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 The Effect of Intravitreal Ranibizumab on Visual Acuity and Hard Exudate Resolution in the Treatment of Diabetic Macular Edema With Center Involved Edema and Lipid Exudates (NCT02448446), a randomized phase 1, phase 2 study. The primary outcome is Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02448446 |
| Phase | Phase 1, Phase 2 |
| Condition | Diabetic Macular Edema, Hard Lipid Exudates |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | South Coast Retina Center; Carson, McBeath, Boswell, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People with diabetic macular edema and lipid exudates in the central subfield were eligible for this trial. The registry lists diabetic macular edema and hard lipid exudates as the conditions studied. It does not report additional eligibility details, such as baseline visual acuity or the amount and location of lipid exudate.
Intervention
Both groups received intravitreal ranibizumab 0.3mg. Group 2 continued treatment until both macular edema and lipid exudate resolved. The record describes Group 1 treatment as based on the DRCR protocol I 4:2:7 strategy according to the presence of macular edema.
Comparator
The comparison was between two ranibizumab treatment strategies, not between ranibizumab and no treatment or a placebo. The record describes a randomized, parallel-group trial with no masking. It does not report further details about how assignment was generated or concealed.
Primary question
The primary outcome was best corrected visual acuity, measured as the number of letters read correctly on an ETDRS eye chart at a starting test distance of 4 meters. The registry specifies assessment at 6 and 12 months. It does not report the group means, standard deviations, or a statistical comparison, so the primary question cannot be answered from the posted results.
3. Trial Design
This completed study is described as a randomized, open-label Phase I/II trial using a parallel-group design. The registry lists enrollment as 25. It names intravitreal ranibizumab 0.3mg as the intervention and describes two groups with different treatment strategies. Group 1 received treatment based on the presence of macular edema, following the stated DRCR protocol I 4:2:7 strategy. Group 2 continued treatment until both the edema and lipid exudate were resolved.
The design therefore compares two approaches to continuing the same drug, rather than comparing an active treatment with a control receiving no active treatment. Because masking was listed as none, participants and study personnel were not masked according to the registry entry. The record does not report whether outcome assessors were masked, how random assignment was generated or concealed, or whether any protocol deviations occurred.
The primary outcome was best corrected visual acuity measured by the number of ETDRS letters read correctly. The stated time frame is 6-12 months, and the outcome description specifies assessments at 6 and 12 months. Secondary outcomes address lipid deposits in the central subfield and throughout the macular grid, as well as ocular and other adverse events. The record lists 9 outcome measures but does not provide results for these outcomes.
The trial is marked completed, with a listed start of 2015-08 and primary completion of 2018-05. The registry enrollment figure and the safety group denominators describe different record fields; they should not be treated as interchangeable. The analysis populations and the number of participants included in the primary outcome analysis are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
|---|---|---|
| STARTED | 13 | 12 |
| COMPLETED | 12 | 12 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
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 | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Total |
|---|---|---|---|---|
| Participants analysed | 12 | 12 | 24 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 | 7 | 15 |
| Age, Categorical: >=65 years | Participants | 4 | 5 | 9 |
| Age, Continuous | years | 64.5 (SD 8.46) | 67 (SD 8.83) | 65.75 (SD 8.65) |
| Sex: Female, Male: Female | Participants | 6 | 8 | 14 |
| Sex: Female, Male: Male | Participants | 6 | 4 | 10 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United States | participants | 12 | 12 | 24 |
6. Primary Endpoint
The registry lists the primary outcome as Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months, measured over 6-12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | letters read correctly |
| Endpoint classification | Continuous Endpoint |
Best corrected visual acuity is the primary endpoint. It is recorded as the number of letters read correctly on an ETDRS eye chart, beginning at a test distance of 4 meters. The registry specifies measurements at 6 and 12 months and states that the mean and standard deviation are the intended summary statistics.
Visual acuity is relevant to this trial because it describes a participant's ability to read letters under a standardized test procedure. The mean gives a group-level summary, while the standard deviation describes the spread of individual measurements around that mean. Neither alone identifies how many participants improved, worsened, or remained unchanged. A comparison between groups would need to account for the actual measurements and the analysis method used.
The record describes a comparison of Group 1 and Group 2, but it does not report the observed means, standard deviations, changes from baseline, or a group contrast. It also does not specify whether the primary analysis was based on measurements at each follow-up separately or on another summary across visits. Thus, the endpoint definition is available, but its observed results and statistical precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a clinical question about visual acuity under two ranibizumab treatment strategies for diabetic macular edema with lipid exudates. Both groups received the same named drug and dose, while the continuation strategy differed. This design means that the intended comparison concerns the strategies as described, rather than the effect of ranibizumab compared with no active treatment.
