A Randomized Study in Children Ages Birth Through Three Years Undergoing Unilateral Cataract Extraction With or Without Lens Replacement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized Study in Children Ages Birth Through Three Years Undergoing Unilateral Cataract Extraction With or Without Lens Replacement (NCT02132312), a randomized phase 3 study. The primary outcome is Intraoperative Pupil Diameter.

2. Clinical Question

The registry describes a study of OMS302 compared with phenylephrine during cataract extraction. Its stated aims also include acute postoperative pain and safety, but the posted primary outcome is intraoperative pupil diameter. The result therefore addresses the specified pupil-diameter measure, rather than every aim listed in the study summary.

The primary outcome is described as the mean area under the curve of change from baseline in pupil diameter during surgery. Baseline was before incision, and the measurement period ran through the end of surgery, specified as cortical clean-up or wound closure. The registry reports 61 evaluable videos, one for each subject contributing to that analysis. The groups were compared using the posted mean values and mean difference.

This is a comparison of two irrigation-solution strategies in a defined surgical setting and age range. It does not directly answer questions about other ages, other procedures, or outcomes that were not posted. The registry record does not report a posted secondary outcome result for acute postoperative pain.

3. Trial Design

This was a Phase 3, randomized, quadruple-masked, parallel-group study. The registry lists Omeros Corporation as the sponsor and describes the study as completed. Enrollment is listed as 78. The recorded start is 2014-07, and primary completion is listed as 2016-09-12.

Participants were assigned to receive either OMS302 or phenylephrine HCl in balanced salt solution as irrigation solution during unilateral cataract extraction. The two arms therefore share the route and procedural context described in the record, while differing in the named study drug. The registry does not report further details about how allocation was generated or concealed, so those features cannot be characterized from this record.

Quadruple masking indicates that the record classifies the study as masked at four roles or levels, but the registry record does not report which specific people were masked or how masking was maintained. The parallel-group model means the posted comparison is between groups rather than a crossover comparison within the same participant.

The planned enrollment and the primary analysis population are not interchangeable. The primary outcome description reports 61 evaluable videos, one per subject, and says subjects with unevaluable videos were excluded. The record does not report the reasons videos were unevaluable or further details about the participants included in other analyses. The displayed group counts for the primary outcome are 30 for OMS302 and 31 for phenylephrine HCl.

Although the study summary identifies acute postoperative pain and safety among the topics evaluated, the record reports no posted secondary outcome results. It lists three outcome measures and no analyses. The study's own design assumptions, including any planned target difference or sample-size justification, 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.

Before assignment: 78 participants enrolled in the study. 6 participants were consented and randomized but did not receive OMS302 or Phenylephrine HCl. Out of the 72 participants who received OMS302 or Phenylephrine HCl, 3 participants did not complete the study. One participant was randomized to OMS302, but received Phenylephrine HCl. This participant was included in the OMS302 group in baseline analyses and in the Phenylephrine HCl group in safety analyses.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: There were 61 evaluable videos, one for each subject.

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: 78 participants enrolled in the study. 6 participants were consented and randomized but did not receive OMS302 or Phenylephrine HCl. One out of 72 participants was randomized to OMS302 but received Phenylephrine HCl. This participant was included in the OMS302 group in baseline analyses and in the Phenylephrine HCl group in safety analyses.

6. Primary Endpoint

The registry lists the primary outcome as Intraoperative Pupil Diameter, measured over From surgery baseline (pre-incision) through surgery end (time of cortical clean-up/wound closure), the mean time of surgery duration is 35.46 minutes with a standard deviation of 19.98..

The primary endpoint is intraoperative pupil diameter, expressed as a mean area-under-the-curve analysis of change from baseline during surgery. Baseline is defined as the pre-incision measurement. The observation window extends to surgery end, specified as the time of cortical clean-up or wound closure. The registry describes the mean surgery duration as 35.46 minutes with a standard deviation of 19.98.

