Evaluation of Prototype Lenses With Experimental UV/HEV Blocker: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Prototype Lenses With Experimental UV/HEV Blocker (NCT04885296), a randomized na study. The primary outcome is Overall Quality of Vision Score.

2. Clinical Question

3. Trial Design

The registry describes a randomized, controlled, subject-masked, bilateral crossover study with 2-week dispensing. Eligible subjects were randomized to one of two lens-wear sequences: Test/Control or Control/Test. The interventions are listed as TRP-200 and JJVC Marketed Contact Lens, while the outcome groups are labelled Test (Senofilcon A C3) and Control (Senofilcon A C3). The record does not explain the relationship among these labels beyond those descriptions.

The study model is crossover, meaning participants experienced both lens conditions in different sequences. In general, a crossover design can make within-participant comparisons possible, but sequence, period, and carryover effects may matter to analysis. The registry reports a Linear Mixed Model for the sponsor's listed analyses; detailed model terms are not reported in the registry record.

Enrollment was 228. The trial status is completed, with a start date of 2021-05-10 and primary completion date of 2021-08-09. The primary outcome population is described as all subjects who completed all study visits without a major protocol deviation. Each posted outcome group has 216 observations. How those outcome counts relate to enrollment, including reasons for any missing observations or exclusions, is not reported in the registry record.

The primary endpoint and two secondary endpoints were assessed at 2-Week Follow-up. The study is listed as phase NA. The original design's sample-size justification, planned analysis details beyond the reported method, and any planned interim analyses are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Period 1

Reasons for not completing this period:

Period 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects that completed all study visits without a major protocol deviation.

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 Overall Quality of Vision Score, measured over 2-Week Follow-up.

The primary endpoint was the Overall Quality of Vision Score at 2-Week Follow-up, measured with the Contact Lens User Experience (CLUE) questionnaire. CLUE is described as a validated patient-reported outcomes questionnaire for contact-lens experience, including comfort, vision, handling, and packaging, in a US contact-lens-wearing population ages 18-65. The endpoint focuses on participants' reported experience of vision rather than an objective vision test.

The record reports average CLUE vision scores by lens type. Derived CLUE scores use Item Response Theory and follow a normal distribution with a population average score of 60 and SD 20. Scores range from 0-120, with higher scores indicating a more favorable or positive response. These scale properties provide context for interpreting the group means, but do not define a clinically important difference. Such a threshold is not reported in the registry record.

A patient-reported vision score is relevant because it captures the wearer's perception of lens-related visual experience. It should be interpreted as a score on this questionnaire, not as a direct measure of a specific visual function or a guarantee of how an individual will experience a lens.

7. Results Posted in the Registry

• Test (Senofilcon A C3): mean 69.30 versus 69.00 on control; difference 0.30 (95% CI -3.75 to 4.35), standardized effect d = 0.01; z-test p = 0.885.

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.

Overall Comfort Scores

• 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:
  • Test (Senofilcon A C3): mean 68.10 versus 69.00 on control; difference -0.90 (95% CI -5.49 to 3.69), standardized effect d = -0.04; z-test p = 0.701.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Test (Senofilcon A C3) and the control. The interval gives the range of effects that remain compatible with the data.

Overall Handling Scores

• 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:
  • Test (Senofilcon A C3): mean 66.90 versus 68.60 on control; difference -1.70 (95% CI -6.10 to 2.70), standardized effect d = -0.07; z-test p = 0.449.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Test (Senofilcon A C3) and the control. The interval gives the range of effects that remain compatible with the data.

The two secondary outcomes, overall comfort and overall handling, follow a pattern similar to the primary result: their recalculated mean differences are modest in scale and their 95% confidence intervals include zero. In both cases, the point estimates are in the direction of lower mean scores for the test lens than for the control. The sponsor's Linear Mixed Model estimates are also close to zero, with intervals spanning values on both sides. The individual endpoint values and intervals are reported with the outcome results.

This broad pattern is consistent with the primary outcome's lack of a clearly separated mean score in the posted comparisons. It does not establish that all aspects of lens experience are the same, nor does it demonstrate that a potentially meaningful difference is absent. Each score measures a different patient-reported attribute, and uncertainty remains in each comparison.

Secondary outcomes generally carry less inferential weight than a prespecified primary outcome. When several outcomes are tested, the chance of at least one apparently notable result can increase. General statistical approaches may address multiplicity by adjusting inference or by defining a hierarchy, but an adjustment or testing hierarchy is not reported in the registry record. The secondary recalculated p-values are unadjusted, so they should not be treated as confirmatory evidence on their own.

