Clinical Outcomes of Bromday (Bromfenac Ophthalmic Solution) 0.09% QD vs. Nevanac (Nepafenac Ophthalmic Suspension) 0.1%: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Outcomes of Bromday (Bromfenac Ophthalmic Solution) 0.09% QD vs. Nevanac (Nepafenac Ophthalmic Suspension) 0.1% (NCT01310127), a randomized phase 4 study. The primary outcome is Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuities.

2. Clinical Question

This is a randomized, active-comparator study of clinical outcomes after cataract surgery. The primary outcome is a continuous measure: ETDRS visual acuity in letters. The scale is described as ranging from 30 to 90 letters, with higher scores indicating better visual acuity. The posted arm means are 51.3 letters for Bromday and 52.0 letters for Nevanac. The estimated mean difference is 0.7 letters, with the Nevanac mean higher in the posted summaries.

The question is about the measured group averages at the specified follow-up, not whether either regimen is generally effective or preferable. The confidence interval around the estimated difference is important because a small difference between the observed means does not, on its own, establish that the underlying group means are alike. The interval extends from -5.246 to 6.646 letters, leaving substantial uncertainty about the direction and size of the difference compatible with these results.

3. Trial Design

The registry identifies this as a completed Phase 4 study with randomized allocation, single masking, and a parallel-group model. The brief summary further describes a single-center, investigator-masked, active-comparator-controlled study. The record does not specify who, apart from the investigator, was masked, or provide further details of the randomization procedure.

The two named groups received different topical ophthalmic regimens. Bromday was bromfenac 0.09% once daily, starting 3 days before cataract surgery and continuing on the surgery day and for 21 days postoperatively. Nevanac was nepafenac 0.1% three times daily over the corresponding preoperative, surgery-day, and postoperative period. The Nevanac description also notes the usual cataract procedure. The record does not provide additional information about adherence, treatment changes, or co-interventions.

Enrollment is recorded as 23. For the primary outcome, the arm summaries list 10 participants for Bromday and 10 for Nevanac. The registry record does not explain the relationship between the enrollment figure and the outcome-specific arm counts, so no reason for that difference can be established from the record. Safety summaries use separate at-risk counts: 12 for Bromday and 11 for Nevanac.

The study started in 2010-11, had primary completion in 2011-04, and is marked completed. The sponsor is Toyos Clinic. The registry record does not report the protocol's sample-size justification, the original target for enrollment beyond the recorded enrollment, or details of any interim analyses. It also does not give enough information to assess implementation of allocation concealment or the conduct of masking.

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.

Before assignment: Subjects were randomized to receive bromfenac(n=12) QD or nepafenac(n=11) TID. Dosing was 3 days before cataract surgery through day 21 postop. Subjects could not have used ocular/topical, systemic NSAIDs, gentamicin, or cyclosporine ophthalmic emulsion 7 days or prostaglandins 30 days prior to initial dosing of test article or during the study.

Overall Study

Reasons for not completing this period:

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: 1 nepafenac patient did not use test article prior to surgery. 1 bromday patient used nsaid during study. 1 bromday patient had advanced psc cataract.

6. Primary Endpoint

The registry lists the primary outcome as Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuities, measured over Week 6.

The primary endpoint is Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity at Week 6 after uncomplicated phacoemulsification. It is recorded as a mean, with standard deviations, in letters. ETDRS charts are described in the registry as standardized eye charts accepted by the National Eye Institute and the Food and Drug Administration. The stated scale runs from 30 to 90 letters, and higher values signify improved visual acuity.

Visual acuity is relevant to this study because the stated purpose was to investigate clinical outcomes after cataract extraction with posterior chamber intraocular lens implantation. A standardized letter score provides a numerical way to summarize visual performance and compare group averages at a specified follow-up. Because it is continuous, the result can be described using a mean and a measure of spread, and the between-group comparison can be expressed as a mean difference with a confidence interval.

The posted means are 51.3 letters for Bromday and 52.0 letters for Nevanac. The standard deviations are 6.818 and 6.75, respectively. These summaries describe the observed distribution in each arm; they do not by themselves show how precisely the group difference has been estimated. The registry record reports this endpoint at Week 6 and does not provide further detail about other assessment times for this measure.

7. Results Posted in the Registry

• Nevanac: mean 52.00 versus 51.30 on control; difference 0.70 (95% CI -5.25 to 6.65), standardized effect d = 0.10; z-test p = 0.818.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measurement, so the registry reports a mean for each arm and a standard deviation to describe spread within each arm. The Bromday mean is 51.3 letters, with a standard deviation of 6.818; the Nevanac mean is 52.0 letters, with a standard deviation of 6.75. A mean condenses the observed scores into a group average. A standard deviation describes how dispersed scores are around that average. Neither statistic alone communicates the uncertainty in the comparison between group means.

