Japanese Phase 3 Study of Aflibercept in Neovascular Glaucoma Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Japanese Phase 3 Study of Aflibercept in Neovascular Glaucoma Patients (NCT02396316), a randomized phase 3 study. The primary outcome is Change in Intraocular Pressure (IOP) From Baseline to Pre-dose at Week 1.

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel-group Phase 3 study. It compared aflibercept 2 mg by intravitreal injection with sham injection in Japanese patients with neovascular glaucoma. The registry record lists 54 participants enrolled and shows 27 participants in each group for the primary outcome. The trial status is completed.

Random allocation is intended to make the treatment groups comparable, on average, with respect to factors that could influence outcomes. Masking is intended to reduce the influence of expectations on care, outcome assessment, and reporting. The record labels the study triple-masked, but does not specify which individuals or roles were masked, or how masking was maintained.

The parallel design means participants were assigned to one group rather than receiving both study procedures in sequence. The main comparison therefore concerns the outcome distributions in the two randomized groups. The registry record identifies the primary endpoint as change in intraocular pressure from baseline to pre-dose at Week 1. It also reports a secondary outcome concerning improvement in iris neovascularization grade over the same interval.

The record gives the enrollment total and the analysis-group counts, but the exact number randomized and the number included in each analysis are not separately described beyond the outcome counts. The original sample-size justification, planned allocation details beyond the randomized design, masking procedures, and any protocol-specific analysis decisions are not reported in the registry record. The record also does not give a detailed account of participant flow or reasons for any exclusions. These omissions limit how fully the conduct and design rationale can be reconstructed from the registry entry alone.

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: A total of 63 subjects were screened and 54 subjects were randomized into the aflibercept group (N=27) and the sham group (N =27).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS: The Full Analysis Set (FAS) included all randomized subjects who have received any study drug (including sham injection) and had had a baseline and at least one post-baseline IOP measurement on a posterior date. The FAS was analyzed as randomized.

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 Change in Intraocular Pressure (IOP) From Baseline to Pre-dose at Week 1, measured over From baseline to pre-dose at Week 1.

The primary endpoint measures the change in intraocular pressure from baseline to the pre-dose assessment at Week 1. Intraocular pressure is recorded in mmHg, and the registry describes the endpoint using the mean change. A change value represents the difference between the follow-up measurement and baseline as defined by the study; negative group means indicate a decrease over that interval. The endpoint compares the average change in the aflibercept group with the average change in the sham group.

Change from baseline is used in clinical trials to describe how a measurement moves during the specified follow-up period, while retaining the baseline reading as the reference point. Comparing changes between randomized groups can help distinguish the observed course in the intervention group from changes that also occur in the control group. A sham comparison is relevant because procedures, attention, and the natural course of a condition may influence measurements independently of the active intervention.

The recorded time point is limited: the outcome is assessed at pre-dose at Week 1, not over a longer follow-up period. The registry record does not report a longer-term primary assessment in this entry. Nor does it provide a minimum clinically important change or a threshold for interpreting a difference in mmHg. Statistical evidence about the group contrast therefore needs to be read alongside the short assessment interval and the uncertainty around the estimated difference.

7. Results Posted in the Registry

• Aflibercept 2 mg Intravitreal (IVT) Injection Group: mean -8.50 versus -4.90 on control; difference -3.60 (95% CI -8.83 to 1.63), standardized effect d = -0.37; z-test p = 0.177.

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.

Percentage of Subjects Who Had Improved Neovascularization of the Iris (NVI) Grade From Baseline to Pre-dose at Week 1

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Aflibercept 2 mg Intravitreal (IVT) Injection Group: 70.4% (19/27) versus 11.1% (3/27) on control; risk difference 59.3 percentage points (95% CI 38.4 to 80.2), risk ratio 6.33 (2.12–18.92); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Aflibercept 2 mg Intravitreal (IVT) Injection Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry reports one secondary endpoint: improvement in neovascularization of the iris grade from baseline to pre-dose at Week 1. This measures a different clinical feature from intraocular pressure, even though both are assessed over the same interval. It therefore adds information about a separate outcome rather than providing a second measurement of the primary endpoint.

The secondary result has a distinct pattern from the primary intraocular-pressure comparison: its posted group percentages are separated, and the recalculated interval for the risk difference does not include zero. The registry’s Mantel Haenszel estimate is also reported with a confidence interval. These results should be read using their stated methods and scales, and should not be taken to resolve the uncertainty around the primary outcome. A finding for one endpoint does not automatically establish the same pattern for another.

