This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Comparison of Tear Evaporation Rate With Systane Complete in Dry Eye and Non-Dry Eye (NCT04091581), a non-randomized phase 4 study. The primary outcome is Tear Evaporation Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04091581 |
| Phase | Phase 4 |
| Condition | Evaporative Dry Eye |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Waterloo |
| Results posted | Yes |
2. Clinical Question
Population
Participants were classified into dry-eye and non-dry-eye groups using ocular-surface criteria. The non-dry-eye group had an Ocular Surface Disease Index score <13 and a non-invasive Keratograph break-up time >= 10 seconds in the worst eye. The dry-eye group had an Ocular Surface Disease Index score >= 13 and a break-up time <= 5 seconds in the worst eye. The registry record reports 21 participants enrolled.
Intervention
Participants received Systane Complete, an eye drop described in the study summary as containing nano-sized oil droplets. Tear evaporation was measured before instillation and at 10, 30 and 60 minutes afterward.
Comparator
The groups were compared by dry-eye classification, not by treatment assignment. Both groups received the eye drop, and allocation was non-randomized. There was no untreated or alternative-treatment comparison group reported in the registry record.
Primary question
The study objective was to compare tear evaporation rates in dry-eye and non-dry-eye participants before and during the hour after instillation. The primary outcome was the mean tear evaporation rate, expressed as % relative humidity per second. The registry record does not report the measured values or the estimated difference between groups.
This is therefore a question about a physiological measurement over time and across two participant categories, rather than a randomized test of one treatment against another. The measurements after instillation can describe the observed course of evaporation in the enrolled participants. A comparison between the categories may describe whether their recorded patterns differed, but without reported outcome values or an analysis estimate, the direction and precision of any difference cannot be assessed.
The objective, as stated in the registry record, focuses on evaporation measured with a novel evaporimeter. The record does not report a clinical symptom outcome or a comparison against another eye drop. The clinical question is consequently limited to the specified measurement and observation period, not broader claims about symptoms or comparative treatment effects.
3. Trial Design
The registry record identifies this as a Phase 4, completed study sponsored by the University of Waterloo. The recorded start date is 2019-11-21 and the primary completion date is 2020-02-06. Enrollment was 21. The design is described as parallel, non-randomized and unmasked. These features matter because the dry-eye and non-dry-eye categories were not formed through random assignment to different treatments: both received Systane Complete, and group membership depended on the ocular-surface criteria.
The study included a baseline measurement before instillation and follow-up measurements at 10, 30 and 60 minutes after instillation. The primary outcome description specifies that data from the right eye were analyzed. It describes the evaporation-rate slope as calculated from changes in humidity during stated open-eye and closed-eye intervals. The registry record does not report further details about the measurement protocol, such as how many readings were taken at each time or how repeated readings were combined.
The registry describes the analyzed population as participants exposed to Systane Complete, excluding one dry-eye participant lost to follow-up. The record does not report additional details about participant flow or the number contributing a usable primary outcome at every scheduled measurement. The adverse-event denominators are reported separately for the two groups.
Because both groups received the same eye drop and there was no random allocation, group differences cannot be interpreted as an unbiased treatment contrast. The categories may differ in ways other than the criteria used to define dry eye, and the registry record does not report adjustment for such differences. Nor does it report an untreated group that could separate changes after instillation from changes over time that might have occurred without the drop.
The registry record does not report a detailed protocol, recruitment setting, eligibility criteria beyond the group definitions, or a statistical analysis plan. It lists one primary outcome measure, but does not report numerical outcome results or the methods used for the two listed analyses. The design can describe measurements in these enrolled groups; the available record does not establish a causal comparison between treatments.
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
| Stage | Non-Dry Eye | Dry Eye |
|---|---|---|
| STARTED | 10 | 11 |
| COMPLETED | 10 | 10 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Non-Dry Eye | Dry Eye |
|---|---|---|
| Lost to Follow-up | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis population includes all participants that were exposed to Systane Complete, and excludes the one dry eye subject that was lost to follow-up.
