A Safety and Efficacy Study of NS2 in Patients With Anterior Uveitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety and Efficacy Study of NS2 in Patients With Anterior Uveitis (NCT02406209), a randomized phase 2 study. The primary outcome is Anterior Chamber Cell Grade at Week 8.

2. Clinical Question

The registry describes the study as a Phase 2 randomized trial of NS2 eye drops in patients with acute, non-infectious anterior uveitis. The brief description says participants were assigned in a 1:1:1 ratio to NS2, the combination, or Pred Forte. The primary efficacy assessment was at Week 8, with baseline identified as Day 1. The clinical question is therefore about the measured change in an inflammation-related clinical grade over that assessment period, rather than an outcome such as time to an event.

3. Trial Design

The registry identifies NCT02406209 as a completed Phase 2, randomized, parallel-group, comparator-controlled trial. Its official title describes an investigator-masked study of NS2 eye drops. The masking field lists triple masking, while the brief description specifically calls the study investigator-masked; the registry record does not explain the roles covered by the masking designation. The study is also described as multi-center.

The listed study start was 2015-03, and the primary completion date was 2016-04. Enrollment is reported as 45. Participants were assigned to three groups: NS2 ophthalmic drops at 0.5%, NS2 at 0.5% with Pred Forte, or Pred Forte at 1%. The arm descriptions say the drops were administered in the affected eye. The concentration of Pred Forte in the combination group is not consistent across record entries: the combination arm title and primary-outcome description say 0.1%, while the brief summary and arm description say 1%. The registry record does not resolve this discrepancy.

The primary efficacy outcome is anterior chamber cell grade at Week 8, expressed as change from baseline. The outcome description says the least-squares mean and standard error were derived using analysis of covariance, with baseline as a covariate and treatment group as a factor. The primary outcome population is identified as modified intent-to-treat. The registry record does not report the precise criteria defining that population, the randomization procedure, allocation concealment, or the original sample-size justification. It lists one outcome measure and no posted secondary outcomes. The detailed protocol, full statistical analysis plan, and any interim-analysis plan are not reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: Modified intent-to-treat

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.

6. Primary Endpoint

The registry lists the primary outcome as Anterior Chamber Cell Grade at Week 8, measured over The efficacy assessment period was assessed at Week 8; baseline was Day 1..

The primary endpoint is the change from baseline in anterior chamber cell grade at Week 8. The registry describes a scale from 0, meaning absent, to 4, meaning severe. The measure records the grade of cells in the anterior chamber, an assessment used in the trial to quantify an aspect of anterior uveitis. A change score expresses how the recorded grade at the assessment differs from the baseline grade; negative group means in the posted results indicate average decreases from baseline.

The registry reports least-squares means and standard errors, derived by analysis of covariance (ANCOVA), using baseline grade as a covariate and treatment group as a factor. General explanation: adjusting for baseline can account statistically for differences in starting measurements when estimating group means. A least-squares mean is a model-based estimate, not simply the unadjusted arithmetic mean. The standard error describes the estimated sampling uncertainty around a mean, rather than the spread of individual participants’ measurements.

The endpoint is useful for comparing the groups on a defined clinical scale at a specified assessment time. However, the registry record does not report a threshold for a clinically meaningful change, a responder definition, or additional context for interpreting the scale. The group means therefore describe the posted measurements but do not establish the importance of a particular change for an individual participant.

7. Results Posted in the Registry

• NS2 (0.5%) and Pred Forte® (0.1%) Ophthalmic Drops: mean -0.90 versus -0.70 on control; difference -0.20 (95% CI -1.03 to 0.63), standardized effect d = -0.17; z-test p = 0.638.
• Pred Forte® (1%) Ophthalmic Drops: mean -0.50 versus -0.70 on control; difference 0.20 (95% CI -0.67 to 1.07), standardized effect d = 0.17; z-test p = 0.654.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure: an anterior chamber cell grade recorded on a numeric scale and summarized as change from baseline. General explanation: continuous outcomes can take values along a measurement scale, and investigators often summarize them with means and measures of uncertainty. Here the registry reports least-squares means with standard errors for each group. The analysis population is labelled modified intent-to-treat, though the registry record does not define the inclusion rules for that population.

The outcome description says the least-squares means came from analysis of covariance (ANCOVA). Baseline grade was included as a covariate and treatment group as a factor. General explanation: a covariate is a measured characteristic incorporated into a statistical model; adjusting for baseline can improve the comparison by accounting for starting values. The group factor represents the treatment groups being compared. A least-squares mean is the model’s estimated group mean under its adjustment, rather than a raw average calculated without reference to the model.

