The Effects of Cyclosporin A in a Low Humidity Environment, on the Ocular Surface: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effects of Cyclosporin A in a Low Humidity Environment, on the Ocular Surface (NCT02199964), a randomized na study. The primary outcome is Corneal Fluorescein Staining.

2. Clinical Question

The clinical question concerns how the two assigned eye-drop regimens relate to corneal staining under an environmental stress procedure. The registry summary describes a hypothesis that cyclosporin would minimize irritation and ocular-surface disease resulting from short-term low humidity. That hypothesis is the study’s stated rationale, not a conclusion established by the posted results.

Eye irritation symptoms are listed as a secondary outcome, but their results are not reported in the registry record. The primary data are too limited to establish a dependable comparison between the treatment groups. They describe the observed group summaries, rather than a precise estimate of the treatment effect or evidence that one regimen is superior.

3. Trial Design

The study is registered as randomized, double-masked, and parallel-group. Participants were assigned to cyclosporin 0.05% emulsion or Endura Refresh artificial tears. Both regimens were to be used in the eye 4 times a day. The registry identifies Baylor College of Medicine as the sponsor and lists dry eye as the condition under study.

The record gives enrollment as 4. It also states that the study was not completed because of loss of funding, and that data from only 2 subjects per group were analyzed. Its status is terminated. The start is recorded as 2014-03, and primary completion is recorded as 2015-12. These registry dates do not establish when every participant was treated or when each analysis was conducted.

The primary outcome is corneal fluorescein staining, measured at the 6-week timeframe. The described assessment uses an adjusted CCLR global staining score before and after environmental challenge at baseline and Visit 3/Day 42. The challenge involved 90 minutes in a low-humidity environment. The registry says staining was graded across 5 corneal zones and that the total score ranges from 0 to 500, with higher values indicating greater corneal disease induced by low humidity on Day 42.

The record lists Eye Irritation Symptoms as a secondary outcome. It does not give a detailed analysis plan, a sample-size justification, or the rationale for the selected follow-up schedule; these are not reported in the registry record. It also does not report a full participant flow or explain how the analyzed subjects were selected from those enrolled. The design labels indicate the intended randomized comparison, while the early termination and limited analyzed data constrain what can be learned from the observed summaries.

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: There were no pre-assignment details.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Due to loss of funding, this study was not completed and enrollment ended. Data from only 2 subjects per group was analyzed

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 Corneal Fluorescein Staining, measured over 6 weeks.

Corneal fluorescein staining is an assessment of the ocular surface. In this study, staining was graded using an adjusted CCLR global score across 5 zones on the cornea. The registry describes scores from 0 to 500 and says that a higher score indicates greater corneal disease induced by the low-humidity stress on Day 42.

The stated primary outcome concerns the mean difference in staining before and after environmental challenge, assessed at baseline and Visit 3/Day 42. The challenge was a 90-minute exposure to low humidity. The outcome is listed as a mean of a continuous measure, with standard deviation as its measure of dispersion, and the timeframe is 6 weeks.

Staining is used as an objective measure of ocular-surface changes associated with the environmental challenge. A continuous score can retain gradations in the measured response rather than reducing the assessment to a simple yes-or-no outcome. That makes it useful for describing the degree of staining, but interpretation still depends on how the score was collected, how the challenge affected measurements, and how consistently the assessments were made.

The registry does not report the detailed scoring procedures beyond the stated scale and zones, nor does it provide individual measurements or an uncertainty interval for the group summaries. The posted arm values therefore should be read as limited descriptive statistics, not as a complete account of the before-and-after response or a precise estimate of the difference between regimens.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, double-masked, and parallel-group. Randomization is a method for assigning participants to groups by chance, intended to reduce systematic differences between groups at the outset. Masking is intended to limit the influence of treatment knowledge on participants or study personnel. The record states these design features, but further details about how randomization and masking were implemented are not reported in the registry record.

What does a mean describe?

The primary outcome is treated as a continuous measure, and the reported arm values are means. A mean describes the arithmetic average of the observations included in a group summary. It provides a concise description of the observed scores, but can be sensitive to unusually high or low observations. With only 2 subjects per group analyzed, a mean may not characterize the range of responses among a broader group of people.

What does a standard deviation describe?

A standard deviation describes the spread of observed values around a mean. A larger standard deviation indicates that observations are more dispersed, while a smaller one indicates less dispersion. It is not the same as a confidence interval: a standard deviation describes variation among observations, whereas a confidence interval is used to express uncertainty about an estimated quantity. No confidence interval for the group means or their comparison is reported in the registry record.

Why does the comparison matter?

For a randomized trial, the central statistical question is commonly the contrast between outcomes in the assigned groups. The posted means describe each group separately. The registry record does not provide an estimable two-arm comparison for this continuous endpoint, nor does it report a test statistic, p-value, or confidence interval for a contrast. Without an analysis of the between-group comparison, the group summaries alone do not quantify the treatment effect or its uncertainty.

