A Study of the Safety and Efficacy of Bimatoprost in Patients With Glaucoma or Ocular Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Safety and Efficacy of Bimatoprost in Patients With Glaucoma or Ocular Hypertension (NCT00538304), a randomized phase 2 study. The primary outcome is Change From Baseline in Mean Peak Macroscopic Conjunctival Hyperemia at Month 1.

2. Clinical Question

3. Trial Design

The registry identifies this as a randomized, quadruple-masked, parallel-group Phase 2 study. The groups received bimatoprost eye drops or placebo. The record describes the study as lasting one month and lists safety and efficacy among its aims. The enrollment entry is 222. The recorded study status is completed, with a start date of 2007-11 and a primary completion date of 2008-05.

Randomized allocation is intended to create groups that can be compared while reducing the influence of systematic differences at assignment. The record does not describe how the random sequence was generated, how allocation was concealed, or whether any stratification was used. Those procedural details are not reported in the registry record. Quadruple masking indicates the masking category recorded by the registry; the record does not specify which roles were masked or how masking was maintained.

The parallel model means the record describes separate groups assigned to the two study interventions, rather than a crossover comparison. No further details about visits, adherence procedures, rescue treatment, or concomitant care are reported in the registry record. The brief summary describes a one month study, and the primary endpoint timeframe is baseline and Month 1.

The modified Intent-to-Treat population for the primary endpoint was defined as enrolled patients who received at least one dose and had hyperemia evaluated both at baseline and at the month 1 visits. This definition is more specific than enrollment alone. The number included in that endpoint population, and the number analyzed in each group, are not reported in the registry record.

The record lists six outcome measures and describes secondary outcomes concerning conjunctival hyperemia, intraocular pressure, willingness to continue or use the medication, and perceived eye appearance. It lists no analyses. The statistical plan, sample-size justification, interim analyses, and handling of protocol deviations are not reported in the registry record. The design labels establish the broad structure of the trial, but do not fill in those operational or analytic details.

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: Modified Intent-to-Treat (m-ITT). The m-ITT population included all patients who were enrolled in the study, received at least 1 dose of study medication and were evaluated for macroscopic conjunctival hyperemia at baseline and the month 1 visits.

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 Mean Peak Macroscopic Conjunctival Hyperemia at Month 1, measured over Baseline, Month 1.

The primary endpoint is change from baseline in mean peak macroscopic conjunctival hyperemia at Month 1. Macroscopic conjunctival hyperemia means visible eye redness. An investigator grades redness by comparing the eye’s appearance with standard photographs on a 5-point scale, described as Scale 0 to +3: none, trace, mild, moderate, severe.

The record defines peak change separately for each eye. It compares the largest score across the hourly measurements at baseline with the largest score across the hourly measurements at month 1. A positive severity-grade change indicates an increase in redness. The primary outcome is expressed as a mean, with standard deviation specified as its dispersion measure. The registry record does not report the observed means, standard deviations, or a between-group estimate.

Using a peak score is intended to represent the most pronounced observed redness during the measurement period, rather than an average across all hourly observations. A change-from-baseline measure also expresses the month-one score relative to the participant’s own baseline score. These are general descriptions of how the defined endpoint works; the record does not report why this endpoint was selected or how it was expected to relate to other outcomes.

The endpoint is limited to investigator-rated appearance on the specified scale and to the recorded timeframes. It is not a direct measure of every aspect of eye comfort, function, or patient experience. The registry record lists separate secondary outcomes that address some other reported measures, but does not supply their results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the study as randomized, quadruple-masked, and parallel. These terms describe the intended design structure, not the quality or success of implementation. Randomization is generally used to reduce systematic differences between groups at assignment. Masking is generally used to limit the influence of knowledge about assigned treatment on care, assessment, or reporting. The registry does not give procedural details sufficient to assess how randomization or masking was carried out.

The primary endpoint is continuous in the record’s statistical description: its parameter is a mean and its dispersion measure is standard deviation. The measured score itself is based on ordered grades of visible redness. A mean summarizes the central level of change across observations, while a standard deviation describes how spread out individual values are around that mean. These are general explanations; the registry does not report the actual group summaries.

What does the endpoint’s change score represent?

The change score compares the peak score at baseline with the peak score at Month 1, separately for each eye. The peak is the largest score across hourly measurements in the relevant period. A positive change is defined as an increase in redness severity. The registry does not report how scores from the two eyes were combined for the mean endpoint, or whether any additional rules were applied when a measurement was unavailable.

In general, a change-from-baseline analysis can account for starting values by expressing follow-up relative to baseline. Its interpretation still depends on the analysis population, the handling of missing measurements, and the statistical model. None of those additional analytic details, beyond the stated modified Intent-to-Treat definition, is reported in the registry record.

What would a confidence interval contribute?

