RTA 408 Ophthalmic Suspension for the Prevention of Corneal Endothelial Cell Loss Following Cataract Surgery - GUARD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RTA 408 Ophthalmic Suspension for the Prevention of Corneal Endothelial Cell Loss Following Cataract Surgery - GUARD (NCT02128113), a randomized phase 2 study. The primary outcome is Change From Baseline in Central Corneal Endothelial Cell Counts.

2. Clinical Question

3. Trial Design

GUARD was a phase 2, randomized, double-masked, vehicle-controlled, parallel-group study sponsored by Biogen. It assessed the efficacy and safety of omaveloxolone ophthalmic suspension for the prevention of corneal endothelial cell loss following cataract surgery. The registry record lists enrollment of 307 and a completed study. The recorded start date is 2014-05-31, and the primary completion date is 2015-02-28.

The treatment groups were vehicle ophthalmic solution, omaveloxolone 0.5%, and omaveloxolone 1%. Each regimen used a single drop in the study eye twice daily, approximately 12 hours apart, for a maximum of 28 days. Dosing began 3 to 7 days before cataract surgery and continued on the day of surgery and for 3 weeks after surgery. The parallel-group design means that participants were assigned to one regimen rather than crossing between treatments. Randomization and double masking are stated in the record; details of the randomization procedure and how masking was maintained are not reported in the registry record.

The primary outcome was change from baseline in central corneal endothelial cell counts at 12 weeks. The primary population is described as intent-to-treat, including all randomized patients. The posted arm-level summaries list 98 participants for vehicle, 94 for omaveloxolone 0.5%, and 101 for omaveloxolone 1% for this outcome. These outcome denominators differ from the safety groups at risk, and reasons for the difference are not reported in the registry record.

The registry also lists secondary outcomes concerning anterior chamber cells and flare, clinical cure, pain one day after surgery, and endothelial cell counts. The protocol’s original sample-size assumptions, the detailed analysis plan, and the handling of missing observations are not reported in the registry record. The planning illustrations accompanying the posted statistics are calculations based on observed effects, not documentation of the trial’s original design.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population (all randomized patients)

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Intent-to-treat population (all randomized patients)

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Central Corneal Endothelial Cell Counts, measured over 12 weeks.

The primary endpoint is the change from baseline in central corneal endothelial cell counts at 12 weeks after cataract surgery, measured in cells/mm^2. A change score compares a participant’s follow-up count with the baseline count; a negative mean change indicates that the measured count was lower on average at follow-up than at baseline. The endpoint is continuous, so the registry summarizes each group with a mean and standard deviation.

Endothelial cell counts are used in this study because the stated research question concerns cell loss following cataract surgery. A comparison of mean changes can describe whether the average measured change differs between a treatment group and the vehicle group. It does not show how every participant changed, and a group mean alone cannot describe the full spread of individual outcomes. The standard deviation provides information about that spread.

The 12-week outcome is identified as the primary endpoint, while the registry also lists endothelial cell count change at 6 weeks among the secondary results. The later assessment addresses the primary time point specified in the record; the earlier assessment provides an additional view of the same type of measure. Why 12 weeks was selected, whether that timing was chosen for a particular biological or operational reason, and what magnitude of change would be considered clinically important are not reported in the registry record.

7. Results Posted in the Registry

• Omaveloxolone Opthalmic Suspension 0.5%: mean -184.80 versus -243.40 on control; difference 58.60 (95% CI -24.12 to 141.32), standardized effect d = 0.20; z-test p = 0.165.
• Omaveloxolone Opthalmic Suspension 1%: mean -260.30 versus -243.40 on control; difference -16.90 (95% CI -106.76 to 72.96), standardized effect d = -0.05; z-test p = 0.712.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Central Corneal Endothelial Cell Counts

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Omaveloxolone Opthalmic Suspension 0.5%: mean -193.90 versus -238.20 on control; difference 44.30 (95% CI -43.81 to 132.41), standardized effect d = 0.14; z-test p = 0.324.
  • Omaveloxolone Opthalmic Suspension 1%: mean -242.20 versus -238.20 on control; difference -4.00 (95% CI -94.44 to 86.44), standardized effect d = -0.01; z-test p = 0.931.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Omaveloxolone Opthalmic Suspension 0.5% and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Omaveloxolone Opthalmic Suspension 1% and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering anterior chamber cells, anterior chamber flare, clinical cure defined by absence of both, pain-free status one day after surgery, and endothelial cell count change. These measures address related but distinct aspects of recovery after cataract surgery. Endothelial cell count change is most directly connected to the primary question, while the inflammatory signs and pain outcome represent other clinical observations.

