A Study Designed to Evaluate Tear Production: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Designed to Evaluate Tear Production (NCT06544707), a na phase 3 study. The primary outcome is Mean Change From Baseline in Tear Meniscus Height (TMH) at Minute 3 - Stage 1.

2. Clinical Question

The study evaluates tear production following acute administration of 0.003% AR-15512 in subjects with dry eye disease. Tear meniscus height (TMH) is the endpoint used to represent tear volume at the lower eyelid. A positive change is defined in the registry description as an improvement. However, the numerical mean change, its standard deviation, and the number of participants contributing primary outcome data are not reported in the registry record. The direction and size of the observed change therefore cannot be described from this record.

The question is about change after administration, not about a treatment-versus-control difference. Without a comparator group, the endpoint cannot isolate the change attributable to the intervention from other influences, such as measurement variation or changes that could occur over time without treatment. The study's open-label design also means that the registry does not describe masking of participants or study personnel. Those features should shape how the study is read, without substituting for the missing outcome results.

3. Trial Design

This is a Phase 3b, open-label, single-group study designed to evaluate tear production stimulated by 0.003% AR-15512. The registry lists Dry Eye Disease as the condition, Alcon Research as the sponsor, and 81 as the enrollment. The study status is COMPLETED. The recorded study start is 2024-10-15 and the primary completion date is 2025-01-30.

Participants received one drop of 0.003% AR-15512 ophthalmic solution in each eye. Dosing was staggered: the left eye was dosed first, followed by the right eye approximately 2-4 hours later. The primary outcome description specifies that only one eye, the left study eye, contributed data to that analysis. The outcome was assessed on Day 1 at Minute 3 after instillation, with a pre-instillation measurement serving as baseline.

The study has no separate control arm and no randomized allocation is listed. The treatment stages in the adverse-event record are labeled Stage 1 and Stage 2, but those labels do not create a randomized treatment comparison. The record does not report why these stages were used or how participants were assigned to them. Consequently, their adverse-event counts should be read as stage-specific descriptions, not as a like-for-like comparison between independently assigned treatments.

The registry lists two outcome measures and two analyses, but only the primary outcome details are available in the record summarized for this analysis. The protocol, detailed statistical analysis plan, and explanation of the analysis stages are not reported in the registry record. In particular, the record does not state a sample-size justification, an interim-analysis plan, or methods for handling missing outcome measurements.

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.

Before assignment: This reporting group includes all subjects treated with 0.003% AR-15512 (81).

Overall Study

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set

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: Full Analysis Set: All subjects who have received at least one dose of 0.003% AR-15512 and have pre-drop and 3-minute post-drop tear meniscus height measurements.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Tear Meniscus Height (TMH) at Minute 3 - Stage 1, measured over Day 1, Minute 0 pre-instillation (Baseline); Day 1, Minute 3 post-instillation.

The primary endpoint is mean change from baseline in tear meniscus height at Minute 3 during Stage 1. TMH measures the distance from the line of reflection along the top of the tear prism to the edge of the central lower eyelid. Measurements are taken in micrometers using optical coherence tomography (OCT), a non-invasive imaging test that uses light waves to produce cross-section pictures of the eye. The registry specifies that the left eye is the study eye and is the only eye contributing to this endpoint analysis.

The baseline is the Day 1 measurement at Minute 0 before instillation; the follow-up measurement is at Minute 3 after instillation. The endpoint is a change, rather than the post-instillation measurement alone. A positive change is described in the registry as an improvement. The registry also notes a normal TMH range of 200 to 400 micrometers and that measurements lower than this range may indicate dry eye disease. That context describes the measure; it does not replace the need to see the trial's actual baseline and follow-up results.

As a continuous measure, TMH can retain information about the size of a measurement rather than classifying each person only as meeting or not meeting a threshold. The mean change describes the average within-person change among those included in the analysis. Its interpretation depends on both the estimated change and its uncertainty, and neither the primary mean change nor its variability is reported in the registry record. The clinical meaning of any numerical change would also require context beyond the endpoint definition alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

General statistical explanation: For a continuous endpoint measured at baseline and after an intervention, each participant can have a change calculated from the two measurements. A mean change summarizes the average of those individual changes in the analysis population. It is distinct from comparing the average follow-up value with an unrelated group's average. In this study, the endpoint is defined as mean change in TMH from the Day 1 pre-instillation measurement to the Minute 3 post-instillation measurement in the left study eye.

The registry describes the endpoint as a mean and identifies standard deviation as its dispersion measure. A standard deviation describes how spread out individual measurements or changes are around their mean. It does not by itself quantify how precisely the mean is estimated. A confidence interval, when reported, would express uncertainty around an estimate under the assumptions of the analysis. The primary mean change, standard deviation, and confidence interval are not reported in the registry record, so none can be interpreted for this endpoint.

What can a single-group change show?

General statistical explanation: A before-and-after change describes how the measured outcome differs over time in the observed group. It does not create the counterfactual comparison that a separate control group would provide: what would have happened over the same period without the intervention. Consequently, a change can be compatible with an intervention effect, but other explanations—including measurement variability and time-related changes—cannot be separated by the change alone. This is a design limitation, not a claim that any particular alternative explanation occurred in this trial.

