OTX-14-003: A Phase 3 Study Evaluating the Safety and Efficacy of OTX-DP for the Treatment of Ocular Inflammation and Pain After Cataract Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for OTX-14-003: A Phase 3 Study Evaluating the Safety and Efficacy of OTX-DP for the Treatment of Ocular Inflammation and Pain After Cataract Surgery (NCT02089113), a randomized phase 3 study. The primary outcome is Number of Participants With an Absence of Anterior Chamber Inflammation.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, parallel-arm, double-masked, vehicle-controlled study evaluating OTX-DP for ocular inflammation and pain after cataract surgery. The official title describes it as prospective, multicenter, and Phase 3B. The registry record lists enrollment of 241 and a completed status. It gives the study start as 2014-04 and primary completion as 2015-01.

The OTX-DP arm received a dexamethasone insert at 0.4 mg for intracanalicular use. The comparator was a placebo drug delivery vehicle. The study objective was to evaluate safety and efficacy when the insert was placed in the eyelid canaliculus in participants following cataract extraction with intraocular lens implantation. Other procedural details, including the schedule of study visits beyond the primary endpoint timeframe, are not reported in the registry record.

The primary endpoint was the number of participants with absence of anterior chamber inflammation at Day 14, defined as no cells in the anterior chamber of the study eye, or a score of 0. The posted arm counts for that endpoint are 63 of 161 in the OTX-DP arm and 25 of 80 in the Placebo Vehicle arm. The adverse-event results use different arm denominators: 160 and 80 participants at risk for the reported serious and other adverse-event counts. The registry record does not explain the difference between the OTX-DP endpoint and safety denominators.

Details about the randomization procedure, allocation concealment, masking procedures, stratification, and analysis populations are not reported in the registry record. The registry record also does not report the original sample-size justification or the statistical analysis plan.

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

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 Number of Participants With an Absence of Anterior Chamber Inflammation, measured over Day 14.

The primary endpoint counts participants whose study eye had no cells in the anterior chamber at Day 14. The record defines absence as a cell score of 0. This is a binary outcome: each participant either met the stated endpoint at that assessment or did not. The posted counts are 63 of 161 participants in the OTX-DP arm and 25 of 80 in the Placebo Vehicle arm.

Anterior chamber cells are the recorded sign used for this endpoint to describe ocular inflammation. Counting participants who reach the defined absence state provides a direct comparison of the proportion meeting that endpoint in each randomized arm. It does not describe the full course of inflammation over time, nor does it capture every aspect of ocular inflammation or pain. The endpoint timeframe is Day 14; results at other timepoints are not reported in the registry record.

Endpoint definitions matter when interpreting the comparison. This result concerns the specified threshold—no cells, score 0—not a change in average inflammation score or a separate pain measure. The registry record lists two outcome measures but posts no secondary outcomes. It therefore does not provide a broader set of outcome results with which to assess other aspects of the study objective.

7. Results Posted in the Registry

• OTX-DP: 39.1% (63/161) versus 31.2% (25/80) on control; risk difference 7.9 percentage points (95% CI -4.8 to 20.5), risk ratio 1.25 (0.86–1.83); unadjusted two-proportion z-test p = 0.231.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint count?

A binary endpoint assigns each participant to one of two outcome states under a defined rule. In this study, the rule is absence of cells in the anterior chamber of the study eye at Day 14, defined as a score of 0. The posted event counts are 63 of 161 for OTX-DP and 25 of 80 for Placebo Vehicle. The corresponding proportions listed in the comparison are 0.391 and 0.312. These values describe the share in each arm meeting the endpoint, rather than a mean score or a change from baseline.

What does the risk difference express?

The risk difference puts the arm comparison on an absolute scale: it expresses the difference between the proportions meeting the endpoint. The unadjusted recalculated estimate is 0.079. A value of zero represents no difference on this scale. Its 95% confidence interval is -0.048 to 0.205, so the estimate is not precise enough to rule out zero or differences in either direction within that interval. The interval is an estimate of uncertainty about the risk difference, not a range containing a specified share of individual participant outcomes.

