Non Interventional Study in Patients With Open Angle Glaucoma and/or Ocular Hypertension Treated With XALATAN®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Non Interventional Study in Patients With Open Angle Glaucoma and/or Ocular Hypertension Treated With XALATAN® (NCT00486252), a registered phase not stated study. The primary outcome is Change in Intraocular Pressure (IOP): Baseline to Month 3.

2. Clinical Question

3. Trial Design

This is a completed, non-interventional study listed under NCT00486252. The registry describes latanoprost treatment in patients with open-angle glaucoma and/or ocular hypertension. Its official title identifies first-line monotherapy and second-line monotherapy after beta-blocker therapy failure as treatment contexts. The registry intervention itself is classified as observational, rather than as an assigned experimental treatment.

The registry lists enrollment of 996. The study began in 2007-06, and primary completion was recorded as 2008-01. These dates describe the registered study; they do not establish how long any individual participant was followed. The stated primary evaluation period was 3 months, and the primary outcome timeframe is baseline to Month 3.

No comparator arm is described, and the registry gives no applicable arm descriptions. The record therefore does not establish a randomized or controlled comparison between treatment strategies. The number of analyses recorded is 0. Four outcome measures are recorded, including the primary change outcome and secondary outcomes for percentage change and categorized percentage change in intraocular pressure. Numerical results for these outcomes are not reported in the registry record.

The primary outcome description says intraocular pressure was measured with a non-contact or Goldmann tonometer. Three readings were taken in each eye, alternating between eyes and starting with the right eye. The mean of the three readings was used; if both eyes were study eyes, their means were averaged. These details define how the recorded measurement was formed, but the registry does not report the actual outcome values or additional details about site procedures, treatment adherence, or follow-up completeness.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) included all patients who received at least 1 dose of latanoprost (Xalatan®), had baseline IOP recorded, \& at least one postbaseline IOP measure recorded (at either Month 1 or Month 3). No imputation techniques used for missing data; only observed data reported. "n"=number of participants in each group for that category.

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 in Intraocular Pressure (IOP): Baseline to Month 3, measured over Baseline, Month 3.

The primary endpoint is change in intraocular pressure from baseline to Month 3, expressed in mmHg. The registry defines change as the Month 3 observation minus the baseline observation. Under that convention, a negative change would represent a lower measured pressure at Month 3 than at baseline; this explains the sign of the measure and does not state what the study observed.

Intraocular pressure is the measurement selected for the stated objective of evaluating the pressure-reducing effect of Xalatan over 3 months. The endpoint is continuous, and the registry specifies that its summary measure is the mean, with standard deviation as the dispersion measure. A mean describes the average observed change in the analysis population. A standard deviation describes how variable individual changes are around that mean; it is not the uncertainty interval for the mean.

Measurements were obtained using a non-contact or Goldmann tonometer. Three readings were made in each eye, alternating eyes and beginning with the right eye. The mean of the readings was used for an eye, and when both eyes were study eyes, the two eye means were averaged. This approach defines the measurement used for the endpoint. Numerical means and standard deviations for the endpoint are not reported in the registry record, so the direction, magnitude, and spread of the recorded changes cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it records a pressure value and a change in that value, rather than assigning each patient to a simple category. The registry specifies a mean as the summary measure and a standard deviation as the measure of dispersion. The mean describes the average change in the analyzed observations. The standard deviation describes how spread out individual changes are around that average. A small standard deviation would indicate less variation among individual observed changes than a larger one, but the registry does not report a numerical standard deviation for this outcome.

A standard deviation should not be confused with a confidence interval. A confidence interval is an inferential range intended to convey uncertainty about an estimated quantity, such as the population mean change. Its width depends on the estimate's uncertainty and the analysis method. The registry record does not report a confidence interval for the primary outcome. Without an estimate and an uncertainty measure, readers cannot judge the precision of the mean change or how compatible the data are with different possible underlying changes.

The change score is defined as the Month 3 intraocular pressure observation minus the baseline observation. This direction matters when interpreting the sign: a negative value corresponds to a lower recorded pressure at Month 3 than at baseline. This is a definition of the measure, not a statement about the study's result. The registry also describes how measurements were obtained: three readings per eye, alternating between eyes and beginning with the right eye, with the mean used for each eye. If both eyes were study eyes, the two eye means were averaged. Averaging repeated readings can reduce the influence of variation among readings, but it does not remove all measurement error or make an observational comparison causal.

In general, repeated measurements within a person, and measurements from two eyes of one person, may be related rather than independent. The registry describes averaging measurements to form the outcome, but does not report an analysis that models eye-level or repeated-measure correlation. No such model should be assumed. The outcome is presented as a mean change, and the record does not provide details of a more complex statistical model.

