Management of Signs and Symptoms Associated With Dry Eye Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Management of Signs and Symptoms Associated With Dry Eye Disease (NCT04015219), a randomized na study. The primary outcome is Corneal Fluorescein Staining.

2. Clinical Question

The study was designed to compare the addition of PROKERA SLIM to standard of care with standard of care alone. Its primary outcome is a sign-based measure of corneal staining, with higher scores indicating worse staining. This makes the outcome relevant to the trial’s stated focus on signs and symptoms associated with dry eye disease, but the registry record does not report a treatment-effect estimate or an inferential analysis.

The posted results include a mean and standard deviation for each arm at the one-month time point. The treatment arm has 2 participants in the posted outcome summary, and the control arm has 1. This sparse information is not enough to establish whether the arm summaries reflect a reproducible difference, or to quantify uncertainty around a between-arm comparison. The registry also lists Eye Dryness Score and Ocular Surface Disease Index as secondary outcomes, but outcome results and analyses for those measures are not reported in the registry record.

3. Trial Design

This was a prospective, randomized, controlled, parallel-arm study. The planned comparison was PROKERA SLIM plus standard of care against standard of care alone. The registry classifies the study as single-masked; which participants or study personnel were masked is not reported in the registry record. The phase is listed as not applicable.

The registry lists enrollment as 3 and the study status as terminated. The recorded start date is 2018-07-18, and the primary completion date is 2020-10-05. The reason for termination and the timing of that decision are not reported in the registry record. The number of participants enrolled should not be interpreted as evidence that the planned recruitment target was reached, because the target and its justification are not reported in the registry record.

The posted primary outcome is corneal fluorescein staining at 1 month. Arm summaries show 2 participants in the treatment arm and 1 in the control arm. These outcome counts are consistent with the registry’s overall enrollment listing, but the record does not describe participant flow, exclusions, or whether all enrolled participants contributed data to each outcome. Random allocation is reported, but the sequence-generation method, allocation concealment, and any procedures used to preserve masking are not reported in the registry record.

The registry identifies BioTissue Holdings, Inc as sponsor. It describes the treatment arm as PROKERA SLIM plus standard of care and the control arm as standard of care. The intervention listing also includes lifitegrast ophthalmic solution; whether it was used as standard of care or in another way is not reported in the registry record. Details such as treatment duration, adherence, and permitted additional care are not reported in the registry record. These omissions limit how specifically the design can be reconstructed from the registry entry.

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 Corneal Fluorescein Staining, measured over 1 month.

The primary endpoint is corneal fluorescein staining, recorded as a mean with a standard deviation and measured in units on a scale. The registry gives the assessment time as 1 month. The study-eye score ranges from 0 to 9, with 9 described as worse. It is the sum of scores for the upper, middle, and lower thirds of the cornea. Each part is graded from 0 for no staining to 3 for diffuse staining.

This type of endpoint is used to quantify a clinical sign: the degree of staining observed across the cornea. A higher score on the stated scale represents worse staining, so the score has an interpretable direction. In general, a continuous outcome can be described by a mean to represent its central level and by a standard deviation to describe variation among observations. Those summaries are most informative when there are enough observations to characterize the group distribution.

The registry reports a treatment-arm mean of 0.5 and standard deviation of 0.7, based on 2 participants, and a control-arm mean of 3.0 and standard deviation of 0.0, based on 1 participant. With only one control observation, the posted standard deviation of 0.0 does not demonstrate an absence of variation in the underlying population. The registry does not report baseline scores or an adjusted analysis, so the posted endpoint summaries alone do not show change from baseline or an adjusted treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, single-masked, parallel-arm design and a continuous primary outcome summarized by means and standard deviations. It does not report a statistical analysis plan or a completed analysis for comparing the arms. The endpoint-specific record says values were missing or not estimable for a two-arm comparison. These registry entries constrain what can be concluded from the posted results.

What does a mean summarize?

In general, a mean is the arithmetic average of observed values in a group. It offers a compact description of the group’s central level, but it does not show the full distribution. A mean can be sensitive to unusually high or low values, and it conveys no direct information about how precisely the underlying group mean has been estimated. Precision depends on features including the amount of data and the variability of observations.

Here, the registry reports a mean for each arm at 1 month. The treatment-arm mean is 0.5; the control-arm mean is 3.0. These arm summaries can be read as descriptions of the posted observations, but a comparison of means generally requires an estimate of the contrast and its uncertainty. The registry does not post such an estimate, and explicitly states that a two-arm comparison is not estimable from the available values.

What does a standard deviation describe?

In general, a standard deviation describes how dispersed observations are around their group mean. It is not the same as a confidence interval, and it does not measure uncertainty in a treatment effect. A small standard deviation in an adequately observed sample suggests that its values lie relatively close to the mean; a large one suggests greater spread. The interpretation also depends on the sample size and how the data were collected.

