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

1. Trial at a Glance

This page covers the registry results for Phase 3 Study Evaluating Safety and Efficacy of OTX-DP for Treatment of Ocular Inflammation and Pain After Cataract Surgery (NCT02034019), a randomized phase 3 study. The primary outcome is Absence of Cells in Anterior Chamber of the Study Eye.

2. Clinical Question

The registry describes a study of post-surgical inflammation and pain in participants who had cataract extraction with intra-ocular lens implantation. The treatment question was whether a sustained-release dexamethasone depot placed in the eyelid canaliculus differed from a placebo plug on the posted primary outcome: absence of cells in the anterior chamber of the study eye at Day 14. The record reports participant counts by randomized arm and a risk-difference comparison, alongside relative-risk and odds-ratio estimates.

This is a comparison of two assigned study arms, not a comparison with no procedure or with a different cataract-surgery approach. The endpoint focuses on an observed sign in the operated eye. The record does not give a separate primary result for pain, nor does it post secondary outcome results. It also does not specify how participants with missing Day 14 assessments were handled. Those details limit what can be concluded from the posted result beyond the recorded endpoint and comparison.

3. Trial Design

The registry identifies NCT02034019 as a phase 3, randomized, double-masked, parallel-group study sponsored by Ocular Therapeutix, Inc. The trial enrolled 247 participants and is recorded as completed. The listed start is 2014-02, and primary completion is listed as 2014-12. Randomization indicates assignment to study arms by a chance-based process; double masking indicates that the record describes masking of two groups involved in the study, but it does not say which roles were masked or how masking was maintained.

The active arm received OTX-DP, described as a resorbable hydrogel delivery vehicle containing dexamethasone. The comparator arm received PVPP, a resorbable hydrogel vehicle containing no drug. Both are punctum plugs, so the comparison uses a placebo device as well as an active drug-delivery device. The registry does not provide details about the allocation procedure, concealment, site structure, or treatment administration beyond the brief description of placement in the eyelid canaliculus.

The posted primary outcome is the number of participants with absence of cells in the anterior chamber of the study eye at Day 14. The arm counts are 54 of 164.0 for OTX-DP and 12 of 83.0 for PVPP. The comparison record identifies PVPP as the control. The record does not explain the difference between the total enrollment and the arm-specific denominators reported for this outcome, or describe whether those denominators represent all randomized participants or an analysis subset.

Although the registry identifies the trial as randomized and parallel, the original protocol and the trial's statistical analysis plan are not reported in the registry record. The originally planned sample size and its justification are not reported in the registry record. Details about interim analyses, prespecified analysis populations, and planned handling of missing outcome data are also 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: One subject inadvertently received PVPP instead of OTX-DP, as they had been randomized. This subject was followed safety but not included in the PP analysis.

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 Absence of Cells in Anterior Chamber of the Study Eye, measured over Day 14.

The primary endpoint counts participants whose study eye had no cells in the anterior chamber at Day 14. It is a binary outcome at the participant level: each participant either meets the stated condition at the assessment or does not. The posted result is therefore a count of participants meeting the endpoint in each arm, rather than a continuous measurement of the amount of inflammation.

In general, an endpoint based on an observed clinical sign can give a defined way to compare groups at a specified assessment time. A binary endpoint can be interpreted directly as the number who met the criterion, while an arm comparison can express the difference or relative contrast between those outcomes. The Day 14 time point supplies the reference for interpreting this particular result; the record does not establish what happened at other assessment times.

The registry title and description identify the sign and the study eye, but provide no grading rules, examiner procedures, or threshold details beyond the absence of cells. The meaning of an assessment recorded as absent therefore depends on the study's operational definition, which is not reported in the registry record. The endpoint should not be taken as a direct measure of every aspect of inflammation or pain. Pain is named in the study aim and condition, but the posted primary outcome is the anterior chamber cell finding.

7. Results Posted in the Registry

• OTX-DP (Dexamethasone Punctum Plug): 32.9% (54/164) versus 14.5% (12/83) on control; risk difference 18.5 percentage points (95% CI 8.0 to 28.9), risk ratio 2.28 (1.29–4.02); unadjusted two-proportion z-test p = 0.002.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents a binary endpoint: participants either had no cells in the anterior chamber of the study eye at Day 14 or did not meet that condition. For this kind of outcome, arm-level counts and comparisons of proportions are common descriptive and inferential tools. The posted counts are 54 of 164.0 in the OTX-DP arm and 12 of 83.0 in the PVPP arm. The comparison reports a risk difference, relative risk, odds ratio, confidence intervals, and an unadjusted p-value.

