Investigation of Ocular Signs & Symptoms in Wearers Fitted With Contact Lenses Following Digital Device Use: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of Ocular Signs & Symptoms in Wearers Fitted With Contact Lenses Following Digital Device Use (NCT02394756), a randomized na study. The primary outcome is Subjective Overall Comfort.

2. Clinical Question

3. Trial Design

This was a randomized, unmasked crossover study, recorded as completed. The registry lists an enrollment of 52 and describes each participant as wearing each of three contact lens types for a 4-week period. The lenses were the marketed soft contact lens, AIR OPTIX® AQUA, and Biofinity®. The primary completion date is recorded as 2015-09, and the study start as 2015-02.

A crossover design exposes participants to multiple conditions in sequence, so comparisons may use information from the same participants under different lenses. That feature can be useful when outcomes vary substantially from person to person. However, the registry record does not report the treatment sequence details, any washout arrangements, or the statistical handling of within-participant correlation. Those details matter when interpreting a crossover analysis and cannot be inferred from the design label alone.

The primary outcome population is defined as subjects who completed all study visits without a major protocol deviation. The lens-level outcome summaries each list 37 observations. The record does not explain how this population relates to the enrollment entry or to the safety groups, for which 42 are listed at risk in each lens group.

The study was unmasked. The record does not describe whether outcome collection or any other study procedures were masked. No further details about sequence generation, allocation concealment, or implementation of randomization are reported in the registry record. The trial has two outcome measures recorded and no analyses listed in the analysis count, although arm summaries and pairwise estimates are posted for the primary outcome.

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 52 subjects were enrolled in this study. Of the enrolled subjects 10 subjects did not meet the eligibility criteria and 42 subjects were dispensed study lenses. Of the dispensed subjects 37 completed the study while 5 subjects were discontinued.

Period 1

Reasons for not completing this period:

Period 2

Reasons for not completing this period:

Period 3

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

Population: All subjects that were dispensed at least one study lens.

6. Primary Endpoint

The registry lists the primary outcome as Subjective Overall Comfort, measured over 1-Day Follow-up.

The primary endpoint is Subjective Overall Comfort, measured using CLUE, the Contact Lens User Experience Comfort scores. CLUE is described as a validated patient-reported outcomes questionnaire for assessing patient-experience attributes of soft contact lenses, including comfort, vision, handling, and packaging. Its use makes the endpoint a report of participants’ experiences rather than an objective measure of visual function.

The registry describes derived CLUE scores as following a normal distribution with a population average score of 60 and a standard deviation of 20. Scores range from 0-120, with higher values indicating a more favorable or positive response. The posted outcome is a mean with standard deviation, expressed in units on a scale, at the 1-Day Follow-up.

A patient-reported comfort measure is relevant to a study focused on lens wear during digital-device use because it captures an experience that may not be represented by a clinical examination alone. The registry does not report a threshold for a meaningful difference in CLUE scores, so the clinical importance of a particular numerical contrast cannot be determined from these results alone.

7. Results Posted in the Registry

• Lotrafilcon B: mean 53.60 versus 65.00 on control; difference -11.40 (95% CI -21.25 to -1.55), standardized effect d = -0.53; z-test p = 0.023.
• Comfilcon A: mean 61.90 versus 65.00 on control; difference -3.10 (95% CI -12.80 to 6.60), standardized effect d = -0.15; z-test p = 0.531.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports continuous outcomes as means and standard deviations. A mean describes the central level of the observed scores, while a standard deviation describes how spread out individual scores are around that mean. These answer different questions: two lens groups can have similar means but different variability, or different means with considerable overlap in their score distributions. The reported standard deviations are substantial relative to the score differences, so the individual experience represented by a group mean should not be confused with every participant’s experience.

What does a mean difference express?

A mean difference subtracts one group’s mean from another according to the comparison’s stated direction. Here, the reference mean is the Senofilcon A mean, and the two posted contrasts are for Lotrafilcon B and Comfilcon A. Negative estimates indicate lower means for the comparison lens relative to the reference as reported. The estimate is in the original outcome scale units, which makes it interpretable in the same scale as the mean scores.

