Identifying health economic considerations to include in the research protocol of a randomized controlled trial (the REDUCE-RISK Trial): Systematic literature review and assessment

Mattias Neyt; Annick Christiaens; Marina Aloi; Lissy de Ridder; Nicholas M. Croft; Sibylle Koletzko; Arie Levine; Dan Turner; Richard K. Russell; Frank M. Ruemmele; Gigi Veereman

doi:10.2196/13888

Identifying health economic considerations to include in the research protocol of a randomized controlled trial (the REDUCE-RISK Trial): Systematic literature review and assessment

Mattias Neyt^*, Annick Christiaens, Marina Aloi, Lissy de Ridder, Nicholas M. Croft, Sibylle Koletzko, Arie Levine, Dan Turner, Richard K. Russell, Frank M. Ruemmele, Gigi Veereman

^*Corresponding author for this work

Faculty of Medicine

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

Abstract

Background: The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years). Objective: The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished. Methods: The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD’s National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected. Results: A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children’s school attendance and parents’ productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument. Conclusions: The review of the economic literature on ADA for the treatment of patients with CD supports the performance of a trial with biologicals in pediatric patients, including making a distinction according to disease severity. Conducting an economic literature review enabled us to decide which variables should be added to the research protocol from an economic point of view. Measurements for children’s and parents’ QoL (EuroQol 5-Dimension questionnaires), children’s school attendance, and parents’ productivity (WPAI-CD-CG questionnaire) were added to the research protocol. This will provide support for the calculation of the cost-effectiveness of the interventions evaluated in the REDUCE-RISK trial.

Original language	American English
Article number	e13888
Journal	JMIR Formative Research
Volume	5
Issue number	1
DOIs	https://doi.org/10.2196/13888
State	Published - Jan 2021

Bibliographical note

Funding Information:
LR received a consultancy fee or a grant from Pfizer, Abbvie, Celltrion, ZonMw in the previous 3 years. NC’s institution received speaker fees, advisory board fees, and research funding from Abbvie, Eli Lilly, Takeda, Shire, Pfizer, Jansenn, Allergan, 4D Pharma. SK reports grants from Mead Johnson, Nestec Nutrition, BioGaia, personal fees from Nestle, Danone, Biocodex, Shire, Abbvie, R-Biopharm, Vifor, Pharmacosmos, Celgene, ThermoFisher, Pfizer, Janssen, outside the submitted work. AL report to have IP or received travel grants, speakers’ honoraria, research grants from Nestle, Janssen, AbbVie, Megapharm and Takeda. DT received consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Atlantic Health, Shire, Celgene, Lilly, Roche, ThermoFisher, BMS during the last 3 years. FR received consultation fee, research grant, or honorarium from Janssen, Pfizer, Abbvie, Takeda, Celgene, Nestlé Health Science, Nestlé Nutrition Institute during the last 3 years.

Funding Information:
The REDUCE-RISK trial, an international multicenter open-label prospective randomized controlled trial (RCT), has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 668023. This trial has been reviewed and approved by the National Ethics Services of participating countries and is prospectively registered (ClinicalTrials.gov Identifier: NCT02852694; date of registration: June 9, 2016; EudraCT Number: 2016-000522-18).

Publisher Copyright:
© Mattias Neyt, Annick Christiaens, Marina Aloi, Lissy de Ridder, Nicholas M Croft, Sibylle Koletzko, Arie Levine, Dan Turner, Richard K Russell, Frank M Ruemmele, Gigi Veereman.

Keywords

Adalimumab
Biomedical
Clinical trial
Cost-benefit analysis
Crohn disease
Protocol
Technology assessment

UN SDGs

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

Access to Document

10.2196/13888

Cite this

Neyt, M., Christiaens, A., Aloi, M., de Ridder, L., Croft, N. M., Koletzko, S., Levine, A., Turner, D., Russell, R. K., Ruemmele, F. M., & Veereman, G. (2021). Identifying health economic considerations to include in the research protocol of a randomized controlled trial (the REDUCE-RISK Trial): Systematic literature review and assessment. JMIR Formative Research, 5(1), Article e13888. https://doi.org/10.2196/13888

