DE-111 Against Tafluprost Ophthalmic Solution 0.0015% Alone and Concomitant Use of Tafluprost Ophthalmic Solution 0.0015% Plus Timolol Ophthalmic Solution 0.5%: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for DE-111 Against Tafluprost Ophthalmic Solution 0.0015% Alone and Concomitant Use of Tafluprost Ophthalmic Solution 0.0015% Plus Timolol Ophthalmic Solution 0.5% (NCT01342081), a registered phase 3 study. The primary outcome is Change From Baseline in Mean Diurnal IOP(Intraocular Pressure) at End of Study.

2. Clinical Question

The registry record identifies a single primary outcome: change from baseline in mean diurnal intraocular pressure at the end of the study. It defines the mean as an average of measurements taken at 9:30 before dosing, 11:30, and 17:30. The stated measurement period is Week 0 at baseline and Week 4 at the end of the study.

The comparison involves three treatment groups, but the record does not provide the numerical change in pressure for any group, the estimated contrasts between groups, or uncertainty measures such as confidence intervals. The superiority and non-inferiority objectives therefore describe questions the study set out to examine, not conclusions that can be drawn from the registry record. The record also does not give the non-inferiority margin or additional detail about the statistical tests used to address either objective.

Safety was also to be compared and evaluated, according to the brief summary. The available adverse-event figures report counts of affected participants, but they do not supply a narrative of the safety findings or clarify the handling of missing observations. The clinical question is thus identifiable, while the numerical evidence needed to judge the primary comparison is not reported in the registry record.

3. Trial Design

This is a Phase 3 study with a parallel-group design. The registry record lists 489 participants as the enrollment and describes the study as completed. The listed conditions are open-angle glaucoma and ocular hypertension. The start is recorded as 2011-05, and primary completion as 2012-09.

Three interventions are listed: DE-111 ophthalmic solution; tafluprost ophthalmic solution 0.002%; and concomitant use of tafluprost ophthalmic solution 0.002% plus timolol ophthalmic solution 0.5%. The registry’s arm descriptions correspond to these three regimens. A parallel-group design assigns participants to treatment groups for comparison rather than describing a sequence of treatments within each participant. The registry record does not give details about treatment duration beyond the primary endpoint’s Week 4 end-of-study time point.

The brief summary calls the study multicenter, randomized, and double-masked. The official title also describes it as double-masked, while the registry’s masking field says triple. These descriptions are not fully aligned. The allocation information is listed as not stated, so the record does not give the allocation method or enough information to resolve the differing descriptions. The trial should not be characterized as a clearly documented randomized comparison on the basis of this record alone.

The stated objectives distinguish the two comparisons: superiority of DE-111 versus tafluprost alone, and non-inferiority of DE-111 versus tafluprost used with timolol. The brief summary says safety would be compared and evaluated as well. The registry lists one primary outcome measure and two analyses, but detailed analysis specifications and numerical efficacy results are not reported in the registry record. The record names Santen Pharmaceutical Co., Ltd. as sponsor.

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: Switched to following three arms randomly from Tafluprost ophthalmic solution 0.0015% (one drop at a time, once daily).

Overall Study

Reasons for not completing this period:

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: Subjects who have instilled the investigational drug at least once. Excluded from analysis in Tafluprost (n=1). Reason: Protocol Violation

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Mean Diurnal IOP(Intraocular Pressure) at End of Study, measured over Week 0(Baseline) and Week 4(End of Study).

The primary endpoint is change from baseline in mean diurnal intraocular pressure at the end of the study. Intraocular pressure is the clinical measure named by the trial as its treatment-effect outcome. The registry defines the diurnal mean as the average of measurements at 9:30 before dosing, 11:30, and 17:30. It identifies Week 0 as baseline and Week 4 as the end-of-study time point, with results expressed in mmHg.

Using measurements at several times of day is intended to represent pressure across the specified daily measurement schedule rather than relying on a single reading. Averaging those readings produces one continuous outcome for each participant at the time point. Comparing change from baseline focuses on how the measure differs from its starting value, rather than only comparing end-of-study values. These are general features of a change-from-baseline continuous endpoint; the registry does not report the specific rationale for choosing this endpoint or measurement schedule.

