Effects of Supplementation With PUFAs and Antioxidants for Contact Lens Discomfort: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Supplementation With PUFAs and Antioxidants for Contact Lens Discomfort (NCT04163328), a randomized phase 4 study. The primary outcome is Average Contact Lens Dry Eye Questionnaire (CLDEQ-8) Score.

2. Clinical Question

This is a question about a measured symptom score in the trial population, not a direct measure of every aspect of dry eye or contact lens comfort. The record also lists outcomes covering tear LTB4, questionnaire responses, neuropathic pain symptoms, tear breakup time, Schirmer I testing, and ocular staining. Those outcomes may offer different perspectives, but the primary endpoint remains the CLDEQ-8 average at the stated assessment time.

3. Trial Design

The registry record identifies this as a Phase 4, randomized, quadruple-masked, parallel-group trial. Random allocation is intended to make treatment groups comparable on average, while masking is intended to limit the influence of treatment knowledge on participants’ responses, care, and assessment. The record does not specify which four roles were masked or how randomization and masking were implemented.

The study began on 2022-09-16, and its primary completion date is 2024-08-21. Its status is terminated. The listed enrollment is 31. That enrollment figure should not be treated as the number contributing to the posted primary outcome: the outcome results list six participants for HydroEye® and six for placebo. Reasons for termination and the relation between enrollment and outcome results are not reported in the registry record.

The two arms are HydroEye® and placebo, and the arm descriptions specify matching capsule schedules. The registry record identifies the control arm as placebo and gives the primary outcome timeframe as 6 months. It does not describe additional follow-up schedules, treatment adherence, or changes in assigned treatment.

The primary outcome is a continuous score summarized as a mean with a standard deviation. The registry record lists seven secondary outcomes and eight outcome measures overall. No statistical analyses are posted in the record. Details such as the planned analysis model, handling of missing observations, analysis population, and adjustment for multiple outcomes are not reported in the registry record. Those omissions matter when interpreting the posted group summaries: the summaries describe the observed results recorded for each arm, but do not by themselves establish a treatment comparison or explain how participants were selected for analysis.

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.

Overall 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.

Population: The study was terminated by the sponsor before completing enrollment.

6. Primary Endpoint

The registry lists the primary outcome as Average Contact Lens Dry Eye Questionnaire (CLDEQ-8) Score, measured over 6 months.

The primary endpoint is the average Contact Lens Dry Eye Questionnaire (CLDEQ-8) score at 6 months. The CLDEQ-8 is described as a contact lens-specific symptoms survey, with scores from 0-37 and higher values indicating more symptoms. Using a questionnaire makes symptoms the direct focus of the primary measure, rather than relying only on clinical tests of the eye or tears.

The registry record reports the endpoint as a mean and standard deviation for each arm. The posted mean is 15.0 for HydroEye® and 11.3 for placebo; the corresponding standard deviations are 2.6 and 6.4. The record lists six participants in each arm for these results. The means describe the reported average scores, while the standard deviations describe variation among the recorded scores within each arm. Neither summary shows the individual participant values.

As a general statistical point, a patient-reported measure can capture symptoms that may not be fully represented by a physical test. Its interpretation depends on how the questionnaire was administered, the completeness of responses, and whether the score’s meaning is appropriate for the population under study. Those implementation details are not reported in the registry record. The endpoint is also limited to the stated scale and assessment time; it is not, by itself, a comprehensive measure of all symptoms, function, or ocular findings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes the primary outcome as a continuous measure, summarized by a mean and standard deviation. It reports no formal analysis for that outcome. The concepts below explain how these summaries and common statistical methods are generally interpreted; they do not describe analyses confirmed to have been performed in this trial.

What does a mean describe?

In general, a mean is an arithmetic summary of the observed scores in a group. It gives a central value but does not show the full pattern of individual observations. Two groups can have different means while their individual scores overlap substantially. Conversely, groups with similar means may differ in other features, such as the spread or shape of their score distributions. The registry record gives the mean CLDEQ-8 score for each arm but does not provide individual scores or a distributional summary beyond the standard deviation.

What does a standard deviation describe?

In general, the standard deviation describes how dispersed observations are around their group mean. A smaller standard deviation indicates scores are more concentrated around that mean; a larger one indicates greater spread. It is not the same as a confidence interval and does not directly quantify uncertainty about a treatment comparison. For the primary outcome, the posted standard deviations are 2.6 for HydroEye® and 6.4 for placebo. The registry record does not say whether these values were used in a particular inferential procedure.

How would a comparison be made?

For a continuous endpoint in a randomized, parallel-group trial, an analysis commonly estimates a difference between the arm means. A statistical model can also account for design features or prespecified covariates when the study plan calls for them. The model, covariates, and prespecified comparison for this trial are not reported in the registry record. The posted arm means alone are not a substitute for a reported analysis: they do not quantify uncertainty around the contrast or establish whether a model’s assumptions are reasonable.

