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 Treatment for CI-DME in Eyes With Very Good VA Study (NCT01909791), a randomized phase 3 study. The primary outcome is Number of Eyes With at Least 5-letter Decrease in E-ETDRS Visual Acuity Letter Score From Baseline.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01909791 |
| Phase | Phase 3 |
| Condition | Diabetic Macular Edema |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 702 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Jaeb Center for Health Research |
| Results posted | Yes |
2. Clinical Question
Population
Eyes with central-involved diabetic macular edema and good visual acuity, defined in the protocol summary as a Snellen equivalent of 20/25 or better and an electronic E-ETDRS letter score of 79 or better. The study addresses a group that earlier DME studies described in the registry summary had not systematically addressed.
Intervention
Prompt intravitreal aflibercept, given at baseline and every 4 weeks as needed. Deferred laser could be added if certain criteria were met.
Comparator
Initial focal/grid laser photocoagulation followed by deferred aflibercept if vision worsened, or initial observation with deferred aflibercept if vision worsened. The observation strategy could include deferred laser with aflibercept if certain criteria were met.
Primary question
At 2 years, how many eyes in each initial-treatment group had lost at least 5 letters on the E-ETDRS visual acuity score compared with baseline? The registry record describes this as the primary objective across the three strategies.
The clinical question is about the timing and initial choice of treatment in eyes with central-involved DME that already have very good visual acuity. It is not simply a comparison of treatment with no treatment: the laser and observation strategies allowed deferred aflibercept if vision worsened, while the prompt-aflibercept strategy began with aflibercept. Thus, the comparison concerns initial management strategies as described in the registry, rather than an isolated comparison of receiving versus never receiving aflibercept. The primary outcome focuses on loss of visual-acuity letters over the stated follow-up, while secondary outcomes include changes in visual acuity and OCT central subfield thickness. The registry record does not report a primary two-arm comparative estimate for this count outcome.
3. Trial Design
The registry identifies this as a randomized, phase 3, parallel-group trial with single masking. It is marked completed. The reported enrollment is 702. The trial is sponsored by Jaeb Center for Health Research, and its listed condition is diabetic macular edema. The registry record gives a start of 2013-10 and a primary completion date of 2018-09-11.
The three groups were initiation with aflibercept, initiation with laser photocoagulation, and initiation with observation. The protocol descriptions make clear that the latter strategies could include deferred aflibercept if vision worsened. Deferred laser could also be added to aflibercept under specified criteria in the observation and prompt-aflibercept strategies. The record therefore describes comparisons of treatment approaches with different initial actions and possible later treatment, rather than fixed treatment exposure throughout follow-up.
The primary outcome timeframe is 2 years. The registry lists a number of secondary outcomes concerning visual acuity, OCT thickness, DME status, injections, and diabetic retinopathy worsening. The record reports 18 outcome measures and 17 posted secondary outcomes. It does not report further details of the masking procedure, the allocation method beyond randomization, or how the reported analysis populations were defined. Those design details are not reported in the registry record.
The reported enrollment and the numbers contributing to particular outcome summaries are not interchangeable descriptions of the analysis population. For example, the primary outcome summaries list different group-specific counts from the enrollment figure, and the continuous secondary outcomes also list their own group-specific counts. The registry record does not explain the reasons for these differences or describe how missing outcomes were handled.
