A Bayesian Analysis of a Randomized Clinical Trial Comparing Antimetabolite Therapies for Non-Infectious Uveitis
Open accessAbstract
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.
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Statistics
Claims the paper makes
0 of 17 cited sources checked · 0 supported · 0 flagged
- Findingown data
Corticosteroid-sparing control was achieved by 15 of 32 (47%) patients on mycophenolate mofetil and 24 of 35 (69%) on methotrexate.
“15 of 32 patients (47%) taking mycophenolate mofetil achieved corticosteroid-sparing control of inflammation compared with 24 of 35 (69%) taking methotrexate”
Quote in the paperSubstantial claim - Findingown data
The group prior mean odds ratio for treatment success with mycophenolate mofetil versus methotrexate was 1.4, with a 95% credible interval of 0.03 to 45.0.
“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).”
- Also stated in: § Group prior belief · hedged
“The odds of treatment success for those taking mycophenolate mofetil was estimated to be 1.4-fold the odds of those taking methotrexate (mean odds ratio 1.4, 95% CrI 0.03–45.0).”
Quote in the paperNot a substantial claim - Also stated in: § Group prior belief · hedged
- Findingown data
The posterior distribution peaked at an odds ratio of one.
“The posterior distribution has a peak at an odds ratio of 1.”
Quote in the paperNot a substantial claim - Findingown data
The randomized trial mean odds ratio for treatment success with mycophenolate mofetil versus methotrexate was 0.4, with a 95% confidence interval of 0.1 to 1.2.
“The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1–1.2)”
- Also stated in: § Trial results · plain
“15 of 32 patients (47%) taking mycophenolate mofetil achieved corticosteroid-sparing control of inflammation compared with 24 of 35 (69%) taking methotrexate (mean odds ratio mycophenolate mofetil to methotrexate 0.4, 95% confidence interval, CI, 0.1–1.2, P=0.09).”
Quote in the paperSubstantial claim - Also stated in: § Trial results · plain
- Findingown data
The Bayesian posterior mean odds ratio for treatment success with mycophenolate mofetil versus methotrexate was 0.7, with a 95% credible interval of 0.2 to 1.7.
“The mean odds ratio was 0.7 (95% CrI 0.2–1.7), meaning the odds of treatment success for a patient taking mycophenolate mofetil was 0.7 times the odds of a patient taking methotrexate.”
- Also stated in: § Results · plain
“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.”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
The posterior probability to the right of an odds ratio of one was 0.28.
“The area to the right of 1 is 0.28.”
Quote in the paperSubstantial claim - Findingown data
The posterior distribution indicated almost a 50% probability that methotrexate has at least 1.5-fold the odds of success compared with mycophenolate mofetil.
“However, the wide CrI leaves open the possibility of a treatment effect; based on the posterior distribution, there is nearly 50% chance that the odds of treatment success with methotrexate are ≥1.5-fold the odds of success with mycophenolate mofetil.”
Quote in the paperSubstantial claim - Study design and conductown data
Before the trial results were known, expert opinion on the relative effectiveness of methotrexate and mycophenolate mofetil was gathered through an online survey of the American Uveitis Society executive committee.
“Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey.”
- Also stated in: § Construction of prior probability distribution from expert opinion · plain
“The prior distribution was created by surveying expert opinion on methotrexate and mycophenolate mofetil for the treatment of noninfectious intermediate, posterior, and pan-uveitis before the release of the trial results.”
Quote in the paperSubstantial claim - Also stated in: § Construction of prior probability distribution from expert opinion · plain
- Interpretationown data
The broad credible interval does not rule out a meaningful treatment effect.
“However, the wide credible interval leaves open the possibility of a substantial treatment effect.”
Quote in the paperSubstantial claim - Premisecitation
A retrospective cohort study from 2008 reported 6-month corticosteroid-sparing success in 79% of mycophenolate mofetil patients and 42% of methotrexate patients.
“A retrospective cohort study published in 2008 comparing antimetabolite efficacy in intermediate, posterior, and pan-uveitis patients suggested corticosteroid-sparing success was achieved by 6 months in 79% of patients on mycophenolate mofetil and 42% on methotrexate.11”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] source
Not checked in the free run.
- Premisecitation
Non-comparative retrospective case series reported success rates of 37-76% for methotrexate and 54-96% for mycophenolate mofetil.
“Overall, non-comparative retrospective case series have reported success rates ranging from 37–76% for methotrexate11–13,23 and 54–96% for mycophenolate mofetil.11,14,15,24,25”
Quote in the paperSubstantial claim0 of 8 sources checked- cites [11] source
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- cites [12] source
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- cites [13] Foeldvari I, 2005, J Rheumatol
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- cites [23] source
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- cites [14] source
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- cites [15] source
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- cites [24] source
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- cites [25] source
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- Interpretationreasoning
The findings imply that clinical equipoise exists to justify a larger, more definitive randomized trial.
“This suggests clinical equipoise necessary to allow a larger, more definitive RCT.”
