Piiloset Trehalose Emulsion Eye Drop Study in Moderate or Severe Dry Eye: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Piiloset Trehalose Emulsion Eye Drop Study in Moderate or Severe Dry Eye (NCT03569202), a randomized na study. The primary outcome is Change From Baseline OSDI.

2. Clinical Question

3. Trial Design

The registry describes a randomized, active-controlled, parallel-group study with quadruple masking. The two interventions were Piiloset Trehalose Emulsion Eye Drops and control hyaluronic acid eye drops. The arm descriptions specify daily treatment. The stated treatment period was up to 30 days, and the primary outcome timeframe was baseline to Day 30.

The study enrolled 64 participants and is marked completed. The record lists a start date of 2018-05-21 and a primary completion date of 2018-11-08. The listed phase is NA. The sponsor was Kuopio University Hospital. The record does not report a trial phase beyond that listing or explain why that phase category appears.

Randomization is intended to make treatment groups comparable on average, including for characteristics that are not measured, although randomization cannot ensure exact balance in a study of this size. An active control means the comparison estimates the difference between two eye-drop approaches under the study conditions, rather than the effect of either approach against no treatment. Parallel assignment means participants were assigned to one study arm rather than crossing between treatments in a sequence.

Quadruple masking is the registry's masking description. The registry record does not identify which specific roles were masked, so those roles cannot be specified. It also does not report the allocation procedure, the sample-size justification used when designing the trial, or whether any interim analyses were planned or conducted. Those details should not be inferred from the randomized designation or from the final enrollment.

The primary outcome is identified as a mean change in OSDI in the intent-to-treat dataset. The posted group summaries each include 26 participants. Enrollment of 64 and outcome summaries based on 26 participants per arm are distinct pieces of information; the registry record does not explain the difference between the enrollment figure and the primary outcome counts. Interpretation of the posted outcome therefore rests on the reported analysis population and summaries, not on an assumption about why participants are absent from those summaries.

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.

Part 1

Part 2

Part 3

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) dataset

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: Part 3: 52 eyes of 26 pts treated with Emulsion Eye Drops and 52 eyes of 26 pts treated with Control Eye Drops. Results are reported for Part 3 only.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline OSDI, measured over From baseline to Day 30 (Part 3).

OSDI is a questionnaire intended to measure dry-eye-related symptoms and their effects. The registry describes 12 questions covering symptom frequency, vision-related quality of life and environmental triggers during the previous week. Each question is answered on a scale from 0, none of the time, to 4, all of the time. Total and subscale scores run from 0 to 100, with higher scores representing greater disability.

The primary outcome is the mean change in OSDI from baseline to Day 30. A change score compares a participant's score at follow-up with that participant's baseline score, and a group mean summarizes those changes across participants. The reported mean changes are negative in both arms. On this scale, negative change indicates that the measured score fell from baseline; the registry's score description says that higher scores represent greater disability. The group comparison, rather than either within-group change alone, addresses whether the average change differed between randomized arms.

Using a patient-reported measure gives the outcome a direct connection to participants' reported symptoms and functional effects. It also means the result depends on questionnaire responses and the scoring approach described in the registry. The record does not report a threshold for a change considered important to patients. Statistical evidence about a difference between group means therefore cannot, by itself, establish whether the size of a difference is practically meaningful.

7. Results Posted in the Registry

• Emulsion Eye Drops: mean -24.64 versus -26.53 on control; difference 1.89 (95% CI -6.49 to 10.27), standardized effect d = 0.12; z-test p = 0.659.

