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 Central Retinal Vein Occlusion (CRUISE) (NCT00485836), 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 | NCT00485836 |
| Phase | Phase 3 |
| Condition | Macular Edema, Retinal Vein Occlusion |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 392 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genentech, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants had macular edema secondary to central retinal vein occlusion. The registry describes 392 enrolled patients and identifies the intent-to-treat population as the randomized population. The study took place at investigational sites in the United States.
Intervention
The active interventions were intravitreal ranibizumab injections at doses of 0.3 mg and 0.5 mg. The registry describes a treatment period followed by an observation period.
Comparator
The comparator was sham injection. The study is described as randomized, double-masked, and sham injection-controlled.
Primary question
The listed primary endpoint is mean change from baseline in best corrected visual acuity score at 6 months. The registry record does not report the results for this endpoint, so the size and precision of any between-group differences are not reported in the registry record.
In statistical terms, the trial was designed to compare visual-acuity changes across the sham group and the two ranibizumab dose groups. The endpoint concerns change from each participant’s baseline score, rather than the score at follow-up alone. That distinction matters because participants can begin the study with different levels of visual acuity; assessing change focuses the outcome on how scores moved during follow-up.
The registry record identifies the primary analysis population as the intent-to-treat, or randomized, population. It also states that missing values were imputed using last observation carried forward. However, it does not report the group-level mean changes, the between-group estimates, confidence intervals, or p-values for the primary endpoint. Thus, the clinical question is identifiable, but its answer cannot be quantified from the posted results in the registry record.
3. Trial Design
CRUISE is described as a Phase III, multicenter, randomized, double-masked, parallel-group study with sham injection as the control. The registry lists three intervention groups: sham injection, ranibizumab injection 0.3 mg, and ranibizumab injection 0.5 mg. The brief summary describes intravitreal administration of ranibizumab. Further details about the procedures used to generate the random allocation or maintain masking are not reported in the registry record.
The registry lists enrollment of 392 and reports that participants were enrolled at 95 investigational sites in the United States. It records a start date of 2007-07, primary completion in 2009-06, and a completed study status. The study included a treatment period of 6 months and an observation period of 6 months. The registry record does not describe the observation-period procedures or specify how treatment was handled during that period.
The parallel-group structure means that participants were assigned to a study group and followed within that group, rather than crossing between interventions. Randomization is intended, in general, to reduce systematic differences between groups at the start of a trial. Masking is intended, in general, to reduce the influence of treatment knowledge on study conduct or assessment. These are general explanations of the design features; the registry record does not give enough detail to describe their implementation.
The registry record does not report the allocation ratio, eligibility criteria in detail, planned sample-size justification, or the statistical plan. It also does not report how many participants completed follow-up or were included in each endpoint analysis. Enrollment should therefore not be treated as a substitute for endpoint-specific analysis counts. The available design description establishes the comparison structure and follow-up schedule, but does not establish the extent of missing outcome data or the particulars of the analysis beyond the stated primary population and imputation method.
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 | 130 | 132 | 130 |
| Received Study Drug (Safety Population) | 129 | 132 | 129 |
| COMPLETED | 115 | 129 | 119 |
| NOT COMPLETED | 15 | 3 | 11 |
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 | 130 | 132 | 130 | 392 | |
| Age, Continuous | years | 65.4 (SD 13.1) | 69.7 (SD 11.6) | 67.6 (SD 12.4) | 67.6 (SD 12.5) |
| Age, Customized: < 45 years | participants | 10 | 5 | 5 | 20 |
| Age, Customized: 45 to < 65 years | participants | 50 | 36 | 46 | 132 |
| Age, Customized: 65 to < 85 years | participants | 67 | 80 | 71 | 218 |
| Age, Customized: ≥ 85 years | participants | 3 | 11 | 8 | 22 |
| Sex: Female, Male: Female | Participants | 58 | 61 | 50 | 169 |
| Sex: Female, Male: Male | Participants | 72 | 71 | 80 | 223 |
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 using Early Treatment Diabetic Retinopathy Study visual acuity charts, with the score based on the number of correct letters. Testing began at a distance of 4 meters. The registry describes the measure in units on a scale, with mean and standard deviation as the stated summary statistics.
