Three Daily Wear Monthly Replacement Silicone Hydrogel Contact Lenses With Two Multi-purpose Disinfecting Solution Combinations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Three Daily Wear Monthly Replacement Silicone Hydrogel Contact Lenses With Two Multi-purpose Disinfecting Solution Combinations (NCT04789382), a randomized na study. The primary outcome is Average Percent Area of Corneal Staining.

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, crossover study with enrollment of 36. The record lists the study as completed and gives its start as 2021-04-07 and primary completion as 2021-05-07. The registry identifies refractive errors as the condition and Alcon Research as sponsor.

Participants were assigned to one of four sequences. In each sequence, one lens-and-solution combination was worn in the right eye and another in the left eye during the first period; the combinations were then changed for the second period. The sequence descriptions specify two hours of wear for each period. The allocation of combinations across eyes and periods varied among the four sequences, allowing each combination to appear in different positions in the sequence.

The four reported combinations were LID018869+RepleniSH, LID018869+Biotrue, Biofinity+RepleniSH, and PV+Biotrue. The control designation is LID018869+RepleniSH. The primary endpoint describes each eye separately, consistent with the record’s statement that each eye was treated differently and graded separately.

The registry labels the study randomized, double masked, and crossover, but does not report who was masked or the procedures used to maintain masking. Details such as a washout period, handling of period or sequence effects, and the statistical method planned for crossover data are not reported in the registry record. The record also says no hypotheses were formulated and no inferences were made; only descriptive statistics were used in reporting the primary endpoint.

4. Participant Flow and Accounting

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

Before assignment: This reporting group includes all enrolled subjects.

First Wear Period (2 Hours)

Washout (Day of & Day Prior to Visit 3)

Second Wear Period (2 Hours)

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set

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: Safety Analysis Set: All subjects/eyes exposed to any study lens, whether or not presoaked in the study multi-purpose disinfecting solution (MPDS)

6. Primary Endpoint

The registry lists the primary outcome as Average Percent Area of Corneal Staining, measured over Hour 2 (each wear period).

The primary endpoint is the average percent area of corneal staining, assessed at hour two of each wear period. An investigator used a slit lamp examination to assess solution-related staining in five corneal regions: central, superior, nasal, inferior, and temporal. The recorded endpoint is the average across these regions. Each eye was treated differently and graded separately.

This continuous measure describes the extent of the corneal area showing staining under each lens-and-solution condition. Reporting an average gives a concise summary across the five assessed regions, while the standard deviation describes variation in the endpoint values. Both are descriptive measures; neither on its own establishes that one condition caused more or less staining than another.

The endpoint was chosen to address the study’s stated purpose of evaluating corneal staining after two hours of wear. The registry does not report a threshold for a clinically important difference or a hypothesis test for this measure. It explicitly states that no hypotheses were formulated and that the primary results were reported descriptively. Therefore, the endpoint results describe staining in this study’s assessed eyes and periods, rather than demonstrating a prespecified inferential conclusion.

7. Results Posted in the Registry

• Biofinity+RepleniSH: mean 0.45 versus 2.93 on control; difference -2.48 (95% CI -5.39 to 0.43), standardized effect d = -0.39; z-test p = 0.095.
• LID018869+Biotrue: mean 6.06 versus 2.93 on control; difference 3.13 (95% CI -2.49 to 8.75), standardized effect d = 0.26; z-test p = 0.275.
• PV+Biotrue: mean 3.52 versus 2.93 on control; difference 0.59 (95% CI -4.25 to 5.43), standardized effect d = 0.06; z-test p = 0.811.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe?

A mean is the arithmetic average of the measured values for a condition. For this endpoint, the reported mean summarizes average percent area of staining across the observations in a lens-and-solution group. It gives a central summary, but it does not show whether most observations lie near that average or whether a smaller number of high values influence it. The accompanying standard deviation describes the spread of measurements around the mean. A larger standard deviation indicates more variability in the observed values, not necessarily a difference in the average treatment effect.

In this study, the means range from 0.45 for Biofinity+RepleniSH to 6.06 for LID018869+Biotrue, while the standard deviations range from 1.03 to 14.75. The especially wide spread relative to some means makes it important not to interpret a mean as a typical value for every eye. The registry does not provide the underlying observations or other summaries of distribution shape, so the extent of skewness or the influence of unusually large measurements is not reported.

How should the mean differences be read?

