A Study of Patients With Primary Open Angle Glaucoma or Ocular Hypertension Who Were Insufficiently Responsive to Monotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Patients With Primary Open Angle Glaucoma or Ocular Hypertension Who Were Insufficiently Responsive to Monotherapy (NCT01637246), a registered phase not stated study. The primary outcome is Change From Baseline in Intraocular Pressure (IOP).

2. Clinical Question

The study’s brief description identifies it as a retrospective chart review of patients who had previously received monotherapy and then received any fixed combination. Thus, the clinical question concerns pressure measurements recorded during routine treatment rather than an assigned treatment contrast described in the registry. The record does not specify how long patients had received monotherapy, the reasons for changing treatment, or the exact timing of measurements within the stated baseline and 12-week timeframe.

Four secondary outcomes are named: patient and physician tolerability assessments using a 4-point scale, maintenance of better treatment compliance, and continuation of therapy after 12 weeks. Numerical results for those outcomes are not reported in the registry record. Without the numerical estimates and details of the contributing observations, the clinical question can be described, but its answer cannot be quantified from this record.

3. Trial Design

The registry describes this study as a retrospective chart review. Its stated purpose was to assess changes in intraocular pressure after treatment with any fixed combination in patients who had previously received monotherapy. This design uses information recorded in patient charts; it is not described as a prospective randomized assignment of treatment.

The listed group is “POAG or OHT”: patients with primary open-angle glaucoma or ocular hypertension previously treated with monotherapy and currently treated with any fixed-combination therapy. The intervention is listed broadly as any fixed-combination therapy. The registry does not identify individual treatment combinations, explain how a particular combination was chosen, or describe a separate concurrent control group. Allocation is not stated, and the record specifically cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison.

Enrollment is reported as 4385. That figure is not necessarily the number with a recorded baseline and 12-week pressure measurement: the primary-outcome population is defined as eligible patients who have data for the outcome, and its analyzed count is not reported in the registry record. The registry lists the primary timeframe as baseline and 12 weeks. The primary completion is recorded as 2011-11, and the study status is COMPLETED.

The primary endpoint is change from baseline in intraocular pressure, expressed in millimeters of mercury, with the mean and standard deviation specified. The record names four secondary outcomes concerning tolerability, compliance, and continuation of therapy. It does not report numerical outcome results or analysis records; the number of analyses is listed as 0. A protocol-level account of eligibility rules, chart abstraction, treatment selection, measurement procedures, or statistical methods is not reported in the registry record. Consequently, the design supports a description of the intended assessment, but the record does not permit a detailed reconstruction of how the chart review was conducted.

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

Analysis population for the primary outcome, as defined in the registry: All patients who met the study entry criteria and have data for this outcome measure

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 Change From Baseline in Intraocular Pressure (IOP), measured over Baseline, 12 Weeks.

The primary endpoint is change from baseline in intraocular pressure, measured in millimeters of mercury (mmHg), at the stated baseline and 12-week time points. Intraocular pressure is the fluid pressure inside the eye. The registry specifies that the endpoint is summarized as a mean and standard deviation, and defines a negative change from baseline as an improvement.

Change scores address how measurements differ from a participant’s own baseline rather than describing only the pressure at follow-up. In general, this can make the direction of change easier to interpret when participants begin at different pressure levels. The mean provides a summary of the average change in the outcome population; the standard deviation describes the spread of individual change values around that mean. Neither summary alone shows the full distribution of responses or how many participants had a change in either direction.

The endpoint is relevant to the stated study aim because the chart review was intended to assess pressure changes after fixed-combination treatment in patients previously treated with monotherapy. The registry does not report the baseline mean, the 12-week mean, the mean change, its standard deviation, or a confidence interval. The observed magnitude and precision of the endpoint therefore are not reported in the registry record. The endpoint definition establishes what was intended to be measured, not what the study found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is enough to identify the primary measure and some planning assumptions, but not enough to reproduce an analysis. It specifies a mean change in intraocular pressure with standard deviation, and gives baseline and 12 weeks as the timeframe. Numerical endpoint results and analysis records are not reported in the registry record.