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.
| Characteristic | Unit | Non-Dry Eye | Dry Eye | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 11 | 21 | |
| Age, Continuous | years | 32.6 (SD 12.8) | 45.4 (SD 22.7) | 39.3 (SD 19.4) |
| Sex: Female, Male: Female | Participants | 7 | 10 | 17 |
| Sex: Female, Male: Male | Participants | 3 | 1 | 4 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Canada | participants | 10 | 11 | 21 |
6. Primary Endpoint
The registry lists the primary outcome as Tear Evaporation Rate, measured over Baseline (Prior to instillation); 10, 30 and 60 minutes post instillation of eye drop.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | % relative humidity per second |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is tear film evaporation rate, reported as a mean continuous measure in % relative humidity per second. The study description says a novel evaporimeter was used for this non-invasive measurement. The slope was based on humidity change during an interval when the eye was open and an interval when it was closed; the right eye was analyzed. Measurements were scheduled before instillation and at 10, 30 and 60 minutes after the eye drop.
In general, a continuous endpoint retains the scale of the measurement rather than reducing observations to categories such as improved or not improved. A mean can describe the group’s central level of the measure, while the standard deviation describes how dispersed individual observations are around that mean. Those summaries can help readers understand both the average pattern and variation among participants.
Evaporation rate was selected because the stated objective was to compare tear evaporation after instillation in participants classified by dry-eye status. It is a physiological measure, not itself a direct measure of symptoms or daily functioning. A change in this measure cannot, by itself, establish a change in how participants felt or functioned.
The registry record gives the endpoint definition and timepoints but does not report the mean values, standard deviations, changes from baseline, or group contrasts. Consequently, the recorded endpoint cannot be interpreted for direction, magnitude, or precision from the registry record alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The key interpretive constraint is that the registry record does not report numerical results for tear evaporation rate. Although it identifies a continuous primary endpoint, its unit, measurement approach and scheduled timepoints, it provides no group means, standard deviations, changes from baseline, confidence intervals, p-values or estimated group differences. The magnitude and direction of the observed data are therefore not reported in the registry record. It is not possible to assess whether the measurements rose, fell or remained similar after instillation, or whether the two participant groups had different patterns.
The study enrolled 21 participants and classified them as dry eye or non-dry eye. That enrollment total describes the study size, not the number contributing to each primary outcome analysis. The primary-outcome population is described as exposed participants, excluding one dry-eye participant lost to follow-up. The record does not provide primary endpoint denominators at each measurement time. No estimate of precision can be recovered from the enrollment count alone.
The non-randomized design also limits interpretation of any group contrast that might have been reported elsewhere. Dry-eye status was the basis for grouping, and treatment was not varied between groups. As a general statistical principle, a difference between non-randomized groups may reflect measured or unmeasured baseline differences as well as the characteristic used to define the groups. An association between group membership and a measurement is not equivalent to a causal effect of treatment. The registry record does not report an adjusted analysis that could address differences between groups.
Repeated measurements in the same participant are generally correlated: observations from one person tend to share characteristics. In general, analysis of measurements over time should account for this dependence rather than treating each observation as independent. The registry record does not report the model or test used for the repeated measurements, nor does it say whether the comparison focused on changes from baseline, differences at individual times, or an overall group-by-time pattern.
Precision is also unknown. In general, a confidence interval expresses a range of values compatible with the data and the method used, while a p-value summarizes evidence against a specified null hypothesis under model assumptions. Neither can be interpreted without the estimate and analysis details. The registry record does not report either quantity for the primary endpoint. The posted record therefore supports a description of the study question and design, but not a conclusion about the size, direction, or statistical certainty of an outcome difference.