The comparison is reported as a mean difference of 0.7 letters, with an interval from -5.246 to 6.646. The direction follows the posted group values: the Nevanac mean is higher, and the estimated difference is positive. The confidence interval gives a range of values compatible with the data under the assumptions of the interval procedure. It expresses estimation uncertainty; it is not a range containing a specified proportion of individual participants' scores, and it does not mean that every value in the interval is equally likely.

Because the interval includes zero and extends in both directions, it does not pin down whether the population mean difference is positive, negative, or near zero. The width matters as much as the point estimate: a point estimate can appear close to zero while the range of compatible values remains broad. The interval therefore conveys that the posted comparison is imprecise, not that the groups have been demonstrated to be identical.

The registry also gives an unadjusted p-value of 0.818. In general, a p-value describes how unusual the observed data, or data more extreme, would be under a specified null hypothesis and the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not quantify the probability that the result will replicate. A large p-value does not prove equivalence or show that there is no effect. The registry record does not report the test procedure or a prespecified decision threshold for the trial's analysis, so the p-value should be read as the posted unadjusted result rather than as evidence of a documented analysis plan.

The record identifies the endpoint as a mean and gives a standard deviation for each arm. It does not explain the method used to construct the listed confidence interval or calculate the p-value. The posted comparison also gives a pooled standard deviation of 6.784 and standard errors of 2.156 for Bromday and 2.135 for Nevanac. Standard errors describe uncertainty in estimated quantities, rather than the spread of individual measurements. These quantities do not fill in the missing description of the analysis procedure.

Randomization is intended, in general, to make treatment assignment independent of participants' characteristics, reducing systematic differences between groups at baseline. It does not guarantee that the groups will be identical, especially in a small trial. The record identifies randomized allocation but does not describe sequence generation, concealment, or whether randomization was stratified. Those details are not reported in the registry record and should not be inferred from the allocation label.

Masking can reduce the potential for knowledge of treatment assignment to influence care, assessment, or reporting. The record says single masking, and the study description calls it investigator-masked. It does not say whether participants, outcome assessors, or other personnel were masked. The effect of masking on this endpoint cannot be assessed from the label alone, and no further masking procedure is reported.

For a continuous endpoint, over-dispersion means that variability is greater than a statistical model allows for. In general, if a model understates variability, its standard errors can be too small and its confidence intervals too narrow. That general concern does not establish that over-dispersion occurred in this study: the registry record does not identify the model or provide diagnostic checks. The posted standard deviations show observed spread, but they are not evidence on their own of a particular model's adequacy.

The sample-size illustrations use the observed effect and state assumptions of a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. They show planning scenarios for fractions of the observed effect. In general, detecting a smaller effect requires more participants when the other assumptions remain fixed. These calculations are illustrations rather than a record of the trial's original design process. The original design assumptions and sample-size justification are not reported in the registry record.

The registry lists 0 analyses and 0 posted secondary outcomes. That limits what can be said about statistical methods beyond the posted outcome summaries and comparison. There is no reported description of a prespecified analysis plan, model diagnostics, covariate adjustment, handling of missing data, or multiplicity procedure. Statistical interpretation should distinguish the numerical result from methods that are not documented.

10. Confidence Intervals and Precision

The estimated Week 6 mean difference is 0.7 letters, with a confidence interval from -5.246 to 6.646 letters. The point estimate is the central comparison reported by the registry, while the interval communicates uncertainty around it. Since the interval includes zero, values compatible with the data include a small difference near zero as well as differences in either direction.

The interval is wide relative to the point estimate. Its lower and upper endpoints are separated by a substantial range of possible differences, so the estimate is not precise enough to identify a clear direction or tightly constrain the size of the difference. The study's arm summaries each list 10 participants for this outcome, and the standard deviations are 6.818 for Bromday and 6.75 for Nevanac. Those features provide context for the uncertainty, but they do not justify calculating a different interval or drawing conclusions beyond the posted one.

A confidence interval is not a guarantee that the true effect lies within its limits, nor does it assign a probability to each possible effect. In general, it describes the range generated by a statistical procedure with stated coverage properties under its assumptions. The registry record does not describe the procedure used for this interval. The interval should therefore be interpreted as the posted measure of precision, while recognizing that the underlying method is not reported.

