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 Prevention of Macular Edema In Patients With Diabetic Retinopathy Undergoing Cataract Surgery (NCT01988246), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Ocular and Non-Ocular Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01988246 |
| Phase | Phase 1, Phase 2 |
| Condition | Diabetic Retinopathy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Rishi Singh |
| Results posted | Yes |
2. Clinical Question
Population
People with diabetic retinopathy undergoing cataract surgery. The registry record describes the condition and surgical setting but does not report further eligibility details or a fuller description of the enrolled population.
Intervention
Intravitreal aflibercept injection at the time of surgery. The arm description specifies Aflibercept 2 mg via intravitreal injection after cataract excision.
Comparator
A sham injection at the time of surgery. The description says this involved pressing an empty syringe against the eye wall without penetration, after cataract excision.
Primary question
How many participants in each arm had ocular or non-ocular adverse events by Day 90? The stated primary outcome is a count of participants with adverse events. Although the study objective also refers to safety and efficacy in preventing macular edema, the registry record does not provide a single primary efficacy comparison for macular edema.
The trial addresses a perioperative question: whether giving aflibercept into the eye during cataract surgery is associated with a different observed safety profile from a sham procedure in participants with diabetic retinopathy. The registry describes randomized allocation and a parallel design, so participants were assigned to one of the listed treatment arms rather than crossing between treatments. The study is classified as Phase 1 and Phase 2.
The primary outcome is a participant count, not a measure of the amount of macular edema or a change in vision. A secondary outcome is change from baseline in best-corrected visual acuity score, but results for that outcome are not reported in the registry record. The adverse-event outcome therefore frames the posted results as a safety description over the stated Day 90 timeframe; it cannot by itself answer every part of the broader study objective.
3. Trial Design
The registry describes a randomized, single-masked, parallel-group study with 30 participants enrolled. The two arms are sham injection and intravitreal aflibercept injection. The study is listed as Phase 1 and Phase 2 and has a completed status. Its recorded start is 2013-12, and its primary completion date is 2018-04-25.
Both arm descriptions place the intervention after cataract excision at the time of surgery. Participants assigned to aflibercept were to receive Aflibercept 2 mg by intravitreal injection. The sham procedure is described as pressing an empty syringe against the eye wall without penetration. The aflibercept arm description says the patient would be masked to assignment. The registry classifies masking as single, but does not report further detail about who else, if anyone, was masked.
Randomization can help create groups that are comparable on average at assignment, while a parallel design keeps each participant in the assigned arm. These are general features of the design; they do not establish that the realized groups were balanced on every characteristic. Baseline characteristics, allocation concealment procedures, and details about the randomization sequence are not reported in the registry record.
The stated primary outcome is the number of participants with ocular and non-ocular adverse events, assessed at Day 90. A secondary outcome is change from baseline in best-corrected visual acuity score. The registry lists three outcome measures, but the other outcome details and corresponding results are not fully described in the posted record. Enrollment is 30 overall, and the adverse-event results list 15 participants at risk in each arm for serious and other events.
The record gives no further protocol-level explanation of the planned sample size, target enrollment, or operational study procedures. The date and status entries describe the trial’s registry milestones, but do not explain why recruitment or follow-up took the recorded course.
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 | Sham Injection | Intravitreal Aflibercept Injection |
|---|---|---|
| STARTED | 15 | 15 |
| COMPLETED | 14 | 15 |
| NOT COMPLETED | 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 | Sham Injection | Intravitreal Aflibercept Injection | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 15 | 30 | |
| Age, Customized | years | 66 (47 to 80) | 66 (53 to 80) | 66 (47 to 80) |
| Sex: Female, Male: Female | Participants | 10 | 6 | 16 |
| Sex: Female, Male: Male | Participants | 5 | 9 | 14 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 3 | 5 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 13 | 12 | 25 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 | 3 | 9 |
| Race (NIH/OMB): White | Participants | 6 | 10 | 16 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 3 | 2 | 5 |
| Region of Enrollment: United States | participants | 15 | 15 | 30 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Ocular and Non-Ocular Adverse Events, measured over Day 90.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with ocular and non-ocular adverse events by Day 90. It is expressed as a count of participants, rather than a count of all individual events. That distinction matters: a participant with multiple events is still counted once in a participant-level outcome if the measure is whether the participant experienced an event.
Safety outcomes are used to describe harms observed during a defined follow-up period. Reporting the number of affected participants in each randomized arm makes the event experience visible for the groups enrolled in this trial. It does not, by itself, establish that an event was caused by the assigned injection, nor does a count indicate the event’s severity, duration, or clinical consequences.