The adverse-event record reports no participants with serious adverse events in either group. It separately reports other adverse events affecting 1 of 10 non-dry-eye participants and 2 of 11 dry-eye participants, and deaths of 1 and 2 participants, respectively. The registry record does not provide event descriptions, timing, causes, or attribution to the eye drop. Those safety figures should not be used to infer causation or to resolve the unreported primary-outcome findings.
9. Statistical Methods Explained
The registry record identifies the primary outcome as a mean of a continuous measure and identifies standard deviation as its dispersion measure. It does not report the actual means or standard deviations. The following explains these statistical concepts generally; it does not identify methods as having been used in this study unless the record says so.
What does a mean and standard deviation describe?
In general, the mean is an average of measured values, expressed in the endpoint’s original unit. The standard deviation describes how widely individual values vary around that average. A small standard deviation indicates values are more concentrated around the mean; a larger one indicates greater spread. These summaries do not reveal the full distribution, and the mean may not represent every participant’s experience. Neither summary alone gives the uncertainty of a comparison between groups.
Standard error and standard deviation are different concepts. In general, standard deviation describes variation among observations, whereas standard error describes the uncertainty of an estimated quantity under a statistical model. A confidence interval typically uses an estimate and its uncertainty to show a range of values compatible with the data and method. The registry record reports no confidence interval or standard error for the primary endpoint, so the precision of any estimate is unknown.
Why do repeated measurements matter?
The endpoint was scheduled at baseline and at 10, 30 and 60 minutes after instillation. These measurements come from the same participants over time, so they are not generally independent observations. In general, repeated-measures methods account for within-person correlation. Treating correlated observations as though they were unrelated can misstate uncertainty. The record does not identify whether a repeated-measures model, a comparison at each time, or another approach was used.
There are several possible statistical questions for repeated data. One could describe the average change from baseline at each follow-up, compare groups at specific times, or test whether the pattern over time differs by group. These questions do not have identical interpretations. A group-by-time analysis, for example, concerns whether the course across time differs between the categories. The registry record states the outcome timepoints and study objective, but does not specify which estimand or test was used.
What does non-randomized grouping imply?
In general, random assignment can make treatment groups more comparable on average, including for characteristics that were not measured. This study instead classified participants by dry-eye criteria and administered the same named eye drop to both groups. Thus, a comparison between groups is a comparison of participant categories, not a randomized treatment contrast. Other group differences could contribute to any observed outcome difference. The registry record does not report covariate adjustment or enough information to assess whether potential confounding was addressed.
The study is also unmasked, according to the record. In general, lack of masking can affect behavior, measurement, or decisions about recording and analyzing outcomes, depending on how a study is conducted. The record does not describe safeguards or the degree to which the evaporimeter readings could be influenced by awareness of group status. This is a design consideration, not evidence that bias occurred.
What can be inferred from significance testing?
In general, a p-value is interpreted relative to a stated hypothesis and statistical model. It does not measure the size or clinical importance of an effect, and it does not give the probability that a hypothesis is true. A confidence interval is often more informative about the range and precision of an estimated effect. The registry record does not report a p-value, confidence interval, effect estimate, hypothesis test, or significance threshold for the primary outcome. Statistical significance therefore cannot be assessed.
More broadly, a statistical analysis plan specifies how outcomes, timepoints, missing values, and comparisons will be handled. The registry record does not report the detailed plan, nor does it describe the methods for the two listed analyses. There is no basis in the record for attributing a particular test, model, or adjustment procedure to the investigators.
Sample-size calculations are planning tools, not evidence that a result was observed or that an analysis had a particular probability of detecting an effect. The registry record does not report its own sample-size justification or assumptions. Any planning illustration based on an observed effect would be a separate hypothetical calculation, not a substitute for reported outcome estimates and not “observed power.” In general, interpretation should focus on the observed estimate and its uncertainty, neither of which is reported for this primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint has measurements at baseline and at 10, 30 and 60 minutes after instillation. Considering multiple follow-up times can create multiple opportunities to test for a difference. In general, when several hypotheses are tested, the chance of obtaining at least one apparently notable result can increase unless the analysis plan addresses multiplicity. The registry record does not report whether the investigators tested each time separately, used an overall longitudinal test, selected a particular time as primary, or adjusted for multiple comparisons. It also does not report a multiplicity strategy.
