Evaluation of the Efficacy of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Efficacy of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease (NCT03636061), a randomized phase 2 study. The primary outcome is Mean Change in Schirmer's Test Score From Baseline to 28 Days.

2. Clinical Question

This question focuses on between-group differences in change, rather than on whether any group changed from its own baseline. The primary endpoint is a continuous measure, and the record reports least-squares means with standard errors for each group. The comparisons discussed in the results are unadjusted recalculations from the posted group summaries; the registry record does not include reported inferential analyses for the primary endpoint. Consequently, the estimates and their uncertainty are useful descriptions of the posted summaries, but they should not be mistaken for an analysis plan or for a complete account of the trial's sponsor analysis.

3. Trial Design

ONSET-1 is identified as a phase 2, multicenter, randomized, controlled, double-masked clinical trial. Its official title describes a parallel-group design evaluating OC-01 nasal spray for signs and symptoms of dry eye disease. The registry lists four arms: three OC-01 dose levels and placebo. The record gives an overall enrollment of 182. The trial status is completed; the recorded start date is 2018-08-15 and the primary completion date is 2018-09-26.

Randomization and masking are design features intended, in general, to limit systematic differences between groups and expectations that might influence assessment or reporting. A parallel design means participants are assigned to a group and outcomes are compared across groups; it is distinct from a design in which each participant receives multiple study conditions in sequence. The precise randomization procedure, allocation ratio, masking roles, and steps used to maintain masking are not reported in the registry record.

The primary endpoint is assessed at 28 days, and the record also lists secondary outcomes at 28 days and 21 days. Its primary population is described as ITT-LOCF. Details about how participants were assigned to that analysis population, the handling of deviations from assigned treatment, and the rules for missing measurements are not reported in the registry record. The original protocol's sample-size justification and design assumptions are also not reported in the registry record. The planning illustrations accompanying the results are based on observed effects and should not be read as documentation of the trial's original design.

Although the record identifies a controlled randomized design, a full evaluation of conduct and analysis would require information beyond the posted summary. For example, the registry record does not report the statistical analysis plan, the exact model used to obtain the least-squares means, or whether any planned interim analyses occurred. These absences limit assessment of how closely the displayed summaries reflect the original protocol, but do not change the basic description of the study design and its listed outcomes.

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

Analysis population for the primary outcome, as defined in the registry: Subjects in ITT-LOCF population

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in Schirmer's Test Score From Baseline to 28 Days, measured over 28 Days [Visit 1 (baseline) and Visit 5 (28 days)].

The primary endpoint is the mean change from baseline to 28 days in anesthetized Schirmer's Test Score (STS) in the study eye. The registry describes the measurement as a score from 0-35 mm and states that a higher score indicates a better outcome. The endpoint is presented as a least-squares mean with a standard error for each treatment group, in the ITT-LOCF population.

Schirmer's Test Score is used as a sign of dry eye disease, rather than as a direct measure of a participant's reported symptoms. In general, a change-from-baseline endpoint expresses how a measurement differs from its starting value. Comparing these changes across randomized groups helps distinguish a group difference from a change that might also occur over time in the comparator group. The trial's posted primary summaries report changes of 10.1 for low-dose OC-01, 11.7 for mid-dose OC-01, and 11.0 for high-dose OC-01; the placebo mean change is 3.2.

The record does not state a clinically meaningful threshold for STS change, nor does it report a minimum difference that would be considered important to participants. It also does not provide a detailed account of the measurement procedure beyond describing the test as anesthetized and identifying the study eye. Thus, the endpoint can be interpreted as a measured sign with a specified direction, while the clinical importance of a particular numerical difference cannot be established from the registry summary alone.

7. Results Posted in the Registry

• OC-01 Low Dose, 0.12 mg/mL: mean 10.10 versus 3.20 on control; difference 6.90 (95% CI 3.34 to 10.46), standardized effect d = 0.80; z-test p = <0.001.
• OC-01 Mid Dose, 0.6 mg/ML: mean 11.70 versus 3.20 on control; difference 8.50 (95% CI 4.92 to 12.08), standardized effect d = 0.99; z-test p = <0.001.
• OC-01 High Dose, 1.2 mg/mL: mean 11.00 versus 3.20 on control; difference 7.80 (95% CI 4.06 to 11.54), standardized effect d = 0.90; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Eye Dryness Score From Baseline to Day 28