Secondary outcomes are often useful for exploring additional aspects of a trial, but they typically carry less confirmatory weight than the designated primary outcome. When multiple outcomes are assessed, the opportunity for at least one result to appear noteworthy by chance can increase. The registry record does not report a multiplicity adjustment or a hierarchy for testing the primary and secondary outcomes. The secondary p-value from the recalculation is unadjusted, and the registry does not report a p-value for its Mantel Haenszel analysis. Those features make cautious interpretation appropriate.

The record reports only one secondary outcome in this entry, while also stating that there are two outcome measures and two analyses overall. It does not provide a fuller endpoint hierarchy or explain whether other planned outcomes were omitted from the posted results. The secondary finding can be considered alongside the primary result, but not as a replacement for a prespecified primary comparison or as evidence about outcomes that were not reported.

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

• Percentage of Subjects Who Had Improved Neovascularization of the Iris (NVI) Grade From Baseline to Pre-dose at Week 1

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: intraocular pressure is measured on a numerical scale, and the registry reports the mean change and standard deviation for each group. A mean summarizes the center of the observed measurements. A standard deviation describes how spread out participant-level values are around the group mean. Greater spread means individual outcomes vary more, which can make a group comparison less precise even when group averages differ.

What does the unadjusted mean difference represent?

The recalculated primary contrast is the aflibercept group mean change minus the sham group mean change. It is -3.6 mmHg. Because more negative change represents a larger decrease over the interval, the negative contrast points toward a larger mean decrease in the aflibercept group. This is a simple, unadjusted comparison based on the posted group summaries. It does not account for baseline values or other participant characteristics through a regression model.

The reported group standard deviations are 8.7 mmHg for aflibercept and 10.8 mmHg for sham. The recalculation uses a pooled standard deviation of 9.806 mmHg and reports a standardized effect estimate of -0.367. A standardized effect expresses a mean contrast relative to variability, which can aid comparison across scales; it does not replace the original-unit estimate or its confidence interval. The registry record does not report an adjusted standardized effect for the primary outcome.

Why can an adjusted analysis differ from a simple comparison?

The registry reports an ANCOVA analysis with a difference of least-squares mean change. ANCOVA is a regression approach that can estimate a group contrast while adjusting for selected covariates. Least-squares means are model-based estimates, rather than simple arithmetic averages of the observed group outcomes. When an analysis adjusts for baseline or other variables, its estimate may differ from a contrast calculated directly from group means. The registry record does not report the model covariates, the treatment of missing observations in that model, or further model diagnostics. It is therefore not possible to attribute the numerical difference to a particular modeling choice.

The recalculated p-value for the primary contrast is 0.177. A p-value describes how unusual data at least this discrepant would be under a specified null model and its assumptions; it is not the probability that the null hypothesis is true. The sponsor-reported p-value is 0.064 for its ANCOVA analysis. The two p-values relate to distinct analyses and should not be treated as interchangeable. The confidence intervals are more informative about the range of effects compatible with each estimate, subject to each analysis’s assumptions.

How should the binary secondary outcome be read?

The secondary endpoint is a binary status: whether a participant had an improved iris neovascularization grade from baseline to pre-dose at Week 1. The group percentages summarize the proportion meeting that outcome. The recalculated risk difference is the aflibercept proportion minus the sham proportion, expressed as a proportion, and is reported as 0.593. Its interval from 0.384 to 0.802 describes uncertainty in that unadjusted contrast. The recalculated p-value is < 0.001. The registry’s own analysis used a Mantel Haenszel method and reported an adjusted difference of 59.1 with a 95% confidence interval from 37.0 to 81.2. The registry record does not report a p-value for that analysis.

For binary outcomes, the risk difference describes the difference between the two group proportions. It remains tied to the observed outcome definition and follow-up time. Other relative measures can describe the contrast differently, but should not be substituted for the absolute difference without considering the question being asked. The posted summaries do not provide a detailed account of any stratification used for the Mantel Haenszel analysis.

Why does over-dispersion matter in general?

