Direct Application of Systane Complete to Contact Lenses: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Direct Application of Systane Complete to Contact Lenses (NCT03848221), a randomized phase 4 study. The primary outcome is Difference in Ocular Surface Damage as Measured by the Brien Holden Vision Institute (BHVI Grading Scale) at Two Weeks.

2. Clinical Question

This question concerns both the observed score patterns and how precisely the differences are estimated. The registry record describes a randomized, triple-masked, parallel-group study, but does not report the details of masking or the randomization procedure. It also does not report the eligibility thresholds used to define a significant questionnaire score. The three groups allow the direct-use regimen to be considered alongside both another drop regimen and a no-treatment condition, but each comparison addresses a different contrast.

The clinical rationale in the registry record is that contact lens wearers may experience dryness or discomfort, and that artificial tears are not specifically indicated for direct use with contact lenses even though clinicians may prescribe them. The trial was designed to investigate direct use of Systane Complete in contact lens wearers. The posted results describe a short-term assessment at two weeks; they do not establish what may happen over longer periods or in people outside the stated study population.

3. Trial Design

The registry record identifies a randomized, triple-masked, parallel-group, phase 4 study with total enrollment of 73. The study status is completed. Its start date was 2019-05-28 and its primary completion date was 2019-10-20. The groups were Systane Complete, Sensitive Eyes Rewetting Drops, and no treatment. The recorded group sizes for the primary outcome were 25, 24, and 24, respectively.

Participants in the Systane Complete group were to use it before, during, and after contact lens use. The Sensitive Eyes group followed the same timing with its rewetting drops. The no-treatment group was not allowed to use artificial tears or rewetting drops during the study. The registry record does not report further details on adherence, how the products were dispensed, or whether any other aspects of contact lens care were standardized.

The primary endpoint was ocular surface damage, measured by corneal staining on the Brien Holden Vision Institute grading scale at two weeks. A secondary endpoint measured change in the Contact Lens Dry Eye Questionnaire-4 Items between baseline and two weeks. The posted primary results include means and standard deviations by group. A sponsor-reported analysis is identified as an ANOVA across all three groups and is labelled as an equivalence analysis. The record also contains pairwise recalculations based on the group summaries; these are unadjusted comparisons and are not the sponsor's analysis.

The registry record does not report the original sample-size justification, a detailed statistical analysis plan, or the planned allocation ratio. Nor does it report the methods used to preserve masking or who was masked. These missing details limit assessment of how the original design and analyses were planned. The group counts and outcomes describe the posted results, but do not by themselves identify the analysis population or explain whether all randomized participants contributed data.

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

Analysis population for the primary outcome, as defined in the registry: Generally healthy adults who had a significant CLDEQ-8 score and were contact lens wearers.

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: Subjects were included if they were generally healthy adult (18 years or older) contact lens wearer who had significant contact lens and dry eye questionnaire cldeq8 scores of 12 or greater.

6. Primary Endpoint

The registry lists the primary outcome as Difference in Ocular Surface Damage as Measured by the Brien Holden Vision Institute (BHVI Grading Scale) at Two Weeks, measured over 2 Weeks.

The primary endpoint is the difference in ocular surface damage at two weeks, assessed through corneal staining scores on the Brien Holden Vision Institute grading scale. The registry record describes the scale as a reference for signs associated with contact lens-related inflammation and infection, and as a way to indicate how much normal ocular appearance has changed. The total score sums assessments across five regions, with a stated scale range of 0-4 in each region and a total sum score of 20. Lower scores indicate a better outcome.

Corneal staining is used as an ocular surface measure: it captures visible signs that can be graded using a specified reference scale. In this trial, it complements the symptom-focused secondary questionnaire measure. The endpoint is therefore about a clinical sign of ocular surface change, not a direct measure of discomfort itself. A difference in staining scores should be interpreted in relation to the scale and its direction, as well as the uncertainty around the estimated group contrast.

