title: Expert prior elicitation and Bayesian analysis of the Mycotic Ulcer Treatment Trial I.
abstract: OBJECTIVE
  To perform a Bayesian analysis of the Mycotic Ulcer Treatment Trial I (MUTT I) using expert opinion as a prior belief.
  
  
  METHODS
  MUTT I was a randomized clinical trial comparing topical natamycin or voriconazole for treating filamentous fungal keratitis. A questionnaire elicited expert opinion on the best treatment of fungal keratitis before MUTT I results were available. A Bayesian analysis was performed using the questionnaire data as a prior belief and the MUTT I primary outcome (3-month visual acuity) by frequentist analysis as a likelihood.
  
  
  RESULTS
  Corneal experts had a 41.1% prior belief that natamycin improved 3-month visual acuity compared with voriconazole. The Bayesian analysis found a 98.4% belief for natamycin treatment compared with voriconazole treatment for filamentous cases as a group (mean improvement 1.1 Snellen lines, 95% credible interval 0.1-2.1). The Bayesian analysis estimated a smaller treatment effect than the MUTT I frequentist analysis result of 1.8-line improvement with natamycin versus voriconazole (95% confidence interval 0.5-3.0, P = 0.006). For Fusarium cases, the posterior demonstrated a 99.7% belief for natamycin treatment, whereas non-Fusarium cases had a 57.3% belief.
  
  
  CONCLUSIONS
  The Bayesian analysis suggests that natamycin is superior to voriconazole when filamentous cases are analyzed as a group. Subgroup analysis of Fusarium cases found improvement with natamycin compared with voriconazole, whereas there was almost no difference between treatments for non-Fusarium cases. These results were consistent with, though smaller in effect size than, the MUTT I primary outcome by frequentist analysis. The accordance between analyses further validates the trial results. (ClinicalTrials.gov number, NCT00996736.).
authors.affiliation: Francis I. Proctor Foundation, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Catherine Q
authors.initials: CQ
authors.lastname: Sun
authors.forename: N Venkatesh
authors.initials: NV
authors.lastname: Prajna
authors.forename: Tiruvengada
authors.initials: T
authors.lastname: Krishnan
authors.forename: Jeena
authors.initials: J
authors.lastname: Mascarenhas
authors.forename: Revathi
authors.initials: R
authors.lastname: Rajaraman
authors.forename: Muthiah
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Anita
authors.initials: A
authors.lastname: Raghavan
authors.forename: Kieran S
authors.initials: KS
authors.lastname: O'Brien
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Ray
authors.forename: Stephen D
authors.initials: SD
authors.lastname: McLeod
authors.forename: Travis C
authors.initials: TC
authors.lastname: Porco
authors.forename: Nisha R
authors.initials: NR
authors.lastname: Acharya
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lietman
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D001499:Bayes Theorem; D003320:Corneal Ulcer / Q000188:drug therapy*; D015821:Eye Infections, Fungal / Q000188:drug therapy*; D060585:Fusariosis / Q000188:drug therapy; D006801:Humans; D010866:Natamycin / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D010866:Natamycin; D065819:Voriconazole
keywords: Bayesian; clinical trial; corneal ulceration; fungal keratitis; statistics