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 Blink Rate

• 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 deviations.
• Result:
  • Emulsion Eye Drops: mean 0.02 versus -2.15 on control; difference 2.17 (95% CI -2.98 to 7.32), standardized effect d = 0.23; z-test p = 0.409.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Emulsion Eye Drops and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline Ocular Protection Index (OPI)

• 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 deviations.
• Result:
  • Emulsion Eye Drops: mean 0.56 versus 0.05 on control; difference 0.51 (95% CI 0.02 to 1.00), standardized effect d = 0.57; z-test p = 0.041.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Emulsion Eye Drops than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline Corneal Staining

• 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 deviations.
• Result:
  • Emulsion Eye Drops: mean -0.38 versus -0.22 on control; difference -0.16 (95% CI -0.51 to 0.19), standardized effect d = -0.26; z-test p = 0.364.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Emulsion Eye Drops and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts five secondary outcome results, covering blink rate, ocular protection index, corneal staining and temporal and nasal conjunctival staining. These measures extend the assessment beyond the questionnaire-based primary outcome, including measures of blinking, ocular protection and staining. They do not replace the primary endpoint, and they may capture different aspects of the study's clinical and physiological response.

Across these results, the statistical pattern is mixed rather than uniformly pointing in one direction. At least one secondary comparison has a nominal p-value below 0.05, while other comparisons are less conclusive. The record includes both mean-based comparisons and rank-based tests, so the results do not all summarize or test the same statistical feature. Any apparent signal should therefore be interpreted in light of its endpoint, method and uncertainty, rather than as a single coherent confirmation of the primary result.

The primary OSDI comparison does not show a clear between-group difference, and secondary outcomes do not resolve that uncertainty. A secondary measure can be informative, but a result on one measure does not establish a difference on the primary patient-reported outcome. Conversely, a nonsignificant primary result does not make every secondary result irrelevant. The outcomes are complementary, but they answer distinct questions.

Multiplicity matters because the registry reports 13 outcome measures and 33 analyses. When many tests are conducted, the chance of seeing one or more nominally unusual results increases, even if there is no underlying difference for any endpoint. The registry record does not report a multiplicity adjustment or a testing hierarchy. Accordingly, unadjusted secondary p-values carry less weight than a prespecified primary analysis and are best treated as exploratory. They can motivate further study, but the record does not support treating an isolated nominal result as definitive evidence.

The registry does not report enough detail to determine whether all secondary results were prespecified in the same way, how missing data were handled for each outcome, or whether any analyses were selected after observing the data. Those unknowns further limit the strength of conclusions from secondary endpoints. The overall pattern is useful for context, but it should not be used to overrule the primary comparison.

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

• Change From Baseline Blink Rate
• Change From Baseline Ocular Protection Index (OPI)
• Change From Baseline Corneal Staining
• Change From Baseline Conjunctival (Temporal) Staining
• Change From Baseline Conjunctival (Nasal) Staining

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical OSDI change score, summarized by a mean and standard deviation for each arm. A mean describes the central average of observed changes, while a standard deviation describes how spread out the individual changes are around that mean. The primary group summaries are -24.64 with a standard deviation of 16.19 for the emulsion arm, and -26.53 with a standard deviation of 14.62 for the control arm. These summaries alone do not show the shape of the individual data or whether every participant changed in the same direction.

The simple recalculation compares the two arm means. Its estimated mean difference is 1.89 units, with the emulsion group subtracted against the control group. A positive estimate means the emulsion mean change is numerically higher, or less negative, than the control mean change. This sign convention describes the arithmetic of the contrast, not which outcome is preferable. The clinical interpretation must also account for the scale's meaning and the uncertainty around the estimate.

A confidence interval gives a range of values compatible with the data and the statistical model at the stated confidence level. The recalculated 95% interval is -6.494 to 10.27. Its width reflects that the estimate is uncertain, and its inclusion of zero means the data do not clearly separate the estimated contrast from no difference. A confidence interval is not a guarantee that the true value lies in the interval, nor does it assign a probability to a particular value after the data have been observed. It is a procedure that, under its assumptions, produces intervals that cover the target value at the stated rate across repeated studies.

The recalculated p-value is 0.659. A p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the model assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The sponsor analysis reports p = 0.662. The record flags a discrepancy, so the sponsor's own analysis takes precedence over the unadjusted calculation from summaries.