The standard error reported beside each least-squares mean describes uncertainty in estimating that mean. General explanation: a standard error is not the standard deviation of individual observations. The standard deviation describes how measurements vary among individuals, while the standard error describes the expected sampling variation of an estimated mean. A smaller standard error generally indicates a more precise estimate, conditional on the model and data used. The registry record does not post standard deviations for the endpoint or the detailed ANCOVA output.

The comparison results are identified as recalculated, unadjusted comparisons from posted summary statistics. For each comparison, the reported mean difference and confidence interval are therefore not the trial’s stated ANCOVA contrast. The recalculations use approximate standard deviations inferred from the reported standard errors, as indicated in the comparison details. General explanation: an unadjusted comparison does not account for covariates in the way an ANCOVA contrast does. It can be useful as a transparent summary-data check, but it should not replace the sponsor’s own analysis when that analysis is available. The registry record does not post that analysis; the recalculated results should consequently be read as separate from the stated ANCOVA method.

A confidence interval gives a range of values compatible with the observed data under the calculation and its assumptions. General explanation: the interval reflects uncertainty in an estimated difference, not a range containing a known proportion of individual participant outcomes. Its width depends in part on the amount of information and the variability represented in the analysis. These comparison intervals are recalculated from summary statistics, so their interpretation depends on the approximation used as well as the underlying posted values.

The p-values for the two comparisons are also unadjusted recalculations. General explanation: a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the model assumptions. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of a difference. Because no formal analysis results are posted, the recalculated p-values should not be attributed to the trial’s reported ANCOVA.

There are two comparisons against the NS2-alone group in the posted results. General explanation: when several hypotheses are tested, the chance of at least one apparently unusual result can increase if no multiplicity strategy is used. Possible strategies include adjusting the testing procedure or defining a primary comparison in advance, but the registry record does not report such a strategy. It also does not report whether interim analyses were planned or conducted. No assumption about either issue can be made from the posted results.

The analysis population is described as modified intent-to-treat, but the registry record does not define how participants entered that population or how missing Week 8 measurements were handled. General explanation: missing outcome data can affect the interpretation of a group comparison, depending on why observations are missing and how the analysis treats them. The record does not state whether imputation, a complete-case approach, or another method was used. Outcome arm counts are reported as 15, 16, and 13; the safety denominators differ for the Pred Forte group. These separate denominators should be retained as reported rather than reconciled by assumption.

The registry lists no formal analyses and no secondary outcomes. It provides one primary outcome measure, group-level least-squares means and standard errors, and recalculated comparisons. It does not report the full statistical analysis plan, model diagnostics, assumptions checks, exact analysis software, or the trial’s original power calculation. General explanation: model diagnostics are checks of whether the model’s assumptions and fit are adequate for the data. Without those details, a reader can describe the registered method and posted summaries, but cannot independently assess every aspect of the analysis implementation.

10. Confidence Intervals and Precision

The registry’s primary outcome means are reported with standard errors: -0.7 (0.31) for NS2 alone, -0.9 (0.29) for NS2 with Pred Forte, and -0.5 (0.32) for Pred Forte alone. These standard errors characterize the estimated means, not the spread of individual change scores. The registry does not report confidence intervals for the least-squares means themselves.

The recalculated unadjusted comparison of the combination group with NS2 alone is -0.2 units, with a 95% confidence interval from -1.032 to 0.632. The recalculated unadjusted comparison of Pred Forte alone with NS2 alone is 0.2 units, with a 95% confidence interval from -0.673 to 1.073. Both intervals extend across zero. Their breadth means the summary-data comparisons do not pin down a narrow range of possible differences. The intervals also allow values on either side of zero, so the direction of a difference is uncertain under these recalculations.

General explanation: a confidence interval expresses uncertainty in an estimated parameter under a method and its assumptions. It does not show where most individual observations fall, and it is not a guarantee that the true value is inside the interval. Here the intervals are recalculated from posted summary statistics using an approximation, rather than taken from the stated ANCOVA analysis. The registry record does not provide adjusted confidence intervals or formal analysis results, so the precision of the trial’s model-based treatment contrasts cannot be assessed from the posted record.

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 illustrations are planning calculations, not a report of the trial’s original design assumptions. They use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to a stated fraction of the observed effect. The registry record does not report the trial’s original sample-size justification or its design assumptions. The figures are participants per arm, not total participants or total events.

