Predictive factors for the placebo effect in clinical trials for dry eye: a pooled analysis of three clinical trials.
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.
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.
Takahiro
T
Imanaka
Department of Pharmacoepidemiology, Graduate School of Medicine, Kyoto University, Yoshida Konoecho, Sakyoku, Kyoto, Japan.|The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX).
Izumi
I
Sato
Department of Pharmacoepidemiology, Graduate School of Medicine, Kyoto University, Yoshida Konoecho, Sakyoku, Kyoto, Japan.
Shiro
S
Tanaka
Department of Pharmacoepidemiology, Graduate School of Medicine, Kyoto University, Yoshida Konoecho, Sakyoku, Kyoto, Japan.
Koji
K
Kawakami
D003315:Cornea / Q000473:pathology*; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000008:administration & dosage*; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic; D013666:Tears / Q000378:metabolism
D009883:Ophthalmic Solutions
clinical Trial; cornea; drugs