Efficacy and Safety of Lucentis® (Ranibizumab Intravitreal Injections) in Chilean Patients With Diabetic Macular Edema.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Lucentis® (Ranibizumab Intravitreal Injections) in Chilean Patients With Diabetic Macular Edema. (NCT02140411), a na phase 4 study. The primary outcome is Mean Change From Baseline in Best Correct Visual Acuity (BCVA).

2. Clinical Question

3. Trial Design

This was a completed interventional, open-label pilot study in Chile, registered as Phase 4. The registry lists enrollment as 21 and describes a single-group model, with no allocation and no masking. Participants received ranibizumab intravitreal injections; no placebo or active control arm is described. The study began on 2015-04-25 and its primary completion date was 2016-12-21.

The design follows participants receiving treatment and assesses changes over time rather than comparing randomized groups. The primary endpoint is change in best-corrected visual acuity from baseline to week 48. Secondary outcomes include visual-acuity changes at week 4, 8, 12, 24 and 36; change over time in intraretinal thickness measured by optical coherence tomography; injections received over a 48 week treatment period; letter gain or loss at week 52; and change in the Visual Function Questionnaire. The registry lists six outcome measures.

Because there is no control group and the study is open label, observed changes cannot by themselves distinguish a treatment effect from other influences on visual acuity over time. The record does not report a protocol-level rationale for the enrollment target, details of follow-up completeness, or a statistical analysis plan. The registry lists Retinal Vein Occlusion and Age Related Macular Degeneration among conditions, while the study title and summary focus on diabetic macular edema; the record does not explain this difference in condition listings.

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 (FAS) include all patients who received at least one dose of study medication, and have at least one post-baseline efficacy assessment. The FAS is analyzed according to the intention to treat ideal.

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.

Population: Full Analysis Set (FAS) include all patients who received at least one dose of study medication, and have at least one post-baseline efficacy assessment. The FAS is analyzed according to the intention to treat ideal.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Best Correct Visual Acuity (BCVA), measured over baseline, week 48.

The primary endpoint is mean change from baseline in best-corrected visual acuity (BCVA), expressed in letters, at baseline and week 48. BCVA is a measure of visual acuity assessed under standardized testing conditions. In this study, it was measured using an Early Treatment Diabetic Retinopathy Study-like chart, with participants sitting at a testing distance of 4 meters. The stated chart range is 0 to 100 letters. The registry defines a positive change from baseline as improvement.

Change from baseline is used to describe how the measured outcome differs after treatment from each participant’s initial assessment. Reporting a group mean summarizes the average change, while a standard deviation describes how widely individual changes vary around that average. These are complementary: the mean describes the central result, and the standard deviation describes variability among the observations.

The endpoint is specified, but the numerical mean change and standard deviation at week 48 are not reported in the registry record. A confidence interval, which would convey uncertainty around an estimated mean change, is also not reported in the registry record. Consequently, the endpoint definition alone does not establish the size or precision of the observed change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: continuous outcomes are measurements that can take a range of values. A mean summarizes the average observed value or change, while a standard deviation describes variation among observations. The primary outcome is a continuous measure because it is defined as mean change in BCVA letters. The registry names the mean and standard deviation as the summary measures, but does not report their primary-outcome values. Without those estimates, readers cannot assess the average change or the spread of individual changes in the study population.

What does change from baseline represent?

For each participant with the required assessments, a change score represents the follow-up measurement relative to that participant’s baseline measurement. The group mean of those changes describes the average within-participant change. This differs from comparing the final group mean with an unrelated external value: the baseline measurement is the reference for each participant’s follow-up. The registry specifies baseline and week 48 for the primary outcome and says that a positive BCVA change indicates improvement. It does not provide the actual change scores or the group estimate.

General statistical explanation: a standard deviation is a measure of dispersion among observations, not a measure of how precisely the group mean has been estimated. A confidence interval is commonly used to express uncertainty around an estimate; its width depends in part on the amount of information and variability in the data. No confidence interval for the primary mean change is reported in the registry record. A p-value, if reported, would address compatibility with a specified statistical null hypothesis under the analysis assumptions; it would not by itself describe the size or clinical importance of a change. The registry record does not report a primary-outcome p-value or the associated testing procedure.

Why does the study structure matter?

General statistical explanation: a single-group study can describe change over time in participants receiving an intervention, but it cannot estimate a between-group contrast when no control group is present. Randomized allocation, when used, supports a comparison by creating groups intended to be comparable in expectation. This study has no allocation and is described as single group, so there is no randomized treatment contrast to interpret. Its open-label status means masking was absent. These design features do not invalidate descriptive measurements, but they limit what can be attributed to the intervention.

