Efficacy and Safety of PRO-148 Ophthalmic Solution Versus SYSTANE® in the Treatment of Patients With Dry Eye Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of PRO-148 Ophthalmic Solution Versus SYSTANE® in the Treatment of Patients With Dry Eye Syndrome (NCT01541891), a randomized phase 2 study. The primary outcome is Tear Film Break-up Time (TBUT).

2. Clinical Question

The registry record describes a comparison of PRO-148 ophthalmic solution with SYSTANE® ophthalmic solution in patients with mild-to-moderate dry eye syndrome. Its stated purpose is to evaluate efficacy and safety, with tear film break-up time (TBUT) identified as the primary outcome. The record describes TBUT assessment at baseline and at the end of the study, during 60 days.

The information available establishes the question and the planned comparison, but not the answer. No numerical TBUT values, between-arm estimate, confidence interval, or test result are reported in the registry record. It is therefore not possible to describe the direction or size of any difference, or the precision with which a difference was estimated. The registry record also does not report an analysis of the primary endpoint.

3. Trial Design

This is a phase 2, randomized, double-masked, parallel-group study. The registry record gives an enrollment of 30. It lists PRO-148 ophthalmic solution and SYSTANE® ophthalmic solution as the two study treatments, with SYSTANE® identified as the active comparator. Both arm descriptions specify application to the ocular surface q.i.d. For 60 days.

Random allocation means that treatment assignment is determined by a chance-based process rather than chosen by the participant or investigator. In general, randomization is intended to reduce systematic differences between groups at the start of a trial. The record does not report how the allocation sequence was generated, how assignments were concealed, or whether the allocation ratio was equal.

Double masking indicates that the registry characterizes the study as masked, but the record does not specify which roles were masked or how masking was maintained. The parallel model means participants were assigned to one treatment group rather than described as crossing between treatments. The record identifies the study as completed and gives a start date of 2011-10 and a primary completion date of 2012-03.

Enrollment is not the same thing as the number included in every outcome analysis. The safety listing identifies 14 participants at risk in each arm for the reported event categories. The registry record does not explain the relationship between those safety denominators and the enrolled total, nor does it report the number analyzed for TBUT. Participant flow, withdrawals, adherence, and analysis-population definitions are not reported in the registry record.

The registry record does not describe the study’s sample-size justification, the randomization procedures, or any interim monitoring. Those design details should not be inferred from the trial’s phase, enrollment, or completion status.

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: Elegible patients were de novo patients diagnosed with mild to moderate dry eye disease

Overall Study

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: 14 patients of each group were included in the analysis (28 i total), the other 2 patients (1 of each group) were excluded due to lack of follow-up

6. Primary Endpoint

The registry lists the primary outcome as Tear Film Break-up Time (TBUT), measured over During 60 days.

The primary endpoint is tear film break-up time (TBUT), a continuous measure recorded in seconds. The registry record says it was evaluated at baseline and at the end of the study, during 60 days. It specifies that the outcome is expressed as a mean with standard deviation, but supplies no numerical means or standard deviations.

In general, TBUT measures the time until the tear film begins to break up after a blink. It is used as an indicator of tear-film stability: a longer time indicates that the tear film remains intact for longer under the measurement conditions. This explains why TBUT can be used to assess a sign associated with dry eye. It is a clinical measurement, not a direct measure of every symptom or experience a participant may have.

A comparison of group means can describe the average endpoint in each group, but interpretation also depends on the size and precision of the estimated difference and on how the analysis handles baseline values and missing measurements. The registry record does not report those results or methods. Because the endpoint is assessed at baseline and at the end of the study, a single endpoint summary would not by itself disclose how values changed over time. No numerical TBUT result is reported in the registry record, so the magnitude and direction of change cannot be assessed from it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are important because the same observed measurements can yield different estimates depending on the analysis question and assumptions. For this study, the registry describes a continuous endpoint measured at baseline and at the end of the study, summarized as a mean and standard deviation. It does not report the analysis method used for TBUT, any model, or any numerical analysis result. The explanations below are general and do not imply that a particular method was used in this trial.

