Clinical Evaluation of Etafilcon A Contact Lenses Using a Novel Molding Process: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Evaluation of Etafilcon A Contact Lenses Using a Novel Molding Process (NCT03605303), a randomized na study. The primary outcome is Overall Comfort Scores.

2. Clinical Question

3. Trial Design

The study was registered as a randomized, double-masked, crossover trial. Its brief summary describes a multi-site, group sequential, adaptive design with a 2×2 crossover and 1-week dispensing periods. Participants were to wear both test and control lenses bilaterally, in a random order, as daily disposables. Each wearing period was planned to last 1-week, with a wash-out period of 1 week between periods. The two registered sequences were Test/Control and Control/Test.

The control was etafilcon A made using the current molding process, identified as 1-Day ACUVUE® MOIST. The test was etafilcon A made using a novel molding process and identified as an investigational contact lens. Double masking indicates that the study was intended to mask participants and relevant study personnel, but the registry record does not describe how masking was maintained.

Enrollment was 3. The study start date was 2018-07-03, and the primary completion date was 2018-07-05. Its status is TERMINATED. The reason for termination is not reported in the registry record. Although the brief summary describes group sequential and adaptive features, the record does not report how those features were to be implemented, including any planned interim analyses or decision rules. The crossover procedures are described as intended study conduct; they do not establish that all planned periods were completed by participants.

4. Participant Flow and Accounting

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

Period 1

Reasons for not completing this period:

Period 2

Analysis population for the primary outcome, as defined in the registry: Study terminated early. No data was analyzed.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

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

The primary endpoint was Overall Comfort Scores at 1-Week Follow-up. Comfort was to be assessed using the Contact Lens User Experience (CLUE) questionnaire, a validated patient-reported outcomes questionnaire for soft contact lenses. The registry description says CLUE assesses comfort, vision, handling, and packaging. Its composite scores are derived using Item Response Theory and follow a normal distribution, with a population average score of 60 and SD 20. Higher scores indicate a more favorable response.

A patient-reported measure can capture the wearer’s experience directly, rather than relying only on a clinical or device-based measurement. That makes comfort a relevant outcome for a contact lens comparison. The registry description states that a 5-point increase in an average CLUE score translates into a 10% shift in the distribution of scores for the population of soft disposable contact lens wearers. This describes the questionnaire’s score interpretation, not a finding from this trial.

No comfort scores, treatment contrast, or variability estimate were analyzed for this study. The endpoint definition therefore explains what the trial intended to measure, but it does not establish whether either lens received more favorable comfort ratings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered design is a randomized, double-masked crossover. In general, a crossover design lets participants receive each of the compared interventions in different periods. This can make within-participant comparisons informative because each participant contributes experience under both conditions. It also means that the analysis must respect the paired structure; treating observations from the same participant as independent would not reflect the design. Here, the planned sequences were Test/Control and Control/Test, with bilateral daily disposable wear during each 1-week period and a wash-out period of 1 week between periods.

What does randomization contribute?

Random assignment of treatment order is intended to reduce systematic differences between the sequence groups and to make treatment order less predictable. It does not guarantee that the groups will be alike, particularly when enrollment is limited. The registry record names the two sequences but does not report their realized participant counts or whether every participant completed both periods. It also does not report the method used to generate or conceal the random sequence.

Why can period and carryover matter?

In general, a crossover comparison can be influenced by period effects, such as changes in participants’ experience over time, and by carryover, when experience with an earlier treatment affects measurements in a later period. A wash-out period is intended to help separate periods, but its presence alone does not demonstrate that carryover was absent. The registry record does not report how period, sequence, or carryover effects were to be assessed or handled. Nor does it give the planned statistical model for the comfort outcome.

What does the endpoint scale represent?

CLUE composite scores are described as derived using Item Response Theory (IRT). In general, IRT uses patterns of responses to questionnaire items to estimate an underlying attribute, such as a patient-reported experience. The registry describes CLUE scores as following a normal distribution, with a population average score of 60 and SD 20, and says higher values indicate more favorable responses. These are characteristics and interpretation guidance for the instrument; they are not observed scores from this trial. The record does not describe the scoring details used for trial participants or how incomplete questionnaire responses would be handled.