The registry lists the outcome timeframe as Day 90, which sets the period to which the stated endpoint refers. The record also supplies serious and other adverse-event counts separately. These categories provide useful descriptive context, but the registry does not report a single statistical comparison that combines all components of the primary outcome. A secondary outcome, change from baseline in best-corrected visual acuity score, addresses a different domain; its results are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted adverse-event counts describe what was recorded in the enrolled groups, not a definitive estimate of treatment effect. For serious adverse events, the registry reports 2 affected participants among 15 at risk in the sham arm and 3 among 15 at risk in the aflibercept arm. For other adverse events, it reports 14 among 15 at risk in the sham arm and 10 among 15 at risk in the aflibercept arm. The registry reports no deaths in either group.
These are small group counts from a trial with 30 participants enrolled. Counts can be informative as a description of the observed experience, but they provide limited precision for distinguishing a genuine group difference from chance variation. The registry record does not report confidence intervals or a statistical test for these safety counts. It also does not report a single comparison for the primary outcome: the record indicates that the outcome has several categories or time points and was not reduced to one comparison. Accordingly, a treatment-effect estimate and its precision cannot be read from the posted primary result.
The adverse-event categories should not be conflated. The serious-event figures are separate from the figures reported under other adverse events. The registry also lists three serious-event terms with percentages: Paracentesis, 13.3%; Rash and Swelling on Limbs, 13.3%; and Cough/Vomiting, 6.7%. Those term-level entries do not substitute for an arm-level inferential analysis, and the record does not give enough detail to establish how each term is distributed between arms.
The study’s stated objective refers to safety and efficacy for preventing macular edema, but the primary endpoint described in the record is adverse events. The listed secondary outcome is change from baseline in best-corrected visual acuity score. Neither a macular-edema outcome result nor a visual-acuity result is included in the posted results summarized by the registry record. Therefore, these safety counts do not answer whether aflibercept changed macular edema or visual acuity.
Any interpretation should remain tied to the measured follow-up and the participants represented. The record describes an adverse-event assessment at Day 90; it does not establish what happened outside that timeframe. It also does not report the analysis population, missing-outcome handling, or participant flow through follow-up. Without those details and without an inferential comparison, the counts are best read as descriptive evidence about events recorded in this trial, with substantial uncertainty about how well they characterize differences between the arms.
9. Statistical Methods Explained
The registry reports a randomized, parallel-group design and participant-level adverse-event counts. It does not report an inferential analysis for the primary outcome. The explanations below describe general statistical concepts and distinguish them from methods documented for this trial.
What does a participant count measure?
General: A binary event outcome classifies each participant according to whether an event occurred during the specified period. Summing those classifications gives the number of participants with an event. This is different from counting every event, because one person may experience more than one event. The registry’s primary outcome is explicitly a count of participants with ocular and non-ocular adverse events, with Day 90 as the timeframe.
The posted arm-level safety entries give the number at risk and the number affected for serious and other adverse events. These figures describe observed participants in each arm. They are not adjusted for baseline characteristics in the information reported by the registry, and the record does not state that an adjusted model was used. No adjusted effect estimate is reported.
What can randomization contribute?
General: Random assignment is intended to reduce systematic differences between treatment groups at the time of assignment. It does not guarantee that small groups will have the same distribution of every prognostic factor. Randomization also does not remove uncertainty from outcome measurement, missing follow-up, or chance variation. The registry identifies the study as randomized but does not describe sequence generation, allocation concealment, or baseline balance.
In a parallel design, participants remain in their assigned treatment group for the comparison. This is the design classification in the record. The record does not report whether analyses followed assignment regardless of treatment received, or whether another analysis population was used.
What would an effect estimate and confidence interval add?
General: A treatment-effect estimate expresses the contrast between groups using a stated scale, such as a difference in risks or a relative measure. A confidence interval describes the precision of that estimate under the assumptions of the analysis. A wide interval signals that a range of effects remains compatible with the data; an interval alone does not establish clinical importance or causation. For this trial, no primary-outcome effect estimate or confidence interval is reported in the registry record, so none can be interpreted from the posted entries.
A statistical test addresses compatibility of data with a specified null hypothesis under the chosen model. Its result does not measure the size or importance of an effect. No primary-outcome test result is reported, and the record does not give a p-value for the adverse-event counts. A numerical comparison should not be created by treating the descriptive counts as if they were a sponsor-reported analysis.
Why does outcome structure matter?
The registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. General: A single, clearly defined comparison makes the target estimand and analysis easier to identify. When an outcome includes multiple event categories or assessment times, the analysis needs to state how those components are handled. Different choices can answer different questions, and selecting among many possible comparisons can raise multiplicity concerns. The registry record does not specify a summary rule or identify a primary contrast across the listed outcome components.