@article{f96d361f83eb4652818362e2fb52dee7,

title = "Identifying health economic considerations to include in the research protocol of a randomized controlled trial (the REDUCE-RISK Trial): Systematic literature review and assessment",

abstract = "Background: The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years). Objective: The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished. Methods: The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD{\textquoteright}s National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected. Results: A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children{\textquoteright}s school attendance and parents{\textquoteright} productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument. Conclusions: The review of the economic literature on ADA for the treatment of patients with CD supports the performance of a trial with biologicals in pediatric patients, including making a distinction according to disease severity. Conducting an economic literature review enabled us to decide which variables should be added to the research protocol from an economic point of view. Measurements for children{\textquoteright}s and parents{\textquoteright} QoL (EuroQol 5-Dimension questionnaires), children{\textquoteright}s school attendance, and parents{\textquoteright} productivity (WPAI-CD-CG questionnaire) were added to the research protocol. This will provide support for the calculation of the cost-effectiveness of the interventions evaluated in the REDUCE-RISK trial.",

keywords = "Adalimumab, Biomedical, Clinical trial, Cost-benefit analysis, Crohn disease, Protocol, Technology assessment",

author = "Mattias Neyt and Annick Christiaens and Marina Aloi and {de Ridder}, Lissy and Croft, {Nicholas M.} and Sibylle Koletzko and Arie Levine and Dan Turner and Russell, {Richard K.} and Ruemmele, {Frank M.} and Gigi Veereman",

note = "Funding Information: LR received a consultancy fee or a grant from Pfizer, Abbvie, Celltrion, ZonMw in the previous 3 years. NC{\textquoteright}s institution received speaker fees, advisory board fees, and research funding from Abbvie, Eli Lilly, Takeda, Shire, Pfizer, Jansenn, Allergan, 4D Pharma. SK reports grants from Mead Johnson, Nestec Nutrition, BioGaia, personal fees from Nestle, Danone, Biocodex, Shire, Abbvie, R-Biopharm, Vifor, Pharmacosmos, Celgene, ThermoFisher, Pfizer, Janssen, outside the submitted work. AL report to have IP or received travel grants, speakers{\textquoteright} honoraria, research grants from Nestle, Janssen, AbbVie, Megapharm and Takeda. DT received consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Atlantic Health, Shire, Celgene, Lilly, Roche, ThermoFisher, BMS during the last 3 years. FR received consultation fee, research grant, or honorarium from Janssen, Pfizer, Abbvie, Takeda, Celgene, Nestl{\'e} Health Science, Nestl{\'e} Nutrition Institute during the last 3 years. Funding Information: The REDUCE-RISK trial, an international multicenter open-label prospective randomized controlled trial (RCT), has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under grant agreement number 668023. This trial has been reviewed and approved by the National Ethics Services of participating countries and is prospectively registered (ClinicalTrials.gov Identifier: NCT02852694; date of registration: June 9, 2016; EudraCT Number: 2016-000522-18). Publisher Copyright: {\textcopyright} Mattias Neyt, Annick Christiaens, Marina Aloi, Lissy de Ridder, Nicholas M Croft, Sibylle Koletzko, Arie Levine, Dan Turner, Richard K Russell, Frank M Ruemmele, Gigi Veereman.",

year = "2021",

month = jan,

doi = "10.2196/13888",

language = "American English",

volume = "5",

journal = "JMIR Formative Research",

issn = "2561-326X",

publisher = "JMIR Publications Inc.",

number = "1",

}

Neyt, M, Christiaens, A, Aloi, M, de Ridder, L, Croft, NM, Koletzko, S, Levine, A, Turner, D, Russell, RK, Ruemmele, FM & Veereman, G 2021, 'Identifying health economic considerations to include in the research protocol of a randomized controlled trial (the REDUCE-RISK Trial): Systematic literature review and assessment', JMIR Formative Research, vol. 5, no. 1, e13888. https://doi.org/10.2196/13888

Identifying health economic considerations to include in the research protocol of a randomized controlled trial (the REDUCE-RISK Trial): Systematic literature review and assessment. / Neyt, Mattias; Christiaens, Annick; Aloi, Marina et al.
In: JMIR Formative Research, Vol. 5, No. 1, e13888, 01.2021.