What does the risk difference describe?

In general, a risk difference is the proportion meeting an outcome in one group minus the corresponding proportion in another group. It measures an absolute contrast on the proportion scale. A positive value for the arm named in the comparison indicates a higher observed proportion in that arm than in the control arm. The registry reports a positive risk difference for OTX-DP, and the confidence interval endpoints are both positive. That direction is consistent with the posted arm counts. The record's risk-difference estimate is recorded to more decimal places than the maximum displayed in these explanatory materials, so the estimate is described by direction rather than reproduced with additional precision.

How do relative risk and odds ratio differ?

In general, relative risk is the proportion with the outcome in one arm divided by the proportion in the comparator arm. An estimate above one indicates a higher observed proportion in the named arm. The posted relative-risk estimate is 2.277, with an interval from 1.292 to 4.015. An odds ratio instead compares the odds of the outcome in one arm with the odds in the other. The posted odds-ratio estimate is 2.905, with an interval from 1.452 to 5.808. These are separate scales, and an odds ratio is not the same quantity as a relative risk. When an outcome is not rare, odds ratios can appear farther from one than relative risks; that is a general property of the measures, not a separate finding from this registry.

What does the p-value tell the reader?

The reported p-value is unadjusted and equals 0.002. In general, a p-value is calculated under a null hypothesis and a statistical model. It describes how unusual data at least as discrepant as those observed would be if the null model and its assumptions held. It is not the probability that the treatment has no effect, and it is not a measure of the size, reliability, or practical importance of a result. The registry does not identify the full testing procedure used to obtain the reported value, so its exact modeling assumptions are not reported in the registry record.

Why do the confidence intervals matter?

In general, a confidence interval gives a range of values compatible with the observed data and the procedure's assumptions. It conveys uncertainty around an estimate, not a guarantee that the true value lies within the particular interval. For the relative risk and odds ratio, the posted intervals exclude one; for the risk difference, the endpoints are on the positive side of zero. Those features describe the reported intervals. They do not account for uncertainty arising from design or reporting limitations that are not represented in the statistical calculation, such as missing outcome data or unreported analysis choices.

What is not established about the analysis?

The registry identifies the outcome and the numerical comparison, but the detailed statistical analysis plan is not reported in the registry record. The analysis model, any covariate adjustment, assumptions used for the p-value and intervals, and the prespecified analysis population are not reported in the registry record. No analysis records are posted. The record also does not specify whether the reported outcome counts include all randomized participants or only participants with an observed Day 14 assessment. Without those details, the comparison can be described as posted, but its full analytic implementation cannot be reconstructed from the registry entry alone.

The registry does not flag a discrepancy between its posted arm counts and its comparison results. That allows the comparison to be discussed as the result recorded there. If a discrepancy were recorded, the sponsor's own analysis would take precedence; that condition is not present in the registry record. General statistical interpretation still depends on the trial's design, data quality, and analysis choices, many of which are not detailed in the entry.

10. Confidence Intervals and Precision

Precision concerns how narrowly an estimate is pinned down by the observed data under the analysis assumptions. A confidence interval communicates that uncertainty by giving a range of values compatible with the data and procedure. It does not mean that every value in the interval is equally likely, nor does it capture every possible source of bias or uncertainty in how the study was conducted.

For the risk difference, the registry reports an interval with a positive lower bound and a positive upper bound. For the relative risk, the estimate is 2.277 and its interval runs from 1.292 to 4.015. For the odds ratio, the estimate is 2.905 and its interval runs from 1.452 to 5.808. In general, the null value for a difference is zero, while the null value for a ratio is one. The reported intervals lie on the effect side of those respective null values. This describes the intervals, but does not address potential analysis bias, missing data, or multiplicity.

The ratio intervals cover a range of possible effect magnitudes rather than a single precise value. The risk-difference interval likewise expresses uncertainty about the absolute contrast. The posted p-value, 0.002, is an unadjusted measure and should not be used as a substitute for examining the estimates and intervals. Precision is tied to the sample and analysis; it does not determine clinical importance by itself.

Some features needed to fully evaluate precision are not reported in the registry record, including the method used to construct the intervals, the handling of missing outcomes, and the analysis population. The endpoint is reported at Day 14, so these intervals also do not describe uncertainty about results at other times or for other 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 figures are participants per arm, not total events. They are illustrations based on the observed effect, not a report of the trial's own original sample-size planning. The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect assumed for planning is a stated fraction of the observed effect. The trial's original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the number of participants per arm under which the planning calculation would have an 80% chance of detecting the assumed effect at the stated significance level, if the assumptions of the calculation hold. The 90% power column gives the corresponding per-arm planning number for 90% power. In general, higher target power requires more participants when the other assumptions are held constant. These are planning quantities, not a description of what happened in the completed trial.

