Heterogeneity in Definitions of Efficacy and Safety Endpoints for Clinical Trials of Crohn's Disease: A Systematic Review

Christopher Ma, Isra M. Hussein, Yousef J. Al-Abbar, Remo Panaccione, Richard N. Fedorak, Claire E. Parker, Tran M. Nguyen, Reena Khanna, Corey A. Siegel, Laurent Peyrin-Biroulet, Rish Pai, Niels Vande Casteele, Geert R. D'Haens, William J. Sandborn, Brian G. Feagan, Vipul Jairath

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Background & Aims: Endpoints in randomized controlled trials (RCTs) of Crohn's disease (CD) are changing. We performed a systematic review of efficacy and safety outcomes reported in placebo-controlled RCTs of patients with CD. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Library through March 1, 2017 for placebo-controlled RCTs of adult patients with CD treated with aminosalicylates, immunomodulators, corticosteroids, biologics, and oral small molecules. Efficacy and safety outcomes, definitions, and measurement tools were collected and stratified by decade of publication. Results: Our final analysis included 116 RCTs (81 induction, 44 maintenance, 7 postoperative prevention trials, comprising 27,263 patients). Clinical efficacy endpoints were reported in all trials; the most common endpoint was CD activity index score. We identified 38 unique definitions of clinical response or remission and 32 definitions of loss of response. Definitions of endoscopic response, remission, and endoscopic healing were also heterogeneous, evaluated using the CD endoscopic index of severity, the simple endoscopic score for CD, ulcer resolution, and Rutgeerts’ Score for postoperative endoscopic appearance. Histologic outcomes were reported in 11.1% of induction trials, 2.3% of maintenance trials, and 14.3% of postoperative prevention trials. Biomarker outcomes were reported in 81.5% induction trials, 68.2% of maintenance trials, and 42.9% of postoperative prevention trials. Safety outcomes were reported in 93.8% of induction trials, 97.7% of maintenance trials, and 85.7% of postoperative prevention trials. Conclusions: In this systematic review, we demonstrate heterogeneity in definitions of response and remission, and changes in outcomes reported in RCTs of CD. It is a priority to select a core set of outcomes to standardize efficacy and safety evaluation in trials of patients with CD.

Original languageEnglish (US)
Pages (from-to)1407-1419.e22
JournalClinical Gastroenterology and Hepatology
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

Crohn Disease
Clinical Trials
Safety
Randomized Controlled Trials
Maintenance
Placebos
Immunologic Factors
Biological Products
MEDLINE
Libraries
Ulcer
Publications
Adrenal Cortex Hormones
Biomarkers

Keywords

  • Effects
  • IBD
  • Inflammatory Bowel Disease
  • RCT
  • Treatment

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Ma, C., Hussein, I. M., Al-Abbar, Y. J., Panaccione, R., Fedorak, R. N., Parker, C. E., ... Jairath, V. (2018). Heterogeneity in Definitions of Efficacy and Safety Endpoints for Clinical Trials of Crohn's Disease: A Systematic Review. Clinical Gastroenterology and Hepatology, 16(9), 1407-1419.e22. https://doi.org/10.1016/j.cgh.2018.02.051

Heterogeneity in Definitions of Efficacy and Safety Endpoints for Clinical Trials of Crohn's Disease : A Systematic Review. / Ma, Christopher; Hussein, Isra M.; Al-Abbar, Yousef J.; Panaccione, Remo; Fedorak, Richard N.; Parker, Claire E.; Nguyen, Tran M.; Khanna, Reena; Siegel, Corey A.; Peyrin-Biroulet, Laurent; Pai, Rish; Vande Casteele, Niels; D'Haens, Geert R.; Sandborn, William J.; Feagan, Brian G.; Jairath, Vipul.

In: Clinical Gastroenterology and Hepatology, Vol. 16, No. 9, 01.09.2018, p. 1407-1419.e22.