However, the posted results do not include the primary outcome values. There are no reported group means or standard deviations for ETDRS letters at 6 or 12 months, and no reported estimate of the difference between groups. The registry lists 0 analysis entries. Consequently, the available record does not establish the direction or size of any visual-acuity difference, nor how precisely such a difference was estimated. There is no basis in the registry record for concluding that one strategy produced better or worse visual acuity.
The record also names several secondary outcomes concerning improvement or resolution of lipid deposits, alongside ocular and other adverse events. Their outcome results are not reported in the registry record. The existence of an outcome definition is not evidence that a result was observed or that it favored either group.
Safety information is posted separately. For serious adverse events, the registry lists 3 affected participants among 12 at risk in Group 1 and 2 among 12 at risk in Group 2. For other adverse events, it lists 9 affected among 12 at risk in each group, and deaths are listed as 0 in both groups. These figures describe the posted safety entries; they do not provide a complete comparison of risk over time or establish whether events were caused by treatment.
Statistical interpretation is therefore constrained by missing efficacy results and limited reporting about the analysis. The record does not report confidence intervals, p-values, baseline characteristics, missing outcome data, or the analysis population. Without those details, neither the magnitude of a treatment-strategy contrast nor its uncertainty can be assessed from the registry entry.
9. Statistical Methods Explained
Statistical methods explain how trial observations are converted into estimates and how uncertainty is assessed. In this record, the stated primary outcome is continuous: best corrected visual acuity expressed as ETDRS letters read correctly. The registry says that the outcome is summarized using a mean and standard deviation. These definitions indicate the intended form of the data summary, but the registry does not report the observed summaries or the analysis used to compare groups.
What does a mean describe?
General: A mean is an average across the observations included in an analysis. It provides a concise description of the center of a group’s measurements, but it does not show the full distribution. Two groups can have similar means while having different patterns of individual values. The mean is also affected by which participants have measurements available and by the rules used to include observations.
The standard deviation describes how spread out observations are around their group mean. It is not the uncertainty of the estimated mean and it is not a confidence interval. The registry identifies standard deviation as the dispersion measure for the primary outcome but does not publish its values. Without the group means and standard deviations, readers cannot inspect either the central measurements or their variability.
What would a group comparison show?
General: A comparison of group means estimates how far apart the group averages are on the measured scale. A confidence interval, when reported, describes a range of values compatible with the data and the statistical model at a stated confidence level. Its width reflects precision: a narrower interval indicates greater precision under that model, while a wider interval indicates more uncertainty. A p-value addresses compatibility with a specified null hypothesis under the analysis assumptions; it does not measure the size or clinical importance of an effect.
No group contrast, confidence interval, or p-value for the primary endpoint is reported in the registry record. The primary outcome has more than one stated time point, 6 and 12 months, and the record does not report whether the analysis treated these as separate comparisons or used another approach. It also does not report adjustment for baseline visual acuity or other covariates. Those analytic choices should not be inferred from the outcome description.
Why does the analysis population matter?
General: Results can depend on which assigned participants are included and how missing measurements are handled. An analysis may include everyone as randomized, only participants with observed outcomes, or another defined population. These approaches answer somewhat different questions and can yield different estimates. The registry does not report the primary analysis population, the number with outcome measurements at either visit, or the reasons for any missing data. Therefore, the extent to which the posted safety denominators correspond to the efficacy population is not reported in the registry record.
How should planning illustrations be read?
The planning illustrations use the stated assumptions of a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They describe participants per arm for 80% power and other stated power targets, with the effect to detect expressed as a fraction of the observed effect. These are planning calculations, not results observed in the trial, and they are not the trial's original design justification. The registry does not report a sample-size justification or the assumptions used by the trial investigators when planning enrollment. A planning illustration based on an observed effect should not be described as observed power.
General: Power is a property of a planned test under assumed conditions, including an assumed effect and variability. It is not a retrospective measure of whether a completed trial found a meaningful effect. Planning estimates can help show how sample size relates to assumptions, but they cannot replace an estimate and confidence interval from the actual trial results. Since the primary outcome results are not reported, the planning illustrations do not reveal the trial's observed visual-acuity contrast.
Why might variability affect precision?
General: Greater variation among individual measurements makes a group mean less precisely estimated when other design features are held constant. For continuous outcomes, the standard deviation is one part of assessing this variation. In count or rate outcomes, over-dispersion means that variability exceeds what a simple model assumes; accounting for it can widen uncertainty and affect tests. The registry does not report an over-dispersion analysis, and the primary visual-acuity outcome is described as a continuous measure. These concepts are general and do not imply that over-dispersion occurred in this trial.