Change from baseline expresses how the measured score moved between the starting assessment and follow-up. A group mean change describes the average movement in that group; it does not imply that every participant had the same change. In a randomized comparison, the difference between group mean changes is a way to summarize how the groups’ average trajectories differ. This is a general interpretation of continuous outcomes, not a reported CRUISE result.
Visual acuity is used as an outcome because the chart score directly records performance on a standardized letter-reading assessment. The registry’s description specifies the study eye and the assessment procedure, but does not report the primary endpoint values or the contrast between any ranibizumab group and sham. It also does not report a confidence interval or p-value for this endpoint. Consequently, the measurement and its intended time point are clear, while the magnitude and precision of the trial’s primary result are not reported in the registry record.
The primary population is described as intent to treat, comprising randomized participants, with missing values imputed by last observation carried forward. How that rule affected the endpoint estimates cannot be determined from the registry record because the outcome results and details of missingness are not reported.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the central efficacy question: whether mean BCVA change from baseline at 6 months differed among the sham group and the two ranibizumab dose groups. It does not report the numeric results for that primary endpoint. There is therefore no posted group mean change, between-group estimate, confidence interval, or p-value from which to describe the direction, size, or precision of the primary comparison. No conclusion about the primary outcome can be drawn from the registry record alone.
That absence is important for interpretation. A study design and an endpoint definition describe what investigators intended to compare; they do not reveal what the comparison found. Enrollment, treatment assignment, and follow-up duration cannot substitute for the outcome estimates. Nor can the secondary endpoint titles supply the missing primary result. The registry lists secondary visual-acuity, retinal-thickness, and questionnaire outcomes, but does not provide their numerical results in this record.
In general, a confidence interval communicates the range of estimates compatible with the observed data under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, while an interval that includes values on both sides of a null contrast may leave the direction or size of the difference uncertain. These concepts cannot be applied to the CRUISE primary comparison because no confidence interval or estimate is reported in the registry record. A p-value alone, even if available, would not describe the size of an effect; in this case, the registry record does not report a primary p-value either.
The safety entries do contain counts for serious and other adverse events by study group. These are descriptive safety data, not a substitute for the primary visual-acuity outcome. The record lists serious adverse events affecting 13 participants in the sham group, 16 in the 0.3 mg group, and 13 in the 0.5 mg group, with the corresponding numbers at risk listed as 129, 132, and 129. These counts should be read as registry entries for the stated groups, not as evidence about the unreported primary endpoint.
Overall, the registry record supports a careful description of the trial question, design, endpoint definition, and certain safety counts. It does not support a quantitative account of the primary treatment comparisons. Any interpretation that claims a particular benefit, lack of benefit, or degree of certainty would go beyond the results reported in the registry record.
9. Statistical Methods Explained
The primary endpoint is a continuous measure: change in BCVA score from baseline to 6 months. For a continuous outcome, a mean summarizes the average observed value or change within a group, while the standard deviation describes the spread of participant values around that mean. The mean is useful for comparing group averages, but it does not describe the full distribution. Participants may have changes that differ substantially from the group average. These are general statistical explanations; the registry does not report the CRUISE endpoint means or standard deviations.
A randomized parallel-group comparison typically estimates how the outcome differs between assigned groups. For a change endpoint, that can be expressed as a contrast between the groups’ average changes. The estimate is the magnitude and direction of the contrast under the stated analysis; its uncertainty is commonly described with a confidence interval. The registry record gives neither the estimates nor their confidence intervals for the primary endpoint. It is therefore not possible to explain the observed size or precision of the CRUISE comparison from this record.
The stated analysis population is intent to treat, described as the randomized population. In general, an intent-to-treat approach aims to retain participants in the groups to which they were randomized, preserving the comparison created by random allocation. The record does not provide endpoint-specific participant counts, so it is not possible to establish how many randomized participants contributed observed or imputed values to the primary analysis.
