Evaluation of Toric Soft Contact Lenses Containing a Chromophore to Block High-Energy Visible Light: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Toric Soft Contact Lenses Containing a Chromophore to Block High-Energy Visible Light (NCT05344560), a randomized na study. The primary outcome is CLUE Comfort Score.

2. Clinical Question

The question is about a patient-reported comfort score, not a direct measurement of visual acuity or a clinical diagnosis. The score ranges from 0 to 120, and higher scores indicate a more favorable response. The reported means are 63.5 for the test condition and 65.28 for the control condition. The unadjusted recalculation estimates a mean difference of -1.78, with a confidence interval extending from -6.928 to 3.368. The sponsor’s generalized linear mixed model reports a mean difference of -2.92, with a 95% confidence interval from -6.92 to 1.07. These are estimates with uncertainty, not a guarantee about the comfort experience of any individual wearer.

3. Trial Design

The registry describes a completed randomized, controlled, single-masked crossover study with bilateral lens wear. Its brief summary characterizes the study as a four-visit dispensing study with two treatments, two sequences, and three wear periods. Participants were habitual contact lens wearers. In the test/control/control sequence, participants wore the two study lenses one at a time bilaterally across the wear periods. The control/test/test sequence used the other ordering. The registry record does not say which people were masked.

The study enrolled 126. The primary endpoint is reported for the population that completed all visits without substantial protocol deviations, according to a determination made by the trial cohort review committee before database hard lock. The registry reports 119 for the test condition and 119 for the control condition in the endpoint results. Because this is a crossover design, those figures should be read as the reported condition-level results, not as evidence that the conditions involved separate groups of participants.

The study began on 2022-05-09, reached primary completion on 2022-08-09, and is listed as completed. The registry identifies Visual Acuity as a condition. The official title describes evaluation of toric soft contact lenses containing a chromophore to block high-energy visible light produced on commercial manufacturing lines. The interventions and endpoint labels are not fully consistent: the intervention listing names ACUVUE OASYS 1-Day for Astigmatism, whereas the control outcome label says Senofilcon A (C3). The registry record does not explain this difference.

The trial’s original design assumptions, including any original sample-size rationale or planned analysis details beyond what is recorded, are not reported in the registry record. The planning illustrations based on the observed effect are separate from the trial’s original design.

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.

Period 1

Reasons for not completing this period:

Period 2

Reasons for not completing this period:

Period 3

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects who successfully complete all visits and do not substantially deviate from the protocol as determined by the trial cohort review committee prior to database hard lock.

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: All subjects dispensed at least one study lens.

6. Primary Endpoint

The registry lists the primary outcome as CLUE Comfort Score, measured over 1-Week Follow-up.

The primary endpoint is the CLUE Comfort Score at 1-Week Follow-up. CLUE stands for Contact Lens User Experience. The registry describes it as a validated patient-reported outcomes questionnaire for assessing experience attributes of soft, disposable contact lenses, including comfort, vision, handling, and packaging. In this trial, the reported endpoint is the comfort component.

The score runs from 0 to 120, follows a normal distribution according to the registry description, and has a stated population average of 60 with a standard deviation of 20. A higher score represents a more favorable or positive response. The endpoint therefore gives a numerical summary of participants’ reported comfort rather than an objective examination finding. The average score is reported separately for each lens condition.

A patient-reported measure is useful when the outcome of interest is an experience that participants themselves can assess. It can capture differences that may matter to contact lens wearers even when those experiences are not represented by an instrument-based clinical measurement. At the same time, a group average does not describe every participant’s response, and the score’s interpretation depends on the questionnaire, the assessment time, and the population represented.

The registry reports the endpoint at 1-Week Follow-up. It does not report a threshold for a clinically important difference in comfort. Without such a threshold, the numerical difference can be described and its uncertainty assessed, but the registry alone does not establish how large a difference would be important to participants.

7. Results Posted in the Registry

• Test [Senofilcon A (C3) HEV Chromophore]: mean 63.50 versus 65.28 on control; difference -1.78 (95% CI -6.93 to 3.37), standardized effect d = -0.09; z-test p = 0.498.

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a continuous measure, so the registry reports a mean and standard deviation for each condition. A mean is the arithmetic average of the recorded scores. A standard deviation describes how dispersed individual scores are around that average. The test condition has a reported mean of 63.5 and standard deviation of 19.58; the control condition has a reported mean of 65.28 and standard deviation of 20.91. These summaries describe the endpoint population identified in the registry, not necessarily every person enrolled.

What does a mean difference represent?

The unadjusted recalculation expresses the comparison as test minus control. Its estimate is -1.78 score units, meaning that the test-condition mean is lower than the control-condition mean in this calculation. This direction is descriptive. The negative sign does not establish that the difference is meaningful, and the score description alone does not provide a threshold for importance.