The primary analysis population is described as the Full Analysis Set. It includes patients who received at least one dose and had at least one post-baseline efficacy assessment, and the record says the set is analyzed according to the intention-to-treat ideal. This definition identifies who could contribute to efficacy analyses, but the number included and the precise analysis procedures are not reported in the registry record. It also does not specify how missing week 48 measurements were handled.

How should repeated measurements be understood?

The registry lists visual-acuity assessments at baseline and multiple follow-up weeks, alongside a primary endpoint at week 48. Repeated observations can describe the course of a measure over time, but observations from the same participant are related rather than independent. General statistical explanation: an analysis of repeated measurements should account for this within-participant relationship when estimating trends or comparing time points. The registry record does not describe a repeated-measures model, a covariance structure, or another method for analyzing the sequence of measurements. It also does not report the numerical results for those follow-up visual-acuity outcomes.

Intraretinal thickness measured by optical coherence tomography is another listed outcome. General statistical explanation: anatomical and functional measures describe different aspects of an outcome and need not change in parallel. The record identifies change over time in intraretinal thickness but does not report estimates or methods for that outcome. It also lists injections received over a 48 week treatment period, letter gain or loss at week 52, and change in the Visual Function Questionnaire; their numerical results are not reported in the registry record.

What can a planning illustration tell a reader?

General statistical explanation: a sample-size calculation is a planning exercise for a future study. Its output depends on assumptions about the effect to detect, significance level, allocation, and analysis method. It is not a measure of the probability that a completed study detected an effect. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such assumptions do not describe this single-group study’s design, and any planning illustration is not observed power. The registry record does not report a trial-specific sample-size justification or numerical planning results.

The record lists no analyses. It does not report whether any interim analyses were conducted, which statistical tests were used, or whether the primary endpoint analysis was adjusted for other factors. These details should not be inferred from the endpoint definition or the design description. Statistical interpretation is consequently limited to the registered outcome definitions, analysis-population description, design characteristics, and reported safety counts.

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("Ranibizumab")
n   <- c(20)
m   <- c(9.55)
sp  <- c(6.57)
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  Ranibizumab  20  9.550  6.570  6.475  12.625

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary BCVA outcome and secondary outcomes covering visual acuity at several follow-up weeks, intraretinal thickness, injections, letter gain or loss, and visual function. Considering multiple outcomes or time points can increase the chance of apparently notable findings when many statistical tests are performed. General statistical explanation: a multiplicity plan specifies how such testing will be interpreted or controlled. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified method for interpreting multiple comparisons. It lists no analyses, so no conclusion can be made about how multiplicity was handled in reported results.

The Full Analysis Set is defined as patients who received at least one dose and had at least one post-baseline efficacy assessment. The registry describes this population as analyzed according to the intention-to-treat ideal. The number included in this set is not reported in the registry record. The record also does not report how many participants had a week 48 BCVA assessment, the extent of missing data at other time points, reasons for missing assessments, or any imputation or sensitivity-analysis method.

General statistical explanation: missing outcomes can affect an estimate if participants with missing data differ systematically from those with observed measurements. The consequences depend on why values are missing and on the analysis method. Because those details are not reported, the effect of missingness on the endpoint cannot be assessed. The registry’s analysis-population definition should not be taken as evidence that all enrolled participants contributed complete follow-up data.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: conjunctival haemorrhage (4.8%), vitreous haemorrhage (4.8%), pharyngitis (4.8%), pneumonia (4.8%), pyelonephritis (4.8%).

The safety record lists Ranibizumab 0.5 mg, with 21 participants at risk for the serious-event category and 6 participants affected. In the other adverse-event category, 21 were at risk and 17 were affected. The record reports 0 deaths. These are descriptive counts in a single-group study, not comparisons between treatments.

The listed serious-event terms are conjunctival haemorrhage, vitreous haemorrhage, pharyngitis, pneumonia, pyelonephritis, and ischaemic stroke. Each term is listed at 4.8%. These registry entries identify reported terms and their listed percentages; they do not establish that ranibizumab caused an event. The record does not provide a comparison group, and it does not describe event-level timing or attribution in the information.

General statistical explanation: safety counts from a study of this size provide limited information about uncommon events and about comparative risks. The count of participants affected is not interchangeable with a count of event episodes, since an individual may experience more than one event. The record does not specify how many events occurred in total for each term. The reported counts should therefore be read as descriptive safety information, not as evidence of a causal relationship or a comparative safety estimate.