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • OC-01 Low Dose, 0.12 mg/ml: mean -11.60 versus -5.40 on control; difference -6.20 (95% CI -16.50 to 4.10), standardized effect d = -0.25; z-test p = 0.238.
  • OC-01 Mid Dose, 0.6 mg/ml: mean -18.90 versus -5.40 on control; difference -13.50 (95% CI -23.85 to -3.15), standardized effect d = -0.54; z-test p = 0.011.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OC-01 Low Dose, 0.12 mg/ml and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for OC-01 Mid Dose, 0.6 mg/ml than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline to Day 21 in Eye Dryness Score at 5 Minutes Post Treatment in the CAE.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • OC-01 Low Dose, 0.12 mg/ml: mean -8.10 versus -4.40 on control; difference -3.70 (95% CI -11.32 to 3.92), standardized effect d = -0.21; z-test p = 0.341.
  • OC-01 Mid Dose, 0.6 mg/ml: mean -16.00 versus -4.40 on control; difference -11.60 (95% CI -19.22 to -3.98), standardized effect d = -0.64; z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between OC-01 Low Dose, 0.12 mg/ml and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for OC-01 Mid Dose, 0.6 mg/ml than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry posts two secondary eye-dryness outcomes: change from baseline to Day 28 and change from baseline to Day 21 at 5 minutes post treatment in the CAE. Across these summaries, the OC-01 groups tend to have more negative mean changes than placebo, but the pattern is not uniform across dose groups or endpoints. The direction and practical meaning of a negative score change depend on the scale's interpretation, which is not described in enough detail in the registry record to assign a clinical meaning.

These outcomes add symptom-score context to the primary Schirmer's Test Score, which is a measured sign. The secondary summaries do not replace the primary endpoint, and they do not establish that the observed sign and symptom changes have a particular relationship. The registry does not report a threshold for meaningful change on the eye-dryness measures, nor does it provide reported analyses that establish a confirmatory relationship between secondary outcomes and the primary result.

In general, results from several endpoints and treatment contrasts create multiple opportunities to observe apparently notable findings. The registry record contains no reported analysis results for these secondary outcomes and does not state a multiplicity adjustment or hierarchical testing plan. Their accompanying recalculated comparisons are unadjusted. Therefore, the secondary results are best read as exploratory context, with less inferential weight than a prespecified primary analysis supported by a stated testing strategy. This does not mean the summaries have no value; it means their uncertainty and the number of questions considered need to be taken into account.

The record also does not report whether these secondary outcomes were prespecified in a protocol, how their scales were administered, or how missing observations were handled. Those omissions make it difficult to judge the intended role and robustness of the secondary findings. They can describe the posted pattern, but should not be used alone to settle the overall interpretation of the trial.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Eye Dryness Score From Baseline to Day 28
• Change From Baseline to Day 21 in Eye Dryness Score at 5 Minutes Post Treatment in the CAE.

9. Statistical Interpretation

10. Statistical Methods Explained

In general, a continuous outcome is measured on a numerical scale, so results can be described with a mean and a measure of uncertainty. Here, the primary outcome is a change score on the Schirmer's Test Score scale. The registry labels each group summary a least-squares mean and reports a standard error. A least-squares mean is generally a model-based estimate of a group mean, potentially adjusted for variables in the model; the model and any adjustment variables used in this trial are not reported in the registry record. The posted group means should therefore be described using the registry's label without inferring how they were obtained.

A standard error describes the uncertainty in an estimated mean, rather than the spread of individual participant measurements. In general, it is used to assess how precisely an estimate has been obtained. The primary group standard errors are 1.26, 1.27, 1.39, and 1.31 for low-dose OC-01, mid-dose OC-01, high-dose OC-01, and placebo, respectively. The registry does not supply group confidence limits for these means. Those standard errors also do not reveal the full distribution of individual scores.

A between-group mean difference compares the average change in one group with the average change in another. For each primary contrast, the posted low-, mid-, or high-dose mean is compared with the placebo mean. The displayed differences of 6.9, 8.5, and 7.8 are simple unadjusted recalculations from those group summaries. They are not direct comparisons between OC-01 doses and are not described as adjusted estimates from the trial's original analysis model. In general, the between-group contrast is more informative for a randomized comparison than considering whether one group's change alone is statistically distinguishable from zero.

The comparison confidence intervals are also recalculated from the posted summary statistics. They use an approximate pooled standard deviation derived from the reported standard errors and group sizes. This is a simple approach, not a reconstruction of the unreported sponsor model. In general, a confidence interval gives a range of effect estimates compatible with the data and the calculation's assumptions. It communicates both the estimated direction and the uncertainty around the estimate. The endpoints should therefore be read as approximate, and not as registry-reported model-based intervals.

