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 A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion (BRAVO) (NCT00486018), a randomized phase 3 study. The primary outcome is Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00486018 |
| Phase | Phase 3 |
| Condition | Macular Edema, Retinal Vein Occlusion |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 397 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genentech, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with macular edema secondary to branch retinal vein occlusion (BRVO). The trial enrolled 397 patients at investigational sites in the United States. The primary endpoint population is described as the intent-to-treat randomized population.
Intervention
Intravitreal ranibizumab injection at doses of 0.3 mg or 0.5 mg. The registry record identifies both dose groups but does not describe the injection schedule in the arm descriptions.
Comparator
Sham injection. The study is described as randomized, double-masked, and sham injection-controlled.
Primary question
How did mean best corrected visual acuity (BCVA) score change from baseline to 6 months in the study eye, comparing the ranibizumab groups with the sham injection group? The registry record identifies this as the primary outcome but does not report numerical group results or a treatment comparison.
3. Trial Design
BRAVO was a Phase III, multicenter, randomized, double-masked, parallel-group, sham injection-controlled study of ranibizumab for macular edema secondary to BRVO. The registry record lists an enrollment of 397. The study included a 6-month treatment period and a 6-month observation period. Its listed start was 2007-07, primary completion was 2009-05, and status is completed.
The intervention groups received ranibizumab injection 0.3 mg or ranibizumab injection 0.5 mg. The comparison group received sham injection. The record does not provide arm-specific descriptions of the treatment schedule, details of allocation concealment, or further information about how masking was maintained. These features are not reported in the registry record.
Random allocation is intended, in general, to make treatment groups comparable at the point of assignment with respect to both measured and unmeasured characteristics. Double masking is intended, in general, to reduce the influence of treatment knowledge on participants’ experiences and on assessment or reporting. These are general purposes of the design features, not evidence about how completely they were achieved in this trial.
The primary outcome was mean change from baseline in BCVA score at 6 months. The registry describes the score as the number of correct letters read on Early Treatment Diabetic Retinopathy Study visual acuity charts, with testing beginning at a distance of 4 meters. The primary analysis population is identified as the intent-to-treat randomized population, with missing values imputed using last observation carried forward. Numerical primary results, estimates of between-group effects, and confidence intervals are not reported in the registry record.
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
| Stage | Sham Injection | Ranibizumab Injection 0.3 mg | Ranibizumab Injection 0.5 mg |
|---|---|---|---|
| STARTED | 132 | 134 | 131 |
| Received Drug (Safety Population) | 131 | 134 | 130 |
| COMPLETED | 123 | 128 | 125 |
| NOT COMPLETED | 9 | 6 | 6 |
Analysis population for the primary outcome, as defined in the registry: Intent to treat (randomized) population. Missing values were imputed using the last-observation-carried-forward (LOCF) method.
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.
| Characteristic | Unit | Sham Injection | Ranibizumab Injection 0.3 mg | Ranibizumab Injection 0.5 mg | Total |
|---|---|---|---|---|---|
| Participants analysed | 132 | 134 | 131 | 397 | |
| Age, Continuous | years | 65.2 (SD 12.7) | 66.6 (SD 11.2) | 67.5 (SD 11.8) | 66.4 (SD 11.9) |
| Age, Customized: < 45 years | participants | 8 | 5 | 4 | 17 |
| Age, Customized: 45 to < 65 years | participants | 59 | 51 | 51 | 161 |
| Age, Customized: 65 to < 85 years | participants | 60 | 74 | 69 | 203 |
| Age, Customized: ≥ 85 years | participants | 5 | 4 | 7 | 16 |
| Sex: Female, Male: Female | Participants | 58 | 67 | 60 | 185 |
| Sex: Female, Male: Male | Participants | 74 | 67 | 71 | 212 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months, measured over Baseline and 6 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is mean change from baseline in best corrected visual acuity (BCVA) score at 6 months. BCVA in the study eye was assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts. The registry describes the score as the number of correct letters, assessed at a starting distance of 4 meters.