For the comparison of the combination group with NS2 alone, the planning illustration for 100% of the observed effect gives 547 participants per arm for 80% power and 732 participants per arm for 90% power. Planning for 75% of the observed effect gives 972 participants per arm for 80% power and 1,301 participants per arm for 90% power. Planning for 50% of the observed effect gives 2,185 participants per arm for 80% power and 2,926 participants per arm for 90% power.

For the comparison of Pred Forte alone with NS2 alone, the corresponding figures are 546 participants per arm for 80% power and 731 participants per arm for 90% power when planning for 100% of the observed effect; 971 and 1,299 participants per arm when planning for 75% of the observed effect; and 2,183 and 2,923 participants per arm when planning for 50% of the observed effect.

General explanation: 80% and 90% power describe the probability, under the planning assumptions and specified effect, of detecting a difference at the chosen significance level. Smaller effects require more participants per arm to detect with the same planned power. These figures are planning illustrations based on the observed effects, not observed power for the completed trial.

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 = -0.200; pooled standard deviation σ = 1.180.
2. n = 2 × (1.96 + 0.842)² × 1.180² / -0.200² = 546.2, rounded up to 547 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 <- -0.2                      # observed difference in means
sigma <- 1.17978665517293                     # 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(2406209)
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 = 547 (80% power), 732 (90% power)
 75% of observed effect: n per arm = 972 (80% power), 1,301 (90% power)
 50% of observed effect: n per arm = 2,185 (80% power), 2,926 (90% power)
power.t.test: 547.2 
Simulated power at n = 547 per arm: 0.804 (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 one primary outcome measure and no posted secondary outcomes. It provides two recalculated comparisons, each against the NS2-alone group. The registry record does not report a prespecified hierarchy for those comparisons, a multiplicity adjustment, or another strategy for controlling the interpretation of multiple tests. The recalculated p-values are unadjusted and should be read as such. The record also lists no formal analyses, so it does not provide a sponsor-reported testing framework against which to assess the comparisons.

The endpoint population is described as modified intent-to-treat. The registry record does not define that population, state the eligibility rules for inclusion in the endpoint analysis, or explain whether participants were analyzed according to their randomized group. Outcome counts are 15 for NS2 alone, 16 for the combination group, and 13 for Pred Forte alone. The record does not explain why these counts differ from the enrollment figure or whether all randomized participants had Week 8 measurements.

Missing-data handling is not reported in the registry record. It does not say whether missing measurements were imputed, omitted, or addressed through another method, nor does it describe sensitivity analyses. General explanation: the consequences of missing data depend partly on the reasons observations are unavailable and on the method used to handle them. Without that information, it is not possible to assess how missing outcomes may have affected the estimates.

The safety denominators are reported separately from the outcome counts, including a denominator of 14 for the Pred Forte safety group and an outcome count of 13 for that arm. The registry record does not explain this difference. The trial’s original sample-size calculation, interim-analysis plan, and full statistical analysis plan are also not reported. These omissions limit assessment of the planned analysis, multiplicity, and the relationship between enrollment and each analysis population.

14. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures report zero affected participants in each group: the denominators at risk are 15 for NS2 alone, 16 for the combination group, and 14 for Pred Forte alone. The registry also reports zero deaths in each group. No serious adverse event terms are listed among the posted top terms. These are the registry’s reported counts; they do not establish that no events of any kind occurred.

For other adverse events, the reported affected counts are 8 among 15 at risk for NS2 alone, 8 among 16 at risk for the combination group, and 3 among 14 at risk for Pred Forte alone. These figures describe participants reported as affected, not event totals or event rates. No percentages are calculated.

General explanation: safety counts need to be read alongside their group-specific denominators and the registry’s definitions of serious and other adverse events. The registry record does not provide event descriptions for the other adverse events in these summary figures, exposure-adjusted rates, or a detailed account of collection and coding methods. The counts alone do not establish whether an event was caused by a treatment, and they do not support a broad safety conclusion.

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

The posted primary outcome describes average change in anterior chamber cell grade from baseline to the Week 8 assessment. All three reported least-squares means are negative: -0.7 for NS2 alone, -0.9 for the combination, and -0.5 for Pred Forte alone. These are group-level model estimates on the stated 0-to-4 scale. They do not show how measurements changed for each participant or whether a particular change would matter clinically.