Overall, the record provides the outcome definition and some design details, but not the primary analysis results or enough information to reproduce its statistical analysis. The number of analyses listed in the record is 0. A more complete statistical interpretation would require the reported outcome estimates, their uncertainty, the analysis population, and the methods used to address repeated measurements and missing data.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is specified at 6 and 12 months. Considering more than one time point can create a multiplicity issue if each is tested as a separate primary comparison: conducting multiple tests can increase the chance of at least one statistically significant result when no true difference exists. General approaches include defining one primary time point, specifying a joint analysis, or adjusting inference across tests. The registry record does not report which approach was planned or whether any adjustment was made.
The record also names secondary outcomes covering lipid deposits in the central subfield and throughout the macular grid, including improvement and complete resolution, as well as ocular and other adverse events. Evaluating multiple outcomes can raise similar concerns. No hierarchy of outcomes, multiplicity adjustment, or distinction between confirmatory and exploratory analyses is reported in the registry record. The presence of several outcome definitions alone does not show that all were analyzed or that any particular result was selected.
Missing-data information is not reported in the registry record for the primary endpoint. The record does not give the number with visual-acuity measurements at each follow-up, reasons for missing assessments, or the method used to handle missing values. It also does not report whether the analysis used all randomized participants or another analysis population. These omissions limit assessment of potential bias and the extent to which the outcome analysis follows the randomized assignment.
The registry lists 0 analysis entries. Thus, a reader cannot determine whether a prespecified statistical plan was followed, how repeated measurements were handled, or whether any sensitivity analyses were conducted. The protocol-level statistical plan and interim analyses are not reported in the registry record.
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 |
|---|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | 3 | 12 | 25.0% |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | 2 | 12 | 16.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | 0 of 12 |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | 0 of 12 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | 9 of 12 |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | 9 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
|---|---|---|---|
| Cysticercosis | Gastrointestinal disorders | 1 of 12 | 0 of 12 |
| Low Hemoglobin | Cardiac disorders | 1 of 12 | 0 of 12 |
| Congestive Heart Failure | Cardiac disorders | 1 of 12 | 0 of 12 |
| Kidney Infection | Infections and infestations | 1 of 12 | 0 of 12 |
| Stroke | Vascular disorders | 0 of 12 | 1 of 12 |
| Appendix Surgery | Infections and infestations | 0 of 12 | 1 of 12 |
| Heart Attack | Cardiac disorders | 0 of 12 | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
|---|---|---|---|
| Influenza | Infections and infestations | 0 of 12 | 3 of 12 |
| Elevated Blood Pressure | Blood and lymphatic system disorders | 1 of 12 | 1 of 12 |
| Visual Acuity Loss | Eye disorders | 1 of 12 | 1 of 12 |
| Ear Infection | Ear and labyrinth disorders | 0 of 12 | 1 of 12 |
| Decreased Liver Function | Renal and urinary disorders | 0 of 12 | 1 of 12 |
| Branch Retinal Artery Occlusion | Eye disorders | 0 of 12 | 1 of 12 |
| Headache | Vascular disorders | 1 of 12 | 0 of 12 |
| Shingles | Immune system disorders | 1 of 12 | 0 of 12 |
| Elevated Triglycerides | Blood and lymphatic system disorders | 1 of 12 | 0 of 12 |
| Central Retinal Vein Occlusion | Eye disorders | 1 of 12 | 0 of 12 |
Serious events with the highest arm-level rate: cysticercosis (8.3%), low hemoglobin (8.3%), congestive heart failure (8.3%), kidney infection (8.3%), stroke (8.3%).
The registry reports serious adverse events for each group using the number at risk and the number affected. Group 1 has 3 affected among 12 at risk; Group 2 has 2 affected among 12 at risk. The entry lists 0 deaths in each group. For other adverse events, it reports 9 affected among 12 at risk in each group. These are the safety figures as recorded, not estimates of a causal treatment effect.
The listed serious-event terms include Cysticercosis, Low Hemoglobin, Congestive Heart Failure, Kidney Infection, Stroke, and Appendix Surgery, each reported as 8.3%. The record does not provide a group-specific breakdown for these terms in the listed information. It also does not report event timing, duration, recurrence, exposure-adjusted rates, or whether investigators considered an event related to treatment. The numbers affected therefore should not be interpreted as the total number of events.
General: Adverse-event counts need context, including how events were defined and collected, the time each participant was observed, and whether events were counted by person or event. A small difference in counts does not by itself demonstrate a safety difference. The registry's safety entries can be described, but their precision and comparability cannot be fully evaluated from the reported information.
12. What the Result Does, and Does Not, Mean
The trial record addresses a focused comparison: two strategies for continuing intravitreal ranibizumab 0.3mg in people with diabetic macular edema and lipid exudates. The primary outcome is best corrected visual acuity measured as ETDRS letters read correctly at 6 and 12 months. This gives readers a clear description of the clinical measurement the study intended to compare.
