Factors associated with response to placebo in patients with irritable bowel syndrome and constipation

Sarah Ballou, Alissa Beath, Ted J. Kaptchuk, William Hirsch, Thomas Sommers, Judy Nee, Johanna Iturrino, Vikram Rangan, Prashant Singh, Mike Jones, Anthony Lembo

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background & Aims: A high proportion of patients with irritable bowel syndrome (IBS) respond to placebo in clinical trials (estimated at about 40%). We aimed to identify factors that contribute to the high placebo response rate using data from a placebo-controlled trial of patients with IBS. Methods: We performed a retrospective analysis of 599 women with IBS with constipation who were in the placebo group of a 12-week, randomized, double-blind, phase 3 trial of the experimental medication renzapride. Primary analyses evaluated frequency of abdominal pain in patients who received placebo, defined as ≥30% pain improvement from baseline for ≥6 of the 12 study weeks. We performed backward elimination regression with bootstrapping to identify factors associated with response to placebo. Results: In the placebo group, 29.0% of the patients had an abdominal pain response. Factors associated with a response to placebo were baseline variation in abdominal pain (odds ratio [OR], 1.71), maximum baseline pain severity (OR, 1.34), and placebo response in study week 2 (OR, 2.23) or week 3 (OR, 3.69). Factors associated with lack of response to placebo were number of baseline complete spontaneous bowel movements (OR, 0.73; P = .019) and final baseline pain ratings (OR, 0.73; P < .001). Conclusions: We identified factors associated with a response in abdominal pain to placebo using original data from an IBS clinical trial. Baseline factors associated with the placebo response in women with IBS and constipation included variation in baseline pain symptoms, severity of baseline symptoms, and early improvement of abdominal pain. These findings have significant implications for clinical trial design.

LanguageEnglish
Pages1738-1744.e1
Number of pages8
JournalClinical Gastroenterology and Hepatology
Volume16
Issue number11
DOIs
Publication statusPublished - 1 Nov 2018

Fingerprint

Irritable Bowel Syndrome
Constipation
Placebos
Abdominal Pain
Odds Ratio
Pain
Clinical Trials

Keywords

  • CSBM
  • IBS-C
  • predict
  • outcome

Cite this

Ballou, Sarah ; Beath, Alissa ; Kaptchuk, Ted J. ; Hirsch, William ; Sommers, Thomas ; Nee, Judy ; Iturrino, Johanna ; Rangan, Vikram ; Singh, Prashant ; Jones, Mike ; Lembo, Anthony. / Factors associated with response to placebo in patients with irritable bowel syndrome and constipation. In: Clinical Gastroenterology and Hepatology. 2018 ; Vol. 16, No. 11. pp. 1738-1744.e1.
@article{bcd1df4e910c4a28a577dfa620afeccf,
title = "Factors associated with response to placebo in patients with irritable bowel syndrome and constipation",
abstract = "Background & Aims: A high proportion of patients with irritable bowel syndrome (IBS) respond to placebo in clinical trials (estimated at about 40{\%}). We aimed to identify factors that contribute to the high placebo response rate using data from a placebo-controlled trial of patients with IBS. Methods: We performed a retrospective analysis of 599 women with IBS with constipation who were in the placebo group of a 12-week, randomized, double-blind, phase 3 trial of the experimental medication renzapride. Primary analyses evaluated frequency of abdominal pain in patients who received placebo, defined as ≥30{\%} pain improvement from baseline for ≥6 of the 12 study weeks. We performed backward elimination regression with bootstrapping to identify factors associated with response to placebo. Results: In the placebo group, 29.0{\%} of the patients had an abdominal pain response. Factors associated with a response to placebo were baseline variation in abdominal pain (odds ratio [OR], 1.71), maximum baseline pain severity (OR, 1.34), and placebo response in study week 2 (OR, 2.23) or week 3 (OR, 3.69). Factors associated with lack of response to placebo were number of baseline complete spontaneous bowel movements (OR, 0.73; P = .019) and final baseline pain ratings (OR, 0.73; P < .001). Conclusions: We identified factors associated with a response in abdominal pain to placebo using original data from an IBS clinical trial. Baseline factors associated with the placebo response in women with IBS and constipation included variation in baseline pain symptoms, severity of baseline symptoms, and early improvement of abdominal pain. These findings have significant implications for clinical trial design.",
keywords = "CSBM, IBS-C, predict, outcome",
author = "Sarah Ballou and Alissa Beath and Kaptchuk, {Ted J.} and William Hirsch and Thomas Sommers and Judy Nee and Johanna Iturrino and Vikram Rangan and Prashant Singh and Mike Jones and Anthony Lembo",
year = "2018",
month = "11",
day = "1",
doi = "10.1016/j.cgh.2018.04.009",
language = "English",
volume = "16",
pages = "1738--1744.e1",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC",
number = "11",

