Study of Brimonidine Tartrate Nanoemulsion Eye Drop Solution in the Treatment of Dry Eye Disease (DED): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Brimonidine Tartrate Nanoemulsion Eye Drop Solution in the Treatment of Dry Eye Disease (DED) (NCT03785340), a randomized phase 3 study. The primary outcome is Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, placebo-controlled, parallel-group study of brimonidine tartrate nanoemulsion eye drops in people with dry eye disease. The registry lists the masking as quadruple. It does not identify which participant, clinician, investigator, or assessor roles were masked, nor does it describe how masking was maintained.

The planned treatment period was 4 weeks. OCU-310 was brimonidine tartrate nanoemulsion eye drops at 0.20%, used 2 times a day. The comparator was ophthalmic buffered saline eye drops, also used 2 times a day for 4 weeks. The study enrolled 252 participants. The registry describes an equal division between the two groups in its brief summary; the adverse-event record lists 126 participants at risk in each group.

The primary efficacy outcome was change from baseline to 4 weeks (Day 28) in SANDE score. The listed secondary outcomes include change from baseline to 2 weeks (Day 14) in SANDE score and change from baseline to 2 weeks (Day 14) in Lissamine Green Conjunctival Staining Scores. The record lists 4 outcome measures, but does not give the full details of every measure in the information.

The study is marked completed. Its start date is 2018-12-03 and its primary completion date is 2019-02-25. A planned sample-size rationale, detailed allocation procedure, and fuller analysis protocol are not reported in the registry record. Neither are the actual primary endpoint results.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Intention-to-treat (ITT) set is the primary analysis set for the efficacy endpoints and includes all randomized participants who have at least one post-baseline efficacy measurement. Here, the overall number of participants analyzed is the number of participants with evaluable data at each time point.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Randomized set: All randomized participants who previously signed the informed consent.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score, measured over Baseline, 4 weeks (Day 28).

The primary endpoint is change from baseline to 4 weeks (Day 28) in the Symptom Assessment in Dry Eye (SANDE) Questionnaire Score. SANDE is a short visual analogue scale assessment intended to quantify both the frequency and severity of current dry eye symptoms. Its two questions use 100-mm horizontal scales: symptom frequency ranges from rarely to all of the time, and symptom severity from very mild to very severe.

The overall SANDE score is calculated by multiplying the frequency score by the severity score and taking the square root. The resulting score ranges from 0 to 100, with 100 described as the maximal amount of dry eye symptoms and 0 as the minimal amount. The endpoint is a mean of a continuous measure, with standard deviation identified as the measure of dispersion.

A change score compares a participant’s measurement at follow-up with that participant’s baseline measurement. Comparing changes between randomized groups can describe whether the groups’ symptom scores changed differently over the study period. The endpoint is patient-reported symptom measurement, which makes it relevant to participants’ experienced symptoms. However, the registry record does not report the group means, the treatment-group contrast, or uncertainty around that contrast. It is therefore not possible to assess the direction, size, or precision of the primary endpoint result from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is randomized and parallel-group, with brimonidine compared against ophthalmic buffered saline. Randomization is intended to make treatment groups comparable on average at the start of a trial, including with respect to measured and unmeasured factors. It does not guarantee that every feature is balanced in a particular study. The record identifies quadruple masking, but details about who was masked and the procedures used to preserve masking are not reported in the registry record.

What does the primary endpoint represent?

The endpoint is change from baseline to 4 weeks (Day 28) in SANDE score. SANDE combines reported symptom frequency and severity into an overall score. The record describes the overall score as the square root of the product of the frequency and severity scores, with a range from 0 to 100. A change endpoint focuses on how the score differs between baseline and follow-up, rather than on the follow-up score alone. The registry specifies the mean and standard deviation as the summary and dispersion measures, but does not report the observed values.

For a continuous endpoint, a group mean describes the average measurement or change among participants with evaluable data. A standard deviation describes how dispersed individual measurements are around that mean. These answer different questions: the mean describes the group’s average, while the standard deviation describes participant-to-participant variability. Neither is reported for the primary outcome in the record.

What would a treatment contrast show?

A between-group contrast would compare the average change in the brimonidine group with the average change in the placebo group. It would describe the observed difference in changes, not just whether either group changed from baseline. A contrast is most informative when accompanied by a confidence interval, which conveys the statistical uncertainty around the estimate, and a test result where appropriate. The contrast, interval, and test result are not reported in the registry record.