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 | Initiation With Aflibercept | Initiation With Laser Photocoagulation | Initiation With Observation |
|---|---|---|---|
| STARTED | 226 | 240 | 236 |
| COMPLETED | 205 | 212 | 208 |
| NOT COMPLETED | 21 | 28 | 28 |
Reasons for not completing this period:
| Reason | Initiation With Aflibercept | Initiation With Laser Photocoagulation | Initiation With Observation |
|---|---|---|---|
| Death | 9 | 8 | 4 |
| Withdrawal by Subject | 5 | 9 | 13 |
| Lost to Follow-up | 5 | 11 | 10 |
| Missed Visit | 2 | 0 | 1 |
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 | Initiation With Aflibercept | Initiation With Laser Photocoagulation | Initiation With Observation | Total |
|---|---|---|---|---|---|
| Participants analysed | 226 | 240 | 236 | 702 | |
| Age, Continuous | years | 59 (52 to 65) | 60 (53 to 66) | 60 (53 to 67) | 60 (52 to 66) |
| Sex: Female, Male: Female | Participants | 95 | 82 | 87 | 264 |
| Sex: Female, Male: Male | Participants | 131 | 158 | 149 | 438 |
| Race/Ethnicity, Customized: Race/ethnicity – Non-Hispanic White | Participants | 145 | 160 | 161 | 466 |
| Race/Ethnicity, Customized: Race/ethnicity – Non-Hispanic Black/African American | Participants | 37 | 36 | 41 | 114 |
| Race/Ethnicity, Customized: Race/ethnicity – Hispanic or Latino | Participants | 31 | 35 | 25 | 91 |
| Race/Ethnicity, Customized: Race/ethnicity – Asian | Participants | 6 | 1 | 5 | 12 |
| Race/Ethnicity, Customized: Race/ethnicity – American Indian or Alaskan Native | Participants | 1 | 1 | 0 | 2 |
| Race/Ethnicity, Customized: Race/ethnicity – Native Hawaiian or other Pacific Islander | Participants | 0 | 3 | 1 | 4 |
| Race/Ethnicity, Customized: Race/ethnicity – More than one race | Participants | 4 | 2 | 1 | 7 |
| Race/Ethnicity, Customized: Race/ethnicity – Unknown or not reported | Participants | 2 | 2 | 2 | 6 |
| Region of Enrollment: Canada | Participants | 1 | 2 | 4 | 7 |
| Region of Enrollment: United States | Participants | 225 | 238 | 232 | 695 |
| Diabetes type: Type 2 | Participants | 211 | 221 | 210 | 642 |
| Diabetes type: Type 1 | Participants | 13 | 18 | 18 | 49 |
| Diabetes type: Uncertain | Participants | 2 | 1 | 8 | 11 |
| Duration of diabetes | years | 15 (10 to 21) | 15 (10 to 20) | 16 (10 to 24) | 15 (10 to 21) |
| Insulin used | Participants | 161 | 145 | 160 | 466 |
| Hemoglobin A1c | Hemoglobin A1c percentage | 7.6 (6.8 to 9.1) | 7.6 (6.6 to 8.6) | 7.6 (6.8 to 8.7) | 7.6 (6.7 to 8.8) |
| Arterial blood pressure | mmHg | 99 (91 to 107) | 98 (89 to 105) | 98 (91 to 105) | 98 (90 to 106) |
| Prior myocardial infarction | Participants | 11 | 21 | 19 | 51 |
| Prior stroke | Participants | 16 | 6 | 9 | 31 |
| Body mass index | kg/m^2 | 32.3 (27.6 to 37.0) | 32.1 (28.2 to 37.4) | 32.3 (28.0 to 37.5) | 32.2 (28.0 to 37.3) |
| Daily cigarette smoking: Never | Participants | 165 | 157 | 141 | 463 |
| Daily cigarette smoking: Prior | Participants | 46 | 67 | 75 | 188 |
| Daily cigarette smoking: Current | Participants | 15 | 16 | 20 | 51 |
| Recent or planned diabetic macular edema treatment in non-study eye | Eyes | 86 | 90 | 92 | 268 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Eyes With at Least 5-letter Decrease in E-ETDRS Visual Acuity Letter Score From Baseline, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Units |
| Measure of spread | not applicable |
| Unit | Eyes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of eyes with at least a 5-letter decrease in E-ETDRS visual acuity letter score from baseline at 2 years. The registry describes visual acuity as best-corrected following protocol-defined refraction and measured with the electronic Early Treatment Diabetic Retinopathy Study test. Its stated scale runs from 100 letters, corresponding to a Snellen equivalent of 20/12, to 0 letters, corresponding to 20/800.