The p-values accompanying the comparisons are unadjusted recalculations. In general, a p-value measures how incompatible data are with a specified null hypothesis under the assumptions of a statistical test; it is not the probability that the null hypothesis is true, and it does not measure clinical importance. Because these p-values are unadjusted, they do not account for the number of outcomes, doses, or comparisons considered. The record lists no reported analyses for the posted endpoints, so the recalculated p-values should not be attributed to a sponsor-reported analysis.

General explanation: least-squares mean comparisons can account for covariates or other features through a model, while a simple comparison reconstructed from summary values may not. Consequently, an estimate from a recalculation may not match a prespecified model-based result if the original analysis used adjustment, a different variance estimate, a different analysis set, or another method. The registry record does not report enough detail to determine whether those methods were used in the original analysis. No discrepancy is identified in the registry summary, but that does not turn the recalculation into an official analysis.

For a continuous measure, variability among participants matters because it affects how clearly group means can be distinguished. In general, greater variability makes an estimate less precise if other study features are held constant. The comparisons use approximate pooled standard deviations of 8.615, 8.602, and 8.688 for the three primary dose contrasts, respectively. These are derived approximations, not additional observed summaries in the registry record. The record reports standard errors for group means, not individual-level standard deviations for the endpoint.

General explanation: multiplicity arises when several statistical questions are examined, such as multiple treatment comparisons or multiple outcomes. If each is assessed separately without adjustment, the chance of at least one apparently notable result can increase. Whether and how to control this depends on the trial's prespecified testing strategy. That strategy is not reported in the registry record. Accordingly, the unadjusted comparisons are best treated as descriptive evidence rather than as a complete confirmatory testing framework.

The primary population is labeled ITT-LOCF. In general, an intention-to-treat approach aims to analyze participants according to their randomized assignment, while last observation carried forward refers to using an earlier observed value to fill a later missing value under a specified rule. The registry uses the population label, but does not report the detailed implementation, the amount or pattern of missing data, or the assumptions used for imputation. It is not possible to assess from the summary whether this approach was applied uniformly or whether sensitivity analyses were conducted.

Finally, statistical significance and clinical importance are different questions. A confidence interval and p-value describe evidence and precision under statistical assumptions. Clinical importance requires context about the measurement scale, meaningful change, participant experience, and possible harms. A threshold for meaningful change is not reported in the registry record. The numerical summaries can inform the first type of question, but they do not answer the second on their own.

11. Confidence Intervals and Precision

For the primary contrasts, recalculated confidence intervals are 3.338 to 10.46 for low-dose OC-01 versus placebo, 4.924 to 12.08 for mid-dose OC-01 versus placebo, and 4.056 to 11.54 for high-dose OC-01 versus placebo. Each interval lies above zero. In general, an interval that lies on one side of zero is consistent with a contrast in that direction under the calculation used. These intervals are approximate recalculations from the posted group summaries, not confidence intervals reported as sponsor analyses in the registry record.

The intervals do not pinpoint a single effect size. For example, the low-dose contrast is compatible with values across its reported interval, rather than only the point estimate of 6.9. The same principle applies to the other contrasts. In general, narrower intervals indicate greater precision, while wider intervals indicate more uncertainty about the magnitude. Precision should be judged by the range of plausible values and the relevance of those values, not only by whether the interval crosses zero.

Interpretation is limited by what is available: group least-squares means and standard errors, rather than individual participant data or a fully described analysis model. The comparison intervals use an approximate pooled standard deviation derived from these summaries. The registry record does not report sponsor confidence intervals or the model-based variance calculation, and the recalculated intervals should not be presented as substitutes for them. The original analysis's treatment of covariates, missing data, and multiplicity is not reported.

Even a relatively precise estimate would not establish clinical importance without a meaningful-change threshold or supporting clinical context. Such a threshold is not reported in the registry record. The intervals therefore communicate statistical uncertainty in the approximate difference in score, not certainty about symptoms, durability, or the clinical value of the observed difference.

12. 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 illustrations based on observed effects, not a record of the trial's original sample-size design. They assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each row considers detecting the stated fraction of the observed effect. For these continuous outcomes, the displayed counts are participants per arm, not total events. The event-count convention for time-to-event outcomes does not apply to this trial's continuous measures.

The 80% power column gives the number of participants per arm that the illustration estimates would be needed to have an 80% chance of detecting the specified effect under its assumptions, if that effect were the true one. The 90% power column expresses the corresponding planning target for a 90% chance. These are prospective planning quantities; they do not describe what happened in the completed trial. This is not observed power.

