Assessment of Contact Lens Wettability Using Wavefront Aberrometry: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment of Contact Lens Wettability Using Wavefront Aberrometry (NCT02349438), a randomized na study. The primary outcome is Higher Order Root Mean Square (HO RMS) - Near Target in Downgaze With Natural Blinking.

2. Clinical Question

The study is described as a feasibility test of whether differences in contact-lens wettability can be measured with a wavefront sensor. The registry identifies the device as a COAS wavefront sensor and the endpoint as the average higher-order root mean square value for each lens. Results are reported as means with standard deviations, in microns.

The central comparison is between the two lens types under the stated measurement conditions, at two hours after insertion. Because this is a crossover study, each participant may contribute measurements under both lens conditions; however, the registry record does not specify the sequence, washout, or paired statistical method. The posted arm summaries therefore describe the reported measurements, but alone do not establish how within-participant dependence was handled in the comparison.

3. Trial Design

The registry describes a randomized, single-masked, crossover study of two contact-lens devices. Its listed status is completed, and the listed study dates are 2014-12 for start and 2015-05 for primary completion. Enrollment is reported as 25. The record names Johnson & Johnson Vision Care, Inc. as sponsor and lists the phase as NA.

The two lenses were senofilcon A and lotrafilcon B. Each was worn in both eyes for two hours, and neither was dispensed. The study's brief summary describes the goal as testing the feasibility of measuring differences in lens wettability with a wavefront sensor. The registry does not report the randomized sequence, whether participants received the lenses in a particular order, or how time or carryover effects were addressed.

The primary outcome was measured two hours after insertion. Participants fixated on a near digital device while looking down, with natural blinking. The outcome description says the average higher-order root mean square value was reported for each lens. The analysis population is described as all subjects who completed all study visits. The posted outcome summaries list 21 observations for each lens.

The record lists three outcome measures but no posted secondary outcomes. It lists no analyses. The relationship between the enrollment figure and the number of observations in the primary-outcome summaries is not explained in the registry record. It also does not report the masking procedure, the specific randomization method, or the original design assumptions, including any planned sample-size justification.

There is a naming inconsistency in the arm descriptions: one description says lotrafilcon A, while the intervention listing and outcome results identify lotrafilcon B. The interpretation of the posted comparison follows the intervention and outcome labels, which both name lotrafilcon B. The record does not resolve the difference in wording.

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: A total of 25 subjects were enrolled into this study. Of the enrolled subjects 4 did not meet the eligibility criteria and 21 were dispensed study lenses. Of the dispensed subjects all 21 completed the study.

Period 1

Period 2

Analysis population for the primary outcome, as defined in the registry: All subjects that have completed all study visits.

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 that were dispensed at least 1 study lens throughout the duration of the study.

6. Primary Endpoint

The registry lists the primary outcome as Higher Order Root Mean Square (HO RMS) - Near Target in Downgaze With Natural Blinking, measured over 2 hours post insertion.

The primary endpoint is the higher-order root mean square (HO RMS) measured in microns by a COAS wavefront sensor. The measurement was taken two hours after insertion while a participant fixated on a near digital device in downgaze and blinked naturally. The record reports an average value for each lens and identifies the endpoint as a continuous measure summarized by its mean and standard deviation.

HO RMS is an optical wavefront metric: it describes the magnitude of higher-order aberrations in the measured wavefront. In general, a continuous sensor-based endpoint can provide a quantitative signal for comparing conditions under controlled measurement circumstances. The registry's stated interpretation is that lower values indicate a better outcome. In this study, the endpoint was selected to test whether a wavefront sensor could measure a difference associated with lens wettability; it is not itself a direct measurement of wettability.

The measurement context matters. Near fixation, downgaze, natural blinking, and the time after insertion define the conditions under which the reported averages were obtained. They help specify what the numbers represent, but the registry does not report additional measurements or validation results linking this particular HO RMS endpoint to patient experience. Nor does it report a threshold that would distinguish a practically important difference from a small one. The result therefore speaks to the reported sensor metric under the stated conditions, rather than to every aspect of lens performance.

