Clinical Evaluation of a Multifocal Contact Lens on Symptomatic Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Evaluation of a Multifocal Contact Lens on Symptomatic Patients (NCT01016652), a randomized na study. The primary outcome is Subject Reported Overall Vision Quality Using (CLUE)TM Questionnaire.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, double-masked, crossover trial of an etafilcon A multifocal contact lens and an etafilcon A sphere contact lens. The stated condition is presbyopia, and the brief summary says the study evaluated the effect of a multifocal contact lens on symptomatic patients. Enrollment is listed as 49. The registry lists 49 participants for each treatment arm; because this is a crossover design, those arm entries should not be added to infer a total number of distinct participants.

The two randomized sequences differed in the order of lens use. One sequence wore the multifocal lens during period 1 and the sphere lens during period 2; the other sequence wore the sphere lens during period 1 and the multifocal lens during period 2. The registry record does not report the duration of each period, whether there was a washout between periods, or how the order was generated or concealed. Those details should not be assumed from the design label alone.

The primary outcome was participant-reported overall vision quality using the CLUE Questionnaire at week 4. The record also lists outcomes concerning near vision symptoms, lens comfort, comfortable wearing time, and benefit from a binocular accommodative flipper. Numerical results are posted for some, but not all, of these secondary outcomes. The registry reports six outcome measures and two analyses; further details of the analysis set-up are not reported in the registry record.

The study status is completed. The registry record does not report a phase, which is listed as not applicable. Its description does not identify a parallel-group comparison or provide a protocol rationale for the chosen design. Although crossover trials can compare conditions within participants, the analysis must account for the paired structure and possible period or sequence effects. The posted primary analysis is described as a mixed models analysis, but its full model specification 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: A screening questionnaire (Near Vision Questionnaire, (NVQ)) was used to recruit subjects and to provide information about the wider population.

Period 1

Period 2

Analysis population for the primary outcome, as defined in the registry: Analysis was on those subjects enrolled, randomized into one of two randomized arms, and who completed the study.

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 Subject Reported Overall Vision Quality Using (CLUE)TM Questionnaire, measured over week 4.

The primary endpoint is participant-reported overall vision quality on the Contact Lens User Experience (CLUE) Questionnaire at week 4. The registry describes CLUE as a validated patient-reported outcomes questionnaire for assessing experiences with soft, disposable contact lenses in the US among people ages 18-65. It states that scores follow a normal distribution with a population average score of 60 and SD 20, and that scores range from 0-120. Higher scores indicate a more favorable or positive response. These are properties described for the questionnaire; they do not establish that the trial participants had a particular age or score distribution.

A patient-reported outcome captures the participant’s own assessment rather than relying only on an external observer. Overall vision quality is relevant to a contact lens evaluation because it describes the experience being studied from the participant’s perspective. The registry reports the endpoint using medians and inter-quartile ranges for each lens condition. It also reports a mixed models analysis of the mean difference in final values. Those are different summaries: the medians describe the middle of each posted arm distribution, while the model result estimates a mean contrast under the reported analysis.

The primary endpoint is not, by itself, a complete account of lens comfort, symptoms, or visual function. Those topics appear among the secondary outcomes. Nor does a questionnaire score alone establish a clinical benefit or a treatment recommendation. Its meaning depends on the study design, analysis, precision, and the interpretation criteria set for the outcome. A threshold for a clinically important difference is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design change?

In a crossover design, participants receive the study conditions in an order, rather than remaining in only one condition throughout the study. The registry describes two sequences: multifocal followed by sphere, and sphere followed by multifocal. This makes period and order relevant to interpretation. General statistical principle: analyses of crossover data should account for the repeated observations from the same participant and consider whether period or sequence affects the outcome. The primary result is described as a mixed models analysis, a general approach that can model correlated observations. The exact model terms, assumptions, and treatment of period or sequence are not reported in the registry record.

The crossover label does not itself show that all design or analysis concerns were addressed. For example, a reader would need the protocol and full analysis specification to assess how the model handled the within-participant structure and whether any period-related effects were considered. Those details are not reported in the registry record. It is therefore appropriate to describe the reported model and its estimate, but not to reverse-engineer the analysis or assume unreported methods.