An area under the curve combines measurements across a defined period, rather than representing only one measurement at one instant. In general, this can describe the accumulated pattern of change over the observation window. In this study, the endpoint is based on the change in pupil diameter from the baseline measurement. The record labels the unit as millimeters*minutes, while the endpoint description also uses mm/min; both notations appear in the registry record.

The posted analysis is a mean-based summary. It reports a group mean and standard deviation for each arm, then a mean difference and an interval estimate for the comparison. The endpoint description excludes subjects with unevaluable videos. The registry reports 61 evaluable videos, one per subject, for this outcome.

In general, a prespecified intraoperative measurement can focus attention on a procedure-related feature over the operation itself. The record identifies this measure as the primary endpoint, but does not report the clinical threshold, if any, that would define a meaningful difference. It also does not report a posted result for the stated acute postoperative pain outcome.

7. Results Posted in the Registry

• Phenylephrine HCl: mean 0.20 versus 0.14 on control; difference 0.06 (95% CI -0.21 to 0.33), standardized effect d = 0.11; z-test p = 0.664.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean difference describe?

The endpoint is continuous: it is a numerical measurement summarized by a mean. A mean difference compares the average outcome in one group with the average in another. Here, the reported comparison is phenylephrine HCl minus OMS302, with a mean difference of 0.06. The group means are 0.2 and 0.14, respectively. The estimate describes the observed difference in the analyzed outcome; it does not, by itself, establish that the treatments caused a difference.

In general, the direction of a mean difference depends on the subtraction order. A positive value for phenylephrine HCl minus OMS302 indicates that the posted mean was numerically higher in the phenylephrine HCl group for this coded endpoint. Whether a higher value is preferable, harmful, or clinically important cannot be determined from the statistical direction alone. The registry record does not report a threshold for interpreting the endpoint clinically.

Why report standard deviations?

A mean gives a central summary, while a standard deviation describes how spread out individual observations are around that mean. The posted standard deviations are 0.474 for OMS302 and 0.6 for phenylephrine HCl. In general, greater spread means individual measurements vary more around the group average. A standard deviation is not the same as the standard error or the confidence interval: it describes the observations, whereas standard errors and intervals describe uncertainty in an estimate.

The outcome is an area-under-the-curve measure derived from changes over surgery. The registry reports that surgery duration had a mean of 35.46 minutes and a standard deviation of 19.98. In general, variation in observation duration can matter for interpreting an accumulated measure, though the record does not provide enough detail to assess how duration was handled in the analysis beyond its stated endpoint window.

What does the p-value say?

The unadjusted p-value is 0.664. In general, a p-value measures how compatible the observed data are with a specified null model, under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. A large p-value does not prove the groups are identical; it indicates that the analysis did not yield strong evidence against its null model.

The registry labels this p-value unadjusted. The record does not report whether it was the planned primary test, what test procedure generated it, or whether other analyses were planned. It also does not report a trial-specific significance threshold. The planning illustration separately specifies a two-sided significance level of 0.05, but that assumption belongs to the planning calculation and should not be attributed to the original trial analysis.

How should the interval be read?

The comparison has an interval estimate extending from a negative value to a positive value, including zero. In general, a confidence interval presents a range of effect estimates compatible with the data and the method's assumptions at a stated confidence level. A range that crosses zero is consistent with both a negative and positive mean difference, as well as no difference. The registry record does not state the confidence level, so it is not appropriate to assign one to the posted interval.

The interval's breadth conveys uncertainty: the estimate does not pin down the mean difference precisely. In general, uncertainty depends on the variability of observations, the amount of information in the analysis, and the analysis method. Here, interpretation is also bounded by the evaluable-video population and the absence of reported details about exclusions and missing data.

What does randomization contribute?

Random allocation is intended, in general, to make comparison groups similar on average with respect to measured and unmeasured characteristics. It supports a causal comparison when allocation, follow-up, outcome measurement, and analysis are implemented appropriately. The registry identifies the study as randomized, but the record does not report the allocation sequence method or concealment details. Randomization does not remove uncertainty, prevent missing data, or ensure that a result generalizes beyond the enrolled population and setting.

