Clinical Trial to Evaluate the Symptoms in Symptomatic Contact Lens Wearers Following Application of Intranasal Tear Neurostimulator Versus Control: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial to Evaluate the Symptoms in Symptomatic Contact Lens Wearers Following Application of Intranasal Tear Neurostimulator Versus Control (NCT03325673), a randomized na study. The primary outcome is Contact Lens Dry Eye Questionnaire (CLDEQ-8) Score in the Study Eye.

2. Clinical Question

This was a randomized, parallel-group comparison with triple masking recorded. The central statistical question is about the difference in average reported symptoms between the assigned groups at the stated assessment time, not about each participant's change or an individual response. The registry record describes the trial as evaluating symptoms and comfortable contact lens wear time, but the posted primary endpoint is the symptom questionnaire score. Other endpoint details and secondary results are limited in the registry record.

3. Trial Design

The registry record describes CORIANDER, NCT03325673, as a randomized, double-arm, controlled clinical trial with a parallel design and triple masking. Its status is completed. The recorded start date is 2017-11-22 and the primary completion date is 2018-11-29. Phase is recorded as NA. The sponsor is Allergan. The condition listed is dry eye syndromes.

The planned comparison was between TrueTear, an intranasal tear neurostimulator, and TrueTear Sham Control. The sham device was not electrically active and had limited tip insertion depth. Both devices were used intranasally on contact lens wear days. Use on non-contact-lens days was optional, and the number of applications was determined by the participant. The registry record does not state the exact randomization procedure, allocation ratio, or which roles were masked.

Enrollment is recorded as 84. For the primary endpoint, the posted group summaries include 38 participants in the TrueTear arm and 40 in the sham arm. The primary outcome population is described as all eligible participants with data available for analysis at the given time point. The record does not explain the difference between enrollment and the endpoint analysis counts, give a participant flow account, or state how missing measurements were handled.

The primary endpoint was the Contact Lens Dry Eye Questionnaire (CLDEQ-8) score in the study eye at Day 28. The registry record lists four outcome measures and six analyses, but does not give details for all of them in the posted results. No secondary results are posted. Details of the trial's original statistical plan, including its design assumptions and any planned interim analyses, are not reported in the registry record.

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: All eligible participants with data available for analysis at the given 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: All eligible participants.

6. Primary Endpoint

The registry lists the primary outcome as Contact Lens Dry Eye Questionnaire (CLDEQ-8) Score in the Study Eye, measured over Day 28.

The primary endpoint is the Contact Lens Dry Eye Questionnaire (CLDEQ-8) score in the study eye at Day 28. The questionnaire asks participants to report how their contact lenses performed over the preceding 2-week period. It includes questions about eye discomfort, dryness, changeable blurry vision, closing the eyes, symptoms near the end of wearing time, and lens removal. The responses are combined into a total score ranging from 1, best, to 37, worst.

The endpoint is a continuous symptom measure, so the posted group summaries are means with standard deviations. A lower group mean corresponds to a better symptom score on the stated scale; this describes the questionnaire's scoring direction and is not by itself a conclusion about the treatment. The study eye was defined as the qualified eye with the greatest increase in tear production after stimulation by a cotton swab at screening. If both eyes qualified, the right eye was designated as the study eye.

Using a specified eye and a validated questionnaire gives the comparison a common measurement target across participants. The score compresses several symptom responses into one summary measure, making an average difference between randomized groups interpretable on the questionnaire's scale. It also means the result does not describe every symptom separately, contact lens wear duration, or outcomes in both eyes. The endpoint's measurement at Day 28 concerns the preceding 2-week reporting period, rather than symptoms at a single instant.

7. Results Posted in the Registry

• TrueTear: mean 15.30 versus 17.20 on control; difference -1.90 (95% CI -4.30 to 0.50), standardized effect d = -0.35; z-test p = 0.121.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant has a questionnaire score on a numeric scale. For a continuous outcome, a common summary is the group mean together with a measure of spread. The posted standard deviations describe variability in individual scores within each group; they are not standard errors and do not describe the precision of the mean difference by themselves.

What does the mean difference represent?

The recalculation defines the difference as the TrueTear mean minus the sham mean. The observed means are 15.3 and 17.2, and the recalculated difference is -1.9. A negative value therefore points toward a lower average score in the TrueTear group. The sign depends on the chosen order of subtraction: reversing the order would reverse the sign without changing the underlying comparison. Since lower CLDEQ-8 scores are better on the instrument's stated scale, the direction can be described, but the estimate remains uncertain.

What does an independent t-test assess?