The posted mean difference for Lotrafilcon B is -11.4. The estimate for Comfilcon A is -3.1. These values summarize contrasts in average scores; they do not describe the range of individual responses, and they do not by themselves show whether a difference matters to participants. No minimally important difference is reported in the registry record.

How should the confidence intervals be read?

A confidence interval communicates the statistical uncertainty around an estimated contrast. It gives a range of values compatible with the data and the estimation procedure, rather than a guarantee that the true value lies within the displayed endpoints. A narrower interval indicates greater precision than a wider interval, but precision does not by itself establish clinical importance.

The Lotrafilcon B interval extends from -21.25 to -1.546, and the Comfilcon A interval extends from -12.8 to 6.597. The latter crosses zero, which is the value representing no mean difference. The former does not cross zero. The confidence level and the specific method used to construct these intervals are not reported in the registry record, so no further claim about their construction should be assumed.

What do the p-values contribute?

The posted p-values are unadjusted: 0.023 for Lotrafilcon B versus Senofilcon A and 0.531 for Comfilcon A versus Senofilcon A. A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the statistical procedure. It is not the probability that the null hypothesis is true, nor is it a measure of the size or importance of the effect.

Because the values are unadjusted, they do not reflect any correction for considering multiple comparisons or endpoints. The registry does not report the analysis plan, a multiplicity strategy, or whether these p-values came from a crossover-specific procedure. They should be interpreted in that limited context and alongside the estimates and intervals, rather than as a standalone verdict.

Why does the crossover structure matter?

In a crossover study, participants receive more than one condition. If the analysis pairs scores within the same participant, each person can act as their own reference, potentially accounting for stable personal differences. Such an analysis must handle the dependence between repeated observations. Alternatively, treating all lens observations as independent can fail to reflect that dependence. Period, sequence, or carryover effects can also be relevant to a crossover design.

The study description says each participant was to wear each lens type for a 4-week period, but the registry record does not report the order, washout details, or analysis model. It also does not say whether the comparison estimates use within-participant pairing. Consequently, the posted group summaries and comparisons cannot be used to identify the exact modeling approach.

What does the scale description add?

The registry describes CLUE scores as derived using Item Response Theory and following a normal distribution with population average score 60 and standard deviation 20. These are properties described for the score interpretation, not additional findings about these trial groups. The instrument’s stated range is 0-120, and higher scores represent more favorable responses. The primary measure is a mean, so group-level differences should be interpreted alongside both the observed dispersion and uncertainty intervals.

The registry record does not report a detailed statistical analysis plan, model specification, missing-data method, or adjustments for potential design effects. Those omissions limit the methodological conclusions that can be drawn from the posted summaries. The safest interpretation distinguishes the descriptive scores and posted contrasts from any unreported inferential choices.

10. Confidence Intervals and Precision

The confidence intervals indicate the range of uncertainty around the two reported mean differences. For Lotrafilcon B compared with Senofilcon A, the estimate is -11.4 and the interval runs from -21.25 to -1.546. For Comfilcon A compared with Senofilcon A, the estimate is -3.1 and the interval runs from -12.8 to 6.597. The second interval includes zero; the first does not.

Both intervals cover a range of plausible differences, rather than identifying an exact effect. Their width reflects uncertainty in the posted estimates. The interval for the Comfilcon A contrast extends across values below and above zero, so it leaves uncertainty about the direction of the mean contrast. The Lotrafilcon B interval is on the negative side, but still permits a range of possible magnitudes.

The outcome standard deviations are 19.76 for Senofilcon A, 23.34 for Lotrafilcon B, and 22.7 for Comfilcon A. These describe variability among scores and help distinguish score dispersion from uncertainty about a group mean or a mean difference. The confidence level and construction method for the intervals are not reported in the registry record. The registry also does not report a threshold for a clinically meaningful difference, so statistical precision cannot resolve clinical importance.

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 accompanying planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses a stated fraction of the observed effect. These are planning illustrations based on the observed contrast, not the trial’s own original design assumptions, which are not reported in the registry record. This is not observed power.

