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 Safety, Efficacy, and Acceptability Study of an Eye Drop Formulation in Subjects With Dry Eye Disease (NCT01459588), a randomized phase 3 study. The primary outcome is Change From Baseline in Ocular Surface Disease Index© Questionnaire Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01459588 |
| Phase | Phase 3 |
| Condition | Dry Eye Syndromes |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 315 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Allergan |
| Results posted | Yes |
2. Clinical Question
Population
People with dry eye disease were eligible for the study. The primary outcome population is described as the intent-to-treat population, including all randomized participants. Further eligibility criteria and participant characteristics are not reported in the registry record.
Intervention
The study included Carboxymethylcellulose Based Eye Drop Formulation A and Carboxymethylcellulose Based Eye Drop Formulation B. Each regimen specified 1-2 drops in each eye as needed, at least 2 times daily for 30 days.
Comparator
The other study regimens were Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops and Carboxymethylcellulose Based Lubricant Eye Drops. Each was also described as 1-2 drops in each eye as needed, at least 2 times daily for 30 days. The registry record does not identify a single comparator for the primary outcome.
Primary question
The primary measure was change from baseline in Ocular Surface Disease Index© Questionnaire score at Baseline, Day 30. The record does not report arm-specific changes or a statistical comparison, so it does not establish how the formulations compared on this measure.
3. Trial Design
The registry describes a randomized, triple-masked, parallel Phase 3 study sponsored by Allergan. Enrollment was 315. The study status is COMPLETED, with a start date of 2011-10-01 and a primary completion date of 2012-02-15. These record details establish the broad design and timing, but do not supply the results of the primary efficacy analysis.
Four interventions are named: Carboxymethylcellulose Based Eye Drop Formulation A, Carboxymethylcellulose Based Eye Drop Formulation B, Carboxymethylcellulose Based Preservative-Free Lubricant Eye Drops, and Carboxymethylcellulose Based Lubricant Eye Drops. The arm descriptions give each regimen as 1-2 drops in each eye as needed, at least 2 times daily for 30 days. The record does not state a more specific dosing schedule or describe adherence.
Randomization means allocation is intended to reduce systematic differences between treatment groups at the outset. Masking is intended to limit the influence of treatment knowledge on trial conduct or assessment. The registry identifies the study as triple masked but does not specify which roles were masked or how masking was maintained. The randomization sequence, allocation concealment, and details of the parallel-group procedures are not reported in the registry record.
The record names dry eye disease as the condition and describes the study purpose as evaluating safety, efficacy, and acceptability. Its primary measure was a questionnaire score, and its secondary outcomes included tear break-up time, corneal staining, conjunctival staining, and Schirmer test results. Although the trial is marked completed, the record does not report a single primary-outcome comparison, its estimate, or its uncertainty.
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 | Carboxymethylcellulose Based Eye Drop Formulation A | Carboxymethylcellulose Based Eye Drop Formulation B | Carboxymethylcellulose Preservative-Free Lubricant Eye Drops | Carboxymethylcellulose Based Lubricant Eye Drops |
|---|---|---|---|---|
| STARTED | 105 | 51 | 103 | 56 |
| COMPLETED | 104 | 49 | 102 | 55 |
| NOT COMPLETED | 1 | 2 | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population included all randomized participants.
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 | Carboxymethylcellulose Based Eye Drop Formulation A | Carboxymethylcellulose Based Eye Drop Formulation B | Carboxymethylcellulose Preservative-Free Lubricant Eye Drops | Carboxymethylcellulose Based Lubricant Eye Drops | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 105 | 51 | 103 | 56 | 315 | |
| Age, Customized: <30 years | Participants | 9 | 5 | 6 | 5 | 25 |
| Age, Customized: 30 to 40 years | Participants | 10 | 3 | 12 | 3 | 28 |
| Age, Customized: >40 years | Participants | 86 | 43 | 85 | 48 | 262 |
| Sex: Female, Male: Female | Participants | 83 | 44 | 87 | 41 | 255 |
| Sex: Female, Male: Male | Participants | 22 | 7 | 16 | 15 | 60 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Ocular Surface Disease Index© Questionnaire Score, measured over Baseline, Day 30.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in Ocular Surface Disease Index© Questionnaire score, assessed at Baseline, Day 30. The registry describes the questionnaire as a 12-item measure of the overall severity of dry eye disease per patient. Responses use a 5-point scale from 0=none of the time to 4=all of the time, and the total possible score ranges from 0=No disease to 100=Maximum severity of disease. A negative change from baseline is defined as improvement.
In general, a patient-reported questionnaire can capture symptoms and their perceived effect that may not be fully represented by clinical examination measures. A change score expresses how a participant’s measured score differs from their baseline measurement. The endpoint therefore focuses on change over the stated assessment period, rather than only the score at the later assessment.