The registry record describes the primary measure as a mean with standard deviation and gives the assessment time as two weeks. It does not report a threshold for a clinically important difference, a specific equivalence margin, or additional details on the grading procedure. Without those details, the magnitude of a score difference can be described, but its clinical importance cannot be determined from the posted summary alone.

7. Results Posted in the Registry

• Sensitive Eyes Rewetting Drops: mean 1.08 versus 0.44 on control; difference 0.64 (95% CI 0.02 to 1.26), standardized effect d = 0.59; z-test p = 0.042.
• No Treatment: mean 0.83 versus 0.44 on control; difference 0.39 (95% CI -0.47 to 1.25), standardized effect d = 0.26; z-test p = 0.373.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Identifying Contact Lens (CL) Participants With Dry Eye Disease (DED), as Measured by the Contact Lens Dry Eye Questionnaire-4 Items (CLDEQ-4) Between Two Weeks and Baseline.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Sensitive Eyes Rewetting Drops: mean -8.25 versus -8.52 on control; difference 0.27 (95% CI -1.24 to 1.78), standardized effect d = 0.10; z-test p = 0.727.
  • No Treatment: mean -11.50 versus -8.52 on control; difference -2.98 (95% CI -4.68 to -1.28), standardized effect d = -0.99; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sensitive Eyes Rewetting Drops and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for No Treatment than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary endpoint concerns the change in Contact Lens Dry Eye Questionnaire-4 Items score between baseline and two weeks. The posted group means and pairwise recalculations produce a different pattern across the two comparisons than a single uniform contrast would imply. The sponsor's reported analysis is an ANOVA across all three groups and is labelled as equivalence. These results are not a substitute for the primary endpoint: the questionnaire and corneal staining measure different aspects of the study question.

Because the secondary outcome is a symptom questionnaire, it complements the primary ocular-surface measure, but the registry record does not provide a stated direction of benefit for the change score or a threshold for meaningful change. The outcomes should not be combined into one conclusion. The overall sponsor analysis and the recalculated contrasts also answer different questions, and the reported equivalence label cannot be fully evaluated without an equivalence margin and further analysis details.

Secondary findings generally carry less evidential weight than a prespecified primary endpoint, especially when the registry record does not report the full analysis plan or whether multiplicity was addressed. Testing several outcomes and contrasts can increase the chance that at least one result appears statistically notable by chance. The record lists one secondary endpoint, but it does not report the complete set of planned analyses or a correction strategy. The recalculated secondary p-values are unadjusted, so they should be viewed as exploratory evidence rather than as definitive confirmation of a treatment effect.

The secondary results can help describe whether the symptom measure follows a pattern similar to the primary sign-based outcome, but they do not independently resolve the discrepancy between the sponsor analysis and the pairwise recalculations. A robust interpretation considers endpoint relevance, uncertainty, multiplicity, and missing analytic information rather than giving a single secondary p-value decisive weight.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Identifying Contact Lens (CL) Participants With Dry Eye Disease (DED), as Measured by the Contact Lens Dry Eye Questionnaire-4 Items (CLDEQ-4) Between Two Weeks and Baseline.

9. Statistical Interpretation

10. Statistical Methods Explained

The registry record reports continuous outcomes as means with standard deviations. A mean describes the group average on the outcome scale, while a standard deviation describes the spread of individual observations around that average. The primary endpoint is a score for which lower values are stated to indicate a better outcome. For the secondary questionnaire measure, the posted values are changes from baseline to two weeks; the record does not state the direction that should be considered better, so the sign of a change should not be assigned a clinical meaning without additional scale information.

What does a mean difference describe?

A mean difference compares the average outcome in one group with the average in another. Its sign depends on the order used to subtract the group means. For the primary pairwise recalculations, the reference group is Systane Complete and the contrast is against one comparator at a time. The resulting estimate describes the observed separation in group averages, in score units. It is not an adjusted estimate and does not account for participant-level information beyond the posted summaries.

