Comparison of Two Marketed Silicone Hydrogel Lenses: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Two Marketed Silicone Hydrogel Lenses (NCT02495948), a randomized na study. The primary outcome is Mean Ex-vivo Cholesterol Deposits After 30 Days of Wear.

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-masked, crossover study of two marketed silicone hydrogel lenses. Its official title identifies a one-month clinical comparison of lotrafilcon B and samfilcon A. The study is marked completed, with enrollment of 168. Its recorded start was 2015-07 and primary completion was 2015-10.

Participants were assigned to one of two product sequences. In one sequence, lotrafilcon B, identified as AIR OPTIX AQUA, was worn first and samfilcon A, identified as ULTRA, followed. The other sequence reversed that order. Both eyes were to wear each product in daily-wear modality for 30 days, with a minimum of 5 days/week and 8 hours/day. The registry does not describe a washout period or provide further details about the conduct of the crossover.

The primary endpoint is a continuous measure of total cholesterol deposits, reported as a mean and standard deviation. The endpoint description says that the right-eye lens was removed, stored dry and frozen, and later analyzed for cholesterol and cholesterol esters. The posted product summaries report 167 observations for each lens product. The endpoint description also says the study originally intended to analyze 36 lenses per arm and that fewer were analyzed because of measurement error. Those statements do not align with the posted product counts, and the registry record does not explain the inconsistency.

The record lists hydrogen peroxide solution and saline solution as interventions, but does not specify their use in the posted primary comparison. It reports no posted secondary outcomes and no analysis entries. Details such as the identity of the masked party, the crossover analysis model, and the original statistical analysis plan 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.

Before assignment: Of the 168 enrolled, 1 participant was exited as a screen failure prior to randomization. This reporting group includes all randomized participants (167).

Period 1, First 30 Days of Wear

Reasons for not completing this period:

Period 2, Second 30 Days of Wear

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat 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: This analysis population includes all randomized participants (Intent-to-Treat (ITT) analysis set).

6. Primary Endpoint

The registry lists the primary outcome as Mean Ex-vivo Cholesterol Deposits After 30 Days of Wear, measured over Day 30, each product.

The primary endpoint is mean ex-vivo cholesterol deposits on a contact lens after 30 days of wear, measured in micrograms. The material extracted from the lens includes total cholesterol deposits: cholesterol and cholesterol esters. The registry describes removal of the right-eye lens, dry and frozen storage, extraction, and measurement. The endpoint is listed for each product at Day 30.

This is a continuous outcome: each analyzed lens contributes a measured amount, and the group summary is a mean with a standard deviation. A mean describes the central level of the measured deposits, while the standard deviation describes how dispersed individual measurements are around that mean. The registry states that lower deposits indicate increased lens performance. That statement gives the endpoint’s intended direction, but it does not by itself establish how the measurement relates to other aspects of lens performance or to a participant’s experience.

The endpoint is used to compare the two products on a defined laboratory measurement after wear. The posted means are 1.63 for AIR OPTIX AQUA and 4.89 for ULTRA. The reported mean difference is 3.26, expressed as ULTRA relative to AIR OPTIX AQUA. The registry does not report additional primary endpoints, and it does not provide a separate clinical outcome alongside this ex-vivo measurement.

7. Results Posted in the Registry

• ULTRA: mean 4.89 versus 1.63 on control; difference 3.26 (95% CI 2.68 to 3.84), standardized effect d = 1.21; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe?

For a continuous endpoint, the mean is the arithmetic average of the recorded measurements in the group being summarized. Here the measured quantity is total cholesterol deposits extracted from a contact lens, expressed in micrograms. The posted mean is 1.63 for AIR OPTIX AQUA and 4.89 for ULTRA. A mean is useful for describing the center of a distribution, but it does not show the full spread, shape, or presence of unusually high or low observations.

The standard deviations are 2.21 for AIR OPTIX AQUA and 3.12 for ULTRA. Standard deviation describes the variability of measurements around the mean in the same units as the endpoint. It is not the same as the uncertainty in the mean or the uncertainty in the difference between means. The registry reports the standard deviations but does not provide distributions or individual measurements in the registry record recorded for this result.

What is a mean difference?