This endpoint is a count of eyes meeting a specified visual-acuity loss threshold, not a mean change in visual acuity and not a time-to-event measure. Such a threshold can make a clinically interpretable event count available alongside continuous measures of average change. The registry’s primary summaries report 33 eyes among 205 for initiation with aflibercept, 36 among 212 for initiation with laser photocoagulation, and 39 among 208 for initiation with observation.
The record does not post a confidence interval or a two-arm comparative estimate for this primary count outcome. It states that values were missing or not estimable for a two-arm comparison. Consequently, the group counts describe the posted outcome, but do not by themselves quantify the uncertainty in a comparison between strategies.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
For the primary outcome at 2 years, the registry reports 33 eyes with at least a 5-letter decrease in the initiation-with-aflibercept group, 36 in the initiation-with-laser group, and 39 in the initiation-with-observation group. The corresponding group counts listed with these results are 205, 212, and 208. These are descriptive counts. The registry record does not post a confidence interval or an estimable two-arm comparison for this outcome, so the counts alone do not establish the precision of differences between strategies.
The secondary visual-acuity summaries give a different kind of information: average change in letter score. At 1 year, the posted mean changes were 2.1 with aflibercept, 0.1 with laser, and 0.0 with observation. The recalculated unadjusted mean difference for aflibercept versus observation was 2.1, with a 95% confidence interval from 1.117 to 3.083 and p < 0.001. The corresponding recalculated estimate for laser versus observation was 0.1, with a 95% confidence interval from -0.912 to 1.112 and p = 0.846.
For the 2-year visual-acuity area-under-the-curve outcome, the mean changes were 1.5 with initial aflibercept, 0.0 with initial laser and deferred aflibercept if needed, and -0.4 with observation. The recalculated unadjusted mean difference was 1.9 for initial aflibercept versus observation, with a 95% confidence interval from 1.109 to 2.691 and p < 0.001. For initial laser versus observation, the mean difference was 0.4, with a 95% confidence interval from -0.376 to 1.175 and p = 0.312.
These secondary calculations are unadjusted comparisons reconstructed from the posted summary statistics, not registry-reported analyses. A confidence interval that includes zero is compatible with a range of effects on either side of no mean difference under the calculation used; a p-value does not show the probability that a treatment strategy is effective. The registry record reports no sponsor analyses for these comparisons. These results should therefore be read as exploratory numerical summaries, with the primary count endpoint remaining without a posted comparative estimate.
9. Statistical Methods Explained
The registry posts a primary outcome that is a count: eyes meeting the specified visual-acuity loss threshold. It also posts secondary outcomes summarized as means and standard deviations for continuous measures. These outcome types answer related but different questions. A threshold count concerns how many eyes crossed a particular boundary; a mean change describes the average shift in a measured scale and can conceal variation among individual eyes.
What do the recalculated comparisons represent?
The secondary mean differences are recalculated unadjusted comparisons based on posted group summaries. For the comparisons against observation, the estimated difference is expressed as the active strategy’s mean minus the observation group’s mean. A positive estimate for visual acuity therefore indicates a higher mean change in the named strategy group in these calculations. A negative estimate for OCT thickness indicates a larger decrease in thickness in that group than in observation, given the direction of the measurement as reported. The registry record does not post sponsor analyses for these comparisons, so the recalculated estimates should not be mistaken for adjusted or model-based trial analyses.
A confidence interval describes a range of estimates compatible with the data and the calculation’s assumptions. Its width reflects uncertainty: a wider interval is less precise than a narrower one. When an interval includes zero for a mean difference, the data do not distinguish that estimate from no mean difference at the confidence level used. The interval does not prove that the true effect is zero, nor does it describe the range of individual responses. The registry’s recalculated intervals are reported with the secondary comparisons, not with the primary count outcome.
The p-values listed for the secondary comparisons are unadjusted. They quantify how unusual a test statistic at least as extreme as the observed one would be under a null hypothesis of no mean difference, subject to the calculation’s assumptions. They are not the probability that the null hypothesis is true, and they do not measure clinical importance. Because multiple outcomes and comparisons are listed, unadjusted p-values should not be treated as if they were the result of a single prespecified test without multiplicity concerns.
Why do the sample-size illustrations vary?