Each comparison is a separate question. A comparison with rewetting drops does not answer the same question as a comparison with no treatment. Nor does either pairwise comparison answer the overall question tested by an analysis that considers all three groups together. These distinctions matter when reading an overall test alongside pairwise results.

What does an ANOVA test?

ANOVA is a method for assessing whether group means differ in an overall comparison. The registry record reports an ANOVA across the three groups for each posted outcome, labelled as an equivalence analysis. The record does not report the model details or the equivalence margin. A conventional overall test of differences and an equivalence test have different aims: a failure to find evidence of a difference is not, by itself, evidence that groups are sufficiently similar. An equivalence conclusion depends on a prespecified acceptable range and uncertainty around the estimate relative to that range.

The sponsor-reported ANOVA results should be distinguished from the pairwise recalculations. The recalculations use the posted means, standard deviations, and group sizes to estimate unadjusted pairwise differences and intervals. They are not a reproduction of an analysis that may have used participant-level data, adjustments, or other procedures. The registry record does not report enough detail to establish how the sponsor's analysis was implemented. Because the record flags a discrepancy, the sponsor's own analysis takes precedence over the simple recalculations.

How should p-values be read?

A p-value describes how incompatible the observed data are with a specified statistical null model, assuming that model and its assumptions are appropriate. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The unadjusted pairwise p-values relate to individual contrasts, while the sponsor's ANOVA p-value concerns the reported three-group analysis. Their values need not agree because the tests ask different questions and may use different methods.

The pairwise recalculations are marked unadjusted. When many outcomes or comparisons are tested, the chance of obtaining a small p-value by chance across the full set can increase. An adjustment can account for multiple testing, but the registry record does not report whether one was planned or applied. Therefore, the pairwise p-values should be read as unadjusted evidence for their specific comparisons, not as a multiplicity-controlled family of tests.

Why do confidence intervals matter?

A confidence interval expresses uncertainty around an estimated difference under the method used to calculate it. It shows a range of values reasonably compatible with the data and model, rather than a guarantee that the true value lies in that particular interval. The intervals for the pairwise recalculations help distinguish estimates that are comparatively precise from those that remain compatible with a wider range of differences. Whether an interval includes zero is relevant to a test of no difference, but does not establish equivalence or clinical importance.

General statistical considerations also apply to standard deviations and group sizes. Greater variation within groups or fewer observations generally leads to less precision in estimating a mean difference. The posted standard deviations vary across groups, so the outcome summaries reflect differing amounts of observed spread. The registry record does not report diagnostic checks, distributional assumptions, transformations, or robust alternatives used in the sponsor analysis. Consequently, the appropriateness of those procedures cannot be independently assessed from the registry record.

What is not documented?

The registry record does not report the original sample-size justification, the trial's planned statistical analysis in detail, handling of missing data, or the analysis population. It also does not report an equivalence margin, confidence intervals for the sponsor-reported ANOVA, or a multiplicity strategy. Those omissions are important to interpretation: the posted group summaries allow simple unadjusted calculations, but do not fill in the choices that would be needed to evaluate the original design or reconstruct the sponsor's analysis.

11. Confidence Intervals and Precision

The confidence intervals around pairwise estimates communicate how precisely the group differences are estimated. For the primary comparison between Systane Complete and Sensitive Eyes Rewetting Drops, the recalculated mean difference is 0.64 and the interval excludes zero. Under the assumptions of this unadjusted comparison, the interval is consistent with a positive difference in the direction of the higher mean score in the Sensitive Eyes group. The interval does not establish that the difference is clinically important, because the registry record does not report a clinically important threshold.

For Systane Complete versus no treatment, the recalculated mean difference is 0.39, but its interval includes zero. This means the posted summaries are compatible with no difference as well as with differences in either direction within the interval. It is not proof that the groups are identical. The greater uncertainty in this comparison is also consistent with the larger standard deviation reported for the no-treatment group.

