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 Repeated Eye Injections of Aflibercept for Treatment of Wet Age Related Macular Degeneration (NCT01773954), a na na study. The primary outcome is Mean Change in Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01773954 |
| Phase | NA |
| Condition | Age-Related Macular Degeneration, Macular Degeneration |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 40 |
| Arms in the primary outcome | n/a |
| Lead sponsor | MidAtlantic Retina |
| Results posted | Yes |
2. Clinical Question
Population
People with subfoveal neovascular age-related macular degeneration, described in the registry summary as wet age-related macular degeneration. The record lists an enrollment of 40. Further eligibility criteria and the characteristics of the enrolled participants are not reported in the registry record.
Intervention
Intravitreal aflibercept injection delivered in an OCT-guided treat-and-extend approach. The stated aim was to evaluate visual outcome and the number of injections required under this regimen.
Comparator
No separate comparator group is described. The record identifies a single-group study, and allocation is listed as NA. The listed study arms therefore do not provide a like-for-like control comparison.
Primary question
What was the mean change in best-corrected ETDRS letter score from baseline to Week 52 during treatment with intravitreal aflibercept?
The clinical question concerns change in visual acuity over the stated follow-up period while treatment intervals are adjusted using OCT-guided treat-and-extend criteria. The intervention description says treatment was given at baseline and at the week 4 visit. It also describes extending follow-up intervals after extension criteria are met, with the interval adjustments depending on whether the criteria are met for the first time or again. The stated maximum interval is 16 weeks. The available arm description ends partway through a sentence about follow-up at an 8-week interval, so the remainder of that instruction is not reported in the registry record.
This design can describe outcomes observed among participants receiving the regimen, but it cannot directly estimate how those outcomes compare with a separate untreated group or a different treatment strategy. The primary outcome is named, but the mean change and its 95% confidence interval are not reported in the registry record. The stated objective also includes the number of injections required; a numerical result for that objective is not reported in the registry record.
3. Trial Design
The registry describes the ATLAS study as a completed, single-group study of intravitreal aflibercept for neovascular age-related macular degeneration. Enrollment was 40. The study start is listed as 2013-02 and primary completion as 2016-03. The phase is listed as NA, allocation is listed as NA, and masking is listed as none. MidAtlantic Retina is identified as the sponsor.
Participants received aflibercept injections under an OCT-guided treat-and-extend approach. The arm description specifies treatment at baseline and the week 4 visit. It describes an increase in the follow-up interval by 4 weeks the first time extension criteria are met, followed by increases of 2 weeks each time the criteria are met, up to a maximum interval of 16 weeks. The available description is truncated while describing follow-up at an 8-week interval. Further details of the regimen are not reported in the registry record.
The design is important for interpreting the findings: this is not a randomized comparison, and the record does not describe a separate control group. Outcomes can therefore be read as observations from participants treated in this study, not as a direct estimate of the treatment difference versus another strategy. The record identifies 2 outcome measures and 0 analyses. It names a primary endpoint for change in ETDRS letter score from baseline to Week 52, but does not report the numerical result or its confidence interval. The registry record does not report a protocol-level sample-size justification or further details of the statistical analysis plan.
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 | Intravitreal Aflibercept |
|---|---|
| STARTED | 40 |
| COMPLETED | 31 |
| NOT COMPLETED | 9 |
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 | Intravitreal Aflibercept |
|---|---|---|
| Participants analysed | 40 | |
| Age, Continuous | years | 81.3 (SD 7.4) |
| Sex: Female, Male: Female | Participants | 23 |
| Sex: Female, Male: Male | Participants | 17 |
| Region of Enrollment: United States | participants | 40 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Change in Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score, measured over Baseline to Week 52.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | letters |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean change in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline to Week 52, measured in letters. A letter score expresses visual acuity as a numerical measure, and a change score describes how that measure differs from its baseline value over the specified follow-up period. The endpoint is intended to summarize visual outcome during the OCT-guided aflibercept regimen.
Using a mean change gives a group-level summary of the direction and average size of change. It does not show how much individual participants varied, nor does it describe the full distribution of outcomes. The record specifies a 95% confidence interval as the measure of dispersion. In general, a confidence interval conveys uncertainty around an estimated group mean; a narrower interval indicates greater precision than a wider interval, although it does not by itself establish that a change is clinically important.