7. Results Posted in the Registry

• Lotrafilcon B: mean 0.14 versus 0.16 on control; difference -0.02 (95% CI -0.06 to 0.02), standardized effect d = -0.27; z-test p = 0.385.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each measurement is a numerical HO RMS value in microns. For a continuous outcome, the mean describes the average observed value, while the standard deviation describes how much individual measurements vary around that average. A smaller standard deviation indicates values that cluster more closely around the mean; it does not indicate that the mean estimate is more accurate by itself. Accuracy of an estimated mean also depends on the number of observations and, in a crossover study, potentially on the correlation between measurements from the same participant.

What does the mean difference represent?

The posted means are 0.159 for senofilcon A and 0.142 for lotrafilcon B. The comparison is expressed as lotrafilcon B relative to senofilcon A, with an estimated mean difference of -0.017 microns. This is a difference on the original measurement scale, so its units remain microns. The sign communicates direction according to the stated comparison: negative means the lotrafilcon B mean is lower than the senofilcon A mean. The registry describes lower HO RMS as better, but this direction does not by itself establish whether the difference matters in practice.

A difference in means is often easier to interpret in the original measurement unit than a standardized effect. It retains the endpoint's scale, but its practical meaning depends on understanding how much change is meaningful for this sensor measure. The registry record does not report a meaningful-difference threshold. No threshold should be inferred from the difference or from the variation in the observed measurements.

Why report standard deviations and a standardized effect?

The standard deviations are 0.066 microns for senofilcon A and 0.060 microns for lotrafilcon B. The comparison also reports a pooled standard deviation of 0.063 and a standardized effect, d, of -0.268. A pooled standard deviation combines information about variability across the compared conditions under the calculation's assumptions. A standardized effect expresses the mean difference relative to that variability, removing the original measurement unit. It can provide a scale-free description of the observed contrast, but it may be less intuitive than the micron-scale difference.

The pooled-standard-deviation approach is not the same as a paired analysis. In general, a crossover design measures participants under more than one condition, so the measurements may be correlated within a participant. A paired analysis can use the within-participant differences and their variability. That correlation can affect the uncertainty of the comparison. The registry reports a crossover design and arm-level summaries, but does not report the paired differences, their standard deviation, or a paired analysis. The posted comparison is an unadjusted recalculation from summary statistics, and the record does not establish that it accounts for the crossover pairing.

How should the p-value be read?

The unadjusted p-value is 0.385. In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified statistical model in which the null hypothesis holds. It is not the probability that the null hypothesis is true, nor the probability that chance alone caused the result. Its meaning depends on the model and analysis used. The registry lists no analyses and does not report a trial-specific statistical plan or decision threshold. The p-value therefore should be read alongside the estimate and its interval, rather than used alone to label the result conclusive or inconclusive.

“Unadjusted” indicates that the reported p-value has not been adjusted for multiple comparisons. The primary comparison is the focus of this interpretation, and no secondary analyses are posted. The record lists three outcome measures, but does not provide details allowing a full assessment of how many tests were planned or how multiplicity was considered. A p-value should not be interpreted as though a multiplicity plan is known when it is not reported.

What does an interval add?

An interval around a difference describes a range of values compatible with the observed data and the assumptions of the calculation. In general, wider intervals signal less precision than narrower intervals. The reported interval for the mean difference extends from -0.055 to 0.021 microns, covering both negative and positive possibilities. The confidence level for this interval is not reported in the registry record. The bounds therefore communicate uncertainty in the estimate, but the record does not provide every detail needed to evaluate its construction.

Interval interpretation relies on the method used to calculate it. For a crossover trial, a method that incorporates paired data can differ from one based only on separate group summaries. The posted standard errors are 0.014 for senofilcon A and 0.013 for lotrafilcon B, but the registry does not report the within-participant covariance or the original analysis method. Those omissions limit what can be inferred about whether the interval reflects the trial design fully.

Why does over-dispersion matter in general?