Why are medians and inter-quartile ranges reported?

The primary endpoint is reported with a median and inter-quartile range for each lens condition. A median describes the central value after ordering the observations; the inter-quartile range describes the span from the lower quartile to the upper quartile. These summaries indicate the center and spread of the posted values, but they do not provide the participant-level pairing needed to reproduce a crossover analysis. They also do not by themselves yield the model-based mean difference reported by the sponsor.

The CLUE description states that scores follow a normal distribution with a population average score of 60 and SD 20. That questionnaire description does not replace the observed trial summaries, and it does not establish that the trial’s endpoint values followed that distribution. General statistical principle: choosing a summary measure and model should reflect the endpoint and the analysis plan. The registry does not report why the arm-level summaries use medians while the model analysis is expressed as a mean difference.

How should the primary confidence interval be read?

The reported primary estimate is a mean difference in final values of -4.14, with a 95% confidence interval from -9.86 to 1.59. General statistical principle: a confidence interval describes the range of estimates reasonably compatible with the data and the analysis assumptions at the stated confidence level. It conveys precision as well as direction. Here, the interval spans zero, so it does not rule out a zero difference under the reported model. It also spans values on both sides of zero. The interval is not a probability statement that the true effect falls within its limits, and it does not establish that the lens conditions are equivalent.

For a non-inferiority or equivalence assessment, the estimate and interval must be evaluated against a prespecified margin and a specified decision rule. The registry labels the analysis as a non-inferiority or equivalence type, but the margin and decision rule are not reported in the registry record. The result therefore cannot be classified as demonstrating either property from the posted interval alone. A p-value is also not reported for this primary analysis.

What do the secondary risk differences represent?

The numerical secondary comparisons are recalculated, unadjusted comparisons of proportions using posted counts. A risk difference is the proportion in one condition minus the proportion in the reference condition; its sign depends on that ordering. For the near vision symptom result, the recalculation compares sphere with multifocal and gives -0.102. For the baseline flipper result, the same ordering gives 0.061. These are simple unadjusted re-calculations from the posted summary statistics. They are not the sponsor’s model-based primary analysis, and they do not account for the crossover structure or any adjustment not represented in the posted summaries.

The corresponding intervals quantify uncertainty around those unadjusted differences. Both intervals include zero and include values in opposite directions. General statistical principle: an interval that spans zero is consistent with no difference as well as with effects in either direction, under the calculation’s assumptions. The unadjusted p-values are 0.312 and 0.543, respectively. They should not be interpreted as probabilities that the null hypothesis is true or as measures of effect size. A p-value does not indicate whether an effect is important to participants.

Binary comparisons can also be expressed as relative risks or odds ratios, but those measures answer different questions from a risk difference. The recalculated summaries include relative and odds measures, but the risk difference gives an absolute comparison in proportions. Any such recalculation is limited by the posted aggregate data. Individual participant data and the trial’s planned statistical analysis would be needed to assess the paired crossover comparison directly.

Why do planning illustrations not describe observed power?

The planning illustrations are explicitly based on the observed effect and use stated assumptions: a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They show participants per arm for 80% and 90% power when planning for 100%, 75%, or 50% of the observed effect. These are planning illustrations, not the trial’s original sample-size justification and not observed power. The registry does not report the trial’s own sample-size assumptions or justification.

General statistical principle: planning calculations depend on the assumed effect, variability, allocation, significance level, and target power. If the assumed effect is smaller, a design generally needs more information to detect it at the same target power. A calculation based on the observed effect is especially dependent on that estimate, which may be imprecise. The posted illustrations should therefore be read as conditional design scenarios, not as evidence about whether the completed trial had adequate power. The crossover structure and any within-participant correlation also matter to design, but the planning illustration is described as an equal-allocation, normal-approximation calculation and does not report a crossover-specific variance assumption.

10. Analyses Reported by the Sponsor

The sponsor-reported primary analysis is a mixed models analysis of the mean difference in final values. It estimates -4.14, with a 95% confidence interval from -9.86 to 1.59. No p-value is reported. This sponsor analysis is the relevant posted model-based result for the primary endpoint. The arm-level medians and inter-quartile ranges are descriptive summaries and are not a recalculation of that model result.