The sponsor reports an ANOVA comparison. ANOVA, or analysis of variance, is a model-based method for comparing group means. The primary outcome description concerns change from baseline, whereas the registry's reported analysis label says “Mean Difference (Final Values).” The record does not explain this labeling or provide enough detail to determine the exact model specification, covariate adjustment, or handling of repeated measurements. The safest reading is to describe the registered endpoint as change from baseline and the sponsor's posted test as labeled in the record, without assuming an unreported model detail.

General explanation: Randomization supports a comparison of groups by reducing systematic differences in treatment assignment. Statistical adjustment can sometimes improve precision or account for prespecified variables, but the registry record does not state whether the sponsor adjusted for baseline OSDI or other covariates. The recalculation is explicitly unadjusted and uses the posted summary values. It should therefore be viewed as a simple check, not as a reconstruction of the full sponsor analysis.

General explanation: A standard mean-based analysis relies on assumptions about the outcome distribution and the sampling behavior of the estimated means. With continuous questionnaire scores, the actual distribution may be bounded or asymmetric. The registry record does not report diagnostic checks or sensitivity analyses for those assumptions. This does not by itself invalidate the reported analysis; it means the available record does not permit a full assessment of robustness.

Several secondary outcomes are also continuous measures, including blink rate, ocular protection index and staining scores. The posted secondary analyses do not all use the same method: the record includes ANOVA results and Wilcoxon rank sum tests. The Wilcoxon rank sum test compares the rank distributions of observations between groups; it is not generally a test of a difference in arithmetic means. The registry also posts means and standard deviations for some secondary outcomes, but those summaries do not change the method named for the sponsor's analysis. The particular interpretation of a rank-based test depends on distributional conditions, and the record does not report further details.

The trial reports 13 outcome measures and 33 analyses in total, while five secondary outcome results are posted in the record. Multiple outcomes and analyses create more opportunities for apparently notable results to arise by chance. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a detailed statistical analysis plan. Accordingly, secondary p-values should be treated as exploratory signals rather than as confirmatory evidence.

General explanation: Missing outcome data can affect an estimate if the participants with observed measurements differ systematically from those without them. An intent-to-treat label describes the stated analysis population, but it does not by itself specify an imputation procedure or show that every randomized participant contributed to every endpoint. The registry record does not describe missing-data methods for the primary result. This limits evaluation of the assumptions behind the analysis and of the potential effect of missingness.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 1.89 OSDI units, with a 95% confidence interval from -6.494 to 10.27. The interval is wide relative to the point estimate and includes zero. Thus, the best single estimate is a small positive contrast in the stated direction, but the data remain compatible with a negative contrast as well as a positive one. The interval communicates this uncertainty more directly than the point estimate alone.

Precision depends in part on the amount of information in the analysis. The primary summaries include 26 participants in each arm, with standard deviations of 16.19 and 14.62. Variation among participants makes it harder to estimate a group mean difference precisely. A larger study can often narrow an interval if the outcome variation and analysis are similar, although no guarantee follows for any particular future study.

The confidence interval concerns the mean contrast under the recalculation's assumptions. It does not describe the range of individual participants' changes, and it is not a prediction interval for a new participant. Nor does it tell whether the interval's endpoints correspond to important differences for patients. The registry does not report an OSDI threshold for a clinically important between-group difference, so the clinical implications of the interval's range cannot be classified from these data alone.

The sponsor's reported p-value is 0.662, while the unadjusted recalculated p-value is 0.659. Because the record flags a discrepancy, the sponsor analysis is the primary reported inferential result. The closeness of the p-values does not remove the issue, and the recalculated confidence interval should not be mistaken for the sponsor's model-based interval. The sponsor's analysis is the one that takes precedence.

In general, a nonsignificant result can arise when an effect is absent, when an effect is present but estimated imprecisely, or both. Here, the interval's span and inclusion of zero are central to interpretation. They support a conclusion of substantial uncertainty about the between-group mean difference, not a conclusion of equivalence or proof of no effect.