The detailed secondary results include a 6-week assessment of endothelial cell count change. Its unadjusted comparisons do not establish a precise separation between either omaveloxolone concentration and vehicle; their estimates are uncertain in relation to the variability in the groups. The posted results also include sponsor ANCOVA analyses for this time point. Numerical results for the listed secondary measures concerning cells, flare, clinical cure, and pain are not reported in the registry record. They cannot support a conclusion about whether those outcomes differed between groups.

The 6-week cell-count assessment offers a shorter-term counterpart to the 12-week primary endpoint, but it does not replace the primary result. Looking across multiple secondary outcomes can provide context, yet isolated findings should be interpreted cautiously. When many outcomes and comparisons are examined, the chance of at least one apparently notable result can increase. The registry does not report a multiplicity strategy for secondary testing, and the recalculated comparisons are unadjusted. Secondary results therefore carry less inferential weight than the prespecified primary endpoint, particularly when the analysis plan and adjustment approach are not reported.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Patients With Absence of Anterior Chamber Cells at 2 Weeks After Cataract Surgery
• Percentage of Patients With Absence of Anterior Chamber Flare at 2 Weeks After Cataract Surgery
• Percentage of Patients With Clinical Cure (Absence of Anterior Chamber Cells + Flare) at 2 Weeks After Cataract Surgery
• Percentage of Patients Who Were Pain Free 1 Day After Cataract Surgery
• Change From Baseline in Central Corneal Endothelial Cell Counts

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous measure, and the posted arm summaries report a mean change and standard deviation for each group. A mean describes the average change in the group. A standard deviation describes how dispersed individual changes are around that average; it is not the uncertainty of the mean itself. The primary endpoint is identified as change from baseline at 12 weeks, and the stated analysis population is all randomized patients.

What does the unadjusted comparison estimate?

The recalculated comparisons subtract the vehicle-group mean from the mean in each omaveloxolone group. This is a simple, unadjusted difference between group means. A positive estimate means the treatment-group mean change is numerically higher, or less negative, than the vehicle mean; a negative estimate means it is numerically lower. These contrasts use the posted summary statistics and do not account for covariates through an adjusted model.

The recalculated standard errors and intervals describe uncertainty in those estimated mean differences under the calculation assumptions. A confidence interval is a range of values compatible with the observed estimate under a specified statistical procedure. It is not a range containing a known proportion of individual participant outcomes, nor does it assign a probability to a particular treatment effect. The confidence level for the recalculated intervals is not reported in the registry record. When an interval includes zero, the observed summaries are compatible with no mean difference as well as with differences in either direction.

Why use a standard deviation and pooled variation?

The standard deviations indicate that participants’ changes varied considerably within each group. The recalculated comparisons use pooled variation to represent within-group spread when expressing the mean difference relative to outcome variability. This can aid interpretation of the scale of an effect, but it does not replace the original outcome units. In clinical interpretation, the mean difference in cells/mm^2 remains more directly connected to the measured endpoint than a standardized effect measure.

Unequal variability across groups can matter because a pooled estimate compresses the groups’ spreads into a common summary. If variation differs meaningfully between groups, the pooled value may not represent every group equally well. The registry does not report a variance assessment or a rationale for a particular variance model. The arm-specific standard deviations remain useful context alongside the recalculated comparison.

How does ANCOVA differ from the recalculation?

The sponsor reports analysis of covariance, or ANCOVA, results as net least-squares mean differences. ANCOVA is a regression-based approach that can estimate group differences while adjusting for variables specified in the model. In a baseline-adjusted analysis, the baseline measure may be included to account for baseline differences and improve precision. The exact covariates, model specification, and missing-data method used in this trial are not reported in the registry record, so the adjusted results cannot be reconstructed from the posted group means and standard deviations alone.

