Clinical Trial to Evaluate the Chronic Efficacy of OC-01 Nasal Spray on Signs of Dry Eye Disease (The MYSTIC Study): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial to Evaluate the Chronic Efficacy of OC-01 Nasal Spray on Signs of Dry Eye Disease (The MYSTIC Study) (NCT03873246), a randomized phase 2 study. The primary outcome is Mean Change in Schirmer's Test Score From Baseline to 84 Days.

2. Clinical Question

3. Trial Design

The registry record describes a completed, randomized, parallel-group phase 2 clinical trial sponsored by Oyster Point Pharma, Inc. It lists dry eye disease as the condition, an enrollment of 123, a start date of 2019-02-18, and a primary completion date of 2020-01-07. The study objective was to evaluate chronic safety and effectiveness of OC-01 nasal spray compared with placebo on signs of dry eye disease.

Three groups are represented in the primary outcome: OC-01 0.1%, 0.6 mg/ml; OC-01 0.2%, 1.2 mg/ml; and placebo. Each group has 41 participants in the outcome record. The placebo arm is described as vehicle control. The two OC-01 arms are compared separately with placebo, rather than with each other, in the posted comparisons.

The registry’s masking field says DOUBLE, while the official title describes the study as single-masked. The registry record does not explain this difference. It would therefore be inappropriate to infer from these descriptions which trial personnel or participants were masked, or how masking was implemented.

The primary endpoint is the mean change in Schirmer’s test score from baseline to 84 days, with measurements identified as Visit 1 and Visit 6. The analysis population is labeled ITT Population-LOCF. The posted results give least-squares means with standard errors for the arms and mean differences with confidence intervals for each OC-01 dose versus placebo. The registry lists seven outcome measures but no secondary outcomes in the posted results summary. It reports no analyses in its analysis count. The trial’s original statistical analysis plan, sample-size justification, and other design details 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: Subjects in the ITT Population-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.

Population: Subjects in the ITT population

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in Schirmer's Test Score From Baseline to 84 Days, measured over Visit 1 (baseline) and Visit 6 (84 days).

The primary endpoint is mean change in Schirmer’s test score from baseline to 84 days. Schirmer’s test assesses tear production: after the eye is numbed, a paper strip is placed in the eye for 5 minutes, and the distance wetted is recorded. The measure is reported in millimeters. The registry describes a score range of 0-35 mm and states that a higher score indicates a better outcome.

Change from baseline is used to express how the measured score at follow-up differs from the participant’s starting measurement. Comparing average changes between a treatment arm and placebo focuses the result on between-group differences over the stated follow-up period. The posted endpoint is a group-level summary, not an account of every participant’s score or experience.

The registry identifies the reported arm values as least-squares means and their dispersion as standard errors. The reported mean changes were 10.8 for the 0.1% dose, 11.0 for the 0.2% dose, and 6.0 for placebo. The corresponding reported comparisons are against placebo. These measurements describe this endpoint at the stated visit; they do not capture every aspect of dry eye disease, and the registry record does not report the endpoint’s relationship to symptoms or other outcomes.

7. Results Posted in the Registry

• OC-01 0.1%, 0.6 mg/ml: mean 10.80 versus 6.00 on control; difference 4.80 (95% CI 1.22 to 8.38), standardized effect d = 0.58; z-test p = 0.009.
• OC-01 0.2%. 1.2 mg/ml: mean 11.00 versus 6.00 on control; difference 5.00 (95% CI 1.42 to 8.58), standardized effect d = 0.61; z-test p = 0.006.

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: each participant’s Schirmer’s test score is measured on a numerical scale, and the primary result is expressed as a mean change. The posted arm values are least-squares means. In general, a least-squares mean is a model-based estimate of a group average; it can differ from a simple arithmetic average if the analysis model accounts for other factors. The registry record does not describe the model or list covariates, so the details of how these estimates were obtained are not reported in the registry record.

The comparison is a mean difference between each OC-01 arm and placebo. For the 0.1% dose, the posted mean difference is 4.8 mm; for the 0.2% dose, it is 5.0 mm. Positive differences indicate that the reported average change was higher in the OC-01 arm than in placebo for this endpoint. A general way to interpret a mean difference is to compare its size and uncertainty with the scale and context of the outcome. The registry record does not report a threshold for a clinically important difference, so statistical evidence alone does not tell readers how important a difference would be to participants.