In general, over-dispersion means that observed variability is greater than a statistical model expects. For count or binary data, this can make standard errors too small if the model assumes less variability than the data contain. Wider uncertainty intervals may be appropriate when over-dispersion is present. The registry record does not report an over-dispersion assessment, and the outcomes do not establish whether it was a concern for the sponsor’s analyses.

All recalculated estimates are descriptive re-analyses of posted summaries, not replacements for the registry’s own analyses. They cannot reproduce participant-level adjustment, account for unreported design features, or verify the assumptions used in the sponsor’s model. Interpretation should keep the endpoint, time point, analysis method, and uncertainty together rather than focusing on a single point estimate or p-value.

11. Confidence Intervals and Precision

Confidence intervals communicate uncertainty around an estimated effect. They indicate a range of values that are compatible with the data and the statistical procedure, under its assumptions. They are not guarantees that the true effect lies within the reported range, and they do not describe the range of outcomes for individual participants.

For the recalculated primary comparison, the estimated mean difference is -3.6 mmHg, with a 95% confidence interval from -8.831 to 1.631. The interval includes zero, which represents no average difference between groups. It also includes values favoring either direction. This means the observed point estimate is not highly precise as a standalone description of the group contrast. The estimate is compatible with a range of differences, including no difference, rather than identifying a narrow effect.

The registry-reported ANCOVA estimate is -4.9 mmHg, with a 95% confidence interval from -10.2 to 0.3. This interval also includes zero. Its endpoints indicate that the adjusted estimate remains uncertain, despite the negative point estimate. Because the sponsor analysis and the unadjusted recalculation use different methods, their intervals should be interpreted as results from their respective analyses, not as repeated estimates from one model.

For the secondary outcome, the recalculated risk difference has a 95% confidence interval from 0.384 to 0.802. The registry-reported Mantel Haenszel adjusted difference has a 95% confidence interval from 37.0 to 81.2. Both intervals are reported with their own analysis scales and should not be conflated. The registry record does not report a p-value for the Mantel Haenszel analysis.

Precision depends on factors such as the number of analyzed participants, outcome variability, and the analysis method. The primary comparison has 27 participants per group in the posted outcome summaries, and the reported standard deviations indicate participant-level variation. The confidence intervals make that uncertainty visible; a point estimate alone would not. The short follow-up also constrains what these estimates can say about longer-term patterns.

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

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the selected effect under the stated assumptions, if that effect were the true one. The 90% power column gives the corresponding number per arm for a design with a 90% chance. These are planning concepts, not probabilities that the observed result is correct or that a treatment has a particular effect.

For the primary continuous outcome, the planning illustration at 100% of the observed effect gives 117 participants per arm for 80% power and 156 participants per arm for 90% power. At 75% of the observed effect, the figures are 208 and 278 participants per arm. At 50% of the observed effect, they are 466 and 624 participants per arm. For the secondary binary outcome, the corresponding figures are 10 and 13 participants per arm at 100% of the observed effect, 17 and 22 at 75%, and 34 and 44 at 50%.

Smaller effects are harder to distinguish from random variation, so detecting a smaller effect generally requires more participants under otherwise similar assumptions. The two outcomes have different scales and observed effects, so their planning illustrations should not be compared as if they were estimates of the same question. These figures are not observed power: they do not measure the probability that the completed trial detected an effect, and they do not change the uncertainty in the posted results.

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 = -3.600; pooled standard deviation σ = 9.806.
2. n = 2 × (1.96 + 0.842)² × 9.806² / -3.600² = 116.5, rounded up to 117 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 <- -3.6                      # observed difference in means
sigma <- 9.80637547720869                     # 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(2396316)
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 = 117 (80% power), 156 (90% power)
 75% of observed effect: n per arm = 208 (80% power), 278 (90% power)
 50% of observed effect: n per arm = 466 (80% power), 624 (90% power)
power.t.test: 117.4 
Simulated power at n = 117 per arm: 0.800 (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’s own primary analysis is an ANCOVA comparing the difference of least-squares mean change between groups. It reports an estimate of -4.9 mmHg, a 95% confidence interval from -10.2 to 0.3, and p = 0.064. The simple recalculation from the posted group summaries estimates an unadjusted mean difference of -3.6 mmHg, with a 95% confidence interval from -8.831 to 1.631 and p = 0.177.

These values are not a direct disagreement over one identical calculation. The recalculation uses the two group means and their reported variability without covariate adjustment. ANCOVA is a model-based adjusted analysis, and its estimate can differ from a simple difference in observed means. The registry record does not describe the ANCOVA covariates or all model details, so the source of the numerical difference cannot be determined from the record.