The registry record does not report the mean change or the 95% confidence interval. It also does not report the analysis population, the number of participants contributing endpoint data, or how missing Week 52 measurements were handled. Consequently, the endpoint definition is available, but its observed magnitude and precision cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a relevant clinical outcome and a defined observation period: mean change in best-corrected ETDRS letter score from baseline to Week 52. It also identifies the intended treatment approach as OCT-guided treat-and-extend aflibercept. However, the primary endpoint’s numerical result is not reported in the registry record. Neither the mean change nor its 95% confidence interval is available, so the direction, magnitude, and precision of the observed change cannot be evaluated from this record.
The registry summary says the study was designed to evaluate visual outcome and the number of injections required. A numerical result for the injection count is not reported in the registry record. The record lists 2 outcome measures but 0 analyses. The presence of an outcome definition is not the same as a posted estimate: without an estimate and an account of the analyzed participants, readers cannot assess how the recorded outcome data relate to the stated objective.
The single-group design also sets a boundary on interpretation. It can describe outcomes among participants who received the regimen, but it does not provide a randomized control comparison. In general, an observed change over time in a single group can reflect multiple influences, including the treatment course, the condition’s progression, participant characteristics, and other care. Without a comparison group, those influences cannot be separated by a direct between-group estimate. No conclusion about comparative benefit or harm follows from the design alone.
The registry lists serious adverse events affecting 2 participants in the Intravitreal Aflibercept group, with 40 participants at risk for serious adverse events. It separately lists 0 other adverse events affecting participants in that group and records 2 deaths. The listed serious terms are Fatal MI and Endophthalmitis, each shown as 2.5%. These entries should be read as registry safety reports, not as proof that the intervention caused the events. The record does not report enough context to establish event timing, attribution, or the relationship between the event listings and deaths.
Overall, the registry gives a design description, endpoint definition, and limited safety counts, but does not post the primary outcome estimate. Statistical interpretation should therefore emphasize what was planned to be measured and what is actually reported, rather than infer efficacy, precision, or causality from absent results.
9. Statistical Methods Explained
The registry record specifies a continuous primary outcome: mean change in ETDRS letter score from baseline to Week 52, with a 95% confidence interval. It lists 0 analyses, and does not report an analysis method for the primary endpoint. The following statistical explanations are general; they describe how such results are commonly interpreted and do not assert that a particular method was used in this study.
What does a mean change describe?
General: A mean change summarizes the average difference between a measurement at follow-up and the corresponding baseline measurement across participants included in an analysis. It is a group-level summary. It can conceal variation: participants may have changes that differ in size or direction even when the group mean is near a particular value. A mean is most informative when read alongside a measure of uncertainty and clear information about which participants contributed data.
For this trial, the registry names the score, unit, and timeframe. It does not report the mean change, the number of participants included in that calculation, or participant-level variability. Readers therefore cannot determine the observed average change or how representative it may be of the range of participant outcomes.
How should a confidence interval be read?
General: A confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the method used to construct it. It is not a range containing a known proportion of individual participant outcomes. Its width is affected by the variability of the outcome and the amount of usable data, among other features of the analysis. A confidence interval should be interpreted together with the estimate it surrounds, the study design, and the analysis population.
The endpoint description specifies a 95% confidence interval, but the interval itself is not reported in the registry record. Without both the mean change and the interval, neither the estimated size of the change nor its precision can be assessed. The registry also does not state whether the interval was adjusted for other factors or how missing outcome measurements were treated.
What does a single-group design allow?
General: A single-group study can describe measurements observed among participants receiving an intervention. If measurements are available at baseline and follow-up, a within-group change can be estimated. Such a change is not automatically an intervention effect: in the absence of a separate comparison group, the study cannot directly distinguish the contribution of treatment from other explanations for change over time.
In this record, allocation is listed as NA, masking as none, and the model as single group. No randomized comparator is described. Thus, even if a numerical within-group change were available, it would answer a descriptive question about participants in this study rather than a direct question about the difference between treatment strategies. The primary result is not reported in the registry record in any case.
What does the sample-size illustration represent?
