This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Efficacy of Changing to DuoTrav in Patients Uncontrolled on Timolol (NCT01336569), a na phase 4 study. The primary outcome is Mean Intraocular Pressure (IOP) Change at the Final Visit From Baseline (Prior Beta-blocker Monotherapy).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01336569 |
| Phase | Phase 4 |
| Condition | Glaucoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 50 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alcon Research |
| Results posted | Yes |
2. Clinical Question
Population
Participants had open-angle glaucoma or ocular hypertension that was uncontrolled on beta-blocker monotherapy with timolol 0.5%. The primary outcome population is described as the Intent-to-Treat (ITT) group: participants who received study medication and had at least one on-therapy study visit. The registry record does not report how many participants contributed primary outcome measurements.
Intervention
Participants changed to a fixed combination of travoprost 0.004% and timolol maleate 0.5%, identified as DuoTrav. The regimen was one drop in the study eye nightly for up to 6 weeks.
Comparator
There was no concurrent control group. The comparison for the primary outcome is each participant’s baseline IOP while on prior beta-blocker monotherapy versus IOP at the final visit after changing treatment. The registry lists allocation as NA and describes a single-group study.
Primary question
The study asked how mean IOP changed from the baseline measured during prior beta-blocker monotherapy to the final visit, within the period of up to 6 weeks. IOP was measured in millimeters mercury (mmHg) using Goldmann applanation tonometry. A more negative change represents a greater reduction in IOP. The registry record does not report the observed mean change or its variability, so the size and precision of the change cannot be assessed from the posted results.
3. Trial Design
This was a Phase 4, completed, single-group study registered as NCT01336569. Its stated purpose was to assess safety and IOP-lowering efficacy after changing to DuoTrav from prior timolol 0.5% monotherapy. The study population was described as participants with open-angle glaucoma or ocular hypertension uncontrolled on beta-blocker monotherapy.
All participants in the intervention group received the travoprost 0.004%/timolol maleate 0.5% fixed combination. The recorded regimen was one drop to the study eye nightly for up to 6 weeks. The primary outcome compared baseline, defined in relation to prior beta-blocker monotherapy, with the final visit. The record gives the outcome timeframe as baseline to up to 6 weeks.
The registry records enrollment of 50, but that figure should not be treated as the primary-outcome analysis count. The outcome population is defined as participants who received study medication and had at least one on-therapy study visit; the number meeting that definition and contributing data is not reported in the registry record. The record lists allocation as NA, masking as none, and the model as single group. There is therefore no randomized, concurrent comparison in the registered design. The study started in 2011-02, had primary completion in 2012-03, and is marked completed.
Because the study uses a before-and-after comparison in one group, changes over the observation period cannot be separated from other changes over time using a concurrent control. The design can describe the participants’ measured change after switching, but the registry record does not establish what would have happened to comparable participants who continued their prior treatment.
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 50 enrolled, 1 participant did not meet inclusion/exclusion criteria and was exited from the study prior to receiving study product. This reporting group includes all participants who received study product.
Overall Study
| Stage | DuoTrav |
|---|---|
| STARTED | 49 |
| COMPLETED | 45 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | DuoTrav |
|---|---|
| Lost to Follow-up | 4 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT): All participants who received study medication and had at least one on-therapy study visit.
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 reporting group includes all participants who received study product.
| Characteristic | Unit | DuoTrav |
|---|---|---|
| Participants analysed | 49 | |
| Age Continuous | years | 63.3 (SD 10.6) |
| Sex: Female, Male: Female | Participants | 36 |
| Sex: Female, Male: Male | Participants | 13 |
| Region of Enrollment: Brazil | participants | 49 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Intraocular Pressure (IOP) Change at the Final Visit From Baseline (Prior Beta-blocker Monotherapy), measured over Baseline, up to 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | millimeters mercury (mmHg) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean change in intraocular pressure from baseline on prior beta-blocker monotherapy to the final visit. IOP is recorded in millimeters mercury (mmHg) and measured with Goldmann applanation tonometry. The registry describes high IOP as a risk factor for developing glaucoma or for glaucoma progression, and specifies that a more negative change indicates a greater reduction.