The record specifies the intent-to-treat population, including all randomized participants, for this outcome. However, it does not report the group-level baseline or Day 30 scores, mean changes, standard deviations, confidence intervals, or a comparison between formulations. Without those results, the endpoint definition explains what was intended to be measured but does not show the observed change or how precisely it was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives a clear definition of the primary measure, but does not provide an interpretable primary efficacy estimate. It describes change from baseline in Ocular Surface Disease Index© Questionnaire score at Baseline, Day 30, and notes that negative change indicates improvement. No arm-specific mean changes, standard deviations, confidence intervals, or statistical test results are reported. Consequently, the posted record does not establish the direction or size of any between-group difference on the primary measure.
The record also does not reduce the primary outcome to a single comparison because it has several categories or time points. That is an important constraint for interpretation: a trial with several arms, outcome categories, or assessment times can yield multiple possible comparisons, and the selected comparison affects what an estimate means. The registry does not identify a primary contrast among the four formulations or report a statistical procedure for choosing or evaluating comparisons.
In general, a mean change describes the average movement in a continuous outcome, while the standard deviation describes how much individual measurements vary around that mean. A confidence interval conveys the range of estimates compatible with the data and the method used to construct it. Such an interval helps distinguish a relatively precise estimate from one with substantial uncertainty. Those quantities are not reported for the primary outcome in this registry record, so the precision of the trial’s efficacy findings cannot be assessed from the posted information.
There are listed safety counts. Serious adverse events are recorded in the Formulation A and lubricant eye drop groups, while no serious adverse events are recorded for the Formulation B and preservative-free groups. The record also lists no other adverse events in any group. These are descriptive counts, not evidence by themselves that an event was caused by a formulation or that the groups differ reliably. The registry gives no comparative safety analysis or uncertainty for these counts.
The listed secondary outcomes concern tear break-up time, corneal staining, conjunctival staining, and Schirmer test results. Their names indicate additional clinical measurements, but the registry record does not report their numerical results. Overall, the record supports description of the design, outcome definitions, and recorded adverse-event counts. It does not support a quantitative conclusion about comparative efficacy, nor a precise comparative safety conclusion.
9. Statistical Methods Explained
The registry describes a randomized, triple-masked, parallel study and identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. It lists 0 analyses. No primary-outcome estimate, comparison, confidence interval, or p-value is reported in the registry record. The methodological discussion below distinguishes these record details from general statistical explanations; it cannot reconstruct an analysis that is not reported.
What does a mean change represent?
In general, a mean change is the average of participants’ differences between measurements at follow-up and baseline. It retains the direction of change: for this questionnaire, the record states that a negative change indicates improvement. The mean is useful for describing the average response, but it does not show the full distribution of individual changes. Participants can have different responses even when their group mean is similar.
The standard deviation describes spread around the mean. It is not the same as the uncertainty in the estimated mean. That uncertainty also depends on the amount of information contributing to the estimate and the analysis method. The record specifies mean and standard deviation as the measure and dispersion for the primary outcome, but does not give their observed values by group. It therefore does not allow readers to assess either the average change or its variability.
Why does a comparison need a defined contrast?
In general, a treatment comparison is defined by the groups being contrasted and the outcome being analyzed. A difference between group means answers a different question from a within-group change. A trial may also make comparisons at different follow-up times or across different outcome measures. When several plausible contrasts are available, a clearly stated primary contrast helps readers understand which estimate was designated as the main test of the research question.
Here, the registry names four formulations and gives the primary outcome’s assessment time frame as Baseline, Day 30. It does not identify a single primary contrast or report estimates for the possible comparisons. The registry’s note that the primary outcome was not reduced to one comparison because it has several categories or time points further limits interpretation. The record does not say whether the categories reflect response groupings, assessment occasions, or another structure, so those details should not be inferred.
What would a confidence interval add?
In general, a confidence interval presents uncertainty around an estimated quantity under a stated statistical method. A narrow interval indicates greater precision than a wide interval, though interpretation also depends on the clinical meaning of the outcome and the comparison. An interval for a between-group contrast would help readers judge which values are consistent with the observed data; a p-value alone would not describe the full range of uncertainty.
No confidence interval or p-value for the primary outcome is reported in the registry record. There is therefore no posted estimate around which to assess precision, and no basis for describing statistical evidence for a specific contrast. Recalculating a result from summary statistics is not possible because the relevant group-level outcome summaries are not reported.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variability in data is greater than a statistical model assumes. If a model understates variability, its standard errors can be too small and its confidence intervals too narrow, making the evidence appear more precise than it is. Appropriate modeling can account for extra variability when the data structure and outcome support that approach. This is a general statistical consideration, not a feature established for this trial: the record does not report model diagnostics, an over-dispersion assessment, or the primary analysis model.