The endpoint description refers to measurements before and after environmental challenge at baseline and Visit 3/Day 42. A direct analysis could depend on whether the outcome is defined as a change from baseline, a post-challenge score, or another prespecified summary. The registry does not report a complete statistical specification resolving that detail. It is therefore important not to infer an analysis method from the outcome title or to treat the listed means as a particular calculated change unless the record identifies them that way.

Why does over-dispersion matter?

In general, over-dispersion means that observed variability is greater than assumed by a statistical model. When a model understates variability, its standard errors may be too small and uncertainty may appear less than it is. This is a general statistical concern, not a reported finding from this trial. The registry does not report an assessment of over-dispersion or a model-based analysis. Given the very small analyzed groups, the main limitation is that variability and precision are difficult to characterize, rather than that a particular variance model has been shown to fail.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the analysis. A narrow interval indicates greater precision, while a wide interval indicates less precision. A p-value, when reported, evaluates the compatibility of the data with a specified statistical null model; it is not the probability that a treatment works or that a finding is true. Neither a confidence interval nor a p-value is reported for the primary comparison in this record. No statistical significance conclusion can therefore be drawn from a registry analysis result.

The registry marks the continuous two-arm comparison as not estimable. This means the record does not furnish a calculated comparison suitable for interpreting as an inferential treatment effect. The listed group summaries remain descriptive. Recalculation from summary statistics would not resolve the missing analysis details or turn the small set of observations into a complete trial result.

Sample-size calculations, when used in planning, estimate how many participants per arm might be needed under stated assumptions about the effect, variability, significance level, allocation, and statistical method. They are planning illustrations, not observed power and not evidence about the chance that a completed study has found a true effect. The registry record does not report the trial’s own sample-size justification. Any planning illustration based on the observed effect should be distinguished from the original study design, especially because the observed summaries come from groups of only 2 subjects.

The registry’s stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those assumptions describe a planning framework, not the trial’s reported inferential analysis. The record does not give a sample-size justification or indicate that these assumptions were used to design the trial. Such calculations should not be read as evidence that the study had adequate power, nor should they be called observed power.

Finally, the registry lists no analyses. This absence matters: the arm means and standard deviations do not substitute for a prespecified statistical analysis, documentation of model assumptions, or an uncertainty estimate for the contrast. The design labels and endpoint description explain the intended framework, but the statistical plan and inferential results are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Cyclosporin 0.05% Emulsion", "Endura Refresh, Artificial Tears")
n   <- c(2, 2)
m   <- c(21.5, 29)
sp  <- c(13.44, 15.6)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Cyclosporin 0.05% Emulsion  2  21.500  13.440  -99.254  142.254
CARM  Endura Refresh, Artificial Tears  2  29.000  15.600  -111.160  169.160

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, time points, treatment contrasts, or statistical tests. If many tests are conducted, the chance of at least one apparently notable result can increase. Statistical plans sometimes address this by identifying a primary outcome, setting a hierarchy for testing, or adjusting interpretation for multiple comparisons. The registry identifies corneal fluorescein staining as the primary outcome and Eye Irritation Symptoms as a secondary outcome, but a multiplicity strategy is not reported in the registry record.

The record lists 3 outcome measures and 1 secondary outcome, but does not report the full set of analyses or how any multiple outcomes or assessments would be handled. The number of outcome measures does not reveal how many statistical tests were planned or conducted. Because no analyses are listed, there is no reported set of inferential results from which to assess multiplicity adjustments.

Missing-data procedures and analysis populations are also not reported in the registry record. The record says the study was not completed because of loss of funding and that data from only 2 subjects per group were analyzed. It does not explain whether other enrolled participants had missing measurements, why they were not included in the posted summaries, or how missing observations were handled.

The registry does not identify an intention-to-treat, per-protocol, or other analysis population. It also does not report whether all randomized participants were analyzed according to their assigned group. These details matter because exclusions or incomplete measurements can affect the comparability established by randomization. Without this information, the posted summaries should be understood as results for the analyzed subjects described in the record, not assumed to represent a defined analysis population.

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.

The registry reports serious adverse event figures separately for the cyclosporin and artificial-tears groups. For each group, 2 subjects were listed as at risk and 0 as affected by serious adverse events. The record also lists 2 at risk and 0 affected for other adverse events in each group, with 0 deaths in each group. No top serious-event terms are listed.

These are counts from a very small analyzed study population. A count of 0 affected participants means that the registry did not record an event in the listed category among those at risk; it does not establish that an event cannot occur or that the regimens have equivalent safety. With so few participants and a study that ended before completion, uncommon or delayed events could not be meaningfully characterized from these figures.

The record does not provide additional detail about adverse-event collection, duration of safety follow-up, severity grading beyond the serious-event classification, or causal assessment. These items are not reported in the registry record. The figures should therefore be read as limited event counts, not as a comprehensive safety comparison or a basis for medical advice.