The recalculated mean difference subtracts the posted control mean from the posted mean for a comparison condition. Negative values point toward a smaller mean in the named condition, while positive values point toward a larger mean. These are simple, unadjusted recalculations from the posted summary statistics. They are not described as the sponsor’s prespecified crossover analysis, and the registry says no inferential analyses were made.

The crossover structure matters when considering such comparisons. Measurements from the same participant may be related, and measurements from the two eyes may also be related. Wear period and assigned sequence can be relevant features of a crossover study. General statistical practice may account for such structure in an analysis, but whether or how this was done is not reported in the registry record. The recalculations should therefore not be interpreted as adjusted for participant, eye, period, or sequence effects.

What does a confidence interval communicate?

A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the method used to calculate it. A narrower interval indicates greater precision, while a wider interval leaves more uncertainty about the size and direction of the difference. The reported recalculated intervals all include zero. That means the posted intervals do not rule out no mean difference, and they also include values on both sides of zero. An interval crossing zero is not proof that two conditions are equivalent.

Confidence intervals must be considered alongside the design and analysis. These intervals accompany unadjusted calculations from arm summaries in a crossover study, and the registry does not report a crossover-specific inferential method. They cannot resolve uncertainty about dependence among measurements or sequence and period effects. The endpoint description also does not specify a clinically important difference, so the intervals cannot be judged against a registry-defined clinical threshold.

What is the role of a p-value?

A p-value is a measure calculated under a statistical model and a null hypothesis; it describes how unusual data at least as incompatible with that null would be under the model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The posted unadjusted p-values are 0.095, 0.275, and 0.811 for the three comparisons. Since the registry states that no hypotheses were formulated and only descriptive statistics were used, these recalculated p-values should not be presented as the trial’s own confirmatory findings.

Each p-value comes with limitations from the calculation and design. The comparisons are unadjusted and multiple conditions are contrasted with a control. The registry does not report a multiplicity procedure, a prespecified significance threshold for these recalculations, or an inferential crossover model. A p-value alone cannot address these omissions or make a result more precise.

Why can variability affect precision?

General statistical principle: when measurements are more dispersed, a mean difference is often estimated less precisely if sample size and other design features are held constant. This is why standard deviations matter alongside means. The posted spreads are notably different across the four conditions, so readers should not focus on the differences in means without considering uncertainty. The calculated confidence intervals reflect dispersion under their calculation method, but they do not incorporate an unreported crossover adjustment.

General statistical principle: over-dispersion occurs when observed data vary more than a statistical model expects. A model that understates variability can produce intervals that are too narrow and p-values that are too small. The registry does not report a distributional model or an over-dispersion assessment for this continuous endpoint. The variability shown by the standard deviations is relevant descriptively, but it does not by itself establish that a particular model was needed or used.

How does the crossover design affect interpretation?

In a crossover study, each participant experiences more than one condition, and results can depend on the condition order or the period in which it is measured. The record describes four sequences, two wear periods, and different treatment assignments for the right and left eyes. These details establish that order and eye allocation were part of the design. They do not establish how results were statistically adjusted for those features. Details on washout, carryover assessment, handling of missing observations, and crossover-specific analysis are not reported in the registry record.

Accordingly, the endpoint means are best read as the registry’s descriptive summaries for each combination. The mean differences, intervals, and p-values are unadjusted recalculations and should be distinguished from a design-aware analysis. This distinction does not invalidate the descriptive summaries; it defines the limits of what can be concluded from them.

10. Confidence Intervals and Precision

The mean differences have 95% confidence intervals of -5.394 to 0.434 for Biofinity+RepleniSH, -2.491 to 8.751 for LID018869+Biotrue, and -4.249 to 5.429 for PV+Biotrue, each compared with LID018869+RepleniSH. All three intervals include zero and extend to both negative and positive values. Thus the recalculated results leave uncertainty about both the direction and magnitude of each difference.

The intervals are not equally wide. The Biofinity+RepleniSH comparison has a lower point estimate, but its interval also includes a value above zero. The LID018869+Biotrue and PV+Biotrue intervals include a range of possible differences on either side of zero. Their width means the point estimates should not be treated as precise descriptions of the underlying difference. A confidence interval is not a range that contains every individual eye’s result; it describes uncertainty about the estimated mean difference under the calculation method.

These intervals accompany unadjusted recalculations from posted summary statistics. They do not represent a reported sponsor analysis and do not show adjustment for the crossover design, multiple comparisons, or any missing-data process. The registry does not report a clinically important difference threshold, so the precision cannot be evaluated against a registry-defined threshold for importance. The registry also states that no hypotheses were formulated and that results were descriptive only. The intervals therefore help describe uncertainty but do not turn the results into a prespecified inferential conclusion.