The sponsor’s ANCOVA estimates are therefore distinct from the simple recalculated differences. The recalculations are descriptive, unadjusted checks based on summary statistics; they are not a replacement for the trial’s own analysis. The record does not flag a discrepancy, but the sponsor’s reported analysis remains the primary source for the trial’s adjusted inference. Its reported p-values are not accompanied by confidence limits in the posted results.

Why is multiple testing relevant?

The record contains a primary outcome, multiple treatment comparisons, and several secondary outcomes. Testing many hypotheses creates more opportunities to see an apparently notable result by chance, even when no adjustment is made to each individual test. The registry does not report whether a multiplicity procedure was prespecified, whether testing was hierarchical, or whether secondary outcomes were considered exploratory. The recalculated p-values are unadjusted and should not be treated as a family-wise conclusion across all outcomes and comparisons.

Randomization supports comparisons between assigned groups, but it does not resolve every analytic issue. The record does not describe the amount or pattern of missing primary endpoint data, the imputation method if any, or sensitivity analyses. It also does not report protocol deviations or the number included in each sponsor ANCOVA. These details affect how fully the posted results can be evaluated.

11. Confidence Intervals and Precision

Precision concerns how tightly the data locate an estimated treatment difference. At 12 weeks, the recalculated interval for omaveloxolone 0.5% versus vehicle extends from -24.12 to 141.3 cells/mm^2. It includes zero, so the summaries are compatible with no difference, while also allowing a positive difference. The interval is wide enough to leave substantial uncertainty about the size and direction of the contrast.

For omaveloxolone 1% versus vehicle, the interval extends from -106.8 to 72.96 cells/mm^2. It also includes zero and spans both negative and positive values. This means the estimate does not precisely establish either a smaller or a larger mean change relative to vehicle. The standard deviations in the arms, which range from 237.0 to 340.6 cells/mm^2, provide context for why an estimated mean contrast can remain uncertain even when group averages are available.

An interval is more informative than a point estimate alone because it displays the range of values compatible with the observed data under the calculation method. It does not show that every value inside the interval is equally likely, and it does not address whether a difference would matter clinically. The registry does not report a clinically important difference threshold or the confidence level for the recalculated intervals. The sponsor’s ANCOVA estimates are posted without confidence limits, which further limits direct assessment of their precision.

These intervals are unadjusted recalculations from the posted summary statistics. They do not incorporate any multiplicity adjustment and may not match the precision of the sponsor’s covariate-adjusted analysis. The sponsor’s own analysis takes precedence for the trial’s reported inference.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed recalculated effect, not the trial’s original design assumptions. For these continuous-outcome comparisons, the figures are participants per arm, not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The trial’s own original sample-size justification is not reported in the registry record.

The 80% power column describes the planned number of participants per arm under those assumptions for a procedure with an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column describes the corresponding planning target for a 90% chance under the same assumptions. These are properties of hypothetical future study designs, not probabilities that this completed trial detected an effect.

The rows for 100%, 75%, and 50% of the observed effect illustrate how the planning target changes when the assumed effect to detect is varied. A smaller target effect requires more participants because it is harder to distinguish from random variation. This is especially consequential when the observed mean difference is small relative to within-group variability. The figures should not be read as a recommendation or as evidence about what the original investigators planned. They depend on the observed estimates, and estimates from a study can be imprecise.

This is not observed power. Observed power would not add a useful interpretation to the results after the data have been collected; the estimates, intervals, and design assumptions provide more direct information about what the data can support.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 58.600; pooled standard deviation σ = 294.468.
2. n = 2 × (1.96 + 0.842)² × 294.468² / 58.600² = 396.4, rounded up to 397 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 58.6                      # observed difference in means
sigma <- 294.468356183961                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2128113)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 397 (80% power), 531 (90% power)
 75% of observed effect: n per arm = 705 (80% power), 944 (90% power)
 50% of observed effect: n per arm = 1,586 (80% power), 2,123 (90% power)
power.t.test: 397.3 
Simulated power at n = 397 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports sponsor ANCOVA analyses for the primary outcome: a three-group analysis and separate vehicle comparisons with each omaveloxolone concentration. The reported net least-squares mean differences are 26.95 for the three-group analysis, 64.31 for vehicle versus 0.5%, and -11.08 for vehicle versus 1%. Their reported p-values are 0.453, 0.128, and 0.800, respectively. Confidence limits are not reported for these analyses.