The record identifies the endpoint as a mean and lists standard deviation as its dispersion measure. However, numerical means, standard deviations, treatment contrasts, and uncertainty estimates are not reported in the registry record. Consequently, the endpoint’s definition and units are available, but the magnitude and precision of the observed changes cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure represent?

The primary outcome is continuous: it is a change in mean diurnal intraocular pressure, expressed in mmHg. A continuous outcome can take a range of measured values, rather than being limited to categories such as event versus no event. The registry says the diurnal mean averages measurements at 9:30 before dosing, 11:30, and 17:30, and defines baseline and end-of-study as Week 0 and Week 4. These are endpoint-definition details; the record does not give the observed means or changes.

For a continuous measure, a treatment comparison is often expressed as a difference between group averages. Such an estimate describes the average contrast, while a measure of uncertainty indicates how compatible the data are with a range of possible contrasts. A confidence interval is a general way to express that uncertainty: it gives a range of values generated by a specified procedure, with a stated coverage level. No confidence interval or group contrast is reported in the registry record, so neither the estimate nor its precision can be interpreted.

What do superiority and non-inferiority ask?

The trial summary describes DE-111 as being evaluated for superiority against tafluprost alone and for non-inferiority against tafluprost used with timolol. These are different statistical questions. In general, superiority concerns whether evidence supports a difference under the chosen hypothesis test. Non-inferiority concerns whether the data rule out a loss larger than a margin selected in advance. That margin is essential for interpreting a non-inferiority result; it is not reported in the registry record. The record also does not state the statistical tests, hypotheses, or decision criteria used.

A non-inferiority conclusion cannot be inferred solely from a small or non-significant difference. General statistical interpretation requires the estimate, its uncertainty, the non-inferiority margin, and details of the analysis. Likewise, a superiority objective alone does not show that superiority was demonstrated. The numerical results and analysis details needed to evaluate either objective are not reported in the registry record.

How should the group design be read?

The registry identifies a parallel-group model and three treatment arms. In general, a parallel-group comparison evaluates outcomes across groups assigned to different regimens. The brief summary describes randomization, but allocation is listed as not stated. The record also describes masking as double in the title and summary and as triple in the masking field. These inconsistencies limit what can be said about the allocation and masking procedures; the record does not explain them.

Masking, when used, is intended to reduce the influence of treatment knowledge on participant behavior, care, or outcome assessment. Which parties were masked and how masking was maintained are not reported in the registry record. The parallel model and named regimens are identifiable, but those descriptions do not establish the detailed procedures used to conduct or analyze the trial.

What can a standard deviation tell a reader?

The registry lists standard deviation as the dispersion measure for the primary continuous outcome. In general, a standard deviation describes how spread out individual observations are around their group mean. It is not the same as a confidence interval: the standard deviation describes variability among observations, while a confidence interval describes uncertainty around an estimate under a statistical procedure. Neither the group standard deviations nor confidence intervals are reported in the registry record.

Variation in clinical measurements can reflect differences among participants and measurement variability. When observations are more variable, a group mean alone gives a less complete picture of the data. For this reason, readers generally need both a summary of the average and information about dispersion or uncertainty. Here, the endpoint’s intended dispersion measure is specified, but the numerical summaries are absent.

What do the planning illustrations mean?

The record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect considered is a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s own design justification. The record does not report the protocol’s sample-size rationale.

In general, a planning sample size estimates how many participants per arm might be needed to detect an assumed effect under specified assumptions. It is conditional on the effect size, variability, significance level, allocation, and statistical model used. When planning is based on the observed effect, the illustration should not be interpreted as observed power or as independent confirmation of the trial’s result. No planning values are stated in the registry record, and no new values can be inferred from the design description.

The registry record also distinguishes participant-per-arm planning quantities from total event counts for time-to-event settings. The primary endpoint in this trial is continuous, not identified as a time-to-event outcome. The planning description alone does not establish which analysis procedure was used for the primary endpoint.

What is missing for a complete statistical reading?

The record lists one primary outcome measure and two analyses, but does not report the numerical results or the analysis plan. It does not state the primary model, covariates, treatment contrast definition, assumptions about the distribution, or approach to repeated measurements. In general, those choices determine how the estimate is constructed and what population-level question it answers. The absence of those details means the statistical analysis cannot be reconstructed from the registry record.