The adverse-event count outcome is distinct from the secondary measure, change from baseline in best-corrected visual acuity score. General: A change score compares a follow-up measurement with a baseline measurement, but interpretation depends on the scoring scale, measurement schedule, and analysis method. Those details and the visual-acuity results are not reported in the registry record.
How should the planning assumptions be read?
The record describes sample-size calculations as planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence that a trial had a particular probability of success. Sample-size planning illustrations are not observed power and do not show the probability that the treatment effect is real.
General: Planning estimates depend on the assumed effect, variability or event frequency, significance threshold, allocation, and analysis method. If the effect used as a planning reference is uncertain, the resulting illustration is uncertain too. The registry record does not report the trial’s own sample-size justification, and the posted primary outcome was not reduced to one comparison. No specific planning sample-size result is reported in the registry information.
The record lists no analyses for the outcomes. It does not report interim analyses, model specifications, covariate adjustment, handling of repeated measures, or a prespecified analysis plan. In the absence of such details, the posted figures support descriptive reading only; additional model-based claims would require information not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures and identifies adverse events as the primary outcome, while also listing change from baseline in best-corrected visual acuity score as a secondary outcome. It says the primary outcome contains several categories or time points and was not reduced to one comparison. The record does not report how multiple categories, time points, or outcomes were prioritized for statistical testing, nor whether any multiplicity adjustment was planned.
General: When several hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for the set of comparisons. A prespecified primary contrast and a clear hierarchy of secondary analyses can help readers distinguish confirmatory from exploratory results. This record does not provide that level of detail, and it reports no outcome analyses.
Missing-data methods are not reported in the registry record. The posted safety figures include 15 participants at risk in each arm for serious and other adverse events, but the record does not describe completeness of follow-up, withdrawals, or how unavailable event information was handled. The analysis population is also not reported. It is therefore not possible to determine from the registry whether every randomized participant was included in each outcome analysis or whether another population definition was used.
The registry does not report an interim-analysis plan or stopping rules. These absences do not show that such procedures were or were not used; they indicate that the details are not reported in the registry record. The lack of a documented analysis plan limits assessment of how the posted outcomes relate to prespecified hypotheses.
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 |
|---|---|---|---|
| Sham Injection | 2 | 15 | 13.3% |
| Intravitreal Aflibercept Injection | 3 | 15 | 20.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sham Injection | 0 of 15 |
| Intravitreal Aflibercept Injection | 0 of 15 |
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 |
|---|---|
| Sham Injection | 14 of 15 |
| Intravitreal Aflibercept Injection | 10 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Sham Injection | Intravitreal Aflibercept Injection |
|---|---|---|---|
| Paracentesis | Eye disorders | 0 of 15 | 2 of 15 |
| Rash and Swelling on Limbs | Skin and subcutaneous tissue disorders | 2 of 15 | 0 of 15 |
| Cough/Vomiting | Gastrointestinal disorders | 0 of 15 | 1 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sham Injection | Intravitreal Aflibercept Injection |
|---|---|---|---|
| Foreign Body Sensation | Eye disorders | 3 of 15 | 3 of 15 |
| Blurred Vision | Eye disorders | 4 of 15 | 2 of 15 |
| Floaters | Eye disorders | 4 of 15 | 2 of 15 |
| Eye Irritation/Pain | Eye disorders | 2 of 15 | 2 of 15 |
| Eye Itching | Eye disorders | 1 of 15 | 2 of 15 |
| Photophobia | Eye disorders | 3 of 15 | 0 of 15 |
| Lacrimation Increased | Eye disorders | 1 of 15 | 1 of 15 |
| Corneal Edema | Eye disorders | 0 of 15 | 1 of 15 |
Serious events with the highest arm-level rate: paracentesis (13.3%), rash and swelling on limbs (13.3%), cough/vomiting (6.7%).
The registry reports serious adverse events separately by randomized arm. In the sham arm, 2 participants were affected among 15 at risk; in the intravitreal aflibercept arm, 3 were affected among 15 at risk. The registry records 0 deaths in each arm. Under other adverse events, it reports 14 affected among 15 at risk in the sham arm and 10 among 15 at risk in the aflibercept arm.
These entries are counts of participants, not necessarily counts of every event experienced. The serious-event terms listed in the record are Paracentesis, 13.3%; Rash and Swelling on Limbs, 13.3%; and Cough/Vomiting, 6.7%. The registry does not report the arm-specific distribution of these terms in the information, so they should not be assigned to an arm based on the overall listing.
General: Seriousness and frequency are different dimensions of safety reporting. A count alone does not communicate event severity beyond the category used in the record, causality, duration, or outcome. These small descriptive counts should not be interpreted as a precise estimate of comparative risk, particularly because no inferential comparison or confidence interval is reported for them.
