Techniques to Reduce the Placebo Effect in Glaucoma Clinical Trials

Abstract

Aim: To evaluate techniques used to reduce the placebo effect in prior well-controlled, single or double-masked placebo-controlled glaucoma trials. Methods: This study was a retrospective, non-patient-based, observational review of phase I-III trials with a placebo arm for glaucoma medicines available after 1977. Results: This study included 20 articles with 20 placebo control arms consisting of 458 patients evaluating 10 different glaucoma medications with 58 treatment arms. There was no statistical difference across the evaluated types of study designs to limit the placebo effect either for the morning trough or diurnal curve. The average reduction of the intraocular pressure in the placebo groups was 1.6 ± 1.5 mm Hg for the morning trough and 1.3 ± 1.3 mm Hg for the diurnal curve across all studies. Conclusion: The results of this study suggest that current design techniques described in the literature to limit the placebo effect appear ineffective compared to no additional techniques.

Factors Influencing the Placebo Effect in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: An Analysis of Two Randomized Clinical Trials

“…A previous study on glaucoma patients reported that the regression towards the mean might influence the placebo effect [ 22 ]. The results of the present study are not consistent with the findings of a previous study, which showed that setting a separate day entry criterion of IOP did not effectively restrain the placebo effect [ 20 ]. However, because the previous study only used averages rather than pulling the data from each patient individually, the obtained results would be expected to differ from those of the current study.…”

“…However, because the previous study only used averages rather than pulling the data from each patient individually, the obtained results would be expected to differ from those of the current study. In particular, the use of only summaries of published data, rather individual patient data [ 20 ], meant the association between the glaucoma patients’ individual characteristics and placebo effects could not be fully ascertained. In this regard, the strength of the present study was the inclusion of individual-level patient data from the clinical trials.…”