The interval's inclusion of zero does not establish equivalence. To claim equivalence, the study would need a clinically justified margin and an analysis designed to assess whether the interval falls within that margin; neither is reported in the registry record. The interval instead shows that the data leave substantial uncertainty about the group difference.

11. 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 effect, not the original trial design. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The registry record does not report the original design assumptions or a sample-size justification.

The displayed quantities are participants per arm, not a total across arms and not total events. The rows consider planning for 100%, 75%, and 50% of the observed effect. At 100% of the observed effect, the illustration gives 1,475 participants per arm for 80% power and 1,974 participants per arm for 90% power. At 75% of the observed effect, the corresponding figures are 2,622 and 3,510 participants per arm. At 50% of the observed effect, they are 5,898 and 7,896 participants per arm.

In general, power is the chance that a study will detect an effect of the specified size under the assumed model and analysis when that effect is present. The 80% column describes a planning scenario with that target power; the 90% column uses a higher target power and therefore requires more participants under these assumptions. Smaller effects are harder to distinguish from random variation, so planning to detect a smaller fraction of the observed effect requires more participants.

The curve represents the same kind of planning relationship: as the target effect becomes smaller, the required sample size rises under the stated assumptions. These are hypothetical design calculations, not observed power for the completed trial. The calculation is based on the observed effect and should not be read as a recommendation or as evidence about the trial's original planning.

12. 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 = 0.700; pooled standard deviation σ = 6.784.
2. n = 2 × (1.96 + 0.842)² × 6.784² / 0.700² = 1,474.4, rounded up to 1,475 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 <- 0.700000000000003                      # observed difference in means
sigma <- 6.78408519993669                     # 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(1310127)
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 = 1,475 (80% power), 1,974 (90% power)
 75% of observed effect: n per arm = 2,622 (80% power), 3,510 (90% power)
 50% of observed effect: n per arm = 5,898 (80% power), 7,896 (90% power)
power.t.test: 1475.4 
Simulated power at n = 1,475 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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures, but the primary result described in detail is Week 6 ETDRS visual acuity. It lists 0 posted secondary outcomes and 0 analyses. The record therefore does not provide a set of secondary-outcome estimates that could be examined alongside the primary result.

When a study tests multiple outcomes, time points, subgroups, or treatment contrasts, the chance of finding at least one apparently notable result can increase. Statistical methods for multiplicity can address that issue, but their choice depends on the trial's prespecified questions and analysis plan. The registry record does not report whether multiplicity adjustments were planned or used, nor does it describe the full set of planned comparisons. It would not be appropriate to assume either that an adjustment was made or that none was made in the study's original analysis.

The record also does not state how missing outcome data were handled, whether participants were analyzed according to randomized assignment, or which analysis population was used for the primary result. The arm summaries list 10 participants for each group, but the registry does not explain exclusions, missing measurements, or the relation between these endpoint counts and the enrollment of 23. No reason for the difference can be established from the available record.

Further information about outcome definitions, the planned analysis, missing-data methods, and analysis populations is not reported in the registry record. These omissions limit assessment of whether the posted summaries reflect the intended analysis and how robust they are to missing observations or alternative analysis choices. The randomized design is reported, but randomization alone does not answer these questions about the analysis population or reporting process.

14. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0.05% reporting threshold.

Most frequent non-serious adverse event terms

The safety summaries list serious adverse events for 0 of 12 participants at risk in the Bromday group and 0 of 11 at risk in the Nevanac group. No serious adverse-event terms are listed. These figures describe the registry's recorded serious-event counts; they do not establish that the regimens have identical safety profiles or rule out uncommon events.

For other adverse events, the record lists 0 of 12 participants at risk for Bromday and 1 of 11 for Nevanac. These are separate safety counts and should not be confused with the primary-outcome arm counts, which are 10 for each group. The record does not provide further detail about the non-serious event or its severity, timing, or relationship to treatment.

Deaths are not reported in the registry record. The safety summaries are limited in size and detail, and should be read as recorded event counts rather than as a complete assessment of comparative safety.

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

The posted results describe mean ETDRS visual acuity at Week 6 after cataract surgery. The group means were 51.3 letters for Bromday and 52.0 letters for Nevanac, with an estimated difference of 0.7 letters. The confidence interval, -5.246 to 6.646 letters, is broad and includes differences in either direction. The evidence therefore does not precisely determine the direction or magnitude of the difference in this outcome.

That uncertainty is not evidence that the treatments are equivalent. Equivalence requires a prespecified margin defining how close the effects must be, alongside an analysis suited to that question. No such margin or analysis is reported in the registry record. Nor does the unadjusted p-value of 0.818 prove that there is no difference. It indicates that the posted comparison does not provide strong evidence against a null difference under the assumptions of the underlying test, whose method is not described.