In general, a change-from-baseline endpoint compares a participant’s measurement at follow-up with that participant’s starting measurement. Summarizing these changes as a group mean gives an estimate of the average change in the analyzed population. Comparing group means can describe how average change differed between randomized groups, although interpreting such a contrast requires the actual estimates and their uncertainty. Those numerical results are not reported in the registry record.
Visual acuity is a direct measure of visual performance, making it relevant to a study focused on macular edema and vision. That explains the general rationale for using a visual-acuity measure; the registry record does not state a separate rationale for selecting this endpoint. It also does not report a score range or a threshold for interpreting the size of a change. The endpoint is expressed in units on a scale, with standard deviation as the stated measure of dispersion.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies mean change from baseline in BCVA score at 6 months as the primary outcome. It does not report the mean change for any group, a between-group estimate, a confidence interval, or a p-value. Consequently, the magnitude and precision of the primary treatment comparisons cannot be described from the registry record. The study’s primary outcome has several categories or time points and is not reduced to one comparison in the posted data.
This absence matters for interpretation. A mean change for each group would describe average change within that group; a between-group contrast would address how those averages differed. Neither can be reconstructed from the endpoint description alone. A confidence interval, if reported, would indicate a range of estimates compatible with the analysis and its assumptions, and would help convey uncertainty. No such interval is reported for the primary outcome.
General statistical context: a p-value addresses how compatible the observed data are with a specified null model, under the assumptions of the analysis. It does not measure the size or importance of an effect. A p-value alone would also not establish that an effect is precise. Here, the registry record does not provide a primary-outcome p-value, and no conclusion about statistical evidence for a difference can be drawn from that missing result.
The trial was randomized and included two ranibizumab doses and a sham injection group. Those design features define the intended comparisons, but do not substitute for reporting their results. The registry record gives no numerical BCVA results by dose, so it cannot support a comparison between the ranibizumab doses or between either dose and sham on the primary endpoint.
The record reports safety counts separately. Serious adverse events affected 6 of 131 participants at risk in the sham injection group, 14 of 134 in the ranibizumab 0.3 mg group, and 14 of 130 in the ranibizumab 0.5 mg group. These counts describe the posted safety data; without additional context and an analysis plan, they do not establish why events occurred or whether the groups differed beyond chance. The primary efficacy results and the safety counts answer different questions and should not be treated as substitutes for one another.
Overall, the registry record supplies the design and endpoint definition but not the numerical primary efficacy findings. Statistical interpretation of the primary question therefore remains limited: the observed average changes, between-group contrasts, and their uncertainty are not reported in the registry record.
9. Statistical Methods Explained
What does the reported mean represent?
The primary endpoint is a continuous measure: change in BCVA score from baseline to 6 months. The registry specifies the mean as the summary measure and the standard deviation as the measure of dispersion. In general, the mean describes the average observed value or change in a group. The standard deviation describes how spread out individual values are around that group mean; it is not the uncertainty around the mean itself.
For a randomized comparison, a treatment effect is commonly expressed as a contrast between groups. That contrast would describe the difference in average change between a ranibizumab group and the sham group. The registry record does not report the group means, standard deviations, or a numerical contrast for the primary outcome. It is therefore not possible to assess the direction, size, or precision of that comparison from the record.
Why does randomization matter?
In general, randomization assigns participants to groups by chance and is intended to reduce systematic differences at baseline. It supports a fair comparison by making treatment assignment independent of participant characteristics in expectation. It does not guarantee that every characteristic will be balanced in a particular trial, and the design description alone does not show the actual baseline balance. Detailed information about baseline characteristics and allocation procedures is not reported in the registry record.
The study is described as double-masked and sham injection-controlled. In general, masking can reduce the potential for expectations to influence participant experience, outcome assessment, or decisions during follow-up. Sham control is intended to make the comparison more similar in experience apart from the active injection. The registry record does not give further details on masking procedures or whether masking was assessed.
How should uncertainty be understood?
General statistical explanation: an estimate is a summary of the data, while uncertainty describes how much that estimate could vary across repeated studies under an assumed model. A confidence interval is one way to communicate that uncertainty. It is interpreted in relation to the estimate and the analysis assumptions, rather than as a guarantee about an individual participant’s outcome. The registry record does not report confidence intervals for the primary outcome.