The recalculated comparison uses posted summary statistics and is described as simple and unadjusted. It does not incorporate the sponsor’s model structure. In a crossover study, the same participant may contribute experience under more than one condition, and the order of conditions can matter to analysis. The unadjusted recalculation should therefore not be treated as a substitute for a model that accounts for the trial design. The registry reports a generalized linear mixed model for the sponsor’s analysis but does not report its detailed specification.

How should the confidence interval be read?

A confidence interval conveys uncertainty around an estimated difference. In general, a narrower interval indicates greater precision, while a wider interval leaves more values compatible with the data and analysis. The recalculated interval is -6.928 to 3.368. Because it spans zero, it is compatible with a negative difference, a value near zero, and a positive difference under the recalculation. The interval does not mean that every value inside it is equally likely, nor does it account for uncertainties not represented by that analysis.

The sponsor’s 95% confidence interval is -6.92 to 1.07. It is attached to the generalized linear mixed model estimate of -2.92. The confidence interval is specific to that model and analysis. Comparing it with the recalculated interval is useful for seeing that the approaches produce different estimates and uncertainty limits; it does not reveal why the analyses differ, because the model details needed to explain that are not reported in the registry record.

What does the unadjusted p-value say?

The recalculation reports an unadjusted p-value of 0.498. A p-value measures how compatible the observed data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it is not a measure of the size or importance of the difference. The value belongs to the unadjusted recalculation, not the sponsor’s generalized linear mixed model. The sponsor analysis has no p-value reported in the registry record.

Why can crossover structure matter?

In general, crossover studies compare conditions while accounting for the fact that participants may experience more than one condition. This can make within-participant comparisons relevant, but it also means that sequence, period, and possible carryover effects can be important analytical considerations. Those are general features of crossover designs, not claims that such effects occurred in this trial. The registry identifies two sequences and three wear periods, but does not report the sponsor model’s terms for sequence or period, whether carryover was assessed, or whether a washout was used.

Randomization assigns participants to a sequence, while masking can reduce some sources of expectation-related bias. The registry labels the study randomized and single-masked, but does not identify who was masked or describe the randomization procedure. The record also does not report how protocol deviations or missing endpoint values were handled analytically beyond the stated population definition.

What is over-dispersion, and is it relevant?

In general, over-dispersion describes variability greater than a statistical model expects. It can affect standard errors and confidence intervals when the chosen model does not adequately represent the data. The registry reports a continuous comfort score, its standard deviations, and a generalized linear mixed model for the sponsor analysis; it does not report an over-dispersion assessment. No conclusion about over-dispersion in this trial can be drawn from the posted record.

The population definition matters to interpretation. The endpoint is described for subjects who successfully completed all visits and did not substantially deviate from protocol, subject to a committee determination. That is narrower than simply referring to everyone enrolled. The registry reports enrollment of 126 and endpoint condition counts of 119, but does not explain the individual reasons why those counts differ from enrollment or how incomplete data were handled.

10. Confidence Intervals and Precision

The unadjusted estimate of the mean difference is -1.78 score units. Its confidence interval, from -6.928 to 3.368, is wide enough to include values below and above zero. This indicates limited precision for distinguishing the direction of the average difference using that recalculation. The interval should be interpreted in the units of the CLUE Comfort Score, whose range is 0 to 120.

The sponsor’s generalized linear mixed model reports an estimate of -2.92 and a 95% confidence interval from -6.92 to 1.07. That interval also extends across zero. It is narrower than the recalculated interval, but the two intervals come from different analyses and should not be treated as direct replications of one another. The registry does not report enough model detail to attribute the difference in precision to a particular modeling choice.

A confidence interval is not a guarantee that the true difference lies within its endpoints. In general, it summarizes sampling uncertainty under the assumptions of the analysis. It does not incorporate every possible source of uncertainty, such as uncertainty about the measurement, the endpoint population, or the model specification. Nor does an interval that crosses zero establish equivalence or non-inferiority. A non-inferiority interpretation requires a prespecified margin and an analysis rule; the margin is not reported in the registry record.

The registry gives standard deviations of 19.58 for the test condition and 20.91 for the control condition, indicating substantial spread of individual comfort scores around their respective averages. The group means therefore do not describe the experience of each participant. The posted results quantify an average comparison, with uncertainty, rather than the proportion of individuals who had a better or worse experience on either lens.

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 planning figures are participants per arm, not total events. They are illustrations calculated from the observed effect, rather than the original study’s design justification. The original design assumptions are not reported in the registry record.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses a chosen fraction of the observed effect as the effect to detect. The figures therefore depend on both the observed difference used as a reference and the fraction selected for planning.

