A Bayesian Analysis of a Randomized Clinical Trial Comparing Antimetabolite Therapies for Non-Infectious Uveitis

ABSTRACT

Purpose: To conduct a Bayesian analysis of a randomized clinical trial (RCT) for non-infectious uveitis using expert opinion as a subjective prior belief.

Methods: A RCT was conducted to determine which antimetabolite, methotrexate or mycophenolate mofetil, is more effective as an initial corticosteroid-sparing agent for the treatment of intermediate, posterior, and pan-uveitis. Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey. Members of the American Uveitis Society executive committee were invited to provide an estimate for the relative decrease in efficacy with a 95% credible interval (CrI). A prior probability distribution was created from experts’ estimates. A Bayesian analysis was performed using the constructed expert prior probability distribution and the trial’s primary outcome.

Results: A total of 11 of the 12 invited uveitis specialists provided estimates. Eight of 11 experts (73%) believed mycophenolate mofetil is more effective. The group prior belief was that the odds of treatment success for patients taking mycophenolate mofetil were 1.4-fold the odds of those taking methotrexate (95% CrI 0.03–45.0). The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1–1.2) and 0.7 (95% CrI 0.2–1.7) from the Bayesian analysis.

Conclusions: A Bayesian analysis combining expert belief with the trial’s result did not indicate preference for one drug. However, the wide credible interval leaves open the possibility of a substantial treatment effect. This suggests clinical equipoise necessary to allow a larger, more definitive RCT.

KEYWORDS:

• Antimetabolite
• Bayesian
• clinical trial
• non-infectious uveitis
• statistics

Acknowledgments

The authors thank the members of the American Uveitis Society executive committee for their participation.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the writing and content of this article.

Funding

Funding for this trial was provided by That Man May See and The South Asia Research Fund. Dr Acharya is currently supported by an NEI U10 EY021125-01 grant. The UCSF Department of Ophthalmology is supported by the National Eye Institute and Research to Prevent Blindness Foundation. The sponsor or funding organization had no role in the design or conduct of this research.

Additional information

Funding

Funding for this trial was provided by That Man May See and The South Asia Research Fund. Dr Acharya is currently supported by an NEI U10 EY021125-01 grant. The UCSF Department of Ophthalmology is supported by the National Eye Institute and Research to Prevent Blindness Foundation. The sponsor or funding organization had no role in the design or conduct of this research.