The parallel-group model compares separate groups. The quadruple-masked designation indicates the registry's masking classification, but the specific roles masked and masking procedures are not reported. Masking can, in general, reduce the chance that knowledge of assignment influences care or outcome assessment; the record does not allow assessment of how well it was achieved.

What should be kept separate?

The primary endpoint result, planning calculations, and safety counts answer different questions. The endpoint comparison estimates a mean difference in pupil-diameter change. Planning illustrations describe hypothetical participant requirements under stated assumptions. Adverse event counts describe recorded events or affected participants in each listed group. None substitutes for the others.

The registry lists no analyses and no posted secondary outcomes. It does not report multiplicity procedures, a detailed statistical analysis plan, or an analysis population definition beyond the evaluable-video description. These omissions limit assessment of whether the posted comparison represents the prespecified analysis or how other endpoints and missing observations were handled.

10. Confidence Intervals and Precision

The mean difference estimate is 0.06 for phenylephrine HCl compared with OMS302. Its interval extends from a negative value to a positive value, including zero. That pattern means the estimate is not precise enough to rule out no mean difference under the interval's method. It also leaves uncertainty about the direction and magnitude of the underlying difference.

In general, a confidence interval communicates precision by showing a range of values compatible with the observed data and the assumptions used to construct the interval. Narrower intervals indicate more precise estimation; wider intervals indicate greater uncertainty. This interval's inclusion of values on both sides of zero cautions against treating the point estimate as a settled difference. The registry record does not report the confidence level for the interval.

The group standard deviations are 0.474 for OMS302 and 0.6 for phenylephrine HCl. These describe variability among the analyzed observations, not uncertainty in the mean difference itself. The primary outcome is based on evaluable videos, with 30 in the OMS302 group and 31 in the phenylephrine HCl group. The registry reports 61 evaluable videos, one per subject.

Precision is also affected by what was included in the analysis. Subjects with unevaluable videos were excluded, but the number and reasons are not reported. The record does not describe imputation or other missing-data methods. As a result, the interval quantifies uncertainty for the reported comparison, but it cannot resolve possible uncertainty related to video evaluability or selection into the analyzed population.

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 display gives planning illustrations based on the observed effect, not the original trial's design assumptions. These figures are participants per arm, not total participants or total events. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect.

The rows for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect show how the planning estimate changes when the target effect is reduced. For each row, the 80% power column gives the estimated participants per arm for an analysis with an 80% chance of detecting the specified effect under the assumptions. The 90% power column gives the corresponding estimate for a 90% chance. These are conditional planning quantities, not guarantees about a future study.

The displayed participant requirements increase as the effect to detect becomes smaller, because a smaller difference is harder to distinguish from random variation. They also increase when the target power is higher. For example, the displayed estimates for 100% of the observed effect are 1,280 participants per arm for 80% power and 1,714 participants per arm for 90% power. At 75% of the observed effect, the estimates are 2,276 and 3,046 participants per arm; at 50%, they are 5,119 and 6,853 participants per arm.

The curve presents the planning relationship visually; the tabulated values give specific planning scenarios. These are not observed power for this completed trial. The trial's own sample-size justification and original planning assumptions are not reported in the registry record. The enrollment of 78 should not be interpreted as having been chosen under the illustration's assumptions.

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 = 0.060; pooled standard deviation σ = 0.542.
2. n = 2 × (1.96 + 0.842)² × 0.542² / 0.060² = 1,279.7, rounded up to 1,280 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 <- 0.06                      # observed difference in means
sigma <- 0.541742386710992                     # 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(2132312)
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 = 1,280 (80% power), 1,714 (90% power)
 75% of observed effect: n per arm = 2,276 (80% power), 3,046 (90% power)
 50% of observed effect: n per arm = 5,119 (80% power), 6,853 (90% power)
power.t.test: 1280.7 
Simulated power at n = 1,280 per arm: 0.801 (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 three outcome measures and no posted secondary outcome results. It also lists no analyses. The primary endpoint is identified as intraoperative pupil diameter, but details of the full statistical analysis plan are not reported in the registry record. In particular, the record does not report whether multiple outcomes, time points, or analyses were considered in the trial's planned inference.

