Goblet Cell Degranulation Produced by Intranasal Tear Neurostimulator (ITN) in Dry Eye Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Goblet Cell Degranulation Produced by Intranasal Tear Neurostimulator (ITN) in Dry Eye Disease (NCT03827564), a randomized na study. The primary outcome is Difference in Ratio of Degranulated Goblet Cells..

2. Clinical Question

This is a biological-measure question, rather than a question about symptoms, daily functioning, or a longer-term clinical outcome. The record does not report a threshold for a meaningful change in the ratio. Consequently, the arm summaries can describe the recorded outcome, but they do not by themselves indicate whether a change would be important to participants or clinicians.

3. Trial Design

The study was randomized, controlled, and parallel-group, with no masking reported. Its two application approaches were intranasal and extranasal use of the Intranasal Tear Neurostimulator. The registry lists the phase as not applicable. Enrollment is recorded as 14, and the primary endpoint population description says that 13 randomized participants received a single application. The reason for the difference between those figures is not reported in the registry record.

The study began on 2019-06-24, and the primary completion date is recorded as 2020-06-08. Its status is terminated. The reason for termination, whether the planned recruitment or follow-up was completed, and whether termination affected the analyses are not reported in the registry record. The status alone does not establish why the study ended or what conclusions should be drawn about the intervention.

The primary endpoint is described as the mean change in the ratio of degranulated goblet cells from screening to the application visit. Screening is specified as Day -60 to Day -30, and the application visit as Day 0. The registry’s endpoint description refers to post-intranasal use at the application visit compared with assessment without device use at screening. The posted arm summaries, however, are labelled intranasal and extranasal application. The record does not further explain how those arm summaries relate to the endpoint wording.

Arm-level summaries are reported for 6 participants in the intranasal arm and 5 in the extranasal arm. The registry also states that 13 participants received a single application. It does not explain the relationship between these group denominators and the stated endpoint population, or identify which participants were included or excluded from each summary. These details matter when assessing how complete the outcome data are and how representative the summaries may be.

The sponsor is Allergan. No additional design details, such as the randomization procedure, allocation concealment, masking of outcome assessment, or planned statistical analysis, are reported in the registry record. The record does not state a reason for choosing the comparator or give a sample-size justification.

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: Of the 14 Randomized participants, 13 received a single application of the Intranasal Tear Neurostimulator (ITN)

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: All 14 enrolled participants were randomized to study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Difference in Ratio of Degranulated Goblet Cells., measured over Screening (Day -60 to Day -30) to Application Visit (Day 0).

The primary endpoint is titled “Difference in Ratio of Degranulated Goblet Cells.” It is a continuous measure reported as a ratio, and the registry describes the summaries as means with standard deviations. The stated timeframe is change from screening (Day -60 to Day -30) to the application visit (Day 0). The endpoint description frames the assessment as the change after intranasal device use compared with the screening assessment without device use.

Goblet-cell degranulation is the biological feature this study set out to assess after acute device application. A continuous outcome can describe both the direction and the amount of change in the measured ratio, while the mean gives a summary of the observed values and the standard deviation describes their spread. These are general interpretations of the statistical measures; the registry record does not explain how the ratio was measured, how specimens were assessed, or whether the measure has a validated threshold for meaningful change.

The posted arm means are 0.007 for intranasal application and 0.124 for extranasal application. The record does not post confidence intervals or an estimable result for the two-arm comparison. The endpoint therefore offers descriptive information about the recorded changes in each arm, but it does not establish a precise comparative effect. Nor does the record connect a particular value or change in this ratio with symptoms or another clinical outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary endpoint summarized by a mean and standard deviation. It does not report an inferential analysis for the comparison between application arms. The posted information can therefore be read descriptively, but not as a complete estimate-and-uncertainty analysis.

What does a mean summarize?

For a continuous outcome, the mean is the arithmetic average of the observed values in the analysis group. It gives a compact description of the group’s central location, but it does not show the full distribution. Different sets of participant values can have the same mean. In this study, the reported means describe changes in the ratio of degranulated goblet cells for the participants included in the arm summaries. They are not, by themselves, estimates of a difference between arms.

What does a standard deviation add?

A standard deviation describes how spread out observed values are around their group mean. A larger standard deviation indicates more variation in the recorded values; it is not a measure of uncertainty in the mean itself. The standard deviation of a mean estimate depends on both the observed spread and the amount of information available. General statistical interpretation: estimates based on limited observations are often less precise, but the registry does not post confidence intervals that would quantify precision for these arm means.

Why is an arm comparison different from comparing summaries?

A comparative analysis estimates the contrast between groups using a specified statistical approach. It should also communicate uncertainty, commonly with a confidence interval, and may report a p-value for a defined hypothesis test. A confidence interval gives a range of effect estimates compatible with the data and the chosen method; it is not a guarantee that the true effect lies within that range. A p-value is interpreted relative to a null hypothesis and modeling assumptions; it does not measure the probability that a treatment works or the clinical importance of an effect. These are general concepts. The registry record posts neither a confidence interval nor a p-value for the primary comparison.