A standard error describes the estimated uncertainty in a mean, rather than the spread of individual participant values. Each arm’s standard error is reported as 1.29. Standard errors are used in estimation and inference, including construction of confidence intervals. They should not be interpreted as showing that individual scores cluster closely around the mean: individual variability is a different quantity. The arm-level values do not include a directly reported standard deviation. The comparison summary includes an approximate pooled standard deviation of 8.26, derived for the recalculated planning illustration from posted summary statistics. It is not the sponsor’s reported participant-level variability measure.

A confidence interval gives a range of values reasonably compatible with the observed data and the statistical procedure used, under its assumptions. It expresses estimation uncertainty, not the probability that the true difference falls within this particular calculated interval. For each comparison the interval is a 95% confidence interval. Its width reflects the uncertainty in the estimated difference; a narrower interval would indicate greater precision, while a wider interval would leave more uncertainty about the size of the effect. The intervals are for the between-arm differences, not for individual outcomes.

The posted p-values are labeled unadjusted. In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that null hypothesis and the analysis assumptions held. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. Here, the comparisons are the two OC-01 dose groups versus placebo. The registry record does not report a multiplicity adjustment or explain whether the overall analysis plan accounted for testing more than one comparison. When several hypotheses are tested, multiplicity can make false-positive findings more likely if the tests are interpreted without an appropriate plan. No correction or adjusted result should be inferred when it is not reported.

The endpoint population is labeled ITT Population-LOCF. In general, an intention-to-treat approach seeks to analyze participants according to their randomized group, while LOCF means carrying the last observed value forward when a later value is missing. This method can preserve an analysis set but relies on assumptions about what an unobserved later measurement would have been. Its use can affect estimates if missingness or participant trajectories differ in ways that the carried-forward value does not represent. The registry record does not report how many endpoint measurements were missing, why they were missing, or what sensitivity analyses were conducted. It is not possible to assess the impact of missing data from the posted summary alone.

The trial is described as randomized and parallel-group, so the groups are intended to be compared as distinct assigned arms. Randomization can help balance measured and unmeasured characteristics on average, but it does not guarantee balance in a particular trial. Baseline characteristics and allocation details are not reported in the primary outcome summary. The registry’s masking field and official-title wording differ: the field says double masking, while the title says single-masked. Implementation details are not reported.

The registry reports an analysis count of 0, while the outcome record includes the primary endpoint estimates and contrasts. This field does not provide the full analysis methods. Details such as model specification, handling of protocol deviations, a prespecified hypothesis-testing hierarchy, and any interim analysis are not reported in the registry record. General statistical explanations above describe what the methods mean; they do not fill in those missing protocol details.

10. Confidence Intervals and Precision

The 95% confidence interval for the mean difference between OC-01 0.1%, 0.6 mg/ml and placebo extends from 1.224 to 8.376 mm. For OC-01 0.2%, 1.2 mg/ml versus placebo, it extends from 1.424 to 8.576 mm. Each interval is entirely above zero, but each also spans a range of possible difference sizes. The reported point estimates, 4.8 mm and 5.0 mm, should therefore be read as estimates with uncertainty, not as exact effects.

Confidence intervals convey precision: their width indicates how much uncertainty remains around an estimate under the statistical method used. A confidence interval is not a range containing every participant’s result, and it is not a statement that a particular probability applies to the fixed underlying effect. In repeated use of a procedure under its assumptions, a 95% confidence-interval method has its usual long-run coverage interpretation. That interpretation depends on the method and assumptions being suitable.

The posted arm standard errors are 1.29 for all three groups, each of which has 41 participants in the outcome record. The comparison intervals are the most direct indication of precision for the dose-versus-placebo estimates. The registry record does not report details of the model used to construct the least-squares means and intervals, so the method cannot be independently evaluated from the summary alone. No adjusted confidence intervals are reported.

Precision should be considered separately from importance. A statistically distinguishable estimate does not by itself establish whether the difference matters to participants. The registry record does not report a clinical-importance threshold for Schirmer’s test change. Nor do these intervals establish the precision of results for symptoms, other outcomes, or follow-up beyond the specified 84-day endpoint.

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 sample-size figures are planning illustrations based on the observed mean differences, not the original trial’s documented design calculations. They are reported as participants per arm for 80% power and participants per arm for 90% power. These are not total enrollment figures and are not total event counts. The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect.