These outcomes can provide supportive context about comfort and handling alongside the vision score. They do not replace the primary result, and the record does not report whether the study was designed or powered to make definitive claims about the secondary outcomes.

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

• Overall Comfort Scores
• Overall Handling Scores

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score, and the registry reports group means and standard deviations. A mean describes the center of the observed scores, while the standard deviation describes their spread. The posted means are 69.3 for the test lens and 69.0 for the control lens; the corresponding standard deviations are 20.84 and 22.12. These summaries describe the outcome group observations, not the precision of the difference by themselves.

What does the mean difference represent?

The recalculated mean difference is the test mean minus the control mean, reported as 0.3 points. A positive value means the test group's mean score is higher in this comparison; it does not by itself establish a meaningful or reliable advantage. The scale description says higher CLUE scores are more favorable. The pooled standard deviation used for the simple recalculation is 21.49, and the standardized mean difference is 0.014. Standardizing expresses the difference in relation to the observed spread, which can help describe its size without changing the original score scale. It does not supply a threshold for clinical importance.

Why are there two kinds of estimates?

The recalculated estimate is a simple unadjusted calculation from posted summary statistics. The sponsor's analysis is reported as a Linear Mixed Model estimate of the least-squares mean difference. In general, a mixed model can account for structure in the observations and can estimate adjusted means, depending on the model terms. The registry does not give those terms, so it is not possible to determine exactly what was adjusted for or how sequence and period were handled. The two estimates are similar, but the methods and estimands need not be identical.

The crossover design means that lens conditions were assigned in sequences, rather than as permanently separate groups. General statistical practice for crossover trials considers whether observations from the same participant are related and whether period or sequence effects matter. The sponsor lists a Linear Mixed Model, but the detailed model specification and any diagnostics are not reported in the registry record. The simple recalculation should therefore be understood as a summary-statistic comparison, not as a reconstruction of the sponsor's full model.

What does the confidence interval add?

A confidence interval gives a range of values compatible with the data and the calculation's assumptions. For the recalculated primary difference, the 95% confidence interval runs from -3.753 to 4.353. Its inclusion of zero means the data do not clearly distinguish a positive difference from a negative one at that interval level. Its width also indicates that the estimate is not precise enough to rule out differences of several score points in either direction. A confidence interval is not a probability statement about the true value after the data are observed.

The p-value of 0.885 is an unadjusted result for the recalculated comparison. In general, a p-value measures how unusual data at least as discrepant as those observed would be under a specified null model. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The registry's sponsor analysis does not list a p-value.

Why can over-dispersion matter?

For continuous outcomes, variability is represented by the spread of scores. More variability relative to a mean difference makes that difference harder to estimate precisely. For outcomes with counts, over-dispersion means that variability exceeds what a chosen model assumes; ignoring it can make uncertainty appear too small. This trial's posted endpoints are continuous scores, and the record does not describe an over-dispersion issue or a count-outcome model.

The sample-size illustrations use a normal approximation, equal allocation between two arms, a two-sided significance level of 0.05, and fractions of the observed effect. These are planning calculations based on the posted effect, not a reconstruction of the trial's original design. The original design assumptions are not reported in the registry record. The illustrations do not establish that the trial was adequately powered for its intended question.

The record identifies the primary population as subjects completing all study visits without a major protocol deviation. It does not describe how missing values were handled, whether an intention-to-treat population was analyzed, or how protocol deviations were classified. Those details matter because the population included in an analysis can affect what the estimate represents.

11. Confidence Intervals and Precision

The recalculated 95% confidence interval for the primary mean difference is -3.753 to 4.353 points. The point estimate, 0.3, lies near zero, but the interval includes both negative and positive values. Thus, the data are compatible with the test score being somewhat lower or somewhat higher than the control score, as well as with little difference. The interval does not establish equivalence, because equivalence requires a prespecified margin and a suitable analysis; that margin is not reported in the registry record.

The sponsor-reported Linear Mixed Model estimate is 0.4, with a 95% confidence interval from -2.2 to 3.0. Its interval is also centered near zero and spans values on both sides. The sponsor estimate and recalculation are close, but their intervals differ, reflecting that they are outputs from different analyses. The registry does not report enough model detail to explain the difference in interval width.

Precision concerns how tightly an estimate is determined, not whether an outcome is important. In general, a narrower interval indicates greater precision under the analysis assumptions, while a wider interval leaves more uncertainty about the size and direction of the difference. The primary interval permits a range of effects rather than a single settled value. No clinically important difference threshold is reported, so the interval cannot be classified against such a threshold.

