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 SYSTANE® BALANCE Symptoms (OSDI) & Inflammatory Biomarkers (NCT01733732), a randomized na study. The primary outcome is Ocular Comfort Measured as Mean Change From Baseline in OSDI Score by Visit.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01733732 |
| Phase | NA |
| Condition | Dry Eye Syndrome |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 54 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alcon Research |
| Results posted | Yes |
2. Clinical Question
Population
Subjects with dry eye and lipid deficiency. The primary-outcome population included randomized subjects who attended at least one post-baseline study visit; the number with non-missing OSDI values could vary by time point.
Intervention
SYSTANE® BALANCE Lubricant Eye Drops, described as one drop in each eye four times a day for 30 days.
Comparator
SYSTANE® Gel, described as one drop in each eye four times a day for 30 days.
Primary question
How did mean OSDI score change from baseline by visit in the two randomized groups? A negative baseline change is defined in the registry record as indicating perceived improvement in ocular comfort. Numerical group results are not reported in the registry record.
The study title also identifies inflammatory biomarker expression as an area of interest. Listed secondary outcomes include tear inflammatory cytokine expression and HLA-DR expression, along with visual acuity, ocular surface assessments, tear-film measures, and meibomian gland expression. These additional measures address different aspects of dry eye signs and symptoms; they do not replace the stated primary endpoint of OSDI score change.
The registry record describes the study purpose as evaluating comfort with SYSTANE® BALANCE and SYSTANE® Gel. It does not report numerical results that permit a direct estimate of the difference in OSDI change between groups, or an assessment of the precision of that difference. The clinical question can therefore be described, but the comparative effect on the primary outcome cannot be quantified from the registry record.
3. Trial Design
The record describes a randomized, double-masked, parallel-group study of SYSTANE® BALANCE Lubricant Eye Drops and SYSTANE® Gel in subjects with dry eye and lipid deficiency. The record lists an enrollment of 54 and a completed status. The study began in 2013-03, with primary completion in 2013-10. The phase is listed as not applicable.
Both arm descriptions specify one drop in each eye four times a day for 30 days. This makes the assigned products and stated dosing schedules comparable in the description, but the registry record does not report adherence, treatment exposure, or deviations from the stated schedules. The record labels the trial double-masked, but does not report which study roles were masked or how masking was maintained.
The primary endpoint was mean change from baseline in OSDI score by visit. The stated time points were Baseline (Day 0), Day 14, and Day 30. The analysis population was defined as randomized subjects who attended at least one post-baseline study visit. For each arm and time point, the stated value of n refers to subjects with non-missing values at that specific time point. Thus, the endpoint population definition and the number contributing data at an individual visit are not necessarily the same.
Secondary outcomes include change in best-corrected visual acuity, normal slit-lamp assessment, meibomian gland expression, non-invasive keratographic tear break-up time, tear meniscus height, ocular surface staining, tear inflammatory cytokine expression, and HLA-DR inflammatory biomarker expression. These are separate outcomes with different measurement characteristics. Their inclusion does not establish that results or statistical comparisons for each are available. Numerical outcome results and analysis details are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: A total of 54 subjects were screened and randomized. This reporting group includes all randomized subjects (54).
Overall Study
| Stage | Systane Balance | Systane Gel |
|---|---|---|
| STARTED | 27 | 27 |
| COMPLETED | 25 | 27 |
| NOT COMPLETED | 2 | 0 |
Reasons for not completing this period:
| Reason | Systane Balance | Systane Gel |
|---|---|---|
| Adverse Event | 1 | 0 |
| Did not attend all study visits | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: This analysis population includes all subjects who were randomized and attended at least one post-baseline study visit. Here, "n" is the number of subjects with non-missing values at the specific time point for each arm group, respectively.