General: A planning sample-size calculation estimates how many participants a future or planned comparison might require under stated assumptions. It is not a measure of the probability that a completed study found a true effect, and it is not an observed result. The registry’s sample-size assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the stated convention is participants per arm.
Those assumptions are planning assumptions, not evidence that this single-group study had two equally allocated arms. The registry record does not report the observed primary effect needed to interpret such an illustration, and does not provide a numerical planning result in the registry record for this account. It does not report the trial’s own sample-size justification. The illustration should not be interpreted as observed power or as a retrospective validation of the study’s design.
Why does dispersion matter?
General: Dispersion describes how spread out observations are around a central value. For a continuous outcome, substantial participant-to-participant variation can make a group mean less precise, even when the mean itself is calculated correctly. A confidence interval for the mean addresses uncertainty about that group-level estimate; it is not a substitute for a description of individual variation.
The primary endpoint’s specified 95% confidence interval is the only dispersion measure named for that outcome. No interval value or additional measure of outcome variability is reported in the registry record. This limits assessment of precision and heterogeneity. It also prevents readers from checking whether any reported conclusion is supported by the endpoint estimate and its uncertainty, because neither is posted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures and 0 analyses. It identifies the mean change in ETDRS letter score from baseline to Week 52 as the primary outcome, but does not report the numerical result. The registry record does not report whether multiple outcomes or time points were considered in a formal testing strategy, whether any adjustment for multiple comparisons was planned, or whether an outcome hierarchy beyond the named primary outcome was specified. Multiplicity procedures should not be assumed.
The record does not describe how missing outcome data were handled. It does not report the number of participants with a Week 52 measurement, reasons for missing measurements, imputation procedures, or sensitivity analyses. These details matter in general because an analysis of only participants with observed follow-up data may represent a different set of participants from the original enrolled group. Without a reported missing-data approach and analysis population, the potential effect of incomplete follow-up cannot be assessed.
The analysis population is also not reported in the registry record. The enrollment of 40 does not establish that all participants contributed to the primary endpoint or safety summaries. The record does not specify whether analyses followed an intention-to-treat principle, included participants who completed treatment, or used another population definition. No claims about these methods can be made from the posted registry entries.
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 |
|---|---|---|---|
| Intravitreal Aflibercept | 2 | 40 | 5.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Intravitreal Aflibercept | 2 of 40 |
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 |
|---|---|
| Intravitreal Aflibercept | 0 of 40 |
Most frequent serious adverse event terms
| Event term | Organ system | Intravitreal Aflibercept |
|---|---|---|
| Fatal MI | Cardiac disorders | 1 of 40 |
| Endophthalmitis | Eye disorders | 1 of 40 |
Serious events with the highest arm-level rate: fatal mi (2.5%), endophthalmitis (2.5%).
For the Intravitreal Aflibercept group, the registry lists 40 participants at risk for serious adverse events and 2 participants affected. It lists 40 participants at risk for other adverse events and 0 affected. The record also lists 2 deaths. These are separate registry entries and should be read as counts for the categories recorded, not combined or reinterpreted as a single outcome.
The top listed serious-event terms are Fatal MI at 2.5% and Endophthalmitis at 2.5%. The record does not provide event-level details, timing, severity beyond the listed categorization, or an assessment of whether the events were related to treatment. The term Fatal MI should not be taken to establish a causal link between treatment and death. Nor does the registry record establish whether the two listed terms correspond to the deaths recorded elsewhere in the safety information.
These safety entries describe what the registry reports for this group. With no separate comparator group, they do not support a direct comparison of event frequency between treatment strategies. They also do not establish the broader safety profile beyond the reported entries. Further attribution and contextual details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record documents a study of OCT-guided treat-and-extend intravitreal aflibercept for neovascular age-related macular degeneration. It identifies the intended primary outcome as mean change in best-corrected ETDRS letter score from baseline to Week 52, and it states that visual outcome and injection number were objectives. It also reports limited safety counts for the treated group.
What the record does not establish is the observed primary outcome. The mean change and its 95% confidence interval are not reported in the registry record. The numerical result for injection number is also not reported. Therefore, the magnitude and precision of visual change, as well as the treatment burden in terms of injections, cannot be assessed from the record. An endpoint definition alone is not a result.