11. Planning a Similar Trial: Sample Size

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

The sample-size figures are planning illustrations, not a record of the trial’s enrollment target or its original sample-size justification. For these continuous-outcome comparisons, the figures are participants per arm, not total events. The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each illustration uses an effect equal to the stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm for a planning scenario designed to have an 80% chance of detecting the chosen effect under the stated assumptions, if that effect and assumptions were correct. The 90% power column uses a higher target chance of detecting that effect and consequently calls for more participants per arm. These are hypothetical planning targets, not evidence about the chance that the completed study detected an effect.

Rows planning for 100%, 75%, and 50% of the observed effect show how the assumed effect size changes the planning requirement. A smaller effect is harder to distinguish from random variation, so detecting a smaller fraction of the observed effect requires more participants. The tables and curve should be read as sensitivity illustrations: their values change with the effect size and target power, while the calculation assumptions remain as listed. These are planning illustrations, not observed power.

The trial enrolled 36 participants, but the sample-size illustrations should not be treated as a retrospective verdict on the study. They use an observed effect to construct hypothetical designs, and the registry does not report that these calculations were part of the trial’s original planning. The record also does not report a justification for the enrollment target or a prespecified statistical test for the primary outcome.

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 = -2.480; pooled standard deviation σ = 6.307.
2. n = 2 × (1.96 + 0.842)² × 6.307² / -2.480² = 101.5, rounded up to 102 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 <- -2.48                      # observed difference in means
sigma <- 6.30715863126971                     # 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(4789382)
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 = 102 (80% power), 136 (90% power)
 75% of observed effect: n per arm = 181 (80% power), 242 (90% power)
 50% of observed effect: n per arm = 407 (80% power), 544 (90% power)
power.t.test: 102.5 
Simulated power at n = 102 per arm: 0.794 (20000 replicates)

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

13. Multiplicity, Missing Data and Analysis Populations

The primary endpoint description states that no hypotheses were formulated, no inferences were made, and only descriptive statistics were used in reporting. The record lists one primary outcome measure and no posted secondary outcome measures. The recalculated comparisons contrast three conditions with the designated control. Because these are recalculations rather than reported inferential analyses, their unadjusted p-values should not be interpreted as a set of confirmatory tests.

The registry does not report a multiplicity adjustment, a testing hierarchy, or a family-wise error strategy. In general, making multiple statistical comparisons can increase the chance of a false-positive finding if each is treated as an independent confirmatory test without adjustment. That general issue does not change the registry’s stated descriptive intent, but it is relevant to how the recalculated p-values should be read. No conclusion about statistical significance across a prespecified family of tests can be attributed to the trial record.

The primary endpoint is reported for the Safety Analysis Set. The record does not define the set in further detail or describe exclusions from it. It does not report missing outcome counts, an approach to missing data, or whether all randomized participants contributed to every period and eye-specific endpoint. It also does not describe any imputation or sensitivity analysis.

The study’s crossover design raises questions about how within-participant and within-eye dependence, period, sequence, and possible carryover were handled. The arm summaries do not answer these questions. A statistical analysis plan, model specification, and details of any adjustment for the design are not reported in the registry record. The record also does not report interim analyses, a stopping rule, or a prospective sample-size justification. These absences limit assessment of the planned inferential framework; they do not alter the descriptive values that are posted.

14. 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 lists six safety groups: Pretreatment, each of the four ocular lens-and-solution groups, and All Nonocular. Each group lists 36 at risk. In every group, the number affected by serious adverse events is 0, the number affected by other adverse events is 0, and deaths are 0. No serious adverse-event terms are listed.

These figures describe what the registry records for the listed groups and the trial’s enrolled sample. They do not show that an event is impossible or establish a general safety profile. The record does not provide event narratives, severity or relatedness details, or additional follow-up information beyond the listed groups. The figures should be read as registry-reported counts, not as a comparison establishing a safety difference among conditions.

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

The posted results describe average percent area of corneal staining at hour two for four lens-and-solution combinations. The observed means and standard deviations show that both central values and variability differed across the reported groups. The unadjusted recalculated mean differences and confidence intervals offer a numerical description of comparisons with LID018869+RepleniSH, but each interval includes zero and remains compatible with differences in either direction.