For the secondary outcome, the interval for the comparison with Sensitive Eyes includes zero, while the interval for the comparison with no treatment does not. These are unadjusted intervals for pairwise recalculations, and the record does not report whether intervals were adjusted for multiple comparisons. The sponsor-reported analyses do not include confidence intervals in the registry results.

In general, an interval is more informative than a point estimate alone because it conveys the range of uncertainty associated with an estimate under the calculation method. It does not represent a range containing most participant outcomes, nor does it resolve unreported analytic choices. The small group sizes and observed variation mean that estimates should be interpreted with caution. The sponsor-reported overall analyses, the recalculated pairwise intervals, and the missing equivalence details should be considered together rather than treating one interval as a complete account of the evidence.

12. 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 planning figures are illustrations based on the observed effect, not the trial's original design. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each comparison, the assumed effect is set at the observed effect or at a stated fraction of that observed effect. These figures describe participants per arm for 80% power and participants per arm for 90% power. They are not total enrollment counts or event counts; these outcomes are continuous, and the figures are participants per arm.

The 80% power column gives the illustrative number of participants in each of two equally sized groups under the stated assumptions to have an 80% chance of detecting the assumed effect if that effect is present. The 90% column uses a higher target probability of detecting that effect and therefore generally requires more participants. These are design-planning concepts, not statements about what happened in this completed trial.

Rows for smaller assumed effects require more participants per arm. This is expected because a smaller difference is harder to distinguish from variation in outcomes. The planning illustrations use the observed effects from these results, so they are sensitive to the estimates from a relatively small trial. In particular, a planning estimate based on an observed effect should not be treated as a validated estimate of the effect that a future study will find.

These numbers are not observed power. They do not describe the probability that the completed study detected an effect after its results were known. The original trial's sample-size assumptions and justification are not reported in the registry record, so the planning illustrations cannot be used to infer why the trial enrolled its recorded number of participants.

13. 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 = 0.640; pooled standard deviation σ = 1.094.
2. n = 2 × (1.96 + 0.842)² × 1.094² / 0.640² = 45.8, rounded up to 46 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 <- 0.64                      # observed difference in means
sigma <- 1.09362563122697                     # 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(3848221)
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 = 46 (80% power), 62 (90% power)
 75% of observed effect: n per arm = 82 (80% power), 110 (90% power)
 50% of observed effect: n per arm = 184 (80% power), 246 (90% power)
power.t.test: 46.8 
Simulated power at n = 46 per arm: 0.789 (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.

14. Analyses Reported by the Sponsor

The sponsor-reported primary analysis is an ANOVA across the Systane Complete, Sensitive Eyes Rewetting Drops, and no-treatment groups, with p=0.30, and is labelled as an equivalence analysis. The registry record reports no estimate, confidence interval, or equivalence margin for this analysis. The margin is essential for evaluating whether an equivalence conclusion is supported; the p-value alone is not enough to establish that the groups are equivalent.

The recalculated comparisons are separate, unadjusted pairwise calculations from posted group means, standard deviations, and sizes. They produce different evidence for the two primary contrasts: the comparison with Sensitive Eyes has an interval excluding zero and an unadjusted p-value of 0.042, while the comparison with no treatment has an interval including zero and an unadjusted p-value of 0.373. These calculations do not reproduce or supersede the sponsor's overall analysis. The discrepancy between the reported analysis and the recalculations is flagged in the record, so the sponsor's own analysis takes precedence.

The registry record does not provide sufficient detail to explain the discrepancy, such as the sponsor model specification, analysis population, or any adjustments. The contrast between the analyses should therefore be reported transparently, not resolved by assuming which method the original investigators intended or by treating the pairwise recalculations as a replacement for their analysis. The same caution applies to the secondary endpoint, for which the sponsor reports a three-group ANOVA labelled as equivalence.