What does a mean change describe?

For a continuous outcome, a mean change summarizes the average difference between a participant’s measurement at follow-up and that participant’s baseline measurement. The registry defines a negative value as an improvement for this outcome. A group mean can be useful because it gives a compact description of the average change, but it does not imply that every participant changed by that amount. Some observations can be above the mean and some below it. The mean also does not reveal the shape of the distribution, possible outliers, or the proportion of participants whose measurements moved in either direction.

The standard deviation describes dispersion: how spread out individual change values are around the group mean. It is not the same as the uncertainty in the estimated mean. In general, a confidence interval for a mean expresses a range of values compatible with the data and the method used, while reflecting sampling uncertainty. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. No confidence interval for the primary change is reported in the registry record, so neither its width nor the precision of the estimate can be assessed from this record.

What can a before-and-after comparison establish?

In general, comparing measurements at baseline and follow-up describes how the measured outcome changed among the people with observations at both times. A retrospective chart review does not, by that description alone, establish what would have happened over the same period without the treatment change. The registry does not describe a randomized allocation, and it cautions that the arms are not a like-for-like control comparison. Changes could coincide with treatment changes, clinical decisions, measurement conditions, or other events; whether and how such factors were addressed is not reported in the registry record.

A baseline measurement can help describe the starting point, and a within-person change can account for that starting measurement in the outcome definition. It does not by itself remove biases arising from who entered the chart review, why treatment changed, which measurements were recorded, or who had follow-up data. The registry does not report adjustment methods or a detailed analysis plan. No adjusted treatment effect can therefore be inferred from the endpoint description.

How should the planning assumptions be read?

The registry describes sample-size illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study used that design or that the listed treatment groups formed a valid randomized comparison. The registry itself describes this as a retrospective chart review and does not state allocation.

Any sample-size illustration under those assumptions is a planning calculation, not observed power and not a result of the chart review. It cannot substitute for a confidence interval around the observed endpoint or for a reported analysis. The numerical planning estimates are not reported in the registry record. The record also does not report the observed effect needed to interpret such illustrations in clinical units. For time-to-event outcomes, the registry’s stated illustration convention concerns total events; for other outcomes it concerns participants per arm. That general convention does not change the fact that the primary endpoint is a continuous measure and that no analysis result is posted.

What does the absence of analysis records mean?

The registry lists 0 analyses. This is a statement about the analysis information recorded there, not proof that no analysis was conducted outside the registry. It means the record does not supply a statistical test, an estimate, an interval, or the details needed to assess an analysis. The test procedure, treatment of repeated or incomplete measurements, covariate adjustment, and handling of unusual values are not reported in the registry record.

For a continuous measure, a statistical test might address whether a mean change is distinguishable from a specified reference under its assumptions. A confidence interval can communicate the range of effect sizes compatible with the data and is often more informative about precision than a test result alone. These are general concepts; no test result or interval is available for this study in the registry. Without those quantities, the record cannot support a claim about statistical significance or quantify uncertainty in the estimated change.

Likewise, the stated normal approximation belongs to the sample-size planning assumptions. It should not be treated as proof that the outcome analysis used a normal model, or that the observed change values met any particular distributional condition. The analysis model and its diagnostics are not reported in the registry record. The endpoint definition and planning assumptions should therefore be kept separate from any claims about the actual statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies change from baseline in intraocular pressure as the primary outcome and names secondary outcomes for patient tolerability, physician tolerability, better compliance, and continuation on therapy after 12 weeks. The numerical findings for these outcomes are not reported in the registry record. It lists 0 analyses, so it does not show which outcomes were analyzed, which comparisons were made, or whether any inferential results were generated.