- Also stated in: § DISCUSSION · hedged
“However, combining the two in a Bayesian analysis suggests there is clinical equipoise necessary to allow a larger, more definitive RCT.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · hedged
- Interpretationown data
The Bayesian combination of the expert prior and the trial result showed no preference between the two drugs.
“A Bayesian analysis combining expert belief with the trial’s result did not indicate preference for one drug.”
Quote in the paperSubstantial claim - Premisecitation
Multiple retrospective studies have reported that methotrexate and mycophenolate mofetil control ocular inflammation.
“Several retrospective studies have shown these treatments to be effective in controlling ocular inflammation11–15”
Quote in the paperSubstantial claim0 of 5 sources checked - Interpretationown data
The Bayesian combination of survey belief and trial results implies clinical equipoise sufficient to justify a larger, more definitive randomized trial.
“However, combining the two in a Bayesian analysis suggests there is clinical equipoise necessary to allow a larger, more definitive RCT.”
Quote in the paperSubstantial claim - Interpretationown data
Because the posterior mean odds ratio was close to one, the analysis did not provide enough evidence to favor either medication given the prior belief.
“The posterior’s mean odds ratio was near one, suggesting there is insufficient evidence to prefer one medication over the other, given the available prior belief.”
Quote in the paperSubstantial claim - Interpretationreasoning
The prior's wide tails reflect the experts' uncertainty about which drug is better, not the small number of experts surveyed.
“Of note, the wide tails of the prior distribution are not the result of surveying a small number of experts but rather a reflection of the experts’ uncertainty in which drug is better.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Because the survey included only a small group of content experts, its results may not generalize to all ophthalmologists.
“The survey was limited to a small group of content experts, which may not make it generalizable to all ophthalmologists.”
Quote in the paperNot a substantial claim - Premisecitation
Small trials with inadequate power can produce non-significant P-values despite clinically meaningful effects.
“It is well known that insufficient power accompanying small trials may lead to insignificant P-values even when clinically meaningful effects are observed.2,4”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [2] source
Not checked in the free run.
- cites [4] Brophy JM, 1995, GUSTO revisited by Reverend Bayes. JAMA
Not checked in the free run.
- Interpretationreasoning
Using only one prior distribution was a limitation, since another expert group or a non-informative prior might have produced a different posterior.
“Another limitation was performing the analysis with only a single prior distribution; using a different group of experts or a non-informative prior distribution may have given a different posterior distribution.”
Quote in the paperNot a substantial claim
- Classified as probably not a substantial claim. 16
- May combine two claims. 9
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataEvery one of the twelve invited uveitis specialists completed the survey.
“All 12 invited uveitis specialists responded to the survey.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
FindingreasoningThe group prior placed a 0.70 probability that mycophenolate mofetil was superior to methotrexate.
“The area to the right of 1 is 0.70, implying the community of experts felt there was a 70% chance mycophenolate mofetil was better than methotrexate.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataTen of the twelve specialists gave estimates of the relative difference in treatment success.
“10 of 12 (83%) provided estimates for the relative difference in treatment success for the drugs.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataFour experts predicted no difference between the drugs.
“Four (40%) estimated the trial would see no difference between the two drugs.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataSixty-seven of the eighty enrolled patients were included in the primary analysis.
“Of the 80 patients enrolled, 67 contributed to the primary analysis.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataEleven of the twelve invited uveitis specialists submitted estimates.
“11 of 12 invited uveitis specialists provided estimates.”
Quote in the paperNot a substantial claimMay combine two claims.
FindingreasoningThe posterior gave a 72% probability that methotrexate was better than mycophenolate mofetil, a 46% probability of at least 1.5-fold odds favoring methotrexate, and a 30% probability of at least 2-fold odds favoring methotrexate.
“Therefore, the posterior probability suggests there is a 72% chance that methotrexate is superior to mycophenolate mofetil, a 46% chance that methotrexate has at least 1.5-fold odds of success compared with mycophenolate mofetil, and a 30% chance of at least a 2-fold odds of success compared with mycophenolate mofetil.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataEight of the eleven experts considered mycophenolate mofetil the more effective drug.
“Eight of 11 experts (73%) believed mycophenolate mofetil is more effective.”
- Also stated in: § Survey results · plain
“Overall, 8 of 11 experts (73%) thought mycophenolate mofetil is better for controlling ocular inflammation.”
Quote in the paperNot a substantial claim- Also stated in: § Survey results · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataHalf of the ten experts thought methotrexate would be at least 25% less effective than mycophenolate mofetil.
“Five of the 10 experts (50%) believed methotrexate would be ≥25% less effective than mycophenolate mofetil.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataA single expert considered methotrexate the more effective drug.
“Only one expert (10%) thought that methotrexate would be more effective.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe frequentist analysis estimated that methotrexate had nearly 2.5 times the odds of treatment success compared with mycophenolate mofetil, but this was not statistically significant (P=0.09).
“The frequentist analysis found the odds of treatment success for patients taking methotrexate were nearly two and half times the odds for those taking mycophenolate mofetil, although this was not statistically significant (P=0.09).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataMost surveyed specialists preferred mycophenolate mofetil, but half of those who did gave credible intervals wide enough to include methotrexate being more effective.