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: This analysis group includes all randomized subjects.
| Characteristic | Unit | Systane Balance | Systane Gel | Total |
|---|---|---|---|---|
| Participants analysed | 27 | 27 | 54 | |
| Age, Continuous | years | 62.3 (SD 14.5) | 63.8 (SD 12.8) | 63.0 (SD 13.6) |
| Sex: Female, Male: Female | Participants | 17 | 16 | 33 |
| Sex: Female, Male: Male | Participants | 10 | 11 | 21 |
6. Primary Endpoint
The registry lists the primary outcome as Ocular Comfort Measured as Mean Change From Baseline in OSDI Score by Visit, measured over Baseline (Day 0), Day 14, Day 30.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is ocular comfort measured as mean change from baseline in OSDI score by visit. The OSDI is described as a validated 12-question questionnaire covering ocular symptoms, visual function, and environmental factors that may affect vision. Its score ranges from 0 to 100, with lower scores indicating more symptomatic relief from dry eye symptoms. The registry record says baseline-adjusted scores were tabulated and defines a negative change from baseline as perceived improvement in ocular comfort.
Patient-reported symptom measures can capture experiences that clinical signs alone may not describe. This is a general reason to include a questionnaire such as the OSDI when studying dry eye symptoms. At the same time, the score reflects the domains covered by that instrument and should not be treated as interchangeable with tear-film measurements, ocular surface assessments, or inflammatory biomarkers. Those outcomes can provide distinct information.
The endpoint is assessed at Baseline (Day 0), Day 14, and Day 30. Because the primary outcome is specified across multiple visits, interpretation depends on the values at each time point and on how the repeated measurements were analyzed. The numerical mean changes, their variability, and comparisons between groups are not reported in the registry record. Consequently, the direction and precision of the primary outcome cannot be established from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the outcome of interest and the interpretation of its direction: a negative change from baseline in OSDI score indicates perceived improvement in ocular comfort. However, it does not report the numerical OSDI means or changes by group and visit. It also does not report a between-group effect estimate, confidence interval, or statistical test result for the primary outcome. A quantitative comparison of SYSTANE® BALANCE with SYSTANE® Gel therefore cannot be made from the registry record.
This absence is important for interpretation. The endpoint definition alone does not show whether either group had a change, how large a change was, or whether the groups differed. It also does not establish how precisely any observed difference was estimated. Without the actual estimates and uncertainty measures, neither the direction nor the magnitude of a comparative effect can be described responsibly.
The registry record lists the primary outcome at Baseline (Day 0), Day 14, and Day 30. These are repeated assessments, not one self-evident summary contrast. A result at one visit would not by itself describe the pattern over the full follow-up period. The record does not identify one preferred visit comparison or provide an overall repeated-measures result. The listed skip note indicates that the primary outcome has several categories or time points and was not reduced to one comparison.
There are 12 outcome measures and 0 analyses reported in the record. The secondary outcomes span symptoms, visual function, ocular surface findings, tear-film characteristics, and inflammatory markers. Their listing documents what was planned or collected as outcomes in the registry, but does not communicate estimates or findings. Numerical results for these outcomes are not reported in the registry record.
The registry also contains safety figures: the Systane Balance group has 0 serious events among 27 at risk, and the Systane Gel group has 1 among 27 at risk. These figures describe the posted safety counts, not the primary symptom endpoint. They do not establish comparative safety in general, especially without more detailed event context and follow-up information. The record lists two serious-event terms, each at 3.7%, but does not report their assignment to a treatment group in the term listing.
Sample-size figures, when used as planning illustrations based on an observed effect, should not be confused with observed trial power or with the trial's original planning rationale. The record does not report a sample-size justification, and numerical planning illustrations are not reported in the registry record. Overall, the registered design and outcome definitions are available, but the missing numerical outcome results prevent conclusions about the size or precision of treatment differences.
9. Statistical Methods Explained
The registry record identifies the primary measure as a mean of a continuous outcome. In general, a mean describes the central value of measurements, while a standard deviation describes how spread out individual measurements are around that mean. Both are useful for understanding an endpoint such as OSDI score: a group mean change describes the average change, while the spread indicates how much individual changes vary. The record specifies standard deviation as the dispersion measure, but does not report the numerical means or standard deviations.