The recalculated unadjusted comparisons have 95% confidence intervals that include zero: -0.2 units for the combination versus NS2 alone, with an interval from -1.032 to 0.632, and 0.2 units for Pred Forte alone versus NS2 alone, with an interval from -0.673 to 1.073. These estimates are not the trial’s ANCOVA contrasts. The intervals indicate uncertainty in the recalculated comparisons and do not establish that the groups are equivalent. The registry record does not report a clinically meaningful difference threshold that would allow the estimates to be judged against such a benchmark.

The results do not establish that one treatment works or does not work. The registry record posts no formal analysis results, and the comparison p-values are unadjusted recalculations from summary statistics. It also does not report how missing outcome data were handled, the full analysis plan, or the method used to define the modified intent-to-treat population. Those details matter when judging the strength and scope of an inference.

The safety summaries report no serious adverse events and no deaths in the listed groups, alongside other adverse event counts. These observations are limited to the reported denominators and do not establish the presence or absence of all possible safety outcomes. Overall, the registry supports a description of the reported Week 8 endpoint estimates and safety counts, but not a definitive conclusion about comparative efficacy, clinical importance, or broader safety.

16. Why This Trial Matters Statistically

This trial illustrates the distinction between a registered analysis method and a comparison that can be recalculated from summary data. The primary outcome description identifies ANCOVA, with baseline as a covariate and treatment group as a factor, and reports least-squares means with standard errors. The posted comparison intervals and p-values are recalculated, unadjusted summaries, not the model-based contrasts described for the primary endpoint. Keeping those results distinct prevents a recalculation from being mistaken for the trial’s formal analysis.

It also shows why precision matters alongside the direction of group means. The three least-squares mean changes are negative, but the recalculated comparison intervals are broad and span zero. That pattern calls for careful description of uncertainty rather than relying on the sign of the point estimates alone. The registry does not provide a clinical-importance threshold, so statistical estimates cannot be translated into a claim about meaningful benefit.

The record highlights the importance of consistency and completeness in trial reporting. The Pred Forte concentration in the combination group varies across entries, the outcome and safety denominators differ, and missing-data handling and multiplicity methods are not reported. Such details affect how readers understand what was compared, which observations contributed, and how confidently results can be interpreted. The planning illustrations also show that calculations based on an observed effect depend on assumptions about the effect size to detect and desired power; they are not a substitute for the trial’s original design justification.

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 registry record does not provide the full protocol or statistical analysis plan, the trial’s original sample-size justification, or an interim-analysis plan. It also does not report a definition of the modified intent-to-treat population, the handling of missing Week 8 measurements, or sensitivity analyses. These omissions restrict assessment of how the registered analysis was implemented and how robust the endpoint estimates are to analysis choices.

The combination-group Pred Forte concentration is described as 0.1% in the arm title and primary-outcome description, but as 1% in the brief summary and arm description. The record does not resolve which concentration was used in that group. Enrollment is reported as 45, while the outcome arm counts are 15, 16, and 13; the registry does not explain the relationship between enrollment and those outcome counts. The safety denominator for Pred Forte is 14, rather than the outcome count of 13, and the reason is not reported.

The registry reports one primary outcome measure and no secondary outcomes, and lists zero formal analyses. The trial’s stated endpoint method is ANCOVA, but adjusted contrast estimates and their uncertainty are not posted. The available comparisons are unadjusted recalculations from summary statistics, with approximate standard deviations. A clinical threshold for meaningful change and further context on the scale are also not reported in the registry record. These limitations leave the posted results useful for describing the registry entries, but incomplete for a full evaluation of the analysis and its clinical interpretation.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Safety and Efficacy Study of NS2 in Patients With Anterior Uveitis — NCT02406209.
• Registry record last updated 2023-03-27; status last verified 2019-02.
• Results first posted 2023-03-27.
• 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

NCT02406209 is a completed Phase 2 randomized, parallel-group, comparator-controlled study of NS2 eye drops in patients with non-infectious anterior uveitis. The registry reports enrollment of 45 and a primary completion date of 2016-04. Participants were assigned to NS2 alone, NS2 with Pred Forte, or Pred Forte alone. The primary outcome was change from baseline in anterior chamber cell grade at Week 8, summarized with ANCOVA least-squares means and standard errors.

The posted group estimates were -0.7 for NS2 alone, -0.9 for the combination, and -0.5 for Pred Forte alone. Two unadjusted comparisons were recalculated from summary statistics; the registry lists no formal analyses. The record reports no serious adverse events or deaths in the listed safety groups. Important details, including the combination concentration discrepancy, missing-data methods, and original sample-size justification, are not resolved or reported in the registry record.