The recalculated mean differences are 58.6 cells/mm^2 for 0.5% versus vehicle and -16.9 cells/mm^2 for 1% versus vehicle. They are unadjusted calculations from the posted group means and standard deviations, whereas ANCOVA estimates are model-adjusted. Differences between the estimates are therefore not, by themselves, evidence of a data inconsistency. The covariates and full model details needed to explain their exact relationship are not reported in the registry record.

The registry record does not flag a discrepancy. The recalculations can help readers understand the direction and scale of the raw group summaries, but the sponsor’s own analysis takes precedence as the trial’s reported analysis. The sponsor results do not provide confidence limits in the posted record, so their uncertainty cannot be assessed from those analyses as fully as it can for the recalculated contrasts.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome and lists several secondary outcomes, with comparisons involving two omaveloxolone concentrations and vehicle. This creates multiple potential statistical tests. When many hypotheses are assessed, an unadjusted p-value for an individual comparison does not by itself control the overall chance of a false-positive finding across the full set of tests. The record does not report whether the investigators used a multiplicity adjustment, a testing hierarchy, or a prespecified strategy for deciding which outcomes would be confirmatory.

The recalculated p-values are unadjusted pairwise comparisons. They should not be interpreted as adjusted evidence across both treatment contrasts or across the outcome set. The sponsor’s reported ANCOVA p-values are trial analyses, but the registry does not describe their role within a broader multiplicity plan. The absence of such information in the record does not establish that no plan existed; it means the plan is not reported in the registry record.

The primary population is described as intent-to-treat, meaning all randomized patients. The arm-level endpoint summaries list 98 for vehicle, 94 for 0.5%, and 101 for 1%. The registry does not explain why the endpoint denominators differ from the safety groups at risk, or whether every randomized participant contributed a primary endpoint measurement. Details on missing outcome data, reasons for missingness, imputation, and sensitivity analyses are not reported in the registry record.

Information about the ANCOVA covariates, model diagnostics, and exact analysis population is also not reported. Without those details, readers cannot fully reconstruct the adjusted analysis or assess how robust it is to analytic choices. These omissions limit evaluation of the statistical plan but do not change the numerical summaries that the registry posts.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diverticulum (1.0%), gastrointestinal haemorrhage (1.0%), intraocular pressure increased (1.0%), renal failure acute (1.0%), large intestine polyp (1.0%).

The registry reports serious adverse events for safety groups at risk of 103 for vehicle, 102 for omaveloxolone 0.5%, and 102 for omaveloxolone 1%. The corresponding numbers affected were 4, 0, and 4. Deaths were reported as 0 in each group. These are counts of affected participants in the listed safety groups; they are not the same denominators as the primary endpoint summaries.

The record lists serious-event terms including diverticulum, gastrointestinal haemorrhage, increased intraocular pressure, acute renal failure, large intestine polyp, and small intestinal obstruction. Each listed term is shown with a frequency of 1.0%. The registry information presented does not give enough detail to assign these listed terms to a particular treatment group, determine event timing, or establish whether an event was considered related to study treatment.

The counts alone do not establish comparative safety. Interpretation would also depend on the type, timing, severity, duration, and treatment attribution of events, as well as the broader safety follow-up. The registry record does not report those details in the information. The observed counts describe what was recorded, not a causal conclusion.

17. What the Result Does, and Does Not, Mean

The primary endpoint means provide a direct description of average change from baseline in central corneal endothelial cell counts at 12 weeks. The vehicle group and both omaveloxolone groups had negative average changes. The 0.5% group had a numerically less negative mean change than vehicle, while the 1% group had a numerically more negative mean change than vehicle. Neither unadjusted comparison provides a precise estimate that rules out no difference.