The registry reports an independent t-test for the two groups. In general, an independent t-test evaluates whether the observed difference between two group means is large relative to its estimated sampling variability, under assumptions about the outcome and its distribution. Here, the groups are separate randomized arms, rather than paired measurements from the same people. The registry result is p = 0.116. The recalculation from the posted group summaries gives an unadjusted p-value of 0.121. A p-value describes how unusual data at least this incompatible with a zero difference would be under the test's null model; it is not the chance that the null hypothesis is true.

The registry record does not state whether the sponsor's test used additional adjustments, how assumptions were checked, or the exact inferential specification beyond naming the independent t-test. The recalculation is an unadjusted analysis of the posted summaries. It should therefore be read as a transparent check based on the summarized means, standard deviations, and group sizes, not as a replacement for a prespecified analysis plan.

How should the confidence interval be read?

A confidence interval gives a range of effect estimates compatible with the data and the method's assumptions. In general, narrower intervals indicate greater precision, while wider intervals indicate more uncertainty. The recalculated interval crosses zero: its lower endpoint is -4.301 and its upper endpoint is above zero. That means the data do not pin down the direction of the average difference with high precision. The confidence level is not stated in the registry record, so it cannot be attached to a particular coverage percentage.

There is also a distinction between statistical uncertainty and clinical importance. A confidence interval can help assess which effect sizes are compatible with the data, but interpreting those effects as important requires a meaningful-difference threshold or other context. Such a threshold is not reported in the registry record. The interval should not be treated as a range containing every individual participant's response.

What does the standardized effect add?

The recalculated standardized difference is d = -0.352, based on a pooled standard deviation of 5.398. Standardizing expresses a mean difference in units of the outcome's pooled variability, which can help compare effects measured on different scales. It does not alter the direction of the result or resolve uncertainty. The raw difference of -1.9 remains easier to interpret in CLDEQ-8 score units, while the standardized estimate places that difference relative to variation in this sample.

Over-dispersion is a general concern when count outcomes vary more than a simple count model assumes. It is not the issue addressed by this primary endpoint analysis, which is a continuous questionnaire score analyzed with a t-test. For a continuous outcome, the pertinent considerations include the score distribution, variability, independence of observations, and missingness. The registry record does not report diagnostic checks or alternative models, so no conclusions about those checks can be drawn.

10. Confidence Intervals and Precision

The group mean estimates are based on 38 participants in the TrueTear arm and 40 in the sham arm. The standard deviations, 5.6 and 5.2 respectively, describe the spread of scores among participants with endpoint data. The recalculated mean difference is -1.9 points. Its confidence interval crosses zero, with a lower endpoint of -4.301 and an upper endpoint above zero. This interval indicates that the direction and size of the underlying average difference remain uncertain.

Precision is not determined by the point estimate alone. It depends on the amount of variability and the amount of information in the analysis. The group standard deviations show that individual scores vary around their respective means, while the confidence interval reflects uncertainty in the difference between those means. The upper endpoint is not repeated numerically because the record's value has more than three decimal places; the relevant interpretation is that it lies above zero.

The registry does not report the confidence interval's confidence level. It also does not report a threshold for a clinically meaningful score difference. As a result, the interval can be described as spanning zero, but its nominal coverage level and the clinical importance of its plausible values cannot be specified from the registry record. The p-values provide a related test-based summary, not a substitute for considering the interval's width and direction.

Confidence intervals concern uncertainty in a group-level effect estimate under a statistical method's assumptions. They do not describe the range of scores among individuals or imply that a particular proportion of participants experienced a benefit. The published summaries also do not show participant-level results, baseline scores, or changes over time for this endpoint. Those omissions limit assessment of within-person variation and of how the Day 28 comparison relates to baseline.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total sample sizes or event counts. The illustration uses the observed effect as a starting point and considers planning for 100% of that observed effect, 75% of the observed effect, and 50% of the observed effect. For 100% of the observed effect, the figures are 127 per arm for 80% power and 170 per arm for 90% power. For 75% of the observed effect, they are 226 and 302 per arm. For 50% of the observed effect, they are 507 and 679 per arm.

In general, 80% power means that a study designed under the stated assumptions would have an 80% chance of detecting the chosen effect using the specified test and significance level, if that effect were the true one. The 90% column uses a higher target chance of detection and therefore requires more participants under otherwise identical assumptions. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants per arm.

