Study of DE-114 Ophthalmic Solution in Patients With Allergic Conjunctivitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of DE-114 Ophthalmic Solution in Patients With Allergic Conjunctivitis (NCT01363700), a registered phase 3 study. The primary outcome is Mean Ocular Itching Score Compared to Placebo Period1.

2. Clinical Question

The stated purpose was to assess the safety and efficacy of DE-114 compared with placebo and olopatadine in patients with allergic conjunctivitis. The primary outcome is specifically a short-term, challenge-based measure of itching, rather than a general measure of symptoms over an extended period. A conjunctivitis allergic challenge was performed 4 hours after drop instillation, and the score was averaged across three post-challenge assessment times.

The clinical question has an important design limitation: the registry record does not describe allocation, and the listed arms cannot be assumed to be randomized or directly comparable. Its own record flags the comparison as not a randomized comparison and cautions that the arms are not a like-for-like control comparison. Consequently, the endpoint name identifies the intended comparison, but does not by itself establish that observed groups were exchangeable or that a causal treatment effect can be inferred.

3. Trial Design

This is a completed Phase 3 study of DE-114 ophthalmic solution in patients with allergic conjunctivitis. The official title describes it as a double-masked comparison study and a confirmatory study. The registry record lists enrollment of 87 and primary completion in 2012-06. The sponsor is Santen Pharmaceutical Co., Ltd.

The listed interventions are DE-114 ophthalmic solution, placebo ophthalmic solution, and olopatadine hydrochloride 0.1% ophthalmic solution. The primary outcome is a comparison of mean ocular itching score with placebo in Period1. Secondary outcomes compare mean ocular itching and mean hyperemia scores with olopatadine in Period2. Safety groups are also labelled for Period1 and Period2, including DE-114, placebo, and olopatadine groups.

The period labels are part of the outcome and safety descriptions; they do not establish the sequence of treatment, whether participants crossed between treatments, or how observations from different periods were handled. Those design details are not reported in the registry record. Although the official title says double-masked, the record does not provide the masking procedures or say which people were masked.

Most importantly, allocation is not stated. The registry record explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The arm descriptions are blank. Thus, the listed intervention groups and periods should not be treated as evidence of random assignment, balanced baseline characteristics, or a particular crossover or parallel-group structure. The analysis can describe what the record reports, but the design information available does not establish the basis for a causal comparison.

The registry record does not report a statistical analysis plan, sample-size justification, or details of treatment assignment. These omissions matter when interpreting both the primary endpoint and the comparisons with olopatadine. The record establishes the study’s broad purpose, named interventions, endpoint definitions, and completion status, but not enough design detail to reconstruct how the reported comparisons were generated.

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: All participants completed Period 1 were randomized 1:1 to 2 groups in Period 2.

Epinastine vs Placebo Period1

Reasons for not completing this period:

Epinastine vs Olopatadine Period2

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 Mean Ocular Itching Score Compared to Placebo Period1, measured over Visit 5 (3, 5, and 10 minutes post-CAC).

The primary endpoint is titled “Mean Ocular Itching Score Compared to Placebo Period1.” It measures itching reported by the subject after a conjunctivitis allergic challenge. The challenge took place 4 hours after drop instillation. At Visit 5, subjects assessed ocular itching at 3, 5, and 10 minutes post-challenge, using a 5 points scale from 0 to 4: 0 means no itching and 4 means incapacitating itch. The endpoint is the average score across those three assessment times. The count unit is each eye.

A mean is a way to summarize the central level of a numeric measure across observations. Because this score has a defined ordered scale, its mean can provide a concise group-level summary, although that summary does not show how individual scores were distributed. The endpoint’s averaging across assessment times represents the specified post-challenge interval; it is not a measure of symptoms across the entire day or across an extended follow-up period.

