A meta-analysis of the placebo rates of remission and response in clinical trials of active ulcerative colitis.
OBJECTIVE
Knowledge of the placebo outcomes and understanding specific study features that influence these outcomes is important for designing future clinical trials evaluating therapy of ulcerative colitis (UC). The aims of this study were to estimate the placebo rates of remission and response in placebo-controlled, randomized clinical trials for active UC and to identify factors influencing these rates.


METHODS
We performed a systematic review and meta-analysis of placebo-controlled, randomized clinical trials evaluating therapies for active UC identified from MEDLINE from 1966 through 2005.


RESULTS
Forty studies met the inclusion criteria. The pooled estimates of the placebo rates of remission and response were 13% (95% confidence interval, 9%-18%; range, 0%-40%; median, 12%) and 28% (95% confidence interval, 23%-33%; range, 0%-67%; median, 30%), respectively, both with significant heterogeneity. Studies that used more stringent definitions of outcomes had lower placebo rates of remission and response. Study duration, number of study visits, disease duration, baseline composite and rectal bleeding scores of the disease activity index, and inclusion of endoscopic mucosal healing as the remission definition all were associated with the placebo remission rate.


CONCLUSIONS
Rates of remission in the placebo arm of UC clinical trials ranges from 0% to 40%. The placebo remission rates are influenced by the trial length, number of study visits, use of stricter remission definitions, and design features that enroll patients with more active disease. These factors should be considered when designing future placebo-controlled clinical trials in patients with active UC.
Su
Chinyu
C
Division of Gastroenterology, Department of Medicine, Hospital of the University of Pennsylvania and University of Pennsylvania Presbyterian Medical Center, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. chinyu.su@uphs.upenn.edu
Lewis
James D
JD
Goldberg
Brittany
B
Brensinger
Colleen
C
Lichtenstein
Gary R
GR
D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003627:Data Interpretation, Statistical; D006801:Humans; D016017:Odds Ratio; D018579:Patient Selection; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D012074:Remission Induction; D012107:Research Design; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome