Intravitreal Ranibizumab 0.5MG, or 1.0mg for RVO With Macular Edema Previously Receiving Bevacizumab: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intravitreal Ranibizumab 0.5MG, or 1.0mg for RVO With Macular Edema Previously Receiving Bevacizumab (NCT01471691), a randomized phase 1, phase 2 study. The primary outcome is Mean Change From Baseline BCVA.

2. Clinical Question

3. Trial Design

This is a phase I/II, randomized, open-label, parallel-group study. The registry lists an enrollment of 14 and a completed status. The study start is recorded as 2011-11, and primary completion as 2014-02. These registry entries describe the study record; they do not establish how many participants contributed data to every outcome.

The two arms received intravitreal ranibizumab at 0.5mg or 1.0mg. The registry identifies random allocation, but the sequence-generation process, allocation concealment, and procedures for assigning participants are not reported in the registry record. Masking is listed as none. The record does not describe whether outcome assessors or data analysts were masked separately.

The primary outcome is mean change from baseline in best corrected visual acuity, measured in letters on an ETDRS chart, with a timeframe from baseline to month 6. The description says vision was measured at baseline and each subsequent monthly visit. The registry lists five secondary outcomes: mean change in center point thickness, change in mean best corrected visual acuity from baseline, the percentage of patients with CFT less than 300um, excess foveal thickness, and the total number of ranibizumab injections. Numerical results for these secondary outcomes are not reported in the registry record.

The primary outcome summaries list 8 participants in the 0.5mg arm and 5 in the 1.0mg arm. Safety summaries use at-risk counts of 8 and 6, respectively. These outcome-specific denominators should be kept distinct; the record does not explain the difference between the denominators or provide a participant flow account. Treatment frequency, follow-up beyond the stated primary endpoint timeframe, and discontinuation details 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

Reasons for not completing this period:

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 Mean Change From Baseline BCVA, measured over Baseline to month 6.

Best corrected visual acuity is a measure of vision under the best correction used for testing. In this study, it was assessed with a standard ETDRS chart and expressed in letters. The primary endpoint is the mean change from baseline to month 6. Change scores describe how the measurement at follow-up differs from a participant’s baseline measurement; the posted arm summaries report the average change for each group.

As general statistical context, a continuous outcome such as letter score can be summarized by its mean, while the standard deviation describes how spread out individual measurements are around that mean. These summaries give a sense of the group-level result and the variation among observations. They do not, by themselves, show how precisely the difference between treatment groups has been estimated.

The registry reports a mean change of 14.0 letters with a standard deviation of 10.0 in the 0.5mg arm, based on 8 participants. For the 1.0mg arm, it reports a mean change of 5.0 letters with a standard deviation of 6.0, based on 5 participants. No confidence interval or p-value for the two-arm comparison is reported in the registry record. Without a comparison estimate and its uncertainty, the arm summaries alone do not establish the precision of a between-dose contrast.

The endpoint is relevant to the study question because it records a measured vision outcome over the stated follow-up interval. It remains one outcome at a particular time point: it does not by itself describe other visual measures, retinal thickness, injection burden, safety, or outcomes beyond month 6.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: mean change in ETDRS letters from baseline to month 6. A continuous outcome can take values across a scale rather than being limited to categories such as event or no event. Reporting an arm mean is a way to describe the central value of the observed changes. The standard deviation is a measure of dispersion among individual changes, not a measure of uncertainty in the estimated mean or treatment contrast.

What do the arm summaries describe?

For the 0.5mg arm, the posted mean change is 14.0 letters, the standard deviation is 10.0, and the outcome count is 8. For the 1.0mg arm, the posted mean change is 5.0 letters, the standard deviation is 6.0, and the outcome count is 5. The summaries characterize the data recorded for those arms. They do not show how individual participants changed, whether observations were complete for everyone assigned, or why the primary-outcome counts differ from the safety denominators.

As general statistical context, a treatment comparison for a continuous outcome often estimates a difference between group means. An inferential analysis may then report an uncertainty measure, such as a confidence interval, and potentially a test result. These quantities answer different questions: the estimated contrast describes the direction and size of the group difference under the chosen analysis, while an interval communicates its precision. The registry record does not report a two-arm comparison estimate, confidence interval, or p-value for this primary endpoint. The registry marks values as missing or not estimable for a two-arm comparison of the continuous endpoint.

Why not calculate a contrast from the summaries?

Simple arithmetic on two posted means would not reproduce a sponsor analysis, account for the planned analysis, or resolve the registry’s indication that a comparison is unavailable. The record does not explain why the comparison is missing or not estimable. It also does not provide details such as participant-level data, covariate adjustments, or the analysis population that could be needed to interpret or reconstruct a comparison. The arm summaries should therefore be read as descriptive results rather than used to create an unreported inferential result.

As general statistical context, standard deviations and standard errors are not interchangeable. A standard deviation reflects variation among observations; a standard error reflects uncertainty in an estimated quantity and depends on the analysis and data available. A confidence interval for a contrast would use an estimate and its uncertainty under a specified method. No such contrast interval is reported, so the degree of precision cannot be judged from the standard deviations alone.

What does randomization contribute?

Random allocation is intended to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics at assignment. In a small study, chance imbalances can still occur. The record identifies the study as randomized but does not report the randomization procedure, concealment method, or any baseline balance details. It would be inappropriate to infer those procedures or the success of balance from the randomization label alone.

The study is open-label, with masking listed as none. In general, masking can reduce the influence of knowledge about assigned treatment on assessment or other study processes. Open-label design does not automatically invalidate an outcome, but the possibility of influence is relevant when interpreting a clinical measurement. The registry does not report whether the visual-acuity assessors were masked independently or how outcome measurement was standardized beyond use of a standard ETDRS chart at baseline and subsequent monthly visits.

How should planning estimates be read?

The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. The stated assumptions include a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. As general statistical context, a planning calculation asks how many participants might be needed under chosen assumptions to target a specified power for a future comparison. It does not measure the power actually achieved by this completed study, and it is not an outcome observed in participants.

Because the record does not give numerical planning outputs in the information summarized for this analysis, no specific participant requirement can be quoted. Any planning illustration should be considered hypothetical and assumption-dependent. In particular, using an observed effect as an input does not make that effect a reliable estimate for a future study; estimates from small datasets may be uncertain. The registry does not report a sample-size justification for the original study or its statistical design rationale.

What other analysis details are missing?

The record lists no analysis entries. It does not report the statistical model, handling of repeated monthly measurements, adjustment for baseline values, treatment of missing data, or a prespecified hierarchy of outcomes. It also does not specify an analysis population such as all randomized participants or a subset with observed follow-up. These are material details for interpreting a comparison, and they should not be inferred from the trial’s phase, design label, or posted summary statistics.

In general, missing observations can affect a mean if the participants with available measurements differ from those without them. A method for handling missing data depends on the pattern of missingness and the analysis plan. Since neither participant flow nor missing-data methods are reported, the available arm means cannot be assumed to represent all randomized participants. This limits interpretation of both the observed summaries and any broader claim about the groups originally assigned.

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("Intravitreal Ranibizumab 0.5mg", "Intravitreal Ranibizumab 1.0mg")
n   <- c(8, 5)
m   <- c(14, 5)
sp  <- c(10, 6)
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  Intravitreal Ranibizumab 0.5mg  8  14.000  10.000  5.640  22.360
CARM  Intravitreal Ranibizumab 1.0mg  5  5.000  6.000  -2.450  12.450

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five secondary outcomes in addition to the primary outcome. They concern center point thickness, mean best corrected visual acuity change, the percentage with CFT less than 300um, excess foveal thickness, and the total number of ranibizumab injections. Numerical results for these secondary outcomes are not reported in the registry record. The record also lists six outcome measures overall.