The record says missing values were imputed using last observation carried forward (LOCF). Under this approach, a participant’s last recorded outcome is carried forward to fill a later missing value. This is an imputation rule, not an observed follow-up measurement. As a general limitation, carrying a prior value forward can fail to represent the outcome that would have been measured later, particularly if outcomes change over time or if missingness is related to participants’ condition or treatment. The registry record does not report the amount or pattern of missing data, the reasons for missingness, or sensitivity analyses assessing alternative assumptions.
Randomization and masking are design features rather than statistical results. In general, randomization helps make assigned groups comparable in expectation, while masking can reduce bias that might arise when participants or study personnel know an assignment. The record identifies the study as randomized and double-masked but does not describe the randomization procedure, who was masked, or how masking was maintained. Those operational details are not reported in the registry record.
The registry lists 7 outcome measures and 14 analyses. The primary outcome is described as having several categories or time points and is not reduced to one comparison in the posted results. Multiple outcome measures or analyses can raise multiplicity concerns: when many statistical questions are tested, the chance of at least one apparently notable result can increase. This is a general property of repeated testing. The registry record does not report a multiplicity adjustment, a hierarchy for secondary outcomes, or a complete statistical analysis plan. It is therefore not possible to determine how the reported analyses, if any, were intended to be interpreted jointly.
The sample-size planning description states that its illustration is based on the 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 a stated fraction of the observed effect. It is explicitly described as a planning illustration rather than the trial’s own design. The registry record does not report a trial sample-size justification, and no observed primary effect is reported to evaluate such an illustration. A planning calculation estimates requirements under assumptions; it is not observed power and does not show the probability that a particular finding is true.
In general, over-dispersion refers to variability greater than a model assumes. If a model understates variability, standard errors and uncertainty intervals may be too small, making estimates appear more precise than warranted. The listed primary endpoint is continuous and summarized with a mean and standard deviation; the registry does not identify an over-dispersion model for this endpoint. Any discussion of over-dispersion is therefore general rather than a description of an analysis reported for CRUISE.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures and 14 analyses, including the primary BCVA change endpoint and secondary outcomes concerning visual-acuity thresholds, central foveal thickness, and NEI VFQ-25 subscales. When multiple outcomes or analyses are considered, multiplicity can affect how statistical evidence should be interpreted. In general, conducting many tests without adjustment can increase the chance of a result appearing statistically notable by chance. The registry record does not report whether an adjustment was used, how outcomes were prioritized, or which secondary comparisons were prespecified as confirmatory. Those details are not reported in the registry record.
The primary analysis population is described as intent to treat, meaning the randomized population. Missing values were imputed using last observation carried forward. This identifies the stated handling rule but does not describe the extent of missingness or show how results might change under different assumptions. The number of participants with observed primary endpoint values, the number with imputed values, and the reasons for missingness are not reported in the registry record.
The primary outcome is noted as having several categories or time points and is not reduced to one comparison in the posted results. The registry record does not provide a set of primary estimates from which to assess consistency across those categories or time points. It also does not report sensitivity analyses, a missing-data model beyond LOCF, or a full statistical analysis plan. These omissions limit assessment of how robust the findings would be to alternative analytic choices. Since the primary endpoint results themselves are not reported, multiplicity and missing-data procedures cannot be evaluated against the observed estimates.
