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 language | English (US) |
|---|---|
| Pages (from-to) | 1407-1419.e22 |
| Journal | Clinical Gastroenterology and Hepatology |
| Volume | 16 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2018 |
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Keywords
- Effects
- IBD
- Inflammatory Bowel Disease
- RCT
- Treatment
ASJC Scopus subject areas
- Hepatology
- Gastroenterology
Cite this
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 journal › Review article
}
TY - JOUR
T1 - Heterogeneity in Definitions of Efficacy and Safety Endpoints for Clinical Trials of Crohn's Disease
T2 - A Systematic Review
AU - Ma, Christopher
AU - Hussein, Isra M.
AU - Al-Abbar, Yousef J.
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.
AU - Sandborn, William J.
AU - Feagan, Brian G.
AU - Jairath, Vipul
PY - 2018/9/1
Y1 - 2018/9/1
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.
KW - Effects
KW - IBD
KW - Inflammatory Bowel Disease
KW - RCT
KW - Treatment
UR - http://www.scopus.com/inward/record.url?scp=85051144025&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051144025&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2018.02.051
DO - 10.1016/j.cgh.2018.02.051
M3 - Review article
C2 - 29596987
AN - SCOPUS:85051144025
VL - 16
SP - 1407-1419.e22
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 9
ER -