To Assess the Efficacy and Safety of Intravitreal Ranibizumab in People With Vision Loss Due to Macular Edema: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Assess the Efficacy and Safety of Intravitreal Ranibizumab in People With Vision Loss Due to Macular Edema (NCT01846299), a randomized phase 3 study. The primary outcome is Change From Baseline in Best-corrected Visual Acuity (BCVA) in Study Eye.

2. Clinical Question

The primary outcome was expressed in ETDRS-like visual acuity letters. A positive change from baseline represents improvement on that measure. The question therefore concerns the average short-term change in a standardized vision score between the trial’s assigned strategies, rather than the result for every participant or a direct measure of all aspects of vision.

The comparator is important to the interpretation. The sham strategy was not a no-treatment strategy throughout the study: the record describes possible sham treatment at Month 1 and a switch to open-label ranibizumab at Month 2. The primary comparison is consequently tied to the recorded timing and treatment rules, and should not be read as a comparison against continued sham beyond the described period.

3. Trial Design

This was a randomized, parallel-group phase 3 study sponsored by Novartis Pharmaceuticals. The registry records an enrollment of 181 and a study start of 2013-10, with primary completion in 2015-09. Its official title describes a 12-month, randomized, double-masked, sham-controlled, multicenter study. The structured registry record lists masking as triple; the reason for the difference in masking descriptions is not reported in the registry record.

Participants were assigned to ranibizumab or a sham-control strategy. In the ranibizumab group, a 0.5 mg intravitreal injection was given to the study eye at baseline, with subsequent treatment as needed based on disease activity. In the sham group, sham was given at baseline; if treatment was needed at Month 1, sham was administered, and participants switched to open-label ranibizumab on an as-needed basis at Month 2.

The primary endpoint was change from baseline in best-corrected visual acuity in the study eye at Month 2. The primary analysis population was the full analysis set, defined in the registry as all randomized participants who received at least one dose of study treatment. The record reports 117 participants in the ranibizumab primary-outcome group and 60 in the sham-with-ranibizumab group.

The registry lists 14 outcome measures and one analysis for the primary outcome. It also lists secondary measures including visual acuity, retinal thickness and volume, retinal fluid, active macular edema leakage, and rescue treatment. The trial is marked completed. Details of the original sample-size justification, randomization procedure, and protocol deviations 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:

Analysis population for the primary outcome, as defined in the registry: Full analysis set: The full analysis set included all randomized participants who received at least one dose of study treatment.

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 Best-corrected Visual Acuity (BCVA) in Study Eye, measured over Baseline, Month 2.

The primary endpoint is change from baseline in best-corrected visual acuity (BCVA) in the study eye, measured in letters at baseline and Month 2. The registry describes an ETDRS-like visual acuity chart assessment, performed with participants sitting and an initial testing distance of 4 meters. A positive change from baseline indicates improvement in the measured score.

BCVA is a continuous outcome: it records a value on a scale rather than simply classifying each participant as improved or not improved. Comparing group means can capture the average change across participants while retaining more information than a binary outcome would. The registry’s reported analysis estimates a net mean difference between groups, while the posted arm results give least-squares mean changes and standard errors.

Best-corrected acuity is used in this trial to quantify visual performance under a standardized testing approach. It is one specific measure of visual function; it does not describe every aspect of vision or the experience of each individual participant. The Month 2 timing is also consequential because the sham group’s treatment strategy changed at that point according to the registry description. The endpoint therefore addresses the contrast at the specified assessment time, not a general comparison across all later follow-up.

7. Results Posted in the Registry

• Ranibizumab: mean 5.70 versus 2.90 on control; difference 2.80 (95% CI 0.44 to 5.16), standardized effect d = 0.34; z-test p = 0.020.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants With Presence of Active Macular Edema (ME) Leakage

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Ranibizumab: 82.1% (96/117) versus 88.3% (53/60) on control; risk difference -6.3 percentage points (95% CI -17.0 to 4.4), risk ratio 0.93 (0.82–1.05); unadjusted two-proportion z-test p = 0.278.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Ranibizumab and the control. The interval gives the range of effects that remain compatible with the data.