A standard deviation and a confidence interval serve different purposes. The standard deviation describes participant-to-participant variability in the measured outcome. A confidence interval describes uncertainty in an estimate, such as a group mean or a between-group contrast. The registry identifies standard deviation as the endpoint’s dispersion measure but does not report a corresponding primary-result estimate or confidence interval.
What does last observation carried forward mean?
The primary population is described as intent to treat among randomized participants, and missing values were imputed using last observation carried forward (LOCF). In general, LOCF fills a missing later measurement with the participant’s last recorded measurement. It can retain participants with missing follow-up measurements in an analysis, but it relies on an assumption that carrying that earlier value forward is a reasonable representation of the missing later value. That assumption may not fit every participant’s course.
LOCF does not recover the unobserved value; it substitutes an imputed value according to a rule. The resulting analysis can be affected if missingness is related to outcomes or if participants’ measurements would have changed after their last observation. The registry record does not report the amount or pattern of missing primary-outcome data, reasons for missingness, or sensitivity analyses comparing LOCF with other approaches.
What can the planning illustration tell readers?
The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. For time-to-event tables, the stated convention is total events; for all other outcomes, it is participants per arm. No numerical planning counts or primary observed effect are reported in the registry record.
General explanation: a planning calculation estimates how many participants might be needed for a chosen statistical power under specified assumptions about the effect and variability. Such an illustration is not observed power and does not indicate the probability that a result is true. If based on an effect observed in the same trial, it is also conditional on that estimate and can be sensitive to its uncertainty. The registry record does not provide the trial’s own sample-size justification or further details about its original design calculation.
Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. If a model understates variability, its uncertainty estimates can be too small and its inferences too optimistic. The registry record does not identify an over-dispersion issue or describe a model requiring an over-dispersion adjustment. This general concept therefore should not be read as a feature of the trial’s reported analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures and 14 analyses. The primary outcome is mean change from baseline in BCVA score at 6 months. Listed secondary outcomes include BCVA responder and loss measures, central foveal thickness measures, and changes in NEI VFQ-25 near and distance activities subscale scores. Considering multiple outcomes or analyses can raise a multiplicity concern: when many statistical questions are tested, the chance of at least one apparently unusual result can increase. This is general statistical context.
The registry record does not report whether the analysis plan adjusted for multiplicity, designated a testing hierarchy, or treated secondary outcomes as exploratory. It also does not report an interim analysis plan. Those details are not reported in the registry record, so no claim can be made about how multiplicity was handled.
For the primary endpoint, the record identifies the intent-to-treat randomized population and says missing values were imputed using last observation carried forward. In general, an intent-to-treat approach analyzes participants according to randomized group, preserving the comparison created by randomization. The available description does not specify details such as how participants with no post-baseline measurement were handled.
The record does not report the amount, timing, or reasons for missing primary outcome data, or provide sensitivity analyses for the LOCF assumption. Missing-data methods can affect estimates when the likelihood of missingness or the unobserved outcomes differ across participants. Because the missing-data pattern and alternative analyses are not reported, the robustness of the primary result to missingness cannot be assessed from the registry record. Numerical primary results are also not reported, further limiting evaluation.
