Clinical Assessment of a HYDRAGLYDE® Regimen: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Assessment of a HYDRAGLYDE® Regimen (NCT03026257), a randomized na study. The primary outcome is Ex Vivo Total Cholesterol Uptake at Day 30.

2. Clinical Question

The central statistical question is whether the mean measured cholesterol uptake differs between the AOHG regimen groups and the habitual-lens groups, and how precisely those group differences are estimated. The record also supports a recalculated comparison of the two AOHG regimen groups, although a sponsor-reported result for that pair is not listed. The regimen comparisons involve both lens material and care solution, so the posted summaries do not isolate the contribution of either component. The record identifies the study as randomized and double masked, but details about the randomization procedure and who was masked are not reported in the registry record.

3. Trial Design

This was a randomized, double-masked, parallel-group study. Its phase is listed as NA, and its status is completed. The registry record lists enrollment of 323 and identifies Alcon, a Novartis Company, as sponsor. The listed study start was 2017-02-13 and primary completion was 2017-08-18. Further details about recruitment, study sites, or the methods used to generate and conceal the allocation are not reported in the registry record.

The AOHG regimen involved lotrafilcon B contact lenses with an added wetting agent, worn in both eyes for 30 days in a daily wear modality. The lenses were cared for with either a hydrogen peroxide-based solution with an added wetting agent or a POLYQUAD/ALDOX-preserved solution with an added wetting agent. The habitual regimen involved participants’ habitual silicone hydrogel lenses, also worn in both eyes for 30 days in daily wear, with their habitual multi-purpose solution. The registry lists several habitual-lens groups, including Biofinity, Vita, Ultra, and Oasys.

The primary outcome was a continuous measure: ex vivo total cholesterol uptake at Day 30, reported as a mean and standard deviation in micrograms. The right contact lens was removed, stored dry and frozen until analysis, and a sample of right lenses from each site was evaluated. The primary population is described as the Full Analysis Set with cholesterol uptake measured. The record lists one outcome measure and eight sponsor-reported analyses. It does not describe the randomization ratio, allocation concealment, masking procedures, handling of protocol deviations, or the planned statistical analysis in sufficient detail to assess those features.

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 323 enrolled, 66 subjects exited as screen failures prior to randomization. An additional 5 subjects were randomized but discontinued prior to treatment. This reporting group includes all randomized and exposed subjects (252). Subject distribution in As Randomized and As Treatment differs due to 3 subjects with lens/solution misallocations.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set with cholesterol uptake measured

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: This analysis population includes all randomized and exposed to a study lens on Day 1 or a study regimen (lens and lens care system (LCS)) thereafter (Full Analysis Set).

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Ex Vivo Total Cholesterol Uptake at Day 30, measured over Day 30.

The primary endpoint is ex vivo total cholesterol uptake at Day 30. Cholesterol uptake includes cholesterol and cholesterol esters measured from a sample of the right contact lenses. The right lens was removed, stored dry and frozen until laboratory analysis. Results are reported in micrograms, with the group summaries expressed as means and standard deviations.

This endpoint quantifies a material measured on the lens after wear and care under the assigned regimen. The registry states that lower total cholesterol uptake indicates increased lens performance. It is therefore a laboratory measure relevant to the study’s stated comparison of lens-and-care regimens. It does not directly measure comfort, vision, adherence, ocular symptoms, or a longer-term clinical outcome; those outcomes are not reported as primary endpoints in this record.

Because the intervention and comparator differ in both lens and care regimen, a group difference in uptake cannot be attributed to the lens alone or the solution alone from these summaries. The record does not report a detailed assay protocol, the properties of the sampled lenses beyond the endpoint description, or a clinical threshold that would define a meaningful difference in uptake. Those omissions limit interpretation of how a measured contrast maps to real-world experience.

7. Results Posted in the Registry

• AOHG/OFPM: mean 0.28 versus 0.28 on control; difference 0.00 (95% CI -0.20 to 0.20), standardized effect d = 0.00; z-test p = 1.000.
• Biofinity/HMPS: mean 2.17 versus 0.28 on control; difference 1.89 (95% CI 1.30 to 2.48), standardized effect d = 1.79; z-test p = <0.001.
• Vita/HMPS: mean 4.18 versus 0.28 on control; difference 3.90 (95% CI 2.57 to 5.23), standardized effect d = 1.69; z-test p = <0.001.
• Ultra/HMPS: mean 2.07 versus 0.28 on control; difference 1.79 (95% CI 1.14 to 2.44), standardized effect d = 1.76; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: each reported group mean represents the average measured cholesterol uptake in that group, and the standard deviation describes the spread of individual measurements around the mean. A mean is a useful way to summarize the group’s central value, but it can conceal the shape of the data and the influence of unusually high or low measurements. The registry does not report individual-level data, distribution plots, or checks of model assumptions, so those features cannot be evaluated from the record.

