Placebo Rates in Inflammatory Bowel Disease: An Individual Patient Data Meta-analysis of Randomized Controlled Trials

Lead Investigator: Vipual Jairath, Alimentiv Inc.
Title of Proposal Research: Placebo Rates in Inflammatory Bowel Disease: An Individual Patient Data Meta-analysis of Randomized Controlled Trials
Vivli Data Request: 7288
Funding Source: Alimentiv is providing funding in in the form of resources to conduct the analysis. Alimentiv is a contract research organization that uses the profits from delivery of commercial services to reinvest in academic research that aligns with its partners shared purpose to accelerate drug discovery.
Potential Conflicts of Interest: Vipual Jairath and Christopher Ma received consulting fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena pharmaceuticals, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, GlaxoSmithKline, Genetech, Gilead, Janssen, Merck, Mylan, Pendopharm, Pfizer, Roche, Sandoz, Takeda, Topivert; speaker’s fees from, Abbvie, Ferring, Janssen Pfizer Shire, Takeda. The research outlined in this study is not receiving funding from any of the outlined companies with the exception of Alimentiv Inc which is the sponsor and funder of this study. Guangyong Zou and Robyn Garrels are employees of Alimentiv Inc.

Summary of the Proposed Research:
Inflammatory bowel disease (IBD) is a condition that causes swelling and pain in the digestive tract, which is the tube that carries food from the mouth to the stomach and subsequently to the anus. IBD is a common disease and 6.8 million people around the world suffer from it – and that number is growing. While there is no cure for IBD, there are several therapies available to treat the disease and more that are in development.

To learn whether a new therapy works to treat IBD, it must be tested in research studies. One way to do this is to compare the therapy to a placebo, which is a “fake” copy of the real therapy. The placebo looks like the real therapy, but it contains none of the medicine. In such a study, some IBD patients will be given therapy while others will be given placebo. Usually this is decided randomly (like the flip of a coin) and neither the patients nor their doctors know what they are taking until the study is over. If a therapy works, the group treated with the real therapy should do better than the group that received the placebo. Sometimes a therapy works very well and there is a big difference between the groups; other times the therapy has a small effect, or none at all, and the difference between the groups is lessened or disappears. But seeing the real benefit of a new therapy is made harder by something called the “placebo effect.” The placebo effect is a benefit that a person feels because of their belief in a therapy even though the improvement is not due to the therapy itself. For example, in a study where participants do not know if they are receiving therapy or placebo, it is common for those in the placebo group to still report some improvement in symptoms despite not receiving any medicine. There are many possible reasons for the placebo effect and previous research has identified several study-specific factors that contribute. However, more research is needed.

In this study, we want to take a close look at both study factors and independent study participant characteristics that are linked to the placebo effect. By identifying these factors, this study aims to estimate placebo response in IBD studies and improve the design of future studies in IBD by reducing the impact of the placebo effect and making it easier to estimate the real benefit of any new therapies.

Requested Studies:
A Multi-Center, Randomized, Double-blind, Placebo-controlled Study of Adalimumab for the Induction of Clinical Remission in Japanese Subjects With Crohn’s Disease
Data Contributor: AbbVie
Study ID: NCT00445939
Sponsor ID: M04-729

A Multi-Center, Randomized, Double-blind, Placebo-controlled Study of Adalimumab for the Maintenance of Clinical Remission in Japanese Subjects With Crohn’s Disease
Data Contributor: AbbVie
Study ID: NCT00445432
Sponsor ID: M06-837

A Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Adalimumab for the Induction and Maintenance of Clinical Remission in Chinese Patients With Moderately to Severely Active Crohn’s Disease and Elevated High-Sensitivity C-reactive Protein
Data Contributor: AbbVie
Study ID: NCT02499783
Sponsor ID: M14-233

A Multicenter, Randomized, Double-blind Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: AbbVie
Study ID: NCT00385736
Sponsor ID: M06-826

A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: AbbVie
Study ID: NCT00408629
Sponsor ID: M06-827

A Multi-Center, Randomized, Double-Blind, Placebo-controlled Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis.
Data Contributor: AbbVie
Study ID: NCT00853099
Sponsor ID: M10-447

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT00783718
Sponsor ID: C13006

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn’s Disease
Data Contributor: Takeda
Study ID: NCT00783692
Sponsor ID: C13007

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction of Clinical Response and Remission by Vedolizumab in Patients With Moderate to Severe Crohn’s Disease
Data Contributor: Takeda
Study ID: NCT01224171
Sponsor ID: C13011

Phase III, Multicenter, Randomized, Double-blinded, Placebo-controlled, Parallel-group Study to Examine the Efficacy, Safety, and Pharmacokinetics of Intravenous MLN0002 (300 mg) Infusion in Induction and Maintenance Therapy in Japanese Patients With Moderately or Severely Active Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT02039505
Sponsor ID: MLN0002/CCT-101

Phase III, Multicenter, Randomized, Double-blinded, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Intravenous MLN0002 (300 mg) Infusion in Induction and Maintenance Therapy in Japanese Subjects With Moderate or Severe Crohn’s Disease
Data Contributor: Takeda
Study ID: NCT02038920
Sponsor ID: MLN0002/CCT-001

A Phase 2/3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Golimumab Induction Therapy, Administered Subcutaneously, in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00487539
Sponsor ID: CR014176