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

The posted results establish that the registry contains descriptive primary outcome summaries for a small number of analyzed participants in a randomized, double-masked comparison. The cyclosporin group mean is 21.5, with a standard deviation of 13.44; the artificial-tears group mean is 29.0, with a standard deviation of 15.6. The score is described as increasing with greater corneal disease induced by low-humidity stress. These values report what was observed in the analyzed groups, not a definitive comparison of the assigned regimens.

The record does not provide an estimable two-arm comparison, confidence interval, or p-value. It does not establish how large a treatment effect might be, how precise such an estimate would be, or whether the observed group pattern is distinguishable from random variation. No conclusion about efficacy or lack of efficacy follows from the absence of a reported inferential result.

The study also does not provide results for its listed secondary outcome, Eye Irritation Symptoms. Detailed participant characteristics, the analysis population, missing-data handling, and a statistical plan are not reported in the registry record. Those omissions limit assessment of who contributed data, how the endpoint summaries were constructed, and how the planned clinical question relates to the posted values.

The termination due to loss of funding and the limited analyzed groups are important context for interpreting the result. The record is evidence that a study was undertaken and that a small set of outcome summaries was posted. It is not sufficient evidence to decide whether either regimen changes corneal staining under low-humidity stress, or whether any observed difference is clinically important. The appropriate reading is cautious: the posted data are descriptive and highly imprecise, and the comparative question remains unresolved by this record.

14. Why This Trial Matters Statistically

This trial illustrates why a randomized design does not, by itself, guarantee an informative result. Random assignment and masking can help protect a comparison from bias, but meaningful interpretation also depends on completion, adequate information, clearly defined analyses, and transparent reporting. Here, the record identifies randomization, double masking, and parallel groups, yet the study ended before completion and the primary summaries are based on only 2 subjects per group.

It also demonstrates the distinction between descriptive statistics and inferential evidence. Means and standard deviations tell readers about the observed data, but they do not establish the size or precision of a treatment contrast. Without a reported comparison and uncertainty interval, readers cannot assess how compatible the observations are with a range of possible effects. The outcome’s clinical direction is stated—higher staining scores indicate greater disease induced by low humidity—but that definition alone does not resolve the comparative question.

The record is also a reminder that an incomplete trial can leave important questions unanswered even when an endpoint and treatment groups are specified. A stated hypothesis is not a result, a planned outcome is not an analyzed outcome, and zero recorded adverse events in a very small group does not settle safety. Reporting why enrollment ended is useful context, while details about missing observations and analysis populations would be needed for a fuller appraisal.

For biostatistical interpretation, the central lesson is to match the strength of a conclusion to the amount and type of evidence available. In this record, that means recognizing what the summaries describe while avoiding claims that require an unreported comparison or a more complete dataset.

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 most direct limitation is the small amount of analyzed data: the registry states that only 2 subjects per group were analyzed. Such limited information makes group means sensitive to individual observations and leaves variability and precision difficult to characterize. The record states that the study was not completed because of loss of funding and that enrollment ended. It does not explain whether the analyzed subjects were selected because their measurements were complete or for another reason.

The primary endpoint description refers to a mean difference in staining before and after challenge at baseline and Visit 3/Day 42, but the registry does not fully explain how that description maps to the posted group means. It does not report individual measurements, the exact analysis population, missing-data handling, or an inferential comparison. This makes it difficult to reconstruct the intended endpoint analysis or assess whether the arm summaries represent change, a post-challenge value, or another summary.

Participant characteristics beyond the dry-eye condition are not reported in the registry record. Detailed information about the environmental challenge procedure, adherence to the assigned eye drops, and the conduct of masking is also not reported. These omissions limit assessment of how consistently the intervention and challenge were delivered and how broadly the observations might apply.

The record lists Eye Irritation Symptoms as a secondary outcome but does not report its result. It also does not provide a statistical plan, a sample-size justification, or a multiplicity approach. Taken together, the early termination, limited analyzed groups, absent inferential results, and incomplete reporting mean that the registry offers only a narrow descriptive account rather than a complete evaluation of the comparative question.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Effects of Cyclosporin A in a Low Humidity Environment, on the Ocular Surface — NCT02199964.
• Registry record last updated 2020-02-20; status last verified 2020-02.
• Results first posted 2020-02-05.
• 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

NCT02199964 is a randomized, double-masked, parallel-group study sponsored by Baylor College of Medicine in people with dry eye. It compared cyclosporin 0.05% emulsion, used in the eye 4 times a day, with Endura Refresh artificial tears, also used in the eye 4 times a day. The registry lists enrollment as 4 and records the study as terminated after loss of funding.

The primary outcome was corneal fluorescein staining at the 6-week timeframe, assessed in connection with a 90-minute low-humidity environmental challenge. The posted means are 21.5 for cyclosporin and 29.0 for artificial tears; the corresponding standard deviations are 13.44 and 15.6. The registry states that only 2 subjects per group were analyzed and marks the continuous two-arm comparison as not estimable.

Eye Irritation Symptoms is listed as a secondary outcome, but its results are not reported in the registry record. No inferential comparison, confidence interval, or p-value is reported. The available data are descriptive and too limited to resolve the comparative clinical question.