Clinical Evaluation of a Silicone Hydrogel Daily Wear Monthly Replacement Contact Lens: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Evaluation of a Silicone Hydrogel Daily Wear Monthly Replacement Contact Lens (NCT04422990), a randomized na study. The primary outcome is Least Squares Mean Contact Lens Corrected Distance Visual Acuity (CLCDVA) at Week 1 Follow-Up.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-masked, parallel-group device study, with a completed status. The sponsor is Alcon Research. The listed phase is NA. The record gives a study start date of 2020-10-01 and a primary completion date of 2021-02-22, and lists enrollment as 158. Its stated purpose was to evaluate the safety and performance of an investigational soft contact lens against a commercially available soft contact lens when worn in a daily-wear modality.

The two lens groups were Lehfilcon A, labeled LID018869, and Comfilcon A, labeled Biofinity. Both descriptions specify lenses worn in both eyes during waking hours only, monthly planned replacement over 3 months, and nightly cleaning and disinfection with CLEAR CARE. The intervention list also identifies CLEAR CARE as a device. These descriptions establish the intended wear and care conditions recorded for the comparison; further details about adherence, deviations, or actual wearing time are not reported in the registry record.

For the primary and secondary hypothesis testing, the registry describes a predefined subset with best-corrected visual acuity of 20/20 or better in each eye at baseline or dispense, combined with subjects from another similar completed registration study. The primary outcome arms list n=88 for Biofinity and n=170 for LID018869. Those analysis counts should be read alongside, not substituted for, the enrollment figure: the record explicitly describes combining data from another study for the planned testing. Further detail on how subjects from the two studies were combined, or whether study source was accounted for in the models, is 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 158 enrolled, 11 subjects were not dispensed study lenses and were exited from the study as screen failures. This reporting group includes all subjects who were dispensed study lenses (147).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PP: A predefined subset of subjects (those with BCVA of 20/20 or better in each eye at baseline/dispense) from another similar completed registration study, CLY935-C010 (NCT04178720) was combined with this study to attain adequate power for the planned hypothesis testing of the primary and secondary endpoints. This included 49 subjects from CLY935-C012 and 39 subjects from CLY935-C010 in the Biofinity group and 92 subjects from CLY935-C012 and 78 subjects from CLY935-C010 in the LID018869 group.

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: Per Protocol (PP): All randomized subjects exposed to any study lenses evaluated in this study with at least one post-baseline (post-dispense) contact lens corrected distance visual acuity (CLCDVA) assessment, minus all data/subjects that met any of the pre-defined critical deviation or evaluability criteria.

6. Primary Endpoint

The registry lists the primary outcome as Least Squares Mean Contact Lens Corrected Distance Visual Acuity (CLCDVA) at Week 1 Follow-Up, measured over Week 1 Follow-Up.

The primary endpoint is least squares mean contact lens corrected distance visual acuity (CLCDVA) at week-one follow-up, expressed in logMAR. Visual acuity was assessed for each eye individually with the study lenses in place, using a letter chart. Measurements were collected in Snellen notation and converted to logMAR. The registry explains that a logMAR value of 0 corresponds to 20/20 Snellen visual acuity, with lower logMAR values indicating better visual acuity.

Distance visual acuity is relevant to the stated evaluation because it describes visual performance while the study lenses are being worn. Reporting the least squares mean presents a model-based group average, rather than simply describing an unadjusted average of recorded observations. The registry identifies the primary time point as week-one follow-up. It does not report further details about how the two eyes were incorporated into the primary analysis, how observations from subjects with data at different visits were handled, or which model terms were used beyond identifying a mixed effects repeated measures model.

The endpoint is a continuous measure. Its interpretation depends on both the estimated difference and its uncertainty, as well as the study’s non-inferiority criterion. The record does not state that criterion’s margin, which is necessary for judging whether a confidence interval satisfies a non-inferiority rule.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary analysis is identified as a mixed effects repeated measures model, with the reported parameter being the least squares mean difference. The secondary sponsor analysis is identified as a generalized linear mixed model, reporting a difference in proportion. The registry does not give the model specifications, covariates, correlation structure, handling of missing observations, or other implementation details. The explanations below describe the general statistical ideas, not unreported features of this trial’s analyses.

What does a least squares mean represent?