15. Multiplicity, Missing Data and Analysis Populations

The record includes a primary endpoint, a secondary endpoint, an overall three-group analysis for each, and recalculated pairwise contrasts. Multiple statistical questions create a multiplicity issue: if enough tests are conducted, some may yield apparently strong evidence even when no underlying effect exists. Adjusting for multiplicity can help control that risk, but may also alter the interpretation and precision of results.

The registry record does not report whether the original analysis plan specified a hierarchy among endpoints, which pairwise comparisons were prespecified, or whether multiplicity adjustment was used. The pairwise recalculations are explicitly unadjusted. Their p-values therefore apply to individual comparisons and should not be interpreted as controlling the error rate across all outcomes and contrasts. The reported sponsor ANOVA p-values are for overall group analyses; they do not explain whether any follow-up comparisons were planned or adjusted.

Missing-data handling is also not reported. The listed primary group sizes add up to the enrollment total, but that fact alone does not establish that every randomized participant was analyzed as assigned, that all outcome data were complete, or how any missing values were handled. The registry record does not specify an intention-to-treat or per-protocol analysis population, exclusions, imputation, or sensitivity analyses. The actual analysis population and the consequences of missing observations therefore cannot be assessed from the posted summaries.

The record also does not report the original sample-size justification, the detailed statistical model, distributional checks, or the equivalence margin used by the sponsor. These omissions are especially relevant because the reported analyses are labelled as equivalence analyses. Without a margin and supporting intervals, the basis for an equivalence conclusion cannot be evaluated. The recalculated comparisons do not supply these missing protocol or analysis details.

These gaps do not invalidate the descriptive group means, but they limit how strongly the inferential results can be interpreted. Clear reporting of prespecified outcomes, analysis populations, missing-data procedures, multiplicity control, and equivalence criteria would be needed to assess the full statistical plan.

16. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The posted safety figures show zero serious adverse events among 25 participants at risk in the Systane Complete group, 24 in the Sensitive Eyes Rewetting Drops group, and 24 in the no-treatment group. The record also shows zero other adverse events in each group and zero deaths in each group. No serious adverse-event terms are listed.

These figures describe the events reported in the registry record for the participants counted as at risk. They should not be read as proof that no adverse event could occur, or that the regimens have established safety in other populations or over longer periods. With these group sizes, the absence of recorded events provides limited information about uncommon events.

The registry record does not report further details about how adverse events were collected, the observation period for safety, seriousness criteria, attribution to a study product, or whether any events led to withdrawal. The figures therefore support a narrow description of the posted counts, not a broad conclusion about safety. They also do not change the distinction between the sponsor-reported outcome analyses and the recalculated comparisons for efficacy-related endpoints.

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

The posted results describe a randomized comparison of three groups of contact lens wearers at a two-week assessment. For the primary staining score, the Systane Complete group had a lower mean than the other two groups, and lower scores are defined as better. The unadjusted recalculations show differing levels of statistical evidence across the two pairwise contrasts. The sponsor-reported overall analysis is labelled as equivalence and has p=0.30; it takes precedence over recalculated pairwise statistics, but the record lacks the equivalence margin and other details needed to assess that label.

These results do not establish a definitive difference between Systane Complete and both comparators, and they do not demonstrate equivalence. A non-significant result is not proof of no difference, while an equivalence label without the margin and supporting analysis does not establish that differences are acceptably small. The results also do not show that an observed score difference is clinically important, because the registry record does not state a meaningful-change threshold.

The secondary questionnaire endpoint provides a separate symptom measure, but the sponsor's overall analysis and pairwise recalculations must be interpreted in light of their different methods, unadjusted testing, and unreported multiplicity strategy. Results at one assessment time do not establish what might happen with longer use. The record does not support conclusions about people who were not represented in the stated population of generally healthy adults with contact lens wear and a significant questionnaire score.