What does a mean describe?

General: a mean is an average that summarizes the values in a group. It can be useful for a continuous measurement such as TBUT, expressed in seconds, because it provides a single description of the group’s central level. A mean does not show how widely individual values vary, whether the distribution is symmetric, or whether a small number of extreme values have substantial influence. The standard deviation describes the spread of individual values around the mean. The registry record specifies these summary measures but does not report their values.

To compare randomized groups, an analysis might compare endpoint means, changes from baseline, or endpoint values adjusted for baseline. These approaches answer related but not identical questions and can have different precision. General: adjustment for baseline can account for the relationship between participants’ starting values and their later values. The registry record does not state which approach was used, whether baseline adjustment was planned, or how repeated measurements were handled. No approach should be attributed to the investigators without a registry description or posted analysis.

What does a confidence interval add?

General: a confidence interval presents a range of values compatible with the data and the assumptions of an estimation procedure. Its width reflects precision: wider intervals indicate greater uncertainty about the estimated contrast, while narrower intervals indicate greater precision. An interval also helps readers judge which magnitudes of difference remain plausible. It is not a range that contains every individual participant’s measurement, and it does not on its own determine clinical importance.

The registry record does not report a TBUT contrast or confidence interval. Without them, neither the estimated direction nor the precision of the comparison can be described. A statistical significance test alone, if one had been reported, would not replace an estimate and interval: the test result does not convey the full range of plausible effect sizes.

Why can baseline and endpoint handling matter?

General: when a continuous outcome is recorded at baseline and later follow-up, analysis choices determine how those measurements contribute to the comparison. A change score focuses on within-participant difference over time. An endpoint comparison focuses on the follow-up measurement, and baseline-adjusted analysis incorporates initial values while comparing follow-up outcomes. These methods rely on assumptions and may differ in precision. The registry record reports the measurement occasions but not how the data were analyzed, whether a change score was used, or whether baseline values were included in a model.

Missing endpoint observations can also affect interpretation. General: an analysis restricted to participants with observed follow-up values may differ from one that uses additional assumptions or methods to account for missingness. The registry record does not report missing TBUT data, reasons for missingness, imputation, or sensitivity analyses. It is therefore not possible to assess how incomplete follow-up, if any, affected the endpoint estimate.

What is the role of a significance level?

General: a significance level is a threshold used in a testing procedure to define how unusual the data must be under a specified null hypothesis before the result is treated as statistically significant. The planning-illustration assumptions state a two-sided significance level of 0.05. That assumption is attached to the illustration, not evidence that the trial’s primary analysis used that threshold. The registry record does not report the trial’s statistical analysis plan, the test used, or a primary-outcome p-value.

A two-sided approach considers departures in either direction under the specified test. The distinction between a planned threshold and a reported result is essential: the threshold alone says nothing about the observed data. Statistical significance also does not establish the size or practical importance of a difference. Those judgments require an estimate, uncertainty information, and appropriate context, none of which is reported for TBUT in the registry record.

How should the planning illustration be read?

General: a sample-size calculation estimates how many participants may be needed under specified assumptions to detect a target effect with a chosen probability under a statistical model. A planning illustration based on a fraction of an observed effect is conditional on that effect estimate, the chosen fraction, significance level, allocation, and approximation. It is not a record of the trial’s actual design calculation, and it is not observed power. The record’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation. It does not report the trial’s own sample-size justification.

Observed power is not a substitute for interpreting an estimated effect and its uncertainty. General: after a study, a confidence interval directly communicates the precision of an estimate, whereas post hoc power calculations based on the observed effect largely restate information in the estimate and its standard error. The registry record does not report a TBUT effect estimate or a numerical planning output. No specific planning requirement or power statement can be inferred from the available information.

