title: A model-based dose-response meta-analysis of ocular hypotensive agents as a drug development tool to evaluate new therapies in glaucoma.
abstract: OBJECTIVE
  To characterize dose and response for intraocular pressure (IOP) reduction and incidence of hyperemia using a model-based meta-analysis of IOP-lowering monotherapy studies to evaluate new ocular antihypertensive therapies for glaucoma.
  
  
  METHODS
  Published randomized controlled trials, regulatory documents, and sponsor reports of IOP-lowering monotherapies were used to develop dose-response models to characterize efficacy (IOP change from baseline) and safety (incidence of hyperemia) profiles.
  
  
  RESULTS
  The meta-analysis for efficacy included 31 trials with 6,516 patients receiving bimatoprost, latanoprost, travoprost, timolol, or placebo. Estimated IOP reduction with placebo was -2.01 mmHg. Maximal IOP reduction was similar among the prostaglandin analogs (estimate, -6.27 mmHg; baseline, 25 mmHg). Estimated median effective IOP-lowering dose (ED50) was 0.002%, 0.00098%, and 0.00063% daily with bimatoprost, latanoprost, and travoprost, respectively. The hyperemia (safety) analysis included 25 trials with 6,244 patients. Typical maximal estimated difference between drug and placebo was 43%, and estimated ED50 of 0.011%, 0.014%, and 0.0015% daily for bimatoprost, latanoprost, and travoprost, respectively. Latanoprost treatment was predicted to incur the lowest rate of hyperemia of the prostaglandins, for equivalent IOP reduction.
  
  
  CONCLUSIONS
  Model-based meta-analyses for IOP reduction and incidence of hyperemia among prostaglandin analogs are well described by maximal efficacy models and can provide a useful methodology for evaluating glaucoma therapies.
authors.affiliation: 1 Pfizer Inc. , San Diego, California.
authors.forename: Susan
authors.initials: S
authors.lastname: Raber
authors.forename: Jaap W
authors.initials: JW
authors.lastname: Mandema
authors.forename: Hanbin
authors.initials: H
authors.lastname: Li
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Nickens
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D015233:Models, Statistical; D009798:Ocular Hypertension / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000959:Antihypertensive Agents