Study to Evaluate the Safety, Tolerability, and Efficacy of OTX-CSI in Subjects With Dry Eye Disease.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety, Tolerability, and Efficacy of OTX-CSI in Subjects With Dry Eye Disease. (NCT04362670), a randomized phase 1, phase 2 study. The primary outcome is Number of Subjects With At Least One (1) Treatment Emergent Adverse Event.

2. Clinical Question

3. Trial Design

The registry describes a randomized, multi-center, double-masked, vehicle-controlled Phase 1/2 study of OTX-CSI for dry eye disease. Its design model is sequential. The record lists the study as completed and reports enrollment of 153. The recorded start date is 2020-04-23, and the primary completion date is 2021-08-11.

The intervention was OTX-CSI, described as a cyclosporine ophthalmic insert for intracanalicular use. The record also lists Placebo Vehicle. The posted outcome results, however, are arranged by OTX-CSI formulation cohort: Cohort 1 F2A, Cohort 2 F1, Cohort 2 F2A, Cohort 2 F2B, and Cohort 2 F3. The arm descriptions associate these labels with formulations 2A, 1, 2A, 2B, and 3, respectively. A placebo vehicle result is not included among the posted primary outcome groups.

The primary outcome is the number of participants with at least one treatment-emergent adverse event, from screening to study exit, approximately 156 days. Although the brief summary says the study assessed safety, tolerability, and efficacy, the posted primary outcome concerns adverse events. The registry record does not post a primary efficacy result or an analysis comparing an OTX-CSI cohort with vehicle.

The record does not report the randomization procedure, the sequence or timing of cohort progression, or how the study’s masking was implemented. It also does not report the planned sample-size justification or a statistical analysis plan. Those details cannot be inferred from the design labels 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.

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 Subjects With At Least One (1) Treatment Emergent Adverse Event, measured over From Screening to Study Exit, approximately 156 days..

The primary endpoint counts participants who experienced at least one treatment-emergent adverse event during the period from screening to study exit, approximately 156 days. It is reported as a count, not as a measure of the number of events each participant experienced or how long an event lasted. A participant with multiple events still contributes to the endpoint as a participant with at least one event.

Counting participants with an event is a common way to describe whether an adverse event occurred during a defined observation period. It provides a direct summary of the number of participants affected in each group, while not conveying the event’s severity, duration, or clinical importance. Those features require separate information.

The registry identifies this as the primary outcome and describes it as a count of participants. The posted results give a count and group size for each listed OTX-CSI formulation cohort. The endpoint is not presented as a comparison with placebo vehicle, and no inferential estimate for a treatment contrast is reported. The registry record does not further define which events qualified as treatment-emergent or specify the analysis population used for this outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as the number of participants with at least one treatment-emergent adverse event. For this binary outcome, each participant is classified according to whether at least one qualifying event occurred during the stated observation period. The reported value is a participant count. It is distinct from a total count of all event occurrences, because multiple events in one participant do not necessarily increase the participant count beyond one.

What does a group count tell the reader?

A group count describes what was observed among the participants in that group. Interpreting a count alongside the group size gives context about how many participants were observed, but the count alone does not establish a causal effect. In a randomized comparison, a treatment effect would ordinarily be expressed as a contrast between groups, with an estimate of uncertainty. The posted primary results do not include a vehicle group or a treatment-versus-vehicle estimate.

The five posted cohort results are 0.0 among 5.0 participants for Cohort 1 F2A, 16.0 among 42.0 for Cohort 2 F1, 15.0 among 41.0 for Cohort 2 F2A, 5.0 among 43.0 for Cohort 2 F2B, and 1.0 among 22.0 for Cohort 2 F3. They are reported as cohort-level observations, not as adjusted results. No confidence intervals or p-values are posted for these counts.

Why is the missing comparator important?

The official study title describes a vehicle-controlled design, and the intervention list includes Placebo Vehicle. Nevertheless, the primary outcome results list only OTX-CSI cohorts. A randomized trial’s comparative question depends on outcome information for the treatment and comparator groups, together with a defined method for contrasting them. In the absence of a posted vehicle result, the comparative effect cannot be estimated from these outcome data.

Randomization is intended, in general, to support fair comparisons by assigning participants to groups using a chance-based process. The registry labels this study randomized and double-masked, but does not report the specific allocation method, how masking was maintained, or how the analysis accounted for the sequential cohort structure. The design labels alone do not supply those details.

What does uncertainty mean?