Research output: Contribution to journalReview article

Ma, C, Hussein, IM, Al-Abbar, YJ, Panaccione, R, Fedorak, RN, Parker, CE, Nguyen, TM, Khanna, R, Siegel, CA, Peyrin-Biroulet, L, Pai, R, Vande Casteele, N, D'Haens, GR, Sandborn, WJ, Feagan, BG & Jairath, V 2018, 'Heterogeneity in Definitions of Efficacy and Safety Endpoints for Clinical Trials of Crohn's Disease: A Systematic Review', Clinical Gastroenterology and Hepatology, vol. 16, no. 9, pp. 1407-1419.e22. https://doi.org/10.1016/j.cgh.2018.02.051
Ma, Christopher ; Hussein, Isra M. ; Al-Abbar, Yousef J. ; Panaccione, Remo ; Fedorak, Richard N. ; Parker, Claire E. ; Nguyen, Tran M. ; Khanna, Reena ; Siegel, Corey A. ; Peyrin-Biroulet, Laurent ; Pai, Rish ; Vande Casteele, Niels ; D'Haens, Geert R. ; Sandborn, William J. ; Feagan, Brian G. ; Jairath, Vipul. / Heterogeneity in Definitions of Efficacy and Safety Endpoints for Clinical Trials of Crohn's Disease : A Systematic Review. In: Clinical Gastroenterology and Hepatology. 2018 ; Vol. 16, No. 9. pp. 1407-1419.e22.
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AU - Hussein, Isra M.

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AU - Panaccione, Remo

AU - Fedorak, Richard N.

AU - Parker, Claire E.

AU - Nguyen, Tran M.

AU - Khanna, Reena

AU - Siegel, Corey A.

AU - Peyrin-Biroulet, Laurent

AU - Pai, Rish

AU - Vande Casteele, Niels

AU - D'Haens, Geert R.

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N2 - Background & Aims: Endpoints in randomized controlled trials (RCTs) of Crohn's disease (CD) are changing. We performed a systematic review of efficacy and safety outcomes reported in placebo-controlled RCTs of patients with CD. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Library through March 1, 2017 for placebo-controlled RCTs of adult patients with CD treated with aminosalicylates, immunomodulators, corticosteroids, biologics, and oral small molecules. Efficacy and safety outcomes, definitions, and measurement tools were collected and stratified by decade of publication. Results: Our final analysis included 116 RCTs (81 induction, 44 maintenance, 7 postoperative prevention trials, comprising 27,263 patients). Clinical efficacy endpoints were reported in all trials; the most common endpoint was CD activity index score. We identified 38 unique definitions of clinical response or remission and 32 definitions of loss of response. Definitions of endoscopic response, remission, and endoscopic healing were also heterogeneous, evaluated using the CD endoscopic index of severity, the simple endoscopic score for CD, ulcer resolution, and Rutgeerts’ Score for postoperative endoscopic appearance. Histologic outcomes were reported in 11.1% of induction trials, 2.3% of maintenance trials, and 14.3% of postoperative prevention trials. Biomarker outcomes were reported in 81.5% induction trials, 68.2% of maintenance trials, and 42.9% of postoperative prevention trials. Safety outcomes were reported in 93.8% of induction trials, 97.7% of maintenance trials, and 85.7% of postoperative prevention trials. Conclusions: In this systematic review, we demonstrate heterogeneity in definitions of response and remission, and changes in outcomes reported in RCTs of CD. It is a priority to select a core set of outcomes to standardize efficacy and safety evaluation in trials of patients with CD.

AB - Background & Aims: Endpoints in randomized controlled trials (RCTs) of Crohn's disease (CD) are changing. We performed a systematic review of efficacy and safety outcomes reported in placebo-controlled RCTs of patients with CD. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Library through March 1, 2017 for placebo-controlled RCTs of adult patients with CD treated with aminosalicylates, immunomodulators, corticosteroids, biologics, and oral small molecules. Efficacy and safety outcomes, definitions, and measurement tools were collected and stratified by decade of publication. Results: Our final analysis included 116 RCTs (81 induction, 44 maintenance, 7 postoperative prevention trials, comprising 27,263 patients). Clinical efficacy endpoints were reported in all trials; the most common endpoint was CD activity index score. We identified 38 unique definitions of clinical response or remission and 32 definitions of loss of response. Definitions of endoscopic response, remission, and endoscopic healing were also heterogeneous, evaluated using the CD endoscopic index of severity, the simple endoscopic score for CD, ulcer resolution, and Rutgeerts’ Score for postoperative endoscopic appearance. Histologic outcomes were reported in 11.1% of induction trials, 2.3% of maintenance trials, and 14.3% of postoperative prevention trials. Biomarker outcomes were reported in 81.5% induction trials, 68.2% of maintenance trials, and 42.9% of postoperative prevention trials. Safety outcomes were reported in 93.8% of induction trials, 97.7% of maintenance trials, and 85.7% of postoperative prevention trials. Conclusions: In this systematic review, we demonstrate heterogeneity in definitions of response and remission, and changes in outcomes reported in RCTs of CD. It is a priority to select a core set of outcomes to standardize efficacy and safety evaluation in trials of patients with CD.

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