Multiplicity is a general statistical concern when several outcomes or comparisons are assessed: the more opportunities there are to find an apparently notable result, the greater the chance of a misleading finding if the analyses are interpreted without accounting for that scope. A prespecified hierarchy or adjustment method can help clarify how multiple tests should be interpreted. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or whether outcomes were selected or adjusted after review of the data. No conclusion about multiplicity handling can be drawn from the outcome list alone.

The primary-outcome population includes eligible patients who have data for the outcome, while enrollment is reported as 4385. The number with usable baseline and follow-up measurements is not reported in the registry record. The record does not describe missing-data reasons, the amount of missingness, an imputation method, or a sensitivity analysis. It is therefore not possible to determine whether patients with recorded follow-up differed from those without it, or how missing observations may have affected the endpoint summary.

Details of the analysis population beyond the stated eligibility and data requirement are also not reported in the registry record. In particular, the record does not describe exclusions from the endpoint analysis or whether all eligible observations were included. These omissions matter because outcome availability and analysis choices can affect both the estimated mean change and its precision. The enrollment figure alone does not resolve those questions.

11. 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.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: keratitis (0.0%), dyspnoea (0.0%), keratitis herpetic (0.0%).

The registry lists one group, POAG or OHT, with 4385 reported as at risk for serious adverse events and 4 reported as affected by serious adverse events. For other adverse events, the at-risk figure is 4385 and the affected count is 0. Deaths are not reported in the registry record. These counts should be read as the registry’s recorded safety fields, not as a complete description of event timing, severity, clinical course, or relationship to treatment.

The most frequent serious-event terms listed are Keratitis, Dyspnoea, and Keratitis Herpetic, each with a reported value of 0.0%. The record does not provide further case-level information or clarify the interpretation of those term-level percentages. A reported 0.0% should not be expanded into claims about why an event was or was not observed, or about treatment causation.

Safety counts are descriptive. The record does not describe an untreated or randomized comparison group, and it does not report a method for attributing events to the fixed-combination therapy. The at-risk figure is not a measure of follow-up duration, and the registry does not report exposure time or details of safety surveillance. The figures therefore do not quantify comparative risk or establish whether the treatment caused an event. They should be interpreted alongside the limited design and reporting information available in the registry.

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

The record defines a study question about mean intraocular-pressure change over 12 weeks among patients with primary open-angle glaucoma or ocular hypertension who had previously received monotherapy and were currently receiving any fixed-combination therapy. It specifies the units, summary measure, and direction considered an improvement. Those details make clear what the primary endpoint was intended to describe.

The record does not report the numerical primary outcome. The size and direction of the observed mean change, the spread of individual changes, and the uncertainty around any estimate are not reported in the registry record. It is therefore not possible from this record to state whether pressure decreased on average or how precisely the change was estimated. The listed enrollment of 4385 does not tell how many participants contributed measurements to the primary outcome.

The design also limits what a change could mean even if a numerical estimate were available. A retrospective chart review of patients receiving treatment does not, by itself, separate a treatment-associated change from changes due to other factors over time. The registry does not describe a like-for-like control comparison or randomized allocation; it explicitly cautions that the arms are not a like-for-like control comparison. Consequently, the record cannot establish a causal effect of fixed-combination therapy.

Four secondary outcomes are named, but their numerical findings are not reported in the registry record. No analysis records are listed, and details about missing measurements, outcome analysis, or multiplicity are not reported. Those gaps prevent a full assessment of the evidence’s completeness and statistical uncertainty.

The appropriate reading is therefore narrow: the registry records an intended assessment of pressure change after treatment with any fixed combination in a specified patient group. It does not provide the result needed to quantify that change, and it does not establish comparative effectiveness, causation, or a treatment recommendation. The safety fields are also descriptive and do not supply a comparative estimate of risk.