For planning at 100% of the observed effect, the illustration gives 2,034 participants per arm for 80% power and 2,723 participants per arm for 90% power. At 75% of the observed effect, it gives 3,616 participants per arm for 80% power and 4,840 participants per arm for 90% power. At 50% of the observed effect, it gives 8,134 participants per arm for 80% power and 10,889 participants per arm for 90% power.

In general, power is the chance that a specified analysis will detect an effect of the size assumed, if that effect is present and the planning assumptions hold. The 80% and 90% columns show planning targets for that chance under the stated calculation, not results observed in this trial. Smaller effects require more participants to detect, which is why the illustrations rise as the assumed fraction of the observed effect becomes smaller. These planning figures are 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 = -1.780; pooled standard deviation σ = 20.259.
2. n = 2 × (1.96 + 0.842)² × 20.259² / -1.780² = 2,033.4, rounded up to 2,034 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 <- -1.78                      # observed difference in means
sigma <- 20.2589830198853                     # 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(5344560)
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 = 2,034 (80% power), 2,723 (90% power)
 75% of observed effect: n per arm = 3,616 (80% power), 4,840 (90% power)
 50% of observed effect: n per arm = 8,134 (80% power), 10,889 (90% power)
power.t.test: 2034.4 
Simulated power at n = 2,034 per arm: 0.801 (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. Analyses Reported by the Sponsor

The sponsor’s reported analysis is a generalized linear mixed model, with a mean difference in final values of -2.92 and a 95% confidence interval from -6.92 to 1.07. The registry classifies the analysis as non-inferiority. It does not report a p-value for this model or the non-inferiority margin.

The unadjusted recalculation uses posted summary statistics and gives a mean difference of -1.78, a confidence interval from -6.928 to 3.368, and an unadjusted p-value of 0.498. It is a simple recalculation, not a reproduction of the sponsor’s model. The estimates and intervals are not identical, so each should be attributed to its own analysis rather than combined into a single result.

The registry does not flag a discrepancy between the posted summary statistics and the recalculation. Even so, the sponsor’s model remains the registry’s reported analysis for the non-inferiority question, while the unadjusted calculation offers a separate summary-statistic comparison. A conclusion about non-inferiority cannot be reconstructed from the estimate and interval alone without the margin and decision rule. Those details are not reported in the registry record.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and one reported analysis, and it reports no secondary outcomes. It does not report a multiplicity adjustment or a broader testing hierarchy. Consequently, the record does not establish whether any additional analyses were considered when defining or interpreting the primary result. No adjustment should be assumed.

The endpoint population is described as participants who successfully completed all visits and did not substantially deviate from protocol, as determined by the trial cohort review committee before database hard lock. That definition identifies a selected analysis population, but the registry does not report the committee’s criteria for substantial deviation or the number of participants excluded under that definition. The record also does not describe a separate intention-to-treat analysis or other analysis populations.

Enrollment is reported as 126, while the outcome summaries list 119 for each lens condition. These figures do not, by themselves, explain participant flow or missingness. The reasons for the difference, whether participants lacked endpoint data, and whether the same participants contributed data under both conditions are not reported in the registry record.

Details of missing-data handling are also not reported. The record does not specify whether missing scores were excluded, imputed, or handled through the mixed model, nor does it report sensitivity analyses for missingness. Because the study is a crossover, the treatment of incomplete sequences and period-specific observations could affect interpretation; the registry does not describe that handling.

The study is described as randomized and single-masked, but the identity of the masked party and the masking procedures are not reported. The registry identifies the sponsor model as a generalized linear mixed model but does not give its covariates, covariance structure, or other specification details. The record therefore supports describing the analysis label and reported estimate, but not independently reproducing all design or model decisions.

15. 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 5% reporting threshold.

The registry reports zero serious adverse events and zero other adverse events for the test group, with 125 at risk for each category. For the control group, it also reports zero serious adverse events and zero other adverse events, with 125 at risk for each category. Deaths are reported as 0 in each group. No serious adverse event terms are listed.

These figures are counts in the registry’s safety record. They do not show that no adverse experiences occurred outside the recorded categories or reporting period. The adverse-event time window, event collection procedures, and definitions used for serious and other events are not reported in the registry record. The at-risk counts are safety reporting figures and should not be substituted for the endpoint condition counts.

Zero reported events is not proof that an event is impossible or that the lenses have no safety risks. It means only that the registry reports no events in these categories for the stated groups. The record does not provide additional detail for evaluating the completeness or duration of safety monitoring.

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

The results describe average self-reported comfort at 1-Week Follow-up. The test-condition mean is 63.5, and the control-condition mean is 65.28. The unadjusted mean difference is -1.78, while the sponsor’s model gives -2.92. Both reported confidence intervals include zero. These estimates indicate uncertainty about the direction and size of the average difference rather than a precise separation between conditions.