Challenge-based symptom scores are used to assess a response under a specified testing condition. In general, this can make timing and measurement conditions more consistent, but it also means the result addresses that test context rather than every experience of allergic conjunctivitis. The registry record describes the endpoint and its measurement but does not report the mean values, a comparison estimate, its uncertainty, or the analysis population used for this outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

For a continuous measure, a mean summarizes the average of the observed values. In this study, the primary measure is a score on a defined scale, and the endpoint averages the subject’s assessments at 3, 5, and 10 minutes post-challenge. A mean can make groups easier to compare, but it compresses the underlying data. It does not show whether scores were concentrated near the mean, spread broadly, or clustered at particular values on the scale. The registry record does not report score distributions or group means.

When observations are summarized by a mean, a comparison should ideally include an estimate of the difference between groups and a measure of uncertainty. A difference communicates the direction and size of the contrast; uncertainty indicates how precisely the data estimate that contrast. Neither is available for the primary outcome in the registry record. The endpoint title specifies a comparison but does not provide its result.

What does a standard error mean?

The primary outcome description identifies dispersion as a standard error. In general, a standard error describes the sampling uncertainty of an estimate, such as a mean. It is not the same as the spread of individual participants’ scores: a measure of spread describes variation among observations, while a standard error concerns uncertainty in an estimated quantity. A standard error can help construct an interval estimate when the relevant estimate and analysis assumptions are known. The record does not post a primary mean or standard error, so the precision of that endpoint cannot be evaluated from the information available.

A confidence interval is, in general, a range of values compatible with the data and the method used to calculate it. Its width conveys precision: a wider interval indicates less precise estimation than a narrower interval. A confidence interval does not guarantee that the true effect lies in the interval, and it does not by itself establish clinical importance. No primary confidence interval is reported in the registry record. It would be inappropriate to infer one from the endpoint description alone.

How should a p-value be understood?

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be, under that hypothesis and the statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. A small p-value cannot repair limitations in the study design or establish that a comparison is free of bias. The registry record does not report a p-value for the primary outcome in the information, so no significance conclusion can be drawn from the endpoint definition.

What can planning estimates tell readers?

A sample-size calculation is a prospective planning exercise: it estimates how much information a proposed study would need under assumptions about the outcome, effect, allocation, and analysis. The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and effects defined as a stated fraction of the observed effect. For time-to-event outcomes, such illustrations are expressed as a total number of events; for other outcomes, they are expressed as participants per arm. The primary outcome is continuous, so the relevant convention is participants per arm.

These calculations are described as illustrations based on the observed effect, not as the trial’s own design. They do not report observed power. Observed power is not a substitute for examining an effect estimate and its confidence interval; in general, a calculation made using an observed effect largely restates information about the estimate and its uncertainty. Because the record does not report the primary effect estimate, numerical planning conclusions cannot be independently interpreted from the information available.

Why do allocation and analysis details matter?

Random allocation, when used and properly implemented, can support comparability of groups by balancing known and unknown prognostic factors on average. The registry record does not state allocation and flags the comparisons as not randomized and not like-for-like. That caveat means the reader cannot assume that a group contrast isolates the intervention effect. The record also does not say whether analyses adjusted for baseline values, participant characteristics, period, or other factors.

The endpoint’s count unit is each eye, while the assessment is described as made by the subject. In general, two eyes from one person may not provide independent observations, because measurements from the same person can be related. If both eyes contribute, an analysis may need to account for that dependence. The record does not report how eye-level observations were handled, whether one or both eyes contributed to the primary analysis, or how the averaging across time points was implemented in the statistical model.

Repeated observations can also be related over time. In general, a model that accounts for correlation among repeated measurements may estimate uncertainty differently from one that treats every measurement as independent. Here, the endpoint definition says the three post-challenge scores were averaged. It does not specify whether the analysis used that average directly, whether missing assessments were handled in a particular way, or whether another model was used. The registry record does not report those analytical details.

Over-dispersion is a general issue for count outcomes when variability exceeds what a simple count model assumes; methods that account for it can produce more appropriate uncertainty. The primary outcome in this study is a mean of a score, not a count of events, so over-dispersion should not be assumed to be the analysis issue for this endpoint. More broadly, the model and assumptions for the continuous outcome are not reported in the registry record. No particular statistical method can be attributed to the investigators without that information.