What does a mean difference represent?

General: A mean difference compares the average outcome in one group with the average in another. In the recalculations, the named comparator group is contrasted with AOHG/CCP. A positive estimate therefore corresponds to a higher mean uptake in the named comparator group. The estimate is expressed in the endpoint’s units, micrograms, which keeps the comparison tied to the measured quantity rather than converting it to a standardized scale.

The posted recalculated comparisons are unadjusted: they use the arm-level summary statistics and do not account for covariates or features of the study design that might be included in a fitted model. The record does not specify adjustments used in the sponsor’s General Linear Model, such as covariates or site effects. Thus, the recalculated and sponsor-reported estimates or tests should not be treated as interchangeable. In particular, the recalculated p-values are not replacements for the sponsor’s reported inference.

How should a p-value be read?

General: A p-value describes how incompatible the observed data are with a specified null model, under the assumptions used for the test. It is not the probability that the null hypothesis is true, nor does a small value measure the size or practical importance of a difference. The unadjusted recalculated p-values are reported for the individual comparisons. The sponsor’s reported p-values come from the General Linear Model analyses and are listed as p < 0.001 for the eight AOHG-versus-habitual comparisons. The registry does not report details sufficient to reconstruct those model-based tests.

A p-value should be considered alongside the estimated difference, its interval, the measurement scale, and the analysis that generated it. This matters especially because the record contains multiple comparisons. The registry does not report whether the sponsor’s p-values were adjusted for multiplicity or how the overall family of comparisons was defined. An unadjusted result for a single comparison does not, on its own, account for the possibility of examining several comparisons.

What is the role of the standard deviation?

General: The standard deviation describes variability among measured values within a group; it is not the uncertainty in the group mean itself. The reported standard deviations vary across these groups, with greater spread in several habitual-lens groups than in the AOHG/CCP group. Greater within-group variability can make a mean difference less precisely estimated, all else being equal. However, the registry does not provide individual measurements or distributional diagnostics, so the implications of skewness, outliers, or other departures from a model cannot be assessed. Over-dispersion is a general concern when observed variation is greater than a model allows, but the record does not establish that over-dispersion occurred in this trial.

What do the planning illustrations mean?

The planning illustrations are based on recalculated observed effects, not the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and effects set to 100% of the observed effect, 75% of the observed effect, or 50% of the observed effect. Their outputs are labeled as participants per arm for 80% power and participants per arm for 90% power. These are hypothetical planning quantities under the stated assumptions, not observed power, not the trial’s enrollment rationale, and not evidence that the trial had a particular probability of detecting an effect. The sample-size justification and the assumptions used in the original trial design are not reported in the registry record.

General: Planning calculations based on an observed estimate can be optimistic because the estimate is subject to sampling variation. Smaller assumed effects require more participants for a given target power under otherwise comparable assumptions. Such calculations are most useful as illustrations of how assumptions influence planning; they do not repair uncertainty about the trial’s actual design or the sponsor’s model.

10. Confidence Intervals and Precision

A confidence interval describes a range of values compatible with the data and the calculation’s assumptions. It conveys uncertainty about an estimated difference, rather than showing the full range of individual lens measurements. The confidence level used for the recalculated intervals is not reported in the registry record, so the intervals should not be assigned a particular confidence percentage based on this record alone.

For the AOHG/OFPM versus AOHG/CCP recalculation, the estimate is 0.0 μg and the interval runs from -0.202 to 0.202. For the habitual-lens comparisons against AOHG/CCP, the estimates and intervals are: Biofinity/HMPS, 1.89 μg, from 1.297 to 2.483; Vita/HMPS, 3.9 μg, from 2.57 to 5.23; Ultra/HMPS, 1.79 μg, from 1.137 to 2.443; and Oasys/HMPS, 1.91 μg, from 0.911 to 2.909. The interval for the AOHG regimen comparison includes values on either side of zero. Each interval for the habitual comparisons lies above zero, under the recalculation’s unadjusted approach.

Interval width reflects both the observed variability and the amount of information in the compared groups, as well as the method used to calculate the interval. The group standard deviations differ, and the reported endpoint group sizes also differ. The registry does not provide adjusted sponsor-model estimates or intervals, so the precision of the sponsor’s model-based contrasts cannot be assessed from the posted inferential results. Intervals for the recalculations also do not account for any unreported multiplicity adjustment. They should therefore be read as precision summaries for the recalculated comparisons, not as a full account of uncertainty across the set of trial analyses.