What does baseline change represent?
For a change-from-baseline outcome, each participant's follow-up value is considered in relation to that participant's baseline value. The registry record says baseline-adjusted scores were tabulated and defines a negative change as perceived improvement in ocular comfort. That definition supplies the direction of interpretation, but not the result. A change score is not itself a comparison between randomized groups: the group contrast must also be reported to describe the difference between treatment assignments.
Baseline adjustment can be used to account for initial outcome values when estimating follow-up differences. In general, adjusting for baseline may improve the relevance or precision of a comparison, depending on the analysis and data. The specific model, covariates, estimation procedure, and handling of repeated observations are not reported in the registry record. It is therefore not possible to determine exactly how the registered baseline-adjusted scores were calculated or whether the displayed summaries correspond to an adjusted treatment contrast.
Why are the visits important?
The OSDI outcome is assessed at Baseline (Day 0), Day 14, and Day 30. In general, repeated measurements on the same participant are related rather than independent. An analysis of multiple visits may account for that relationship and may estimate change over time, a treatment difference at a particular visit, or an overall pattern. Those are different statistical questions. The record does not report which repeated-measures method was used, whether a single visit was prioritized, or how any overall treatment effect was defined.
Separate comparisons at multiple time points can also raise multiplicity concerns. In general, the more hypotheses examined, the greater the opportunity for a chance-positive result if no adjustment or prespecified testing strategy is used. The registry record does not report a multiplicity adjustment, an order of testing, or a hierarchy across outcomes and visits. It does not report interim analyses or a statistical analysis plan. Those details should not be inferred from the endpoint list.
What do uncertainty measures add?
A confidence interval is a general way to express the uncertainty around an estimated effect. It gives a range of values compatible with the data under the method used, rather than proving that the true effect lies within a particular range. For a treatment comparison, an interval helps readers judge both the estimated magnitude and its precision. The registry record does not report a confidence interval for the primary endpoint. No conclusion about precision or statistical compatibility can therefore be drawn from a primary estimate in this record.
A p-value, in general, describes how unusual data at least as incompatible with a specified null hypothesis would be under assumptions of the test. It does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. The registry record does not report a primary-outcome p-value or test method. No significance claim can be supported by the endpoint description alone.
What should be made of planning illustrations?
A sample-size planning illustration based on an observed effect is a hypothetical calculation for a future design under stated assumptions. The registry record describes assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such a calculation is not observed power for this completed trial and is not evidence that the original study was planned using those assumptions. The registry record does not report the study's own sample-size justification. Numerical planning illustrations are not reported in the registry record.
In general, assumptions matter: a planning calculation depends on the target effect, variability, significance level, allocation, and analysis method. If the effect used as a planning anchor is estimated from a study, uncertainty in that estimate also matters. A planning illustration should therefore be read as conditional, not as a guarantee that a future study will reach a particular result. It cannot replace the observed outcome estimates and their uncertainty.
Why can over-dispersion matter?
Over-dispersion is a general issue in data where observed variability exceeds what a chosen statistical model expects. When present, a model that understates variability can produce uncertainty estimates that are too narrow. This concept is relevant to some count or event analyses, but the primary endpoint is a continuous OSDI score, and the record does not identify an over-dispersion analysis for it. The concept should not be taken as evidence that over-dispersion occurred in this study.
The registry says the primary analysis population comprises randomized subjects with at least one post-baseline visit, and that n at a time point means the number of subjects with non-missing values for that visit and arm. In general, analyses based on available observations can have different contributing numbers across visits. Missing outcome data can affect estimates if the missingness is related to participants' outcomes or treatment, and methods for handling missing values can influence results. The approach to missing data is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary OSDI outcome is assessed at multiple visits, and the registry lists 12 outcome measures. Testing several outcomes or time points can create multiplicity: in general, a larger collection of tests increases the chance that at least one result appears statistically noteworthy by chance. This does not mean a finding is necessarily false; it means interpretation benefits from knowing which outcomes and comparisons were prespecified and how multiplicity was handled.
