title: Factors Influencing the Placebo Effect in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: An Analysis of Two Randomized Clinical Trials.
abstract: OBJECTIVE
  To explore factors related to the placebo effect in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).
  
  
  METHODS
  This was a retrospective cohort study of patients with POAG and patients with OH who were treated with placebo. The patients' data were extracted from two randomized, double-masked, parallel, multicenter clinical trials (trial 1 and trial 2) in Japan. We explored the baseline factors that were associated with the intraocular pressure (IOP)-lowering effect of placebo ophthalmic solution after 4 weeks of instillation treatment at two time points by using multivariable models. The time points were Hour 0 (between 08:30 and 10:30 before instillation) and Hour 2 (within 1.5 to 2.5 h after instillation and by 12:30) at the baseline date and after 4 weeks. The changes in IOP from baseline to 4 weeks at the two time points were evaluated for the IOP-lowering effect induced by placebo instillation.
  
  
  RESULTS
  Of the 330 patients included in the two trials, 89 patients were eligible for the analysis. The results of the multivariable analysis for Hour 0 indicated a high IOP at the baseline date (coefficient: 0.24, 95% confidence interval (CI): 0.02 to 0.46, P = 0.03), and the magnitude of the IOP fluctuation at the baseline date (coefficient: 0.57, 95% CI: 0.24 to 0.90, P = 0.001) was associated with the IOP-lowering effect after 4 weeks. With respect to Hour 2, the trial type was associated with the IOP-lowering effect (coefficient: -1.15, 95% CI: -2.14 to -0.16, P = 0.02).
  
  
  CONCLUSIONS
  A large fluctuation in IOP during the day is associated with the IOP-lowering effect induced by placebo in patients with POAG or OH. This finding would be helpful to researchers when designing studies related to glaucoma in the early stages of clinical development of drugs.
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, Japan.|Senju Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, Japan.|Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX), Kyoto, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Sato
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D005260:Female; D005902:Glaucoma, Open-Angle / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009798:Ocular Hypertension / Q000453:epidemiology* / Q000503:physiopathology; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012307:Risk Factors