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("Epinastine (DE-114) Ophthalmic Solution", "Placebo Ophthalmic Solution")
n   <- c(87, 87)
m   <- c(0.4, 1.7)
sp  <- c(0.1, 0.1)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Epinastine (DE-114) Ophthalmic Solution  87  0.400  0.933  0.201  0.599
CARM  Placebo Ophthalmic Solution  87  1.700  0.933  1.501  1.899

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and four analyses. The named outcomes include the primary mean ocular itching score compared with placebo in Period1, along with secondary mean ocular itching and mean hyperemia comparisons with olopatadine in Period2. The record does not report whether the analyses were all prespecified, how the primary and secondary outcomes were prioritized in the analysis, or whether any adjustment was made for multiple comparisons.

Multiplicity arises when several hypotheses are tested. In general, the more comparisons considered, the greater the chance that at least one result may appear noteworthy by chance if each is interpreted without accounting for the others. Adjustments can change the threshold for interpretation or the reported uncertainty. Without a stated multiplicity strategy, the registry’s listed analyses should not be treated as if their inferential status were known. The numerical results and p-values for the listed outcomes are not reported in the registry record here, so their findings cannot be compared or evaluated.

Missing-data handling is also not reported in the registry record. The description does not say how participants with incomplete challenge assessments, unavailable visits, or missing eye-level scores were handled. In general, excluding observations with missing outcomes can affect a comparison if missingness is related to symptoms, treatment, or other participant characteristics. Different assumptions and methods for handling missing observations can yield different estimates. No method should be presumed in the absence of a report.

The analysis population is not described for the primary endpoint. The registry record does not say whether the analysis included all enrolled participants, participants who received treatment, participants with an observed endpoint, or another defined group. These distinctions matter because the population analyzed determines what comparison the estimate represents. The record also does not report a statistical plan that would clarify how deviations, missing measurements, or multiple outcomes were to be addressed.

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 record lists five safety groups across Period1 and Period2. For each listed group, the serious-event fields report 0 affected, and the other-event fields also report 0 affected. The at-risk counts differ by group and period, and should be read exactly as listed rather than combined across groups. The record does not establish that these groups are independent or that their counts can be summed to describe a unique participant total.

These figures are registry summaries of the specified safety categories. They indicate that the posted affected counts for those fields are zero; they do not establish that no symptoms, events, or harms of any kind occurred. The registry record does not give further detail about event definitions, observation duration, collection procedures, severity grading, or whether the listed figures include all events. Deaths are not reported in the registry record.

Period labels identify the group entries but do not explain how participants moved between periods or whether the same individuals contributed to multiple entries. The record cautions that the arms are not a like-for-like control comparison. Accordingly, the safety counts should not be interpreted as a direct comparative estimate of risk. They are descriptive posted counts, and the information available does not support a broader conclusion about relative safety.

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

The registry record establishes that this completed Phase 3 study was designed to assess DE-114 ophthalmic solution in patients with allergic conjunctivitis, with placebo and olopatadine also named in the study summary. It specifies a primary outcome based on ocular itching scores collected after an allergen challenge, and it gives the measurement scale, assessment times, and averaging rule. Those details clarify what the endpoint was intended to represent.

The record does not report the primary group means, the estimated comparison, or its uncertainty. As a result, it does not show the direction, size, or precision of the primary outcome contrast. It also does not report numerical results for the named secondary outcomes in the information. The absence of those numerical results should not be interpreted as evidence of no effect, nor as evidence that a difference was present.

The endpoint concerns short-term itching response under a specified challenge condition. It does not, by itself, describe symptoms over longer periods, all aspects of allergic conjunctivitis, or outcomes outside the stated assessment setting. In general, a measure can be relevant to a particular research question while still representing only one part of a broader clinical experience.

The registry record’s design caveat also limits what a group comparison could mean. Allocation is not stated, and the record says the comparison is not randomized and that the arms are not a like-for-like control comparison. Even if numerical contrasts were available, these design features would need to be considered before attributing a difference specifically to treatment.