For count outcomes, over-dispersion means the observed variation exceeds what a simple model assumes; ignoring it can make standard errors too small and intervals too narrow. This endpoint is continuous rather than a count, so that specific issue is not the central concern. More generally, uncertainty calculations need to match the data structure and variability. In this crossover setting, the key design-related detail is the dependence between measurements on the same participant, which is not described in the posted analysis.

The registry does not report an adjusted estimate, covariate model, missing-data method, or sensitivity analysis. It reports no analyses beyond the endpoint summaries. Accordingly, the interpretation stays with the posted means, standard deviations, difference, interval, and p-value, and treats assumptions about the original analysis as unreported rather than filling them in.

10. Confidence Intervals and Precision

The reported mean difference is -0.017 microns, with an interval from -0.055 to 0.021 microns. The span includes values in both directions, so the data do not pinpoint the sign of the underlying difference. The interval is compatible with a lower average HO RMS for lotrafilcon B as well as a higher average relative to senofilcon A. The registry states that lower values indicate a better outcome, but the interval does not identify which direction best describes the underlying comparison.

A confidence interval is a way to express uncertainty around an estimate. In general, narrower intervals indicate greater precision, while wider intervals leave more possible values consistent with the data and the calculation. The confidence level for the posted interval is not reported in the registry record. The interval should therefore be read as the reported range, without assigning it a confidence level that the record does not state.

The standard deviations describe the spread of observed measurements: 0.066 microns for senofilcon A and 0.060 microns for lotrafilcon B. They are not confidence limits. The reported standard errors are 0.014 and 0.013, respectively. Standard errors describe uncertainty in estimates under a particular model, but the record does not give enough detail to assess whether the calculation accounts for the crossover pairing.

Precision is also distinct from practical importance. The registry does not report a threshold for a meaningful change in HO RMS, so the interval cannot be classified against such a threshold. Nor does the interval establish that the sensor can detect differences reliably across other populations, devices, or measurement conditions. It quantifies uncertainty around the posted comparison only to the extent supported by the calculation and the details available in the registry record.

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 comparison is continuous, and the planning illustration uses equal allocation between the two arms. For 100% of the observed effect, the illustration lists 219 participants per arm for 80% power and 293 participants per arm for 90% power. For 75% of the observed effect, it lists 389 participants per arm for 80% power and 520 participants per arm for 90% power. For 50% of the observed effect, it lists 874 participants per arm for 80% power and 1,170 participants per arm for 90% power.

These are planning illustrations based on the observed effect, not the trial's original design assumptions. The calculation assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The original trial's own sample-size assumptions are not reported in the registry record.

In plain terms, the 80% power column describes the planned sample size associated with an 80% chance of detecting an effect of the specified size under the planning assumptions, if that effect is real. The 90% power column uses a higher target chance of detection under those same assumptions and therefore gives larger sample-size requirements. These values do not describe the probability that the posted study result is correct, and they are not observed power.

The rows illustrate that smaller effects need more participants to detect with the same power target. These figures are not a recommendation for a future crossover design: the illustration assumes equal allocation between two arms, while the registry identifies the study as crossover and does not report a design-specific planning method. A calculation tailored to a crossover design could require details about within-participant variability that are not reported in the registry record.

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 = -0.017; pooled standard deviation σ = 0.063.
2. n = 2 × (1.96 + 0.842)² × 0.063² / -0.017² = 218.4, rounded up to 219 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 <- -0.017                      # observed difference in means
sigma <- 0.0634140757245582                     # 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(2349438)
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 = 219 (80% power), 293 (90% power)
 75% of observed effect: n per arm = 389 (80% power), 520 (90% power)
 50% of observed effect: n per arm = 874 (80% power), 1,170 (90% power)
power.t.test: 219.4 
Simulated power at n = 219 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. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and no posted secondary outcomes. It lists no analyses. The available record therefore does not describe a complete analysis plan, the intended hierarchy of endpoints, or whether any multiplicity adjustment was planned. The reported p-value is unadjusted. Without a reported plan, it is not possible to determine how the primary comparison fits into the full set of intended statistical tests or whether the reported test was selected before results were examined.