For the Lotrafilcon B comparison, planning for 100% of the observed effect gives 57 participants per arm for 80% power and 76 participants per arm for 90% power. Planning for 75% of the observed effect gives 101 participants per arm for 80% power and 135 participants per arm for 90% power. Planning for 50% of the observed effect gives 226 participants per arm for 80% power and 303 participants per arm for 90% power.

For the Comfilcon A comparison, planning for 100% of the observed effect gives 740 participants per arm for 80% power and 991 participants per arm for 90% power. Planning for 75% of the observed effect gives 1,316 participants per arm for 80% power and 1,761 participants per arm for 90% power. Planning for 50% of the observed effect gives 2,960 participants per arm for 80% power and 3,962 participants per arm for 90% power.

The 80% and 90% columns describe target probabilities of detecting the stated effect under the planning assumptions if that effect is real. Higher target power requires more participants under the same assumptions. Smaller effects also require more participants, as reflected by the increasing requirements when planning for a smaller fraction of the observed effect. These figures are illustrations, not evidence about the probability that the completed study detected an effect.

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 = -11.400; pooled standard deviation σ = 21.624.
2. n = 2 × (1.96 + 0.842)² × 21.624² / -11.400² = 56.5, rounded up to 57 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 <- -11.4                      # observed difference in means
sigma <- 21.6242132804872                     # 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(2394756)
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 = 57 (80% power), 76 (90% power)
 75% of observed effect: n per arm = 101 (80% power), 135 (90% power)
 50% of observed effect: n per arm = 226 (80% power), 303 (90% power)
power.t.test: 57.5 
Simulated power at n = 57 per arm: 0.798 (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 posts two pairwise comparisons for the primary outcome and identifies both p-values as unadjusted. It also records two outcome measures, but no secondary outcomes are posted. An unadjusted p-value does not account for the number of comparisons or outcomes considered. The registry record does not report whether an adjustment was planned or applied, nor does it describe a prespecified hierarchy for interpreting results. The values should therefore be read as individual comparison results without assuming that family-wise error or another multiplicity concern was addressed.

The primary-outcome population is restricted to subjects who completed all study visits without a major protocol deviation. The registry does not report how many participants were excluded from that population, the reasons for any exclusions, or how missing outcome measurements were handled. It is not clear whether the primary analysis followed an intention-to-treat approach, a per-protocol approach beyond the stated population definition, or another analysis population.

The record lists 37 observations for each lens outcome summary, while enrollment is 52 and the safety groups list 42 at risk for each lens. Because this is a crossover study, these counts should not be added together or treated as separate participants without further information. The record does not explain the relationship between the counts, whether all participants contributed data for every period, or how incomplete sequences were handled.

Statistical details that could clarify these issues—including the analysis model, handling of repeated observations, missing-data method, and multiplicity strategy—are not reported in the registry record. This limits the ability to judge whether the uncertainty estimates account for crossover dependence or whether the inferential results follow a prespecified plan.

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.

Most frequent non-serious adverse event terms

The registry lists 42 participants at risk for serious adverse events in each lens group. The serious adverse event count is 0 for Senofilcon A, 0 for Lotrafilcon B, and 0 for Comfilcon A. The registry does not list serious adverse event terms, and deaths are not reported in the registry record.

These counts describe what is recorded for the listed groups; they do not establish that the risk is absent. With no serious events recorded in these groups, the data do not estimate a comparative risk difference with useful precision. The crossover design and the safety group counts also mean that the group entries should not be interpreted as independent sets of participants without further information.

The record separately lists other adverse events affecting 3 participants in the Senofilcon A group, 0 in the Lotrafilcon B group, and 2 in the Comfilcon A group, with 42 at risk in each. Those are not serious adverse event counts and should not be conflated with the serious-event figures.