The reported group standard deviations, 20.84 for the test and 22.12 for the control, describe score variability. They are not confidence limits for the group means or for the between-lens difference. The uncertainty in a contrast also depends on the analysis and, for a crossover study, on how within-participant structure is handled. Detailed model terms are not reported in the registry record.

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 participants per arm, not total events. They are illustrations based on the observed effect, rather than the trial's original sample-size justification. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original design assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect were present. The 90% power column gives the corresponding planning figure for a 90% chance. These are prospective planning interpretations, not descriptions of what happened in this trial.

The table considers planning for 100%, 75%, and 50% of the observed effect. The participant requirements increase as the effect to detect becomes smaller: a smaller difference is harder to distinguish from random variation at a given level of precision. The listed figures can therefore be read as sensitivity illustrations about how planned size depends on the target effect, not as evidence that the original trial was designed around these targets.

This is not observed power. Observed power calculated from an effect estimated in the trial does not provide a substitute for interpreting the confidence interval, and these figures are planning illustrations rather than an assessment of the trial's success.

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 = 0.300; pooled standard deviation σ = 21.490.
2. n = 2 × (1.96 + 0.842)² × 21.490² / 0.300² = 80,546.9, rounded up to 80,547 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 <- 0.299999999999997                      # observed difference in means
sigma <- 21.4895323355349                     # 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(4885296)
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 = 80,547 (80% power), 107,830 (90% power)
 75% of observed effect: n per arm = 143,195 (80% power), 191,697 (90% power)
 50% of observed effect: n per arm = 322,188 (80% power), 431,319 (90% power)
power.t.test: 80547.9 
Simulated power at n = 80,547 per arm: 0.800 (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's reported primary analysis is a Linear Mixed Model estimate of the least-squares mean difference: 0.4, with a 95% confidence interval from -2.2 to 3.0. It is labelled as a non-inferiority analysis. The recalculation from the posted group summaries gives a mean difference of 0.3, with a 95% confidence interval from -3.753 to 4.353. The estimates are close, but the confidence intervals differ.

The recalculation is an unadjusted comparison of summary statistics; the reported sponsor result is model-based. The registry does not report the mixed model's terms, the non-inferiority margin, or a sponsor p-value. Consequently, the record does not permit independent assessment of the non-inferiority criterion or a full reconciliation of the two intervals. No discrepancy is flagged in the record, but the sponsor's listed analysis remains the reported trial analysis and should be distinguished from the simple recalculation.

Both intervals include zero. This is a description of the estimates and their uncertainty, not a conclusion that the lenses are equivalent. A non-inferiority interpretation depends on the prespecified margin and analysis, and the margin is not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The record reports one primary endpoint and two secondary endpoints. It does not report whether the analysis plan controlled the family-wise error rate or used another approach to account for multiple outcomes or comparisons. The recalculated p-values are unadjusted. As a general matter, interpreting multiple unadjusted tests as independent confirmation can overstate the strength of evidence because repeated testing creates more opportunities for a low p-value.

The sponsor-reported analyses are labelled non-inferiority, but the non-inferiority margin, decision rule, and full testing procedure are not reported in the registry record. Without those details, the label cannot be independently evaluated from the record alone. The sponsor analysis also has no posted p-value for the primary or secondary endpoints.

The primary outcome population is defined as subjects who completed all study visits without a major protocol deviation. How many enrolled subjects did not meet that definition, why they did not meet it, and how missing observations were handled are not reported in the registry record. The record also does not state whether an intention-to-treat analysis or another analysis population was used alongside the stated outcome population.

In general, missing data can affect estimates if the likelihood of missingness is related to the outcome or treatment experience. The available record does not describe missing-data assumptions, imputation, sensitivity analyses, or participant-level outcome completeness. It is therefore not possible to assess the impact of missing observations or exclusions from the posted information.

Detailed statistical-plan elements—including model terms, handling of sequence and period, any interim analyses, and the original sample-size justification—are not reported in the registry record. These omissions limit assessment of whether the posted analyses follow a prespecified plan and how robust the conclusions are to alternative analysis choices.

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 5% reporting threshold.

The adverse-event record lists 227 participants at risk in each of the control and test groups. Serious adverse events affected 0 in each group; other adverse events affected 0 in each group; deaths were 0 in each group. No serious adverse-event terms are listed.

These are the adverse-event figures recorded for the listed groups. A zero in the posted results means no events were recorded in that category for the group; it does not prove that an event could never occur or that every possible harm has been excluded. The record does not provide event descriptions beyond the category counts, further safety detail, or an explanation of how these safety counts relate to the outcome analysis population.

