Acute Comfort and Blurring Profile Evaluation of Marketed Lubricant Eye Drops: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acute Comfort and Blurring Profile Evaluation of Marketed Lubricant Eye Drops (NCT00756093), a randomized na study. The primary outcome is Drop Comfort.

2. Clinical Question

The registry record describes a comparison of drop comfort among people with dry eye receiving four marketed lubricant eye drops. The primary question is whether the mean comfort rating after instillation differed for Optive Lubricant Eye Drops, Blink Tears, or GenTeal Moderate Lubricant Eye Drops, compared with Systane Ultra Lubricant Eye Drops. Comfort was rated once upon instillation on a scale from 0 to 9, where 0 means most comfortable and 9 means most uncomfortable. A lower average score therefore represents a more comfortable rating on this scale.

The central statistical contrast is between the average score for Systane Ultra and the average score for each other product. Because higher scores indicate greater discomfort, a positive mean difference for a comparator corresponds to a higher, less comfortable average rating relative to Systane Ultra. The reported comparisons are simple unadjusted contrasts from the arm summaries; a registry-posted analysis is not available to establish whether a different analysis of the crossover data was performed.

3. Trial Design

This was a randomized, double-masked, crossover trial sponsored by Alcon Research. The registry lists the study as completed and reports enrollment of 20. Its recorded phase is NA. The trial is described as evaluating comfort, acceptability, and blur profile among four marketed artificial tears in people with dry eye; the posted primary outcome is drop comfort.

The four interventions were Systane Ultra Lubricant Eye Drops, Optive Lubricant Eye Drops, Blink Tears, and GenTeal Moderate Lubricant Eye Drops. Each arm description specifies one drop in each eye one time. A crossover design means treatment comparisons are made within a study structured around participants receiving different treatments over the course of the trial, rather than relying only on separate parallel groups. The registry record does not report the treatment sequence, the timing between instillations, or whether any washout period was used. It also does not give details of the randomization procedure or explain how masking was maintained.

The arm summaries list 20.0 observations for each product. In a crossover trial, arm counts should not be added to estimate the number of unique participants, because the same participant may contribute observations under more than one treatment. The record reports enrollment of 20, but does not provide a participant flow, exclusions, or outcome-specific missing-data counts.

The primary endpoint is a continuous mean comfort rating, with standard deviation as the measure of spread. The record lists one outcome measure and no posted analyses. The registry record does not report the original sample-size justification, the intended statistical model, an analysis population, or interim analyses. Therefore, the recalculated comparisons should be read as descriptive, unadjusted summaries and not as a substitute for a documented trial analysis that accounts for the crossover structure.

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: randomized, double-masked, cross-over design

First Intervention

Second Intervention

Third Intervention

Fourth Intervention

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.

6. Primary Endpoint

The registry lists the primary outcome as Drop Comfort, measured over once upon instillation.

The primary endpoint, Drop Comfort, is the participant’s rating of comfort once upon instillation. The registry describes a 0-to-9 grading scale: 0 means most comfortable and 9 means most uncomfortable. The reported summary is the mean rating, accompanied by a standard deviation. The mean describes the average rating in an arm; the standard deviation describes how much individual ratings varied around that average.

Comfort is relevant to the stated study aim because the trial compares the immediate acceptability of four marketed lubricant drops. A numerical scale allows ratings to be summarized and contrasted across products. The direction of the scale matters: a lower mean is more favorable in terms of comfort as defined by this endpoint, while a higher mean indicates more discomfort. In the posted summaries, mean ratings were 0.7 for Systane Ultra, 1.05 for Optive, 1.84 for Blink Tears, and 1.1 for GenTeal Moderate.

The endpoint is narrowly timed and defined. It captures comfort once upon instillation, not comfort over repeated use or change over a longer period. Although the trial’s brief summary also mentions acceptability and blur profile, no secondary outcomes are posted in the registry record. The comfort score should not be interpreted as a measure of other outcomes that are not included in this endpoint, and the record does not describe how the scale was administered beyond its range, anchors, and timing.

7. Results Posted in the Registry

• Optive Lubricant Eye Drops: mean 1.05 versus 0.70 on control; difference 0.35 (95% CI -0.38 to 1.08), standardized effect d = 0.30; z-test p = 0.349.
• Blink Tears: mean 1.84 versus 0.70 on control; difference 1.14 (95% CI 0.03 to 2.25), standardized effect d = 0.64; z-test p = 0.044.
• GenTeal Moderate Lubricant Eye Drops: mean 1.10 versus 0.70 on control; difference 0.40 (95% CI -0.37 to 1.17), standardized effect d = 0.32; z-test p = 0.306.