The recalculated unadjusted comparisons discussed for the secondary outcomes are based on posted proportions and counts. They are separate from the sponsor’s primary mixed models analysis and do not reproduce it. The registry does not report a sponsor analysis for the posted numerical secondary comparisons. There is no stated discrepancy between the sponsor’s result and a recalculation in the registry record. Even so, the sponsor’s model result should be interpreted on its own terms; the full model specification and contrast direction are not reported in the registry record.

The primary analysis is labelled as a non-inferiority or equivalence type, but neither the margin nor its decision rule is reported. The model estimate and confidence interval alone cannot establish that criterion. The endpoint summaries and model result should therefore be described as posted, without assigning a stronger conclusion than the record supports.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures and reports results for the primary endpoint and some secondary outcomes. It does not report a multiplicity adjustment, a hierarchy of hypotheses, or a strategy for controlling error across outcomes. Without this information, the unadjusted secondary p-values should be treated as descriptive or exploratory rather than as a set of confirmatory tests. The posted registry record does not say whether any outcomes were prespecified as key secondary outcomes.

The primary analysis is labelled as a non-inferiority or equivalence type, but the margin, analysis hypothesis, and decision rule are not reported in the registry record. Those elements are necessary to determine how the model estimate and confidence interval relate to the stated analysis type. The record also does not report whether interim analyses were planned or conducted. Their presence or absence should not be inferred.

The primary population is described as participants who were enrolled, randomized into one of the randomized arms, and completed the study. The registry does not report the number who completed the study separately, the number excluded from the analysis, or how missing outcome data were handled. It also does not report whether the analysis followed an intention-to-treat, per-protocol, or other defined population. The arm-level entries list 49 participants for each lens condition, but those entries do not explain completeness or missingness in the crossover analysis.

General statistical principle: missing data can affect both the precision and the direction of an estimate, depending on why values are missing and how they are handled. In a crossover trial, missingness may also affect which periods or paired observations contribute to an analysis. Assessing these issues would require details of the analysis population, participant flow, and missing-data method. These are not reported in the registry record. Consequently, the posted estimates can be described, but their sensitivity to missing data cannot be assessed from the record alone.

12. Safety Results

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

Other (non-serious) adverse events

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

The registry reports zero serious adverse events affecting participants in the multifocal condition among 49 at risk, and zero in the sphere condition among 49 at risk. It also reports zero other adverse events affecting participants among 49 at risk in each condition. No deaths are listed in the adverse-event fields, and no serious adverse event terms are listed.

These are the adverse-event figures recorded for the trial. They should not be interpreted as proof that no adverse events could occur or that the lenses have no safety risks. A trial of this size and duration may not characterize uncommon or delayed events, and the registry record does not provide additional event descriptions or follow-up details. Because the design is crossover, the same participant may contribute experience in both conditions; the at-risk entries should not be added to infer a distinct participant total.

Safety reporting is separate from the vision-quality outcome. Zero recorded serious events does not establish comparative effectiveness, and the primary questionnaire result does not establish safety. The registry record does not report further information about adverse-event collection or attribution.

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

The posted results describe a randomized, double-masked crossover comparison of multifocal and sphere contact lens conditions in symptomatic patients with presbyopia. For the primary CLUE outcome at week 4, the registry reports arm-level medians and inter-quartile ranges, along with a model-based mean difference and 95% confidence interval. The interval spans zero, and no p-value is reported. The record therefore conveys uncertainty about the primary comparison rather than a precise distinction between conditions.

The registry calls the model analysis a non-inferiority or equivalence type, but does not report the margin or decision rule. Without those details, the result cannot be used to claim that the conditions are equivalent or that one is non-inferior to the other. The posted outcome summaries also do not establish whether any observed score difference would be important to participants; a threshold for clinically important change is not reported in the registry record.