In general, multiplicity arises when several statistical tests are conducted. The more opportunities there are to identify a result by chance, the more important it can be to specify which outcomes are primary and whether any adjustment or hierarchy is used. The study identifies a primary outcome, but the registry record does not report a multiplicity strategy. The posted p-value is unadjusted, and it should be read as such rather than as evidence that any broader family of tests was controlled.

The record describes the primary analysis population as 61 evaluable videos, one for each subject, and says subjects with unevaluable videos were excluded. The group counts are 30 for OMS302 and 31 for phenylephrine HCl. Reasons for unevaluable videos, the number of excluded videos, and the relationship of this analysis population to all randomized participants are not reported in the registry record.

In general, missing-data handling can affect both the estimate and its uncertainty, especially if missingness is related to outcomes or treatment assignment. The registry record does not report a missing-data method, imputation, sensitivity analysis, or an intention-to-treat analysis population. It is therefore not possible to assess from this record how conclusions might change under alternative assumptions about unavailable video data.

The record also does not report whether interim analyses occurred, whether any stopping rules were used, or whether the posted analysis followed a prespecified plan. These details should not be inferred from the completion status or the reported result.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchiolitis (3.1%), respiratory syncytial virus infection (3.1%).

The serious adverse event figures are recorded separately by group. In the OMS302 group, 2 participants were listed as at risk and affected by serious adverse events; in the phenylephrine HCl group, 0 were listed as at risk and affected. Deaths are recorded as 0 in both groups.

For other adverse events, 15 participants were listed as at risk and affected in the OMS302 group, and 18 in the phenylephrine HCl group. These counts should be read in the context of the separate group-specific at-risk figures: 32 for OMS302 and 40 for phenylephrine HCl. The counts are descriptive registry entries and do not establish that an event was caused by a study drug.

The registry lists bronchiolitis and respiratory syncytial virus infection among the top serious event terms, each with 3.1%. The record does not specify an arm for those terms in the summary information. It also does not provide enough detail to characterize event timing, duration, severity beyond the serious classification, or relatedness assessments.

In general, adverse-event counts are not a substitute for a comparative safety analysis. Differences in group size, follow-up, definitions, and reporting can affect interpretation. The record's safety figures should therefore be treated as descriptive, not as proof of a causal safety difference.

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

The posted primary result describes a mean difference of 0.06 in the intraoperative pupil-diameter area-under-the-curve change-from-baseline measure, with group means of 0.14 for OMS302 and 0.2 for phenylephrine HCl. The unadjusted p-value is 0.664, and the interval includes zero. These statistics indicate that the observed comparison is uncertain and do not establish a clear difference in the primary endpoint.

This result does not establish equivalence. Equivalence requires a defined margin and an analysis designed to test whether effects fall within that margin; the registry record does not report such a margin or analysis. Nor does the result show that the true difference is exactly zero. The interval includes values on both sides of zero, and the point estimate remains subject to sampling uncertainty.

The finding is specific to the posted endpoint, the surgical setting, and the analyzed videos. It does not by itself answer whether either irrigation solution affects other outcomes named in the study summary, including acute postoperative pain. No secondary outcome result is posted. The separate safety entries are descriptive and do not establish causation or a comparative safety conclusion.

General statistical interpretation separates evidence of an effect from its size and clinical importance. A p-value does not tell whether a difference matters to patients, and an estimated difference cannot be labeled clinically meaningful without an appropriate benchmark. The registry record does not report such a benchmark for pupil diameter.