Each row uses a different fraction of the observed effect. Planning for 75% of the observed effect, for example, means considering a smaller difference than the full observed estimate. Smaller effects are harder to distinguish from random variation, so the illustration requires more participants per arm as the effect being targeted gets smaller. The same principle applies when planning for a higher power level: a stronger chance of detecting an effect generally calls for more participants, given the stated assumptions.

The assumptions do not establish that the original trial was designed around the observed differences, and they do not account for details that are not specified in the planning illustration. The original protocol's sample-size justification and assumptions are not reported in the registry record. Use the figures as hypothetical planning references tied to the observed summaries, not as evidence that the trial was adequately or inadequately powered.

13. 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 = 6.900; pooled standard deviation σ = 8.615.
2. n = 2 × (1.96 + 0.842)² × 8.615² / 6.900² = 24.5, rounded up to 25 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 <- 6.9                      # observed difference in means
sigma <- 8.61530601472012                     # 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(3636061)
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 = 25 (80% power), 33 (90% power)
 75% of observed effect: n per arm = 44 (80% power), 59 (90% power)
 50% of observed effect: n per arm = 98 (80% power), 132 (90% power)
power.t.test: 25.5 
Simulated power at n = 25 per arm: 0.794 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and two secondary outcomes, with three OC-01 dose groups and placebo. The primary summaries support three dose-versus-placebo comparisons, while the secondary summaries include comparisons for some, but not all, listed treatment groups. Examining multiple endpoints and contrasts creates a multiplicity question: results that appear notable in separate unadjusted tests may be less persuasive when the full set of tests is considered.

The registry record does not report a multiplicity adjustment, a hierarchical testing procedure, or another family-wise testing strategy. It also does not report a statistical analysis plan that would establish which comparisons were confirmatory and in what order they were to be tested. The p-values associated with the comparisons are unadjusted recalculations, not reported sponsor analyses. Their interpretation should therefore remain descriptive, particularly for secondary outcomes.

The primary population is labeled ITT-LOCF. That label indicates the intended population and a last-observation-carried-forward approach, but the registry does not report the number of missing endpoint values, their reasons, or the exact imputation rules. It also does not report whether alternative missing-data analyses were performed. In general, missing-data assumptions can affect estimates when observed outcomes differ systematically from unobserved outcomes. Without details about missingness and sensitivity analyses, the extent of that potential effect cannot be assessed.

Other analysis details are also not reported in the registry record, including the exact model for the least-squares means, covariates, handling of protocol deviations, and whether interim analyses took place. The registry does not report the original sample-size justification. These omissions do not prove that such procedures were absent; they mean that the record does not document them. As a result, a full assessment of confirmatory error control, robustness to missing data, and fidelity to the planned analysis cannot be made from the posted summary alone.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (2.1%).

The serious adverse event summary lists 0 affected participants in the low-dose group, 1 in the mid-dose group, 0 in the high-dose group, and 0 in the placebo group. The groups at risk are listed as 47, 48, 44, and 43, respectively. The registry also reports 0 deaths in each group. These are counts from the posted safety summary; they do not describe the nature, timing, duration, or outcome of individual events.

The registry lists Anaemia at 2.1% among the top serious-event terms, but does not identify the associated group or provide further context for that term in the summary. The serious-event figures should be read separately from the counts for other adverse events: the record lists 33, 44, 41, and 11 participants affected by other adverse events in the low-dose, mid-dose, high-dose, and placebo groups, respectively. Those counts are not the same category as serious adverse events.

In general, safety comparisons require context about event definitions, exposure, duration, severity, and how events were collected. Those details are not reported in the registry record. Small group counts also make the summaries descriptive rather than a basis for attributing an event to treatment. These figures alone cannot establish comparative safety.

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

The results describe group-level changes in a measured sign and eye-dryness scores over the listed follow-up periods. For the primary endpoint, each OC-01 group has a higher posted mean change than placebo, and the simple unadjusted recalculations produce positive differences with approximate confidence intervals above zero. This describes the numerical pattern in the registry summary; it is not a treatment recommendation or a definitive statement about clinical effect.

The primary endpoint is Schirmer's Test Score, for which the registry states that a higher score indicates a better outcome. The endpoint is not itself a direct report of how participants felt. Conversely, the posted symptom-score outcomes have a scale interpretation that is not fully described in the registry record. No clinically meaningful threshold is given for either type of outcome, so the numerical results cannot alone show whether the size of a change matters to participants.

The registry record does not include sponsor-reported inferential analyses for the primary or secondary outcomes. The comparisons and p-values described in the statistical interpretation are unadjusted recalculations from summaries, with approximate intervals. The original statistical model, multiplicity plan, and missing-data analyses are not reported. The evidence therefore has important limits in how precisely the estimates can be attributed to the original planned analysis.