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 | 13 | 129 | 10.1% |
| Ranibizumab Injection 0.3 mg | 16 | 132 | 12.1% |
| Ranibizumab Injection 0.5 mg | 13 | 129 | 10.1% |
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 | 116 of 129 |
| Ranibizumab Injection 0.3 mg | 113 of 132 |
| Ranibizumab Injection 0.5 mg | 111 of 129 |
Most frequent serious adverse event terms
| Event term | Organ system | Sham Injection | Ranibizumab Injection 0.3 mg | Ranibizumab Injection 0.5 mg |
|---|---|---|---|---|
| Coronary Artery Disease | Cardiac disorders | 2 of 129 | 1 of 132 | 1 of 129 |
| Retinal Vein Occlusion | Eye disorders | 2 of 129 | 1 of 132 | 1 of 129 |
| Macular Edema | Eye disorders | 2 of 129 | 2 of 132 | 0 of 129 |
| Myocardial Infarction | Cardiac disorders | 0 of 129 | 1 of 132 | 1 of 129 |
| Colitis | Gastrointestinal disorders | 0 of 129 | 1 of 132 | 1 of 129 |
| Diverticulitis | Infections and infestations | 1 of 129 | 0 of 132 | 1 of 129 |
| Syncope | Nervous system disorders | 0 of 129 | 2 of 132 | 0 of 129 |
| Cardiomyopathy | Cardiac disorders | 0 of 129 | 1 of 132 | 0 of 129 |
| Arteriosclerosis Coronary Artery | Cardiac disorders | 0 of 129 | 0 of 132 | 1 of 129 |
| Cardiac Failure Congestive | Cardiac disorders | 0 of 129 | 1 of 132 | 0 of 129 |
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 | 43 of 129 | 57 of 132 | 53 of 129 |
| Retinal Exudates | Eye disorders | 18 of 129 | 36 of 132 | 25 of 129 |
| Retinal Vascular Disorder | Eye disorders | 19 of 129 | 21 of 132 | 19 of 129 |
| Maculopathy | Eye disorders | 13 of 129 | 21 of 132 | 19 of 129 |
| Eye Pain | Eye disorders | 14 of 129 | 12 of 132 | 24 of 129 |
| Retinal Hemorrhage | Eye disorders | 17 of 129 | 15 of 132 | 16 of 129 |
| Retinal Depigmentation | Eye disorders | 8 of 129 | 12 of 132 | 10 of 129 |
| Intraocular Pressure Increased | Investigations | 5 of 129 | 11 of 132 | 11 of 129 |
| Myodesopsia | Eye disorders | 5 of 129 | 9 of 132 | 12 of 129 |
| Eye Irritation | Eye disorders | 6 of 129 | 6 of 132 | 10 of 129 |
Serious events with the highest arm-level rate: coronary artery disease (1.6%), retinal vein occlusion (1.6%), macular edema (1.6%), syncope (1.5%), arteriosclerosis coronary artery (0.8%).
The registry lists serious adverse events and other adverse events separately for each study group. For serious adverse events, the sham group lists 13 affected participants among 129 at risk; the ranibizumab 0.3 mg group lists 16 among 132 at risk; and the ranibizumab 0.5 mg group lists 13 among 129 at risk. For other adverse events, the respective entries are 116 among 129, 113 among 132, and 111 among 129. These are the registry’s group-specific counts; no additional percentages have been calculated from them.
The listed serious adverse-event terms include coronary artery disease, retinal vein occlusion, macular edema, syncope, arteriosclerosis coronary artery, and acute coronary syndrome, each with a percentage recorded in the registry. The term-specific percentages are not presented by study group in the record, so they should not be interpreted as arm-specific comparisons. A listed term also does not by itself establish that the event was caused by the assigned intervention.
Deaths are not reported in the registry record. The entries are descriptive and do not provide adjusted comparisons, confidence intervals, or information about timing and duration for each event. Counts across groups should not be treated as a causal comparison without fuller methods and context. These safety data should also be kept separate from the primary visual-acuity endpoint, whose results are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes the question CRUISE set out to study and describes a randomized, double-masked comparison of ranibizumab doses with sham injection. It also defines a primary visual-acuity endpoint and identifies the randomized population and LOCF approach used for missing values. These design and methods details help readers understand what was planned and how the primary measure was defined.
They do not establish the primary outcome result. The registry record does not report group mean changes, between-group contrasts, confidence intervals, or p-values for BCVA change at 6 months. Without those estimates, the direction, magnitude, and precision of the comparison cannot be described. The record also does not give numerical results for the listed secondary outcomes. Therefore, the study’s efficacy findings cannot be characterized from this record alone.
In general, a statistically estimated difference and its uncertainty are distinct from a clinical interpretation. An estimate indicates the observed contrast under an analysis, while uncertainty describes how imprecisely that contrast has been estimated. Neither design labels nor enrollment figures provide those missing results. This general distinction is especially relevant when a registry identifies an endpoint but does not post its analysis.
