to boost preclinical and clinical drug development with a focus on the cardiovascular field. We highlight advantages and disadvantages of animal experimentation and thoroughly review alternatives in the field of three-dimensional cell culture as well as preclinical use of spheroids and organoids. Microfluidic devices and their potential as organ-on-a-chip systems, as well as the use of living animal and human cardiac tissues are additionally introduced. In the second part, we examine recent gold standard randomized clinical trials and present possible modifications to increase lead candidate throughput: adaptive designs, master protocols, and drug repurposing. In silico and N-of-1 trials have the potential to redefine clinical drug candidate evaluation. Finally, we briefly discuss clinical trial designs during pandemic times.
An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and life-span of our patients. Despite technological advances in the past decade, successful launches of drug candidates per year remain low. We here give an overview about some of these advances and suggest improvements for implementation to boost preclinical and clinical drug development with a focus on the cardiovascular field. We highlight advantages and disadvantages of animal experimentation and thoroughly review alternatives in the field of three-dimensional cell culture as well as preclinical use of spheroids and organoids. Microfluidic devices and their potential as organ-on-a-chip systems, as well as the use of living animal and human cardiac tissues are additionally introduced. In the second part, we examine recent gold standard randomized clinical trials and present possible modifications to increase lead candidate throughput: adaptive designs, master protocols, and drug repurposing. In silico and N-of-1 trials have the potential to redefine clinical drug candidate evaluation. Finally, we briefly discuss clinical trial designs during pandemic times.
An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and life-span of our patients. Despite technological advances in the past decade, successful launches of drug candidates per year remain low. We here give an overview about some of these advances and suggest improvements for implementation to boost preclinical and clinical drug development with a focus on the cardiovascular field. We highlight advantages and disadvantages of animal experimentation and thoroughly review alternatives in the field of three-dimensional cell culture as well as preclinical use of spheroids and organoids. Microfluidic devices and their potential as organ-on-a-chip systems, as well as the use of living animal and human cardiac tissues are additionally introduced. In the second part, we examine recent gold standard randomized clinical trials and present possible modifications to increase lead candidate throughput: adaptive designs, master protocols, and drug repurposing. In silico and N-of-1 trials have the potential to redefine clinical drug candidate evaluation. Finally, we briefly discuss clinical trial designs during pandemic times.
Abstract An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and life-span of our patients. Despite technological advances in the past decade, successful launches of drug candidates per year remain low. We here give an overview about some of these advances and suggest improvements for implementation to boost preclinical and clinical drug development with a focus on the cardiovascular field. We highlight advantages and disadvantages of animal experimentation and thoroughly review alternatives in the field of three-dimensional cell culture as well as preclinical use of spheroids and organoids. Microfluidic devices and their potential as organ-on-a-chip systems, as well as the use of living animal and human cardiac tissues are additionally introduced. In the second part, we examine recent gold standard randomized clinical trials and present possible modifications to increase lead candidate throughput: adaptive designs, master protocols, and drug repurposing. In silico and N-of-1 trials have the potential to redefine clinical drug candidate evaluation. Finally, we briefly discuss clinical trial designs during pandemic times. Graphical Abstract
Author Schmidt, Kevin
Fiedler, Jan
Thum, Thomas
Meinecke, Anna
Kreutzer, Fabian Philipp
AuthorAffiliation 2 REBIRTH Center for Translational Regenerative Medicine, Hannover Medical School , Hannover, Germany
1 Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School , Carl-Neuberg-Str.1, 30625 Hannover, Germany
3 Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) , Hannover, Germany
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– name: 2 REBIRTH Center for Translational Regenerative Medicine, Hannover Medical School , Hannover, Germany
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Author_xml – sequence: 1
  givenname: Fabian Philipp
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  surname: Kreutzer
  fullname: Kreutzer, Fabian Philipp
  organization: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany
– sequence: 2
  givenname: Anna
  surname: Meinecke
  fullname: Meinecke, Anna
  organization: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany
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  givenname: Kevin
  surname: Schmidt
  fullname: Schmidt, Kevin
  organization: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany
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  givenname: Jan
  orcidid: 0000-0002-8855-2883
  surname: Fiedler
  fullname: Fiedler, Jan
  organization: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany
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  givenname: Thomas
  orcidid: 0000-0003-4360-1511
  surname: Thum
  fullname: Thum, Thomas
  email: thum.thomas@mh-hannover.de
  organization: Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, Germany
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Issue 3
Keywords Adaptive design
Alternatives to animal models
Pandemic trials
Clinical trials
3D cell culture
Organ-on-a-chip
Preclinical research
Master protocols N-of-1 trials
Language English
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OpenAccessLink https://dx.doi.org/10.1093/cvr/cvab075
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PublicationDate 2022-02-21
PublicationDateYYYYMMDD 2022-02-21
PublicationDate_xml – month: 02
  year: 2022
  text: 2022-02-21
  day: 21
PublicationDecade 2020
PublicationPlace England
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PublicationTitle Cardiovascular research
PublicationTitleAlternate Cardiovasc Res
PublicationYear 2022
Publisher Oxford University Press
Publisher_xml – name: Oxford University Press
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Snippet Abstract An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and...
An efficient and safe drug development process is crucial for the establishment of new drugs on the market aiming to increase quality of life and life-span of...
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SubjectTerms Animals
Clinical Trials as Topic
Drug Evaluation, Preclinical
Heart
Humans
Lab-On-A-Chip Devices
Organoids
Quality of Life
Reviews
Title Alternative strategies in cardiac preclinical research and new clinical trial formats
URI https://www.ncbi.nlm.nih.gov/pubmed/33693475
https://pubmed.ncbi.nlm.nih.gov/PMC7989574
Volume 118
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