The registry record does not report a multiplicity adjustment, a testing hierarchy, a prespecified primary contrast among visits, or a statistical analysis plan. It reports 0 analyses. The primary outcome is not reduced to one comparison in the record. The appropriate statistical handling of multiple visits and secondary outcomes is therefore not reported in the registry record.
The primary analysis population includes randomized subjects who attended at least one post-baseline visit. The record defines the time-specific n as the number with non-missing values for that arm and visit. This definition means the number of observations contributing to one visit may differ from the number contributing to another. Numerical time-specific counts for the OSDI outcome are not reported in the registry record.
In general, missing-data methods should be described because estimates can depend on why observations are missing and how the analysis treats them. The registry record does not report the amount or reasons for missing OSDI data, the method used to handle missing values, or sensitivity analyses. It also does not report whether the primary analysis followed an intention-to-treat principle beyond its stated population definition. The record's population description should therefore be read as the available definition, not as evidence about unreported analysis procedures.
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 |
|---|---|---|---|
| Systane Balance | 0 | 27 | 0.0% |
| Systane Gel | 1 | 27 | 3.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Systane Balance | 0 of 27 |
| Systane Gel | 0 of 27 |
Most frequent serious adverse event terms
| Event term | Organ system | Systane Balance | Systane Gel |
|---|---|---|---|
| Metastasis to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 27 | 1 of 27 |
| Convulsion | Nervous system disorders | 0 of 27 | 1 of 27 |
Serious events with the highest arm-level rate: metastasis to central nervous system (3.7%), convulsion (3.7%).
The serious adverse event figures list 0 affected subjects among 27 at risk in the Systane Balance group and 1 among 27 at risk in the Systane Gel group. These are registry counts for the listed groups; they should be read as descriptive safety information rather than as a complete comparison of risks. The record also lists 0 other adverse events in each group. Death counts are not reported in the registry record.
The registry lists Metastasis to central nervous system at 3.7% and Convulsion at 3.7% among the top serious-event terms. The term listing does not identify the treatment group for either term, so the terms should not be assigned to an arm based on the group counts. The record does not provide the timing, duration, outcome, relatedness assessment, or fuller clinical context for these events.
In general, a small number of events provides limited information about uncommon harms, and a zero count does not establish that an event cannot occur. The posted figures describe what is recorded, not a broad guarantee about safety. They also do not replace the symptom and biomarker outcomes, which address different questions.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study compared SYSTANE® BALANCE Lubricant Eye Drops with SYSTANE® Gel in randomized, double-masked, parallel groups. It defines the primary endpoint as mean change from baseline in OSDI score across visits and explains that a negative change indicates perceived improvement in ocular comfort. This gives readers the outcome's meaning and direction.
It does not, however, report the numerical primary-outcome results. There is no registered group mean change, treatment contrast, confidence interval, or p-value in the record. As a result, the direction, size, and precision of any between-group difference cannot be described. The same limitation applies to the listed secondary outcomes: their presence in the registry is not a report of their numerical findings.
In general, statistical evidence about a treatment comparison depends on more than whether an outcome was measured. Readers need estimates, measures of uncertainty, and enough information about the analysis to understand what was compared. A point estimate without uncertainty would be incomplete; an endpoint definition without either estimate or uncertainty cannot establish a treatment effect. The posted registry information does not support a conclusion about whether one product changed OSDI scores more than the other.
The safety figures report one serious event in the Systane Gel group and none in the Systane Balance group, with 27 at risk in each group. These limited counts are descriptive and do not establish a general safety difference. The serious-event term list also lacks group attribution. The record should therefore be read as a description of registered design and available counts, not as a complete account of comparative efficacy or safety.