The registry names secondary outcomes across several domains: visual acuity, retinal thickness and volume, retinal fluid, active macular edema leakage, and rescue treatment. These outcomes can add context by assessing aspects of the condition beyond the primary visual-acuity measure. They do not answer precisely the same question as the Month 2 BCVA endpoint, and differences in outcome type and assessment time affect how directly they relate to the primary result.

Numerical results for the secondary outcome of active macular edema leakage at Month 2 are posted, but sponsor-reported analyses for that outcome are not listed. Numerical findings for the other secondary outcomes are not reported in the registry record in the information available for this analysis. As a result, the overall pattern across secondary endpoints cannot be established from the registry record; it would be inappropriate to describe them as consistently supporting or contradicting the primary result.

In general, secondary outcomes can help assess whether an observed primary result is accompanied by related changes in other measures. They are most informative when definitions, timing, analysis populations, and planned comparisons are clear. A multiplicity plan is not reported in the registry record. When many outcomes are tested without a stated adjustment strategy, isolated unadjusted findings carry less weight because the chance of chance findings increases as the number of comparisons grows.

Secondary outcomes should therefore be interpreted as additional context rather than as independent confirmation of the primary result. The registry’s list of outcome measures does not itself establish a consistent pattern, and missing numerical results limit the scope of any comparison across endpoints.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in BCVA in Study Eye up to Month 2
• Change From Baseline in Central Subfield Thickness (CSFT) in Study Eye
• Change From Baseline in Central Subfield Volume (CSFV) in Study Eye
• Number of Participants With Presence or Absence of Intra-retinal Fluid in Study Eye Compared to Baseline
• Number of Participants With Presence or Absence of Subretinal Fluid in Study Eye Compared to Baseline
• Number of Participants With Presence of Active Macular Edema (ME) Leakage
• Number of Participants Requiring Rescue Treatment at Month 1
• Average Change From Baseline in BCVA

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, and the registry reports a least-squares mean change for each arm along with a standard error. A mean summarizes the central tendency of measured changes across a group. The least-squares mean is a model-based estimate; the registry does not report enough model detail to explain which covariates or other adjustments were included. A standard error describes the precision of an estimated mean, rather than the spread of individual participant outcomes.

What does the mixed models analysis estimate?

The sponsor’s reported method is a mixed models analysis, with the result expressed as a net mean difference between the groups. In general, mixed models can represent relationships among repeated measurements and account for variation at different levels of a study. That can be useful when outcomes are measured over time or when observations are not independent. The registry record does not report the specific model formula, covariance structure, missing-data assumptions, or detailed implementation used for this endpoint. Those features should not be inferred from the method label alone.

The registry reports a net mean difference of 2.78 letters, a 95% confidence interval from 0.40 to 5.16, and a p-value of 0.011. The confidence interval expresses a range of values compatible with the estimate under the fitted analysis and its assumptions. The p-value summarizes how inconsistent the observed data are with a specified null hypothesis under the model; it is not the probability that the null hypothesis is true, nor a measure of the clinical importance of the result.

How does the unadjusted recalculation differ?

A recalculated comparison based on the posted group summaries gives an unadjusted mean difference of 2.8 letters. This calculation uses the arm-level means and standard errors to form a simple comparison. It does not reproduce the sponsor’s mixed model. The posted pooled standard deviation is approximate, and the recalculation is a summary-statistic check rather than a reconstruction of participant-level data or of the sponsor’s model. Since the registry does not flag a discrepancy, both estimates can be described, while keeping clear that the sponsor’s mixed-model analysis is the reported trial analysis.

In general, an unadjusted comparison may differ from a model-based estimate when the model accounts for features not represented in a simple summary calculation. A discrepancy between estimates would need investigation of the analysis populations, model specification, and outcome handling; the registry does not flag such a discrepancy. The recalculated estimate should therefore be treated as an analytical cross-check, not as an alternative primary result.

What do the secondary outcome methods imply?

The registry includes continuous secondary measures, such as BCVA and central subfield thickness or volume, and binary measures, such as the presence of retinal fluid or active macular edema leakage. For a binary outcome, a risk difference compares the proportions with the event in the groups. In the posted leakage outcome, the arm counts are 96 of 117 and 53 of 60; the recalculated risk difference is not the sponsor’s reported model result, and no sponsor analysis is listed for that outcome.

For binary outcomes, confidence intervals can be wide when event counts or group sizes are limited. In general, the precision depends on the observed proportions and the amount of information in the data. A non-significant unadjusted result does not demonstrate that the groups are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess whether the interval lies within it; such a margin is not reported in the registry record.