As a general statistical concept, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical procedure. For a between-group comparison, it can show which effect sizes are reasonably compatible with the observed data and model. A narrow interval indicates greater precision than a wide interval, while both the estimate and interval are needed to understand the direction and range of the comparison. The registry record does not report a confidence interval or the estimate it would accompany.

A p-value, in general, summarizes how unusual data at least as incompatible with a specified null hypothesis would be under the model and assumptions used. It does not measure the probability that a treatment works, and it does not describe the size or importance of an effect. No primary-outcome p-value or test is reported in the registry record, so no significance finding can be inferred.

Why do analysis details matter?

Statistical results depend on choices such as the comparison model, the treatment of baseline values, the unit of analysis, and the approach to incomplete observations. For this endpoint, measurements are described for each eye and across hourly observations. In general, repeated or paired measurements may be related rather than independent. A suitable analysis must reflect the data structure, but the registry record does not say how these features were handled.

Over-dispersion is a general issue when observed variability exceeds what a chosen statistical model assumes. If a model understates variability, uncertainty estimates can be too optimistic; if it accounts for the variation appropriately, inference is more credible. The record specifies standard deviation as the primary endpoint’s dispersion measure but does not report a model or any assessment of over-dispersion. It would therefore be inappropriate to claim that over-dispersion was present or that a particular correction was used.

The sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustration considers an effect expressed as a stated fraction of the observed effect. These are assumptions for planning illustrations, not evidence of the trial’s original design calculations or observed power. The numerical illustrations are not reported in the registry record, and the registry does not report the trial’s own sample-size justification. The stated primary effect is also not reported, so the planning illustration cannot be independently interpreted from this record alone.

In general, power is a property of a planned design under specified assumptions about the effect, variability, and analysis. It is not a retrospective measure of whether a result is trustworthy. A planning illustration cannot substitute for an observed estimate and its uncertainty. No sample-size calculation changes the fact that the primary comparison is absent from the posted results.

What can be concluded from the available analysis record?

The registry identifies six outcome measures and lists zero analyses. It does not describe an inferential method, multiplicity procedure, or analysis hierarchy. Consequently, the methods used to reach any efficacy conclusion are not reported in the registry record. The endpoint definition permits a reader to understand what was intended to be measured, but not to reconstruct an unreported analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary endpoint and secondary outcomes concerning hyperemia, intraocular pressure, willingness to use or continue medication, and reported eye appearance. It does not report an analysis hierarchy, a prespecified ordering of hypotheses, or a method for controlling the chance of false-positive findings across multiple outcomes. Whether multiplicity was addressed in the trial’s statistical analysis is not reported in the registry record.

As a general statistical principle, testing multiple outcomes can increase the chance that at least one result appears notable by chance. A prespecified strategy may identify a primary comparison, adjust inference across outcomes, or treat secondary findings as exploratory. The registry identifies a primary endpoint, but does not describe what inferential role was assigned to the secondary outcomes. Their results are not reported in the available record.

The primary endpoint population is defined as enrolled participants who received at least one dose and had assessments at baseline and the month 1 visits. This definition sets eligibility for the endpoint analysis; it does not explain what happened to participants lacking a required measurement. The number in the modified Intent-to-Treat population, the amount of missing endpoint data, and the methods used to handle missingness are not reported in the registry record.

In general, missing data can affect estimates when the reasons for missingness are related to participant characteristics or outcomes. Complete-case analysis, imputation, or model-based approaches make different assumptions. The record does not identify which, if any, approach was used. It also does not report sensitivity analyses assessing the effect of those assumptions.

Information about protocol deviations, excluded observations, and analysis populations beyond the stated modified Intent-to-Treat definition is not reported in the registry record. Without these details, it is not possible to assess whether the reported population and analysis followed a prespecified plan.

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 non-serious adverse event terms

The registry’s serious-adverse-event figures list 0 affected participants among 150 at risk in the bimatoprost eye drops group and 0 among 71 at risk in the placebo group. These are the serious-event counts recorded for the groups. They do not establish that serious events could not occur, and the registry record does not provide event-level descriptions or follow-up detail to interpret the counts further.

For other adverse events, the record lists 10 affected participants among 150 at risk in the bimatoprost eye drops group and 2 among 71 at risk in the placebo group. These figures describe participants recorded as affected, not the total number of individual events. The registry does not give the specific event terms, severity, timing, duration, or attribution for these counts in the information.

The record lists no serious adverse-event terms among its top serious terms. Death figures are not reported in the registry record. The adverse-event entries should therefore be read as a limited registry summary, not as a complete clinical safety narrative. They do not by themselves establish causation or allow a full comparison of safety profiles.