When multiple outcomes are examined, the chance of finding an apparently notable result by chance can increase if each is tested separately. As general statistical context, a statistical plan may address this issue through a prespecified primary outcome, an ordered testing strategy, or an adjustment for multiple comparisons. The registry record does not report a multiplicity strategy, outcome hierarchy beyond naming the primary endpoint, or inferential analyses for the secondary outcomes. It is therefore not possible to determine how multiple testing was handled.

The record contains no analysis entries. It does not describe an intention-to-treat analysis, a per-protocol analysis, or another analysis population. The number contributing to the primary outcome is 8 in the 0.5mg arm and 5 in the 1.0mg arm, while the safety record reports at-risk counts of 8 and 6. Participant flow, reasons for the differing denominators, and outcome-specific missingness are not reported in the registry record.

As general statistical context, missing outcome data can change the composition of the analyzed groups and may affect estimates if availability is related to outcome or treatment. The record does not specify imputation, sensitivity analyses, or another method for addressing missing values. It also does not state whether the monthly measurements were used only to collect the month 6 endpoint or analyzed longitudinally. Without these details, the population represented by the posted summaries and the robustness of any comparison cannot be fully assessed.

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 serious adverse event terms

Serious events with the highest arm-level rate: breast cancer (12.5%), ruptured retinal macroaneurysm (12.5%).

The safety record reports serious adverse events for each dose group using at-risk counts of 8 for ranibizumab 0.5mg and 6 for ranibizumab 1.0mg. The number affected by a serious adverse event is 2 in the 0.5mg group and 0 in the 1.0mg group. The different at-risk denominator for the 1.0mg safety summary compared with its primary-outcome count is not explained in the registry record.

The listed top serious adverse event terms are Breast Cancer and Ruptured Retinal Macroaneurysm, each reported at 12.5%. The record does not establish whether these events were judged related to treatment, provide timing or clinical details, or explain the term-level percentage calculation. The percentage should not be read as evidence of causation.

Other adverse events are reported as 0 among 8 at risk in the 0.5mg group and 0 among 6 at risk in the 1.0mg group. These summaries are limited to the record’s reported categories and denominators. Deaths are not reported in the registry record. In general, safety counts in a small study are descriptive; zero reported events does not establish that an event cannot occur, and event counts alone do not determine comparative risk.

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

The result gives descriptive information about mean change in ETDRS visual-acuity letters from baseline to month 6 among the participants contributing to each arm summary. It reports a mean change of 14.0 letters in the 0.5mg group and 5.0 letters in the 1.0mg group, with standard deviations of 10.0 and 6.0, respectively. The primary outcome counts are 8 and 5. These values describe the posted observations; they do not include a reported between-group estimate.

The registry does not report a confidence interval or p-value for the two-arm comparison and marks the continuous comparison as missing or not estimable. Accordingly, the record does not establish the precision of a difference between doses or report a statistical test of that difference. It also does not provide numerical results for the listed secondary outcomes. The reported arm means should not be treated as proof that either dose is better, equivalent, or worse.

The study’s randomized, parallel-group design is relevant to a comparative question, while its open-label status and limited outcome counts are important context. Randomization alone does not supply the missing comparison analysis or resolve uncertainty. The registry does not describe the allocation procedure, analysis population, missing-data handling, or participant flow, so the effect of these features on the posted summaries cannot be determined.

The safety record reports serious adverse event counts and term percentages, but does not provide enough detail to attribute events to treatment or to make a precise comparative safety assessment. The denominators differ between the primary outcome and safety summaries, and the record does not explain why. No conclusion about uncommon events can be drawn from these limited counts.

Overall, the registry record documents a small randomized study of two intravitreal ranibizumab doses and posts arm-level primary outcome summaries. It does not report the inferential comparison needed to quantify how the groups differed, nor does it report numerical secondary outcome results. Its contents support a description of the available summaries and of what remains unreported, rather than a definitive comparative conclusion.