The result is specific to the reported outcome, follow-up, and trial population. It does not establish what happened for unreported outcomes or at other follow-up times. The registry lists 0 posted secondary outcomes, so the posted primary result cannot be used as a substitute for a complete account of all outcomes assessed or planned.

The trial is recorded as randomized and investigator-masked, but important analysis details are absent. The record does not report missing-data procedures, analysis populations, multiplicity methods, or the original sample-size rationale. These limits affect how confidently the posted comparison can be interpreted. The small outcome-specific arm counts and wide interval reinforce that the estimate is imprecise.

The safety entries also have limited scope: serious-event counts are zero in both groups, while the other-adverse-event counts differ as recorded. These counts do not establish overall safety or rule out events that were not captured. Overall, the registry record supports a careful description of the observed Week 6 summaries and their uncertainty, rather than a broad claim about comparative benefit or safety.

16. Why This Trial Matters Statistically

This trial illustrates why a point estimate and its uncertainty need to be read together. The means are close, and the estimated difference is 0.7 letters, but the confidence interval extends from -5.246 to 6.646. Looking only at the means could make the comparison seem settled; the interval shows that the estimate is not precise enough to establish a narrow range of plausible differences.

It also illustrates the distinction between failing to demonstrate a difference and demonstrating equivalence. The posted unadjusted p-value is 0.818, and the interval includes zero. Neither fact establishes that the treatments have the same effect. An equivalence conclusion would require a prespecified margin and an appropriate analysis, neither of which is reported in the registry record.

The sample-size illustrations make a related planning point. They show that detecting smaller fractions of the observed effect requires larger per-arm samples under the stated assumptions. Those figures are not the original design justification and are not observed power. They help explain why an imprecise result can arise when the outcome-specific groups are small relative to the planning scenarios.

Finally, the registry record distinguishes the primary outcome summaries from other information that would be needed for a fuller statistical assessment. The analysis plan, missing-data methods, analysis populations, and multiplicity procedures are not reported. Recognizing those omissions is part of interpreting a result responsibly: numerical estimates can be described accurately while the limits of what the record establishes remain clear.

17. 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 outcome-specific summaries list 10 participants in each arm, while the registry records enrollment of 23. Safety at-risk counts are 12 for Bromday and 11 for Nevanac. The record does not explain how these counts relate to one another, or why the primary-outcome counts differ from the enrollment and safety figures. No explanation should be inferred.

The primary comparison has a broad confidence interval, extending from -5.246 to 6.646 letters. This limits precision about both the direction and the size of the difference. The registry does not report a clinically meaningful difference threshold for ETDRS letters, so the clinical importance of values within the interval cannot be assessed against a trial-specific threshold.

The study is described as single-center, which limits what can be inferred about settings beyond the one recorded. Details of eligibility criteria and the characteristics of the participants are not reported in the registry record. The record also does not detail randomization procedures, the exact masking arrangements, adherence, or treatment changes.

For statistical interpretation, the test and confidence-interval methods, missing-data handling, analysis populations, covariate adjustment, and multiplicity procedures are not reported. The original sample-size justification and any interim analyses are not reported in the registry record. These gaps prevent a fuller assessment of the analysis and its robustness. The registry's safety summaries are also limited in detail, including no reported death counts and no descriptive information about the other adverse event.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Clinical Outcomes of Bromday (Bromfenac Ophthalmic Solution) 0.09% QD vs. Nevanac (Nepafenac Ophthalmic Suspension) 0.1% — NCT01310127.
• Registry record last updated 2020-10-28; status last verified 2020-10.
• Results first posted 2013-09-26.
• 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.

21. Record Summary

NCT01310127 is recorded as a completed Phase 4, randomized, single-masked, parallel-group comparison of Bromday and Nevanac after cataract surgery. The study is described as single-center and investigator-masked. Enrollment is 23; the sponsor is Toyos Clinic. The recorded start is 2010-11, with primary completion in 2011-04.

The primary outcome is mean ETDRS visual acuity in letters at Week 6. The arm means are 51.3 for Bromday and 52.0 for Nevanac, with an estimated mean difference of 0.7 and a confidence interval from -5.246 to 6.646. The unadjusted p-value is 0.818. The interval indicates considerable uncertainty about the direction and size of the difference.

The registry lists 0 analyses and 0 posted secondary outcomes. Important details of the statistical plan, missing-data handling, and analysis populations are not reported in the registry record.