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, 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

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.

Trial registration: ClinicalTrials.gov NCT02852694; https://ichgcp.net/clinical-trials-registry/NCT02852694.

Keywords: Crohn disease; adalimumab; clinical trial; cost-benefit analysis; protocol; technology assessment, biomedical.

Conflict of interest statement

Conflicts of Interest: 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.

©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. Originally published in JMIR Formative Research (http://formative.jmir.org), 25.01.2021.

Figures

Figure 1
Figure 1
Selection of relevant articles.

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