A mean change combines individual measurements into a group-level estimate of the direction and average size of change. Its interpretation depends on the values contributing to the baseline and final-visit measurements, as well as the amount of variation among participants. The registry record identifies standard deviation as the measure of dispersion, but it does not post the mean change, standard deviation, or analysis count. Those omissions prevent assessment of the observed magnitude and precision of the endpoint.
The endpoint is a change over time within the study group, not a difference between randomized treatment groups. A before-and-after measurement can describe what was observed among participants who met the outcome-population definition. By itself, it does not isolate the effect of the treatment change from other influences that may coincide with the observation period.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically interpretable outcome: change in mean IOP from baseline on prior timolol monotherapy to the final visit after changing to the fixed combination. It also explains the direction of the measure: a more negative change indicates a greater reduction. However, the posted record does not include the observed mean change or its standard deviation. It therefore does not show whether the group’s mean IOP increased or decreased, how large any change was, or how variable the changes were across participants.
Precision cannot be evaluated without an estimate and its uncertainty. In general, a confidence interval describes a range of values compatible with the data under the analysis assumptions; its width conveys how precisely an effect has been estimated. No confidence interval for the primary outcome is reported in the registry record. Nor are the baseline and final mean IOP values, the number of participants included in the primary outcome calculation, or the analysis details reported. A p-value for that outcome is not reported either.
The design is also important to interpretation. Participants were changed from prior beta-blocker monotherapy to DuoTrav, and the primary comparison is within the single group. Without a concurrent control group, the observed before-and-after difference, if reported, would not by itself distinguish a treatment-associated change from other influences over time. The registry lists allocation as NA and masking as none; it does not describe a randomized, masked comparison.
Enrollment is recorded as 50. This is a registry enrollment figure, not a reported outcome denominator. The ITT definition requires receipt of study medication and at least one on-therapy study visit, and the actual number meeting that definition is not reported in the registry record. The adverse-event risk group is separately listed as 49; that count should not be substituted for the missing primary-outcome analysis count.
The sample-size assumptions describe planning illustrations based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such illustrations are not observed power and do not describe this single-group study’s design. The observed primary effect needed for those illustrations is not reported in the registry record. Consequently, neither those assumptions nor the enrollment figure can establish the precision of an unreported outcome estimate.
The registry record lists one outcome measure and zero analyses. This supports a narrow reading: the record identifies the intended endpoint and some design and safety details, but does not post the primary efficacy analysis. No conclusion about the direction, magnitude, or statistical uncertainty of the primary IOP change can be drawn from the posted results.
9. Statistical Methods Explained
The registry describes the primary outcome as a mean, a summary suited to a continuous measurement such as IOP. For each participant with the relevant measurements, a change can be defined by comparing the final-visit value with the baseline value. The group mean change then summarizes the average direction and magnitude of those individual changes. In this study, the stated interpretation is that a more negative change represents a greater reduction in IOP.
What does the standard deviation describe?
The standard deviation describes how spread out individual values are around their mean. For a change outcome, it gives information about variation in participants’ changes, rather than the uncertainty of the group mean alone. A mean can mask substantial differences among individuals, so the mean and standard deviation answer different descriptive questions. The registry names standard deviation as the dispersion measure but does not report its value for the primary outcome.
How does a confidence interval help?
In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. It is not a guarantee that the true value lies within a particular interval, and its interpretation depends on the method and data. The registry record does not report a confidence interval for the mean IOP change. Without an estimate and its interval, the precision of the primary result cannot be judged.
What does a p-value address?
In general, a p-value assesses how compatible the data are with a specified null hypothesis under the chosen statistical model. It does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. A p-value is most informative when considered alongside the effect estimate, its uncertainty, the design, and the analysis plan. The primary outcome’s p-value and analysis procedure are not reported in the registry record.
What does the single-group comparison permit?
The primary outcome compares measurements over time within one group: baseline during prior beta-blocker monotherapy and a final visit after the change to DuoTrav. In general, repeated measurements can describe how participants’ values changed during follow-up. Without a concurrent comparison group, however, the analysis cannot separate the change associated with the treatment switch from other events or influences occurring over the same period. The registry lists allocation as NA and the model as single group; no randomized comparison is described.