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

The registry record establishes that a randomized, quadruple-masked, parallel study compared bimatoprost eye drops with placebo in patients with glaucoma or ocular hypertension. It specifies a primary measure of change in mean peak macroscopic conjunctival hyperemia at Month 1 and explains how the eye-redness score was constructed. These details clarify the question the study set out to examine.

The record does not report the primary endpoint’s group estimates or a comparative statistical analysis. It therefore does not show whether the recorded mean change was greater in either group, how large any difference was, or how precisely it was estimated. An absence of reported results is not evidence that the groups were equivalent, nor does it demonstrate benefit or lack of benefit.

The registry also lists secondary measures, but does not report their results. That means the record cannot establish findings for the intraocular-pressure measure, patient or physician willingness measures, or reported changes in eye appearance. The presence of an outcome in the registry is not itself evidence of an observed effect.

The safety summary records no serious adverse events affecting participants in either group and records other adverse events in both groups. Those counts do not establish that an intervention caused or prevented an event, and the event details needed for a fuller interpretation are not reported. Death figures are also not reported in the registry record.

In general, a trial’s observed estimates, uncertainty intervals, analysis population, and missing-data methods are needed to distinguish a precise result from an inconclusive one. Those elements are not reported for the primary comparison in this record. The design and endpoint descriptions can be understood, but a conclusion about comparative efficacy or a broad safety profile cannot be drawn from the posted results.

13. Why This Trial Matters Statistically

This study is statistically notable as a registry record with a clearly described primary endpoint but no reported primary analysis. Knowing that the intended measure was change in mean peak visible eye redness helps clarify what was to be compared. It does not reveal the observed group values or the uncertainty around a comparison.

The endpoint definition also illustrates how a clinical measure can combine repeated observations into a participant-level summary. The record uses the largest hourly score in each measurement period and compares baseline with Month 1. That choice focuses on peak observed redness, rather than the average redness over the measurement period. Such endpoint construction shapes the meaning of any result and should be distinguished from the statistical model used to analyze it.

The stated modified Intent-to-Treat population is another important feature. It requires treatment exposure and evaluations at both baseline and Month 1, so it is not simply all enrolled participants. The absence of the analyzed population size and missing-data approach limits assessment of how the endpoint definition was implemented.

Finally, the record lists several outcomes but does not describe a multiplicity strategy or report outcome analyses. This illustrates why an endpoint list alone cannot establish which findings were tested, how uncertainty was handled, or what conclusions are justified. The central statistical lesson is that a detailed measurement definition and a completed study status cannot substitute for estimates, uncertainty, and transparent analytic methods.

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 most consequential limitation in the registry record is the absence of numerical primary-outcome results. Group means, a comparative estimate, uncertainty intervals, and a test result are not reported. The secondary-outcome results are also not reported, so the record cannot support a complete account of the outcomes listed.

The primary endpoint is described as a mean change on a graded scale, but the statistical analysis is not described. The record does not explain how the two eyes contributed to the mean, how hourly measurements were combined beyond the peak rule, or what model was used. The endpoint population is defined, but its size and the handling of missing assessments are not reported.

Details needed to assess implementation are also absent. The registry does not report the randomization procedure, allocation concealment, the roles covered by quadruple masking, or how masking was maintained. It does not give dosing details or explain concomitant care. These omissions limit evaluation of the design beyond its broad registry classifications.

The record does not report the trial’s own sample-size justification, an analysis plan, interim analyses, or a multiplicity approach. A planning illustration based on the observed effect is described, but its numerical results are not present in the registry record. Such an illustration cannot clarify the original design rationale or replace observed results.

The safety summary provides affected-participant counts but not event terms, severity, timing, duration, or relatedness. Death figures are not reported. Consequently, the listed counts are limited and cannot serve as a full safety assessment. These limitations apply to what the registry record reports; they do not establish what information may exist outside that record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of the Safety and Efficacy of Bimatoprost in Patients With Glaucoma or Ocular Hypertension — NCT00538304.
• Registry record last updated 2019-04-23; status last verified 2019-04.
• Results first posted 2011-10-27.
• 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

The registry describes a completed Phase 2 randomized, quadruple-masked, parallel study of bimatoprost eye drops versus placebo in patients with glaucoma or ocular hypertension. Enrollment is recorded as 222. The study began in 2007-11 and reached primary completion in 2008-05.

The primary endpoint was change from baseline in mean peak macroscopic conjunctival hyperemia at Month 1. Its measurement and modified Intent-to-Treat population are described, but the primary results and statistical analysis are not reported in the registry record. Secondary outcome results, missing-data methods, and multiplicity procedures are also not reported.

The safety summary records no serious adverse events affecting participants in either group and lists other adverse events affecting participants in both groups. Event details and death figures are not reported in the registry record. The design and endpoint can be characterized, but the posted information does not permit a comparative efficacy conclusion.