“Although most uveitis specialists in this survey favored mycophenolate mofetil, half of those favoring mycophenolate mofetil provided wide enough CrIs that allowed for the possibility of methotrexate to be more effective.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAn earlier survey reported that uveitis specialists chose mycophenolate mofetil over other immunosuppressants for initial corticosteroid-sparing therapy in intermediate, posterior, and pan-uveitis.
“This is in line with results from a previous survey where uveitis specialists preferred mycophenolate mofetil over other immunosuppressive agents as an initial corticosteroid-sparing treatment for intermediate, posterior, and pan-uveitis.22”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductown dataEvery expert stated that they did not know the trial results beforehand.
“All confirmed they had no prior knowledge of the trial results.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataThe ophthalmologists and visual acuity examiners were blinded.
“Ophthalmologists and visual acuity examiners were masked.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe study was powered at 80% to detect a 30% difference in treatment success.
“to have 80% power to detect a 30% difference in treatment success.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductown dataEighty patients were assigned in a 1:1 ratio within each clinic using permuted blocks of four and six.
“A total of 80 patients were block-randomized in a 1:1 ratio within clinic (permuted blocks of size 4 and 6)”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe expert survey and the frequentist trial analysis each provided weak evidence for equipoise.
“Neither the expert survey nor the frequentist analysis of the RCT offered particularly compelling evidence for equipoise.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningThe prior elicitation may have been limited because it used credible intervals, which may be less intuitive to experts, and offered only fixed 25% increment choices.
“A possible limitation of this analysis was in the questioning used to elicit the prior. Elicitation was based on CrIs, a statistical concept possibly less intuitive to the experts, and the survey had a fixed set of estimate options (in 25% increments).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningBecause uveitis is heterogeneous, analyzing all uveitis types together limits both the survey and the trial.
“Furthermore, uveitis is a heterogeneous group of conditions and a limitation of the survey and the trial is that all types of uveitis were analyzed together.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
InterpretationreasoningA different elicitation method could have yielded another subjective prior distribution.
“An alternative approach may have produced a different subjective prior distribution.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningThese retrospective studies cannot establish which drug is more effective because they used different definitions of inflammation control and had biases.
“It is difficult to know which drug is more efficacious from these studies because of varying definitions of controlled inflammation and inherent study biases such as treatment-by-indication bias, differences in dosing and differing follow-up times.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningThe prior distribution favored mycophenolate mofetil, with wide tails indicating uncertainty about that view.
“The prior distribution, which is a summary of all specialists’ opinions, leans toward mycophenolate mofetil being more effective, and the wide tails of the distribution reflect the lack of certainty in this opinion.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
There is a lack of comparative prospective studies of methotrexate and mycophenolate mofetil for chronic uveitis.
“but there is a lack of comparative, prospective studies.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
One section says 10 of 12 provided estimates, another says 11 of 12 did
MinorThe survey results section reports that 10 of 12 specialists provided estimates for the relative difference in treatment success, while the abstract reports 11 of 12 invited specialists provided estimates. This is an internal mismatch in the same paper.
“10 of 12 (83%) provided estimates for the relative difference in treatment success for the drugs.”
“11 of 12 invited uveitis specialists provided estimates.”
Conflicting counts of experts who provided efficacy estimates
MinorThe abstract says 11 specialists provided estimates, but the results say only 10 provided estimates of the relative difference in treatment success.
“11 of 12 invited uveitis specialists provided estimates.”
“10 of 12 (83%) provided estimates for the relative difference in treatment success for the drugs.”
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- Authors
- Browne, E. N., Rathinam, S. R., Kanakath, A., Thundikandy, R., Babu, M., Lietman, T. M., & Acharya, N. R.
- Affiliations
- University of California, San Francisco (US)
- Aravind Eye Hospital (IN)
- Aravind Eye Care System, Coimbatore, India
- Corresponding author
- Browne, Erica N.
- Venue
- Ophthalmic Epidemiology
- Publisher
- Informa UK Limited
- Published
- 2016-12-16
- Volume
- 24
- Issue
- 1
- Pages
- 63-70
- ISSN
- 0928-6586 (ISSN-L)
- 1744-5086
- PMC
- PMC5738326
- OpenAlex
- W2563955177
- Cited by
- 11
- References
- 25
- Citations by year
- 2022: 3 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ophthalmic Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Eye Institute (NEI U10 EY021125-01)
- That Man May See (UCSF)
- The South Asia Research Fund (UCSF)
- Topics
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Keywords
- non-infectious uveitis, antimetabolite therapy, methotrexate, mycophenolate mofetil, corticosteroid-sparing agents, Bayesian analysis, intermediate uveitis, posterior uveitis, clinical equipoise, treatment efficacy
- MeSH terms
- Adolescent, Adult, Anti-Inflammatory Agents, Antimetabolites, Bayes Theorem, Female, Humans, Immunosuppressive Agents, Male, Methotrexate, Mycophenolic Acid, Uveitis, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read under definition version 3 (extract-v3) on 2026-09-28.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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