The treatment-arm standard deviation is 0.7, based on 2 participants. The control-arm standard deviation is 0.0, based on 1 participant. With only one observation, the group’s sample standard deviation cannot describe variation among participants. The posted 0.0 should therefore not be read as a precise estimate of population variability. The very limited treatment-arm data likewise make the reported spread an uncertain description of the wider population.

Why is a between-arm result not available?

A comparative analysis typically estimates how the outcome differs between randomized groups, then quantifies uncertainty using a standard error, confidence interval, or a test statistic. The exact method depends on the outcome, design, and analysis plan. In general, uncertainty is large when data are sparse, and some estimates cannot be reliably calculated when one group has only a single observation. The registry explicitly marks the continuous two-arm comparison as missing or not estimable. It gives no contrast, standard error, confidence interval, or p-value for the primary endpoint.

Randomization defines how participants are assigned, not how results must be analyzed. The registry does not report the randomization sequence method, an analysis model, covariate adjustment, or an analysis population. It also does not state whether the primary analysis was intended to use endpoint values, change from baseline, or another estimand. These analysis details are not reported in the registry record, so they should not be reconstructed by assumption.

How should significance and precision be understood?

In general, a p-value addresses how compatible data are with a specified null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. A confidence interval communicates uncertainty in an estimate under the chosen method. Neither quantity is posted for the primary comparison. The absence of a reported p-value is not evidence that a comparison found no effect; in this record, the stated reason is that values were missing or not estimable for the comparison.

The registry’s sample-size planning assumptions describe a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect specified as a stated fraction of the observed effect. These are planning assumptions, not evidence of the trial’s actual analysis plan or of its achieved precision. Any sample-size illustrations based on an observed effect are planning exercises and must not be described as observed power. The registry does not report the trial’s own sample-size justification or the details needed to judge how any planning target was selected.

Why do the outcome scale and design matter?

In general, a continuous scale preserves more gradation than a binary classification, but an analysis still depends on distributional and design assumptions. A normal approximation may be useful for some planning calculations; that assumption alone does not establish that it is suitable for an observed-data analysis. Over-dispersion is a concern when counts vary more than an assumed model allows. It is not the central issue for this continuous endpoint, though assessing the distribution and variability of continuous measurements still matters. With this sparse record, those features cannot be assessed reliably.

A parallel-arm randomized design compares groups assessed under separate assignments. Masking can reduce some sources of bias, but the record’s single-masked label does not identify who was masked or how masking was maintained. The registry does not report whether the primary outcome assessment was masked. No conclusions about those operational details can be drawn from the design label alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and identifies 2 secondary outcomes: Eye Dryness Score and Ocular Surface Disease Index. It does not report results for those secondary outcomes, or specify whether they were analyzed. The primary endpoint is corneal fluorescein staining at 1 month. The number of analyses recorded is 0, and the registry indicates that a two-arm comparison of the continuous endpoint was not estimable.

Multiplicity arises when several outcomes, time points, or statistical tests are considered. In general, examining multiple outcomes can increase the chance that at least one result appears notable by chance. Trial reports may address this by identifying a primary endpoint in advance, adjusting inference, or clearly labeling other analyses as exploratory. The registry identifies a primary outcome, but multiplicity procedures and any hierarchy among outcomes are not reported in the registry record. It is therefore not possible to determine whether or how multiplicity was handled.

Missing-data methods and analysis populations are also not reported in the registry record. The posted arm counts do not explain whether participants were excluded, whether any outcome observations were missing, or how the analysis set was defined. No imputation method, sensitivity analysis, or reason for missingness is reported. These details matter because results can depend on which participants contribute outcome data and on assumptions about absent observations.

Interim analyses, stopping rules, and any adjustments for repeated assessments are not reported in the registry record. The study status is terminated, but the record does not give the reason for termination or connect it to any interim result. It would be speculative to infer that a particular statistical procedure was used or that a specific missing-data or multiplicity approach was planned.

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 0% reporting threshold.

The registry reports no serious adverse events in either arm: 0 serious events among 2 participants at risk in the treatment arm, and 0 among 1 participant at risk in the control arm. It also reports 0 other adverse events among the participants at risk in each arm, and 0 deaths in each arm. These counts describe what the registry records for the listed risk groups.

Zero reported events should not be interpreted as proof that the intervention or standard of care has no safety risks. In general, the chance of observing an event depends on the number of participants followed, the duration and completeness of follow-up, and how events are defined and collected. The registry record does not report the adverse-event observation period, collection methods, or detailed event definitions. With the small arm counts, these summaries cannot provide a precise estimate of event frequency or rule out uncommon events.

The registry lists no top serious-event terms. That is consistent with the reported serious-event counts, but it does not provide additional information about safety assessment procedures. The posted figures should be read as event counts for this terminated study, not as a definitive safety comparison between arms.

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

The result documents one-month corneal fluorescein staining summaries for the two study arms. The treatment arm has a reported mean of 0.5 and standard deviation of 0.7 among 2 participants; the control arm has a reported mean of 3.0 and standard deviation of 0.0 among 1 participant. The scale description says that 9 is worse, with scores ranging from 0 for no staining to 9 for the study-eye score. These summaries characterize only the observations recorded in the registry.