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

The registry record establishes the study question, design, endpoint definition, analysis-population description, and selected safety counts. It does not report the numerical primary BCVA mean change or its standard deviation. It also does not report a confidence interval or p-value for that endpoint. As a result, the size and precision of the primary efficacy result cannot be assessed from this record.

The design is a single-group, open-label study. Any observed change from baseline would describe the course of BCVA among participants who received ranibizumab and met the stated analysis-population criteria. Without a concurrent comparator, that change cannot be separated from changes that could have occurred over time for other reasons. The registry does not establish a causal treatment effect or a comparative effect relative to another intervention.

The record lists several secondary outcomes, but does not report their numerical results. Their presence indicates additional domains of interest, not evidence that those outcomes improved or changed in a particular direction. Likewise, the safety counts describe reported events in the treated group; they do not quantify an excess risk relative to a comparator or prove that the intervention caused an event.

General statistical explanation: an estimate describes the observed data, while its uncertainty communicates how much precision the data support. A statistically significant result, if one were reported, would not by itself establish clinical importance, and a nonsignificant result would not prove the absence of an effect. Here, the primary estimate and its uncertainty are not reported in the registry record, so those distinctions cannot be applied to the efficacy outcome. The defensible interpretation is limited to the study’s design and the registry entries that the registry actually records.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how a clearly named continuous endpoint can still be difficult to interpret when the numerical outcome estimate is absent. The registry defines BCVA change in letters, identifies baseline and week 48 as the primary comparison, describes the measurement method, and states the direction considered improvement. Those details explain what the endpoint was intended to capture, but they cannot replace the observed mean change and its uncertainty.

The single-group, open-label design also makes the distinction between description and causal comparison important. A within-participant change can be summarized, but without a control group it does not identify what would have happened over the same period in the absence of the intervention. This is a design limitation, not something that can be resolved by the wording of the endpoint.

The registry’s stated Full Analysis Set criteria highlight another interpretive issue: enrollment and analysis population are not necessarily the same. Patients needed to receive at least one dose and have at least one post-baseline efficacy assessment to meet the stated definition. The size of that set and the handling of missing week 48 measurements are not reported, leaving uncertainty about the available outcome data.

Finally, the record includes multiple secondary outcome domains and descriptive safety counts. They provide context for what the study intended to assess, but the lack of reported numerical efficacy results and analysis methods limits conclusions about patterns across outcomes, precision, and comparative safety. The study therefore illustrates why endpoint definitions, design, analysis populations, missing-data handling, and numerical estimates all matter to statistical interpretation.

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.

The primary limitation for interpreting efficacy is that the registry record does not report the primary mean change in BCVA, its standard deviation, a confidence interval, or a test result. Numerical findings for the listed secondary outcomes are also not reported. Without outcome estimates, the magnitude and precision of changes cannot be evaluated.

The study has no comparator group, no allocation, and no masking. It can describe within-group change but cannot establish a treatment contrast. Open-label conduct may also matter for measurements or reporting, although the registry record does not describe whether any additional assessment safeguards were used.

The record lists enrollment of 21, but does not report the number meeting the Full Analysis Set definition or the number with a week 48 assessment. Missing-data reasons, methods for handling missing outcomes, and sensitivity analyses are not reported in the registry record. The registry also does not report a detailed statistical analysis plan, multiplicity procedures, or the statistical methods used for the outcomes.

The listed conditions include Retinal Vein Occlusion and Age Related Macular Degeneration, while the title and study summary focus on diabetic macular edema. The registry record does not explain the condition-listing difference. Safety information is descriptive, has no comparison group, and does not report event timing or causal attribution in the information recorded. These limitations restrict both efficacy and safety interpretation to the registry’s stated design and reported counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Lucentis® (Ranibizumab Intravitreal Injections) in Chilean Patients With Diabetic Macular Edema. — NCT02140411.
• Registry record last updated 2019-02-20; status last verified 2018-10.
• Results first posted 2019-02-20.
• 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

NCT02140411 is a completed Phase 4, open-label, single-group interventional pilot study of intravitreal ranibizumab in Chilean patients with visual impairment due to diabetic macular edema. Enrollment was 21. The study began on 2015-04-25, and primary completion was recorded as 2016-12-21.

The primary outcome was mean change from baseline to week 48 in BCVA letters. The registry defines the Full Analysis Set as patients who received at least one dose and had at least one post-baseline efficacy assessment. The numerical primary efficacy result and its uncertainty are not reported in the registry record.

Safety listings include 6 participants with serious adverse events among 21 at risk, 17 in the other adverse-event category among 21 at risk, and 0 deaths. These counts are descriptive and have no comparator group.