Multiplicity arises when many outcomes or comparisons are considered. In general, examining many tests without a planned adjustment increases the chance of at least one apparently unusual result arising by chance. The registry record lists multiple secondary outcomes, but a multiplicity adjustment plan is not reported in the registry record. Secondary findings should therefore be treated as supporting or exploratory unless a prespecified inferential strategy is available.

The sample-size illustrations use a normal approximation and equal allocation between the two arms, with a two-sided significance level of 0.05. They examine planning targets based on fractions of the observed effect. These are general planning calculations using the observed estimate as an input; they do not establish what assumptions were used to design the original trial. The original design assumptions and sample-size justification are not reported in the registry record.

Finally, interpretation depends on the analysis population and handling of incomplete measurements. The registry defines the full analysis set as randomized participants who received at least one dose, but does not state the number with a Month 2 BCVA measurement, the approach to missing outcome data, or sensitivity analyses for missingness. Those details matter because complete-case data, imputation, and model-based handling of incomplete observations can rely on different assumptions. The registry’s method label alone is not enough to determine which assumptions apply.

11. Confidence Intervals and Precision

The sponsor’s estimate of the net mean difference in BCVA change is 2.78 letters, with a 95% confidence interval from 0.40 to 5.16 letters. The interval indicates that the estimated contrast is not pinpoint precise: a range of effects is compatible with the analysis. The lower end is close to no difference, while the upper end allows for a larger mean contrast. This is uncertainty about the group-level estimate, not a range containing a specified proportion of individual participants’ changes.

In general, a confidence interval combines the point estimate with information about its standard error and the chosen confidence level. A narrower interval indicates greater statistical precision, while a wider interval leaves more uncertainty about the effect’s magnitude. The interval should be interpreted with the model’s assumptions in mind; it does not account for every possible source of bias or uncertainty in trial conduct and reporting.

The arm-level standard errors are 0.81 letters for ranibizumab and 0.89 letters for sham with ranibizumab. Standard errors describe uncertainty around the estimated arm means, not the variability of individual outcomes. The registry also reports a recalculated difference of 2.8 letters from posted summaries, with an approximate pooled standard deviation of 8.18; that calculation is unadjusted and distinct from the sponsor’s mixed-model interval.

Precision is limited to the stated outcome, population, and Month 2 assessment. The registry does not report details needed to evaluate the precision of longer-term contrasts or to determine how incomplete outcome data affect the interval. Statistical precision should also be distinguished from clinical importance: the registry does not provide a threshold for a meaningful difference in BCVA letters.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants and not total events. The calculations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at 100%, 75%, or 50% of the observed effect. The trial’s original sample-size assumptions and justification are not reported in the registry record.

The 80% power column describes the planned number of participants per arm for a design that would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and those assumptions held. The 90% power column gives the corresponding planning target for a 90% chance. These are design concepts: power is calculated before outcomes are observed and depends on the effect size, variability, allocation, significance level, and analysis assumptions.

For the primary continuous outcome, planning for 100% of the observed effect gives 134 participants per arm for 80% power and 180 participants per arm for 90% power. Planning for 75% gives 239 participants per arm for 80% power and 319 participants per arm for 90% power. Planning for 50% gives 536 participants per arm for 80% power and 718 participants per arm for 90% power. The secondary leakage outcome has its own set of planning illustrations, based on that outcome’s observed effect.

Smaller effects generally require more participants to detect under otherwise unchanged assumptions, because they are harder to distinguish from random variation. These figures are planning illustrations based on observed effects, not observed power. They do not show the probability that the completed trial’s result is true or establish the design assumptions used by the trial’s investigators.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 2.800; pooled standard deviation σ = 8.180.
2. n = 2 × (1.96 + 0.842)² × 8.180² / 2.800² = 134.0, rounded up to 134 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 2.8                      # observed difference in means
sigma <- 8.17963436137058                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1846299)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 134 (80% power), 180 (90% power)
 75% of observed effect: n per arm = 239 (80% power), 319 (90% power)
 50% of observed effect: n per arm = 536 (80% power), 718 (90% power)
power.t.test: 134.9 
Simulated power at n = 134 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a mixed models analysis. It estimates a net mean difference of 2.78 letters, with a 95% confidence interval from 0.40 to 5.16 and a reported p-value of 0.011. This is the trial’s reported inferential analysis and should be distinguished from the simpler recalculation based on posted arm summaries.