A mean difference expresses the separation between the two group means in the endpoint’s original units. The registry reports a mean difference of 3.26 for ULTRA relative to AIR OPTIX AQUA. The endpoint’s unit is micrograms, so this contrast remains interpretable on the original measurement scale. Since the reported mean for ULTRA is higher, the contrast is positive in the stated direction. No further calculation is needed to interpret that direction.

A mean difference is an estimate, not a guarantee that every measured lens has a value near either group mean. The spread in the observations and the sampling uncertainty both matter. The interval reported for the difference communicates uncertainty in the estimated contrast, while the group standard deviations describe variation among the measured lens values.

What does the p-value address?

The registry reports an unadjusted p-value of <0.001. In general, a p-value measures how compatible the observed data, or results more extreme under a specified test, are with a null model. A small p-value is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. Its meaning depends on the test and analysis assumptions. The registry record does not identify the statistical test or describe the model used to obtain this p-value. It is therefore appropriate to report it as the posted unadjusted value without assigning it to a specific test procedure.

Unadjusted means the recorded value is not presented as adjusted for multiple comparisons. The record lists one primary outcome and no posted secondary outcomes, but it does not report whether other analyses were considered. The multiplicity strategy, if any, is not reported in the registry record.

How should a crossover design affect interpretation?

In general, a crossover design assigns participants to sequences so that they receive more than one study condition at different times. Because the same participant can contribute measurements under both products, an analysis may account for within-participant pairing. Sequence and period can also be relevant to such an analysis. The record identifies randomized sequence and crossover structure, but does not report the model, the handling of sequence or period, or whether the posted contrast is based on paired observations. The results should not be described as a particular paired or adjusted analysis without that information.

The record also does not report a washout period. That absence does not establish that no washout occurred; it means the registry record does not describe one. Similarly, single masking is recorded, but who was masked and how masking was maintained are not reported in the registry record.

What does the standardized difference add?

The posted standardized difference is 1.206, with a pooled standard deviation of 2.704. In general, standardization expresses a mean difference relative to a measure of variability, making the contrast dimensionless. It can help describe the size of a contrast in relation to the observed spread, but it is not on the microgram scale and does not replace the original-unit difference. The record does not give further details about how the pooled standard deviation was selected or how standardization relates to the crossover analysis.

Standardized effects depend on both the difference and the variability used in the denominator. They should not be treated as direct measures of clinical importance. For this endpoint, the mean difference in micrograms is the more direct description of the recorded contrast, while the standardized value is a scale-relative summary.

The registry record does not report an original sample-size justification, formal statistical analysis plan, interim analyses, or details of missing-data methods. These omissions leave uncertainty about planned procedures and the assumptions underlying the posted result. The result can still be described using the reported means, standard deviations, mean difference, interval, and unadjusted p-value, while keeping those unreported methods distinct from the observed summaries.

10. Confidence Intervals and Precision

The mean-difference estimate is 3.26 micrograms, and its reported confidence interval extends from 2.68 to 3.84. A confidence interval gives a range of values compatible with the estimate and the interval procedure under its statistical assumptions. It is not a range containing a specified proportion of individual lens measurements, and it is not a probability statement about the fixed, true difference.

The interval is entirely above zero, matching the positive direction of the reported contrast: the mean for ULTRA is higher than the mean for AIR OPTIX AQUA. The interval’s endpoints indicate the precision reported for this estimated mean difference. They do not resolve whether the analysis appropriately accounted for the crossover structure, because the registry does not describe the model used to obtain the interval.

The group summaries also report standard deviations of 2.21 for AIR OPTIX AQUA and 3.12 for ULTRA. These describe observed variability rather than the precision of the difference estimate. Confidence intervals for the individual product means are not reported in the registry record. Nor does the record provide a confidence interval for the standardized difference.

Interpretation of precision should also take account of the endpoint-description inconsistency: the record says the intended number of lenses was 36 per arm and that fewer were analyzed because of measurement error, while the posted product summaries each list 167 observations. The record does not explain this discrepancy. Thus, although the reported interval is numerically explicit, the available information does not allow a full reconstruction of its analysis population or method.

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. The record describes a continuous endpoint, and its planning assumptions specify equal allocation between two arms, a two-sided significance level of 0.05, and a normal approximation. The planning exercise uses the observed effect or a stated fraction of it as the effect to detect. These are planning assumptions for an illustration; the original trial design assumptions are not reported in the registry record.

