Expert Prior Elicitation and Bayesian Analysis of the Mycotic Ulcer Treatment Trial I
To perform a Bayesian analysis of the Mycotic Ulcer Treatment Trial I (MUTT I) using expert opinion as a prior belief.
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.
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.
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.).
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ABSTRACT: Fungal keratitis is a challenging problem worldwide, and many obstacles remain to the effective prevention, diagnosis, and therapy of this vision-threatening condition. Recent research has highlighted progress in each of these facets of the clinical approach to keratomycosis. Increased awareness of contact lens-associated fungal keratitis has prompted regulators to pay greater attention to testing of contact lens solutions under real-world conditions. Related research has also delved into the mechanisms of fungal biofilm formation and related therapeutic targets. Advances in polymerase chain reaction methodologies promise to increase the rapidity and accuracy of diagnosis, thereby decreasing the delay in instituting appropriate therapy. Antifungal pharmacologic agents remain the first line of therapy, with the newer azole antifungal voriconazole being utilized in innovative ways, such as via intrastromal injection. Large prospective studies such as the Mycotic Ulcer Treatment Trial have helped delineate optimal treatment algorithms, and variations in surgical techniques and postoperative regimens continue to be refined. Natamycin may still be more effective than other recently utilized antifungals for the treatment of Fusarium infections, but treatment failure is still a concern. Post-keratoplasty immunosuppression may benefit from the use of topical calcineurin inhibitors such as cyclosporine and tacrolimus, given their intrinsic antifungal properties. It can be argued that the prevention, diagnosis, and treatment of fungal keratitis lag behind the state of the art for bacterial keratitis, but dramatic improvements are undoubtedly on the horizon.
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