The calculation assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It takes the effect to detect as the stated fraction of the observed effect. The registry record's original design assumptions and sample-size justification are not reported, so these planning illustrations should not be read as the trial's original enrollment target rationale. This is not observed power; it is a planning illustration based on the observed effect, not a measure of the trial's probability of success.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.900; pooled standard deviation σ = 5.398.
2. n = 2 × (1.96 + 0.842)² × 5.398² / -1.900² = 126.7, rounded up to 127 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.9                      # observed difference in means
sigma <- 5.39844032056823                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3325673)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 127 (80% power), 170 (90% power)
 75% of observed effect: n per arm = 226 (80% power), 302 (90% power)
 50% of observed effect: n per arm = 507 (80% power), 679 (90% power)
power.t.test: 127.7 
Simulated power at n = 127 per arm: 0.792 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The registry-reported analysis is an independent t-test comparing the two groups, with p = 0.116. The unadjusted recalculation from the posted means, standard deviations, and group sizes gives a mean difference of -1.9 and p = 0.121. The recalculated confidence interval crosses zero. The registry record does not mark a discrepancy between the sponsor analysis and the recalculation.

The two p-values are close but are not identical. The sponsor's own analysis takes precedence when interpreting the reported trial analysis; the recalculation is a simple check using posted summary statistics and does not reproduce any unreported details of the sponsor's analytic procedure. The record does not provide the sponsor's test statistic, a confidence interval for that analysis, or additional model specifications.

Both analyses support a cautious reading of the primary comparison: the reported data do not establish a clear nonzero mean difference under the stated test. That is not evidence that the groups are identical, and it is not a conclusion about clinical importance. The magnitude and precision of the estimated difference, together with the lack of a reported meaningful-difference threshold, remain relevant to interpretation.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and six analyses, but the complete analysis details are not reported. It records this CLDEQ-8 score as the primary outcome. No secondary results are posted. The analysis plan, hierarchy of outcomes, and any multiplicity adjustment are not reported in the registry record. Therefore, it is not possible to determine whether the displayed p-value was intended to be interpreted among several planned tests or whether any adjustment was prespecified.

Multiplicity is a general statistical issue: when many outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase. Adjustments or a prespecified hierarchy can address that issue, but the record does not state whether either approach was used. No claim about adjustment or its absence should be inferred from the count of posted analyses alone.

The endpoint population is described as eligible participants with data available for analysis at the given time point. The reported primary endpoint groups contain 38 and 40 participants, whereas enrollment is 84. The registry record does not give a participant flow diagram, reasons for missing endpoint data, or the missing-data method. It is therefore unclear from the record whether unavailable data reflect withdrawal, incomplete questionnaires, other eligibility decisions, or another reason.

The analysis population is not otherwise described in detail. The record does not state whether the primary analysis followed an intention-to-treat principle, whether participants were analyzed according to assignment, how protocol deviations were handled, or whether imputation was used. These omissions matter because missingness and exclusions can affect how well a randomized comparison represents the groups as originally assigned. They prevent a fuller assessment of the population underlying the posted estimate.

The record also does not report interim analyses, stopping rules, or the trial's full statistical analysis plan. Those elements should be treated as not reported in the registry record, rather than assumed to be absent. The primary endpoint comparison can be interpreted on its posted terms, but its relation to any broader prespecified testing strategy cannot be established.

15. 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

For serious adverse events, the registry record lists 0 among 42 at risk in the TrueTear group and 0 among 42 at risk in the TrueTear Sham Control group. It also lists 0 deaths in each group. These figures describe the posted serious-event counts and deaths; they do not establish that no other kinds of adverse events occurred.

The record lists 3 other adverse events in the TrueTear group and 4 in the sham group, with 42 participants at risk in each group. The registry does not provide event terms in the serious-event list, because no serious terms are listed, nor does it give further detail about the nature, timing, severity, or relationship of the other events in the information available for this comparison.

The at-risk counts differ from the endpoint analysis counts of 38 and 40. The registry record does not explain the denominator difference, so the safety figures should be read using their stated at-risk denominators rather than substituted for the endpoint analysis population. These counts are descriptive. Without additional information about event definitions, follow-up, and ascertainment, they do not support a broad comparative safety conclusion.

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

The posted primary outcome shows a lower average CLDEQ-8 score in the TrueTear group than in the sham group at Day 28: 15.3 compared with 17.2. The recalculated mean difference is -1.9 points, with negative values favoring a lower score in the TrueTear arm because lower scores are better on this instrument. The recalculated interval crosses zero, and the sponsor-reported independent t-test gives p = 0.116. The posted summaries therefore leave substantial uncertainty about the size and direction of the underlying group difference.

These results do not establish that the groups are identical. A non-significant test does not prove no difference; it indicates that the test did not provide strong evidence against its null model at the reported p-value. Conversely, the lower observed mean in the TrueTear group does not establish a benefit. The interval includes zero, the estimate is imprecise, and the registry record does not state a threshold for a meaningful difference on the CLDEQ-8.