In general, an estimate based on observed participants has sampling uncertainty: other participants might have produced a different observed result. A confidence interval communicates a range of values compatible with the data and the statistical method, subject to its assumptions. It is not a guarantee that the true value lies within that range. No confidence interval is posted for the primary endpoint, and a comparative interval cannot be recovered without a reported comparator result and analysis.

For binary outcomes, analyses may use methods that compare event probabilities or event counts across groups. The choice depends on the design, the data, and the analysis plan. The registry record does not report a statistical analysis for this primary endpoint, and the posted results do not supply a two-arm comparison. No particular inferential method should therefore be attributed to the trial.

How should the cohort structure be read?

The model is recorded as sequential, with results displayed for several formulation cohorts. In general, sequential studies may evaluate groups in an ordered process, but the record does not state the rules governing progression or whether the cohort results were intended for formal comparisons. It would be inappropriate to assume that the cohorts were concurrent, exchangeable, or analyzed as a single randomized comparison. Their observed counts should be read as cohort-specific descriptions.

The record reports a study enrollment of 153, but the primary endpoint results are displayed separately by cohort. This enrollment figure should not be used to infer a missing analysis population, a comparator group size, or participant flow. The registry record does not report exclusions, missing outcome status, or the exact population analyzed for the primary result.

What can the posted analysis support?

The posted information supports a descriptive account of the primary outcome counts for the listed OTX-CSI cohorts and a separate description of serious adverse events. It does not provide an efficacy estimate, a formal treatment comparison, an uncertainty interval, or evidence about the trial’s prespecified analysis procedure. General statistical concepts can clarify what these results mean, but cannot replace the unreported comparator data or analysis details.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("OTX-CSI Cohort 1 F2A", "OTX-CSI Cohort 2 F1", "OTX-CSI Cohort 2 F2A", "OTX-CSI Cohort 2 F2B", "OTX-CSI Cohort 2 F3")
n      <- c(5, 42, 41, 43, 22)
events <- c(0, 16, 15, 5, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  OTX-CSI Cohort 1 F2A  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  OTX-CSI Cohort 2 F1  42  16  38.1  23.6  54.4  25.0  53.2  25.0  53.3
ARM  OTX-CSI Cohort 2 F2A  41  15  36.6  22.1  53.1  23.6  51.9  23.6  52.0
ARM  OTX-CSI Cohort 2 F2B  43  5  11.6  3.9  25.1  5.1  24.5  5.2  24.6
ARM  OTX-CSI Cohort 2 F3  22  1  4.5  0.1  22.8  0.8  21.8  1.1  21.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a hierarchy of outcomes, or a procedure for handling multiple comparisons. The brief summary names safety, tolerability, and efficacy as study aims, while the posted primary result is an adverse-event count. The record lists two outcome measures, but does not report a posted analysis for either as a comparative test. It is therefore not possible to determine how multiplicity was addressed or whether any outcome was designated for formal hypothesis testing beyond the primary outcome label.

Missing-data handling is not reported in the registry record. The posted primary results do not explain whether all enrolled participants had outcome information through study exit, how participants with incomplete follow-up were treated, or whether any imputation was used. The timeframe is stated as from screening to study exit, approximately 156 days, but the record does not describe actual follow-up completeness for each participant.

The analysis population is also not reported in the registry record. The posted results give cohort sizes and event counts, but do not explain whether these counts use all randomized participants, participants who received an intervention, or another population. No participant flow or reasons for exclusion are described in the posted primary outcome data.

These gaps matter because outcome definitions, missing observations, analysis populations, and multiplicity decisions can affect interpretation. They cannot be resolved from the cohort counts alone. No assumptions about these procedures should be treated as part of the trial’s reported methods.

12. 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: covid-19 pneumonia (2.4%), hip fracture (2.4%), hiatus hernia (2.4%).

The registry reports serious adverse events separately from the primary count of participants with at least one treatment-emergent adverse event. The serious-event counts are 0 among 5 participants in Cohort 1 F2A, 1 among 42 in Cohort 2 F1, 2 among 41 in Cohort 2 F2A, 0 among 43 in Cohort 2 F2B, and 0 among 22 in Cohort 2 F3. The record reports 0 deaths in each listed cohort.

The registry also lists COVID-19 Pneumonia, Hip Fracture, and Hiatus Hernia as serious-event terms, each with a reported value of 2.4%. The record does not provide enough detail in this listing to assign each term to a particular cohort or to interpret the percentage as a comparative measure.

Serious-event counts are descriptive observations. They do not show whether events were caused by an intervention, and the registry record does not report a vehicle-group result for comparison. These counts also describe a different category from the primary endpoint, which counts participants with at least one treatment-emergent adverse event of any qualifying severity. The record does not report further detail about event timing, duration, or attribution.

