Comparing Treatment of Dry Eye With Intracanalicular Dexamethasone, Restasis, and/or Lotemax: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparing Treatment of Dry Eye With Intracanalicular Dexamethasone, Restasis, and/or Lotemax (NCT04555694), a randomized phase 4 study. The primary outcome is Mean Ocular Surface Staining From Baseline.

2. Clinical Question

The study asks whether ocular surface staining and other signs and symptoms of dry eye differ among three treatment regimens: Restasis alone, Restasis with Lotemax, and Restasis with Dextenza. The primary outcome is mean ocular surface staining from baseline, assessed at Week 4, Week 8 and Week 12. The registry describes the study as lasting 6 months, while the primary outcome timeframe ends at Week 12.

The secondary outcomes include conjunctival staining, Schirmer tear testing, tear breakup time, tear osmolarity, meibomian gland scores and DEQ-5 score. These measures broaden the clinical assessment, but the registry record does not report their comparative results either. As a result, the question can be described from the planned outcomes and assigned regimens, but not resolved from the posted outcome analyses.

3. Trial Design

This is a Phase 4 randomized, parallel-group study with no masking reported. The registry record gives an enrollment of 30 and describes three regimens, with 10 subjects assigned to each arm in the arm descriptions. The study status is completed. Its listed start date is 2020-10-01 and its primary completion date is 2022-02-16.

The Restasis and Lotemax group received both ophthalmic solutions twice a day in both eyes. The Restasis and Dextenza group received Restasis twice a day in both eyes and Dextenza insertion in both lower lids. The Restasis group received Restasis twice a day in both eyes. The registry identifies the interventions as cyclosporine, loteprednol etabonate and a dexamethasone ophthalmic insert.

Randomization is reported, but the method used to generate or implement the random allocation is not reported in the registry record. Masking is listed as none; further details about whether participants, clinicians or outcome assessors knew treatment assignments are not reported in the registry record. The record does not give additional information about study sites, eligibility criteria, treatment adherence, or the protocol for treatment changes.

The primary outcome covers baseline to Week 4, Week 8 and Week 12. The brief description calls this a 6 month study, but the listed primary outcome timeframe does not extend to the full stated study duration. The registry record does not explain the timing of other measurements or the relationship between the primary outcome schedule and the overall study duration.

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: Thirty patients were enrolled in the study. 10 patients in each treatment group.

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 Mean Ocular Surface Staining From Baseline, measured over Baseline to Week 4, Week 8 and Week 12.

The primary outcome is mean ocular surface staining from baseline, described in the registry as mean corneal surface staining at weeks 4, 8 and 12. Fluorescein and lissamine green are used to guide the assessment, and the National Eye Institute grading scale is named. The listed unit is a score on a scale, with the primary measure summarized as a mean and dispersion described using standard deviation.

The description explains that corneal fluorescein staining is graded from 0 to 3 in five regions of the cornea, with scores summed to a total score of 0-15. The scale ranges from none to heavy staining, with higher scores described as worse. This provides a structured way to represent staining across corneal regions rather than relying only on an overall impression. A mean can describe the average score in a group, while the standard deviation describes how spread out individual scores are around that average.

Ocular surface staining is used as a sign of the ocular surface condition in this study. Repeated assessment from baseline can describe whether average scores change over the listed follow-up times and can support comparisons among treatment groups. However, the registry record does not report the observed means, standard deviations, changes, or comparisons. The measurement description explains what the endpoint is intended to capture; it does not establish what happened to participants’ scores.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized parallel-group design and a continuous primary measure summarized as a mean with standard deviation. It does not report the statistical analysis methods used for the primary or secondary outcomes. The concepts below explain how such data are commonly interpreted; they are general statistical explanations, not claims about analyses performed in this study.

What does a mean describe?

A mean is the arithmetic average of the recorded scores in a group. For a continuous measure such as the staining score described in this study, it gives a group-level summary. It does not show the score of every participant or how observations are distributed. Two groups can have similar means while differing in the spread or pattern of individual scores.

The standard deviation describes variability among observations around the mean. A relatively larger standard deviation indicates more spread in the scores; a smaller one indicates that scores tend to lie closer to the mean. The registry names standard deviation as the dispersion measure but does not report the actual means or standard deviations for the primary outcome. Without those values, neither the average scores nor their variability can be assessed.

What would a treatment contrast represent?

A between-group contrast would describe how the outcome differs between two assigned regimens, or how groups compare under a specified model. A change-from-baseline contrast would additionally use the baseline measurement in defining the outcome or comparison. The choice matters: a comparison of follow-up means is not necessarily the same quantity as a comparison of changes. The registry’s endpoint description says the primary measure is from baseline and lists several follow-up times, but it does not state the exact statistical contrast or model used.

A confidence interval, in general, gives a range of values compatible with the data and the method used to calculate it. Its width conveys precision: a narrower interval indicates greater precision under that method, while a wider interval indicates less. A point estimate without an interval can leave substantial uncertainty hidden. No confidence intervals or primary-outcome point estimates are reported in the registry record.