}

Ballou, S, Beath, A, Kaptchuk, TJ, Hirsch, W, Sommers, T, Nee, J, Iturrino, J, Rangan, V, Singh, P, Jones, M & Lembo, A 2018, 'Factors associated with response to placebo in patients with irritable bowel syndrome and constipation', Clinical Gastroenterology and Hepatology, vol. 16, no. 11, pp. 1738-1744.e1. https://doi.org/10.1016/j.cgh.2018.04.009

Factors associated with response to placebo in patients with irritable bowel syndrome and constipation. / Ballou, Sarah; Beath, Alissa; Kaptchuk, Ted J.; Hirsch, William; Sommers, Thomas; Nee, Judy; Iturrino, Johanna; Rangan, Vikram; Singh, Prashant; Jones, Mike; Lembo, Anthony.

In: Clinical Gastroenterology and Hepatology, Vol. 16, No. 11, 01.11.2018, p. 1738-1744.e1.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Factors associated with response to placebo in patients with irritable bowel syndrome and constipation

AU - Ballou, Sarah

AU - Beath, Alissa

AU - Kaptchuk, Ted J.

AU - Hirsch, William

AU - Sommers, Thomas

AU - Nee, Judy

AU - Iturrino, Johanna

AU - Rangan, Vikram

AU - Singh, Prashant

AU - Jones, Mike

AU - Lembo, Anthony

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background & Aims: A high proportion of patients with irritable bowel syndrome (IBS) respond to placebo in clinical trials (estimated at about 40%). We aimed to identify factors that contribute to the high placebo response rate using data from a placebo-controlled trial of patients with IBS. Methods: We performed a retrospective analysis of 599 women with IBS with constipation who were in the placebo group of a 12-week, randomized, double-blind, phase 3 trial of the experimental medication renzapride. Primary analyses evaluated frequency of abdominal pain in patients who received placebo, defined as ≥30% pain improvement from baseline for ≥6 of the 12 study weeks. We performed backward elimination regression with bootstrapping to identify factors associated with response to placebo. Results: In the placebo group, 29.0% of the patients had an abdominal pain response. Factors associated with a response to placebo were baseline variation in abdominal pain (odds ratio [OR], 1.71), maximum baseline pain severity (OR, 1.34), and placebo response in study week 2 (OR, 2.23) or week 3 (OR, 3.69). Factors associated with lack of response to placebo were number of baseline complete spontaneous bowel movements (OR, 0.73; P = .019) and final baseline pain ratings (OR, 0.73; P < .001). Conclusions: We identified factors associated with a response in abdominal pain to placebo using original data from an IBS clinical trial. Baseline factors associated with the placebo response in women with IBS and constipation included variation in baseline pain symptoms, severity of baseline symptoms, and early improvement of abdominal pain. These findings have significant implications for clinical trial design.

AB - Background & Aims: A high proportion of patients with irritable bowel syndrome (IBS) respond to placebo in clinical trials (estimated at about 40%). We aimed to identify factors that contribute to the high placebo response rate using data from a placebo-controlled trial of patients with IBS. Methods: We performed a retrospective analysis of 599 women with IBS with constipation who were in the placebo group of a 12-week, randomized, double-blind, phase 3 trial of the experimental medication renzapride. Primary analyses evaluated frequency of abdominal pain in patients who received placebo, defined as ≥30% pain improvement from baseline for ≥6 of the 12 study weeks. We performed backward elimination regression with bootstrapping to identify factors associated with response to placebo. Results: In the placebo group, 29.0% of the patients had an abdominal pain response. Factors associated with a response to placebo were baseline variation in abdominal pain (odds ratio [OR], 1.71), maximum baseline pain severity (OR, 1.34), and placebo response in study week 2 (OR, 2.23) or week 3 (OR, 3.69). Factors associated with lack of response to placebo were number of baseline complete spontaneous bowel movements (OR, 0.73; P = .019) and final baseline pain ratings (OR, 0.73; P < .001). Conclusions: We identified factors associated with a response in abdominal pain to placebo using original data from an IBS clinical trial. Baseline factors associated with the placebo response in women with IBS and constipation included variation in baseline pain symptoms, severity of baseline symptoms, and early improvement of abdominal pain. These findings have significant implications for clinical trial design.

KW - CSBM

KW - IBS-C

KW - predict

KW - outcome

UR - http://www.scopus.com/inward/record.url?scp=85051057019&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2018.04.009

DO - 10.1016/j.cgh.2018.04.009

M3 - Article

VL - 16

SP - 1738-1744.e1

JO - Clinical Gastroenterology and Hepatology

T2 - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 11

ER -