Finally, the registry record lists zero analyses. This means that the record does not provide a statistical analysis of the primary outcome in the information available. It does not establish what analyses may have been conducted outside the registry or what results might exist elsewhere; those matters are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures and identifies TBUT as the primary outcome. Presence of adverse events is listed as a secondary outcome. The available information does not name all three outcome measures or explain how they relate to one another. It also does not report a multiplicity strategy, such as a hierarchy of tests or an adjustment for testing multiple outcomes. That strategy is not reported in the registry record.

General: when several outcomes or comparisons are tested, the chance of at least one false-positive result can increase if each is judged separately using the same threshold. Methods for addressing multiplicity can control that risk, but the appropriate method depends on the trial’s objectives and analysis plan. Without a reported plan, readers cannot determine which tests were intended to support confirmatory claims or how any multiplicity was handled. In this record, no primary-outcome analysis or test result is reported.

The primary outcome description includes assessment at baseline and at the end of the study, and the record indicates that the outcome has several categories or time points and is not reduced to one comparison. This means there is no single numerical comparison available in the record to interpret. The registry record does not say whether multiple visits, categories, or contrasts were analyzed or how they were selected.

Missing-data methods are also not reported. The record does not provide the number of participants with TBUT measurements at each occasion, reasons for missing measurements, an analysis population, or a method for handling missing values. It does not describe intention-to-treat, per-protocol, or other analysis populations. These omissions prevent assessment of whether the reported safety denominators represent the population used for efficacy analyses, and whether missingness could have influenced the primary outcome.

General: missing data can affect both the amount of information available and the validity of an estimate if the probability of missingness is related to outcomes or participant characteristics. The implications depend on why values are missing and how the analysis addresses them. Since those details are not reported in the registry record, no conclusion about missing-data bias is warranted.

11. Safety Results

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

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 record lists serious adverse events for 14 participants at risk in each treatment arm. It reports 0 serious events in the PRO-148 arm and 0 in the SYSTANE® arm. It separately lists one other event in the PRO-148 arm and none in the SYSTANE® arm, with 14 at risk in each arm for that event category. Deaths are not reported in the registry record.

These are event counts as listed, not estimates of comparative risk or proof of causation. The registry record does not provide event descriptions, timing, severity details beyond the serious/other categories, or judgments about whether events were related to treatment. It also does not explain whether the counts represent participants with at least one event or total event occurrences. Those details are not reported in the registry record.

Zero serious events in the listed groups does not establish that serious events could not occur, and the counts do not demonstrate that the treatments have identical safety profiles. General: when event counts are small, uncertainty about the underlying event frequency can remain substantial even if no event is recorded. A fuller interpretation would require definitions, follow-up details, complete adverse-event reporting, and appropriate uncertainty estimates. Those are not reported in the registry record.

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

This registry record identifies a randomized, double-masked, parallel phase 2 comparison of PRO-148 ophthalmic solution and SYSTANE® ophthalmic solution for mild-to-moderate dry eye syndrome. It specifies TBUT in seconds as the primary outcome, measured at baseline and at the end of the study during 60 days. It also lists the presence of adverse events as a secondary outcome. These details describe the trial question and the outcomes selected for assessment.

They do not establish the comparative result. No numerical TBUT values, treatment contrast, confidence interval, or p-value are reported in the registry record, and the record lists zero analyses. Therefore the observed direction, magnitude, and precision of the primary outcome comparison are not known from this record. The absence of a reported result cannot be interpreted as evidence of no difference, nor as evidence of a difference.

The safety listing reports 0 serious events in each arm, among 14 at risk in each, and one other event in the PRO-148 arm compared with none in the SYSTANE® arm. The record does not describe the events or report deaths. These counts are limited descriptive information, not a complete basis for assessing comparative safety or attributing events to either treatment.

General: interpreting a trial requires more than knowing that it was randomized and what outcomes it planned to measure. Readers also need results, uncertainty estimates, analysis methods, participant flow, and information about missing data. The design features can help explain how a comparison was intended to be made, but they do not guarantee that the resulting evidence is precise or free of bias.