How should the planning assumptions be understood?
The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is the stated fraction of the observed effect. For time-to-event tables, the stated quantity is the total number of events using the Schoenfeld method; other tables use participants per arm. These are descriptions of planning assumptions, not observed outcomes or evidence about the trial’s achieved power.
The registry does not report the trial’s own sample-size justification, the assumed effect used for its design, or whether the stated illustration assumptions were used to plan the study. A planning calculation asks how much information a hypothetical future study might need under specified assumptions. It does not change the observed data and cannot substitute for a reported estimate and its uncertainty. No planning output values are reported in the registry record, so no sample-size figure can be interpreted from the record alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies the Ocular Surface Disease Index© Questionnaire score as the primary outcome and lists secondary outcomes for tear break-up time, corneal staining, conjunctival staining, and Schirmer test results. It does not report a multiplicity strategy for interpreting results across outcomes, arms, categories, or assessment times. In general, when researchers test several hypotheses, the chance of obtaining at least one apparently noteworthy result can increase. Methods for addressing this issue depend on the prespecified analysis plan and the scientific questions. No such plan is reported in the registry record, so it is not possible to determine how multiplicity was handled.
The primary outcome population is described as intent-to-treat and includes all randomized participants. That definition indicates the intended population for the primary measure; it does not, by itself, describe how missing measurements were handled or which participants contributed to each analysis. The record does not report the amount or pattern of missing outcome data, imputation methods, sensitivity analyses, or exclusions from the outcome analysis. These details are important because missing measurements can affect both the estimate and its uncertainty.
The registry record does not report a statistical analysis plan, the analysis model, or the handling of deviations from assigned treatment. It also does not give analysis-population counts for the primary outcome. Without these details and the outcome estimates, readers cannot assess whether the reported analysis followed a prespecified approach or how robust it was to alternative assumptions. No conclusion about missing-data bias or multiplicity adjustment should be inferred from the record.
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 |
|---|---|---|---|
| Carboxymethylcellulose Based Eye Drop Formulation A | 1 | 105 | 1.0% |
| Carboxymethylcellulose Based Eye Drop Formulation B | 0 | 51 | 0.0% |
| Carboxymethylcellulose Preservative-Free Lubricant Eye Drops | 0 | 103 | 0.0% |
| Carboxymethylcellulose Based Lubricant Eye Drops | 1 | 56 | 1.8% |
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 |
|---|---|
| Carboxymethylcellulose Based Eye Drop Formulation A | 0 of 105 |
| Carboxymethylcellulose Based Eye Drop Formulation B | 0 of 51 |
| Carboxymethylcellulose Preservative-Free Lubricant Eye Drops | 0 of 103 |
| Carboxymethylcellulose Based Lubricant Eye Drops | 0 of 56 |
Most frequent serious adverse event terms
| Event term | Organ system | Carboxymethylcellulose Based Eye Drop Formulation A | Carboxymethylcellulose Based Eye Drop Formulation B | Carboxymethylcellulose Preservative-Free Lubricant Eye Drops | Carboxymethylcellulose Based Lubricant Eye Drops |
|---|---|---|---|---|---|
| Bile duct stone | Hepatobiliary disorders | 1 of 105 | 0 of 51 | 0 of 103 | 0 of 56 |
| Ankle fracture | Injury, poisoning and procedural complications | 0 of 105 | 0 of 51 | 0 of 103 | 1 of 56 |
Serious events with the highest arm-level rate: ankle fracture (1.8%), bile duct stone (1.0%).
The safety record lists serious adverse events by group. Formulation A has 1 serious event among 105 at risk; Formulation B has 0 among 51; the preservative-free lubricant has 0 among 103; and the lubricant eye drops have 1 among 56. The record lists 0 other adverse events for every group. Deaths are not reported in the registry record.
These entries are descriptive counts with their recorded at-risk group sizes. They should not be treated as a comparative statistical analysis. A count does not establish whether an event was caused by treatment, and a zero recorded count does not prove that an event could not occur. The registry does not report comparative estimates, confidence intervals, or an analysis of differences in adverse events.
The listed serious-event terms are “Ankle fracture” at 1.8% and “Bile duct stone” at 1.0%. The record does not provide further detail about event timing, participant characteristics, or attribution. These percentages should therefore be read as reported terms rather than as evidence of a causal relationship. The safety information is limited to the recorded categories and counts and does not replace the missing comparative analysis.
12. What the Result Does, and Does Not, Mean
The registry record can establish what the study set out to measure and how it was broadly organized. It describes a randomized, triple-masked, parallel Phase 3 study of four carboxymethylcellulose-based eye drop formulations in people with dry eye disease. It defines the primary outcome as change from baseline in Ocular Surface Disease Index© Questionnaire score at Baseline, Day 30, and specifies that a negative change indicates improvement.