The single-group design means that the study does not directly compare aflibercept with another treatment or with no treatment. In general, changes measured within a treated group do not by themselves identify how outcomes would have differed under an alternative strategy. The registry record therefore cannot support a comparative estimate based on a control group that is not described.
The listed serious adverse events and deaths should be understood as reported safety observations, not proof of treatment causation. The record does not provide enough detail to establish attribution or connect the event terms to the recorded deaths. Likewise, a zero count for other adverse events in the posted group is a registry entry, not a guarantee that no other events occurred or were collected under different definitions.
The defensible conclusion is limited: the registry describes the study design, intervention, endpoint, and some safety information, but does not report the main efficacy estimate or its precision. Any stronger claim about the size of visual change, comparative effects, injection burden, or causal safety findings would go beyond what the registry record reports.
13. Why This Trial Matters Statistically
This study illustrates why an endpoint definition and an endpoint result must be distinguished. Naming mean change in ETDRS letter score and specifying baseline to Week 52 tell readers what the investigators intended to measure. They do not tell readers what the estimate was, how uncertain it was, or how many participants contributed to it. Without the mean and its 95% confidence interval, the core statistical question cannot be answered from the registry record.
The study design is equally important. A single-group study can describe the course of outcomes among participants receiving a regimen, but it does not provide the direct treatment contrast available from a suitable comparison group. This distinction remains important even when a clinical outcome is measured on a defined scale and over a defined period. A within-group observation and a comparative treatment effect are different estimands.
The record also highlights the value of transparent reporting about analysis populations and missing data. Enrollment alone does not show how many participants contributed endpoint information. Clear reporting of follow-up, analysis methods, and uncertainty allows readers to judge how robustly a result addresses its stated question. These items are not reported in the registry record.
Finally, safety counts require context. Counts, event terms, and deaths should be interpreted as the categories recorded, without assuming causal attribution or a comparison that the study design does not provide. The statistical importance of this trial record lies in what it makes explicit—the intended question and study structure—and in recognizing the limits imposed by results and analysis details that are not 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.
The main limitation for statistical interpretation is that the registry record does not report the primary endpoint estimate or its 95% confidence interval. The result therefore cannot be evaluated for direction, magnitude, or precision. The record also does not report a numerical result for the stated objective concerning injection number.
The single-group design has no described like-for-like control comparison. This limits interpretation to description of outcomes in the treated group and prevents a direct estimate of a treatment difference. Allocation is listed as NA and masking as none. The record does not report a protocol-level sample-size justification or the statistical analysis plan.
Additional analysis details are absent. The analysis population, number of participants contributing to the primary endpoint, handling of missing Week 52 data, and sensitivity analyses are not reported in the registry record. It is also not reported whether multiplicity was addressed or which methods were used to calculate the confidence interval. The available intervention description is truncated during its account of follow-up intervals, leaving part of the regimen description unavailable.
For safety, the record lists serious-event counts, other adverse-event counts, deaths, and two serious-event terms, but does not report event timing, treatment attribution, or enough information to determine how the terms relate to the death count. These limitations concern what can be concluded from the registry record and do not establish what may have been collected or analyzed elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Repeated Eye Injections of Aflibercept for Treatment of Wet Age Related Macular Degeneration — NCT01773954.
- Registry record last updated 2018-05-02; status last verified 2018-04.
- Results first posted 2018-05-02.
- 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
NCT01773954 is a completed, single-group study sponsored by MidAtlantic Retina. It lists enrollment of 40 and evaluates intravitreal aflibercept using an OCT-guided treat-and-extend approach for neovascular age-related macular degeneration. The listed primary outcome is mean change in best-corrected ETDRS letter score from baseline to Week 52, with a 95% confidence interval specified.
The registry record lists 2 outcome measures and 0 analyses. It does not report the primary endpoint estimate, its confidence interval, or a numerical result for injection number. No separate comparator group is described. Safety entries include 2 participants affected by serious adverse events, 0 affected by other adverse events, and 2 deaths; Fatal MI and Endophthalmitis are each listed at 2.5%. Event attribution and additional analysis details are not reported in the registry record.