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

TY - JOUR

T1 - Identifying health economic considerations to include in the research protocol of a randomized controlled trial (the REDUCE-RISK Trial)

T2 - Systematic literature review and assessment

AU - Neyt, Mattias

AU - Christiaens, Annick

AU - Aloi, Marina

AU - de Ridder, Lissy

AU - Croft, Nicholas M.

AU - Koletzko, Sibylle

AU - Levine, Arie

AU - Turner, Dan

AU - Russell, Richard K.

AU - Ruemmele, Frank M.

AU - Veereman, Gigi

N1 - Funding Information: LR received a consultancy fee or a grant from Pfizer, Abbvie, Celltrion, ZonMw in the previous 3 years. NC’s institution received speaker fees, advisory board fees, and research funding from Abbvie, Eli Lilly, Takeda, Shire, Pfizer, Jansenn, Allergan, 4D Pharma. SK reports grants from Mead Johnson, Nestec Nutrition, BioGaia, personal fees from Nestle, Danone, Biocodex, Shire, Abbvie, R-Biopharm, Vifor, Pharmacosmos, Celgene, ThermoFisher, Pfizer, Janssen, outside the submitted work. AL report to have IP or received travel grants, speakers’ honoraria, research grants from Nestle, Janssen, AbbVie, Megapharm and Takeda. DT received consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Hospital for Sick Children, Ferring, Abbvie, Takeda, Atlantic Health, Shire, Celgene, Lilly, Roche, ThermoFisher, BMS during the last 3 years. FR received consultation fee, research grant, or honorarium from Janssen, Pfizer, Abbvie, Takeda, Celgene, Nestlé Health Science, Nestlé Nutrition Institute during the last 3 years. Funding Information: The REDUCE-RISK trial, an international multicenter open-label prospective randomized controlled trial (RCT), has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 668023. This trial has been reviewed and approved by the National Ethics Services of participating countries and is prospectively registered (ClinicalTrials.gov Identifier: NCT02852694; date of registration: June 9, 2016; EudraCT Number: 2016-000522-18). Publisher Copyright: © Mattias Neyt, Annick Christiaens, Marina Aloi, Lissy de Ridder, Nicholas M Croft, Sibylle Koletzko, Arie Levine, Dan Turner, Richard K Russell, Frank M Ruemmele, Gigi Veereman.

PY - 2021/1

Y1 - 2021/1

N2 - Background: The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years). Objective: The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished. Methods: The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD’s National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected. Results: A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children’s school attendance and parents’ productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument. Conclusions: The review of the economic literature on ADA for the treatment of patients with CD supports the performance of a trial with biologicals in pediatric patients, including making a distinction according to disease severity. Conducting an economic literature review enabled us to decide which variables should be added to the research protocol from an economic point of view. Measurements for children’s and parents’ QoL (EuroQol 5-Dimension questionnaires), children’s school attendance, and parents’ productivity (WPAI-CD-CG questionnaire) were added to the research protocol. This will provide support for the calculation of the cost-effectiveness of the interventions evaluated in the REDUCE-RISK trial.

AB - Background: The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years). Objective: The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished. Methods: The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD’s National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected. Results: A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children’s school attendance and parents’ productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument. Conclusions: The review of the economic literature on ADA for the treatment of patients with CD supports the performance of a trial with biologicals in pediatric patients, including making a distinction according to disease severity. Conducting an economic literature review enabled us to decide which variables should be added to the research protocol from an economic point of view. Measurements for children’s and parents’ QoL (EuroQol 5-Dimension questionnaires), children’s school attendance, and parents’ productivity (WPAI-CD-CG questionnaire) were added to the research protocol. This will provide support for the calculation of the cost-effectiveness of the interventions evaluated in the REDUCE-RISK trial.

KW - Adalimumab

KW - Biomedical

KW - Clinical trial

KW - Cost-benefit analysis

KW - Crohn disease

KW - Protocol

KW - Technology assessment

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U2 - 10.2196/13888

DO - 10.2196/13888

M3 - Review article

C2 - 33492239

AN - SCOPUS:85100457545

SN - 2561-326X

VL - 5

JO - JMIR Formative Research

JF - JMIR Formative Research

IS - 1

M1 - e13888

ER -

Identifying health economic considerations to include in the research protocol of a randomized controlled trial (the REDUCE-RISK Trial): Systematic literature review and assessment

Abstract

Bibliographical note

Keywords

UN SDGs

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