The registry’s non-inferiority label is not enough, on its own, to establish that the test condition met a non-inferiority criterion. The margin and decision rule are not reported. The confidence interval cannot be judged against an unreported margin, and the sponsor model has no p-value reported in the record.

The result does not establish how each participant responded, whether participants preferred one lens, or whether a score difference would matter to wearers. The registry does not report a threshold for a clinically important difference. Group averages and confidence intervals also do not answer questions about other outcomes, such as long-term comfort or experience outside the recorded assessment time.

The findings apply to the endpoint population described in the record: participants who completed all visits and did not substantially deviate from protocol, subject to committee determination. The record does not provide enough information to assess how missing observations or exclusions affected that population. It also contains a difference between the intervention listing and the outcome control label, which limits certainty about how the control condition should be described.

Accordingly, the posted data support a cautious statistical account of the recorded comfort scores and their uncertainty. They do not establish a broad claim that either lens is superior, equivalent, or non-inferior, and they do not predict an individual wearer’s experience.

17. Why This Trial Matters Statistically

This trial illustrates why design and analysis details matter when interpreting a patient-reported endpoint. Comfort is an experience that participants can report directly, and the CLUE score provides a numerical way to compare average responses. Yet the mean difference alone does not tell whether the difference is important to wearers. Interpretation also depends on the score’s scale, a meaningful-difference threshold, and the uncertainty around the estimate. The registry does not report a threshold for clinical importance.

The crossover structure is statistically relevant because participants were assigned to sequences and wore lenses across multiple periods. In general, crossover analyses may need to account for the relationship among observations from the same participant and for the order and timing of conditions. The registry identifies a generalized linear mixed model for the sponsor analysis, but does not report enough model detail to assess those choices. This makes clear why an unadjusted recalculation and a sponsor model can answer related but not identical analytical questions.

The record also shows the distinction between a non-inferiority label and the information needed to evaluate non-inferiority. The sponsor estimate and interval are reported, but the margin is not. Without that margin, readers cannot assess whether the uncertainty interval satisfies the stated criterion.

Finally, intervention labels are not fully aligned between the intervention listing and outcome results. That documentation issue matters because a statistical comparison is only interpretable when readers can identify the conditions being compared. Clear treatment labels, analysis populations, missing-data methods, and model details help connect numerical results to the actual trial question.

18. 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 leaves several trial-specific details unresolved. It lists the control intervention as ACUVUE OASYS 1-Day for Astigmatism, while the outcome results label the control as Senofilcon A (C3). The record does not explain whether these descriptions refer to the same study condition or how the labels relate. This ambiguity makes the exact comparator difficult to identify from the registry alone.

The study is described as a crossover with two sequences and three wear periods, but the registry does not report the sponsor model’s handling of sequence, period, or possible carryover. It does not describe any washout between wear periods. These details are relevant to evaluating a crossover analysis, but their absence does not establish that the design or analysis was inadequate.

The sponsor analysis is designated non-inferiority, but its margin and decision rule are not reported. The model is named as a generalized linear mixed model, but its detailed specification is absent. The registry also does not report the original sample-size rationale, missing-data methods, or sensitivity analyses.

The endpoint results are restricted by definition to participants who completed all visits without substantial protocol deviation, subject to committee review. The record does not provide participant-level flow explaining the enrolled count and the condition-level endpoint counts, nor does it report the reasons for any missing or excluded observations. These gaps limit assessment of how representative the analyzed population is of all enrolled participants.

Finally, no clinically important difference threshold is reported for the CLUE Comfort Score. The posted estimates can be interpreted statistically, but the record alone cannot establish the practical importance of a score difference.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Evaluation of Toric Soft Contact Lenses Containing a Chromophore to Block High-Energy Visible Light — NCT05344560.
• Registry record last updated 2023-09-15; status last verified 2023-09.
• Results first posted 2023-09-15.
• 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.

22. Record Summary

NCT05344560 is listed as a completed randomized, single-masked crossover study of toric soft contact lenses containing a chromophore to block high-energy visible light. It enrolled 126 habitual contact lens wearers and reports four visits, two sequences, and three wear periods.

The primary outcome is the CLUE Comfort Score at 1-Week Follow-up. The reported means are 63.5 for the test condition and 65.28 for the control condition. The unadjusted recalculation estimates a mean difference of -1.78, with a confidence interval from -6.928 to 3.368. The sponsor’s generalized linear mixed model reports -2.92, with a 95% confidence interval from -6.92 to 1.07, and is designated as a non-inferiority analysis.

The registry does not report the non-inferiority margin, detailed model specification, missing-data methods, or a clinically important difference threshold. It also uses different control labels in the intervention listing and outcome results. These limits should guide interpretation of the posted estimates.