The column for 80% power gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect and the model assumptions held. The 90% power column gives the corresponding planning count for a higher chance of detection under the same framework. The rows describe planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For example, the 80% power figures are 11, 20, and 44 participants per arm for those respective effect assumptions; the 90% power figures are 15, 26, and 58.

Smaller effects are harder to distinguish from random variation, so the planning counts increase as the assumed effect becomes a smaller fraction of the observed effect. These calculations are illustrations based on the posted result, not the trial’s own prospective justification or design. They are not observed power: they do not measure the probability that this completed study detected an effect after its results were known.

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 = 3.260; pooled standard deviation σ = 2.704.
2. n = 2 × (1.96 + 0.842)² × 2.704² / 3.260² = 10.8, rounded up to 11 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 <- 3.26                      # observed difference in means
sigma <- 2.7035624646011                     # 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(2495948)
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 = 11 (80% power), 15 (90% power)
 75% of observed effect: n per arm = 20 (80% power), 26 (90% power)
 50% of observed effect: n per arm = 44 (80% power), 58 (90% power)
power.t.test: 11.8 
Simulated power at n = 11 per arm: 0.771 (20000 replicates)

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

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no posted secondary outcomes. It records zero analyses. The primary outcome is the mean amount of ex-vivo cholesterol deposits after 30 days of wear, with product-specific summaries and a reported mean difference. The record does not say whether additional endpoints or comparisons were considered but not posted.

The reported p-value is explicitly unadjusted. The registry does not describe a plan to control the chance of false-positive findings across multiple outcomes, time points, or comparisons. Whether multiplicity was addressed in a statistical plan is not reported in the registry record. With no secondary results posted, there is no basis in this record to describe a broader multiplicity procedure.

The primary endpoint names the intent-to-treat analysis set, but the record does not define that set or state how participants or lens measurements were included in it. It also does not explain how measurement errors, missing measurements, or incomplete wear information were handled. The endpoint description says fewer lenses than originally intended were analyzed because of measurement error. However, it also reports product summaries with 167 observations for each product, while the description says 36 lenses per arm were intended. The record does not reconcile these counts.

The design is described as randomized and crossover, but the analysis model is not reported. In general, analysis of crossover data may need to reflect repeated measurements within participants and the sequence in which products were used. The registry does not state whether the result comes from a paired analysis or how sequence and period were handled. It also does not report sensitivity analyses, interim analyses, or a complete statistical analysis plan. These details matter for assessing the methods, but their absence does not change the values that the registry posts.

14. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The registry reports serious adverse events and other adverse events by period or product group. In the pretreatment group, 168 were at risk for serious adverse events and 168 for other adverse events; zero were affected in each category. For AIR OPTIX AQUA, 166 were at risk in each category and zero were affected. For ULTRA, 167 were at risk in each category and zero were affected.

These are the counts recorded in the registry for the listed groups. The serious adverse event terms list is empty. Death counts are not reported in the registry record. Zero affected in the posted count means no events were recorded for those categories and groups in this summary; it does not establish that no event of any kind occurred or that every possible safety outcome was assessed.

The record does not provide event definitions, follow-up detail, or an explanation of the different at-risk counts across groups. Because the study uses a crossover design, group labels should be read as the registry presents them rather than assumed to represent independent parallel groups. The safety entries do not provide a basis for comparing risks beyond the recorded counts.

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

The primary result describes a difference in the measured amount of cholesterol deposits extracted from lenses after wear. The posted mean was 1.63 micrograms for AIR OPTIX AQUA and 4.89 micrograms for ULTRA. The mean difference, reported for ULTRA relative to AIR OPTIX AQUA, was 3.26 micrograms, with a confidence interval from 2.68 to 3.84 and an unadjusted p-value of <0.001. Those numbers describe the recorded endpoint and its estimated contrast.

The registry says lower deposits indicate increased lens performance. That interpretation is specific to the endpoint’s stated direction. The data do not, by themselves, establish differences in comfort, vision, fit, tolerability, longer-term use, or any outcome not reported as measured. The endpoint is ex-vivo chemical measurement, not a direct report of a participant’s experience.