In general, a least squares mean is a model-based estimate of a group average. It can differ from a raw arithmetic average because the model may account for specified features of the data. The value and interpretation depend on which terms the model includes and how the data are structured. Since those details are not reported in the registry record, the displayed least squares means should be interpreted as the reported model-based summaries, without assuming a particular adjustment.

A standard error describes the estimated sampling uncertainty of an estimate under the analysis model. The record displays standard errors of 0.0 for both primary arm estimates. Because this is a rounded display, it should not be taken to mean that there is literally no uncertainty. The confidence interval for the between-group difference provides additional information about the reported uncertainty.

How should the confidence interval be read?

In general, a confidence interval gives a range of values compatible with the data and statistical model under the method used to construct it. It is not a guarantee that the true effect lies within the particular interval, nor does it measure the probability that the treatment effect is a specific value. A narrower interval indicates greater precision on the stated scale, while the interval’s position relative to a clinically or scientifically specified threshold matters for the decision being studied.

For a non-inferiority question, the relevant threshold is the non-inferiority margin. The margin defines how much worse the experimental group may be, on the chosen scale, while still meeting the criterion. It must be specified independently of the observed result. The registry record identifies the analyses as non-inferiority analyses but does not report the margin. Consequently, the confidence intervals can be described, but cannot be compared with the required threshold from the information recorded.

Why use a repeated measures model?

As a general method, a repeated measures model can analyse observations from the same participant across more than one measurement occasion while accounting for the fact that those observations may be related. Mixed effects models can represent such dependencies through model components for repeated or grouped data. The record’s identification of this method tells readers the broad class of analysis used, but does not establish which visits, covariance assumptions, or participant-level effects were included. Those details are not reported in the registry record.

The primary outcome is named for week-one follow-up, while the analysis is described as repeated measures. The registry does not explain how the other repeated observations contributed to the week-one estimate, or whether the model included data from additional follow-up times. It would therefore be unwarranted to infer the model’s exact data structure or the influence of any other visit.

What does the secondary analysis estimate?

The secondary endpoint is binary at the subject level: whether the subject achieved the stated visual-acuity threshold in each eye. A difference in proportions compares the share meeting that definition across groups. A generalized linear mixed model is a general modelling approach that can represent binary outcomes and account for specified grouping or correlation structures. The registry does not report its link function, covariates, or other model details, so those cannot be inferred from the method label alone.

The posted secondary recalculation is an unadjusted comparison derived from summary counts. It is useful as a descriptive check, but it is not the same analysis as the sponsor’s generalized linear mixed model. An unadjusted calculation does not account for model terms or clustering unless those are explicitly built into the calculation. The recalculated p-value is also unadjusted for multiple testing. Its interpretation is therefore more limited than a prespecified, fully described primary analysis.

What is over-dispersion, in general?

In general, over-dispersion occurs when observed variability in outcomes exceeds what a statistical model assumes. For binary or count outcomes, unaccounted extra variation can make standard errors too small and confidence intervals too narrow. Mixed models can sometimes represent variation or dependence that a simpler model does not capture, but the appropriateness of a particular method depends on the data and specification. The registry does not report a test for over-dispersion or enough model detail to assess it for these results.

How should the planning illustrations be read?

The planning illustrations use the observed effect as a basis for estimating participants per arm under stated assumptions. The record specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation, with planning effects set to 100%, 75%, or 50% of the observed effect. For 100% of the observed effect, the listed requirements are 962 participants per arm for 80% power and 1,287 participants per arm for 90% power. For 75% of the observed effect, they are 1,525 and 2,040 participants per arm, respectively. For 50% of the observed effect, they are 3,011 and 4,030 participants per arm, respectively.

These are planning illustrations, not observed power and not the trial’s stated design justification. The record explicitly describes them as computed from the observed effect, rather than from the trial’s own design. The sample-size justification and the trial’s original planning assumptions are not reported in the registry record. A planning estimate also depends on its assumptions; it should not be treated as evidence that a trial was adequately powered or that an effect is present.

10. Analyses Reported by the Sponsor

For the primary endpoint, the sponsor’s reported mixed effects repeated measures analysis gives a least squares mean difference of 0.00 logMAR, with a 95% confidence interval from -0.01 to 0.01. The recalculation fields do not provide a separate recalculated primary comparison, and the record reports no p-value for the sponsor’s primary analysis. The most appropriate account of the primary comparison is therefore the sponsor’s posted model-based result, while noting that the non-inferiority margin is not reported.