Why are risk ratios and odds ratios also reported?

A risk ratio compares the arm proportions as a ratio, while an odds ratio compares the odds of meeting the endpoint. The reported risk ratio is 1.252, with a 95% confidence interval from 0.858 to 1.827. The reported odds ratio is 1.414, with a 95% confidence interval from 0.801 to 2.498. For each ratio, a value of 1 represents no relative difference. Both intervals include 1. These measures provide alternative scales for the same binary outcome; they are not separate endpoint findings.

For a binary endpoint, the odds and the proportion are related but are not identical quantities. The odds ratio should therefore not be described as a percentage-point difference or as the same thing as a risk ratio. The risk difference is often the most direct scale for expressing an absolute contrast, while ratio measures express a relative contrast. Each estimate should be read with its interval and with the endpoint definition in mind.

How should the p-value be read?

The unadjusted p-value is 0.231. In general, a p-value describes how compatible the observed data are with a specified null model under the assumptions of the statistical test. It does not give the probability that the null is true, and it does not measure the size or importance of an effect. The registry record does not identify the sponsor's test or report a sponsor analysis for this endpoint. The comparison is an unadjusted recalculation from posted summary statistics, so it should not be mistaken for a reported adjusted trial analysis.

A p-value cannot replace the estimate and its confidence interval. Here, the interval for the risk difference includes zero, while the point estimate is positive. Together these details describe both the direction of the estimate and its uncertainty; the p-value alone does not establish that the arms differ or that they are the same.

What can be concluded about the analysis method?

The registry record identifies the trial as randomized and double-masked, but does not report details of the randomization method, primary statistical model, covariate adjustment, or analysis population. It does not report whether there were interim analyses or how missing observations were handled. Those details cannot be inferred from the counts or the calculated comparisons. In particular, a simple unadjusted comparison cannot substitute for a missing prespecified analysis plan.

The posted summary reports a binary endpoint, counts, and unadjusted effect estimates. Without further analysis details, readers cannot determine whether the sponsor's intended analysis differed from this calculation, whether participants were analyzed according to randomized assignment, or whether additional adjustments were planned. The registry record does not report these matters.

Why does over-dispersion matter in general?

Over-dispersion is a general concern for outcomes modeled as counts when their variability exceeds what the chosen model expects. It can make uncertainty estimates too small if it is ignored. It is not an issue that can be assessed from this endpoint summary: the primary outcome is a count of participants meeting a binary condition, and the registry record does not report a count model or an over-dispersion assessment. It would be inappropriate to infer that such a model was used.

10. Confidence Intervals and Precision

The risk difference estimate is 0.079, and its 95% confidence interval runs from -0.048 to 0.205. In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the method used to calculate it. It is not a guarantee that the true value falls inside the interval, nor does it describe the range of outcomes among individual participants.

The interval includes zero, the value representing no difference in the risk-difference scale. It also includes values below zero and above zero. Accordingly, the observed positive point estimate should not be read as a precise estimate of a positive difference. The width of the interval reflects material uncertainty about both direction and magnitude.

The risk ratio of 1.252 has a 95% confidence interval from 0.858 to 1.827, and the odds ratio of 1.414 has a 95% confidence interval from 0.801 to 2.498. The no-relative-difference value for these ratio measures is 1, and each interval includes it. The ratio intervals therefore also leave uncertainty about whether there is a relative difference.

Precision depends in part on the amount of information in the data, but the registry record does not report a formal precision target for this endpoint. The total enrollment is 241, while the endpoint arm denominators are 161 and 80. The registry record does not explain whether any participants were excluded from this endpoint analysis or why its denominators differ from the safety denominators. The observed counts and intervals describe the posted summary, not missing or unreported outcomes.

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 planning illustrations give participants per arm for 80% power and participants per arm for 90% power. They use equal allocation between the two arms and a two-sided significance level of 0.05, with a normal approximation. The effect to detect is set at the stated fraction of the observed effect: the full observed effect, 75% of the observed effect, or 50% of the observed effect.