The record specifically indicates that the values needed for a two-arm comparison were missing or not estimable. It also lists zero analyses. Without a posted comparison, it is not possible to assess the magnitude or precision of the between-arm effect from the registry results. Comparing the arm means informally would not replace the missing analysis, because that would not account for the uncertainty in each group or establish a valid inferential procedure.

What can randomization contribute?

In general, random assignment is intended to make treatment groups comparable with respect to both measured and unmeasured factors, on average, before intervention. It does not guarantee balance in a particular study, especially when group summaries are limited. Randomization also does not remove the need to report outcome completeness, analysis populations, and an appropriate comparison. The registry labels this study randomized, but the allocation method and related implementation details are not reported.

What do the planning assumptions mean?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The planning target is described as a stated fraction of the observed effect. These are assumptions for illustrative sample-size calculations, not evidence about the trial’s original design. The record does not report the trial’s own sample-size justification or statistical plan. Any such illustration is a planning exercise, not observed power and not a measure of whether the study result is reliable. A sample-size calculation depends on its assumed effect, variability, significance level, allocation, and analysis method; changing assumptions changes the planning result.

General statistical interpretation: power is a design property calculated under assumptions about an effect and variability. It cannot be inferred from a non-significant result, and it does not tell whether an observed estimate is unbiased. Because the registry does not post an estimable comparative result or the underlying planning outputs, no particular sample-size target or power conclusion can be drawn from the record.

Why does endpoint measurement matter?

Statistical summaries are only as interpretable as the outcome definition and measurement process. The record names a ratio of degranulated goblet cells, but does not specify the collection procedure, scoring rules, assessor training, reproducibility, or handling of values that could not be measured. Without those details, readers cannot assess measurement error or whether the outcome was consistently evaluated across groups. The record also does not state whether the outcome distribution was examined or whether a transformation or alternative model was considered.

For a continuous endpoint, methods generally rely on assumptions about the distribution of errors and the relationship between observations. The appropriateness of a method may depend on the outcome’s distribution, influential observations, and missingness. These are general considerations, not claims about what happened in this study. Since no analysis method is reported, the registry does not allow readers to evaluate those assumptions.

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("ITN [TrueTear®] - Intranasal Application", "ITN [TrueTear®] - Extranasal Application")
n   <- c(6, 5)
m   <- c(0.007, 0.124)
sp  <- c(0.171, 0.069)
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  ITN [TrueTear®] - Intranasal Application  6  0.007  0.171  -0.172  0.186
CARM  ITN [TrueTear®] - Extranasal Application  5  0.124  0.069  0.038  0.210

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no posted secondary outcomes. This limits the visible set of outcome questions, but the record does not describe a prespecified testing hierarchy, adjustment for multiple comparisons, or a statistical plan. It is therefore not possible to determine from the registry whether multiplicity was considered in the study’s original analysis.

No analyses are posted for the primary endpoint, and the registry states that values were missing or not estimable for a two-arm comparison of the continuous outcome. It does not report how many measurements were unavailable, why they were unavailable, when missingness occurred, or how missing values were handled. The reason for the lack of an estimable comparison is not explained beyond the registry’s brief note.

The endpoint population description says that 13 of the 14 randomized participants received a single application. The arm summaries report n=6 for intranasal application and n=5 for extranasal application. The record does not explain how these analysis denominators relate to the randomized population or the participants who received an application. It does not identify an intention-to-treat population, a per-protocol population, or another prespecified analysis set.

These omissions matter because missing outcome data can affect both the precision and the interpretation of an estimate. General statistical interpretation: if missingness is related to participants’ outcomes or group assignment, an analysis restricted to observed measurements may not represent the randomized groups. The registry does not provide enough information to assess whether that concern applies here, and no imputation or sensitivity analysis is reported.

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 5% reporting threshold.

The registry reports serious adverse events for the safety groups as follows: 0 among 9 at risk in the intranasal application group, and 0 among 5 at risk in the extranasal application group. Deaths are reported as 0 in each group. Other adverse events are also reported as 0 among 9 at risk in the intranasal group and 0 among 5 at risk in the extranasal group.

These counts describe what the registry records for the stated at-risk groups. They do not establish that an event is impossible or rule out uncommon harms. The record does not explain the safety follow-up period, the definitions used for serious or other adverse events, how events were collected, or how the safety denominators relate to the primary endpoint denominators. The intranasal safety group’s at-risk count is not the same as the n reported for its endpoint summary; the record does not explain this difference.

Zero reported events should be read as a count in this study record, not as evidence that the device is free of risk. The study status is terminated, but the reason is not reported and should not be inferred from the safety counts. These registry figures do not provide a basis for medical advice or for comparing safety beyond the reported counts.

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

The results establish that the registry contains descriptive arm summaries for changes in the goblet-cell ratio after the application visit. The intranasal arm mean change is 0.007, with standard deviation 0.171, and the extranasal arm mean change is 0.124, with standard deviation 0.069. The reported group sizes for those summaries are n=6 and n=5, respectively. These numbers describe the reported observations; they are not a complete estimate of a between-arm treatment effect.