The study is listed as single-group, with no randomized allocation and no masking. Its primary result, if reported, would therefore need interpretation as an observed within-group change, not as a randomized treatment-versus-control contrast. The registry does not report an adjusted analysis or a method for controlling other influences. It would be inappropriate to assume that such methods were used.

Why does the measurement process matter?

General statistical explanation: Continuous measurements can vary because of biological fluctuation, instrument properties, timing, and measurement procedures. Consistent collection procedures can help reduce avoidable variation, while random variation remains relevant to the uncertainty of estimates. The registry says TMH was measured using OCT and identifies the measurement locations and timing. It does not report repeatability data, assessor training, or measurement-quality procedures in the record.

The protocol uses the left eye as the study eye for the primary analysis, rather than treating both eyes as independent observations. In general, two eyes from the same person are not independent in the same way as observations from different people. Using one specified eye avoids counting correlated eye measurements as though they were independent participants. The registry's description establishes which eye contributed, but does not give further details about the statistical implementation.

How should variability and precision be distinguished?

General statistical explanation: The standard deviation describes variation among observations. The standard error describes the uncertainty of an estimated statistic under a specified statistical model. A confidence interval is commonly constructed from an estimate and its standard error, together with assumptions about the sampling process. These quantities answer related but different questions; a measure of participant-to-participant spread is not interchangeable with a measure of precision of the group mean.

For a mean change, precision depends on the distribution of participant changes, the number of observations contributing to the analysis, and the statistical method. The registry names standard deviation as the dispersion measure but does not report the actual value or the number analyzed for the primary endpoint. It also does not report an interval estimate. The precision of the endpoint estimate cannot therefore be assessed from the registry record.

What does over-dispersion mean in general?

General statistical explanation: Over-dispersion arises when observed variability is greater than a statistical model assumes. It is most often discussed for count or binary outcomes, but the broad lesson applies across statistical modeling: if variability is understated, standard errors may be too small and uncertainty may appear narrower than it is. A model should reflect the variability structure of the data. This study's primary endpoint is continuous and is described with a mean and standard deviation; the registry does not report a model specification or evidence of over-dispersion, so no such issue can be diagnosed from the record.

How do the planning assumptions relate to this design?

General statistical explanation: Sample-size calculations are prospective planning tools. They ask how much information might be needed to detect a specified effect under stated assumptions about variability, allocation, significance level, and statistical method. They are not the same as an observed treatment effect, and a retrospective planning calculation based on an observed effect is not observed power.

The registry's stated planning illustration assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes effects as fractions of an observed effect. Those assumptions do not match the recorded single-group design, so the illustration should not be read as the study's own randomized design or as its protocol-based sample-size justification. The record does not report a sample-size justification, and the observed primary effect and calculated planning values are not reported in the registry record summarized for this analysis.

The record also does not state whether the primary analysis used a particular hypothesis test, whether it adjusted for covariates, or whether any sensitivity analysis was conducted. Those methods are not recoverable from the endpoint label or the planning assumptions and are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("0.003% AR-15512 - Stage 1")
n   <- c(40)
m   <- c(519.65)
sp  <- c(515.561)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  0.003% AR-15512 - Stage 1  40  519.650  515.561  354.766  684.534

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses, but the details available for this analysis describe the primary TMH outcome only. The record does not state whether the outcomes were tested as a family, whether a multiplicity adjustment was planned, or whether any result was designated as confirmatory beyond the primary endpoint label. A multiplicity strategy is therefore not reported in the registry record. In general, when several statistical hypotheses are tested, the chance of at least one false-positive finding can increase unless the analysis accounts for the multiple testing. Whether that concern applied to the study's full analysis plan cannot be determined from the record.

The primary outcome population is identified as the Full Analysis Set. The record does not define the set in operational terms, report how many participants were included in the primary analysis, or describe exclusions from it. It also does not report missing-data counts, reasons for missing measurements, imputation methods, or sensitivity analyses. These details matter because the analyzed participants and the handling of missing measurements can affect both the estimate and its uncertainty.

Enrollment of 81 does not establish that all enrolled participants contributed a primary endpoint measurement. Without the analyzed sample size and missing-data information, the completeness of the endpoint analysis cannot be assessed. No assumption should be made that missing data were absent or that a particular method was used to address them. The protocol and detailed statistical analysis plan are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in the pretreatment group, where 81 were at risk, and zero in each treatment stage: Stage 1, where 40 were at risk, and Stage 2, where 41 were at risk. No deaths are listed in these groups. These are the recorded serious-event counts; they do not establish that the risk of serious events is zero.

For other adverse events, the record lists zero affected in pretreatment, 19 affected in Stage 1, and 16 affected in Stage 2. The corresponding at-risk counts are 81, 40, and 41. These are counts as recorded, not percentages or comparative effect estimates. No percentages are calculated.