14. Why This Trial Matters Statistically

This study is statistically notable because it addresses a direct comparison between two active doses in a randomized, parallel design, while the registry record does not provide an estimable comparison for its primary continuous outcome. The distinction between arm summaries and a comparative estimate is central: separate means describe each group, whereas a contrast with an uncertainty measure addresses how precisely the groups differ under a specified analysis.

The sample counts attached to the primary summaries are small, and the safety denominators do not match the primary-outcome count in the 1.0mg arm. These differences make participant flow and analysis-population definitions especially relevant. Yet the record does not report why the denominators differ, how missing measurements were handled, or which participants were included in the primary analysis. Those omissions constrain reproducibility and interpretation.

The study also illustrates why a randomized label cannot substitute for details of implementation and analysis. The record identifies randomization but does not describe sequence generation or concealment, and it lists no masking. It does not report whether visual-acuity assessors were masked separately. Such design information helps readers assess the credibility of a comparison, especially when an outcome involves measurement and the study is open-label.

Finally, the registry names several secondary outcomes but does not report their numerical results or a multiplicity strategy. A clear analysis plan and complete outcome reporting help distinguish confirmatory questions from exploratory ones. For this study, the available record is informative about design and selected descriptive results, while leaving important parts of the comparative statistical evidence unreported.

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.

Several limitations are specific to what is documented for this trial. The primary outcome summaries are based on 8 participants in the 0.5mg arm and 5 in the 1.0mg arm, while safety summaries use at-risk counts of 8 and 6. The registry does not explain the difference between the primary and safety denominators or provide participant flow, reasons for missing data, or the outcome-specific analysis populations.

The primary endpoint has arm-level means and standard deviations, but no reported two-arm comparison estimate, confidence interval, or p-value. The reason the comparison is missing or not estimable is not reported in the registry record. No participant-level results or analysis specification are available in this record to resolve that gap. The sponsor’s own analysis is not identified as discrepant in the record, but no comparison result is posted to interpret.

The open-label design is another relevant limitation. Masking is listed as none; whether outcome assessors were independently masked is not reported. The randomization procedure and allocation concealment are also not described. These omissions limit assessment of how the design was implemented, rather than demonstrating that a particular bias occurred.

Although five secondary outcomes are listed, their numerical results are not reported in the registry record. Multiplicity handling, missing-data methods, and the statistical model are not reported either. The registry does not provide details of treatment schedules, adherence, or discontinuations. Finally, the serious adverse event summary is limited to counts and selected terms; attribution and event timing are not reported, and deaths are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Intravitreal Ranibizumab 0.5MG, or 1.0mg for RVO With Macular Edema Previously Receiving Bevacizumab — NCT01471691.
• Registry record last updated 2015-04-29; status last verified 2015-04.
• Results first posted 2015-04-29.
• 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

The registry describes NCT01471691, a completed, randomized, open-label, phase I/II, parallel-group study of intravitreal ranibizumab 0.5mg and 1.0mg for macular edema associated with retinal vein occlusion after prior treatment that included bevacizumab. Enrollment is listed as 14. The recorded study start is 2011-11 and primary completion is 2014-02.

The primary endpoint is mean change in best corrected visual acuity in ETDRS letters from baseline to month 6. The posted means are 14.0 with a standard deviation of 10.0 for 8 participants in the 0.5mg arm, and 5.0 with a standard deviation of 6.0 for 5 participants in the 1.0mg arm. A two-arm comparison is not reported as estimable. The registry also lists five secondary outcomes, but their numerical results are not reported in the registry record.

Safety summaries report serious adverse events in 2 of 8 at risk in the 0.5mg group and 0 of 6 at risk in the 1.0mg group. The registry does not report a comparison estimate, analysis details, or an explanation for the differing primary-outcome and safety denominators.