Outcome selection for tissue-agnostic drug trials for immune mediated inflammatory diseases: a systematic review of core outcome sets and regulatory guidance

Olalekan Lee Aiyegbusi; Lavinia Ferrante di Ruffano; Ameeta Retzer; Philip Newsome; Christopher Buckley; Melanie Calvert

doi:10.1186/s13063-022-06000-w

Outcome selection for tissue-agnostic drug trials for immune mediated inflammatory diseases: a systematic review of core outcome sets and regulatory guidance

Olalekan Lee Aiyegbusi^*, Lavinia Ferrante di Ruffano, Ameeta Retzer, Philip Newsome, Christopher Buckley, Melanie Calvert

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

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Abstract

Background: Tissue-agnostic drug development provides a paradigm shift in precision medicine and requires innovative trial designs. However, outcome selection for such trials can prove challenging. The objectives of this review were to:(i)Identify and map core outcome sets (COS), across 11 immune-mediated inflammatory diseases (IMIDs) in order to facilitate the selection of relevant outcomes across the conditions for innovative trials of tissue-agnostic drug therapies.(ii)Compare outcomes or endpoints recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to identify and highlight similarities and differences. Methods: The Core Outcome Measures in Effectiveness Trials (COMET), International Consortium for Health Outcomes Measurement (ICHOM), FDA and EMA databases were searched from inception to 28th December 2019. Two reviewers independently screened titles and abstracts of retrieved entries and conducted the subsequent full text screening. Hand searching of the reference lists and citation searching of the selected publications was conducted. The methodological quality of the included peer-reviewed articles was independently assessed by the reviewers based on the items of the COS–Standards for Development recommendations (COS–STAD) checklist. Core outcomes from the included publications were extracted and mapped across studies and conditions. Regulatory guidance from FDA and EMA, where available for clinical trials for the IMIDs, were obtained from their databases and recommendations on outcomes to measure directly compared. Results: Forty-four COS publications were included in the final analysis. Outcomes such as disease activity, pain, fatigue, quality of life, physical function, work limitation/productivity, steroid use and biomarkers were recommended across majority of the conditions. There were significant similarities and differences in FDA and EMA recommendations. The only instance where either regulatory body directly referenced a COS was for jSLE—both referenced the Paediatric Rheumatology International Trials Organization (PRINTO) COS. Conclusions: The findings from this systematic review provide valuable information to inform outcome selection in tissue-agnostic trials for IMIDs. There is a need for increased collaboration between regulators and COS developers and inclusion of regulators as key stakeholders in COS development to enhance the quality of COS. Trial registration: Not registered.

Original language	English
Article number	42
Number of pages	15
Journal	Trials
Volume	23
Issue number	1
Early online date	15 Jan 2022
DOIs	https://doi.org/10.1186/s13063-022-06000-w
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
OLA, PNN and MC were supported by the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC), West Midlands, Birmingham. OLA also receives funding from the Health Foundation and personal fees from Gilead Sciences Ltd.

MC is an NIHR Senior Investigator and reports grants from UKRI, NIHR, Macmillan Cancer Support, PCORI, Innovate UK, NIHR Surgical Reconstruction and Microbiology Research Centre (SRMRC), NIHR Applied Research Collaborative, West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, HDRUK, Gilead, GSK and Janssen and personal fees from Astellas, Aparito Ltd, CIS Oncology, Takeda, Merck, Glaukos, GSK and Daiichi Sankyo outside the submitted work. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

We are grateful to Drs Dan O’Connor and Bellinda L. King-Kallimanis for their helpful comments on the manuscript. The views expressed are not of the MHRA or the FDA.

This paper presents independent research funded by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham (Grant Reference Number BRC-1215-20009). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funder played no role in the design of the study, collection, analysis and interpretation of data and in writing the manuscript.

Publisher Copyright:
© 2022, The Author(s).