Multiplicity matters in general when several hypotheses are tested: the chance of obtaining at least one apparently unusual result can increase as more tests are considered. Methods such as prioritizing a single primary hypothesis or adjusting statistical thresholds can address that issue, but the registry record does not state whether any such approach was used. The listed count of outcome measures alone does not establish how many statistical tests were conducted.

The record identifies the primary-outcome population as all subjects who completed all study visits. It does not report how many participants were excluded from that population, why any participant may not have completed the visits, or how missing measurements were handled. The enrollment figure is 25, while the posted primary-outcome summaries report 21 observations for each lens. The registry does not explain this difference, so no reason for it should be inferred.

The record also does not describe an intention-to-treat population, a per-protocol population, imputation, or sensitivity analyses. In general, missing-data methods matter because conclusions can depend on whether unavailable measurements differ systematically from observed ones. Here, the missing-data mechanism and the analysis approach are not reported in the registry record.

Because the design is crossover, it would also be useful to know how the analysis handled participants with only one lens measurement, if any, and how repeated observations were paired. The record does not report those details. These omissions limit assessment of the analysis population, multiplicity, and robustness, rather than proving that any particular analytic problem occurred.

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 serious adverse event summaries report 0 affected participants for senofilcon A and 0 for lotrafilcon B. Each lens group lists 21 participants at risk. The registry lists no serious adverse event terms for either group. These figures describe the events captured in the posted record for the stated groups; they do not establish that no other symptoms or events occurred.

The other adverse event summaries also list 0 affected participants in each group, with 21 at risk in each. Death counts are not reported. The record does not provide further detail about safety collection, event definitions, observation periods beyond the primary endpoint timing, or whether participants could contribute to both lens groups in these summaries. Because the study is described as crossover, the group labels should not automatically be interpreted as independent sets of participants.

Zero reported affected participants is a descriptive count, not proof that the risk of an event is absent. Safety summaries are most informative when read with their collection period, definitions, and population, some of which are not reported in the registry record. These data do not support advice about whether a person should use either lens.

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

The posted outcome data show similar mean HO RMS measurements for the two lens conditions, with a reported mean difference of -0.017 microns for lotrafilcon B relative to senofilcon A. The interval extends from -0.055 to 0.021 microns, and the unadjusted p-value is 0.385. The estimate is therefore uncertain in direction, and the registry record does not report a threshold for deciding whether a difference of this size is important for the sensor measure.

The study's stated purpose was to test the feasibility of measuring differences in contact-lens wettability with a wavefront sensor. The reported endpoint is an optical metric under a defined task and measurement time. It does not directly measure wettability, comfort, or a broader clinical benefit. The registry does not report validation evidence that would translate a change in HO RMS into a change in those outcomes.

The result also does not establish that the lenses are equivalent. An uncertain estimate is not the same as evidence that two conditions are identical. To assess equivalence or non-inferiority, a study generally needs a prespecified margin and an analysis designed for that question; neither is reported in the registry record. The posted comparison addresses the observed difference and its uncertainty, not a formal claim that the outcomes are interchangeable.

Similarly, the result should not be taken as proof that the sensor can or cannot distinguish lens wettability in other circumstances. The study reports one primary sensor metric, one time point, and a specific near downgaze task with natural blinking. Generalization beyond those conditions requires evidence not reported in this record. The crossover design could provide information from within-participant comparisons, but the posted summary does not report a paired analysis or the within-participant variability.

The safety summaries list no affected participants for serious or other adverse events in the reported groups, while deaths are not reported. These entries are descriptive and should not be expanded into a claim that no event could occur. Overall, the record describes a feasibility comparison and its uncertainty; it does not determine clinical benefit, equivalence, or the suitability of either lens for an individual.