11. 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 |
|---|---|---|---|
| Sham Injection | 6 | 131 | 4.6% |
| Ranibizumab Injection 0.3 mg | 14 | 134 | 10.4% |
| Ranibizumab Injection 0.5 mg | 14 | 130 | 10.8% |
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 |
|---|---|
| Sham Injection | 115 of 131 |
| Ranibizumab Injection 0.3 mg | 125 of 134 |
| Ranibizumab Injection 0.5 mg | 115 of 130 |
Most frequent serious adverse event terms
| Event term | Organ system | Sham Injection | Ranibizumab Injection 0.3 mg | Ranibizumab Injection 0.5 mg |
|---|---|---|---|---|
| Pneumonia | Infections and infestations | 1 of 131 | 2 of 134 | 0 of 130 |
| Small Intestinal Obstruction | Gastrointestinal disorders | 0 of 131 | 1 of 134 | 1 of 130 |
| Hypertension | Vascular disorders | 0 of 131 | 2 of 134 | 0 of 130 |
| Acute Myocardial Infarction | Cardiac disorders | 0 of 131 | 0 of 134 | 1 of 130 |
| Angina Unstable | Cardiac disorders | 0 of 131 | 0 of 134 | 1 of 130 |
| Bradycardia | Cardiac disorders | 0 of 131 | 0 of 134 | 1 of 130 |
| Vertigo | Ear and labyrinth disorders | 0 of 131 | 1 of 134 | 0 of 130 |
| Glaucoma | Eye disorders | 0 of 131 | 1 of 134 | 0 of 130 |
| Gaze Palsy | Eye disorders | 0 of 131 | 0 of 134 | 1 of 130 |
| Visual Acuity Reduced | Eye disorders | 0 of 131 | 1 of 134 | 0 of 130 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sham Injection | Ranibizumab Injection 0.3 mg | Ranibizumab Injection 0.5 mg |
|---|---|---|---|---|
| Conjunctival Hemorrhage | Eye disorders | 55 of 131 | 80 of 134 | 71 of 130 |
| Retinal Exudates | Eye disorders | 20 of 131 | 37 of 134 | 32 of 130 |
| Eye Pain | Eye disorders | 19 of 131 | 33 of 134 | 21 of 130 |
| Retinal Hemorrhage | Eye disorders | 18 of 131 | 23 of 134 | 23 of 130 |
| Ocular Vascular Disorder | Eye disorders | 16 of 131 | 21 of 134 | 10 of 130 |
| Maculopathy | Eye disorders | 11 of 131 | 16 of 134 | 16 of 130 |
| Retinal Vascular Disorder | Eye disorders | 9 of 131 | 10 of 134 | 15 of 130 |
| Hypertension | Vascular disorders | 12 of 131 | 11 of 134 | 10 of 130 |
| Ocular Hyperemia | Eye disorders | 6 of 131 | 13 of 134 | 8 of 130 |
| Retinal Depigmentation | Eye disorders | 6 of 131 | 6 of 134 | 15 of 130 |
Serious events with the highest arm-level rate: pneumonia (1.5%), hypertension (1.5%), acute myocardial infarction (0.8%), angina unstable (0.8%), bradycardia (0.8%).
The registry reports serious adverse events by group as counts of participants affected and participants at risk. In the sham injection group, 6 of 131 participants at risk were affected. In the ranibizumab injection 0.3 mg group, 14 of 134 were affected. In the ranibizumab injection 0.5 mg group, 14 of 130 were affected. These are posted counts; they do not by themselves establish a causal relationship to treatment.
For other adverse events, the registry reports 115 of 131 participants affected in the sham group, 125 of 134 in the 0.3 mg group, and 115 of 130 in the 0.5 mg group. The record lists pneumonia and hypertension at 1.5% each, and acute myocardial infarction, unstable angina, bradycardia, and gaze palsy at 0.8% each among the top serious terms. The listed percentages are not assigned to a specific treatment group in the record, so they should not be attributed to one.
Death counts are not reported in the registry record. The registry entries do not provide the event-level timing, exposure-adjusted rates, or a statistical comparison for these counts. General statistical context: adverse-event counts are descriptive, and interpretation depends on how events were defined, collected, and followed. The posted figures alone do not establish whether a difference between groups is meaningful or treatment-related.
12. What the Result Does, and Does Not, Mean
The trial’s design addresses a clinical question about changes in visual acuity after ranibizumab injection compared with sham injection in patients with macular edema secondary to BRVO. Randomization, double masking, and a sham control are features intended to support a structured comparison. The primary endpoint is defined clearly enough to identify what was to be measured: mean change in ETDRS-based BCVA score from baseline to 6 months.
However, the registry record does not report the numerical primary outcome results. It gives no group means, between-group contrasts, confidence intervals, or p-values. The endpoint definition and design alone cannot show how much BCVA changed, how the groups compared, or how precise any difference was. Therefore, the posted record does not permit a conclusion about the primary efficacy comparison.