8. Statistical Interpretation

9. Statistical Methods Explained

For a continuous endpoint such as a comfort rating, a mean summarizes the central tendency of the observed scores. The standard deviation summarizes their spread. These summaries answer different questions: a mean gives the average rating, while a standard deviation indicates how varied participant ratings were. The posted means were 0.7 for Systane Ultra, 1.05 for Optive, 1.84 for Blink Tears, and 1.1 for GenTeal Moderate. The associated standard deviations were 1.26, 1.1, 2.19, and 1.21, respectively. Since lower ratings indicate greater comfort, the scale’s direction must be kept in mind when describing the means.

What does a mean difference represent?

A mean difference is the mean in one arm minus the mean in the reference arm. Here, the listed reference is Systane Ultra. A positive estimate means that the comparator’s average score is higher, which corresponds to more discomfort on this scale. The recalculated unadjusted estimates were 0.35 for Optive, 1.14 for Blink Tears, and 0.4 for GenTeal Moderate. These estimates describe the size and direction of the observed contrasts. They are not themselves measures of certainty, and they are not an adjusted estimate from an analysis documented in the registry record.

What does a p-value add?

A p-value describes how unusual a result at least as extreme as the observed result would be under a specified null model, assuming that model and its assumptions are appropriate. It does not give the probability that the null hypothesis is true, and it does not measure clinical importance. The posted unadjusted p-values were 0.349 for Optive, 0.044 for Blink Tears, and 0.306 for GenTeal Moderate. They relate to the individual recalculated contrasts and do not, by themselves, account for examining several comparisons. The registry record does not report the trial’s planned statistical test or any multiplicity procedure.

Why does the crossover structure matter?

General statistical explanation: measurements from the same participant are often correlated. A crossover analysis can use that pairing, separating variation between participants from variation in their responses across treatments. Accounting for within-participant correlation can affect the estimated standard error and interval for a treatment contrast. The recalculated comparisons use arm-level means and standard deviations; the registry record does not report the paired data, within-participant correlation, or a crossover model. The exact effect of using a paired analysis therefore cannot be determined from the posted summaries. The arm summaries remain useful descriptions, but their unadjusted contrasts should not be treated as a verified crossover analysis.

How should standard deviations and uncertainty be distinguished?

General statistical explanation: a standard deviation describes variation among observations, whereas a standard error describes uncertainty in an estimated quantity under a statistical model. A confidence interval uses an estimate and its uncertainty to show a range of values compatible with the analysis. Wider intervals indicate less precision. The registry record does not state the confidence level for the comparison intervals, nor does it post an analysis report explaining their construction. The comparison calculations are therefore best read as unadjusted summary-statistic recalculations, rather than as registry-reported inferential results.

What remains undocumented?

The record lists one primary outcome and no posted analyses. It does not report a statistical analysis plan, a model for the crossover data, handling of missing observations, an analysis population, interim analyses, or the sample-size justification used when designing the trial. The displayed planning estimates use an explicitly stated planning approach, but they are not evidence of the original design assumptions. When planned methods are not documented, readers cannot verify whether the reported summaries were selected in advance or how the final analysis handled design-specific features. These gaps limit how far the recalculated comparisons can be taken beyond describing the posted arm summaries.

10. Confidence Intervals and Precision

The comparison intervals communicate uncertainty around the recalculated mean differences. For Optive versus Systane Ultra, the estimated difference was 0.35 and the interval ranged from -0.383 to 1.083. For GenTeal Moderate versus Systane Ultra, the estimate was 0.4 and the interval crossed zero. In both comparisons, the range includes no difference, as does the corresponding interpretation of the unadjusted p-values of 0.349 and 0.306. The intervals also include values in different directions, so the estimates do not pinpoint the direction or magnitude precisely.

For Blink Tears versus Systane Ultra, the estimated difference was 1.14 and the interval extended from a positive lower limit to 2.247. The corresponding unadjusted p-value was 0.044. The interval is still broad relative to the point estimate: it allows a range of possible differences, even though its reported lower endpoint is above zero. Statistical precision is not the same as importance, and the scale’s direction means positive contrasts correspond to higher discomfort ratings.