The rows vary the assumed effect: planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. A smaller assumed effect is harder to distinguish from random variation, so it requires more participants per arm in these illustrations. This pattern is the main sensitivity message to take from the table and curve: planning needs depend strongly on the effect size selected. The figures are not observed power, and they should not be read as an assessment of the trial's probability of success after the data were collected.

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 = 0.145; treatment proportion p₁ = 0.329; average p̄ = 0.237.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6013 = 1.1786.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5870 = 0.4940.
4. n = (1.1786 + 0.4940)² / (0.1847)² = 82.0, rounded up to 83 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 <- 0.144578313253012                          # control proportion
p1 <- 0.329268292682927                          # 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(2034019)
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 = 83 (80% power), 110 (90% power)
 75% of observed effect: n per arm = 137 (80% power), 183 (90% power)
 50% of observed effect: n per arm = 283 (80% power), 379 (90% power)
power.prop.test: 82 
Simulated power at n = 83 per arm: 0.818 (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 identifies a primary endpoint, absence of cells in the anterior chamber of the study eye at Day 14, and reports an unadjusted p-value for its comparison. The record lists two outcome measures in total, but no secondary outcome results are posted. It records no analysis entries. The full list of intended statistical tests and their ordering is not reported in the registry record.

In general, multiplicity arises when several outcomes, time points, subgroups, or treatment comparisons are tested. Conducting multiple tests can increase the chance of at least one apparently notable result under a null model. Study teams may address this through prespecified testing strategies or adjustment procedures. The registry record does not report whether such a strategy was specified or used, and it does not provide an adjusted p-value. The posted p-value should therefore be understood as unadjusted, without assuming a multiplicity correction.

The registry does not report the original analysis population, whether the analysis followed intention-to-treat principles, or whether any participants were excluded from the endpoint analysis. Although the overall enrollment is 247, the primary-outcome denominators are 164.0 and 83.0. The reason for these denominators and any difference from the enrolled population are not reported in the registry record. The record also does not report how missing Day 14 assessments were handled, whether any imputation was used, or whether sensitivity analyses were performed.

These absences do not alter the posted counts or estimates, but they leave uncertainty about how the analysis was implemented and how robust it may be to missing outcomes or analysis choices. No subgroup results, secondary results, or interim analyses are reported in the registry record. The study's statistical analysis plan and original protocol details are also not reported in the registry record.

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

Most frequent non-serious adverse event terms

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

The registry reports serious adverse events for safety groups of 162 participants in the OTX-DP arm and 84 in the PVPP arm. The number affected is 0 for OTX-DP and 1 for PVPP. These figures are counts of participants affected, not a comparison adjusted for differences in exposure or follow-up. The record does not explain why the safety-group denominators differ from the primary-outcome denominators.

The listed leading serious adverse-event term is hypopyon, reported as 1.2%. The record does not provide a corresponding count or clarify the denominator for that percentage in the material available. Death counts are not reported in the registry record.

For other, non-serious adverse events, the record lists 37 of 162 participants in the OTX-DP arm and 31 of 84 in the PVPP arm as affected. These counts are distinct from the serious-event counts and should not be combined with them. The registry entry does not provide event-level details, severity grading for these other events, exposure-adjusted comparisons, or enough information to infer causation. The figures describe the adverse-event reporting recorded for the two safety groups; they are not, by themselves, a complete assessment of comparative safety.

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

The posted primary result shows that, at Day 14, more participants in the OTX-DP arm than in the PVPP arm were recorded as having no cells in the anterior chamber of the study eye. The counts are 54 of 164.0 and 12 of 83.0, respectively. The registry comparison reports a positive risk difference, a relative risk of 2.277, and an odds ratio of 2.905. The unadjusted p-value is 0.002. These findings describe the recorded comparison for this endpoint in this trial.

They do not establish results for outcomes that are not posted. In particular, the primary outcome is not a pain measure, even though pain is part of the study aim. There are no secondary results posted, and the record does not provide a profile of the outcome at other times. The observed comparison also does not by itself show how the endpoint relates to participants' experience or longer-term outcomes.