For the secondary endpoint, the sponsor reports a model-based difference in proportion of -0.01, with a 95% confidence interval from -0.04 to 0.02. The unadjusted recalculation from the posted summary statistics gives p=0.362. The recalculation is a separate, simpler analysis and is not a reproduction of the generalized linear mixed model. It should not be substituted for the sponsor’s estimate or used to claim that the analyses are identical. The record does not flag a discrepancy, but the distinct methods and displayed rounding mean that the results should be interpreted according to the analysis each represents.

For neither sponsor analysis does the registry report a p-value. The primary and secondary model results are described as non-inferiority analyses, but the margin is absent. As a result, readers can compare the posted estimates and intervals descriptively, but cannot verify the formal non-inferiority decision from the registry record alone.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and one posted secondary endpoint, but does not report a strategy for controlling multiplicity. It is not stated whether the secondary result was treated as exploratory, whether endpoints were tested in a fixed order, or whether any adjustment was applied to sponsor analyses. Without that information, secondary findings should be interpreted cautiously; the unadjusted recalculation is not evidence that accounts for multiple comparisons.

Details about missing outcome data are also not reported in the registry record. The record does not say how many endpoint observations were missing, why data might have been missing, whether the analysis used imputation, or how incomplete follow-up was handled in the models. A mixed effects method can use available observations under its modelling assumptions, but the method label alone does not reveal the missing-data approach or establish that those assumptions hold.

The analysis population description is important. The registry says that a predefined subset of subjects with best-corrected visual acuity of 20/20 or better in each eye at baseline or dispense was combined with subjects from another similar completed registration study to attain adequate power for planned testing. It does not provide further details about the combination, including the role of study source in the analysis. The outcome arms list n=88 for Biofinity and n=170 for LID018869, while enrollment for this record is listed as 158. The registry’s description of combining data from another study means the outcome counts should be understood in the context of that analysis population, rather than as a direct restatement of this record’s enrollment.

The record does not report a protocol-based sample-size justification, a non-inferiority margin, interim analyses, or a full statistical analysis plan. Those omissions limit independent assessment of the intended testing strategy, the analysis population, and whether the reported uncertainty addresses the study’s prespecified decision criteria.

12. 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 safety record lists serious adverse events and other adverse events for separate categories: pre-treatment, Biofinity ocular, Biofinity non-ocular, LID018869 ocular, and LID018869 non-ocular. The reported serious adverse event counts are zero in each category. The reported counts for other adverse events are also zero in each category, and deaths are listed as zero throughout.

The numbers at risk differ across the listed categories: the record gives 147 for pre-treatment, 100 for Biofinity ocular, 50 for Biofinity non-ocular, 194 for LID018869 ocular, and 97 for LID018869 non-ocular. These are category-specific counts and should not be added together or treated as a single participant total. The record does not explain the category denominators or the relationship between them.

Zero reported events means that the registry’s posted counts contain no events in those categories; it does not prove that no safety events of any kind occurred or establish safety beyond the recorded reporting. The record does not provide event-term detail, follow-up completeness, or an explanation of the adverse-event collection and attribution procedures. These figures should therefore be read as a limited description of posted safety reporting, not as a comprehensive estimate of risk.

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

The primary result is a model-based comparison of week-one contact lens corrected distance visual acuity. The reported least squares means are -0.06 logMAR in both groups, and the reported difference is 0.00 with a 95% confidence interval from -0.01 to 0.01. These values describe the estimate and its precision as reported; they do not establish that the groups are identical or that one lens is better.

The registry calls the analyses non-inferiority analyses, but does not report the non-inferiority margin. That omission prevents readers from checking whether the primary confidence interval meets the formal criterion. The results can therefore be described as showing a small estimated difference with a narrow reported interval, but they do not, by themselves, support a verified non-inferiority conclusion.

The secondary threshold-based outcome offers a related view of week-one acuity, but it does not replace the primary analysis. Its sponsor-reported model estimate and the unadjusted recalculation are different analyses. The recalculation is not adjusted for multiple testing, and the registry does not report the sponsor’s multiplicity procedure. Neither result answers questions about longer-term performance, outcomes outside the stated visual-acuity measures, or use beyond the recorded wear conditions.