The registry explicitly says that no hypotheses were formulated and no inferences were made. Therefore, the results do not establish a statistically confirmed ranking of the four combinations, nor do they demonstrate equivalence. The recalculated p-values are not the trial’s own inferential findings. The registry does not state a clinically important difference threshold, so the reported estimates cannot be classified against such a threshold using this record.

The trial’s randomized, double-masked crossover structure is relevant to interpreting its design, but the posted summaries do not report a design-aware analysis accounting for participant, eye, period, or sequence. The registry does not report handling of missing data, washout or carryover assessment, or details of masking. These gaps mean the descriptive summaries should not be expanded into claims about the underlying treatment effects beyond the observed measurements and recalculations.

The safety listings record zero affected by serious and other adverse events and zero deaths in each listed group. Those counts apply to the groups and participants recorded in this study. They do not prove that adverse events cannot occur or establish comparative safety beyond the trial record. Overall, the results are most appropriately treated as descriptive evidence about staining measurements in this specific study, with substantial uncertainty in the recalculated comparisons.

16. Why This Trial Matters Statistically

This study illustrates why the label of a design and the form of its reported analysis both matter. A crossover design assigns participants to experience multiple conditions, and the registry specifies assignments by eye and period across four sequences. Those features can create dependence among measurements and make order and period relevant. Descriptive group means alone do not show how such structure was handled statistically.

It also demonstrates the importance of reading a mean alongside its standard deviation and confidence interval. The posted means differ, but the variability is considerable for some combinations, and the recalculated intervals span zero and include values on both sides of it. A single point estimate can sound definitive if its uncertainty and analysis context are omitted. Here, the registry explicitly characterizes the primary reporting as descriptive and says no hypotheses or inferences were made.

The record further distinguishes trial results from planning illustrations. Sample-size calculations based on fractions of an observed effect can help readers understand how assumed effect size and target power influence hypothetical planning. They do not establish the trial’s original design rationale. That rationale is not reported in the registry record.

Finally, the study has a focused outcome and a short, specified wear period, while the registry offers limited information about analysis details and missingness. Keeping those boundaries visible is statistically important: conclusions should reflect the measurements and uncertainty actually recorded, without treating unadjusted recalculations as a prespecified crossover analysis or extending descriptive findings beyond the study.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint is assessed after two hours of wear in each period. The record does not report measurements at other wear durations, so these results do not describe staining beyond the stated assessment time. The study enrolled 36 participants, and the registry does not provide further participant characteristics beyond the condition of refractive errors. The applicability of the observed summaries to populations with other characteristics is therefore not established by the record.

Each eye was treated differently and graded separately, and participants followed one of four sequences across two periods. The registry does not report a crossover-specific statistical model, handling of within-participant or between-eye dependence, or treatment of period and sequence effects. It also does not report washout procedures or assessment of carryover. The posted unadjusted recalculations cannot fill in those design details.

The registry reports means and standard deviations, but not individual observations or distributions. It does not describe missing outcome data, exclusions from the Safety Analysis Set, or a missing-data method. Details of who was masked and how masking was maintained are also not reported. No clinically important difference threshold, inferential analysis plan, multiplicity method, or original sample-size justification is reported in the registry record.

The study’s stated purpose concerns corneal staining, and the listed primary measure captures average stained area across five regions. The record does not report additional outcome measures or longer-term assessments. These limitations define the scope of interpretation: the posted findings describe the registered endpoint and conditions, but do not resolve questions the registry does not address.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Three Daily Wear Monthly Replacement Silicone Hydrogel Contact Lenses With Two Multi-purpose Disinfecting Solution Combinations — NCT04789382.
• Registry record last updated 2022-05-25; status last verified 2022-05.
• Results first posted 2022-05-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

NCT04789382 is a completed randomized, double-masked crossover study sponsored by Alcon Research. It enrolled 36 participants with refractive errors and assessed four contact lens-and-solution combinations in two-hour wear periods across four sequences. The primary endpoint was average percent area of corneal staining, assessed separately for each eye and averaged across five corneal regions.

The registry reports group means and standard deviations and states that the primary results were descriptive, with no hypotheses formulated and no inferences made. Unadjusted recalculations compare the three non-control combinations with LID018869+RepleniSH; all reported confidence intervals include zero. The registry lists zero serious adverse events, zero other adverse events, and zero deaths in each safety group. Details of crossover-specific analysis, missing-data handling, and the original sample-size rationale are not reported in the registry record.