Both analyses place the primary estimate in the direction of a larger mean decrease in the aflibercept group, and both confidence intervals include zero. The registry analysis is the trial’s reported analysis and should be distinguished from the unadjusted recalculation rather than replaced by it. The latter is useful as a transparent check based on the posted summaries, but it does not reproduce the participant-level adjusted model. No discrepancy between the posted values and the recalculation is flagged in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, time points, groups, or statistical contrasts. The more tests considered, the greater the chance that at least one may appear unusual under a null model even when there is no underlying effect for that test. Statistical plans may address this through a prespecified hierarchy, adjusted significance thresholds, or other procedures. The registry record does not report a multiplicity strategy for this trial. The secondary recalculated p-value is unadjusted, so it should not be interpreted as if it accounted for testing across outcomes.

The registry describes the Full Analysis Set as randomized participants who received any study drug, including sham injection, and had a baseline and at least one post-baseline intraocular-pressure measurement on a posterior date. It says this set was analyzed as randomized. This description identifies eligibility for the primary analysis, but it does not provide a complete account of missing-data handling, the number of participants excluded from each endpoint, or how incomplete measurements were treated. The registry record does not report those details.

For the secondary endpoint, the record gives group denominators and outcome percentages, but does not describe the handling of missing iris-grade assessments or whether the analysis population differed from the primary Full Analysis Set. It also does not report sensitivity analyses for missing data. If outcome availability differs between groups or is related to the outcome itself, estimates may be affected; the available registry information does not establish whether that occurred.

The randomized design and the stated analysis-as-randomized approach are relevant strengths in understanding the comparison, but the registry description is not enough to verify every aspect of an intention-to-treat analysis. The record does not report a detailed participant flow, reasons for discontinuation, protocol deviations, or analysis-population counts beyond the posted outcome denominators. The original statistical analysis plan, prespecified model details, and any interim analyses are also not reported in the registry record. These gaps limit assessment of prespecification and robustness, particularly for secondary results.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: myocardial ischaemia (3.7%), diabetic retinopathy (3.7%), retinal artery occlusion (3.7%), retinal vein occlusion (3.7%), pancreatic carcinoma (3.7%).

The registry reports serious adverse events for 27 participants at risk in each group. Three participants in the aflibercept group and three in the sham group were reported as affected by a serious adverse event over the listed study period. The record also reports other adverse events affecting 10 participants in the aflibercept group and 12 in the sham group. These are descriptive counts, not a formal comparison of risk, and the registry entry does not provide a statistical analysis of the safety contrast.

For the period through pre-dose at Week 1, the record lists zero participants affected by serious adverse events in each group, and other adverse events affecting six in the aflibercept group and seven in the sham group. The registry also lists serious adverse event terms, each with a reported percentage of 3.7%. These event terms are not necessarily counts of distinct participants; the record does not explain whether participants could contribute more than one term.

Deaths are not reported in the registry record. The record does not provide a detailed narrative of event timing, severity beyond the serious classification, relatedness assessments, or withdrawals due to adverse events. The figures should therefore be read as the registry’s posted safety summaries, not as a complete account of every event or a basis for causal conclusions.

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

The primary endpoint estimates the contrast in mean intraocular-pressure change between randomized groups at pre-dose at Week 1. The observed group means both show decreases, with a more negative point estimate in the aflibercept group. However, the unadjusted and registry-reported adjusted confidence intervals both include zero. The data therefore leave substantial uncertainty about the magnitude and direction of the between-group difference at that time point. The reported estimates should not be reduced to a binary label based only on a p-value.

The secondary iris neovascularization result is a separate outcome, with a more separated observed group pattern and a recalculated unadjusted p-value below 0.001. It does not answer the same question as the primary endpoint. The lack of a reported multiplicity strategy, along with the absence of a registry-reported p-value for the adjusted secondary analysis, matters when weighing this finding. It should be understood as evidence about the stated secondary measure and interval, not as a universal conclusion about all outcomes.

These results do not establish what happens beyond pre-dose at Week 1, because longer-term estimates are not reported in the registry record. They also do not establish effects in populations or settings outside the Japanese patients described in the trial record. The outcome summaries do not specify a threshold for a clinically important change in intraocular pressure, so statistical estimates alone cannot determine the practical importance of the observed differences.