The record identifies one primary outcome measure and two analyses, but does not describe the analyses or their relationship to each other. It is therefore not possible to determine from the registry record whether the two analyses addressed distinct prespecified questions, repeated timepoints, or another purpose. The number of analyses alone does not establish that multiplicity was or was not handled.
For missing data, the primary outcome population is described as including exposed participants while excluding one dry-eye participant lost to follow-up. The record does not report the reason for loss, the measurement times that were missing, or whether other observations were incomplete. It does not report imputation, a missing-data model, sensitivity analyses, or an assumption about why the measurement was missing. Excluding a participant can affect the analysis if those with missing observations differ from those retained; the direction or size of any such effect cannot be assessed.
The record does not report whether the analysis used all available measurements from each participant or required complete measurements at every timepoint. It also does not report a detailed analysis population definition beyond exposure and the stated exclusion. These omissions limit assessment of both the handling of repeated observations and the potential impact of missing data.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Non-Dry Eye | 0 | 10 | 0.0% |
| Dry Eye | 0 | 11 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Non-Dry Eye | 1 of 10 |
| Dry Eye | 2 of 11 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Non-Dry Eye | 1 of 10 |
| Dry Eye | 2 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Non-Dry Eye | Dry Eye |
|---|---|---|---|
| Fever | Infections and infestations | 0 of 10 | 1 of 11 |
| Steroid injection | Surgical and medical procedures | 0 of 10 | 1 of 11 |
| Common cold | Infections and infestations | 1 of 10 | 0 of 11 |
The adverse-event record lists zero participants with serious adverse events in the non-dry-eye group and zero in the dry-eye group. It lists other adverse events affecting 1 of 10 participants in the non-dry-eye group and 2 of 11 participants in the dry-eye group. The record also lists deaths of 1 and 2 participants, respectively. These are separate reported categories; the registry record does not explain whether the deaths were related to adverse events or to the eye drop.
These counts should be read as descriptive safety entries, not as evidence that the eye drop caused or prevented an event. The record does not report event terms, severity details for the other events, timing, causal assessments, or the circumstances of the deaths. It also does not report a statistical comparison of safety outcomes. With these details absent, the figures cannot establish a cause, quantify comparative risk, or explain the relationship between the listed categories. The absence of reported serious adverse events does not by itself establish that no serious events occurred beyond the recorded information.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed study asking whether tear evaporation measurements differed between participants classified as having dry eye and those classified as not having dry eye, before and after Systane Complete was instilled. It specifies the measurement scale, timepoints, and the right eye as the eye analyzed. It also describes an analysis population that excludes one dry-eye participant lost to follow-up.
However, the record does not report the primary outcome values. There is no numerical basis in the registry record for describing the observed direction or size of change, comparing the groups, or judging how precise an estimate was. No primary endpoint confidence interval or p-value is reported. The outcome therefore cannot be characterized as showing an increase, decrease, similarity, or statistically distinguishable difference.
Even if a group difference were available, the study design would be important to its meaning. Both categories received the eye drop, allocation was non-randomized, and there was no untreated or alternative-treatment group reported. A before-and-after pattern would not by itself distinguish an effect of instillation from other changes over time. A difference between dry-eye and non-dry-eye participants would not establish that dry-eye status caused the difference, nor would it establish that treatment affected the groups differently.
The endpoint is a physiological measurement of tear film evaporation. It is not a reported symptom or functional outcome. The registry record does not support claims about symptom relief, quality of life, comparative effectiveness, or clinical benefit. It also does not provide enough safety detail to attribute the reported events or deaths to treatment.