Safety counts should be read separately from the vision, comfort, and handling scores. They do not determine the size or precision of the patient-reported outcome differences, and the score results do not replace review of the adverse-event record.

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

The results describe average CLUE scores for the stated study population at 2-Week Follow-up. For the primary vision score, the test and control means were close, and the recalculated mean difference was 0.3. The recalculated confidence interval includes zero and spans possible differences in either direction. The sponsor's model-based estimate is also close to zero and has an interval including zero.

These findings do not prove that the lenses are identical. A nonsignificant unadjusted p-value does not establish equivalence, and a confidence interval that includes zero does not show that every clinically relevant difference has been ruled out. The record does not report a clinically important difference threshold or the non-inferiority margin. Therefore, the clinical importance of the interval's possible values cannot be determined from the registry record alone.

The outcomes are questionnaire-based reports of overall vision, comfort, and handling, rather than measures of every aspect of visual function or lens performance. The primary outcome population is limited to subjects who completed all study visits without a major protocol deviation. The record does not report sufficient information about exclusions, missing observations, or broader participant characteristics to determine how well the analyzed population represents other contact-lens wearers.

The study was a randomized, subject-masked crossover, which provides a comparison of two lens conditions in different sequences. Its results apply to the outcomes and follow-up described in the record. They do not establish long-term experience or answer questions not measured by these endpoints. The posted adverse-event counts report zero events in the listed categories, but those counts do not demonstrate the absence of all possible safety concerns.

18. Why This Trial Matters Statistically

This trial illustrates why an estimated difference should be read together with its uncertainty. The primary recalculated estimate is close to zero, but the 95% confidence interval extends to values on either side. Treating the point estimate alone as conclusive would ignore the range of differences compatible with the data and analysis.

It also shows why the reported sponsor analysis and an unadjusted recalculation need to be distinguished. A crossover study has a design structure that can be represented in a model; the registry reports a Linear Mixed Model, while the summary-statistic recalculation is simpler. Without the model specification, readers should not assume that these analyses answer the question in exactly the same way.

The non-inferiority label makes the missing margin particularly important. Non-inferiority is not established merely because an estimate is near zero or an interval includes zero; interpretation depends on a margin and prespecified analysis. Since the margin is not reported in the registry record, the label cannot be fully assessed from the posted information.

Finally, the sample-size illustrations demonstrate how a planning target depends on the effect one wants to detect. Smaller target effects require more participants under the stated assumptions. Those illustrations do not describe the original design or constitute observed power. Together, these points emphasize the value of transparent reporting of margins, analysis populations, model details, missing-data handling, and multiplicity procedures.

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 registry record leaves several trial-specific details unclear. It names TRP-200 and JJVC Marketed Contact Lens in the intervention list, while the outcome groups are labelled Test and Control (Senofilcon A C3). The precise relationship among these labels is not explained. The record describes a bilateral, 2-week dispensing crossover study, but does not give further details about lens-wear adherence or the timing and handling of periods.

The sponsor's Linear Mixed Model is identified, but its terms and treatment of sequence, period, participant-level correlation, and carryover are not reported. This limits assessment of the analysis for a crossover design. The primary outcome population is restricted to subjects completing all visits without a major protocol deviation, while the reasons for exclusions and the handling of missing data are not reported.

The record does not report the non-inferiority margin, a clinically important score difference, a multiplicity strategy, the original sample-size justification, or detailed participant characteristics. These omissions limit interpretation of the sponsor's non-inferiority label, the clinical relevance of the score differences, and the extent to which findings generalize beyond the described study population.

The follow-up endpoint is at 2-Week Follow-up. The record does not provide evidence about longer-term outcomes. The posted adverse-event counts are limited to the listed categories and do not supply detailed event descriptions or broader safety assessments.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Evaluation of Prototype Lenses With Experimental UV/HEV Blocker — NCT04885296.
• Registry record last updated 2022-09-01; status last verified 2022-08.
• Results first posted 2022-09-01.
• 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

NCT04885296 is a completed randomized, subject-masked crossover study of prototype and control contact lenses, with enrollment of 228 and primary completion on 2021-08-09. The primary endpoint was the CLUE Overall Quality of Vision Score at 2-Week Follow-up, in subjects who completed all study visits without a major protocol deviation.

The recalculated primary mean difference was 0.3, with a 95% confidence interval from -3.753 to 4.353. The sponsor-reported Linear Mixed Model estimate was 0.4, with a 95% confidence interval from -2.2 to 3.0, and was labelled non-inferiority. The non-inferiority margin is not reported in the registry record. Secondary comfort and handling comparisons also had intervals including zero. The posted adverse-event counts were zero for serious and other adverse events and deaths in each listed group.