Challenges and pitfalls in clinical trials of treatments for dry eye.

Clinical trials to evaluate the effectiveness of therapy for dry eye disease are challenging because of the nature of the disease, the multiple palliative methods used by patients to control their symptoms, and the potential limitations of the techniques available to evaluate therapeutic outcomes. This review identifies some of the pitfalls encountered in recent clinical trials in dry eye disease. The peculiarities of dry eye disease with respect to symptoms, signs, and patho- physiological changes are discussed. Potential problems that apply to all clinical trials, including patient selection, randomization in small populations, and assessment of the placebo effect, are presented with respect to dry eye clinical trials. Considerations regarding study design address inclusion/exclusion criteria and selection of outcome measures. Special attention is given to methods of symptom analysis, techniques of staining of the ocular surface, and grading systems for surface staining. Alternative methods to the standard clinical trial are mentioned to place them in perspective for overall evaluation of dry eye disease therapy. Finally, caveats are provided to encourage investigators to vigorously conduct future clinical trials in dry eye therapy.