Average versus highest intraocular pressure analyses in glaucoma clinical trials.

PURPOSE: To evaluate methods which account for both eyes as a single, independent variable in glaucoma clinical trials. METHODS: A review of clinical trial articles published between January 1995 and April 2011 evaluating currently used topical glaucoma medications. RESULTS: This analysis included 17 articles with 36 treatment arms of which 14 were prostaglandins, 13 ß-blockers, 6 topical carbonic anhydrase inhibitors and 3 α-agonists. Twenty-four articles used average intraocular pressure (IOP) analysis, 12 used the highest IOP analysis and none utilized the randomized eye method. At untreated baseline, there was a difference in the IOP between average IOP and highest baseline IOP analyses at 8 a.m. (p = 0.001) and for the diurnal curve (p = 0.02) as well as specifically for ß-blockers (p = 0.002) at 8 a.m. and ß-blockers for the diurnal curve (p = 0.01). CONCLUSIONS: This study suggests that the highest IOP analysis method generally provides slightly higher IOPs at baseline than the average IOP analysis method.

Review of the influence of pigment dispersion and exfoliation glaucoma diagnosis on intraocular pressure in clinical trials evaluating primary open-angle glaucoma and ocular hypertension.

PURPOSE: To evaluate published, randomized, prospective, parallel clinical trials utilizing currently approved glaucoma medications to determine what influence, if any, pigment dispersion (PD) or exfoliation glaucoma (XFG) patients had on the intraocular pressure. METHODS: A review of clinical trial articles evaluating currently used topical glaucoma medicines. Articles were published between January 1995 and April 2011. If the articles met the inclusion/exclusion criteria, they were analyzed for PD and XFG. RESULTS: Twenty-four articles were included, containing 49 treatment arms that included PD or XFG patients. The range of PD patients was 0% to 4.5%, with a mean of 1.5±0.9%, and for XFG patients 0% to 6.3%, with a mean of 2.2±2.1%. The treatment arms with PD showed a difference in the intraocular pressures (IOPs), for all studies analyzed together, for the baseline IOPs between clinical trials that did and did not include PD patients (8 AM IOPs: with PD 26.5±0.9 mm Hg and without PD 25.8±1.3 mm Hg, P=0.024; and diurnal curve mean IOPs: with PD 25.3±1.1 mm Hg and without PD 24.5±1.3 mm Hg, P=0.024). The XFG treatment arms showed that there was a difference in the IOPs for all studies analyzed together for diurnal baseline IOPs between clinical trials that did and did not include XFG patients (with XFG 25.2±1.2 mm Hg and without XFG 24.3±1.0 mm Hg, P=0.016). CONCLUSIONS: Trial designs for prospective, parallel, glaucoma clinical studies that are performed in the United States generally can include PD and XFG patients with only a small impact on the IOP and a low number of such subjects enrolled.