A p-value, in general, measures how incompatible the observed data are with a specified null hypothesis under the assumptions of a statistical test. It does not measure the size or clinical importance of an effect, and it is not the probability that the null hypothesis is true. A p-value alone also does not convey the precision of an estimate. The registry record does not report a primary-outcome p-value or identify a test for that outcome.

Why do the several assessment times matter?

The primary outcome is assessed at Week 4, Week 8 and Week 12. Those are repeated measurements over time, and they can be handled in different ways. An analysis might compare groups separately at each time, estimate an overall pattern across time, or focus on a prespecified time point. Each approach answers a somewhat different question. The registry record does not identify which approach was used. It explicitly indicates that the primary outcome has several categories or time points and is not reduced to one comparison.

Repeated measurements on the same participant are generally related rather than independent. Statistical methods for repeated observations account for that relationship when estimating uncertainty. The appropriate method depends on the data structure and analysis plan. The registry record does not describe a repeated-measures model, covariance assumptions, or any other method for accounting for measurements within participants.

What does randomization contribute?

Random allocation is intended to make assigned groups comparable in expectation with respect to measured and unmeasured characteristics. It does not guarantee that the groups will be identical, especially in a study with an enrollment of 30. Baseline characteristics and the randomization procedure help readers assess how assignment was carried out and what differences were present at the outset. These details are not reported in the information available in the registry record.

Randomization also does not by itself determine the analysis population or solve problems from missing measurements, nonadherence or departures from assigned treatment. The handling of these issues should be described in an analysis plan and results report. Such details are not reported in the registry record.

How should planning illustrations be read?

The record describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated effect is a stated fraction of the observed effect. These assumptions describe planning calculations, not observed trial results and not the trial’s own design justification. The registry record does not report the protocol’s sample-size justification. A planning illustration based on an observed effect should not be interpreted as observed power or as proof that the study was adequately powered; its meaning depends on the underlying estimate and assumptions.

In general, a normal approximation uses a mathematical distribution to estimate uncertainty or required sample size. Its suitability depends on the outcome and data behavior. Over-dispersion, in general, means that observed variation is greater than a model expects; if not accounted for, uncertainty can be understated. The record does not report whether over-dispersion was assessed or whether a particular model was used. No numerical planning results for the illustrations are reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, treatment comparisons or time points. If each is tested separately, the chance of at least one apparently positive result can increase. Statistical plans may address this by identifying a primary comparison in advance, adjusting significance thresholds, using a hierarchical testing strategy, or treating some analyses as exploratory. These are general options; the registry record does not report which, if any, were used in this study.

The primary endpoint is described at Week 4, Week 8 and Week 12, and the study has three treatment groups. The registry notes that the primary outcome has several categories or time points and is not reduced to one comparison. It also lists multiple secondary outcomes. The handling of multiplicity across the primary time points, treatment contrasts and secondary outcomes is not reported in the registry record. Thus, the record does not establish whether results were adjusted for multiple testing or how a primary comparison was selected.

Missing-data handling is also not reported in the registry record. There is no description of how unavailable measurements, missed visits or incomplete outcome records were treated, or whether the analysis used imputation or another approach. The record does not state how participants were included in the analysis after randomization, including whether analyses followed assigned groups or a different population definition.

These omissions matter because the analysis population and missing-data assumptions can affect estimates and their uncertainty. With no reported outcome analyses, readers cannot assess the extent of missingness, the assumptions used, or whether alternative analyses were conducted. No conclusion about multiplicity control, completeness of follow-up or analysis-population choice should be inferred from the design information alone.

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.

Most frequent non-serious adverse event terms

The registry reports serious adverse events by treatment group. The number of participants at risk is 10 in each group, and serious adverse events affected 0 participants in the Restasis and Lotemax group, 0 in the Restasis and Dextenza group, and 0 in the Restasis group. Deaths are reported as 0 in each group.

For other adverse events, the registry reports 0 affected participants in the Restasis and Lotemax group, 2 in the Restasis and Dextenza group, and 0 in the Restasis group. The record does not identify the types of these other events, their severity, timing, duration, or relationship to treatment. It also does not provide further detail about how adverse events were collected.

These are counts from a study with an enrollment of 30. A count of 0 serious events means none were reported in the registry for the study; it does not demonstrate that a treatment has no serious risks. Sparse event counts provide limited information about uncommon events, and differences in small counts should not be treated as definitive evidence of a treatment-related difference. The adverse-event information is descriptive and does not replace the unreported primary-outcome analysis.

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

The registry record establishes that the study was randomized, parallel-group and unmasked, with an enrollment of 30 across Restasis alone, Restasis with Lotemax, and Restasis with Dextenza. It defines mean ocular surface staining as the primary outcome and lists follow-up at Week 4, Week 8 and Week 12. This is enough to describe the intended comparison and the measurement strategy.