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

The posted primary outcome describes subjective comfort scores after lens wear. The group means were 65.0 for Senofilcon A, 53.6 for Lotrafilcon B, and 61.9 for Comfilcon A. The pairwise estimates report a mean difference of -11.4 for Lotrafilcon B relative to Senofilcon A and -3.1 for Comfilcon A relative to Senofilcon A. These are group-level contrasts, not predictions of any individual’s score.

The confidence interval for the Lotrafilcon B contrast lies below zero, whereas the interval for the Comfilcon A contrast includes zero. The latter result leaves uncertainty about the direction of the mean difference. Neither the intervals nor the p-values indicate whether a difference meets a threshold of importance to participants; no such threshold is reported in the registry record.

These findings do not establish that a lens is medically appropriate or preferable, and they do not show how scores might differ in other populations or under other conditions of lens wear. The study focused on heavy digital-device users and the posted primary endpoint was measured at the 1-Day Follow-up. Broader effects, longer-term outcomes, and outcomes beyond the recorded measures are not established by these results.

The unmasked crossover design may offer within-participant comparisons, but the posted record does not state how the statistical analysis handled pairing, sequence, or period effects. The estimates should therefore be interpreted as the registry’s reported comparisons, with those methodological details unresolved. The safety entries likewise describe recorded event counts; zero serious adverse events in a group does not prove that serious events cannot occur.

16. Why This Trial Matters Statistically

This trial illustrates why clinical interpretation of a continuous patient-reported outcome requires more than reading group means. The observed variability is notable, and the estimated contrasts have different levels of uncertainty. Looking at the confidence intervals alongside the estimates helps distinguish a clear direction in the posted interval from a result that remains compatible with values on either side of zero.

The crossover design is also statistically important. Repeated measurements from the same participant are related, and methods that account for this relationship may produce different uncertainty estimates than methods that treat every observation as independent. The registry description establishes the crossover structure but does not report the model used for the comparisons. That gap matters when assessing how well the posted intervals and p-values reflect the design.

The record also highlights the difference between statistical evidence and clinical meaning. No clinically meaningful score difference is specified, and the unadjusted p-values do not address multiplicity. The estimates can describe observed differences, but those features constrain how confidently they can be translated into broader conclusions. Finally, the planning illustrations show how the participant requirements depend on the effect size chosen for planning; they are not evidence of the completed study’s power or design rationale.

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 does not report the detailed statistical model, the confidence-interval construction method, or whether the comparisons account for within-participant pairing in the crossover design. It also does not describe sequence generation, allocation concealment, lens order, washout arrangements, or possible period and carryover effects. Without those details, the adequacy of the reported analysis for the design cannot be assessed.

The primary outcome population is defined by completion of all study visits without a major protocol deviation, but the record does not state the number or reasons for exclusions from that population. The relation between the enrollment entry, the 37 observations in each outcome group, and the 42 at-risk safety entries is not explained. Missing-data handling and the analysis population beyond the stated definition are not reported.

The study was unmasked, and the outcome is a participant-reported measure. The registry does not report a meaningful-difference threshold for the score, a multiplicity strategy, or a detailed analysis plan. The record also has no posted secondary outcomes, despite listing two outcome measures. These reporting gaps limit assessment of the full outcome set and the clinical importance of the posted contrasts.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Investigation of Ocular Signs & Symptoms in Wearers Fitted With Contact Lenses Following Digital Device Use — NCT02394756.
• Registry record last updated 2018-06-19; status last verified 2017-03.
• Results first posted 2017-04-25.
• 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 registry record describes a randomized, unmasked crossover study of three contact lens types among heavy digital-device users. It was recorded as completed, with enrollment of 52. The primary outcome was Subjective Overall Comfort measured by CLUE at the 1-Day Follow-up among subjects who completed all visits without a major protocol deviation.

The posted means were 65.0 for Senofilcon A, 53.6 for Lotrafilcon B, and 61.9 for Comfilcon A. The reported mean differences versus Senofilcon A were -11.4 for Lotrafilcon B and -3.1 for Comfilcon A. The record also lists no serious adverse events in the three lens groups and does not report deaths.

Important analysis details—including crossover modeling, missing-data handling, and multiplicity procedures—are not reported in the registry record.