11. Analyses Reported by the Sponsor

The registry reports eight sponsor analyses using a General Linear Model. They compare each of the two AOHG groups with each of the four habitual-lens groups. Every reported comparison is labeled as a superiority analysis and has p < 0.001. The registry does not provide the sponsor’s estimated group differences, confidence intervals, model coefficients, or sufficient model details to interpret the magnitude and precision of those adjusted comparisons.

The recalculated results are different in kind: they are simple unadjusted comparisons derived from posted group means and standard deviations. They include a comparison between AOHG/CCP and AOHG/OFPM, for which the recalculated estimate is 0.0 and p = 1.0; the listed sponsor analyses do not include that pair. The recalculated comparisons against the habitual groups have p < 0.001, whereas the sponsor’s listed model-based analyses have p < 0.001. Those values should not be read as a direct contradiction without the model details and estimates, because the analyses differ in method and the sponsor results may incorporate features absent from the recalculations.

The record flags a discrepancy. Accordingly, the sponsor’s own analysis takes precedence over the recalculated results when describing the sponsor-reported inference. The recalculations remain useful as transparent, unadjusted checks of the posted summaries, but they do not replace the reported General Linear Model findings or resolve why the values differ.

12. Multiplicity, Missing Data and Analysis Populations

The record lists eight sponsor-reported comparisons: each AOHG regimen against each of four habitual-lens groups. Multiple comparisons raise a multiplicity question because testing several contrasts can increase the chance of at least one nominally significant result when all null hypotheses hold. The registry does not report whether the sponsor adjusted for multiplicity, which adjustment was used, or whether a particular comparison was designated as the primary contrast. The reported p-values therefore cannot be assumed to be multiplicity-adjusted.

The posted recalculations are unadjusted and should be read as separate comparisons rather than as a joint family-wise conclusion. The recalculated AOHG/OFPM versus AOHG/CCP comparison is also distinct from the sponsor’s eight listed comparisons. The registry does not describe a hierarchy of testing or a strategy for controlling false-positive risk across endpoints or contrasts.

The primary endpoint population is the Full Analysis Set with cholesterol uptake measured. The record does not report the number of participants included in that set, the number with missing endpoint measurements, reasons for missingness, or the method used to handle missing data. It also does not report whether participants were analyzed according to randomized assignment, how protocol deviations were treated, or whether any sensitivity analyses addressed missingness.

Only one outcome measure is listed, and no secondary outcomes are posted. The registry does not report a protocol-level statistical analysis plan, prespecified covariates, model diagnostics, or interim analyses. This absence does not show that such procedures were or were not used; it means they cannot be evaluated from the registry record. The distinction between what is reported and what is not reported is important when interpreting both nominal significance and the generalizability of the endpoint analyses.

13. 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 separates ocular and nonocular categories for AOHG/CCP, AOHG/OFPM, and habitual silicone hydrogel lenses with multi-purpose solution. Each listed category reports zero participants with serious adverse events, zero with other adverse events, and zero deaths. The numbers at risk differ across categories: the ocular entries list 116 for AOHG/CCP, 130 for AOHG/OFPM, and 258 for habitual SiHy/MPS; the nonocular entries list 58, 65, and 129, respectively. No serious-event terms are listed.

These are the reported registry counts for the safety categories, not a guarantee that no adverse events occurred outside the recorded definitions, observation period, or reporting process. The record does not provide event narratives, event severity details beyond the serious/nonserious grouping, exposure time, or information about how participants with missing safety follow-up were handled. Nor does it provide enough detail to interpret why the ocular and nonocular numbers at risk differ. The figures should be read as reported counts within the registry’s categories, without inferring comparative safety from zero reported events alone.

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

The posted results describe cholesterol uptake from right contact lenses after the study’s 30-day wear and care regimens. The group means for the habitual-lens regimens are higher than the means for both AOHG groups. The recalculated unadjusted comparisons against AOHG/CCP likewise have positive estimates for each habitual-lens group, while the recalculated difference between the two AOHG groups is 0.0. The sponsor’s separate General Linear Model analyses report superiority for all eight AOHG-versus-habitual contrasts, with p < 0.001.

These findings concern a laboratory endpoint and the particular regimens studied. They do not establish that a lens or solution alone accounts for the group differences, because the lens and care regimen vary together across comparisons. The record does not identify a clinical threshold for meaningful cholesterol uptake, and it does not report patient-centered outcomes such as comfort or vision. The endpoint therefore cannot, by itself, quantify the practical importance of the measured difference for an individual wearer.