The 80% power column means the illustrated sample size is intended to give an 80% chance of detecting the assumed difference at the stated significance level if that difference is the true effect and the planning assumptions hold. The 90% power column gives a higher target chance under the same type of assumptions, and therefore generally requires more participants. These percentages describe design properties under assumptions; they do not say how likely the posted result is to be true.

The rows for planning for 100%, 75%, and 50% of the observed effect show how the assumed target difference changes the required sample size. A smaller effect is harder to distinguish from random variation, so it requires more participants per arm to reach the same power target. The calculations are separate for the two OC-01 versus placebo comparisons.

This is not observed power. The trial’s own original sample-size justification and design assumptions are not reported in the registry record. The figures should be read as conditional planning illustrations, not as evidence that the study was designed around these targets or that the observed result had a particular probability of being detected.

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 = 4.800; pooled standard deviation σ = 8.260.
2. n = 2 × (1.96 + 0.842)² × 8.260² / 4.800² = 46.5, rounded up to 47 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 <- 4.8                      # observed difference in means
sigma <- 8.26003026628837                     # 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(3873246)
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 = 47 (80% power), 63 (90% power)
 75% of observed effect: n per arm = 83 (80% power), 111 (90% power)
 50% of observed effect: n per arm = 186 (80% power), 249 (90% power)
power.t.test: 47.5 
Simulated power at n = 47 per arm: 0.793 (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. Multiplicity, Missing Data and Analysis Populations

The posted outcome is the primary mean change in Schirmer’s test score from baseline to 84 days. The registry lists seven outcome measures, but the results summary identifies no posted secondary outcomes. It reports two primary dose-versus-placebo comparisons, each with an unadjusted p-value. The registry record does not report whether those comparisons were part of a prespecified multiplicity strategy, whether other endpoints or time points entered the testing family, or whether any adjusted p-values were calculated. Without that information, multiplicity handling cannot be reconstructed from these results.

Multiplicity matters in general because making several statistical tests increases the chance that at least one result appears statistically notable by chance if the tests are interpreted without adjustment. A planned hierarchy, adjustment method, or other strategy can address this issue, but none is described in the posted record. The unadjusted p-values should therefore be identified as such and not treated as multiplicity-adjusted evidence.

The reported endpoint population is ITT Population-LOCF. This label indicates an intention-to-treat analysis population using last observation carried forward for missing values, but the registry record does not give the number of participants with missing measurements, reasons for missingness, or timing of missing observations. It also does not report sensitivity analyses using alternative missing-data assumptions. As a general matter, carrying a previous value forward assumes that this is a useful substitute for a later unobserved value; departures from that assumption can affect estimated group differences.

The registry record does not report whether every randomized participant contributed to the endpoint analysis, whether any exclusions occurred, or how protocol deviations were addressed. It also does not describe other analysis populations. Randomized group counts and endpoint analysis counts should not be assumed interchangeable beyond the counts explicitly posted. These gaps limit evaluation of the robustness of the reported estimates and prevent a fuller account of the planned statistical approach.

14. 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 non-serious adverse event terms

The serious adverse event figures report zero affected participants in each group: OC-01 0.1%, 0.6 mg/ml; OC-01 0.2%, 1.2 mg/ml; and placebo. Each group lists 41 participants at risk. The deaths field is also 0 for each group. No serious adverse event terms are listed in the registry record.

For other adverse events, the record reports 4 affected in the 0.1% dose group, 5 in the 0.2% dose group, and 4 in the placebo group, with 41 at risk in each. These are counts, not rates calculated. The registry record does not provide event descriptions, severity, timing, duration, or details about how many events each affected participant experienced. It also does not provide enough information in this summary to assess differences in exposure time or ascertainment across groups.

These figures summarize the posted safety counts and should not be read as a complete safety profile or as proof that no serious events could occur. The study objective includes chronic safety, but these counts alone do not establish safety beyond the participants and follow-up represented in the record.

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

The posted primary results describe greater average change in Schirmer’s test score in each OC-01 dose group than in placebo through the 84-day endpoint. The mean differences were 4.8 mm for the 0.1% dose and 5.0 mm for the 0.2% dose, with 95% confidence intervals from 1.224 to 8.376 and from 1.424 to 8.576, respectively. These estimates and intervals summarize the reported outcome in the ITT Population-LOCF population.

They do not establish the size of a difference with certainty. Each confidence interval includes multiple possible values, and the registry does not report a threshold for interpreting the difference as clinically important. The result is specific to a tear-production measure; it does not, on its own, describe symptom relief, all features of dry eye disease, or outcomes at times other than the stated follow-up.