What can the group sequential and adaptive description establish?

The brief summary calls the study group sequential and adaptive. In general, group sequential designs may assess accumulating evidence at planned stages, and adaptive designs may allow specified changes based on interim information. These approaches require prespecified procedures to guide when evidence is reviewed and what actions are permitted. The registry record does not report the number or timing of any interim analyses, stopping boundaries, adaptation rules, or related adjustments to statistical inference. It would therefore be inappropriate to infer a particular monitoring plan or to attribute termination to a statistical stopping rule.

What do the planning assumptions mean?

The registry record describes sample-size planning illustrations using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. Such values are planning illustrations, not observed power and not trial findings. Planning sample sizes cannot replace the actual analysis. The record also says no data were analyzed, and it does not report a trial-specific sample-size justification or explain the planned statistical analysis. The posted assumptions alone do not establish what design choices were used when the trial was planned.

Why are no recalculated comparisons available?

A recalculated comparison would require posted summary statistics for the outcome, such as suitable group or paired summaries. The registry record reports no analyzed comfort data, so there is no trial effect estimate to recalculate or compare with a sponsor analysis. There are no reported estimates, confidence intervals, or test statistics from which to assess agreement or discrepancy. The statistical interpretation must therefore remain focused on the intended design, endpoint, and missing analysis rather than on a numerical treatment effect.

10. Multiplicity, Missing Data and Analysis Populations

The record does not report a multiplicity strategy. CLUE is described as assessing comfort, vision, handling, and packaging, while the registered primary outcome is Overall Comfort Scores. The presence of several questionnaire attributes does not establish that all were analyzed as confirmatory outcomes. The registry record reports two outcome measures but no analyses, and it does not state which outcomes were designated secondary or how any multiple comparisons were to be handled.

The study is described as group sequential and adaptive, but the procedures needed to understand the impact of repeated looks or adaptations are not reported in the registry record. In general, repeated testing or selecting analyses based on accumulating data can affect the interpretation of conventional p-values and confidence intervals unless the plan accounts for those features. No interim analysis schedule, stopping boundaries, or inferential adjustments are reported, so their use cannot be evaluated.

Missing-data procedures are also not reported in the registry record. It does not state how incomplete CLUE questionnaires, missed visits, or incomplete crossover periods were handled, or whether any imputation was planned. The record does not specify an intention-to-treat, per-protocol, or other analysis population. It also does not report whether participants with data from only one lens period would have been included in the primary analysis.

These omissions are particularly relevant to a crossover study because a paired comparison depends on the availability and handling of observations across periods. With no analyzed data, the extent of missingness and its influence on any result cannot be assessed.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The adverse-event record reports no serious adverse events in the Test group, with 2 participants at risk, and none in the Control group, with 1 participant at risk. It also reports no other adverse events in either group, using those same group-specific at-risk counts. Deaths are reported as 0 in both groups. No serious adverse event terms are listed.

These figures are descriptive safety counts, not estimates of comparative risk. The registry record states that the study was terminated early and that no data were analyzed; the adverse-event entries do not provide a formal between-group safety comparison. The at-risk counts should be read as reported for each group and should not be treated as a complete account of exposure across the planned crossover periods.

Zero reported events in these groups does not establish that an event is impossible or that the lenses have equivalent safety. The limited enrollment and early termination restrict what can be learned from the absence of recorded events. Event definitions, collection details, and exposure timing beyond the reported study design are not reported in the registry record.

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

The record establishes that a randomized, double-masked crossover study was planned to compare comfort scores for an investigational etafilcon A lens made with a novel molding process and a control lens made with the current molding process. It identifies CLUE Overall Comfort Scores at 1-Week Follow-up as the primary outcome and describes the intended wearing periods and wash-out. It also records enrollment of 3 and a TERMINATED status.

It does not establish whether comfort ratings differed between the lenses. No outcome data were analyzed, and no group scores, treatment contrast, confidence interval, or test result is reported. The planned use of a patient-reported questionnaire cannot be interpreted as a favorable or unfavorable result for either lens. The registry’s CLUE reference values describe the questionnaire, not participants’ responses in this trial.