The planning illustrations use the observed effect as a starting point and consider planning for 100%, 75%, or 50% of that observed effect. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They are planning illustrations, not observed power, and are not evidence that the trial was designed around those particular effects. The registry record does not report the trial’s own sample-size justification.
When the observed difference is small relative to the variation in the outcome, a planning calculation can require a very large number of participants per arm to detect a fraction of that difference under the stated assumptions. Conversely, an apparently larger observed effect can yield a smaller illustrative sample size. These calculations are sensitive to the observed effect, which is itself uncertain, and should not be interpreted as a guarantee that a future study would obtain the same estimate or achieve the stated power.
What does over-dispersion mean in general?
In general, over-dispersion means that the variation in count outcomes is greater than a model’s assumed count distribution allows. If present and ignored, uncertainty can be understated and statistical tests can be too optimistic. That is a general consideration for count data; the registry record does not report a count model, an over-dispersion assessment, or a model-based primary comparison for this endpoint. No such method should be inferred from the posted group counts.
The continuous secondary summaries include standard deviations, which describe spread around a group mean. The recalculations use the posted means, standard deviations, and group counts. They do not adjust for baseline values, other prognostic factors, repeated observations, or the trial’s randomization structure beyond the simple two-group comparison described by the calculation. Whether the sponsor used a different method is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 18 outcome measures, including the primary outcome and 17 posted secondary outcomes. It does not report a multiplicity plan, such as a hierarchy of outcomes, an adjustment to control family-wise error, or a false-discovery procedure. Without that information, the recalculated secondary p-values should be treated as unadjusted, and their nominal evidence does not account for the number of outcomes or comparisons examined. Whether the sponsor used a prespecified multiplicity strategy is not reported in the registry record.
The registry record also does not report an analysis plan for missing outcome data, the amount or pattern of missingness, or the imputation methods, if any. It does not identify the analysis population for each outcome or state whether analyses followed an intention-to-treat principle. The group-specific counts accompanying the outcome summaries are available, but the reasons for differences between enrollment and outcome counts are not reported. The record does not describe exclusions, withdrawals, or how eyes with incomplete follow-up were handled.
These omissions matter because missing data and analysis-population choices can affect both the estimated group results and their uncertainty. In general, missingness related to outcome status can bias comparisons if the analysis does not address it appropriately. That is a general statistical concern, not a claim that such bias occurred in this trial. Without details on missing data and analysis populations, readers cannot assess how robust the estimates are to those choices.
For the primary endpoint, the registry specifically indicates that values were missing or not estimable for a two-arm comparison. It therefore does not provide a comparative interval or test for that endpoint. The registry record does not explain whether this reflects unavailable summary data, an analysis decision, or another reason. No explanation should be inferred.
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 |
|---|---|---|---|
| Initiation With Laser Photocoagulation | 64 | 240 | 26.7% |
| Initiation With Observation | 77 | 236 | 32.6% |
| Initiation With Aflibercept | 69 | 226 | 30.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Initiation With Laser Photocoagulation | 10 of 226 |
| Initiation With Observation | 9 of 240 |
| Initiation With Aflibercept | 5 of 236 |
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 |
|---|---|
| Initiation With Laser Photocoagulation | 194 of 240 |
| Initiation With Observation | 197 of 236 |
| Initiation With Aflibercept | 185 of 226 |
Most frequent serious adverse event terms
| Event term | Organ system | Initiation With Laser Photocoagulation | Initiation With Observation | Initiation With Aflibercept |
|---|---|---|---|---|