Keywords

COS
IMIDs
core outcome set
rheumatoid arthritis
rheumatology
tissue-agnostic clinical trials
Tissue-agnostic clinical trials
Rheumatoid arthritis
Rheumatology
Core outcome set

ASJC Scopus subject areas

Pharmacology (medical)
Medicine (miscellaneous)

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Cite this

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title = "Outcome selection for tissue-agnostic drug trials for immune mediated inflammatory diseases: a systematic review of core outcome sets and regulatory guidance",

abstract = "Background: Tissue-agnostic drug development provides a paradigm shift in precision medicine and requires innovative trial designs. However, outcome selection for such trials can prove challenging. The objectives of this review were to:(i)Identify and map core outcome sets (COS), across 11 immune-mediated inflammatory diseases (IMIDs) in order to facilitate the selection of relevant outcomes across the conditions for innovative trials of tissue-agnostic drug therapies.(ii)Compare outcomes or endpoints recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to identify and highlight similarities and differences. Methods: The Core Outcome Measures in Effectiveness Trials (COMET), International Consortium for Health Outcomes Measurement (ICHOM), FDA and EMA databases were searched from inception to 28th December 2019. Two reviewers independently screened titles and abstracts of retrieved entries and conducted the subsequent full text screening. Hand searching of the reference lists and citation searching of the selected publications was conducted. The methodological quality of the included peer-reviewed articles was independently assessed by the reviewers based on the items of the COS–Standards for Development recommendations (COS–STAD) checklist. Core outcomes from the included publications were extracted and mapped across studies and conditions. Regulatory guidance from FDA and EMA, where available for clinical trials for the IMIDs, were obtained from their databases and recommendations on outcomes to measure directly compared. Results: Forty-four COS publications were included in the final analysis. Outcomes such as disease activity, pain, fatigue, quality of life, physical function, work limitation/productivity, steroid use and biomarkers were recommended across majority of the conditions. There were significant similarities and differences in FDA and EMA recommendations. The only instance where either regulatory body directly referenced a COS was for jSLE—both referenced the Paediatric Rheumatology International Trials Organization (PRINTO) COS. Conclusions: The findings from this systematic review provide valuable information to inform outcome selection in tissue-agnostic trials for IMIDs. There is a need for increased collaboration between regulators and COS developers and inclusion of regulators as key stakeholders in COS development to enhance the quality of COS. Trial registration: Not registered.",

keywords = "COS, IMIDs, core outcome set, rheumatoid arthritis, rheumatology, tissue-agnostic clinical trials, Tissue-agnostic clinical trials, Rheumatoid arthritis, Rheumatology, Core outcome set",

author = "Aiyegbusi, {Olalekan Lee} and {Ferrante di Ruffano}, Lavinia and Ameeta Retzer and Philip Newsome and Christopher Buckley and Melanie Calvert",

note = "Funding Information: OLA, PNN and MC were supported by the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC), West Midlands, Birmingham. OLA also receives funding from the Health Foundation and personal fees from Gilead Sciences Ltd. MC is an NIHR Senior Investigator and reports grants from UKRI, NIHR, Macmillan Cancer Support, PCORI, Innovate UK, NIHR Surgical Reconstruction and Microbiology Research Centre (SRMRC), NIHR Applied Research Collaborative, West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, HDRUK, Gilead, GSK and Janssen and personal fees from Astellas, Aparito Ltd, CIS Oncology, Takeda, Merck, Glaukos, GSK and Daiichi Sankyo outside the submitted work. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We are grateful to Drs Dan O{\textquoteright}Connor and Bellinda L. King-Kallimanis for their helpful comments on the manuscript. The views expressed are not of the MHRA or the FDA. This paper presents independent research funded by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham (Grant Reference Number BRC-1215-20009). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funder played no role in the design of the study, collection, analysis and interpretation of data and in writing the manuscript. Publisher Copyright: {\textcopyright} 2022, The Author(s). ",

year = "2022",

month = dec,

doi = "10.1186/s13063-022-06000-w",

language = "English",

volume = "23",

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T1 - Outcome selection for tissue-agnostic drug trials for immune mediated inflammatory diseases