There is also no reported description of missing endpoint observations, analysis populations, or sensitivity analyses. These are important because analyses can differ according to who is included and how incomplete data are handled. Such details should be considered alongside the estimated treatment effects, not replaced by the design objectives or enrollment figure.

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("DE-111", "Tafluprost", "Tafluprost Plus Timolol")
n   <- c(161, 163, 163)
m   <- c(-2.6, -0.9, -2.2)
sp  <- c(1.8, 1.7, 1.8)
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  DE-111  161  -2.600  1.800  -2.880  -2.320
CARM  Tafluprost  163  -0.900  1.700  -1.163  -0.637
CARM  Tafluprost Plus Timolol  163  -2.200  1.800  -2.478  -1.922

11. Multiplicity, Missing Data and Analysis Populations

The record lists one primary outcome measure and two analyses. It does not state whether the analyses correspond directly to the superiority and non-inferiority objectives, how the comparisons were specified, or whether any adjustment for multiple testing was planned. Multiplicity concerns the increased chance of misleading evidence when multiple hypotheses or outcomes are tested. In general, a statistical plan may address this through a prespecified testing sequence or another adjustment, but the registry record does not report such a procedure. The consequences of multiplicity cannot be evaluated from the available information.

The registry identifies the endpoint timeframe as Week 0 at baseline and Week 4 at the end of the study. It does not report the number of participants with measurements at either time point, the analysis population, or participant flow by group. It also does not state how missing measurements were handled, whether any imputation was used, or whether sensitivity analyses were performed. Missing-data methods can influence estimates when the amount or pattern of missingness is related to participants’ outcomes; the record does not provide information to assess that possibility.

The record does not describe whether the primary analysis followed an intention-to-treat, per-protocol, or other population definition. This omission is particularly relevant to a non-inferiority objective, for which interpretation can depend on the analysis population and the consistency of results across analyses. This is a general consideration, not a claim about the methods used in this trial.

Although the brief summary describes a randomized study, allocation is listed as not stated. Masking is described as double in the title and summary and as triple in the registry field. The record does not explain these discrepancies or provide enough information to determine how they were resolved. These design-reporting gaps, together with the missing analysis and missing-data details, limit independent evaluation of the results.

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 adverse-event record gives group-specific counts of participants at risk and affected. For DE-111, 161 were listed at risk for serious adverse events and 0 were listed as affected; the other-adverse-event figures are also 161 at risk and 0 affected. For tafluprost, the corresponding figures are 164 at risk and 0 affected for serious adverse events, and 164 at risk and 0 affected for other adverse events. For tafluprost plus timolol, the figures are 163 at risk and 0 affected for serious adverse events, and 163 at risk and 0 affected for other adverse events.

These are registry counts, not a detailed safety analysis. Zero affected in the posted categories means that the record lists no participants as affected in those categories; it does not establish that no adverse events of any kind occurred or provide information about event definitions, collection, duration, or severity. The record lists no top serious-event terms. Death counts are not reported in the registry record.

The at-risk counts should be read as the denominators reported for these adverse-event categories, not as the denominators for the primary efficacy analysis. The record does not provide a narrative interpretation of the safety findings or describe how safety data were analyzed. The figures therefore support only a narrow description of the recorded counts.

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

The registry record establishes what the trial set out to compare and how it defined its primary outcome. It identifies DE-111, tafluprost alone, and tafluprost with timolol as the treatment regimens, and states that the primary measure was change in mean diurnal intraocular pressure from baseline to the end of the study. It also records the study as completed and gives enrollment as 489.

Those details do not establish the direction or size of any treatment effect. The numerical primary-outcome results, treatment contrasts, confidence intervals, and p-values are not reported in the registry record. Consequently, the available information does not show whether the superiority objective was met or whether non-inferiority was demonstrated. The stated aims should not be confused with findings.

Nor does the available record support a detailed assessment of precision. A point estimate describes the observed contrast, while an uncertainty measure indicates how much the data leave open about the underlying contrast. Both are needed for a careful reading of the evidence. Neither is reported for the primary outcome. The outcome’s standard-deviation measure is named, but its values are absent.

The adverse-event figures report zero affected participants in the serious and other categories for each listed group, alongside the corresponding at-risk counts. They do not describe all possible safety outcomes or provide enough detail to infer the broader safety profile. Death counts are not reported in the registry record.