The trial record provides a randomized comparison and posted outcome estimates, but incomplete information about the original analysis plan, missing-data handling, and several design details limits independent assessment. Safety summaries are also descriptive and do not establish that events were or were not caused by either study procedure. The most defensible reading is therefore tied to the observed endpoints, methods, and follow-up actually reported, with uncertainty retained rather than converted into a broader claim.

18. Why This Trial Matters Statistically

This trial illustrates why a point estimate, a confidence interval, and a prespecified analysis all matter. The primary point estimate is in one direction, but its interval includes no difference and a range of effects on either side. A reader who focused only on the group means could miss the uncertainty in the between-group comparison. The registry’s ANCOVA estimate is not identical to the unadjusted recalculation, which highlights how adjustment and model specification can affect reported estimates.

It also demonstrates that separate endpoints can tell different statistical stories. The primary outcome concerns change in intraocular pressure, while the secondary outcome concerns improvement in iris neovascularization grade. A result on one measure does not automatically settle the other. Interpreting the secondary result also requires attention to multiplicity and to whether its analysis was prespecified, details that are not reported in the registry record.

The study is a useful example of the difference between trial planning and trial evidence. Planning illustrations based on observed effects can show how assumed effect size, power target, and sample size relate under stated assumptions. They do not reconstruct the trial’s original design rationale, which is not reported, and they do not represent observed power. The posted outcome uncertainty remains central to interpretation.

Finally, registry summaries are informative but not a substitute for full protocol and analysis-plan details. The description of the Full Analysis Set, reported estimates, and safety counts can orient statistical reading, while missing information about covariates, missing data, multiplicity, and participant flow constrains how deeply the analysis can be audited. Recognizing both what the record documents and what it leaves unresolved is essential to a balanced statistical interpretation.

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 primary assessment is at pre-dose at Week 1, so the posted primary result addresses a short interval. Longer-term outcomes are not reported in the registry record. The registry does not give a clinically important threshold for interpreting the size of an intraocular-pressure difference, which limits translation of the statistical estimates into claims about practical importance.

The outcome summaries include 27 participants per group, but a full participant-flow account is not reported in the registry record. The Full Analysis Set definition requires a baseline and at least one post-baseline intraocular-pressure measurement, yet the number excluded under that definition and the reasons are not described. Missing-data methods, sensitivity analyses, and the treatment of incomplete secondary outcome assessments are also not reported.

The registry’s primary ANCOVA result is reported without the covariates or full model specification. That limits independent reproduction and prevents a more specific explanation of its difference from the unadjusted summary-statistic recalculation. The original sample-size justification, interim analyses, and statistical analysis plan are not reported in the registry record. Nor is a multiplicity procedure described for the secondary outcome.

The record labels the trial triple-masked but does not identify the masked roles or explain how masking was implemented. It also does not provide a detailed account of protocol deviations, treatment adherence, or withdrawals. The safety summaries do not include a full narrative of event timing or relatedness, and deaths are not reported in the registry record. These limitations do not negate the posted results, but they constrain assessment of bias, robustness, and the completeness of the trial account.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Japanese Phase 3 Study of Aflibercept in Neovascular Glaucoma Patients — NCT02396316.
• Registry record last updated 2017-09-15; status last verified 2017-08.
• Results first posted 2017-07-21.
• 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

The registry record describes a completed randomized, triple-masked, parallel-group Phase 3 study of aflibercept 2 mg intravitreal injection versus sham injection in Japanese patients with neovascular glaucoma. It lists 54 participants enrolled, with 27 participants per group in the posted primary outcome summaries.

The primary outcome was mean change in intraocular pressure from baseline to pre-dose at Week 1. The registry-reported ANCOVA estimate was -4.9 mmHg, with a 95% confidence interval from -10.2 to 0.3 and p = 0.064. The unadjusted recalculation was -3.6 mmHg, with a 95% confidence interval from -8.831 to 1.631 and p = 0.177.

The secondary outcome concerned improved iris neovascularization grade at the same time point. Its registry-reported adjusted difference was 59.1, with a 95% confidence interval from 37.0 to 81.2. The record also reports serious adverse events affecting three participants in each group over the listed study period. Important details about the original sample-size rationale, missing data, multiplicity, and model specification are not reported in the registry record.