The safety entries offer group-specific counts for serious and other adverse events and a list of serious event terms with percentages. They provide descriptive information, but the record does not include enough detail to establish causal attribution or to interpret the term percentages as between-group effects. Deaths are not reported in the registry record. Safety counts do not answer the primary visual-acuity question.
The most defensible interpretation is therefore limited: the record describes the trial design, intended primary measure, stated missing-data method, and selected safety entries, while leaving the primary efficacy estimates unreported. This is not evidence for a particular direction of effect, nor evidence that the groups were equivalent. It marks the boundary between what the registry record documents and what would require outcome results and fuller analytic information.
13. Why This Trial Matters Statistically
CRUISE provides a useful example of the distinction between a well-defined trial question and a reported statistical result. The registry specifies a randomized, double-masked, sham-controlled, parallel-group design and identifies mean change in BCVA at 6 months as the primary endpoint. Those details allow the comparison to be understood at a design level. However, without the endpoint estimates and uncertainty measures, readers cannot evaluate the primary comparison’s magnitude or precision.
The record also illustrates why analysis populations and missing-data rules matter. It identifies the intent-to-treat population and LOCF imputation, but does not report the amount or pattern of missingness or the results of sensitivity analyses. In general, an imputation choice can affect an estimate, especially when outcomes change over time. Knowing the stated rule is informative, while lacking missingness details limits assessment of its consequences.
The listed secondary outcomes and analyses raise another general statistical issue: multiple comparisons require careful interpretation. The registry record does not report a multiplicity strategy or analysis hierarchy. This does not establish that no such strategy existed; it means the information is not reported in the registry record. Separating what is documented from what is unreported is essential when interpreting registry entries.
Finally, the record distinguishes efficacy outcomes from safety counts. The serious and other adverse-event entries offer descriptive group-level information, but they do not supply the missing primary visual-acuity estimates or establish causality. Taken together, these features make CRUISE statistically informative as a case in how design, endpoint definition, missing-data handling, multiplicity, and result reporting each shape what can be concluded from a trial record.
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 registry record does not report the numerical primary endpoint results, including group mean changes, between-group estimates, confidence intervals, or p-values. It also does not report numerical results for the listed secondary outcomes. This prevents assessment of the direction, size, and precision of the visual-acuity comparison, and limits evaluation of the secondary findings.
Although enrollment is listed as 392, endpoint-specific analysis counts and follow-up completeness are not reported in the registry record. The record identifies LOCF for missing values but does not describe how many values were missing, when they were missing, or why. It does not report sensitivity analyses that could show whether the findings were robust to different missing-data assumptions.
The record does not report the allocation ratio, detailed eligibility criteria, randomization procedures, masking procedures, or a complete statistical analysis plan. It does not describe a multiplicity adjustment or a hierarchy for interpreting the 7 listed outcome measures and 14 analyses. The stated sample-size illustration is described as separate from the trial’s own design, and the registry does not report the trial’s sample-size justification.
The safety entries are also limited: deaths are not reported, and the listed serious adverse-event terms are not presented as arm-specific comparative estimates. Timing, duration, and causal assessment for individual events are not reported in the registry record. These gaps do not prove that relevant methods or data were absent from the full study record; they indicate that they are not reported in the registry record reviewed.
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 Central Retinal Vein Occlusion (CRUISE) — NCT00485836.
- Registry record last updated 2017-07-28; status last verified 2017-06.
- 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
CRUISE is a completed Phase III, multicenter, randomized, double-masked, parallel-group study of ranibizumab compared with sham injection for macular edema secondary to central retinal vein occlusion. The registry lists enrollment of 392 and 95 investigational sites in the United States. The study included a 6-month treatment period and a 6-month observation period.
The primary endpoint was mean change from baseline in BCVA score at 6 months, assessed with ETDRS visual acuity charts. The stated population was intent to treat, with missing values imputed using LOCF. The registry record does not report the primary outcome estimates or their uncertainty. It lists serious and other adverse-event counts by group, while deaths are not reported in the registry record.