That endpoint definition is not the same as an outcome result. The registry does not report group means, standard deviations, or a contrast between groups at either time point. It therefore cannot show whether the recorded visual-acuity measurements favored Group 1, favored Group 2, or were similar. It also cannot show how precise any estimated difference was. No conclusion about the benefit of either strategy follows from the outcome title or the study's completion status.
The same distinction applies to the lipid-exudate outcomes. The record specifies outcomes for improvement and resolution, but does not report their results. The safety counts are available, but they do not establish that treatment caused or prevented events, and the registry does not give the detail needed for a fully adjusted safety comparison.
General: A randomized design can support comparison of assigned strategies when analyzed appropriately, but randomization does not eliminate the need for transparent outcome reporting. Estimates, uncertainty intervals, analysis populations, and missing-data methods help readers assess how robust a result may be. Those details are not reported for the primary outcome in this registry record.
Accordingly, the record supports description of the study question, design, outcome definitions, and listed safety counts. It does not support a conclusion about the relative visual-acuity effects of the strategies, resolution of lipid exudates, or comparative safety. Such conclusions would require outcome analyses and statistical details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable because it compares two treatment strategies involving the same named drug rather than an active regimen with a no-treatment control. The contrast is therefore about how treatment continuation is determined: Group 1 follows the stated strategy based on macular edema, while Group 2 continues until both edema and lipid exudate resolve. Identifying the contrast precisely is essential when interpreting any future estimate.
The outcome definition also illustrates why endpoint reporting matters. Best corrected visual acuity is measured on a continuous scale as ETDRS letters read correctly, with assessments specified at 6 and 12 months. A result at each visit could carry a different interpretation from a summary across visits, so the analysis plan and the handling of repeated measurements are important. Neither is reported in the registry record.
The record includes a completed status and a primary outcome definition, but no analysis entries or primary outcome estimates. This makes the distinction between trial completion and publicly interpretable evidence especially clear: a study can be marked completed while its registry entry lacks the information needed to evaluate the stated comparison. The separate safety counts offer descriptive information, but are not a substitute for the unreported efficacy analysis.
Planning illustrations can also help explain how assumptions about effect size and variability relate to future study size. They should be kept separate from the trial's observed findings and from any original design justification. In this case, the registry does not report a sample-size justification, and the illustrations are not observed power. Overall, the statistical importance of this record lies in its clearly identifiable comparison and in the substantial gap between the defined outcomes and the outcome analyses reported.
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.
Several limitations in the registry record constrain interpretation of this specific trial. Most importantly, the primary endpoint is defined but no primary outcome values or between-group analysis are reported. The record does not provide means, standard deviations, confidence intervals, or p-values for visual acuity at 6 or 12 months. Results for the named lipid-exudate outcomes are also not reported.
The analysis population is not reported, nor are the number of participants with outcome measurements at each visit, reasons for missing measurements, or the method used to address missing data. The relationship between the listed enrollment of 25 and the safety denominators of 12 at risk in each group is not explained in the registry record. No group allocation details, baseline characteristics, or information about adherence and protocol deviations are reported.
Although the trial is described as randomized, parallel, and unmasked, the record does not describe sequence generation, allocation concealment, or whether outcome assessors were masked. The timing and duration of treatment and follow-up beyond the stated outcome time frame are not detailed. The protocol's statistical analysis plan, sample-size justification, and any interim analyses are not reported in the registry record.
The safety entries lack event timing, relationship to treatment, and detail about how counts were compiled. Consequently, the posted counts do not fully characterize comparative safety. Finally, the registry lists 0 analysis entries. These reporting gaps mean that the design and intended questions can be described, but the primary statistical findings and their reliability cannot be assessed from the registry record alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Effect of Intravitreal Ranibizumab on Visual Acuity and Hard Exudate Resolution in the Treatment of Diabetic Macular Edema With Center Involved Edema and Lipid Exudates — NCT02448446.
- Registry record last updated 2021-07-08; status last verified 2021-07.
- Results first posted 2021-07-08.
- 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
This completed randomized, open-label Phase I/II parallel-group trial studied intravitreal ranibizumab 0.3mg for diabetic macular edema with lipid exudates. Group 1 treatment was based on the presence of macular edema, while Group 2 continued treatment until both the edema and lipid exudate were resolved. The listed enrollment is 25.
The primary outcome was best corrected visual acuity measured by ETDRS letters read correctly at 6 and 12 months. The registry does not report primary outcome results or analysis entries. It lists safety figures of 3 affected among 12 at risk for serious adverse events in Group 1 and 2 among 12 in Group 2; other adverse events affected 9 among 12 in each group, with 0 deaths listed in both groups. Missing-data methods, analysis populations, and the statistical analysis plan are not reported in the registry record.