12. What the Result Does, and Does Not, Mean
The posted results establish that adverse events were recorded in both randomized arms during the study’s stated safety follow-up. They report serious and other adverse events separately, along with no deaths in either arm. The listed serious-event terms provide additional descriptive information. These are observations from this trial, not a complete account of all possible outcomes or all time periods.
The primary endpoint is a safety count, while the stated study objective also refers to preventing macular edema. The registry record does not report a single statistical comparison for the primary endpoint, and it does not include results for the listed secondary visual-acuity outcome. It therefore does not support a conclusion about whether aflibercept prevented macular edema or changed visual acuity. The safety counts alone also do not establish that an adverse event was caused by the assigned intervention.
General: A randomized comparison can support causal interpretation when the analysis preserves the randomized comparison and relevant design and follow-up details are adequately reported. However, randomization does not make a small trial automatically precise. Event counts based on limited enrollment can leave considerable uncertainty, and the absence of confidence intervals or an inferential comparison prevents a reader from quantifying that uncertainty from the registry entries.
The record does not report analysis populations, missing-data procedures, or a full statistical analysis plan. Nor does it provide enough information to assess all sources of bias or generalizability. The appropriate reading is consequently narrow: the registry provides descriptive adverse-event counts for this trial, while important efficacy results and analytical details are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it places a safety endpoint at the center of a study whose stated objective also includes efficacy. The distinction between the objective and the reported primary endpoint matters: a reader should not treat adverse-event counts as evidence about macular-edema prevention when the record does not report a corresponding efficacy result.
The outcome is reported as the number of participants with events, separated into serious and other adverse events. That makes the unit of analysis explicit at a basic level, but the record also notes multiple categories or time points and does not reduce the primary outcome to a single comparison. Without a defined contrast, an effect estimate, or an interval describing precision, the posted counts remain descriptive.
The trial enrolled 30 participants, and the adverse-event entries list 15 at risk in each arm. Such counts can flag what was observed in the enrolled groups, but they offer limited information for estimating uncommon events or for precisely distinguishing groups. This is a general statistical limitation of small samples, not a claim that any particular event is rare or that the observed pattern would persist in another population.
The registry also illustrates why analysis reporting matters. Information about missing data, analysis populations, multiplicity, and the prespecified statistical plan is not reported. Those details would help readers understand which comparisons were intended and how outcome data were handled. A completed trial record can still leave substantial uncertainty when key analyses and precision measures are absent.
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.
The principal limitation for interpreting the posted results is that the registry does not report a single inferential comparison for the primary outcome. It describes the outcome as covering several categories or time points and does not reduce it to one comparison. No effect estimate, confidence interval, or p-value for that outcome is reported in the registry record.
The enrollment was 30 participants, and the safety entries list 15 at risk in each arm. The resulting counts are useful descriptions of the trial experience, but their precision cannot be assessed from the record because uncertainty intervals are not reported. The record does not provide a sample-size justification for the trial, and the planning assumptions are described as illustrations rather than as the trial’s own design rationale.
The registry record does not report baseline characteristics, detailed eligibility criteria, participant flow, missing-data handling, or analysis populations. It also does not provide the allocation-sequence method, allocation concealment details, or a full account of who was masked. The arm description says the patient would be masked in the aflibercept arm, while the registry classifies the study as single-masked; further masking details are not reported.
The study objective includes prevention of macular edema, but the reported primary endpoint is an adverse-event count. Results for the secondary visual-acuity outcome are not reported in the registry record, and no macular-edema result is included in the posted information. The registry’s serious-event terms are not assigned to arms in the available listing. Together, these omissions limit assessment of efficacy, safety comparisons, and the broader applicability of the observed counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Prevention of Macular Edema In Patients With Diabetic Retinopathy Undergoing Cataract Surgery — NCT01988246.
- Registry record last updated 2020-05-22; status last verified 2020-05.
- Results first posted 2020-05-22.
- 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
The registry record describes NCT01988246, titled Prevention of Macular Edema In Patients With Diabetic Retinopathy Undergoing Cataract Surgery. It lists a randomized, single-masked, parallel-group Phase 1 and Phase 2 study with 30 participants enrolled and completed status. The recorded start is 2013-12, and primary completion is dated 2018-04-25.
The arms are sham injection and intravitreal aflibercept injection. The primary outcome is the number of participants with ocular and non-ocular adverse events at Day 90. Posted safety entries include serious and other adverse-event counts, and the registry reports no deaths in either arm. A secondary outcome is change from baseline in best-corrected visual acuity score.
The registry does not report a single primary-outcome comparison, inferential analyses, or results for the secondary visual-acuity outcome. It also does not report several analysis and follow-up details needed for a fuller assessment.