The two comparisons are each against placebo. The posted record does not report a direct statistical comparison of the OC-01 doses, so it cannot establish that one dose performs better than the other or that their effects are equivalent. The unadjusted p-values are reported, but the registry record does not describe a multiplicity plan. This means the p-values should not be treated as adjusted for the two comparisons or other outcomes.

The safety summary reports no serious adverse events affecting participants in any of the three groups and no deaths, alongside the listed counts for other adverse events. These limited counts do not settle broader safety questions. More detailed event descriptions and follow-up information are not reported in the registry record.

Overall, the posted data support a precise statement about the group-level endpoint estimates and their uncertainty. They do not warrant conclusions beyond the studied population, outcome, analysis approach, and follow-up captured in the registry results. Clinical importance, generalizability, and the influence of missing data or multiplicity remain unresolved by the posted summary.

16. Why This Trial Matters Statistically

This trial illustrates why reading an estimate involves more than checking whether a p-value is below a threshold. The mean differences quantify the observed contrast in the primary endpoint, while the confidence intervals show uncertainty around those estimates. Together, they communicate both the direction of the reported comparison and the range of effect sizes compatible with the data under the stated method.

It also highlights the distinction between a continuous endpoint and outcomes that count events. Schirmer’s test is a numerical measure of tear production, and the primary result concerns average change. The serious adverse event summary, by contrast, is based on affected-participant counts. Those two kinds of summaries answer different questions and should not be conflated.

The results also make clear why a trial’s statistical plan matters. Two dose-versus-placebo comparisons are posted with unadjusted p-values, but the registry does not describe how multiplicity was addressed. The endpoint population is labeled ITT-LOCF, yet missing-data counts and sensitivity analyses are not reported. These details affect how confidently readers can assess the robustness of the estimates.

Finally, the planning illustrations show how sample-size requirements depend on the effect assumed for planning: smaller target effects require more participants per arm for the same power target. Those figures are not the trial’s original design rationale and are not observed power. Keeping that distinction clear prevents a post-result planning exercise from being mistaken for evidence about what the trial was designed to detect.

17. 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 posted endpoint results have several limits specific to the record. The outcome is a change in Schirmer’s test score to 84 days, so the summary does not establish what happened for symptoms or other aspects of dry eye disease. The registry lists seven outcome measures but provides no secondary results in the summary. A clinical-importance threshold for the primary measure is not reported.

The record gives the analysis population label ITT Population-LOCF but does not report missing measurement counts, reasons for missingness, or sensitivity analyses. It is therefore not possible to judge from the posted summary how strongly the results depend on carrying the last observed value forward. Details of the least-squares model, covariate adjustment, and analysis set are also not reported.

The two dose comparisons have unadjusted p-values, and the registry does not report a multiplicity plan or adjusted results. The field for masking says DOUBLE, while the official title says single-masked; the record does not explain the difference. The registry also reports an analysis count of 0, and does not provide the original statistical analysis plan or trial-specific sample-size justification.

The safety summary is limited to counts of affected participants and deaths. Event terms, severity, timing, duration, and exposure details are not reported in this summary. The results should therefore be interpreted as a record of the posted outcome and safety data, not as a complete account of all methods or outcomes.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Clinical Trial to Evaluate the Chronic Efficacy of OC-01 Nasal Spray on Signs of Dry Eye Disease (The MYSTIC Study) — NCT03873246.
• Registry record last updated 2022-06-08; status last verified 2022-03.
• Results first posted 2022-06-08.
• 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.

21. Record Summary

NCT03873246 is a completed randomized, parallel-group phase 2 study of OC-01 nasal spray for dry eye disease. The registry reports enrollment of 123, with 41 participants in each of two OC-01 dose groups and the placebo group. Its primary endpoint is mean change in Schirmer’s test score from baseline to 84 days in the ITT Population-LOCF population.

The posted mean differences versus placebo are 4.8 mm for OC-01 0.1%, 0.6 mg/ml and 5.0 mm for OC-01 0.2%, 1.2 mg/ml. Their 95% confidence intervals are 1.224 to 8.376 and 1.424 to 8.576, respectively; the unadjusted p-values are 0.009 and 0.006. Safety counts report zero serious adverse events affecting participants and zero deaths in all groups. Multiplicity handling, missing-data details, and the original sample-size justification are not reported in the registry record.