The most defensible conclusion is limited: the registry records the study question and design, but does not report the numerical primary results needed to evaluate what the study observed. The absence of those results should not be mistaken for evidence of no difference.
13. Why This Trial Matters Statistically
This study raises a useful statistical distinction between comparing participant groups and comparing assigned treatments. The dry-eye and non-dry-eye groups were defined by ocular-surface criteria, and both received Systane Complete. Since allocation was non-randomized, the design addresses how measured evaporation behaves across these categories around instillation, not a randomized contrast between treatments.
The scheduled baseline and follow-up measurements also illustrate why longitudinal data need clear analysis choices. A report can focus on a change from baseline, a difference at a particular time, or a difference in the overall time pattern. Those choices answer different questions, and repeated observations from one participant are generally correlated. The registry record gives the timepoints but does not report which statistical question or method was used.
Another important issue is reporting completeness. Knowing the endpoint, unit, measurement approach and analysis population helps readers understand what was intended, but it is not enough to evaluate the result. Numerical estimates and measures of uncertainty are needed to judge magnitude and precision. Those primary outcome results are not reported in the registry record.
The stated loss to follow-up also makes transparent accounting important. The record identifies one dry-eye participant excluded from the primary analysis, but does not detail the missing measurements or the approach to missing data. Such information helps readers assess whether the analyzed participants represent the enrolled group.
Finally, the study separates physiological measurement from clinical experience. A measurement of evaporation may address the stated mechanistic question, but it cannot stand in for symptom or functional outcomes that are not reported. The statistical value of this record lies in the defined question and design, while its limited results reporting prevents assessment of the primary findings.
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 follow directly from the registry record. First, the numerical primary outcome results are not reported. Group means, standard deviations, changes over time, effect estimates and uncertainty measures are absent, so the primary finding cannot be evaluated for direction, magnitude or precision.
Second, the study is non-randomized and unmasked. The two groups are defined by dry-eye classification rather than assigned to different treatments, and both receive Systane Complete. Any group contrast is therefore vulnerable to differences between participant categories, and any before-and-after pattern lacks an untreated comparison to help separate instillation-related changes from other time-related changes.
Third, the record identifies one dry-eye participant lost to follow-up and excluded from the primary-outcome population, but does not describe the reason, missing timepoints, or missing-data method. Primary-outcome denominators at each follow-up are not reported. The effect of this missingness cannot be assessed.
Fourth, the registry record does not report the statistical model, testing approach, confidence intervals, p-values, or handling of multiple timepoints. The outcome has repeated measurements, but the analysis method for their within-participant dependence is not described. The record also does not report a sample-size justification or a detailed statistical analysis plan.
Finally, the endpoint is a physiological measurement, while symptom or functional outcomes are not reported. Safety entries lack event descriptions, timing and attribution. These gaps limit both clinical interpretation and evaluation of how the analysis was conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Comparison of Tear Evaporation Rate With Systane Complete in Dry Eye and Non-Dry Eye — NCT04091581.
- Registry record last updated 2022-06-22; status last verified 2022-06.
- Results first posted 2022-06-22.
- 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.
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18. Record Summary
The University of Waterloo registered a completed Phase 4, parallel, non-randomized and unmasked study of Systane Complete in dry-eye and non-dry-eye participants. Enrollment was 21. The study measured tear evaporation before instillation and at 10, 30 and 60 minutes afterward, using the right eye for analysis. The registry record describes the endpoint and states that one dry-eye participant lost to follow-up was excluded from the primary analysis.
The record does not report numerical primary outcome results, estimates of uncertainty, or the statistical methods used for the listed analyses. It reports zero participants with serious adverse events in either group, other adverse events affecting 1 of 10 non-dry-eye participants and 2 of 11 dry-eye participants, and deaths of 1 and 2 participants, respectively. Event details and causal attribution are not reported in the registry record.