The endpoint captures a combined symptom score over the preceding 2-week period and uses a specified study eye. It does not provide separate estimates for each symptom, both eyes, or comfortable contact lens wear time. Although the trial summary describes comfort and comfortable wear time as areas of interest, those outcomes cannot be evaluated from the primary endpoint result alone. Further posted endpoint results are not reported in the registry record.

The comparison is between randomized groups, but the endpoint analysis includes only participants with data available at the time point according to the population description. The record does not explain missing data or provide a full analysis plan, which limits assessment of how the analyzed sample relates to all enrolled participants. The interpretation should remain tied to the recorded Day 28 score comparison rather than extended to longer-term outcomes or other populations.

Overall, the registry's primary result is a modestly lower observed mean score in the active-device group, accompanied by uncertainty that includes no average difference. It is a description of the posted data and analysis, not a treatment recommendation or proof of a particular clinical effect.

17. Why This Trial Matters Statistically

This trial illustrates why a clinical comparison should be read through both its effect estimate and its uncertainty. The observed means differ, and the direction is interpretable from the CLDEQ-8 scoring scale. But the confidence interval crosses zero, and the reported test does not provide strong evidence against a zero mean difference. Reporting only the group means or only the p-value would miss an important part of that statistical picture.

It also shows the value of distinguishing an endpoint's measurement target from a broader study question. The trial summary refers to comfort and comfortable contact lens wear time, while the primary endpoint is a symptom questionnaire score in the study eye. A summary score is useful for a defined group comparison, but it does not automatically answer questions about every symptom or wear time. The registry's lack of secondary results makes that distinction particularly important.

The difference between enrollment and the endpoint analysis counts highlights another general issue: results depend on the population contributing data. The record gives the endpoint counts and describes an available-data population, but does not explain missingness or analysis-population procedures. This limits assessment of how missing outcomes might affect the randomized comparison.

Finally, the planning illustration demonstrates that sample-size requirements depend on the effect a future study aims to detect. Smaller target effects require larger groups under the stated assumptions. Those planning numbers are not a retrospective measure of whether the completed trial was adequately powered, nor do they reveal the original design rationale. The original sample-size justification is not reported in the registry record.

18. 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 primary endpoint analysis includes 38 TrueTear participants and 40 sham participants, compared with 84 enrolled. The record does not explain the difference, provide reasons for missing endpoint data, or describe how missingness was handled. This leaves uncertainty about selection into the analysis population and its relationship to the randomized groups.

The registry record does not state the confidence level for the recalculated interval, a threshold for a meaningful CLDEQ-8 difference, or the original sample-size justification. It does not describe the randomization method, allocation ratio, masking roles, or the full statistical analysis plan. Triple masking is recorded, but the specific masked parties are not identified.

Only the primary endpoint results are detailed in the information available. Although four outcome measures and six analyses are listed, no secondary results are posted. Thus, the primary symptom-score comparison cannot address all of the trial's stated areas of interest, including comfortable contact lens wear time. There is no posted participant-level information, baseline comparison, symptom-specific result, or detailed account of score distributions.

The posted safety information gives serious adverse event and death counts, along with counts of other adverse events, but does not provide detailed event descriptions or explain why the safety at-risk denominators differ from the endpoint counts. The trial is described as a parallel randomized comparison, but other design and implementation details that could inform assessment of the results are not reported in the registry record. These are limits on interpretation of the record, not proof that the information was not collected.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Clinical Trial to Evaluate the Symptoms in Symptomatic Contact Lens Wearers Following Application of Intranasal Tear Neurostimulator Versus Control — NCT03325673.
• Registry record last updated 2019-12-18; status last verified 2019-12.
• Results first posted 2019-12-06.
• 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.

22. Record Summary

CORIANDER (NCT03325673) is recorded as a completed, randomized, parallel, double-arm clinical trial with triple masking and phase listed as NA. It enrolled 84 participants with symptomatic contact lens wear and dry eye syndromes. The comparison was intranasal TrueTear versus a non-electrically active sham device.

The primary outcome was the study-eye CLDEQ-8 score at Day 28. Mean scores were 15.3 (standard deviation 5.6; 38 participants) for TrueTear and 17.2 (standard deviation 5.2; 40 participants) for sham. The recalculated mean difference was -1.9, with an interval crossing zero; the registry-reported independent t-test gave p = 0.116.

Serious adverse events and deaths were each listed as 0 in both groups. The registry record does not report the full statistical plan, the reasons for the endpoint analysis counts, or secondary outcome results.