16. Why This Trial Matters Statistically

This trial is statistically interesting because its question is about measurement feasibility rather than simply comparing a clinical outcome. A wavefront sensor records a continuous optical metric, and the study asks whether that metric can reflect differences associated with contact-lens wettability. That distinction matters: evidence about a sensor measurement is not automatically evidence about a patient's visual experience or about the underlying property the sensor is intended to help assess.

The crossover design is also relevant to the statistical interpretation. When the same participant is measured under more than one condition, within-participant comparisons can remove some between-person variability. But this benefit depends on the analysis matching the design and on knowing how the paired measurements relate. The registry identifies a crossover study but does not report the sequence or paired analysis details. That gap illustrates why design labels and summary statistics need to be read together.

The posted mean difference is modest relative to the reported spread, and its interval spans both directions. Such a result illustrates why a point estimate, variability, and uncertainty should be considered together. A p-value alone would not communicate the range of effects compatible with the data, while the point estimate alone would hide its uncertainty. Neither can answer whether a difference is practically important without a threshold or external context, which is not reported.

The record also demonstrates the limits of registry results. It reports a sample-size planning illustration based on the observed effect, but the original design assumptions are not reported. The illustration can show how required sample sizes change when the target effect changes; it cannot be mistaken for the trial's own prospective justification. Likewise, the outcome summaries are available without a full account of missing data, multiplicity, or analysis populations.

For biostatisticians and clinical researchers, the key lesson is methodological: distinguish the measured construct from the clinical question, respect the dependence implied by a crossover design, and interpret estimates with their uncertainty and reporting context. The available data support a bounded description of the posted sensor readings, not a broader efficacy claim.

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.

Several limitations are specific to interpreting this record. The arm descriptions contain a lens-name inconsistency: the intervention listing and outcome results identify lotrafilcon B, but an arm description says lotrafilcon A. The record does not resolve that discrepancy. The interpretation of the comparison follows the intervention and outcome labels, but the inconsistency remains relevant when identifying the comparator.

The study is labeled crossover, yet the registry does not report the lens sequence, the method of randomization, any washout period, or how possible order and carryover effects were addressed. It also does not report a paired comparison or the within-participant correlation. The reported means and standard deviations do not reveal these features. As a result, the posted summary comparison cannot be independently assessed as a crossover analysis.

The outcome was measured at two hours after insertion during a particular near downgaze task with natural blinking. The record does not report additional measurement times or conditions, repeatability of the sensor measurement, or validation against a direct wettability measure. The findings therefore have a narrow measurement context. The clinical importance of the HO RMS difference is also difficult to judge because no meaningful-difference threshold is reported.

The registry lists enrollment as 25, whereas the primary-outcome summaries list 21 observations for each lens. The reason is not reported, and the record does not describe missing-data handling or provide an accounting of participants by analysis population. No statistical analyses are listed, and the original sample-size assumptions, analysis plan, multiplicity approach, and confidence level for the reported interval are not reported in the registry record.

These reporting limitations do not establish that the trial was conducted improperly. They identify details that cannot be evaluated from the registry record and that constrain interpretation of the numerical summaries.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Assessment of Contact Lens Wettability Using Wavefront Aberrometry — NCT02349438.
• Registry record last updated 2018-06-19; status last verified 2016-11.
• Results first posted 2017-01-20.
• 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

The record describes a completed randomized, single-masked crossover study of senofilcon A and lotrafilcon B contact lenses. Enrollment is listed as 25, and the study dates are 2014-12 through primary completion in 2015-05. Each lens was worn in both eyes for two hours and was not dispensed.

The primary endpoint was mean HO RMS in microns, measured by a COAS wavefront sensor during near fixation in downgaze with natural blinking, two hours after insertion. The posted means were 0.159 for senofilcon A and 0.142 for lotrafilcon B; the reported mean difference was -0.017 microns, with an interval from -0.055 to 0.021 and an unadjusted p-value of 0.385. The registry lists three outcome measures, no secondary outcomes, and no analyses.

The record reports 0 affected participants for serious and other adverse events in each lens group; death counts are not reported. The crossover analysis details, missing-data approach, multiplicity plan, and original sample-size assumptions are not reported in the registry record.