As a general statistical explanation, a confidence interval communicates the precision of an estimate under the assumptions used to construct it. A narrow interval indicates greater precision than a wide one, while the interval’s position conveys which effect values are compatible with the data and method. The registry record does not report a confidence interval for the primary comparison. A p-value, if reported, would address compatibility between the data and a specified null model; it would not measure the size or practical importance of an effect. No p-value for the primary comparison is reported.

Why does variability matter?

In general, more variation in outcome scores makes it harder to estimate a group contrast precisely, all else being equal. Statistical methods often rely on assumptions about score distributions and variability. If the variability differs between groups, methods that assume equal variances may be less suitable; alternatives can avoid that assumption. This is a general consideration, not a statement about what analysis this trial used. The registry reports different arm-level standard deviations but does not report an assumption check or choice of method.

What do the planning illustrations mean?

Sample-size planning is different from analysis of observed outcomes. The planning illustrations are described as hypothetical calculations based on the observed effect, with equal allocation, a two-sided significance level of 0.05, and a normal approximation; the target effect is a stated fraction of the observed effect. Such illustrations describe how a future study might be planned under those assumptions. They are not observed outcomes, do not establish the power of this completed trial, and do not show that the registry study was designed using those assumptions. The study’s own sample-size justification is not reported in the registry record. No planning counts are described in this discussion.

How should missing observations be considered?

In general, missing outcome data can affect both the number of observations available and the interpretation of results. The consequences depend on why measurements are missing and on the analysis method. For example, missingness related to symptom severity can create a different concern from missingness unrelated to the outcome. The registry record does not report reasons for missing primary outcome data, a missing-data method, or a sensitivity analysis. Given that the listed enrollment and the outcome-arm counts differ, the unreported handling of participants and measurements is important context.

What can be inferred from the reported summaries?

The arm-level summaries describe the posted scores for the listed outcome participants. They do not reveal whether assignment was preserved in analysis, whether all relevant data were included, or whether the result is robust to alternative assumptions. The record’s lack of a posted analysis means there is no sponsor-reported comparative estimate to interpret. Recalculating a comparison from group summaries would be an unadjusted analysis, and no such recalculation is presented for this endpoint. The defensible statistical reading is therefore descriptive: the record gives mean scores and standard deviations, but not a formal estimate of the primary treatment contrast or its precision.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("HydroEye®", "Placebo")
n   <- c(6, 6)
m   <- c(15, 11.3)
sp  <- c(2.6, 6.4)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  HydroEye®  6  15.000  2.600  12.271  17.729
CARM  Placebo  6  11.300  6.400  4.584  18.016

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the CLDEQ-8 as the primary outcome and seven secondary outcomes. These include tear LTB4, the SPEED questionnaire, a count of participants with a non-zero NPSI score, tear breakup time, Schirmer I testing, and corneal and conjunctival staining. Because several outcomes are assessed, interpreting a collection of results raises a multiplicity question: the more comparisons examined, the greater the chance that some results may appear notable by chance. As a general statistical practice, investigators may specify a hierarchy of outcomes or adjust analyses to address this issue. Any such plan or adjustment is not reported in the registry record.

The record lists no posted analyses, so it does not show which comparisons were tested, whether secondary outcomes were analyzed, or how multiplicity was handled. The endpoint list alone does not establish that every measure was analyzed or that a particular correction was required or used.

Missing-data handling is also not reported. The record lists enrollment of 31, while the primary outcome results list six participants per arm. The reason for the difference is not reported in the registry record. It does not state whether measurements were missing, participants were excluded, or another analysis population was used. The analysis population, missingness reasons, imputation method, and sensitivity analyses are not reported in the registry record.

These omissions limit assessment of how representative the posted summaries are of enrolled or randomized participants. They also prevent evaluation of whether results would change under plausible approaches to missing data or multiple outcomes. The available record supports a description of the posted summaries, but not a reconstruction of the intended statistical plan.

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 0% reporting threshold.

The registry record reports no serious adverse events among the six participants listed as at risk in the HydroEye® arm and no serious adverse events among the six listed as at risk in the placebo arm. It also reports zero other adverse events in each arm and zero deaths in each arm. These are the posted safety counts for the listed groups.

A count of zero observed events does not establish that an intervention carries no risk. It means that the registry record reports no events of that type in the stated at-risk group during the reported period. Small numbers of participants and limited observation can leave uncommon events undetected. The record does not give a detailed adverse-event collection method, exposure duration for safety, or event-specific follow-up information.

The listed at-risk counts for safety match the outcome counts reported for the primary measure, but the registry record does not explain the relationship between those groups and the overall enrollment. It also does not provide serious adverse event terms; the list of top serious terms is empty. These safety figures should therefore be read as recorded counts, not as a complete assessment of safety or a comparison that rules out risk.

