Expert prior elicitation and Bayesian analysis of the Mycotic Ulcer Treatment Trial I

Invest Ophthalmol Vis Sci. 2013 Jun 14;54(6):4167-73. doi: 10.1167/iovs.13-11716.

Abstract

Purpose: 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.).

Keywords: Bayesian; clinical trial; corneal ulceration; fungal keratitis; statistics.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / therapeutic use*
  • Bayes Theorem
  • Corneal Ulcer / drug therapy*
  • Expert Testimony*
  • Eye Infections, Fungal / drug therapy*
  • Fusariosis / drug therapy
  • Humans
  • Natamycin / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Surveys and Questionnaires
  • Triazoles / therapeutic use*
  • Voriconazole

Substances

  • Antifungal Agents
  • Pyrimidines
  • Triazoles
  • Natamycin
  • Voriconazole

Associated data

  • ClinicalTrials.gov/NCT00996736