Is proper methodology associated with the use of a clinically relevant outcome measure? The case of randomized clinical trials on medical treatment of open-angle glaucoma.

Objective: The aim of this study was to assess critically the published literature concerning medical treatment of primary open-angle glaucoma (POAG), and to see whether trial methodologic quality was related to a clinically relevant outcome measure.

Methods: We identified and reviewed the methodologic quality of 102 published randomized clinical trials (RCTs) on treatment of POAG using an explicit protocol and explored the association between selected aspects of design and conduct and the studies' clinical relevance.

Results: Our analysis revealed serious methodologic problems with the trials reviewed. Areas of major concern were: use of unsatisfactory or unspecified methods of randomization (89% of the trials reported no information), exclusion of some patients from the analysis (53% of the studies), failure to provide evidence of having estimated the number of patients needed to detect a prespecified treatment difference (96% failed to provide such an estimate), and incomplete description of patient characteristics (in 39% of the RCTs information on this item was insufficient). Within this generally unsatisfactory picture we found, however, that those studies adopting a double-masked design and those not excluding patients after randomization followed patients for longer periods of time and assessed treatment effectiveness using a clinically relevant outcome (that is, visual field changes) compared to other studies.

Conclusions: For clinicians to make use of the results of clinical trials, future studies must be adequately designed and conducted. In particular, proper method of randomization, masking of the observers, and inclusion of all randomized patients in the analysis must be used. Of perhaps even greater importance is the need for trials to measure clinically relevant outcomes.