What are the planning illustrations?
In general, sample-size calculations use assumptions about a target effect, variability, significance level, power, and allocation to estimate the number of participants needed for a future study. The registry’s stated assumptions describe a planning illustration based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions, not evidence about the power achieved in this study. The registry record does not report the observed primary effect or the numerical planning results, and the registered study is single group rather than an equal-allocation two-arm comparison. A planning illustration should therefore not be read as observed power or as a description of the trial’s design.
More generally, over-dispersion refers to variability greater than a statistical model assumes. When a model underestimates variability, standard errors and uncertainty estimates may be too small, making results appear more precise than warranted. Whether over-dispersion is relevant depends on the outcome and model. The record identifies a continuous mean outcome and standard deviation, but does not report a fitted model or an analysis method that would allow assessment of this issue.
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.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| DuoTrav | 45 | -5.000 | 3.600 | -6.082 to -3.918 |
R code and output
arm <- c("DuoTrav")
n <- c(45)
m <- c(-5)
sp <- c(3.6)
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 DuoTrav 45 -5.000 3.600 -6.082 -3.91811. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure and zero analyses. The primary endpoint is mean IOP change from baseline to the final visit. The record does not describe a multiplicity strategy, such as adjustment for testing several outcomes or several comparisons. With one registered outcome measure, the record alone does not establish whether additional analyses or tests were planned or conducted; that information is not reported in the registry record.
The outcome population is defined as all participants who received study medication and had at least one on-therapy study visit. This definition identifies who would qualify for the stated ITT population, but the record does not report the number included in the primary analysis, the number with missing outcome measurements, or how missing measurements were handled. It does not state whether any imputation, complete-case analysis, or other missing-data method was used. Those choices can affect an estimate when measurement availability is related to participants’ outcomes or characteristics.
The record reports enrollment of 50, but enrollment does not establish how many participants posted data for the primary endpoint. The safety group is reported separately, and its denominator should not be assumed to be the efficacy analysis denominator. The actual primary analysis population and its baseline and final-visit data availability are not reported in the registry record.
Interim analyses and any related statistical safeguards are not reported in the registry record. The analysis plan, including any adjustment or sensitivity analyses, is also not reported. These gaps limit assessment of how the primary outcome was analyzed and how robust any estimate would be to missing data or analytic choices.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| DuoTrav | 1 | 49 | 2.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| DuoTrav | 0 of 49 |
Most frequent serious adverse event terms
| Event term | Organ system | DuoTrav |
|---|---|---|
| Enterorrhagia | Gastrointestinal disorders | 1 of 49 |
Serious events with the highest arm-level rate: enterorrhagia (2.0%).
The registry lists a DuoTrav safety group with 49 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it lists 49 participants at risk and 0 affected. These are separate registry categories; the record does not provide event-level detail sufficient to reconstruct timing, duration, severity beyond the category, or possible relationships to treatment.
The registry also lists Enterorrhagia at 2.0% among the top serious adverse-event terms. The record does not provide further context for that term or explicitly connect it to the group-level count in a way that supports additional interpretation. Deaths are not reported in the registry record.
These figures describe events recorded in this study group. They are not a comparison of event rates between treatments, because the registered design has no concurrent control group. The safety counts should not be interpreted as establishing whether the treatment caused an event or as a complete account of risk. The registry record does not report further details needed to assess causality or compare safety with continued timolol monotherapy.
13. What the Result Does, and Does Not, Mean
The record establishes that the study was designed to assess IOP change and safety after participants with open-angle glaucoma or ocular hypertension uncontrolled on timolol 0.5% monotherapy changed to DuoTrav. It specifies a nightly dose to the study eye for up to 6 weeks and defines the primary outcome as mean IOP change from baseline to the final visit. It also states that a more negative change indicates a greater reduction.
What the registry record does not establish is the observed primary outcome. The mean change, standard deviation, confidence interval, p-value, and primary analysis count are not reported. As a result, the posted results do not show the direction or size of the mean IOP change, or how precisely it was estimated. The absence of a reported estimate is not evidence that there was no change.