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

The primary outcome results establish what the registry record reports for the CLDEQ-8 at 6 months: a mean score of 15.0 in the HydroEye® arm and 11.3 in the placebo arm, with standard deviations of 2.6 and 6.4, respectively. Since higher scores indicate more symptoms, the reported average is higher in the HydroEye® group. The registry does not report a statistical comparison, uncertainty interval, or analysis plan for these results.

That descriptive pattern does not, on its own, show whether an underlying treatment effect exists, how large such an effect might be, or whether a difference would be important to participants. It also does not establish that treatment caused the observed group summaries. Randomization is a feature of the design, but interpreting a randomized comparison still depends on how outcomes were collected and analyzed, and how missing measurements were handled. Those details are not reported in the registry record.

The trial status is terminated, and the listed enrollment does not match the number represented in the primary outcome summaries. The reason for termination and the reason for the difference in counts are not reported. The available information therefore cannot explain whether the posted outcomes represent all participants who began the study or why the record contains results for only the listed outcome groups.

The result also concerns one symptom questionnaire and its stated assessment time. The registry lists other outcomes, but their presence does not make the primary score a measure of every aspect of ocular health or contact lens experience. Nor does a reported mean reveal how individual participants’ experiences varied. The posted data do not establish benefit, lack of benefit, or equivalence between arms. They are best understood as limited descriptive results whose comparative meaning and precision remain uncertain because a formal analysis and relevant methodological details are absent.

14. Why This Trial Matters Statistically

This trial illustrates why a registry result needs more than an outcome value to support a statistical interpretation. The record identifies a randomized, quadruple-masked, parallel-group design and reports arm-level averages for a symptom questionnaire. Those features give context for the intended comparison, but the record does not report a formal analysis, a confidence interval, or a p-value. As a result, readers can describe the reported means but cannot assess the precision of a treatment contrast from the registry entry alone.

The enrollment and outcome counts also make analysis populations important. Enrollment is listed as 31, while the primary outcome results identify six participants in each arm. Without an account of participant flow, missing outcomes, and analysis inclusion, it is difficult to know how the observed summaries relate to the randomized study population. This is a general statistical concern: exclusions or missing measurements can affect interpretation if they are related to outcomes or treatment assignment.

The registry includes multiple secondary outcomes, which highlights the importance of a prespecified analysis plan and transparent handling of multiple comparisons. A list of outcomes does not indicate which were analyzed or how results were interpreted. The analysis plan is not reported in the registry record.

Finally, the status is terminated, but the reason is not reported. That fact underscores the value of clear reporting about recruitment, completion, outcome availability, and analysis. The trial remains informative as a record of its design and posted summaries, while important uncertainties prevent a full statistical appraisal of its primary comparison.

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 limitations of the available record are specific to interpreting this trial. Although enrollment is listed as 31, the primary outcome results list six participants in each arm. The registry record does not explain why the outcome counts differ from the enrollment figure, whether all randomized participants were followed, or which participants were included in the reported means. Reasons for termination are also not reported.

The record gives primary outcome means and standard deviations but no formal comparative result. A confidence interval, p-value, analysis model, or adjusted estimate is not reported in the registry record. Without these, the precision of the primary comparison cannot be evaluated from the posted results. The record also does not report a threshold for interpreting a meaningful change in CLDEQ-8 scores.

Important design and analysis details are absent, including the randomization procedure, the roles masked, the analysis population, and how missing observations were handled. The registry lists seven secondary outcomes but does not report which analyses were conducted or whether multiplicity was addressed. The trial’s sample-size justification is not reported in the registry record; hypothetical planning illustrations should not be mistaken for its original design rationale.

The safety summaries report zero serious and other adverse events and zero deaths in each listed group, but the record does not describe the safety collection period or methods. These limitations do not alter the values posted; they constrain the conclusions that can be drawn from them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of Supplementation With PUFAs and Antioxidants for Contact Lens Discomfort — NCT04163328.
• Registry record last updated 2025-03-06; status last verified 2025-03.
• Results first posted 2025-03-06.
• 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 Phase 4 randomized, quadruple-masked, parallel-group trial of HydroEye® versus placebo for contact lens discomfort. It lists enrollment of 31, a terminated status, and a primary completion date of 2024-08-21. The primary outcome was average CLDEQ-8 score at 6 months, with higher scores indicating more symptoms.

The posted primary outcome results give means of 15.0 for HydroEye® and 11.3 for placebo, with standard deviations of 2.6 and 6.4. Six participants are listed in each arm for those results. No formal comparative analysis is reported. Reasons for termination, the difference between enrollment and outcome counts, analysis populations, and missing-data handling are not reported in the registry record.

The record lists seven secondary outcomes and reports zero serious adverse events, other adverse events, and deaths in each listed arm. These summaries describe the posted record but do not establish a treatment effect or resolve uncertainty about the primary comparison.