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 participants per arm, not total participants across the study and not total events. This is a continuous-outcome comparison. The calculation is a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. The assumed effect to detect is the stated fraction of the observed effect. The registry record does not report the original trial's own sample-size assumptions or justification.

The 80% power column describes the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the specified effect under the calculation's assumptions, if that effect is present and the assumptions hold. The 90% power column gives the corresponding planning number for a 90% chance. These are design probabilities under a specified model, not probabilities that the treatment works or that a future result will be significant.

For example, planning for 100% of the observed primary effect gives 1,046 participants per arm for 80% power and 1,400 participants per arm for 90% power. Planning for 75% of the observed effect gives 1,859 participants per arm for 80% power and 2,488 participants per arm for 90% power. Planning for 50% gives 4,182 participants per arm for 80% power and 5,598 participants per arm for 90% power. The sequence illustrates that smaller effects require more participants to detect with the same target power.

The curve represents the same planning relationship across effect sizes: as the effect assumed for planning becomes smaller, the required sample size rises. A planning calculation based on an observed effect can be unstable because an observed effect in a small study may not be a reliable estimate of the effect in a future study. These figures are not evidence about the trial's actual design rationale. This is not observed power; it is a prospective planning illustration and should not be used to explain the observed p-value.

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 = 1.890; pooled standard deviation σ = 15.423.
2. n = 2 × (1.96 + 0.842)² × 15.423² / 1.890² = 1,045.3, rounded up to 1,046 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 <- 1.89                      # observed difference in means
sigma <- 15.4228887696177                     # 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(3569202)
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 = 1,046 (80% power), 1,400 (90% power)
 75% of observed effect: n per arm = 1,859 (80% power), 2,488 (90% power)
 50% of observed effect: n per arm = 4,182 (80% power), 5,598 (90% power)
power.t.test: 1046.3 
Simulated power at n = 1,046 per arm: 0.799 (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. Analyses Reported by the Sponsor

The registry reports the sponsor's primary comparison as an ANOVA, with p = 0.662. It also reports an estimate of 1.884 and a 95% confidence interval from -6.708 to 10.476. Those detailed values are part of the sponsor analysis, but values with more than three decimal places are not reproduced in this explanation. The sponsor's result is the primary inferential analysis recorded for the comparison.

The simple recalculation from the posted group summaries gives a mean difference of 1.89, a 95% confidence interval from -6.494 to 10.27 and an unadjusted p-value of 0.659. The registry flags a discrepancy between this recalculation and the sponsor analysis. The recalculation is not a corrected version of the sponsor result; it is a simple, unadjusted calculation from the posted summary statistics. The sponsor's own analysis takes precedence.

The estimates point in the same numerical direction and the reported p-values are similar, but their differences should not be erased by treating them as interchangeable. The registry labels the sponsor parameter as a mean difference in final values, while the primary outcome is described as change from baseline. The record does not explain the analysis specification or the source of the discrepancy. No further reconciliation can be made from the registry record alone.

For interpretation, the sponsor's reported test is the main inferential result, while the recalculation offers a transparent check on the summaries. Both should be read alongside the uncertainty and the study's limitations. Neither p-value measures clinical importance, establishes equivalence, or addresses outcomes beyond the reported comparison.

15. Multiplicity, Missing Data and Analysis Populations

The record lists 13 outcome measures and 33 analyses. Testing multiple outcomes or conducting multiple analyses increases the opportunity for nominally significant results to occur by chance. A multiplicity strategy can address this by controlling the error rate across a family of tests, or by specifying a testing order in which later claims depend on earlier results. The registry record does not report such a strategy, so the secondary analyses should not be interpreted as though their p-values were adjusted or protected by a prespecified hierarchy.

The primary outcome is identified as change from baseline in OSDI, which gives it a distinct role in the study. The record does not provide a full statistical analysis plan or explain how the primary outcome was prioritized among the reported outcomes and analyses. It also does not state whether there were interim analyses. These details are not reported in the registry record and should not be inferred from the completed status or the number of posted analyses.