These results do not establish that either concentration prevents endothelial cell loss, nor do they establish that the concentrations have no effect. The recalculated intervals include zero and allow values in both directions. The sponsor’s adjusted ANCOVA results also do not provide confidence limits in the registry record. A lack of a clear statistical separation is not proof that the groups are equivalent; an equivalence conclusion would require an appropriate design, a prespecified margin, and analyses that are not reported.

The endpoint is a group-level average and does not describe each participant’s experience. It also does not, on its own, answer broader questions about pain, inflammation, or other clinical outcomes. The registry lists several such secondary outcomes, but numerical results for most of them are not reported in the registry record. No clinically important difference threshold is reported, so statistical estimates cannot be translated into a judgment about clinical importance from this information alone.

The trial’s findings are best understood as estimates with uncertainty from a randomized comparison, alongside a sponsor-reported adjusted analysis. They may inform further research questions, but the posted results do not determine what an individual patient should do. The registry record does not provide enough information about missing data, multiplicity, or the detailed statistical model to resolve those issues independently.

18. Why This Trial Matters Statistically

This trial illustrates why treatment comparisons should be read through both their estimates and their uncertainty. The point estimate for 0.5% is numerically favorable relative to vehicle on the change scale, while the 1% estimate is numerically in the opposite direction. The intervals for both comparisons include zero and span values in either direction. Looking only at which group mean is numerically higher would therefore overstate what the evidence establishes.

The arm-level standard deviations are large relative to the mean contrasts, underscoring the importance of outcome variability in a continuous endpoint. The unadjusted recalculations and the sponsor’s ANCOVA analyses also demonstrate that an adjusted model and a direct comparison of summary means answer related, but not identical, statistical questions. Reporting the analysis method, model details, and uncertainty helps readers distinguish these analyses.

The record also shows why secondary outcomes and sample-size illustrations need context. Multiple outcomes can invite selective emphasis if a multiplicity strategy is unknown, and observed-effect planning calculations are not evidence of the trial’s original planning or of its success. Finally, separating efficacy summaries from safety denominators prevents confusion between the populations contributing to different analyses. These distinctions are central to a careful reading of clinical trial results.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the protocol’s original sample-size justification, detailed eligibility criteria, randomization procedure, or how double masking was maintained. It also does not provide the covariates and full specification for the sponsor’s ANCOVA. This limits independent reconstruction of the adjusted results and assessment of the planned analysis.

The primary endpoint is presented with arm-level means and standard deviations, but reasons for the differences between outcome and safety denominators are not reported. The amount and pattern of missing primary outcome data, methods for handling missingness, and sensitivity analyses are also not reported. These details matter when evaluating whether the analyzed participants represent the stated intent-to-treat population.

The recalculated comparisons are unadjusted, and the registry does not report whether multiple testing was addressed. Confidence limits for sponsor ANCOVA estimates are absent, and a clinically important difference threshold is not reported. The confidence level for the recalculated intervals is not stated in the record. These gaps limit conclusions about both statistical precision and clinical relevance.

Finally, the listed secondary outcomes are not accompanied by numerical results for most of the measures in the registry record. Serious adverse-event counts are reported, but event timing, treatment attribution, and group assignment for the listed serious-event terms are not described in the results. These limitations constrain interpretation of the posted evidence without altering the values that are reported.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: RTA 408 Ophthalmic Suspension for the Prevention of Corneal Endothelial Cell Loss Following Cataract Surgery - GUARD — NCT02128113.
• Registry record last updated 2025-06-03; status last verified 2025-05.
• Results first posted 2023-05-26.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

GUARD was a completed, randomized, double-masked, parallel-group phase 2 study sponsored by Biogen. It compared vehicle ophthalmic solution with omaveloxolone ophthalmic suspension at 0.5% and 1% in patients undergoing cataract surgery. The primary outcome was change from baseline in central corneal endothelial cell counts at 12 weeks in the intent-to-treat population.

The group means were negative in all arms. The unadjusted recalculated comparisons had intervals that included zero, while the sponsor reported ANCOVA analyses without confidence limits. The registry also lists secondary clinical outcomes and serious adverse-event counts, but important details about multiplicity, missing data, and analysis specifications are not reported in the registry record.