For the full observed effect, the illustration gives 576 participants per arm for 80% power and 770 participants per arm for 90% power. For 75% of the observed effect, it gives 1,011 participants per arm for 80% power and 1,352 participants per arm for 90% power. For 50% of the observed effect, it gives 2,242 participants per arm for 80% power and 3,001 participants per arm for 90% power. These are planning illustrations calculated from the observed effect, not the trial's original design assumptions; the original design assumptions are not reported in the registry record.

In general, 80% power means an 80% chance of detecting the specified effect under the assumptions of the planning calculation if that effect is present. The 90% column describes the corresponding chance as 90%. Seeking greater power or planning to detect a smaller effect requires more participants. The illustrations are not observed power.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.312; treatment proportion p₁ = 0.391; average p̄ = 0.352.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6754 = 1.3237.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6731 = 0.5665.
4. n = (1.3237 + 0.5665)² / (0.0788)² = 575.3, rounded up to 576 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
p0 <- 0.3125                          # control proportion
p1 <- 0.391304347826087                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2089113)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 576 (80% power), 770 (90% power)
 75% of observed effect: n per arm = 1,011 (80% power), 1,352 (90% power)
 50% of observed effect: n per arm = 2,242 (80% power), 3,001 (90% power)
power.prop.test: 575.3 
Simulated power at n = 576 per arm: 0.800 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 record lists two outcome measures, but posts no secondary outcome results. It gives no multiplicity adjustment or testing hierarchy. Multiplicity arises in general when several outcomes, timepoints, or comparisons are tested: without an appropriate plan, the chance of at least one apparently notable result can increase. The record does not provide enough information to determine whether multiplicity was addressed in the study analysis.

The primary endpoint is specified at Day 14. Other endpoint timepoints, additional primary endpoints, and the intended handling of multiple comparisons are not reported in the registry record. The posted unadjusted comparison should therefore be read as a single endpoint comparison, not as evidence about a broader testing strategy.

Missing-data handling is also not reported in the registry record. It does not state whether observations were missing, how any missing endpoint assessments were treated, or whether imputation or sensitivity analyses were used. The endpoint counts and denominators alone do not establish how participants without an assessment were handled.

The analysis populations are not described. The registry record does not state whether the analysis followed randomized assignment, was restricted to participants meeting additional criteria, or used another population definition. Nor does it report the sponsor's statistical model, covariate adjustments, or the analysis plan for the endpoint. These omissions limit assessment of whether the unadjusted recalculation matches the prespecified trial analysis. They do not justify assuming a particular method or that any specific type of analysis was performed.

14. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: mental disorder (1.2%).

The serious adverse-event summary lists 0 affected participants among 160 at risk in the Dexamethasone Punctum Plug group and 1 among 80 at risk in the Placebo Vehicle Punctum Plug group. The other adverse-event counts are 0 among 160 and 0 among 80, respectively. These are descriptive counts with the listed denominators, not adjusted comparisons. The safety denominators differ from the primary endpoint denominators, and the registry record does not explain that difference.

The record lists mental disorder at 1.2% among its top serious terms. It does not identify an arm for that term in the posted summary, so it cannot be assigned to either group from this information. Deaths are not reported in the registry record; a missing death count should not be interpreted as zero. The registry record does not provide additional context about event timing, relatedness, severity beyond the serious-event classification, or the criteria for inclusion in the safety summary.

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

The posted primary result describes the number of participants with no cells in the anterior chamber of the study eye at Day 14. The count was 63 of 161 in the OTX-DP arm and 25 of 80 in the Placebo Vehicle arm. The unadjusted recalculated risk difference is 0.079, with a 95% confidence interval from -0.048 to 0.205 and an unadjusted p-value of 0.231. The point estimate favors a higher proportion meeting the stated endpoint in the OTX-DP arm, while the interval indicates substantial uncertainty about the size and direction of the underlying difference.

This result does not establish that there is no difference between the arms. The interval includes zero and values on both sides of zero, so the estimate is compatible with more than one interpretation. It also does not establish a definite difference. The confidence interval and p-value should be considered with the actual endpoint counts and the limitations of the registry summary.