The registry record should therefore be read as documenting the study’s design and selected outcomes, with limited safety counts, while leaving the primary efficacy result and important analysis details unreported. No conclusion about whether one treatment produced a larger TBUT, or about the clinical meaning of any possible difference, can be drawn from the information recorded.

13. Why This Trial Matters Statistically

This trial is statistically notable because the registry describes a randomized comparison and specifies a continuous primary endpoint, yet provides no numerical primary-outcome analysis. That distinction is central to evidence interpretation. A clear design description can tell readers what was intended, but it cannot substitute for the observed measurements, an effect estimate, or an account of uncertainty.

The record also illustrates why endpoint timing and analysis details matter. TBUT was evaluated at baseline and at the end of the study, during 60 days, but the analysis approach is not reported. A comparison of endpoint values, a comparison of changes, and an endpoint analysis adjusted for baseline can answer related questions while producing estimates with different precision. Without the actual method and results, readers cannot determine how the repeated measurements informed the comparison.

Enrollment is recorded as 30, while the safety listing reports 14 at risk in each arm. This makes it important not to treat enrollment as the denominator for every outcome. The registry does not explain the relationship between those counts or give the TBUT analysis population. Participant flow and missing endpoint data are not reported in the registry record.

The safety entries likewise demonstrate the limits of sparse event summaries. Counts of serious and other events provide a basic description, but event definitions, details, and uncertainty are not available in the record. Descriptive counts do not by themselves establish comparative safety.

Finally, the stated sample-size illustration assumptions are not the same as a trial-specific justification. General: planning calculations depend on assumptions about the effect worth detecting and the analysis. They should not be mistaken for observed power or a finding. Since no primary effect estimate or numerical analysis is reported, the design’s ability to estimate the planned endpoint cannot be judged from the registry record alone.

14. 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.

Several limitations specific to this record constrain interpretation. The registry identifies TBUT as the primary outcome and gives its unit, summary measure, and broad timeframe, but it reports no numerical outcome values. It also lists zero analyses. As a result, the primary comparison cannot be described in terms of direction, magnitude, or precision, and no statistical inference can be checked.

The record gives an enrollment of 30 but does not report the number analyzed for TBUT or the participant flow from enrollment through follow-up. Safety denominators are 14 at risk in each arm; the relationship between those denominators and the enrolled total is not explained. The registry record does not report withdrawals, adherence, or missing endpoint measurements.

Important methodological information is also absent. The record does not state how the randomization sequence was generated or concealed, which roles were masked, what statistical model or comparison was used, or how baseline values were handled. The analysis population, missing-data approach, and sensitivity analyses are not reported. The registry record also does not report a multiplicity plan or a trial-specific sample-size justification.

The safety listing is limited: it reports serious-event counts and other-event counts, but does not include event descriptions or report deaths. The meaning of the other-event category and whether counts represent participants or event occurrences are not clarified in the information available. These limitations do not prove that analyses or details were absent from all study materials; they mean that they are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of PRO-148 Ophthalmic Solution Versus SYSTANE® in the Treatment of Patients With Dry Eye Syndrome — NCT01541891.
• Registry record last updated 2018-10-30; status last verified 2018-02.
• Results first posted 2018-10-30.
• 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.

18. Record Summary

The registry record describes a completed phase 2, randomized, double-masked, parallel study comparing PRO-148 ophthalmic solution with SYSTANE® ophthalmic solution in patients with mild-to-moderate dry eye syndrome. Enrollment is listed as 30. Both treatments were described as applied to the ocular surface q.i.d. For 60 days. The record gives a start date of 2011-10 and a primary completion date of 2012-03.

TBUT, measured in seconds and summarized as a mean with standard deviation, is the primary outcome. It was evaluated at baseline and at the end of the study. No numerical TBUT findings or analysis are reported in the registry record. The safety listing reports 0 serious events in each arm, with 14 at risk in each, and one other event in the PRO-148 arm and none in the comparator arm. Deaths are not reported.