Magnitude and Predictors of the Placebo Effects in the Dry Eye Assessment and Management Study

IF 3.2 Q1 OPHTHALMOLOGY
Katherine Han BS , Aaron T. Zhao BS , Yinxi Yu MS , Penny Asbell MD, MBA , Gui-Shuang Ying PhD , The DREAM Research Group
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引用次数: 0

Abstract

Purpose

To determine the magnitude and predictors of placebo effects on dry eye symptoms and signs in the Dry Eye Assessment and Management (DREAM) study.

Design

Secondary analysis of data from the DREAM study, a large-scale multicenter randomized clinical trial of patients with moderate to severe dry eye disease (DED).

Participants

One hundred sixty-four participants who were randomized to the placebo group (daily oral 1000 mg refined olive oil) and completed a 12-month follow-up in 27 United States centers.

Methods

At baseline, 3, 6, and 12 months, DED symptoms were evaluated using the Ocular Surface Disease Index (OSDI), and signs were assessed using conjunctival staining, corneal staining, tear break-up time (TBUT), Schirmer test, and meibomian gland dysfunction (MGD). Placebo effects were calculated as changes from baseline in DED symptoms and signs over 12 months. Univariable and multivariable models determined predictors for placebo effects.

Main Outcome Measures

Changes from baseline in DED symptoms and signs over 12 months after administration of the placebo.

Results

Among 164 participants (mean age 58 years, 82% female, 74% White) randomized to the placebo group, there were significant placebo effects that were evident by 3 months and remained until 12 months with improvement in OSDI total score (mean decline 10.4 points, P < 0.001), conjunctival staining score (mean decrease 0.5 points, P < 0.001), corneal staining score (mean decrease 0.9 points, P < 0.001), TBUT (mean increase 0.7 seconds, P < 0.001), and MGD score (mean decrease 0.3 points, P = 0.01). In multivariable analysis, a higher baseline OSDI total score (P < 0.001) and absence of rheumatoid arthritis (P = 0.01) predicted more improvement in OSDI total score (R2 = 0.25). More severe DED in OSDI (P = 0.005), conjunctival staining (P = 0.04), and MGD (P < 0.001) at baseline predicted more improvement in MGD score (R2 = 0.25).

Conclusions

The DREAM study revealed significant placebo effects on DED symptoms and signs, with more severe DED predicting larger placebo effects. Future DED trials should consider placebo effects in the trial design, statistical analysis, and result interpretation.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
干眼评估和管理研究中安慰剂效应的大小和预测因素
目的在干眼评估和管理(DREAM)研究中确定安慰剂对干眼症状和体征的影响程度和预测因素。设计对DREAM研究数据进行二次分析,DREAM研究是一项针对中重度干眼病(DED)患者的大规模多中心随机临床试验。参与者:164名参与者被随机分配到安慰剂组(每天口服1000毫克精制橄榄油),并在美国27个中心完成了为期12个月的随访。方法在基线、3,6和12个月时,使用眼表疾病指数(OSDI)评估DED症状,并使用结膜染色、角膜染色、泪液破裂时间(TBUT)、Schirmer试验和睑板腺功能障碍(MGD)评估体征。安慰剂效应是根据12个月内DED症状和体征的基线变化来计算的。单变量和多变量模型确定了安慰剂效应的预测因子。主要结局测量:服用安慰剂后12个月内DED症状和体征与基线相比的变化。结果在随机分配到安慰剂组的164名参与者(平均年龄58岁,82%女性,74%白人)中,安慰剂效应在3个月时明显,并持续到12个月,OSDI总分改善(平均下降10.4分,P <;0.001),结膜染色评分(平均下降0.5分,P <;0.001),角膜染色评分(平均下降0.9分,P <;0.001), TBUT(平均增加0.7秒,P <;MGD评分(平均下降0.3分,P = 0.01)。在多变量分析中,较高的基线OSDI总分(P <;0.001)和无类风湿关节炎(P = 0.01)预测OSDI总分的改善(R2 = 0.25)。OSDI (P = 0.005)、结膜染色(P = 0.04)和MGD (P <;0.001),预测MGD评分的改善更多(R2 = 0.25)。DREAM研究揭示了安慰剂对DED症状和体征的显著影响,更严重的DED预示着更大的安慰剂效应。未来的DED试验应在试验设计、统计分析和结果解释中考虑安慰剂效应。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Ophthalmology science
Ophthalmology science Ophthalmology
CiteScore
3.40
自引率
0.00%
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审稿时长
89 days
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