Over-dispersion is a general concern when data vary more than a chosen statistical model expects. It can make model-based standard errors and uncertainty estimates unreliable if the model does not account for that extra variation. It is most relevant when an analysis uses a probability model with a specified variance structure, such as a model for counts. The primary outcome is described as a continuous mean change with standard deviation, and the registry does not report a model or a dispersion adjustment. There is therefore no basis to say that over-dispersion was tested or addressed in this study.

The registry identifies the analysis population as the Full Analysis Set: patients who received at least one dose, had baseline intraocular pressure recorded, and had at least one postbaseline intraocular-pressure measurement at Month 1 or Month 3. This is an outcome-specific inclusion description, and it does not mean that every member necessarily contributed a Month 3 measurement. The number analyzed for the primary endpoint is not reported in the registry record. The record says only observed data were reported and no imputation techniques were used. In general, imputation fills in missing values under stated assumptions; not imputing means that a missing value is not replaced by an estimated one. It does not by itself show whether the observed cases are representative of all enrolled patients.

Sample-size calculations are planning exercises, not observed results. The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It is described as computed from the observed effect, rather than as the trial's own design. Such an illustration does not establish that the study was designed with those assumptions, and it is not observed power. The registry does not report a randomized two-arm comparison; accordingly, the equal-allocation assumption in a planning illustration should not be mistaken for a description of the observational treatment groups. The numerical observed effect and calculated planning values are not reported in the registry record.

Finally, the record lists 0 analyses and does not report numerical efficacy results, confidence intervals, or p-values. The statistical summaries described in the outcome definition indicate the intended form of reporting, not that those summaries are available. A reader can identify what was meant to be measured and how it was formed, but cannot reconstruct a result or its uncertainty from the registered 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("Latanoprost (All Subjects)", "Latanoprost (no Prior Beta-blocker Therapy)", "Latanaprost (Prior Beta-blocker Failure)")
n   <- c(945, 402, 531)
m   <- c(-5.3, -6.8, -4.1)
sp  <- c(3.9, 3.8, 3.5)
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  Latanoprost (All Subjects)  945  -5.300  3.900  -5.549  -5.051
CARM  Latanoprost (no Prior Beta-blocker Therapy)  402  -6.800  3.800  -7.173  -6.427
CARM  Latanaprost (Prior Beta-blocker Failure)  531  -4.100  3.500  -4.398  -3.802

11. Multiplicity, Missing Data and Analysis Populations

The registry records four outcome measures, including the primary change in intraocular pressure and secondary measures for percentage change and categorized percentage change. It does not report a multiplicity adjustment or a plan for controlling the chance of false-positive findings across multiple outcomes. The statistical plan is not reported in the registry record. Because numerical outcome results and analyses are not reported, there is no basis to assess how multiple outcomes were handled in practice or to compare evidence across them.

The analysis population includes patients who received at least one dose, had baseline intraocular pressure recorded, and had at least one postbaseline measurement at Month 1 or Month 3. The registry states that no imputation techniques were used and only observed data were reported. Thus, missing measurements were not replaced through imputation according to the registry description. The record does not report the amount or pattern of missing data, the number with an observed Month 3 value, or reasons for missingness. Those details matter because an analysis restricted to observed measurements can be affected if those measurements differ systematically from missing ones.

The registry does not report additional sensitivity analyses addressing missing data, an intention-to-treat population, or outcome-specific analysis counts. Those procedures should not be inferred from the Full Analysis Set description. The record also does not specify an interim-analysis plan or a sample-size justification. Without these details, the robustness of the analysis to missing data and multiplicity cannot be evaluated from the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 996 patients at risk for serious adverse events and records 0 affected by serious adverse events. It also records 122 affected by other adverse events. These are the figures in the safety record; the registry does not provide the terms of the reported non-serious events in the information, nor does it list serious adverse-event terms.

The deaths entry is not reported in the registry record. A missing death value should not be interpreted as a confirmed absence of deaths. The serious-event figure of 0 is a recorded count, but it does not establish that no unrecorded or unobserved events occurred. The safety denominator and event counts describe this observational cohort; without a comparator group, they do not estimate a relative safety difference between treatments.

The registry does not provide further information on event severity beyond the serious-versus-other classification, event timing, attribution to treatment, or duration of safety follow-up. These counts therefore give a limited description of the recorded safety data and should not be treated as a complete characterization of risk.

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

The registry establishes that the study was intended to evaluate intraocular pressure change over 3 months among patients treated with latanoprost. It specifies the endpoint, the measurement procedure, and an analysis-population definition. It also records an observational design, enrollment of 996, and safety counts. These details help define the question and the scope of the registered record.