The recalculation estimates a difference of 2.8 letters. It is an unadjusted comparison using the reported arm means and standard errors, and its pooled standard deviation is approximate. The two estimates are close in magnitude, but the recalculation does not reproduce the sponsor’s model or its assumptions. The registry does not flag a discrepancy between the recalculation and sponsor result.

The recalculation is useful as a consistency check on the direction and approximate scale of the contrast, not as a replacement for the mixed-model analysis. The registry does not report full model specifications, so readers cannot independently reconstruct every step of the sponsor’s analysis from the record alone. The sponsor’s reported estimate remains the appropriate result to cite as the registry analysis.

15. Multiplicity, Missing Data and Analysis Populations

The primary analysis population is defined as the full analysis set, comprising randomized participants who received at least one dose of study treatment. The registry reports primary-outcome arm counts of 117 for ranibizumab and 60 for sham with ranibizumab. It does not report how many participants had an observed Month 2 BCVA measurement or whether the analysis population differed for particular outcomes.

The method for handling missing outcome measurements is not reported in the registry record. The record also does not provide the amount or pattern of missing data, the assumptions used for incomplete observations, or sensitivity analyses assessing the effect of alternative assumptions. These omissions limit assessment of whether missing outcomes could affect the estimated group contrast.

The registry lists 14 outcome measures, including the primary and secondary measures, and reports one primary analysis. A plan for controlling multiplicity across the secondary outcomes is not reported in the registry record. In general, testing several outcomes or comparisons raises the probability of obtaining at least one nominally notable result by chance. Without a prespecified hierarchy or adjustment method, unadjusted secondary p-values should not be interpreted as if they were the sole planned test.

Details of interim analyses, stopping rules, and the original statistical analysis plan are not reported in the registry record. The protocol’s sample-size justification and original design assumptions are also not reported. The registry identifies a mixed models analysis for the primary comparison, but further details such as covariates, model structure, and missing-data assumptions are not reported in the registry record. These limitations do not invalidate the posted estimate, but they constrain independent evaluation of how it was obtained and how robust it is to analytic choices.

16. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: basilar artery thrombosis (50.0%), brain stem stroke (50.0%), cardio-respiratory arrest (1.8%), corneal oedema (fellow treated eye) (1.8%), gastritis (1.8%).

The registry records serious adverse events among 15 of 119 participants in the ranibizumab 0.5mg group, 6 of 56 in the sham-with-ranibizumab 0.5mg group, and 1 of 2 in the sham-without-ranibizumab 0.5mg group. The other adverse-event counts are 58 of 119, 21 of 56, and 0 of 2, respectively. These are the registry’s reported counts and at-risk denominators; they should be read in the context of the listed group definitions and exposure periods.

The very small sham-without-ranibizumab group makes its count especially difficult to compare with the larger groups. The record does not provide a comparable randomized-group safety analysis or explain the timing and duration of exposure for these adverse-event groups in the details used. The listed serious-event terms include basilar artery thrombosis, brain stem stroke, cardio-respiratory arrest, corneal oedema in the fellow treated eye, gastritis, and acute pancreatitis. The denominators for the percentages attached to these terms are not reported in the registry record.

Deaths are not reported in the registry record. Adverse-event counts alone do not establish causation, and they do not support conclusions about an individual participant’s risk.

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

The posted primary result estimates a greater average change in BCVA at Month 2 in the ranibizumab group than in the sham-with-ranibizumab group. The sponsor’s mixed-model estimate is 2.78 letters, with a 95% confidence interval from 0.40 to 5.16 letters. The interval conveys uncertainty about the average contrast, while the arm estimates show that changes varied in their mean magnitude across the assigned groups.

This result is specific to the study eye, the BCVA letter measure, the full analysis set, and the Month 2 assessment. It does not show that every participant improved, establish what happened to each individual, or capture every dimension of visual function. The registry does not report a threshold for a clinically meaningful difference, so the statistical estimate alone does not determine the practical importance of the difference.