Confidence intervals are generally used to show which parameter values are reasonably compatible with data under a specified method. They do not guarantee that the true effect lies within a particular interval, and they are sensitive to the model and assumptions used to construct them. The confidence level and the interval method are not reported in the registry record. In addition, the calculations are unadjusted and are based on arm summaries despite the crossover design; the record does not provide the paired information needed to verify uncertainty using a within-participant analysis. The intervals should therefore be read as approximate precision summaries for the recalculated contrasts, not as a substitute for a documented trial analysis.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size estimates are planning illustrations, not counts of participants observed in this trial. For these continuous-outcome comparisons, the figures are participants per arm, not total events. The assumptions listed for the illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect. The original trial’s sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a hypothetical study to have an 80% chance of detecting the chosen effect under those assumptions, if that effect and the statistical model are correct. The 90% power column gives the corresponding planning figure for a 90% chance. These are design calculations, not promises that a study of that size will identify a difference. They also do not account for features not included in the stated assumptions, such as a crossover analysis or missing observations.

The rows describe planning for 100%, 75%, and 50% of the observed effect. A smaller target effect is harder to distinguish from random variation, so the planning estimates require more participants. The curve represents the same planning relationship across effect assumptions; it is not a record of actual enrollment or precision achieved. The trial enrolled 20, and the planning estimates should not be used to claim that the completed study had a particular probability of detecting its observed results. This is not observed power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.350; pooled standard deviation σ = 1.183.
2. n = 2 × (1.96 + 0.842)² × 1.183² / 0.350² = 179.2, rounded up to 180 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.35                      # observed difference in means
sigma <- 1.1827087553578                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(756093)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 180 (80% power), 240 (90% power)
 75% of observed effect: n per arm = 319 (80% power), 427 (90% power)
 50% of observed effect: n per arm = 717 (80% power), 960 (90% power)
power.t.test: 180.2 
Simulated power at n = 180 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure, Drop Comfort, and no posted analyses. It also does not list posted secondary outcomes. The brief summary refers to comfort, acceptability, and blur profile, but outcome results for acceptability and blur are not reported in the registry record. There is no basis in the posted results for evaluating those outcomes or their relationship to comfort.

The recalculated comparisons contrast each of three products with Systane Ultra. Each posted p-value is unadjusted. When several contrasts are examined, the chance of obtaining at least one apparently unusual result by chance can increase if no adjustment or other prespecified strategy is used. General statistical explanation: multiplicity methods can control or otherwise address this issue, but they may change the interpretation of individual p-values and intervals. No multiplicity plan or adjustment is reported in the registry record. The p-value of 0.044 for Blink Tears should therefore be considered alongside the other product comparisons and the absence of a reported analysis plan.

The registry record does not describe missing-data handling, participant exclusions, the set of participants included in each analysis, or a crossover-specific analysis population. Arm summaries list 20.0 observations for each product, but that does not establish that all enrolled participants contributed complete data to every comparison or explain whether any observations were omitted. The record also does not give reasons for missingness or report sensitivity analyses. These details matter because analysis choices can affect the estimates and their uncertainty.

Randomization and double masking are recorded, but the methods used to implement them are not described. The record does not report an interim-analysis plan or any adjustment for interim looks. These items should be treated as undocumented rather than assumed absent from the original study conduct. With no registry-posted analysis results, readers cannot check whether the recalculated contrasts match a prespecified analysis or whether the crossover structure and multiple comparisons were addressed in the trial’s own analysis.

14. 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 0% reporting threshold.

For each of the four products, the registry reports 20 participants at risk for serious adverse events and 0 with a serious adverse event. It also reports 20 at risk and 0 affected for other adverse events in each group. No serious adverse-event terms are listed. The deaths field has no reported value; deaths should therefore be described as not reported in the registry record, not as zero.

These figures are counts in the registry’s safety groups. Because the study is a crossover trial, a person may contribute to more than one treatment group; the group counts should not be added to infer a number of unique participants. The record does not give event definitions, collection procedures, observation duration by treatment, or a narrative safety analysis. The zero counts mean no events were recorded in the posted group summaries; they do not establish that no events occurred outside the reported information or quantify risk with high precision. The safety figures describe the registry entries and should not be used as a broader safety conclusion.

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

The results describe immediate comfort ratings after one-time instillation of four marketed lubricant eye drops in a randomized, double-masked crossover trial enrolling 20 people with dry eye. The mean scores were all near the lower end of the 0-to-9 scale, whose lower values mean greater comfort. The highest posted mean was 1.84 for Blink Tears; the other means were 0.7 for Systane Ultra, 1.05 for Optive, and 1.1 for GenTeal Moderate. The recalculated unadjusted comparison estimates were positive for all three comparators versus Systane Ultra, indicating higher average discomfort ratings in those arms on this scale.

