Background 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.
Methods 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.
Results 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.
Conclusion 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.
- clinical Trial
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Acknowledgements The data set used in this research was provided by Santen Pharmaceutical Co., Ltd. This research was supported by the Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX), established by Human Resource Development Program for Science and Technology, MEXT.
Contributors TI obtained the data, wrote the study protocol and the statistical analysis plan, cleaned and analysed the data, and drafted and revised the paper. IS, ST and KK analysed the data, and drafted and revised the paper. KK is guarantor.
Competing interests TI is an employee of Santen Pharmaceutical Co., Ltd. KK received research funds from Medical Platform Co., Novartis Pharmaceutical K.K. and Bayer; honorarium from Astellas, Novartis Pharmaceutical K.K. and Sanofi K.K. There are no patents, products in development or marketed products to declare relevant to those companies. No other disclosures were reported.
Patient consent This was the secondary analysis using anonymised data of clinical trials. The original clinical trials were conducted on Good Clinical Practice.
Ethics approval The Ethics Committee of the Kyoto University School of Medicine.
Provenance and peer review Not commissioned; externally peer reviewed.