They do not establish a comparative treatment effect. The registry states that the values are missing or not estimable for a two-arm comparison and reports no analysis. A difference between the posted means, by itself, would not show whether an observed contrast is precise, reproducible, or attributable to the assigned intervention. The control summary has only one observation, and its reported standard deviation cannot establish the amount of variation in the wider population.

The result also does not describe change from baseline. Baseline outcome values and a baseline-adjusted analysis are not reported in the registry record. It does not establish how participants’ symptoms changed, because results for the listed secondary outcomes are not reported. Nor does it establish the effectiveness or ineffectiveness of either treatment approach. The record documents a trial design and sparse outcome summaries, rather than a supported inference about comparative benefit.

The absence of a comparative analysis should not be translated into a finding of no difference. It means the registry does not present an estimable statistical comparison. Similarly, the low treatment-arm mean should not be treated as proof of a treatment benefit. Neither interpretation is justified by the information recorded.

The adverse-event record lists no serious events, other events, or deaths in the arm-specific counts. Given the small numbers at risk and the absence of further follow-up details, those counts are not sufficient to characterize safety precisely. Overall, the most defensible reading is narrow: the registry records arm-level one-month staining summaries and event counts, but does not provide enough comparative analysis to draw a reliable conclusion about treatment effects or safety.

13. Why This Trial Matters Statistically

This study is statistically notable because its registry entry shows how design labels and outcome summaries can coexist with very limited evidence for a comparative estimate. Randomization is intended to support a comparison, but valid interpretation also depends on having outcome data and a reported analysis capable of quantifying uncertainty. Here, the registry lists 3 participants enrolled, while the primary endpoint summaries include 2 participants in the treatment arm and 1 in the control arm. It explicitly says the continuous two-arm comparison is not estimable.

The endpoint also illustrates why summary statistics must be read in context. A mean is easy to compare descriptively, but a mean alone is not an estimate of a treatment effect with known precision. The control standard deviation of 0.0 is especially important to interpret carefully: with one participant, it does not characterize the range of values that might occur in a broader population. Reporting a standard deviation without attending to the underlying count can invite overconfidence in a summary that is highly limited.

The trial’s terminated status creates another interpretive boundary. Without a recorded reason for termination, the status cannot be linked to efficacy, safety, recruitment, or any other cause. This is a useful reminder that a registry status is an administrative description, not an explanation of the data or the decision process.

Finally, the registry identifies secondary measures but reports no results for them, and it does not describe missing-data, multiplicity, or analysis-population procedures. These omissions prevent a fuller assessment of the evidence-generating process. The study matters statistically as an example of why posted outcome values, design information, and inferential results are distinct: descriptive figures can be reported even when a reliable between-arm conclusion is unavailable.

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 is the sparse primary outcome record: the treatment summary is based on 2 participants and the control summary on 1. The registry itself states that a two-arm comparison is not estimable. As a result, the posted means and standard deviations cannot support a precise comparative inference, and the single-observation control summary cannot characterize within-group variability.

The registry does not report baseline corneal staining scores, participant-level data, a treatment-effect estimate, a confidence interval, or a p-value. It also does not report the statistical model or the intended analysis population. Without those details, readers cannot assess adjustment choices, verify calculations, or determine how the primary result was meant to be analyzed.

Additional clinical and operational details are limited. The record does not report participant demographics, full eligibility criteria, the contents of standard of care, treatment adherence, or the role of listed lifitegrast ophthalmic solution. It does not identify who was masked or explain the masking procedures. These gaps limit interpretation of the population, comparator, and trial conduct.

The registry lists secondary outcomes but does not report their results. Missing-data methods, multiplicity procedures, interim analyses, and the reason for termination are not reported in the registry record. These limitations leave important questions about participant flow, outcome availability, and the context of study completion unanswered. None should be resolved by speculation from the arm summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Management of Signs and Symptoms Associated With Dry Eye Disease — NCT04015219.
• Registry record last updated 2022-12-23; status last verified 2022-12.
• Results first posted 2022-12-23.
• 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

The registry describes a prospective, randomized, controlled, single-masked, parallel-arm study of PROKERA SLIM plus standard of care versus standard of care alone for dry eye disease. Its status is terminated, with enrollment listed as 3. The recorded study start date is 2018-07-18 and the primary completion date is 2020-10-05.

The primary outcome is mean corneal fluorescein staining at 1 month, on a scale where 9 is worse. The treatment arm summary is 0.5 with standard deviation 0.7 among 2 participants; the control arm summary is 3.0 with standard deviation 0.0 among 1 participant. The registry says the two-arm continuous comparison is missing or not estimable and records 0 analyses.

Eye Dryness Score and Ocular Surface Disease Index are listed as secondary outcomes, without posted results. The reason for termination, analysis plan, missing-data procedures, and multiplicity approach are not reported in the registry record. No serious adverse events, other adverse events, or deaths are recorded in either arm, but the small numbers at risk do not permit a precise safety assessment.