These limitations do not mean that the study had no findings; they mean the results needed to evaluate those findings are not reported in the registry record. The completed status and defined follow-up visits do not substitute for numerical outcome reporting. Interpretation should remain confined to the design, endpoint definitions, and safety counts that are recorded.
13. Why This Trial Matters Statistically
This trial illustrates why a clear endpoint definition is essential but not sufficient for statistical interpretation. The registry describes OSDI, its score direction, the follow-up visits, and the population used for the primary analysis. Those details explain what the study sought to measure and how a change should be interpreted. Without numerical estimates and uncertainty, however, readers cannot assess the observed comparative effect.
The design also highlights the distinction between a symptom outcome and clinical or biological measures. The listed secondary outcomes include ocular surface findings, tear-film measures, and inflammatory biomarkers. In general, these outcomes can address different dimensions of a condition and need not move together. A symptom questionnaire should not be treated as a substitute for biomarker findings, nor should biomarker measurements be assumed to establish changes in reported comfort.
Repeated measurements add another statistical consideration. The outcome is listed at Baseline (Day 0), Day 14, and Day 30, so analysis choices can affect whether the focus is a particular visit or the pattern over time. The registry record does not report the chosen repeated-measures method or a multiplicity strategy. That absence underscores the value of transparent reporting of the estimand, model, uncertainty, and missing-data handling.
Finally, the record distinguishes the primary analysis population from time-specific non-missing observations. This is a useful reminder that enrollment and the number contributing data to an endpoint are not interchangeable. Reporting participant flow and outcome-specific counts helps readers understand the basis of each estimate. Those details are not reported for the primary endpoint in the registry record, limiting statistical appraisal despite the available design description.
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.
The principal limitation for interpreting this study is that numerical results for the primary OSDI outcome are not reported in the registry record. The record identifies the measure and visits but does not provide group estimates, a between-group comparison, or uncertainty measures. Numerical results for the listed secondary outcomes are also not reported in the registry record.
The registry describes the primary population as randomized subjects who attended at least one post-baseline visit, with time-specific n defined by non-missing observations. It does not report the OSDI counts at each visit, the amount or reasons for missing data, or the method used to handle missing observations. The impact of missingness on the primary estimate cannot therefore be assessed.
Details of the statistical analysis are also limited. The model for repeated measurements, the primary contrast, covariate adjustment, multiplicity strategy, and analysis plan are not reported in the registry record. The record does not report a sample-size justification or interim analyses. These omissions prevent assessment of whether the reported design and analyses were aligned with a prespecified statistical plan.
The record identifies the study as double-masked but does not describe which roles were masked or how masking was maintained. It also does not report adherence or treatment exposure. These details could inform appraisal of implementation, but should not be inferred from the design label or assigned dosing schedule.
Safety reporting is limited to the listed counts and event terms. The registry record does not report event timing, relatedness, outcomes, or group attribution for the listed serious-event terms. The figures should be interpreted as limited descriptive information rather than a comprehensive safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: SYSTANE® BALANCE Symptoms (OSDI) & Inflammatory Biomarkers — NCT01733732.
- Registry record last updated 2018-06-29; status last verified 2013-11.
- Results first posted 2014-11-04.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01733732 is a completed randomized, double-masked, parallel-group study sponsored by Alcon Research. It enrolled 54 subjects with dry eye syndrome and compared SYSTANE® BALANCE Lubricant Eye Drops with SYSTANE® Gel. Both arm descriptions specify one drop in each eye four times a day for 30 days.
The primary outcome was mean change from baseline in OSDI score at Baseline (Day 0), Day 14, and Day 30. The record defines a negative change as indicating perceived improvement in ocular comfort and specifies an analysis population of randomized subjects with at least one post-baseline visit. It lists 12 outcome measures and 0 analyses.
Numerical primary and secondary outcome results are not reported in the registry record. Safety figures list 0 serious events among 27 at risk in the Systane Balance group and 1 among 27 at risk in the Systane Gel group. The record does not provide enough outcome detail to quantify comparative symptom effects or their precision.