Imanaka Takahiro, Sato Izumi, Tanaka Shiro, Kawakami Koji
Department of Pharmacoepidemiology, Graduate School of Medicine, Kyoto University, Yoshida Konoecho, Sakyoku, Kyoto, Japan.
Research and Development Division, Santen Pharmaceutical Co., Ltd., Ofuka-cho, Kita-ku, Osaka, Japan.
Br J Ophthalmol. 2017 Nov;101(11):1471-1474. doi: 10.1136/bjophthalmol-2016-309887. Epub 2017 Mar 18.
Placebo effect is one of the methodological difficulties in dry eye clinical trials. If we could elucidate the tendencies of the placebo response and find predictors, we could reduce the placebo response in clinical trials for dry eye. In this study, we investigated the predictive factors for the placebo effect in dry eye clinical trials.
A total of 205 patients with dry eye assigned to the placebo arms of three placebo-controlled randomised clinical trials were analysed by simple and multivariable regression analysis. The corneal fluorescein (FL) staining score and dry eye symptoms were studied at week 4. The variables of interest included gender, age, complications of Sjögren's syndrome, Schirmer's test I value, tear break-up time and conjunctival hyperaemia score. We also conducted a stratified analysis according to the patients' age.
Among all the studied endpoints, the baseline scores were significantly related to the corresponding placebo response. In addition, for the FL score and the dryness score, age was a significant predictor of the placebo response (p=0.04 and p<0.0001, respectively). Stratified analysis by age showed that patients more than 40 years of age are more likely to have a stronger placebo response in the FL and dryness scores.
The baseline scores and age were predictive factors of the placebo response in frequently used endpoints, such as FL score or dryness symptoms. These patient characteristics can be controlled by study design, and our findings enable the design of more efficient placebo-controlled studies with good statistical power.
安慰剂效应是干眼临床试验中的方法学难题之一。如果我们能够阐明安慰剂反应的趋势并找到预测因素，就可以在干眼临床试验中减少安慰剂反应。在本研究中，我们调查了干眼临床试验中安慰剂效应的预测因素。
对三项安慰剂对照随机临床试验安慰剂组中的205例干眼患者进行单因素和多因素回归分析。在第4周研究角膜荧光素（FL）染色评分和干眼症状。感兴趣的变量包括性别、年龄、干燥综合征并发症、Schirmer I试验值、泪膜破裂时间和结膜充血评分。我们还根据患者年龄进行了分层分析。
在所有研究的终点中，基线评分与相应的安慰剂反应显著相关。此外，对于FL评分和干眼评分，年龄是安慰剂反应的显著预测因素（分别为p = 0.04和p < 0.0001）。按年龄分层分析显示，40岁以上患者在FL评分和干眼评分方面更有可能有更强的安慰剂反应。
基线评分和年龄是常用终点（如FL评分或干眼症状）安慰剂反应的预测因素。这些患者特征可以通过研究设计加以控制，我们的研究结果有助于设计出具有良好统计学效力的更高效的安慰剂对照研究。