The finding is specific to absence of anterior chamber cells at Day 14. The registry record does not post a pain endpoint result or secondary outcome results, despite the study objective referring to both inflammation and pain. The result therefore does not describe all aspects of the study objective, nor does it provide evidence about outcomes at other timepoints.

The safety summary is separate from the efficacy endpoint. Its serious and other adverse-event counts are descriptive, and the record does not provide enough detail to interpret the listed serious term by treatment arm. Neither the efficacy comparison nor the safety counts alone resolve questions beyond what the registry record reports. They should be understood as summaries of this study's posted data, not as medical advice or a basis for an individual treatment decision.

16. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition and its timeframe are central to interpreting a clinical comparison. The primary outcome is not a general judgment of inflammation; it is the specific binary state of no cells in the anterior chamber of the study eye at Day 14. A result tied to that definition cannot automatically be extended to pain, other signs of inflammation, or later outcomes.

The posted counts and effect estimates also show why a point estimate should not be read in isolation. The risk difference is positive, but its confidence interval includes zero and extends in both directions. The risk-ratio and odds-ratio intervals likewise include their no-difference values. Reporting the uncertainty alongside the estimate is essential to avoid turning a direction in the data into an overly certain conclusion.

The record also provides an example of the limits of registry results for evaluating analysis decisions. It identifies a randomized, double-masked design, but does not report the analysis plan, missing-data handling, analysis populations, or multiplicity strategy. These details affect how fully a reader can assess the posted comparison and whether it reflects the originally intended analysis.

Finally, planning illustrations based on an observed effect are useful for showing how assumptions about effect size and desired power influence sample-size requirements. They are not evidence about the original design or the likelihood that this completed study detected an effect. Keeping planning calculations separate from observed trial results prevents a retrospective illustration from being mistaken for a 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 provides only the primary endpoint result among its two listed outcome measures; it posts no secondary outcome results. Although the study objective refers to both inflammation and pain, no pain result is included in the posted outcomes. The available efficacy comparison is limited to absence of anterior chamber cells at Day 14.

The record does not report the original sample-size justification, the statistical analysis plan, or the sponsor's analysis for the primary endpoint. It also does not describe the randomization procedure, allocation concealment, analysis populations, covariate adjustment, missing-data handling, interim analyses, or multiplicity strategy. These omissions prevent a full assessment of whether the simple unadjusted comparison corresponds to the prespecified analysis.

The primary endpoint denominators are 161 and 80, while the safety denominators are 160 and 80. The reason for the difference is not reported in the registry record. It does not explain whether the endpoint and safety populations were defined differently or whether any participant lacked a particular assessment.

The safety results are limited to the posted counts. The record does not report deaths, and the serious-term summary does not identify which arm accounts for the mental disorder term. Further details about event timing and attribution are not reported in the registry record. These constraints mean the posted safety summary should be treated as a limited descriptive account, not a complete characterization of safety.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: OTX-14-003: A Phase 3 Study Evaluating the Safety and Efficacy of OTX-DP for the Treatment of Ocular Inflammation and Pain After Cataract Surgery — NCT02089113.
• Registry record last updated 2019-09-26; status last verified 2019-09.
• Results first posted 2016-03-30.
• 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

NCT02089113 is a completed Phase 3 randomized, parallel-arm, double-masked, vehicle-controlled study of OTX-DP for ocular inflammation and pain after cataract surgery. The official title describes a prospective, multicenter Phase 3B study. Enrollment was 241; the registry record gives the study start as 2014-04 and primary completion as 2015-01.

The primary endpoint was absence of anterior chamber cells at Day 14. The posted counts were 63 of 161 for OTX-DP and 25 of 80 for Placebo Vehicle. The unadjusted recalculated risk difference was 0.079, with a 95% confidence interval from -0.048 to 0.205 and an unadjusted p-value of 0.231. The registry record posts no secondary outcome results and does not report the original sample-size justification or primary analysis plan.