The study's randomized and masked design is relevant to the credibility of comparisons, but the record does not describe allocation procedures, specific masking roles, missing-data handling, or a detailed analysis plan. Those limits, along with exclusion of subjects with unevaluable videos, constrain how broadly the posted estimate can be interpreted. The result is best understood as an uncertain estimate for the primary analysis population, not as a general conclusion about treatment effects in all children or settings.

16. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can produce a point estimate that is easy to state but not precise enough to settle the direction or size of an effect. The mean difference is 0.06, while the interval spans both negative and positive values and the unadjusted p-value is 0.664. Reading these quantities together is more informative than focusing on the point estimate alone.

The endpoint also shows why the analysis population matters. The primary measure uses video data collected across the operation, and the registry reports 61 evaluable videos, one for each subject. Excluding subjects with unevaluable videos defines the population represented by the analysis. Without reported reasons for missing or unevaluable data, the potential effect of that exclusion remains uncertain.

The record distinguishes the primary measure from other study aims. Acute postoperative pain and safety appear in the study summary, yet no secondary results are posted. A statistical reader should not transfer the primary endpoint finding to those other outcomes. Similarly, safety counts require separate descriptive interpretation rather than being folded into the efficacy comparison.

The planning illustrations underscore that sample-size requirements depend on the effect targeted and the desired power. They are hypothetical calculations based on the observed effect and specified assumptions, not evidence that the completed trial had adequate power or that the observed result is reliable. The trial's original sample-size reasoning is not reported.

Overall, the record is a useful case in separating design labels, outcome definition, uncertainty, missingness, and planning from conclusions. Each contributes a different part of the statistical interpretation, and none alone resolves the limitations of the posted result.

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 primary analysis excludes subjects with unevaluable videos. The registry reports 61 evaluable videos, one for each subject, but does not report why some videos were unevaluable or how many were excluded. Without that information, it is not possible to judge whether evaluability was related to treatment assignment, participant characteristics, or the endpoint itself.

The registry's description of the endpoint contains differing unit notations: the unit is listed as millimeters*minutes, while the endpoint description uses mm/min. The record does not clarify this notation. That limits clarity about the scale and interpretation of the reported means and mean difference.

The endpoint is an area-under-the-curve summary across an operation, while surgery duration varied, with a reported mean of 35.46 minutes and standard deviation of 19.98. The record does not describe whether or how duration was accounted for beyond defining the measurement window. This should not be taken to imply a flaw, but it leaves an analytic detail unresolved.

The record does not report the trial's original sample-size assumptions, a clinically meaningful difference, a detailed statistical analysis plan, or a multiplicity strategy. It also does not report the confidence level for the interval estimate, allocation-generation details, masking roles, or missing-data sensitivity analyses. No secondary results are posted despite the study summary's mention of acute postoperative pain. These gaps limit assessment of the complete analysis and the broader set of study aims.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Randomized Study in Children Ages Birth Through Three Years Undergoing Unilateral Cataract Extraction With or Without Lens Replacement — NCT02132312.
• Registry record last updated 2021-07-22; status last verified 2021-07.
• Results first posted 2021-07-22.
• 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

NCT02132312 is a completed Phase 3 randomized, quadruple-masked, parallel-group study sponsored by Omeros Corporation. It enrolled 78 children from birth through 3 years undergoing unilateral cataract extraction, with or without lens replacement. The comparison was OMS302 versus phenylephrine HCl, each diluted in balanced salt solution and used as irrigation solution.

The primary outcome was intraoperative pupil diameter, analyzed as mean area under the curve of change from baseline during surgery. The posted means were 0.14 for OMS302 and 0.2 for phenylephrine HCl; the reported mean difference was 0.06, with an unadjusted p-value of 0.664. The interval includes zero. The primary analysis used 61 evaluable videos, one per subject.

The registry lists safety figures but no posted secondary outcome results and no analyses. The study's original sample-size justification, detailed analysis plan, and missing-data methods are not reported in the registry record.