The analysis population also needs context: the registry describes a predefined subset combined with subjects from another similar completed registration study. The outcome-arm counts therefore do not simply represent enrollment in this record. Further details about the combined analysis and handling of missing data are not reported.

Finally, the zero adverse-event counts are limited to the categories and reporting recorded in the registry. They should not be interpreted as proof of absence of risk. Taken together, the posted results describe the reported statistical comparisons and safety counts, while important information needed to verify the non-inferiority decision and assess broader implications is not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a compact headline estimate and the information needed to interpret a formal non-inferiority claim. The primary point estimate is 0.00 logMAR, and its confidence interval is narrow as displayed. Yet a non-inferiority conclusion depends not only on the estimate and its precision, but also on the prespecified margin. Because the margin is not reported, readers cannot independently assess the central decision rule.

The record also highlights the importance of distinguishing the enrolled study population from the analysis population. Enrollment is listed as 158, while the arm-level outcome counts are 88 and 170. The registry explains that the planned hypothesis testing used a predefined subset combined with subjects from another similar completed registration study. This context matters when interpreting denominators and when considering how well the analysis population reflects the trial record alone.

The secondary result illustrates another general issue: an unadjusted recalculation from summary data is not interchangeable with a sponsor’s mixed-model analysis. The statistical method, data structure, adjustment strategy, and multiplicity plan can affect interpretation. A recalculation can offer a useful descriptive cross-check, but it is not a substitute for the reported model or its full specification.

The planning illustrations also need to be kept separate from observed trial findings. They estimate participants per arm under stated assumptions and fractions of the observed effect; they are not observed power, nor do they document the trial’s original design justification. These distinctions help prevent numerical summaries from being read as stronger evidence than the registry record supports.

15. 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 trial-specific limitations restrict independent interpretation. The non-inferiority margin is not reported, even though both posted sponsor analyses are labeled non-inferiority analyses. Without that margin, the formal criterion cannot be checked against the confidence intervals. The registry also does not report p-values for the sponsor’s primary or secondary analyses.

The analysis population is described as a predefined subset with best-corrected visual acuity of 20/20 or better in each eye at baseline or dispense, combined with subjects from another similar completed registration study. Details about study pooling, source effects, and the analysis models’ handling of the combined data are not reported. The listed enrollment and outcome-arm counts consequently require that context, but the record does not explain the counts further.

Model specifications are limited to the method labels. The registry does not report covariates, model terms, the correlation structure, or how observations from the two eyes were incorporated. It does not explain the handling of missing data, protocol deviations, or incomplete follow-up. The statistical analysis plan, multiplicity approach, and interim-analysis information are not reported in the registry record.

For safety, the posted adverse-event categories contain zero reported serious and other adverse events, but the record does not provide event-term detail or explain the category-specific denominators. The zero counts should not be generalized beyond the registry’s reporting.

The study’s recorded outcomes focus on visual acuity at week-one follow-up, with one threshold-based secondary measure. These results do not establish outcomes at unreported time points or address outcomes not listed in the record. The planning illustrations are explicitly based on the observed effect and stated assumptions; they are not the trial’s own sample-size justification.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Evaluation of a Silicone Hydrogel Daily Wear Monthly Replacement Contact Lens — NCT04422990.
• Registry record last updated 2022-03-29; status last verified 2022-03.
• Results first posted 2022-02-24.
• 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.

19. Record Summary

NCT04422990 is a completed, randomized, double-masked, parallel-group device study sponsored by Alcon Research. It compared Lehfilcon A silicone hydrogel contact lenses with Comfilcon A (Biofinity) under daily-wear conditions, with monthly planned replacement over 3 months and nightly cleaning and disinfection using CLEAR CARE. Enrollment is listed as 158.

The primary outcome was week-one least squares mean CLCDVA in logMAR. The sponsor reports a difference of 0.00, with a 95% confidence interval from -0.01 to 0.01. The registry describes the analysis as non-inferiority but does not report the margin. The listed analysis population includes a predefined subset combined with subjects from another similar completed registration study. One secondary visual-acuity threshold outcome and safety counts are also posted, with zero reported adverse events in the listed categories.