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

The posted results show how many participants in each listed OTX-CSI formulation cohort had at least one treatment-emergent adverse event during the specified observation period. They also report serious adverse-event counts and no deaths in the listed groups. These are descriptive findings about the outcomes recorded for those cohorts.

They do not establish whether OTX-CSI is safer or less safe than vehicle. Although the registry identifies the study as vehicle-controlled, a vehicle result is not included in the posted primary outcome groups. Without that comparator result and a reported analysis, the event counts cannot quantify a treatment-versus-vehicle difference. Nor do the counts support a claim that one formulation is safer than another: the registry does not report a formal comparison, uncertainty estimates, or the analysis plan for the sequential cohorts.

The primary result does not measure efficacy. The brief summary states that efficacy was assessed, but an efficacy outcome result is not reported in the registry record. The posted safety counts therefore cannot answer whether the intervention changed dry eye disease symptoms or signs.

In general, observed event counts are influenced by the number of participants observed, the observation period, event definitions, and completeness of follow-up. The registry reports the primary timeframe as from screening to study exit, approximately 156 days, but does not provide detailed follow-up completeness or the analysis population. Those limits constrain interpretation of the cohort summaries.

The results are best understood as reported safety counts for the listed formulation cohorts, rather than as evidence for a comparative treatment effect. They do not establish causation, provide a complete account of each event’s clinical course, or support a conclusion about efficacy. Additional comparative results and analysis details are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates a key distinction in clinical-trial interpretation: a randomized, vehicle-controlled design does not by itself provide a usable treatment comparison in every posted result. The record describes randomization and vehicle control, but the primary outcome results list OTX-CSI formulation cohorts without a vehicle-group result. The distinction between the design description and the data available for a particular outcome is essential when deciding what a result can support.

The sequential structure also makes clear why group labels and observed counts need context. The registry presents results for several formulations and cohorts, but does not report how cohorts were ordered, whether comparisons were planned, or how the analysis accounted for that structure. Descriptive counts across cohorts should not be treated as a formal ranking of formulations.

The endpoint itself is useful as a safety summary because it counts participants with at least one treatment-emergent adverse event during a defined period. At the same time, it is a limited summary: it does not describe the number, duration, or severity of all events. The separate serious-event information adds a narrower description, but still does not supply a comparative estimate.

Finally, the record demonstrates the value of reporting analysis populations, missing-data methods, uncertainty estimates, and outcome-specific comparisons. These details are not reported for the primary result. Their absence limits precision and prevents a formal treatment-versus-vehicle interpretation, even though the registry provides cohort-level counts.

15. 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 main limitation for interpreting this trial’s posted primary result is that the registry lists a vehicle-controlled design but does not post a vehicle-group result for the primary endpoint. The cohort counts therefore cannot be used to estimate a comparison with vehicle. No effect estimate, confidence interval, or inferential test is reported for that contrast.

The result is organized by OTX-CSI formulation cohorts in a sequential study. The registry record does not explain the cohort sequence, whether cohort comparisons were planned, or how any temporal or design differences were handled. The observed counts should not be interpreted as a direct ranking of formulations.

The registry does not report the analysis population, participant flow for the endpoint, or how missing outcome information was handled. It also does not report the statistical analysis plan, multiplicity procedure, or sample-size justification. These omissions prevent assessment of whether the posted summaries follow a prespecified analysis approach.

The primary endpoint counts participants with at least one treatment-emergent adverse event, but the record does not further define event qualification or provide details on duration and severity for the primary outcome. Serious adverse events are presented separately, with no vehicle-group result available for comparison. The brief summary mentions efficacy assessment, but efficacy results are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety, Tolerability, and Efficacy of OTX-CSI in Subjects With Dry Eye Disease. — NCT04362670.
• Registry record last updated 2023-11-14; status last verified 2023-10.
• Results first posted 2023-11-14.
• 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.

19. Record Summary

The registry describes a randomized, double-masked, vehicle-controlled Phase 1/2 study of OTX-CSI for dry eye disease, using a sequential model. It reports enrollment of 153 and lists the study as completed. The primary outcome is the number of participants with at least one treatment-emergent adverse event from screening to study exit, approximately 156 days.

Posted primary results are given for five OTX-CSI formulation cohorts. The registry also reports serious adverse-event counts and 0 deaths in each listed cohort. A vehicle-group primary result, a formal treatment comparison, and efficacy results are not reported in the registry record. Analysis-population details, missing-data methods, and the statistical analysis plan are also not reported.