A randomized design supports a comparison between assigned groups, but interpretation still depends on the conduct and analysis of the trial. Details about allocation, masking procedures, analysis populations, missing assessments, and the statistical analysis plan are not reported in the registry record. The primary-outcome denominators are smaller than the total enrollment, and the reason is not reported in the registry record. Those gaps prevent a full evaluation of how the posted result maps to all enrolled participants.

The statistics quantify the observed group contrast and its uncertainty under the analysis used. They do not prove a mechanism, establish that every participant would have the same outcome, or determine the clinical importance of the difference. The registry result should be read narrowly: it is a Day 14 comparison of a binary anterior chamber finding between OTX-DP and a placebo punctum plug in this completed phase 3 trial.

16. Why This Trial Matters Statistically

This trial is statistically useful as an example of how the same binary endpoint can be expressed on several scales. The arm counts describe how many participants met the Day 14 criterion. The risk difference conveys an absolute contrast, while the relative risk and odds ratio express relative contrasts using different definitions. Considering both absolute and relative measures helps keep the interpretation tied to the outcome's actual scale rather than relying on a single statistic.

The confidence intervals add information beyond the point estimates by showing uncertainty under the analysis procedure. The risk-difference interval is on the positive side of zero, and the relative-risk and odds-ratio intervals are above one. The unadjusted p-value is 0.002. These details help characterize the statistical evidence, but they do not replace attention to design quality, outcome definition, missingness, or prespecified analysis choices.

The trial also illustrates why registry transparency matters. The record identifies randomization, masking, parallel groups, treatment descriptions, an endpoint, and numerical results, while leaving important analysis details unreported. The result can be described accurately, but full appraisal requires knowing how the analysis population was defined, how missing outcomes were addressed, and whether multiple tests were planned. No secondary results are posted, which limits the breadth of statistical interpretation.

Finally, the planning illustration makes the dependence of sample-size requirements on the assumed effect explicit. Smaller effects require more participants per arm under the stated calculation assumptions. Such planning exercises are distinct from retrospective claims about power. Their value is in making assumptions visible, not in explaining whether an observed result should be believed.

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 endpoint is a binary finding assessed at Day 14. The registry does not report outcome results at other time points, and no secondary outcome results are posted. The study's broader aim includes inflammation and pain, but the posted primary result is confined to absence of anterior chamber cells. The record does not provide grading procedures or further operational details for classifying that finding.

The primary-outcome denominators are 164.0 in the OTX-DP arm and 83.0 in the PVPP arm, whereas total enrollment is 247. The reason for the denominator pattern is not reported in the registry record. The safety denominators are 162 and 84, and the reason for their difference from the outcome denominators is also not reported. Missing-outcome handling and analysis-population definitions are not reported in the registry record.

The detailed protocol and statistical analysis plan are not reported in the registry record. The entry does not describe the randomization method, allocation concealment, masking procedures, covariate adjustment, multiplicity handling, or interim analyses. It also does not provide the original sample-size assumptions or justification. These omissions limit assessment of prespecification and analytic robustness.

Safety reporting is limited in the available record: serious-event counts are given, the leading serious term is listed as hypopyon at 1.2%, and deaths are not reported in the registry record. The denominator for that percentage and event-level detail are not given. These limitations call for a narrow reading of the posted primary comparison and safety counts rather than broader conclusions about outcomes or study conduct.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Phase 3 Study Evaluating Safety and Efficacy of OTX-DP for Treatment of Ocular Inflammation and Pain After Cataract Surgery — NCT02034019.
• Registry record last updated 2020-01-31; status last verified 2020-01.
• Results first posted 2020-01-31.
• 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

NCT02034019 is a completed phase 3 randomized, double-masked, parallel-group trial sponsored by Ocular Therapeutix, Inc. It enrolled 247 participants and lists a start of 2014-02 and primary completion of 2014-12. The study compared OTX-DP, a dexamethasone-containing resorbable hydrogel punctum plug, with PVPP, a placebo plug containing no drug, in participants after cataract extraction with intra-ocular lens implantation.

The primary endpoint was absence of cells in the anterior chamber of the study eye at Day 14. The registry reports 54 of 164.0 participants meeting the endpoint in the OTX-DP arm and 12 of 83.0 in the PVPP arm. The unadjusted p-value is 0.002; the relative-risk estimate is 2.277 and the odds-ratio estimate is 2.905. No secondary results or analysis entries are posted.

Serious adverse events affected 0 participants in the OTX-DP safety group and 1 in the PVPP safety group. Additional analysis, missing-data, and protocol details are not reported in the registry record.