Those descriptive results do not establish that the products differ in a larger population. The Optive and GenTeal Moderate intervals cross zero, and their unadjusted p-values were 0.349 and 0.306. The Blink Tears interval had a positive lower endpoint and its unadjusted p-value was 0.044, but the comparison is one among several and no multiplicity adjustment or registry-posted analysis is reported. The crossover structure also matters to uncertainty, and the paired information needed to assess it is not reported.

The outcome is limited to comfort once upon instillation. It does not establish longer-term comfort, repeated-use experience, blur profile, broader acceptability, or outcomes not posted in the registry. The record does not provide a detailed description of participants, treatment sequences, missing-data handling, or a statistical analysis plan. The safest reading is therefore specific: the posted summaries show the recorded average comfort ratings and unadjusted arm-level contrasts, with substantial limitations in inferential detail. They do not answer every question raised by the trial’s broader stated aim or support conclusions beyond the measured endpoint and timing.

16. Why This Trial Matters Statistically

This trial illustrates why design details and statistical summaries need to be read together. A crossover design can make within-person comparisons informative because each participant may contribute ratings under more than one treatment. At the same time, analyses of crossover data need to account for the dependence among measurements from the same person. Arm means and standard deviations alone do not reveal the within-participant correlation, and the registry record does not report a paired model or the data needed to reproduce one.

The endpoint also makes direction easy to misread unless its anchors are kept in view. A larger comfort score means more discomfort, so a positive comparator-minus-control contrast points toward a higher discomfort rating rather than better comfort. Clear interpretation depends on knowing both the contrast direction and the scale direction.

The reported unadjusted comparisons show how an estimate, interval, and p-value provide different information. A point estimate gives a direction and scale; an interval communicates uncertainty; a p-value reflects compatibility with a specified null model under assumptions. None is a substitute for the others. The Blink Tears comparison’s p-value of 0.044 is a single unadjusted result among comparisons, while the record does not document multiplicity handling or the trial’s own analysis.

Finally, planning illustrations based on observed effects should not be confused with the trial’s original design justification. They show how hypothetical sample-size requirements vary with the effect being targeted and stated assumptions. They do not establish the study’s original power or turn a small completed trial into a more precise one. The registry’s absence of an analysis plan and detailed crossover methods makes transparent reporting especially important when interpreting its summary statistics.

17. 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 registry record provides limited detail for assessing how the trial was conducted and analyzed. It identifies randomization, double masking, and a crossover model, but the treatment sequence, period structure, timing between instillations, and any washout are not reported in the registry record. These details are relevant to evaluating whether treatment effects could be separated from period or carryover effects.

The primary outcome is described as a comfort grade on a 0-to-9 scale, but the record does not report how ratings were elicited, whether the scale was validated, or the timing of rating beyond once upon instillation. The record also does not describe the enrolled participants beyond dry eye, so the characteristics of the study population cannot be assessed from these entries.

Although each arm summary lists 20.0 observations, the registry does not provide participant flow, outcome-specific completeness, reasons for missing ratings, or an analysis population. It does not report a statistical model accounting for within-person correlation, or a plan for handling multiple comparisons. The posted contrasts are recalculated from arm summaries and should not be read as the registry’s own analysis. The confidence-interval level and method are not reported in the registry record.

The record lists one outcome measure and no analyses; it does not post results for the broader stated aims of acceptability and blur profile. Follow-up is limited in the outcome description to the single instillation assessment, so the record cannot characterize ongoing use. These limitations constrain interpretation of both the efficacy-style endpoint and the safety summaries, without implying that unreported procedures or outcomes were necessarily absent from the study itself.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Acute Comfort and Blurring Profile Evaluation of Marketed Lubricant Eye Drops — NCT00756093.
• Registry record last updated 2012-02-02; status last verified 2012-01.
• Results first posted 2010-03-11.
• 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.

21. Record Summary

NCT00756093 is a completed, randomized, double-masked crossover study sponsored by Alcon Research. It enrolled 20 people with dry eye and compared one-time instillation of Systane Ultra Lubricant Eye Drops, Optive Lubricant Eye Drops, Blink Tears, and GenTeal Moderate Lubricant Eye Drops. The primary outcome was Drop Comfort, rated once upon instillation on a 0-to-9 scale, with lower values indicating greater comfort.

The posted arm means ranged from 0.7 for Systane Ultra to 1.84 for Blink Tears. Recalculated unadjusted contrasts versus Systane Ultra were 0.35 for Optive, 1.14 for Blink Tears, and 0.4 for GenTeal Moderate. The record lists 0 serious adverse events in each group and no reported death count. It contains no registry-posted analyses, and does not report the original sample-size justification, crossover analysis plan, missing-data methods, or multiplicity strategy.