The record does not report the numerical result for the primary endpoint. It therefore cannot show the average direction or size of change, the variation among participants, or the precision of any estimate. It also does not report numerical secondary-outcome results, confidence intervals, or p-values. No conclusion about statistical significance or clinical importance can be drawn from these registered details alone.

The design does not describe a comparator group or randomized allocation. A before-and-after measure, even if its numerical result were available, would describe change during observation rather than a controlled difference attributable to treatment. Other influences on change could not be separated from treatment effects using the information in this record. The study title describes first-line and second-line treatment contexts, but the registry does not present those contexts as a like-for-like comparison.

The safety record reports 0 serious adverse events and 122 other adverse events, while the deaths entry is not reported. These figures are descriptive counts, not comparative risk estimates, and the registry does not provide further detail needed to interpret event type, timing, or treatment attribution.

In short, the record clarifies what the investigators set out to measure and how selected measurements were summarized, but it does not supply the outcome estimates needed to judge the observed efficacy signal or its precision. It is not evidence of a causal treatment effect or a comparative safety result.

14. Why This Trial Matters Statistically

This study is statistically instructive because it separates an intended clinical question from the evidence needed to answer it. The registry defines a continuous endpoint, a baseline-to-Month 3 change, and a measurement procedure that averages repeated readings. Those details help readers understand what an eventual estimate would represent. At the same time, the absence of numerical outcome results means that the endpoint definition cannot stand in for an estimate.

The observational design is also important. Recording change during treatment is not the same as estimating a treatment effect against a control condition. A controlled contrast can help distinguish treatment-related change from other changes over time; this registry does not describe such a comparator. The title identifies different treatment contexts, but the registered information does not establish a direct comparison between them.

The analysis-population definition and the no-imputation statement illustrate why denominators and missingness matter. Enrollment does not necessarily equal the number contributing to a specific Month 3 analysis. The registry does not report the outcome-specific analysis count or the extent and pattern of missing measurements. Without that information, readers cannot assess how much observed data underpin the primary endpoint or whether missingness may affect interpretation.

Finally, the record separates efficacy reporting from safety counts. The serious and other adverse-event figures provide a limited descriptive account, while the unreported death entry and lack of event detail constrain interpretation. Overall, the record is useful for understanding study structure and measurement, but its statistical value for estimating outcomes is limited because the numerical efficacy results and their uncertainty are not reported.

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 principal limitation is that numerical results for the primary endpoint are not reported in the registry record. Although the endpoint is defined as mean change in intraocular pressure from baseline to Month 3, no mean change or standard deviation is given. Numerical results for the listed secondary outcomes are also not reported. The direction, size, and precision of the observed outcome therefore cannot be evaluated.

The record describes an observational study and does not identify a comparator group or randomized allocation. It cannot support a controlled treatment-effect interpretation based on the information registered. The official title names first-line and second-line treatment contexts, but the record does not give usable arm descriptions or a like-for-like comparison between those contexts.

The registry says the analysis used observed data without imputation. It does not report the number with a Month 3 measurement, the extent or pattern of missing data, or why measurements were missing. Because inclusion in the stated Full Analysis Set requires a postbaseline measure at Month 1 or Month 3, membership in that set does not necessarily establish availability of the primary Month 3 outcome. Outcome-specific denominators are not reported.

Further limitations include the absence of reported confidence intervals, p-values, and a detailed statistical plan. The registry does not report how multiplicity was handled, whether sensitivity analyses were performed, or how potential confounding was addressed. Safety information is also limited: deaths are not reported, and details about other adverse events, timing, and treatment attribution are not available in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Non Interventional Study in Patients With Open Angle Glaucoma and/or Ocular Hypertension Treated With XALATAN® — NCT00486252.
• Registry record last updated 2021-03-01; status last verified 2009-11.
• Results first posted 2009-07-16.
• 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

NCT00486252 is a completed, non-interventional study of latanoprost (Xalatan®) in patients with open-angle glaucoma and/or ocular hypertension. The record lists enrollment of 996, a start date of 2007-06, and primary completion in 2008-01. The stated primary objective was to evaluate intraocular pressure change over 3 months.

The primary endpoint is mean change from baseline to Month 3 in mmHg, with standard deviation specified as the measure of dispersion. The registry describes the measurement procedure and defines a Full Analysis Set based on treatment receipt and recorded baseline and postbaseline measurements. It states that only observed data were reported and no imputation was used.

Numerical efficacy results are not reported in the registry record. No comparator group is described. The safety record lists 0 serious adverse events, 122 other adverse events, and a death count that is not reported.