The results also do not establish the sponsor’s model estimates or their precision, since those estimates and intervals are not posted. The recalculations are unadjusted, and the registry does not state whether multiplicity was addressed. Missing-data handling and analysis-population details beyond the Full Analysis Set with cholesterol uptake measured are not reported. These gaps limit assessment of bias, robustness, and the extent to which the reported comparisons reflect the intended analysis.

Finally, findings from the listed groups and short-term endpoint should not be extended to other lenses, solutions, wear schedules, or outcomes not evaluated in the record. The registry’s statement that lower uptake indicates increased lens performance explains the direction of its endpoint, but it does not establish a broader clinical benefit. Interpretation should remain tied to the measured uptake and the analysis methods actually reported.

15. Why This Trial Matters Statistically

This trial illustrates why a group mean alone is not enough to understand a continuous clinical-trial endpoint. The standard deviations vary across the posted groups, and the endpoint group sizes are not identical. A comparison therefore needs to be read with its uncertainty, not only by ranking the means. The recalculated intervals make that uncertainty visible for unadjusted contrasts, while the lack of posted sponsor estimates and intervals leaves an important gap in evaluating the reported model-based results.

The study also shows how analysis choices affect interpretation. The recalculated mean differences are based on summary statistics and are unadjusted, whereas the sponsor reports General Linear Model tests. The record does not provide enough model detail to reproduce those tests. The discrepancy flag makes it especially important to distinguish a transparent recalculation from the analysis designated by the sponsor, rather than treating their p-values as equivalent evidence.

Multiplicity is another statistical issue: the record lists several comparisons, yet does not say whether the sponsor adjusted for examining them. Similarly, the planning illustrations show how assumed effect size and target power relate to participants per arm under stated assumptions, but they do not reveal the original design rationale or the probability that this completed trial detected an effect. Keeping planning quantities separate from observed results helps avoid interpreting them as trial power.

Overall, the record provides useful descriptive summaries and reported hypothesis tests, while leaving uncertainty about model specification, multiplicity, missing data, and the clinical meaning of the laboratory endpoint. These distinctions are central to responsible interpretation of trial statistics.

16. 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 evaluate the comparisons are not reported in the registry record. The sponsor’s General Linear Model is named, but the model specification, included covariates, site handling, diagnostic checks, and adjusted effect estimates are absent. The confidence level for the recalculated intervals is also not stated. Consequently, the sponsor’s model-based effect size and precision cannot be reconstructed from the posted inferential results.

The outcome is measured from a sample of right contact lenses, while lenses were worn bilaterally. The record does not explain the sampling procedure in detail, whether the laboratory assessment was masked, how sites contributed samples, or how assay variability was controlled. It also does not report whether participants contributed measurements to more than one endpoint group or how any such dependence was handled. No individual data or endpoint distribution information is posted.

The regimens differ in lens and care solution, so the contrasts cannot separate their effects. The labels identify the groups, but the record does not describe the basis for selecting the habitual lenses or solutions. The population is described through refractive-error conditions and an endpoint analysis set; eligibility criteria and demographic characteristics are not reported in the registry record.

Finally, multiplicity adjustment, missing-data procedures, the sample-size rationale, protocol deviations, interim analyses, and the statistical analysis plan are not reported in sufficient detail. The absence of these details prevents a complete assessment of robustness and does not establish that a particular method was or was not used. The endpoint is a short-term ex vivo measurement, and no clinical threshold or patient-centered endpoint is provided to interpret its practical importance.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Clinical Assessment of a HYDRAGLYDE® Regimen — NCT03026257.
• Registry record last updated 2018-08-14; status last verified 2018-07.
• Results first posted 2018-08-14.
• 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.

20. Record Summary

NCT03026257 is a completed, randomized, double-masked, parallel study sponsored by Alcon, a Novartis Company. The registry lists enrollment of 323, phase NA, a study start of 2017-02-13, and primary completion on 2017-08-18. It compares AOHG lenses cared for with HYDRAGLYDE®-containing solutions against habitual silicone hydrogel lenses cared for with habitual multi-purpose solution.

The primary outcome is mean ex vivo total cholesterol uptake in right contact lenses at Day 30, reported in micrograms. Posted group summaries show lower means in the AOHG groups than in the four habitual-lens groups. The sponsor reports eight General Linear Model superiority analyses with p < 0.001; adjusted estimates and intervals are not posted. Recalculated unadjusted comparisons are available, but the discrepancy flag means the sponsor’s own analysis takes precedence. Multiplicity handling, missing-data procedures, model details, and the clinical threshold for meaningful uptake are not reported in the registry record.