General statistical explanation: a p-value is a measure, under a specified statistical model and null hypothesis, of how compatible the observed data are with that hypothesis. It does not measure the size or clinical importance of an effect. A confidence interval provides information about both an estimated effect and its precision. Because the registry record does not report a primary endpoint estimate, interval, or p-value, none of those features can be evaluated for this comparison.

Why does variability matter?

General statistical explanation: variability affects how precisely a group mean or between-group contrast can be estimated. Greater spread in participant outcomes generally makes estimates less precise when other design features are held fixed. The registry identifies standard deviation as the dispersion measure for the primary outcome, but gives no observed standard deviations. The amount of variability in SANDE change and its contribution to uncertainty are therefore unknown.

Over-dispersion is a general issue for count outcomes when observed variability exceeds what a chosen statistical model expects. It can make standard errors and confidence intervals too small if the model does not account for the extra variability. The primary endpoint is continuous, not a count, and the record does not describe an over-dispersion analysis. No claim about over-dispersion is needed to interpret the missing primary result.

How should planning calculations be understood?

The registry’s planning description says that sample-size illustrations are computed from an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. These are planning illustrations, not observed power and not evidence that the trial detected an effect. The record does not give the illustration values or the observed effect used to produce them. The trial’s own sample-size justification is not reported in the registry record.

In general, a planning calculation estimates the sample size needed under specified assumptions to detect a chosen effect with a chosen probability of statistical significance. Its output depends on assumptions about the effect, variability, analysis, and allocation. It cannot substitute for reporting the trial’s actual estimate and uncertainty. The registry’s planning description also does not establish which assumptions informed the original study design.

The adverse-event record reports event counts separately for each group. Counts and numbers at risk can describe what was recorded, but a complete safety interpretation also depends on definitions, observation period, completeness of follow-up, and methods of collecting events. Those details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists more than one efficacy outcome: the primary SANDE change at 4 weeks (Day 28), and secondary outcomes that include SANDE change and Lissamine Green Conjunctival Staining Score change at 2 weeks (Day 14). It also states that the primary outcome has several categories or time points and is not reduced to one comparison. A single primary contrast is therefore not available in the information reported.

When a study assesses multiple outcomes, time points, or comparisons, the chance of at least one apparently notable result can increase if each is tested without accounting for the number of analyses. General statistical methods for addressing multiplicity include prespecifying a primary comparison, adjusting significance thresholds, or treating some analyses as exploratory. The registry record does not report whether any such approach was planned or used, how the primary outcome’s categories or time points were handled, or how the secondary outcomes were interpreted.

The efficacy analysis population is described as the intention-to-treat set, including randomized participants who have at least one post-baseline efficacy measurement. The record also says that the overall number analyzed is the number with evaluable data at each time. Actual endpoint-specific analysis counts are not reported in the registry record.

Missing-data frequency, reasons for missingness, and the methods used to handle missing outcomes are not reported in the registry record. The record does not state whether imputation, a repeated-measures model, or another approach was used. Without those details and the analysis counts, it is not possible to assess whether missing observations could have affected the estimated comparison.

11. 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 5% reporting threshold.

For OCU-310, the registry lists 126 participants at risk for serious adverse events and 0 affected; it lists 126 at risk for other adverse events and 0 affected, with 0 deaths. For placebo, it likewise lists 126 participants at risk for serious adverse events and 0 affected, 126 at risk for other adverse events and 0 affected, and 0 deaths. No serious adverse event terms are listed.

These entries describe the counts recorded in the registry. They do not provide event rates beyond the counts, detailed event definitions, follow-up completeness, or the method used to collect adverse events. The record also does not describe the duration of safety observation beyond the stated 4-week treatment schedule. Zero recorded events in these categories should not be interpreted as proof that the treatment has no safety risks or that no events occurred outside the registry’s reporting scope.

The listed counts are the same in the two groups, but the registry record does not provide a statistical safety comparison or uncertainty estimates. The figures therefore support a limited description of reported events, not a broad conclusion about comparative safety.

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

The record establishes that a randomized, placebo-controlled Phase 3 study evaluated brimonidine tartrate nanoemulsion eye drops for dry eye disease. It identifies a primary symptom endpoint, SANDE change from baseline to 4 weeks (Day 28), and describes the treatment schedule and comparator. It also records adverse-event counts for the two groups.

It does not report the primary endpoint results. There is no group-specific mean change, between-group estimate, confidence interval, or primary endpoint test result in the registry record. As a result, the direction and size of the observed efficacy difference, and the precision of any estimate, cannot be described. The record’s completed status is not a substitute for an outcome result.