The registry identifies the primary population as intent-to-treat. This term generally refers to analyzing participants according to randomized assignment, but the label alone does not describe how missing measurements, treatment discontinuations or protocol deviations were addressed. The primary arm summaries each include 26 participants, whereas enrollment was 64. The registry record does not explain the difference between these numbers or give a missing-data method, reasons for missing observations, or sensitivity analyses. As a result, the effect of missing outcome data on the estimate cannot be assessed from the record.

General explanation: If outcomes are missing for reasons related to participants' underlying outcomes or treatment experience, a complete-case comparison can be biased. Methods such as imputation or model-based approaches rely on assumptions that should be described and examined. No particular method or assumption can be attributed to this trial because the registry record does not report one.

For secondary outcomes, the posted sample sizes differ for some measures, and the analysis methods are not uniform. That variation reinforces the need to read each result in its own context. Without stated multiplicity and missing-data procedures, the strongest interpretation is limited to the posted analyses as exploratory evidence, with the sponsor's primary analysis taking precedence for the main endpoint.

16. 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 registry reports serious adverse events for 38 participants at risk in the emulsion group and 35 participants at risk in the control group. Serious adverse events were reported for 0 participants in each group. Deaths were also reported as 0 in both groups. The record therefore reports no serious adverse events or deaths in either arm during the reported safety accounting.

For other, non-serious adverse events, the registry reports 1 affected participant among 38 at risk in the emulsion group and 0 affected participants among 35 at risk in the control group. These figures describe participants recorded as affected, not the total number of events. The registry does not provide further details in the posted safety summary about the event term, timing, severity or relationship assessment.

These counts should be read as a description of observed reports in a study of this size and duration, not as proof that an event cannot occur. The safety at-risk counts differ from the primary outcome counts, and the registry record does not explain that difference. The reported figures also do not establish comparative safety beyond the events and participants captured in the record.

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

The primary result estimates the difference in mean OSDI change between two randomized groups over the study's baseline-to-Day-30 timeframe. The recalculated mean difference is 1.89 units, with a 95% confidence interval from -6.494 to 10.27. The sponsor reports an ANOVA p-value of 0.662, and the registry flags a discrepancy with the simple recalculation. The sponsor analysis takes precedence. The posted evidence does not provide a precise estimate that clearly distinguishes a between-group difference from no difference.

This finding is not the same as proving that the groups are equal. Failure to show a statistically clear difference can reflect an effect near zero, limited information, or an effect that the study did not estimate precisely. Equivalence requires a prespecified margin defining differences small enough to count as equivalent and a suitable analysis. The registry record does not report such a margin or an equivalence design. The study also cannot establish noninferiority without a prespecified margin and corresponding analysis, which are not reported.

The result concerns mean OSDI change, not every participant's experience. Group averages can conceal variation in individual outcomes, and the posted summaries do not show how responses were distributed. The registry does not report a threshold for a clinically important OSDI difference, so statistical uncertainty cannot be translated into a judgment about whether particular values would matter to patients.

The active comparator is hyaluronic acid eye drops. The result therefore concerns a comparison between these two assigned eye-drop approaches under the conditions recorded in the trial, not a comparison with no treatment or with all possible treatments. The treatment period was described as up to 30 days, so the primary result does not establish outcomes over longer follow-up. It also does not answer questions about people outside the studied adult population with moderate or severe dry eye.

Secondary measures and safety counts provide additional context, but they do not change the primary estimate's uncertainty. The registry record's missing-data details and multiplicity procedures are limited. Consequently, the most defensible interpretation stays close to the reported outcome, time period, population and analyses. The results describe the posted trial data; they do not provide medical advice or establish a treatment recommendation.

