TY - JOUR
T1 - Standardizing Randomized Controlled Trials in Celiac Disease
T2 - An International Multidisciplinary Appropriateness Study
AU - Lebwohl, Benjamin
AU - Ma, Christopher
AU - Lagana, Stephen M.
AU - Pai, Rish K.
AU - Baker, K. Adam
AU - Zayadi, Alexa
AU - Hogan, Malcolm
AU - Bouma, Gerd
AU - Cellier, Christophe
AU - Goldsmith, Jeffrey D.
AU - Lundin, Knut E.A.
AU - Pinto-Sanchez, Maria I.
AU - Robert, Marie E.
AU - Rubio-Tapia, Alberto
AU - Sanders, David S.
AU - Schaeffer, David F.
AU - Semrad, Carol E.
AU - Silvester, Jocelyn A.
AU - Verdú, Elena F.
AU - Verma, Ritu
AU - Wu, Tsung Teh
AU - Feagan, Brian G.
AU - Crowley, Eileen
AU - Jairath, Vipul
AU - Murray, Joseph A.
N1 - Publisher Copyright:
© 2024 AGA Institute
PY - 2024/1
Y1 - 2024/1
N2 - Background & Aims: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. Methods: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. Results: For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal–sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. Conclusions: We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.
AB - Background & Aims: There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. Methods: A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. Results: For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal–sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. Conclusions: We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.
KW - Celiac
KW - Gluten
KW - Histology
KW - Patient-Reported Outcomes
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UR - http://www.scopus.com/inward/citedby.url?scp=85177063866&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2023.08.051
DO - 10.1053/j.gastro.2023.08.051
M3 - Article
C2 - 37704112
AN - SCOPUS:85177063866
SN - 0016-5085
VL - 166
SP - 88
EP - 102
JO - Gastroenterology
JF - Gastroenterology
IS - 1
ER -