The endpoint’s scale description explains what higher and lower SANDE scores represent, but does not tell how participants’ symptoms changed. Likewise, listing secondary outcomes does not establish what those outcomes showed. The outcome results for the listed measures are not reported in the registry record.

The adverse-event entries show 0 serious adverse events, 0 other adverse events, and 0 deaths recorded in each group, with 126 participants at risk in each group. Those counts do not, on their own, demonstrate absence of risk or establish a comparative safety profile. Information about event ascertainment and completeness is not reported.

General statistical interpretation: results are best understood through an estimated group contrast and its uncertainty, alongside the analysis population and missing-data methods. Those elements are absent or incomplete. No conclusion about whether the study met its efficacy objective, whether an observed difference was statistically significant, or whether the groups were meaningfully different can be drawn from the registry record alone.

13. Why This Trial Matters Statistically

This study is statistically notable for its randomized, parallel-group comparison of an active eye-drop formulation with an ophthalmic buffered saline placebo, using a patient-reported symptom measure as the primary endpoint. The registry describes a defined assessment at 4 weeks (Day 28) and reports enrollment of 252. These features frame a comparison of average symptom-score changes over the treatment period.

The endpoint is a continuous score constructed from reported symptom frequency and severity. That makes the choice of summary important: the registry identifies a mean and standard deviation, which would describe average change and the spread of participant outcomes. A treatment contrast would be needed to distinguish a difference between groups from change within either group. Neither that contrast nor its uncertainty is reported.

The record also illustrates why a study’s design and result are distinct. Randomization, masking, a placebo comparator, and a named primary endpoint describe how the trial was organized. They do not supply the estimate needed to judge the observed efficacy comparison. The lack of a reported result limits statistical interpretation even though the study is marked completed.

The record identifies secondary outcomes at 2 weeks (Day 14), as well as an issue with multiple categories or time points for the primary outcome. Without a reported analysis plan or a clearly presented primary contrast, readers cannot determine how multiplicity was handled or which comparison was intended to carry the main inferential weight.

Finally, the adverse-event counts are reported as zero in each group, but the available record gives little context on ascertainment or follow-up completeness. This highlights the distinction between a recorded count and a fully characterized safety analysis. Taken together, the trial’s design is identifiable, while the efficacy estimate and several details needed to assess analysis choices are not reported in the registry record.

14. 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 most important limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. Group means, change estimates, the between-group contrast, confidence intervals, and a statistical test result are absent. The direction, magnitude, and precision of the comparison therefore cannot be assessed.

The primary outcome is described as having several categories or time points and is not reduced to one comparison. The record does not explain the intended primary contrast or the handling of those categories and time points. Although secondary outcomes are named, their results are not reported in the registry record.

The efficacy population is described as randomized participants with at least one post-baseline measurement, with evaluable counts potentially specific to each time. The number analyzed for the primary endpoint, the amount and pattern of missing data, reasons for missingness, and methods used to address missing observations are not reported. Those omissions prevent assessment of the analysis population’s completeness and the sensitivity of the result to missing data.

Other design and analysis details are also not reported in the registry record, including the trial’s sample-size justification, detailed randomization procedures, the roles covered by quadruple masking, and the statistical plan. The record gives a general description of sample-size illustrations but no illustration values or observed effect used in those calculations.

For safety, event counts are listed, but definitions, collection methods, follow-up completeness, and detailed safety comparisons are not reported. These limitations concern the information available in the registry record; they do not establish what may have been reported elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Brimonidine Tartrate Nanoemulsion Eye Drop Solution in the Treatment of Dry Eye Disease (DED) — NCT03785340.
• Registry record last updated 2022-07-18; status last verified 2022-06.
• Results first posted 2022-06-06.
• 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.

18. Record Summary

NCT03785340 is a completed, randomized, placebo-controlled, parallel-group Phase 3 study of brimonidine tartrate nanoemulsion eye drops in dry eye disease. Enrollment was 252. OCU-310 was given at 0.20% 2 times a day for 4 weeks; placebo was ophthalmic buffered saline given on the same schedule.

The primary outcome was change from baseline to 4 weeks (Day 28) in SANDE score. Listed secondary outcomes include SANDE change and Lissamine Green Conjunctival Staining Score change at 2 weeks (Day 14). The registry record does not report the primary efficacy estimate or its uncertainty. It lists 0 serious adverse events, 0 other adverse events, and 0 deaths in each group, with 126 participants at risk per group.