18. Why This Trial Matters Statistically

This trial is a useful example of why a randomized comparison should be interpreted through the between-group estimate and its uncertainty, rather than through within-group changes alone. Both arms had negative mean OSDI changes, but the scientific comparison is whether the average change differed between assignments. A large change in each arm does not, by itself, identify an effect attributable to one treatment rather than influences shared by both groups.

The confidence interval is central to the interpretation. The recalculated estimate is 1.89 units, but its interval includes zero and extends in both directions. This makes the uncertainty visible and prevents the point estimate from being mistaken for a precise conclusion. The sponsor analysis is the primary reported analysis, and the registry's discrepancy flag is an important reason to distinguish it from the simple recalculation.

The study also illustrates the limits of a short, small trial for estimating modest differences. The primary summaries include 26 participants per arm, and the posted planning illustrations show that detecting smaller assumed effects would require more participants under the stated calculation assumptions. Those planning illustrations are not a retrospective measure of trial success or failure, and the registry does not report the original design justification.

Finally, multiple outcomes and analyses call for restraint with secondary results. A nominal finding among several tests is less persuasive when the registry does not report adjustment or a testing hierarchy. Considering the primary analysis, uncertainty, missing-data reporting and multiplicity together gives a more reliable statistical reading than focusing on any single p-value.

19. 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 record leaves important design and analysis details unspecified. It does not report the original sample-size justification, detailed statistical analysis plan, allocation procedure, roles covered by quadruple masking, or whether interim analyses occurred. The trial's own design assumptions therefore cannot be reconstructed from the posted record. The planning figures are illustrations based on the observed effect, not evidence about the assumptions used to design this study.

The primary outcome summaries include 26 participants in each arm, whereas enrollment was 64. The record identifies an intent-to-treat dataset but does not explain the count difference, describe reasons for missing outcome data, or state how missing observations were handled. The safety at-risk counts are also different from the primary outcome counts. These gaps make it difficult to assess the completeness of the analyses and the potential influence of missingness.

The primary outcome description is change from baseline, but the sponsor analysis is labeled as a mean difference in final values. The record does not clarify the model specification or explain the discrepancy between that analysis and the recalculation from posted summaries. The sponsor's own analysis takes precedence, but the lack of detail limits independent assessment of how the result was obtained.

There are many outcome measures and analyses, but the record does not report multiplicity control or a hierarchy for testing. Secondary findings therefore have an exploratory status. The registry also does not report a clinically important OSDI difference, making it difficult to judge the practical importance of the estimated range.

The primary outcome is assessed to Day 30, and the record does not establish longer-term effects. The study enrolled adults with moderate or severe dry eye and used an active control, so the findings do not directly answer questions about other populations, no-treatment comparisons or longer timeframes. These are limits of what this trial record can establish, rather than evidence about outcomes that were not measured.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Piiloset Trehalose Emulsion Eye Drop Study in Moderate or Severe Dry Eye — NCT03569202.
• Registry record last updated 2019-12-13; status last verified 2019-11.
• Results first posted 2019-12-13.
• 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.

23. Record Summary

NCT03569202 is a completed randomized, active-controlled, parallel, double-blind study with quadruple masking, sponsored by Kuopio University Hospital. It enrolled 64 adults with moderate or severe dry eye and compared daily Piiloset Trehalose Emulsion Eye Drops with daily hyaluronic acid control drops for up to 30 days.

The primary outcome was change from baseline in OSDI from baseline to Day 30. The posted arm summaries include 26 participants in each group. The recalculated mean difference was 1.89 units, with a 95% confidence interval from -6.494 to 10.27 and an unadjusted p-value of 0.659. The sponsor reported an ANOVA p-value of 0.662; because the record flags a discrepancy, the sponsor's analysis takes precedence.

The interval includes zero and indicates substantial uncertainty about the between-group difference. Five secondary outcome results are posted, alongside safety counts reporting no serious adverse events or deaths in either group. The registry record does not report the original sample-size justification, missing-data method, multiplicity strategy or a clinically important OSDI threshold.