The comparator strategy also narrows interpretation. The sham group could receive sham at Month 1 if treatment was needed and switched to open-label ranibizumab at Month 2. Thus, the primary contrast is between the baseline ranibizumab strategy and the recorded sham-and-switch strategy at the specified time. It is not a long-term comparison with continued sham treatment.

The estimate does not establish the longer-term course through the stated 12-month study period, because the primary outcome is reported at Month 2. Nor does it establish safety in every population or setting beyond the trial’s recorded groups. The registry’s secondary outcomes address related but distinct measures; the absence of complete numerical results for those measures limits claims about consistency across outcomes.

In general, statistical evidence about an average group difference does not by itself determine an individual outcome, prove a mechanism, or replace consideration of uncertainty and study limitations. The registry result supports a description of the observed Month 2 comparison, with the confidence interval indicating the precision of the estimated contrast.

18. Why This Trial Matters Statistically

This trial illustrates why the estimand and comparator strategy matter as much as the numerical estimate. The primary outcome is a continuous measure of visual acuity, assessed at a specified time, while the control strategy changes around that assessment. A reader needs the treatment timing and endpoint timing to understand what the mean difference represents.

It also offers a comparison between a sponsor-reported mixed-model analysis and a simple unadjusted recalculation from posted summaries. The estimates are close in scale, but they arise from different methods. This distinction is useful in biostatistics: a transparent summary calculation can serve as a reasonableness check, while the prespecified or sponsor-reported model remains the relevant trial analysis when its details are available.

The confidence interval demonstrates that statistical interpretation should include the range of plausible effect sizes, not only the point estimate or p-value. The interval permits a range of positive average differences and communicates uncertainty about the magnitude. Without a reported threshold for clinical importance, statistical evidence and practical interpretation must remain separate.

The registry also makes visible the limits of incomplete reporting. Details of missing-data handling, multiplicity control, interim analysis, and original design assumptions are not reported in the registry record. These omissions affect independent appraisal of robustness and of secondary results. The case therefore underscores that clinical-trial interpretation relies on both the effect estimate and transparent reporting of the analysis plan, population, and supporting outcomes.

19. 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 leaves several trial-specific questions unanswered. The original sample-size justification and design assumptions are not reported, so the planning illustrations cannot be treated as a description of the trial’s intended power. The registry also does not state the randomization procedure or provide the specific model specification for the primary mixed models analysis.

The primary assessment is at Month 2, while the official title describes a 12-month study. Numerical findings for later BCVA time points are not reported in the registry record in the information used for this analysis. The Month 2 result therefore cannot establish persistence or the longer-term pattern of response. The sham group’s switch to open-label ranibizumab at Month 2 further limits interpretation of the comparator as a sustained sham strategy.

Information about missing BCVA measurements, reasons for missingness, and sensitivity analyses is not reported in the registry record. The record defines the full analysis set but does not give the Month 2 measurement count or explain how incomplete observations were handled. This restricts assessment of possible missing-data effects.

The registry lists multiple secondary outcomes, but a multiplicity strategy is not reported, and most secondary numerical results are not available in the information used. No clinical-importance threshold for the letter difference is reported. Safety groups have different at-risk denominators, including a sham-without-ranibizumab group with only 2 participants; the record does not provide enough detail to support direct comparative safety conclusions across those groups.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: To Assess the Efficacy and Safety of Intravitreal Ranibizumab in People With Vision Loss Due to Macular Edema — NCT01846299.
• Registry record last updated 2016-05-23; status last verified 2016-04.
• Results first posted 2016-05-23.
• 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.

23. Record Summary

NCT01846299 is a completed, randomized phase 3 parallel-group study sponsored by Novartis Pharmaceuticals. It evaluated intravitreal ranibizumab for adults with visual impairment due to macular edema. The official title describes a 12-month, sham-controlled, multicenter study; the registry lists triple masking, while the title describes double masking.

The primary outcome was change from baseline in BCVA in the study eye at Month 2, measured in ETDRS-like letters. In the full analysis set, the sponsor’s mixed models analysis estimated a net mean difference of 2.78 letters, with a 95% confidence interval from 0.40 to 5.16. The sham strategy included a switch to open-label ranibizumab at Month 2.

The registry lists a range of secondary visual and retinal outcomes and records adverse-event counts. Original design assumptions, detailed missing-data methods, multiplicity control, and numerical findings for most secondary outcomes are not reported in the registry record.