The result also does not provide a complete account of the analysis. Although the study is identified as randomized and crossover, the record does not specify the statistical model, whether participant-level pairing was used, or how sequence and period were handled. It does not explain the inconsistency between the stated intention to analyze 36 lenses per arm and the posted summaries of 167 observations for each product. These gaps limit assessment of how the estimate was derived.

The confidence interval and p-value characterize statistical uncertainty under the analysis used to produce them; they are not proof of a particular mechanism or a guarantee that the same contrast would occur in other settings. The registry record does not report results for secondary outcomes, further clinical endpoints, or a wider range of populations. The appropriate reading is therefore confined to the posted comparison of ex-vivo cholesterol deposits under the study’s stated wear conditions.

16. Why This Trial Matters Statistically

This trial is statistically instructive because its crossover design and continuous endpoint raise questions that cannot be answered from group means alone. A crossover study uses sequences in which participants wear both products at different times. In general, analyses can use within-participant comparisons, which may differ from comparisons of independent groups. The registry identifies the crossover design but does not report whether the posted estimate uses paired data or how sequence and period were handled.

The result also illustrates the difference between an estimate and its precision. The mean difference is reported in micrograms, while its confidence interval conveys uncertainty around that contrast. The standard deviations describe spread in the lens measurements and are not confidence intervals for the means. The unadjusted p-value adds information about compatibility with a null model, but does not describe clinical importance or replace an effect estimate.

A further statistical issue is the record’s inconsistent account of analyzed lenses. The outcome description says the study intended to analyze 36 lenses per arm and that measurement error reduced the actual number analyzed, while the product summaries list 167 observations for each product. Understanding the analysis unit and missing-measurement process is important when judging the reported precision and potential selection effects. The record does not resolve these questions.

Finally, the planning illustrations show how required sample size depends on the effect assumed for planning. Smaller assumed effects lead to larger participant counts under the listed assumptions. Such calculations are useful for understanding design sensitivity, but they are not a reconstruction of the trial’s original design rationale. The original sample-size assumptions and analysis plan are not reported in the registry record.

17. Limitations

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

The registry record gives limited detail about the crossover analysis. It does not report whether the comparison was paired, how sequence or period effects were considered, or whether a washout period was used. The masking designation is single, but who was masked and how masking was implemented are not reported. These omissions restrict assessment of possible design and analysis influences.

The endpoint description and posted product counts are difficult to reconcile. It says the study originally intended to analyze 36 lenses per arm and that measurement error led to fewer lenses being analyzed, while the results list 167 observations for each product. The record does not clarify the unit represented by the reported counts or explain the apparent inconsistency. The primary outcome is identified as intent-to-treat, but the population definition and missing-data handling are not described.

The endpoint is limited to ex-vivo cholesterol deposits measured after 30 days of wear. The record does not provide other clinical outcomes, secondary results, or longer-term measurements. Although the registry states that lower deposits indicate increased lens performance, this measure alone does not describe all aspects of product performance or participant experience.

The original sample-size justification, full statistical analysis plan, multiplicity approach, and interim-analysis information are not reported in the registry record. The posted p-value is unadjusted. These limitations concern the context and reproducibility of the analysis; they do not alter the numerical result recorded for the primary endpoint.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Comparison of Two Marketed Silicone Hydrogel Lenses — NCT02495948.
• Registry record last updated 2016-12-28; status last verified 2016-11.
• Results first posted 2016-10-19.
• 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

NCT02495948 is a completed randomized, single-masked crossover study comparing lotrafilcon B, identified as AIR OPTIX AQUA, with samfilcon A, identified as ULTRA. The registry lists refractive error as the condition and enrollment of 168. Each product was worn bilaterally for 30 days, with a minimum schedule of 5 days/week and 8 hours/day.

The primary endpoint was mean ex-vivo cholesterol deposits after 30 days, measured in micrograms. The posted means were 1.63 for AIR OPTIX AQUA and 4.89 for ULTRA. The reported mean difference for ULTRA relative to AIR OPTIX AQUA was 3.26, with a confidence interval from 2.68 to 3.84 and an unadjusted p-value of <0.001.

The record does not describe the crossover analysis model or resolve the inconsistency between the stated intended analysis of 36 lenses per arm and posted counts of 167 observations for each product. No secondary outcomes are posted.