Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation

KS Gurusamy; D Moher; M Loizidou; I Ahmed; MT Avey; CC Barron; B Davidson; M Dwek; C Gluud; G Jell; K Katakam; J Montroy; TD McHugh; NJ Osborne; Merel Ritskes-Hoitinga; Kees  van Laarhoven; Jan  Vollert; M Lalu

doi:10.7717/peerj.10673

Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation

KS Gurusamy^* (Corresponding Author)
, D Moher
, M Loizidou
, I Ahmed
, MT Avey
, CC Barron
, B Davidson
, M Dwek
, C Gluud
, G Jell
, K Katakam
, J Montroy
, TD McHugh
, NJ Osborne
, Merel Ritskes-Hoitinga
, Kees van Laarhoven
, Jan Vollert
, M Lalu

^*Corresponding author for this work

Applied Health Sciences

University College London
University of Ottawa
University of Westminster
Copenhagen University Hospital
Responsible Research in Practice, London
Radboud University Medical Center
Imperial College London

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

11 Downloads (Pure)

Abstract

Background
Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases.

Methods
We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds.

Results
This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research.

Conclusion
We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.

Original language	English
Article number	e10673
Number of pages	36
Journal	PeerJ
Volume	9
DOIs	https://doi.org/10.7717/peerj.10673
Publication status	Published - 27 Jan 2021

Bibliographical note

Funding
The authors received no funding for this work.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Preclinical studies
Experimental studies
Animal studies
Clinical relevance

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Gurusami_etal_PeerJ_Clinical_relevance_assessment_VOR
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Cite this

Gurusamy, KS., Moher, D., Loizidou, M., Ahmed, I., Avey, MT., Barron, CC., Davidson, B., Dwek, M., Gluud, C., Jell, G., Katakam, K., Montroy, J., McHugh, TD., Osborne, NJ., Ritskes-Hoitinga, M., van Laarhoven, K., Vollert, J., & Lalu, M. (2021). Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation. PeerJ, 9, Article e10673. https://doi.org/10.7717/peerj.10673

Gurusamy, KS, Moher, D, Loizidou, M, Ahmed, I, Avey, MT, Barron, CC, Davidson, B, Dwek, M, Gluud, C, Jell, G, Katakam, K, Montroy, J, McHugh, TD, Osborne, NJ, Ritskes-Hoitinga, M, van Laarhoven, K, Vollert, J & Lalu, M 2021, 'Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation', PeerJ, vol. 9, e10673. https://doi.org/10.7717/peerj.10673

@article{5b3788364dcb4e26bade555aff82c563,

title = "Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation",

abstract = "Background Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. Methods We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. Results This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. Conclusion We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.",

keywords = "Preclinical studies, Experimental studies, Animal studies, Clinical relevance",

author = "KS Gurusamy and D Moher and M Loizidou and I Ahmed and MT Avey and CC Barron and B Davidson and M Dwek and C Gluud and G Jell and K Katakam and J Montroy and TD McHugh and NJ Osborne and Merel Ritskes-Hoitinga and \{van Laarhoven\}, Kees and Jan Vollert and M Lalu",

note = "Funding The authors received no funding for this work.",

year = "2021",

month = jan,

day = "27",

doi = "10.7717/peerj.10673",

language = "English",

volume = "9",

journal = "PeerJ",

issn = "2167-8359",

publisher = "PeerJ",

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TY - JOUR

T1 - Clinical relevance assessment of animal preclinical research (RAA) tool

T2 - development and explanation

AU - Gurusamy, KS

AU - Moher, D

AU - Loizidou, M

AU - Ahmed, I

AU - Avey, MT

AU - Barron, CC

AU - Davidson, B

AU - Dwek, M

AU - Gluud, C

AU - Jell, G

AU - Katakam, K

AU - Montroy, J

AU - McHugh, TD

AU - Osborne, NJ

AU - Ritskes-Hoitinga, Merel

AU - van Laarhoven, Kees

AU - Vollert, Jan

AU - Lalu, M

N1 - Funding The authors received no funding for this work.

PY - 2021/1/27

Y1 - 2021/1/27

N2 - Background Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. Methods We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. Results This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. Conclusion We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.

AB - Background Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. Methods We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. Results This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. Conclusion We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.

KW - Preclinical studies

KW - Experimental studies

KW - Animal studies

KW - Clinical relevance

UR - http://europepmc.org/abstract/med/33569250

U2 - 10.7717/peerj.10673

DO - 10.7717/peerj.10673

M3 - Article

C2 - 33569250

SN - 2167-8359

VL - 9

JO - PeerJ

JF - PeerJ

M1 - e10673

ER -

Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

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