The safety entries provide counts of participants affected by serious and other adverse events, along with selected serious-event terms and percentages. They are descriptive figures, not proof that an event was caused by an intervention. The record does not provide a statistical safety comparison or the context needed to determine whether observed count differences are meaningful.
General statistical context: a trial result is not simply a yes-or-no label. The estimated effect, its precision, the analysis choices, and the outcome’s clinical interpretation all matter. Even a statistically precise estimate would need to be interpreted in context; conversely, a result with substantial uncertainty would not resolve the treatment comparison. Here, the numerical efficacy estimate and uncertainty are not reported in the registry record.
Thus, the available record supports describing the trial’s design, endpoint, stated missing-data method, and selected safety counts. It does not support a numerical account of the primary treatment effect, a judgment about its precision, or a conclusion about the clinical implications of the comparison.
13. Why This Trial Matters Statistically
BRAVO is statistically notable in its design as a Phase III, randomized, double-masked, sham injection-controlled comparison with two ranibizumab dose groups. Such a design defines comparisons intended to separate the effect associated with the intervention from changes that may occur over time or in the context of trial participation. The study’s primary endpoint is a measured change in visual acuity, rather than a purely subjective description of change.
The registry also makes the analysis population and missing-data rule explicit for the primary endpoint: the intent-to-treat randomized population, with LOCF imputation. These details matter because the population analyzed and the way missing measurements are handled can influence an estimate. LOCF is a specific assumption-based method, and the record does not report sensitivity analyses or the amount of missing outcome data. Those omissions limit assessment of robustness.
Multiple outcomes and analyses are listed, making the question of multiplicity relevant in general. The registry record does not state whether or how it addressed multiplicity, so the statistical implications of the 14 analyses cannot be fully evaluated from the record.
Most importantly, the registry record does not provide numerical primary efficacy results. A well-defined design and endpoint are not substitutes for estimates and uncertainty. This record therefore illustrates why statistical interpretation depends not only on knowing what was planned and measured, but also on having the results and analysis details needed to assess the comparison.
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 for interpreting this trial from the registry record is that numerical results for the primary BCVA endpoint are not reported. The mean change in each group, between-group estimates, confidence intervals, and p-values are absent. As a result, the size, direction, and precision of the primary comparison cannot be evaluated.
The outcome entry notes that the primary outcome has several categories or time points and is not reduced to one comparison. The record therefore does not present a single numerical primary comparison suitable for interpretation. It also does not provide the detailed analysis plan, including whether the primary comparison used an adjusted model or how multiple analyses were managed.
The primary analysis used LOCF for missing values, but the number of missing measurements, their timing, and the reasons for missingness are not reported in the registry record. No sensitivity analyses are described. Since LOCF depends on an assumption about how a last observed value represents a later missing value, the robustness of the endpoint analysis cannot be assessed from the information reported.
The registry record does not provide detailed treatment schedules in the arm descriptions, allocation-concealment procedures, or further information about masking. It does not report the trial’s sample-size justification or interim analysis plan. These details are not reported in the registry record and should not be inferred from the study design description.
Safety information is also limited to reported counts and selected serious-event terms. Death counts are not reported in the registry record, and the selected serious-event percentages are not assigned to treatment groups. The record does not supply enough detail to assess event timing, comparative risk, or causal attribution. These limitations constrain interpretation of both efficacy and safety from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion (BRAVO) — NCT00486018.
- Registry record last updated 2017-05-10; status last verified 2017-04.
- Results first posted 2011-02-25.
- 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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18. Record Summary
BRAVO (NCT00486018) was a completed Phase III, multicenter, randomized, double-masked, parallel-group, sham injection-controlled study of ranibizumab for macular edema secondary to BRVO. The registry lists 397 participants, a 6-month treatment period, and a 6-month observation period. The intervention groups received ranibizumab injection 0.3 mg or 0.5 mg; the comparator group received sham injection.
The primary endpoint was mean change from baseline in BCVA score at 6 months, assessed using ETDRS visual acuity charts. The primary population was the intent-to-treat randomized population, with missing values imputed using LOCF. The registry record does not report numerical primary efficacy results, confidence intervals, or p-values. It lists safety counts and selected serious adverse-event terms, but those entries do not establish causality or provide a comparative analysis.