More generally, statistical results are interpreted in light of design, analysis populations, missing-data handling, multiplicity, and the prespecified comparison. Several of these details are not reported, and the registry’s descriptions of masking and allocation are not fully aligned. These limitations do not prove that the trial was conducted in a particular way or that its findings were biased; they identify what cannot be established from this record. A reader can identify the research question and outcome definition, but cannot independently judge the primary efficacy findings from the numerical information available.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly stated clinical question and a completed study do not, by themselves, provide enough information to interpret treatment comparisons. The registry identifies a Phase 3 parallel-group study, three treatment regimens, and a continuous primary endpoint. It also distinguishes a superiority objective from a non-inferiority objective. These elements matter because each objective calls for a different interpretation of the estimate and its uncertainty.

The endpoint definition is reasonably specific: it describes a change from baseline in mean diurnal intraocular pressure, the measurement times, the units, and the baseline and end-of-study time points. That clarity helps a reader understand what the planned outcome represents. But without the group summaries and treatment contrasts, the outcome definition cannot tell the reader what changes were observed or how precisely the comparison was estimated.

The record also shows why reporting consistency matters. The title and summary describe double masking, while the masking field says triple, and allocation is listed as not stated despite the brief summary’s description of randomization. The record does not explain these differences. Such inconsistencies limit independent assessment of the procedures, even though they do not establish that any particular procedure was or was not followed.

Finally, the record reports sparse safety counts but not a full account of outcome collection, analysis populations, missing data, or multiplicity. These are general features that help readers understand the reliability and scope of statistical conclusions. In this case, the record permits a description of the study’s aims and endpoint, but not an evidence-based judgment about whether either efficacy objective was achieved. That distinction is central to responsible interpretation of trial registrations.

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 this trial from the registry record is the absence of numerical efficacy results. The record does not report group changes in mean diurnal intraocular pressure, between-group estimates, confidence intervals, or p-values. As a result, neither the magnitude nor the precision of the primary comparisons can be described.

Design details are also incomplete or inconsistent. The brief summary calls the study randomized and double-masked, and the official title calls it double-masked. The registry’s masking field says triple, while allocation is listed as not stated. The record does not clarify which description is accurate or give the allocation procedure, who was masked, or how masking was maintained.

The analysis record is limited. It identifies one primary outcome and two analyses but does not describe the statistical methods, analysis populations, missing-data procedures, or multiplicity approach. It does not provide participant flow or the number included in the primary endpoint analysis. The stated non-inferiority objective is not accompanied by a reported margin, which prevents assessment of the criterion that would be needed to interpret that objective.

The safety information is also narrow. Counts of affected participants are reported for serious and other adverse events, but event definitions, collection procedures, and detailed safety results are not described. Death counts are not reported in the registry record. These limitations are specific to what is recorded; they do not establish that information was absent from other trial documents or that particular methods were not used.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: DE-111 Against Tafluprost Ophthalmic Solution 0.0015% Alone and Concomitant Use of Tafluprost Ophthalmic Solution 0.0015% Plus Timolol Ophthalmic Solution 0.5% — NCT01342081.
• Registry record last updated 2015-06-15; status last verified 2015-05.
• Results first posted 2015-05-14.
• 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.

19. Record Summary

The registry record describes a completed Phase 3, parallel-group study sponsored by Santen Pharmaceutical Co., Ltd., with enrollment of 489. The listed conditions are open-angle glaucoma and ocular hypertension. The start is recorded as 2011-05 and primary completion as 2012-09.

The three regimens were DE-111 ophthalmic solution, tafluprost ophthalmic solution 0.002%, and tafluprost ophthalmic solution 0.002% used with timolol ophthalmic solution 0.5%. The stated objectives were superiority of DE-111 versus tafluprost alone and non-inferiority versus the combination regimen. The primary endpoint was change from baseline in mean diurnal intraocular pressure at Week 4, with the mean based on measurements at 9:30 before dosing, 11:30, and 17:30.

The record does not report numerical efficacy results, analysis details, or the non-inferiority margin. It reports zero participants affected in the serious and other adverse-event categories for each group, but does not report death counts. Masking descriptions are inconsistent, and allocation is listed as not stated.