Even if a before-and-after estimate were available, this single-group design would describe change over time rather than provide a randomized comparison with continued timolol monotherapy. Without a concurrent control group, other influences during follow-up cannot be distinguished from the effect of switching treatment based on the design alone. The registry’s allocation and masking fields are NA and none, respectively.
The safety record reports one participant affected by a serious adverse event among 49 at risk and no participants affected in the other adverse-event category among 49 at risk. These counts are descriptive and do not establish causality or provide a treatment comparison. The record also lists Enterorrhagia at 2.0% among top serious terms, but does not report additional context for interpreting that term.
Accordingly, the registry record describes the question, treatment regimen, outcome definition, and some safety counts, but does not post enough primary efficacy results to quantify the observed IOP change or its uncertainty. It does not support a conclusion about comparative effects against a control treatment.
14. Why This Trial Matters Statistically
This study illustrates why an outcome definition and a result are not interchangeable. The registry specifies a continuous endpoint, its measurement method, its timeframe, and the direction of improvement. Those details make the intended question understandable. Yet without the mean change, dispersion, analysis count, or uncertainty interval, the endpoint cannot be evaluated quantitatively from the posted results.
It also highlights the distinction between a within-group change and a controlled treatment contrast. Measuring IOP before and after a treatment switch can describe the pattern in the study group. A concurrent control would address a different question by helping distinguish changes over time from differences associated with treatment assignment. The registry describes a single-group design, so the primary comparison is not a randomized between-group effect.
Finally, the record separates enrollment from the outcome population and safety denominators. Enrollment is listed as 50, while the endpoint definition requires medication receipt and at least one on-therapy visit. The number analyzed for the primary outcome is not reported, and the safety denominator is separately stated. Keeping those populations distinct is essential when interpreting results.
These features matter for statistical reading: clear measurement definitions help explain what a study intended to estimate, while complete outcome reporting and a design suited to the comparison are needed to judge the estimate and its precision.
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 main limitation for interpreting efficacy is that the registry record does not report the primary outcome estimate or its uncertainty. It identifies mean IOP change and standard deviation as the endpoint and dispersion measure, but provides no values for either. The analysis count, confidence interval, p-value, and primary analysis method are also not reported. Thus, the magnitude, direction, variability, and precision of the observed change cannot be assessed from the posted results.
The design is single group, with a before-and-after comparison from prior beta-blocker monotherapy to DuoTrav. There is no concurrent control group in the registry record, so changes over time cannot be separated from the effect of the treatment change by a controlled comparison. The record lists masking as none and allocation as NA.
Enrollment is recorded as 50, but the number in the ITT population or contributing primary outcome measurements is not reported. The record does not explain missing outcome data or describe sensitivity analyses. It also does not report whether any interim analyses or multiplicity procedures were planned or used.
The observation period is described as up to 6 weeks, which limits the endpoint’s timeframe to the recorded short-term follow-up. Further follow-up information is not reported in the registry record. Safety information is also limited: group-level event counts and a top serious-event term are listed, but additional event details and deaths are not reported. These limitations constrain interpretation of both efficacy and safety.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Safety and Efficacy of Changing to DuoTrav in Patients Uncontrolled on Timolol — NCT01336569.
- Registry record last updated 2013-07-08; status last verified 2013-05.
- Results first posted 2013-07-08.
- 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.
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19. Record Summary
NCT01336569 is a completed Phase 4, single-group study sponsored by Alcon Research. It enrolled 50 participants with open-angle glaucoma or ocular hypertension described as uncontrolled on timolol 0.5% monotherapy. Participants changed to a fixed combination of travoprost 0.004% and timolol maleate 0.5%, taken as one drop in the study eye nightly for up to 6 weeks.
The primary outcome was mean IOP change at the final visit from baseline on prior beta-blocker monotherapy, measured in mmHg by Goldmann applanation tonometry. A more negative change indicates a greater reduction. The registry record does not report the primary outcome estimate, its standard deviation, or its analysis count.
The safety record lists 1 serious adverse event among 49 at risk and 0 participants affected in the other adverse-event category among 49 at risk. The primary efficacy result and further details needed for a controlled comparison are not reported in the registry record.