| Cardiac failure congestive | Cardiac disorders | 4 of 240 | 5 of 236 | 5 of 226 |
| Chest pain | General disorders | 4 of 240 | 6 of 236 | 3 of 226 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 4 of 240 | 3 of 236 | 4 of 226 |
| Cerebrovascular accident | Vascular disorders | 5 of 240 | 3 of 236 | 3 of 226 |
| Myocardial infarction | Cardiac disorders | 1 of 240 | 3 of 236 | 5 of 226 |
| Death | General disorders | 3 of 240 | 2 of 236 | 3 of 226 |
| Cellulitis | Skin and subcutaneous tissue disorders | 0 of 240 | 1 of 236 | 6 of 226 |
| Infection | Infections and infestations | 4 of 240 | 0 of 236 | 2 of 226 |
| Renal failure | Renal and urinary disorders | 2 of 240 | 1 of 236 | 3 of 226 |
| Urinary tract infection | Renal and urinary disorders | 4 of 240 | 1 of 236 | 1 of 226 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Initiation With Laser Photocoagulation | Initiation With Observation | Initiation With Aflibercept |
|---|---|---|---|---|
| Vision blurred | Eye disorders | 31 of 240 | 34 of 236 | 40 of 226 |
| Vitreous floaters | Eye disorders | 16 of 240 | 21 of 236 | 27 of 226 |
| Hypertension | Vascular disorders | 20 of 240 | 18 of 236 | 13 of 226 |
| Nasopharyngitis | Respiratory, thoracic and mediastinal disorders | 11 of 240 | 15 of 236 | 23 of 226 |
| Cataract | Eye disorders | 14 of 240 | 14 of 236 | 17 of 226 |
| Visual acuity reduced | Eye disorders | 15 of 240 | 16 of 236 | 6 of 226 |
| Dry eye | Eye disorders | 11 of 240 | 8 of 236 | 17 of 226 |
| Headache | Nervous system disorders | 7 of 240 | 14 of 236 | 15 of 226 |
| Conjunctival haemorrhage | Eye disorders | 8 of 240 | 9 of 236 | 17 of 226 |
| Bronchitis | Respiratory, thoracic and mediastinal disorders | 8 of 240 | 16 of 236 | 9 of 226 |
Serious events with the highest arm-level rate: cellulitis (2.7%), chest pain (2.5%), cardiac failure congestive (2.2%), myocardial infarction (2.2%), cerebrovascular accident (2.1%).
The safety record lists serious adverse event counts by initial-treatment group, along with counts for other adverse events and deaths. For serious adverse events, the listed affected counts are 64 among 240 at risk in the laser group, 77 among 236 at risk in the observation group, and 69 among 226 at risk in the aflibercept group. The record lists other adverse events in 194 among 240, 197 among 236, and 185 among 226, respectively. Death counts are 10, 9, and 5, respectively.
These are descriptive registry counts. They do not by themselves establish that an event was caused by a treatment, and they do not provide a comparative risk estimate or uncertainty interval. The record does not state in these summaries how recurrent events, multiple events in the same person, or event timing were handled. The listed top serious-event terms include cellulitis at 2.7%, chest pain at 2.5%, cardiac failure congestive at 2.2%, myocardial infarction at 2.2%, cerebrovascular accident at 2.1%, and pneumonia at 1.8%. These terms and percentages describe the registry’s serious-event listing; they should not be taken as treatment-specific comparative rates.
12. What the Result Does, and Does Not, Mean
The posted results describe outcomes for randomized groups with different initial management strategies for central-involved DME in eyes with very good visual acuity. The primary registry outcome is the number of eyes with a loss of at least 5 E-ETDRS letters at 2 years. The available record gives group counts for that endpoint but no estimable two-arm comparison, confidence interval, or p-value. It is therefore possible to describe the counts, but not to quantify the uncertainty around a comparative effect from the primary endpoint in the registry record.
The secondary summaries provide additional information. The unadjusted recalculations show differences in mean visual-acuity change for aflibercept versus observation, while the comparisons of laser versus observation and the OCT thickness comparisons have intervals that include zero. These are secondary analyses reconstructed from summaries, without a reported sponsor analysis for those comparisons. They do not resolve the missing comparative estimate for the primary endpoint, and they should be interpreted in light of multiple outcomes and the absence of a reported multiplicity plan.
These results do not establish that any strategy is appropriate for an individual, and they do not prove that a strategy is effective or ineffective. Group averages and counts do not show every participant’s course, and the registry summaries do not describe how missing data were handled. The results also concern the specific population and strategies defined in the record; they should not be extended to eyes with different baseline visual acuity or treatment approaches without further evidence.