The safety entries report zero affected in the posted serious-event and other-event fields for the listed groups. They do not provide a complete account of all possible safety outcomes, and deaths are not reported in the registry record. Overall, the record describes the study question and endpoint but does not contain enough outcome and analysis information to support a conclusion about the size, precision, or causal interpretation of treatment effects.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an outcome result are different kinds of information. The registry record specifies a challenge-based itching score, the scale used, when assessments occurred, and how the primary endpoint was averaged. That information makes the intended measurement more transparent, but it cannot substitute for the group estimates and uncertainty needed to interpret a comparison.

It also highlights the role of design information in statistical interpretation. A comparison of group averages is not automatically a causal estimate. The registry record does not state allocation and explicitly cautions that the comparison is not randomized and that the arms are not a like-for-like control comparison. That caveat is central: numerical results, even if available, would need to be understood in light of how the groups were formed and how period-specific observations were analyzed.

The endpoint is based on eye-level scoring by subjects and an average across three post-challenge times. In general, these details raise analytical questions about related measurements within a person, use of one or both eyes, and handling of incomplete assessments. The record does not describe how these issues were handled. Transparent analysis methods help readers distinguish a clearly defined measurement from an adequately supported statistical comparison.

The registry also lists several outcome analyses, while not reporting a multiplicity strategy or missing-data approach. These omissions show why a list of outcomes alone cannot establish how strongly a particular result should be interpreted. Readers need the analysis plan, estimates, uncertainty, and population definitions to assess robustness and precision.

Finally, the posted safety counts demonstrate the distinction between a reported zero in a specified field and a comprehensive claim that no adverse events occurred. Careful statistical reading keeps conclusions aligned with what the record actually documents.

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.

The primary limitation for interpreting efficacy is that the registry record does not report a numerical result for the primary endpoint. It gives the endpoint definition but not group means, a between-group estimate, uncertainty, or a p-value. The listed secondary outcome results are also not reported in the information. Thus, the direction and precision of the outcome comparisons cannot be evaluated.

Design details are limited. The official title describes a double-masked comparison study, but the registry record does not describe masking procedures. Allocation is not stated, and the record flags the comparison as not randomized and cautions that the arms are not a like-for-like control comparison. Arm descriptions are blank. The period labels do not establish treatment sequence or whether participants contributed observations in more than one period.

The record does not report the statistical model, analysis population, handling of eye-level dependence, or approach to repeated measurements. It also does not describe missing-data methods or whether analyses adjusted for baseline values or other factors. Multiplicity handling for the four listed outcome measures and analyses is not reported. These details are important for assessing whether estimates are unbiased and how precisely they should be interpreted.

The safety information is limited to the listed affected counts and at-risk groups. Event definitions, observation duration, collection methods, and further details are not reported in the registry record. Deaths are not reported. The posted zero counts should therefore be interpreted narrowly and do not amount to a complete safety assessment.

The registry record lists enrollment of 87, but does not provide further participant characteristics in the information available for this analysis. Its sample-size assumptions describe planning illustrations based on an observed effect, not the trial’s own design; the record does not report its sample-size justification. Taken together, these limitations leave the study question and measurement process clearer than the results and their statistical basis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of DE-114 Ophthalmic Solution in Patients With Allergic Conjunctivitis — NCT01363700.
• Registry record last updated 2014-11-19; status last verified 2014-11.
• Results first posted 2014-11-05.
• 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

This completed Phase 3 study concerns DE-114 ophthalmic solution in patients with allergic conjunctivitis. The registry record lists enrollment of 87 and primary completion in 2012-06. The study summary names placebo and olopatadine hydrochloride 0.1% ophthalmic solution as comparators.

The primary outcome is mean ocular itching score compared with placebo in Period1, based on subject assessments at 3, 5, and 10 minutes after an allergen challenge performed 4 hours after drop instillation. The endpoint averages the three scores, which use a 0-to-4 scale.

The record does not report the numerical primary or secondary outcome results, the statistical analysis plan, the analysis population, or methods for missing data and multiplicity. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. Listed safety groups report zero affected for serious and other event fields; deaths are not reported in the registry record.