The recalculated secondary comparisons are unadjusted and have intervals that include zero. They address outcomes different from the primary endpoint, and the flipper result is measured at baseline. They do not provide a basis for a broad conclusion about all outcomes. Numerical results for some listed secondary outcomes are not reported in the registry record.

These results do not establish that either lens works or does not work, and they are not medical advice. They are a statistical account of the estimates and their precision as recorded. A fuller interpretation would require the protocol, analysis plan, crossover model details, missing-data information, and any prespecified clinical or non-inferiority criteria, none of which are reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why the design and the analysis summary both matter. The crossover sequences expose participants to both lens conditions in different orders, so the comparison is not interpreted in the same way as a simple parallel-group trial. A mixed models analysis is reported, but the registry does not provide its full specification. Readers can identify the analysis family while still recognizing that important details about period, sequence, and within-participant correlation are not available.

It also illustrates the difference between descriptive summaries and an inferential estimate. The posted medians and inter-quartile ranges describe the values for each lens condition. The model-based mean difference and confidence interval address a contrast under the sponsor’s analysis. Neither form of summary should be substituted for the other. The confidence interval communicates uncertainty that a point estimate alone would conceal.

The non-inferiority or equivalence label highlights a further statistical distinction. A comparison designed for those purposes requires a margin and decision rule; a confidence interval that spans zero is not enough to establish equivalence. Because the margin is not reported, the label cannot be translated into a conclusion from the posted estimate alone.

Finally, the secondary results and planning illustrations show why exploratory comparisons and post hoc planning scenarios need careful framing. Unadjusted secondary tests do not automatically provide confirmatory evidence when multiple outcomes are considered, and sample-size illustrations based on observed effects are not observed power or proof of the original design’s adequacy. The registry record leaves these issues open, making transparent reporting of the analysis plan especially important.

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 details needed to assess the estimates are not reported in the registry record. These include the full mixed model specification, the contrast direction for the primary mean difference, the treatment of period and sequence, and whether any washout was used. Without those details, the crossover analysis cannot be independently evaluated or reproduced from the registry summaries.

The record does not report the non-inferiority or equivalence margin, the decision rule, or a threshold for a clinically important difference in CLUE scores. This limits interpretation of the primary result beyond its estimate and confidence interval. A p-value is not reported for that primary analysis. The registry also does not report the trial’s sample-size justification, so the planning illustrations based on observed effects cannot be taken as evidence of the original design’s assumptions.

The analysis population is described as enrolled, randomized participants who completed the study, but the record does not give a separate completion count or explain missing-data handling, exclusions, or deviations from randomized sequence. That limits assessment of possible attrition or analysis-set effects. Further participant characteristics and eligibility details are not reported in the registry record, so the applicability of the results to other patient groups cannot be judged from these details alone.

Numerical results are unavailable in the registry record for some listed secondary outcomes, including comfort and comfortable wearing time. The available secondary comparisons are unadjusted, and the registry does not report a multiplicity strategy. The adverse-event figures are also limited to the posted counts; additional collection and follow-up details are not reported. These limitations do not invalidate the recorded estimates, but they constrain the strength and scope of conclusions that can be drawn from them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Evaluation of a Multifocal Contact Lens on Symptomatic Patients — NCT01016652.
• Registry record last updated 2018-06-19; status last verified 2017-08.
• Results first posted 2014-01-23.
• 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

The registry record describes a completed, randomized, double-masked crossover study of an etafilcon A multifocal contact lens and an etafilcon A sphere contact lens in symptomatic patients with presbyopia. Enrollment is listed as 49. The two sequences used opposite lens orders across period 1 and period 2.

The primary outcome was CLUE overall vision quality at week 4. The record reports medians and inter-quartile ranges by lens condition and a sponsor-reported mixed models mean difference of -4.14, with a 95% confidence interval from -9.86 to 1.59. The interval spans zero, and a p-value is not reported. The analysis is labelled non-inferiority or equivalence type, but the margin and decision rule are not reported.

Two secondary outcomes have numerical, unadjusted recalculations; other listed secondary results are not reported in the registry record. The adverse-event entries report zero serious and zero other adverse events affecting participants in each condition. Key analysis details, including missing-data handling and the full crossover model specification, are not reported in the registry record.