13. Why This Trial Matters Statistically

This study raises important statistical issues because it combines a clinically understandable change measure with a retrospective, non-randomized design. Change from baseline in intraocular pressure is a direct way to describe how a continuous measurement varies over time among patients with recorded measurements. The mean and standard deviation would convey an average and the spread around it. But those summaries are not reported in the registry record, so the intended measure cannot be converted into a quantitative finding.

The record also illustrates why enrollment and analysis populations must be distinguished. Enrollment is reported as 4385, while the endpoint population requires both eligibility and data for the outcome. The number contributing to the primary endpoint is not reported in the registry record. Without that count and information about missing measurements, readers cannot judge how broadly the endpoint reflects the enrolled group.

A before-and-after chart review can describe observed change, but the absence of a like-for-like control comparison is central to interpretation. Patients may enter such a review because their prior treatment was insufficiently responsive, and treatment selection is not described in detail. The registry does not establish how those circumstances affected the measurements or whether analytical methods addressed them. This makes it especially important not to interpret a change as a causal treatment effect.

Finally, the record separates planning assumptions from study findings only if readers recognize their different roles. A sample-size illustration based on an observed effect and specified assumptions is not observed power, nor does it replace an estimate with uncertainty. Because the numerical endpoint findings and analysis details are not reported in the registry record, the study’s statistical result cannot be evaluated from the registry entry alone. The value of the record is chiefly in making the study question, outcome definition, and limits of the available reporting explicit.

14. 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 specific to this study is that the registry record describes the intended primary endpoint but does not report its numerical result. No mean change, standard deviation, confidence interval, or test result is reported in the registry record. This prevents assessment of the observed direction, magnitude, and precision of the endpoint.

The retrospective chart-review design also leaves important questions about treatment selection and measurement unavailable. The record does not describe why individual patients moved from monotherapy to a fixed combination, how a specific combination was chosen, or whether pressure measurements were collected under standardized conditions. Allocation is not stated, and the record cautions that the study is not a randomized comparison and that arms are not a like-for-like control comparison. These features limit causal interpretation.

Although enrollment is reported as 4385, the primary outcome is defined for eligible patients with outcome data. The analyzed count, the amount and pattern of missing data, and the handling of incomplete baseline or 12-week measurements are not reported in the registry record. It is not possible to determine whether the endpoint population represents all enrolled patients or whether missingness could have influenced the result.

The registry lists four secondary outcomes, but does not report their numerical results, analysis methods, or a strategy for handling multiple outcomes. It lists 0 analyses. Details of covariate adjustment, model assumptions for the endpoint analysis, sensitivity analyses, and subgroup analyses are not reported in the registry record. The listed sample-size assumptions do not fill these gaps: they are planning assumptions, not evidence about the actual analysis. Safety information is also limited to recorded counts and term percentages, without comparative attribution or follow-up detail. These limitations mean the entry supports a description of the study’s aims and record fields, but not a complete statistical evaluation of its findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Patients With Primary Open Angle Glaucoma or Ocular Hypertension Who Were Insufficiently Responsive to Monotherapy — NCT01637246.
• Registry record last updated 2012-09-21; status last verified 2012-08.
• Results first posted 2012-09-21.
• 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.

18. Record Summary

NCT01637246 is a completed retrospective chart review of patients with primary open-angle glaucoma or ocular hypertension who had previously received monotherapy and were currently receiving any fixed-combination therapy. Enrollment is reported as 4385. The primary outcome is change from baseline in mean intraocular pressure, in mmHg, at baseline and 12 weeks; a negative change is defined as an improvement.

The registry names secondary outcomes concerning patient and physician tolerability, better compliance, and continuation on therapy after 12 weeks. It reports safety counts for the POAG or OHT group, including 4 affected by serious adverse events and 0 affected by other adverse events; deaths are not reported in the registry record.

Numerical primary and secondary outcome results are not reported in the registry record, and the number of analyses is listed as 0. The record does not describe a randomized comparison and cautions that the arms are not a like-for-like control comparison. As a result, it defines the assessment but does not provide a quantitative treatment effect or establish causation.