The registry record is useful for identifying the trial question, design, posted outcome values, and gaps in the reported analysis details. It is less informative about the sponsor’s statistical methods for the primary comparison, missing data, multiplicity, and analysis populations, because those details are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial addresses an important statistical distinction: a treatment question in a population with very good baseline visual acuity cannot be answered solely by importing results from studies of eyes with poorer vision. The registry summary says earlier studies of ranibizumab versus laser included eyes with poorer visual acuity, and that the question of initial management in eyes with good vision had not been addressed systematically by recent studies. The trial therefore frames a population-specific comparison of prompt treatment and strategies that defer treatment unless vision worsens.
The three-arm structure is relevant to interpretation because the strategies differ in their initial action and in the possibility of later treatment. An outcome difference would concern these complete management strategies, not merely the pharmacologic action of aflibercept considered in isolation. The primary threshold count and continuous secondary measures also represent distinct estimands: one focuses on whether an eye crossed a loss threshold, while the others describe average changes in visual acuity or retinal thickness.
Statistically, the registry illustrates why effect estimates and their uncertainty are essential. The primary group counts alone do not supply a comparative estimate or precision measure. Secondary mean comparisons offer estimates and confidence intervals, but these are unadjusted recalculations and are not a substitute for a reported primary analysis. The lack of a registry-reported multiplicity plan, missing-data approach, and analysis-population definitions limits how completely the evidence can be evaluated.
The planning illustrations also demonstrate that sample-size calculations depend strongly on the effect chosen for detection. They are not observed power and do not reveal the trial’s own design rationale. Together, these features make the record useful for teaching the difference between descriptive outcome counts, comparative estimates, uncertainty, and planning assumptions.
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.
A central limitation of the registry record is that it does not include an estimable two-arm comparison for the primary count endpoint. The primary group counts are reported, but there is no comparative confidence interval or test in the record. As a result, the endpoint that defines the main question cannot be evaluated for comparative precision from these posted results alone.
The continuous secondary comparisons are recalculated from summary statistics and are unadjusted. The record does not report sponsor analyses for those comparisons, a multiplicity procedure, or whether the chosen comparisons and outcomes were prespecified. Their nominal p-values therefore should not be treated as definitive evidence across all listed secondary outcomes. The registry record also does not describe the analysis populations or missing-data handling, and does not explain the differences between enrollment and outcome-specific counts.
The treatment strategies permit deferred treatment under stated conditions. The registry summaries do not provide enough detail to assess how often deferred aflibercept or laser was used, how treatment exposure varied over follow-up, or how those later treatments affected the outcomes. The intervention descriptions specify the strategy, but they do not supply detailed adherence or treatment-use results in the outcomes.
Finally, safety counts are descriptive and do not establish causation or comparative risk. The record does not provide event-level timing or a comparative safety analysis in these summaries. These limitations concern what is reported in the registry record; they do not establish that the full trial report lacks additional information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Treatment for CI-DME in Eyes With Very Good VA Study — NCT01909791.
- Registry record last updated 2020-07-31; status last verified 2020-07.
- Results first posted 2020-01-03.
- 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.
Continue through the Clinical Biostats statistical pathway
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18. Record Summary
The registry describes a completed randomized phase 3 parallel-group trial with single masking and reported enrollment of 702. It compares initial aflibercept, initial laser photocoagulation, and initial observation for eyes with central-involved DME and very good visual acuity, with deferred treatment permitted under the strategy descriptions.
The primary endpoint is the number of eyes with at least a 5-letter decrease in E-ETDRS visual acuity from baseline at 2 years. The posted group counts are 33, 36, and 39, respectively, but the registry does not provide an estimable two-arm comparison for this count outcome. Secondary summaries include visual-acuity and OCT measures. Recalculated unadjusted comparisons are available for selected continuous outcomes; sponsor analyses are not reported for those comparisons.
The registry record does not report a multiplicity plan, missing-data methods, analysis-population definitions, or the trial’s sample-size justification. Those omissions constrain interpretation of the posted estimates and planning illustrations.