The results also do not establish durability beyond the outcome time points listed, an effect on outcomes not measured in the posted summaries, or a dose-response relationship. The primary point estimates are not strictly increasing with dose, and no dose-trend analysis is reported. Safety findings are limited to the posted event counts and lack detail about event characteristics and exposure. In general, interpretation of trial results requires weighing the design, estimates, precision, outcome relevance, and safety information together; the registry summary does not answer every one of those questions.

Accordingly, the most defensible reading is that the posted primary summaries show a difference in mean change between each dose group and placebo at 28 days, while important details needed for clinical and confirmatory interpretation are not reported in the registry record. The numerical pattern is informative, but should not be expanded into claims beyond the measured outcomes and the limitations of the recorded analyses.

17. Why This Trial Matters Statistically

This trial illustrates why a result is more than a single mean or p-value. The primary summaries report group means and standard errors, while the between-group contrasts and confidence intervals provide a way to describe the size and uncertainty of differences versus placebo. The distinction matters: a point estimate gives a central summary, whereas an interval communicates that the exact magnitude remains uncertain.

The trial also has multiple dose groups and secondary outcomes. Those features can be valuable for understanding the observed pattern, but they create a need for a prespecified strategy for interpreting multiple comparisons. The registry record does not report such a strategy. Statistical interpretation therefore requires separating the primary endpoint from secondary findings and distinguishing unadjusted recalculations from sponsor-reported analyses.

Another important issue is the difference between a measured sign and a symptom score. The primary outcome and the secondary outcomes address different aspects of dry eye disease. Their numerical patterns should not be assumed to carry identical clinical meaning, especially when the registry does not report meaningful-change thresholds for the scales. Statistical separation alone does not establish the practical importance of an effect.

Finally, a registry result is most useful when read with its limits made explicit. Here, the record specifies a randomized, double-masked, parallel phase 2 trial and gives outcome summaries and safety counts. It does not report the original sample-size justification, the analysis plan, model details, multiplicity procedures, or missing-data sensitivity analyses. Recognizing what is documented and what remains unreported is part of sound biostatistical interpretation, not a reason to discard the available numerical results.

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 registry summary does not report the statistical analysis plan, the detailed model used for least-squares means, or which covariates, if any, were included. The comparison intervals and p-values are unadjusted recalculations from group summaries, with approximate variance assumptions, rather than sponsor-reported inferential analyses. The record lists no reported analyses for these outcomes, so it is not possible to verify whether the recalculations align with the planned primary analysis.

The record does not state the clinically meaningful difference for Schirmer's Test Score or for the eye-dryness scales. It also does not provide full scale interpretation for the secondary score changes. This limits assessment of how important the numerical differences might be, even when their direction is clear for the primary score.

Although the primary population is labeled ITT-LOCF, the amount and pattern of missing data and the precise imputation procedures are not reported. No sensitivity analyses are reported in the registry record. Multiplicity procedures are also not reported despite multiple treatment groups and outcomes. The original sample-size assumptions and justification are not reported, so the planning illustrations cannot be treated as evidence about the trial's initial design.

For safety, the available summary gives affected-participant counts but little detail on event timing, severity beyond the serious-event category, exposure, or clinical course. The Anaemia term is listed without associated group context. Finally, the summaries do not establish longer-term outcomes beyond the listed time points or provide a basis for extrapolating beyond the studied population and setting. These limitations constrain interpretation without changing the numerical values recorded.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Evaluation of the Efficacy of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease — NCT03636061.
• Registry record last updated 2021-10-25; status last verified 2021-08.
• Results first posted 2021-10-25.
• 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

NCT03636061 is the completed phase 2 ONSET-1 study, a multicenter, randomized, controlled, double-masked, parallel trial of OC-01 (varenicline) nasal spray versus placebo for dry eye disease. The registry reports enrollment of 182 and three OC-01 dose groups: 0.12 mg/mL, 0.6 mg/mL, and 1.2 mg/mL.

The primary endpoint is mean change in anesthetized Schirmer's Test Score from baseline to 28 days, in the ITT-LOCF population. Posted group means are 10.1, 11.7, and 11.0 for the three OC-01 groups, and 3.2 for placebo. Unadjusted comparisons and approximate confidence intervals are recalculated from the group summaries; sponsor-reported analyses are not reported in the registry record.

Two secondary eye-dryness outcomes and group safety counts are also recorded. Details of the statistical analysis plan, multiplicity handling, missing-data analyses, and original sample-size justification are not reported in the registry record.