It does not establish whether any regimen produced a larger or smaller change in staining, or whether groups differed at any of the listed follow-up times. The primary-outcome estimates, measures of uncertainty and inferential analyses are not reported in the registry record. The secondary outcome results are also not reported. Therefore, the posted information cannot support a conclusion that one regimen was superior, inferior or equivalent to another on the measured signs or symptoms.

Absence of a reported comparison should not be interpreted as evidence that the treatments had the same effect. Equivalence requires a defined margin and an analysis designed to assess whether uncertainty is sufficiently limited within that margin; neither is reported in the registry record. Likewise, the absence of reported significance tests does not show that no statistical difference existed.

The safety counts give limited descriptive information: no serious adverse events or deaths are recorded, and other adverse events are reported for 2 participants in the Restasis and Dextenza group and 0 in each of the other groups. With no event descriptions or comparative safety analysis, these counts do not establish a causal difference or characterize the types of events.

In practical statistical terms, the record documents a study question and design but leaves the central outcome question unanswered. Any interpretation beyond that would require results and analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why a clear endpoint definition and a reported analysis are both needed to interpret a clinical trial. The record specifies how corneal staining is scored and when it is assessed, so readers can understand the intended measure. But an endpoint definition alone cannot show the direction or size of a treatment contrast. Without outcome estimates and uncertainty, the statistical evidence for the comparison cannot be evaluated.

The design also raises common questions about multi-arm and repeated-measure studies. There are three regimens, several primary assessment times, and multiple secondary measures. Each can contribute useful information, but the analysis plan needs to clarify which comparisons are primary and how the related tests are interpreted. Those details are not reported in the registry record, so multiplicity handling and the intended analysis strategy remain unclear.

The enrollment of 30 is relevant to how much information the trial could provide, but enrollment alone does not determine precision. Precision depends on the observed data and the analysis as well as the sample size. Since the primary-outcome estimates and uncertainty measures are absent, readers cannot assess how precisely the study estimated any difference. Planning illustrations based on an observed effect are not a substitute for reporting the actual trial results or its original sample-size rationale.

Finally, the safety counts show how zero-event reports should be read cautiously when event numbers are limited. They describe what was recorded in this study, not the full range of possible risks. The statistical lesson is broader than any one regimen: transparent reporting of outcomes, analysis choices, missing data and uncertainty is essential before readers can judge what a randomized comparison contributes.

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 consequential limitation for statistical interpretation is that the registry record reports no outcome analyses. It gives no primary-outcome means, changes from baseline, between-group estimates, confidence intervals or p-values. The primary question therefore cannot be answered from the posted results. The record also does not report results for the listed secondary measures.

The primary outcome is assessed at multiple follow-up times, but the registry indicates that it is not reduced to one comparison. It does not explain the planned contrast, whether each time point was analyzed separately, or how repeated measurements within participants were handled. The study also includes multiple treatment groups and secondary outcomes, while multiplicity procedures are not reported.

The record does not describe missing-data methods, participant analysis populations, baseline characteristics, adherence, or departures from assigned treatment. These details are important for understanding whether the analyzed participants and measurements correspond to the randomized groups and planned outcomes. The randomization method is not described beyond the designation randomized.

The enrollment is 30, with 10 subjects described in each arm. The registry record does not provide a sample-size justification, and the planning illustrations it describes are based on an observed effect rather than the trial’s own design justification. Without outcome estimates and uncertainty, the precision of the primary comparison cannot be assessed.

Masking is listed as none, and the record does not give further detail about assessor awareness or safeguards in outcome scoring. The overall study is described as 6 months, whereas the primary outcome timeframe ends at Week 12; the registry does not explain what was assessed during the remainder of the stated duration. Finally, adverse-event counts are reported without event types or additional clinical detail.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparing Treatment of Dry Eye With Intracanalicular Dexamethasone, Restasis, and/or Lotemax — NCT04555694.
• Registry record last updated 2023-10-11; status last verified 2023-09.
• Results first posted 2023-10-11.
• 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

NCT04555694 is a completed Phase 4 randomized, parallel-group study of treatment regimens for dry eye. The enrollment was 30, with 10 subjects described in each of three groups: Restasis with Lotemax, Restasis with Dextenza, and Restasis alone. Masking is listed as none. The registry gives a start date of 2020-10-01 and a primary completion date of 2022-02-16.

The primary outcome is mean ocular surface staining from baseline at Week 4, Week 8 and Week 12. Secondary outcomes include conjunctival staining, Schirmer tear testing, tear breakup time, tear osmolarity, meibomian gland scores and DEQ-5 score. The registry reports 0 analyses, so comparative outcome results are not reported in the registry record.

Serious adverse events and deaths are reported for 0 participants in each group. Other adverse events affected 2 participants in the Restasis and Dextenza group and 0 in each other group. Event details are not reported in the registry record.