The registry does not post an estimable comparison, confidence interval, p-value, or adjusted analysis. Therefore, the summaries do not establish whether the application approaches differ, how precisely any difference is known, or whether the observed values could reflect sampling variation. No clinical threshold for interpreting the ratio is reported. The record also does not connect the endpoint to symptoms or another outcome that would establish clinical importance.

The endpoint is a biological measure assessed over the screening-to-application-visit timeframe. It does not, on its own, establish a durable response, an effect on dry-eye symptoms, or an effect on other aspects of health. The study description concerns acute use, and longer-term outcomes are not reported in the primary endpoint information.

The randomized design is relevant to the intended comparison, but the incomplete outcome reporting limits what can be concluded from the posted results. The registry does not explain why a two-arm analysis was not estimable, how the outcome population was formed, or how missing measurements were handled. The status is terminated, with no reason reported. These gaps prevent a firm interpretation of the comparative result; they do not justify assuming that an unreported analysis would favor either arm.

In short, the record supports a cautious descriptive account of the posted means and variability. It does not support a claim that either application approach is superior, that a difference is statistically significant, or that a measured change is clinically meaningful. Those questions would require a clearly defined comparative analysis, uncertainty estimates, and further information about outcome measurement and missing data.

14. Why This Trial Matters Statistically

This study illustrates why a randomized design and an interpretable result are not the same thing. Randomization is intended to support a fair comparison, but readers still need a clearly reported estimate of the contrast between groups, its uncertainty, and a description of who contributed outcome data. The registry identifies a randomized parallel-group study yet does not provide an estimable two-arm analysis for its primary continuous endpoint.

The arm summaries also show why group means should be read alongside measures of spread and group denominators. The intranasal mean is accompanied by a standard deviation of 0.171, while the extranasal mean is accompanied by a standard deviation of 0.069. These quantities describe the observed summaries, but without a comparative estimate and uncertainty interval they cannot establish the precision of a difference between approaches.

The registry’s population statements raise a separate reporting issue. It describes 14 randomized participants, 13 who received an application, and arm summaries with their own denominators. The record does not explain the relationship among these figures. Clear reporting of analysis populations and outcome availability would help readers understand which randomized participants contributed to the endpoint and why some results could not be estimated.

Finally, the primary endpoint is a biological ratio, not a direct report of symptoms or function. Statistical evidence about such a measure must be interpreted in light of how it was measured and whether changes are meaningful clinically. Those measurement details and a threshold for meaningful change are not reported. The example therefore highlights the importance of pairing a defined endpoint with complete analysis reporting, transparent missing-data information, and an interpretation that does not go beyond the evidence.

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 immediate limitation is that the registry does not post an estimable two-arm comparison for the primary endpoint. Arm means and standard deviations are available, but no confidence interval, p-value, or adjusted effect estimate is reported. The registry’s note says values were missing or not estimable; it does not explain the cause or identify the values needed for the comparison.

The outcome-population information is incomplete. The record reports 14 randomized participants, says 13 received a single application, and gives arm summary denominators of n=6 and n=5. It does not explain how these figures relate, which participants lacked measurements, or how the endpoint analysis population was defined. The handling of missing data is not reported.

Important details about the endpoint and its measurement are also absent. The record does not describe the procedure for assessing the goblet-cell ratio, the measurement’s reliability, or a threshold for clinically meaningful change. Its wording about screening without device use and the reported intranasal and extranasal arm summaries is not further clarified. This limits interpretation of both the biological outcome and the intended contrast.

The registry does not report the randomization method, allocation concealment, masking of outcome assessment, or statistical analysis plan. Although the study is described as unmasked, the record does not clarify whether endpoint assessors knew the application assignment. No reason for termination is reported, and the record does not explain whether termination affected recruitment, follow-up, or analysis. These limitations should be understood as gaps in the registry record, not as evidence of a particular study conduct or result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Goblet Cell Degranulation Produced by Intranasal Tear Neurostimulator (ITN) in Dry Eye Disease — NCT03827564.
• Registry record last updated 2021-08-16; status last verified 2021-07.
• Results first posted 2021-08-16.
• 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 record describes a randomized, controlled, parallel-group study of intranasal versus extranasal application of the Intranasal Tear Neurostimulator in participants with dry eye disease. It is listed as unmasked, with phase not applicable, enrollment of 14, and status terminated. The sponsor is Allergan.

The primary endpoint is the mean change in the ratio of degranulated goblet cells from screening (Day -60 to Day -30) to the application visit (Day 0). The posted mean changes are 0.007 (standard deviation 0.171; n=6) for intranasal application and 0.124 (standard deviation 0.069; n=5) for extranasal application. No analysis is posted, and the registry states that a two-arm comparison was not estimable because values were missing or not estimable.

The record reports zero serious adverse events, other adverse events, and deaths in each safety group, with at-risk counts of 9 for intranasal application and 5 for extranasal application. The reason for termination, the relationship between safety and endpoint populations, the handling of missing outcome data, and the statistical analysis plan are not reported in the registry record.