Those design and endpoint details do not reveal the trial’s observed efficacy results. The registry does not report group-level primary-outcome changes, standard deviations, confidence intervals, or a statistical comparison. It also does not identify a single primary contrast. Consequently, the record cannot show whether the groups differed, the direction of any difference, or how precise a comparison might be. A trial being marked completed does not mean that its results are available in the record.
The safety entries show the serious and other adverse-event counts recorded for each group. They do not establish causality, and they do not provide a reliable comparison of safety between formulations. The absence of a recorded event in a group is not proof of zero risk. The record lacks the details and comparative estimates needed to interpret differences in safety with precision.
In general, evidence about a treatment depends on the observed outcomes, the comparison being made, and the uncertainty around the estimate. A study design and an outcome definition alone cannot answer whether one formulation had a better outcome than another. Nor can a planning illustration answer that question: planning assumptions concern hypothetical study requirements, not the findings of this completed study.
The sound reading is therefore bounded. The registry documents a clinical question, trial structure, outcome definitions, and selected safety counts. It does not report enough efficacy or comparative safety results to support a conclusion about the relative effects of the formulations. No medical recommendation follows from these registry entries.
13. Why This Trial Matters Statistically
This study illustrates why a trial’s design and its reported results need to be read together. Randomization, masking, and a parallel structure describe how the comparison was organized, but they do not supply the effect estimate. For a continuous primary outcome, readers need group-level summaries or a direct contrast, together with information about uncertainty, to understand what the data indicate.
The registry’s primary measure is a patient-reported score with an explicitly described direction of improvement. That makes the endpoint interpretable in principle: the score reflects reported dry eye severity, and negative change is defined as improvement. Yet an endpoint definition is not a result. Without the observed changes and a stated contrast, statistical interpretation cannot move from the question asked to an answer supported by the posted data.
The record also demonstrates the importance of multiplicity and analysis transparency. Multiple formulations and outcome measures create more than one possible comparison. A prespecified contrast and an explained approach to multiple testing would help readers understand which findings are central and how to interpret additional analyses. The registry record does not report those details, so the scope of any statistical claims cannot be evaluated.
Finally, descriptive safety counts and efficacy measures answer different questions and have different limitations. Small counts cannot establish comparative safety, just as an outcome definition cannot establish comparative efficacy. Clear reporting of estimates, uncertainty, missing-data methods, analysis populations, and planned comparisons is essential for a complete statistical account. The record is informative about the study’s framework, while its lack of reported outcome analyses leaves the central comparative question unresolved.
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 main limitation for interpretation is the absence of reported primary-outcome results. The registry gives the endpoint definition and population but no group-specific change estimates, standard deviations, confidence intervals, or comparison. Its note that the primary outcome has several categories or time points and was not reduced to one comparison means that the record does not identify a singular primary contrast for interpretation.
Details needed to assess the conduct and analysis are also not reported in the registry record. These include eligibility criteria beyond the condition, participant characteristics, randomization procedures, the roles covered by triple masking, adherence, and the analysis model. The record does not describe missing outcome data or its handling, provide analysis-population counts, or state how multiplicity was addressed. These omissions prevent assessment of the robustness and precision of any efficacy analysis.
The regimen descriptions specify 30 days of use, and the primary outcome time frame is Baseline, Day 30. The registry does not report longer-term outcome assessment. The safety record presents counts and selected serious-event terms but no comparative analysis, event timing, or causal attribution. Deaths are not reported in the registry record.
These are limitations of the information available in the registry record, not proof that the trial lacked procedures or analyses that were documented elsewhere. They do mean that the posted information does not support a quantitative appraisal of comparative efficacy, precision, or safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Efficacy, and Acceptability Study of an Eye Drop Formulation in Subjects With Dry Eye Disease — NCT01459588.
- Registry record last updated 2019-04-16; status last verified 2019-04.
- Results first posted 2013-03-14.
- 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
NCT01459588 is a completed randomized, triple-masked, parallel Phase 3 study sponsored by Allergan. It enrolled 315 participants and studied four carboxymethylcellulose-based eye drop formulations for dry eye disease. The recorded start date is 2011-10-01, and the primary completion date is 2012-02-15.
The primary outcome was change from baseline in Ocular Surface Disease Index© Questionnaire score at Baseline, Day 30, in an intent-to-treat population including all randomized participants. The record defines negative change as improvement and lists tear break-up time, corneal staining, conjunctival staining, and Schirmer test results as secondary outcomes.
The registry record lists serious and other adverse-event counts by group but does not report a primary-outcome comparison, numerical efficacy estimates, or their uncertainty. It also does not report a comparative safety analysis or key statistical details such as missing-data handling and multiplicity procedures. The study framework is described, but the posted record does not resolve the comparative efficacy question.