T2 - a systematic review of core outcome sets and regulatory guidance

AU - Aiyegbusi, Olalekan Lee

AU - Ferrante di Ruffano, Lavinia

AU - Retzer, Ameeta

AU - Newsome, Philip

AU - Buckley, Christopher

AU - Calvert, Melanie

N1 - Funding Information: OLA, PNN and MC were supported by the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC), West Midlands, Birmingham. OLA also receives funding from the Health Foundation and personal fees from Gilead Sciences Ltd. MC is an NIHR Senior Investigator and reports grants from UKRI, NIHR, Macmillan Cancer Support, PCORI, Innovate UK, NIHR Surgical Reconstruction and Microbiology Research Centre (SRMRC), NIHR Applied Research Collaborative, West Midlands at the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, HDRUK, Gilead, GSK and Janssen and personal fees from Astellas, Aparito Ltd, CIS Oncology, Takeda, Merck, Glaukos, GSK and Daiichi Sankyo outside the submitted work. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We are grateful to Drs Dan O’Connor and Bellinda L. King-Kallimanis for their helpful comments on the manuscript. The views expressed are not of the MHRA or the FDA. This paper presents independent research funded by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham (Grant Reference Number BRC-1215-20009). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funder played no role in the design of the study, collection, analysis and interpretation of data and in writing the manuscript. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Background: Tissue-agnostic drug development provides a paradigm shift in precision medicine and requires innovative trial designs. However, outcome selection for such trials can prove challenging. The objectives of this review were to:(i)Identify and map core outcome sets (COS), across 11 immune-mediated inflammatory diseases (IMIDs) in order to facilitate the selection of relevant outcomes across the conditions for innovative trials of tissue-agnostic drug therapies.(ii)Compare outcomes or endpoints recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to identify and highlight similarities and differences. Methods: The Core Outcome Measures in Effectiveness Trials (COMET), International Consortium for Health Outcomes Measurement (ICHOM), FDA and EMA databases were searched from inception to 28th December 2019. Two reviewers independently screened titles and abstracts of retrieved entries and conducted the subsequent full text screening. Hand searching of the reference lists and citation searching of the selected publications was conducted. The methodological quality of the included peer-reviewed articles was independently assessed by the reviewers based on the items of the COS–Standards for Development recommendations (COS–STAD) checklist. Core outcomes from the included publications were extracted and mapped across studies and conditions. Regulatory guidance from FDA and EMA, where available for clinical trials for the IMIDs, were obtained from their databases and recommendations on outcomes to measure directly compared. Results: Forty-four COS publications were included in the final analysis. Outcomes such as disease activity, pain, fatigue, quality of life, physical function, work limitation/productivity, steroid use and biomarkers were recommended across majority of the conditions. There were significant similarities and differences in FDA and EMA recommendations. The only instance where either regulatory body directly referenced a COS was for jSLE—both referenced the Paediatric Rheumatology International Trials Organization (PRINTO) COS. Conclusions: The findings from this systematic review provide valuable information to inform outcome selection in tissue-agnostic trials for IMIDs. There is a need for increased collaboration between regulators and COS developers and inclusion of regulators as key stakeholders in COS development to enhance the quality of COS. Trial registration: Not registered.

AB - Background: Tissue-agnostic drug development provides a paradigm shift in precision medicine and requires innovative trial designs. However, outcome selection for such trials can prove challenging. The objectives of this review were to:(i)Identify and map core outcome sets (COS), across 11 immune-mediated inflammatory diseases (IMIDs) in order to facilitate the selection of relevant outcomes across the conditions for innovative trials of tissue-agnostic drug therapies.(ii)Compare outcomes or endpoints recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to identify and highlight similarities and differences. Methods: The Core Outcome Measures in Effectiveness Trials (COMET), International Consortium for Health Outcomes Measurement (ICHOM), FDA and EMA databases were searched from inception to 28th December 2019. Two reviewers independently screened titles and abstracts of retrieved entries and conducted the subsequent full text screening. Hand searching of the reference lists and citation searching of the selected publications was conducted. The methodological quality of the included peer-reviewed articles was independently assessed by the reviewers based on the items of the COS–Standards for Development recommendations (COS–STAD) checklist. Core outcomes from the included publications were extracted and mapped across studies and conditions. Regulatory guidance from FDA and EMA, where available for clinical trials for the IMIDs, were obtained from their databases and recommendations on outcomes to measure directly compared. Results: Forty-four COS publications were included in the final analysis. Outcomes such as disease activity, pain, fatigue, quality of life, physical function, work limitation/productivity, steroid use and biomarkers were recommended across majority of the conditions. There were significant similarities and differences in FDA and EMA recommendations. The only instance where either regulatory body directly referenced a COS was for jSLE—both referenced the Paediatric Rheumatology International Trials Organization (PRINTO) COS. Conclusions: The findings from this systematic review provide valuable information to inform outcome selection in tissue-agnostic trials for IMIDs. There is a need for increased collaboration between regulators and COS developers and inclusion of regulators as key stakeholders in COS development to enhance the quality of COS. Trial registration: Not registered.

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Outcome selection for tissue-agnostic drug trials for immune mediated inflammatory diseases: a systematic review of core outcome sets and regulatory guidance

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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