The status and lack of analysis also do not explain why the study ended. The reason for termination is not reported in the registry record. It would be unjustified to infer that the trial stopped because of a benefit, harm, futility, recruitment issue, or statistical boundary. The brief description of an adaptive, group sequential design does not supply those missing details.

The safety entries report no serious events, other events, or deaths in the stated groups, but those small at-risk counts and the early termination do not provide a broad assessment of safety. In statistical terms, a lack of reported events is not the same as evidence of equivalence or evidence that an event cannot occur.

Accordingly, the meaningful conclusion is about the limits of the available record: it documents a planned comparative question and a trial that ended without analyzed comfort results. It cannot answer the comparative question or support a treatment recommendation.

13. Why This Trial Matters Statistically

This study raises useful statistical issues because its intended comparison is a crossover rather than a parallel-group trial. Each participant was to wear both lenses, so the planned comparison could use within-participant information. That structure can improve efficiency when paired measurements are available, but it requires analysis that reflects pairing and considers period and carryover effects. The registry record does not report how those issues were to be addressed.

The design description also calls the study adaptive and group sequential. Such features can be statistically important because the timing and rules for reviewing accumulating evidence can influence estimation and testing. Without reported interim procedures or adaptation rules, the design label alone is not enough to assess those implications. This illustrates why operational details are needed alongside broad design terminology.

Most importantly, a clearly defined endpoint does not guarantee an interpretable result. The record specifies a validated patient-reported comfort measure and gives context for interpreting its scale, but it reports no analyzed participant scores. Without an observed contrast and an uncertainty estimate, readers cannot judge the direction, magnitude, or precision of a treatment comparison.

The record is therefore instructive as a distinction between a planned statistical question and evidence answering that question. Enrollment, endpoint definitions, and a randomized design describe the study’s intent; they do not substitute for analyzed outcomes. Termination and the absence of analysis sharply limit what can be learned from this record, while leaving the reason for termination unknown.

14. 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 main trial-specific limitation is that the study was terminated early and no data were analyzed. Although the record reports enrollment of 3, it gives no analyzed comfort scores, treatment comparison, or uncertainty estimate. The primary clinical question therefore remains unanswered in the registry record.

The record does not report why the study was terminated. It also does not give participant characteristics, realized sequence allocation, period-level completion, or the number of participants with usable paired outcome data. Enrollment alone cannot show how much information was available for a crossover analysis.

Important analysis details are absent. The statistical model, handling of period and sequence effects, assessment of carryover, missing-data procedures, and analysis population are not reported in the registry record. Although the brief summary describes group sequential and adaptive features, the interim schedule, stopping rules, and adaptation procedures are not reported. These omissions prevent evaluation of how the intended analysis would have addressed the design.

The record describes CLUE and its general score interpretation, but does not report study-specific questionnaire data or explain how incomplete responses would be treated. Participant ages and other demographic characteristics are not reported; the questionnaire’s validation population should not be mistaken for the enrolled population.

Finally, the adverse-event entries contain no reported events but involve limited at-risk counts, and the record does not provide a detailed account of exposure across crossover periods. These entries cannot establish comparative safety or rule out uncommon outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Clinical Evaluation of Etafilcon A Contact Lenses Using a Novel Molding Process — NCT03605303.
• Registry record last updated 2019-08-28; status last verified 2019-08.
• Results first posted 2019-07-24.
• 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.

18. Record Summary

NCT03605303 is a randomized, double-masked crossover study of etafilcon A contact lenses using a novel molding process compared with a current-molding control. The planned design included Test/Control and Control/Test sequences, bilateral daily disposable wear for 1-week per lens, and a wash-out period of 1 week. The primary outcome was CLUE Overall Comfort Scores at 1-Week Follow-up.

The registry reports enrollment of 3, a start date of 2018-07-03, a primary completion date of 2018-07-05, and status TERMINATED. No data were analyzed. The record therefore has no reported comfort comparison or inferential result. It reports no serious adverse events, other adverse events, or deaths in the stated groups. The reason for termination and key details of the planned statistical analysis are not reported in the registry record.