The treatment stages should not be treated as randomized comparison groups. The study is single-group and the registry lists no randomized allocation. The record also does not give the event terms, severity details, timing, or a statistical comparison in this summary. Counts should therefore be read descriptively and in the context of the group's stated at-risk count, rather than as evidence that one stage is safer or less safe than another.

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

The registry record establishes the study question, intervention, primary endpoint definition, design, and selected adverse-event counts. It does not report the numerical primary outcome. As a result, the record cannot show whether the mean TMH change was positive or negative, how large it was, or how variable participant changes were. It also does not report a confidence interval or statistical test result for the primary endpoint.

Even if an observed within-group change were available, a single-group before-and-after result would describe the change in the treated group rather than establish what would have happened without treatment. An open-label design with no separate control group cannot, on its own, distinguish the intervention's contribution from other possible influences. This is a general limitation of the design; it is not a statement about the direction or size of any unreported result.

The registry defines a positive change as improvement and gives a normal TMH range of 200 to 400 micrometers. Those definitions help explain the endpoint but do not establish that a particular change occurred or what it would mean clinically. The record does not provide the primary outcome value needed to compare an observed change with the measurement's context.

The adverse-event counts describe what the record lists for pretreatment and the two treatment stages. They do not constitute a randomized safety comparison, and the available summary does not give further details about the events. The absence of recorded serious events in these groups should not be interpreted as proof that serious events cannot occur.

Thus, the statistically supportable conclusion is limited: a completed, open-label, single-group study was registered to assess acute change in TMH after 0.003% AR-15512, but the primary result is not reported in the registry record. The available information is insufficient to judge the estimated effect or its precision.

14. Why This Trial Matters Statistically

This study illustrates why the design and the endpoint must be considered alongside any numerical result. The primary endpoint is a continuous measurement taken before and after acute administration, so its natural summary is a mean change with information about variability and precision. Without the actual estimate and its uncertainty, the clinical question remains unanswered by the registry record.

The study's single-group, open-label structure also matters statistically. A pre/post change can describe observed change, but it is not a randomized contrast. Readers should distinguish a within-group estimate from evidence that compares treatment with an alternative. The registry provides no separate control group or randomized allocation, so a causal comparison cannot be derived from the listed design.

The endpoint is tied to a particular eye and a particular short post-instillation time point. Those details define what the outcome represents and limit the scope of any interpretation: the primary measure concerns the left study eye at Minute 3 on Day 1, not an unqualified measure of long-term effect or outcomes in both eyes. The registry does not report the primary result or longer-term outcome details in the record.

Finally, the record highlights the difference between planning assumptions and trial design. Its planning illustration assumptions include equal allocation between two arms, whereas the registered study is single-group. Keeping such assumptions separate helps prevent planning calculations from being mistaken for the actual analysis or as observed power. The record's missing outcome estimate makes that distinction especially important: no effect size or precision can be assessed from the available primary outcome information.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is that the registry record does not report the primary endpoint result. The mean change, standard deviation, confidence interval, statistical test result, and number analyzed for TMH are not reported in the registry record. Without those data, the observed direction, magnitude, variability, and precision cannot be described.

The single-group, open-label design has no concurrent control group and no randomized allocation. A change from baseline would not by itself distinguish intervention-related change from measurement variation, time-related change, or other influences. This limits causal interpretation even if a numerical within-group result were available.

The primary outcome is restricted to the left study eye and the Minute 3 measurement on Day 1. The record does not establish how well this acute endpoint represents outcomes at other times or other aspects of dry eye disease. It also does not report the distribution of baseline TMH values or participant-level changes in the record.

Methods for missing data, endpoint analysis, multiplicity, and sensitivity analyses are not reported in the registry record. The definition of the Full Analysis Set is also not given. The listed planning illustration assumptions do not substitute for a protocol-based sample-size justification or the analysis plan for this single-group study.

The safety record gives counts of serious and other adverse events by pretreatment and treatment stage, but the event details and comparative analysis are not reported in this summary. Because the stages are not randomized control groups, the counts cannot establish comparative safety. These limitations constrain interpretation of the available record; they do not imply a particular unreported clinical result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Designed to Evaluate Tear Production — NCT06544707.
• Registry record last updated 2026-02-10; status last verified 2026-01.
• Results first posted 2026-02-10.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT06544707 is a completed Phase 3b, open-label, single-group study sponsored by Alcon Research. It enrolled 81 participants with Dry Eye Disease and evaluated acute administration of 0.003% AR-15512 ophthalmic solution. The recorded start date is 2024-10-15 and the primary completion date is 2025-01-30.

The primary endpoint is mean change from baseline in TMH at Minute 3 on Day 1, measured by OCT in the left study eye. The outcome population is identified as the Full Analysis Set. The primary numerical result and its precision are not reported in the registry record.

The adverse-event record lists no serious events or deaths in the pretreatment group or either treatment stage. Other adverse events affected 19 participants in Stage 1 and 16 in Stage 2; no affected participants are listed in pretreatment. These counts are descriptive, not a randomized comparison.