The safety counts report no serious or other adverse events and no deaths in the listed groups. Those counts are not sufficient to rule out uncommon events or to characterize safety beyond the recorded study context. Overall, the results provide short-term group summaries and statistical comparisons, with important uncertainty about the original analysis plan, missing data, and the sponsor's equivalence framework. They should be understood as evidence from this trial record rather than as a complete account of all possible benefits or risks.

18. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should distinguish an overall multi-group analysis from pairwise comparisons. The sponsor-reported ANOVA considers the three groups together, whereas the recalculations compare Systane Complete with one comparator at a time. It is possible for these analyses to yield different results without either being a simple transcription of the other: they may test different hypotheses and may use different analytic details. The registry record does not give enough information to reconcile them.

The example also shows why a p-value is not a complete summary. The primary pairwise estimates have different degrees of precision, and the interval for one comparison includes zero while the other does not. At the same time, a pattern in the pairwise recalculations does not override the sponsor's analysis when a discrepancy is flagged. Results need to be read alongside the stated endpoint, test, interval, and uncertainty about methods.

The equivalence label makes the distinction between absence of evidence and evidence of equivalence especially important. Equivalence is a claim relative to an acceptable margin; without that margin and the relevant uncertainty estimates, readers cannot assess whether the claim is justified. A p-value from an overall analysis cannot supply those missing pieces.

Finally, the trial highlights the importance of reporting plans for multiplicity, missing data, analysis populations, and sample-size justification. Those details affect how confidently readers can interpret nominal statistical findings and whether analyses can be reproduced. Clear reporting is not a technical extra: it determines which questions the results answer and how much weight a comparison can bear.

19. 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 group sizes were 25, 24, and 24, and the assessment occurred at two weeks. The registry record does not provide longer-term outcomes, so the posted results do not describe persistence of any observed pattern. The stated population was generally healthy adults who wore contact lenses and had a significant Contact Lens Dry Eye Questionnaire-8 score; applicability to other populations is not established by this record.

The sponsor's primary analysis is reported as a three-group ANOVA labelled as equivalence, but the equivalence margin, estimate, confidence interval, and model details are not reported in the registry record. This limits evaluation of the sponsor's central inferential result. The unadjusted pairwise recalculations are based on summary statistics and do not reproduce a participant-level analysis. The reported discrepancy means these calculations should not take precedence over the sponsor's analysis.

The registry record does not report the original sample-size rationale, detailed randomization or masking procedures, analysis population, missing-data methods, multiplicity plan, or adherence information. It also does not report a clinically important threshold for the primary score or a direction and meaningful-change threshold for the secondary score. These omissions make it difficult to assess design assumptions, practical importance, and potential analytic sensitivity.

Safety reporting is limited to the event counts shown. Collection methods, attribution, follow-up duration for adverse events, and withdrawals are not reported in the registry record. The zero counts therefore describe only the posted results and cannot exclude uncommon harms. Together, these limitations support a cautious reading of the results as short-term summaries with unresolved inferential and reporting questions.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Direct Application of Systane Complete to Contact Lenses — NCT03848221.
• Registry record last updated 2020-10-08; status last verified 2020-10.
• Results first posted 2020-04-27.
• 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.

23. Record Summary

The registry record describes a completed, randomized, triple-masked, parallel-group phase 4 study with 73 participants. It compared Systane Complete used before, during, and after contact lens use with Sensitive Eyes Rewetting Drops used on the same schedule and with no treatment. The primary outcome was corneal staining on the Brien Holden Vision Institute scale at two weeks, where lower scores indicate a better outcome.

The sponsor-reported primary analysis was an ANOVA across the three groups, labelled as equivalence, with p=0.30. Unadjusted pairwise recalculations from posted summaries show different evidence across the two primary contrasts, but the sponsor's own analysis takes precedence. The registry record does not report an equivalence margin or sufficient detail to evaluate the analysis fully. Secondary results and safety counts also have reporting limitations, including absent detail on multiplicity, missing data, analysis populations, and adverse-event collection.