Study for Recalcitrant Age Related Macular Degeneration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study for Recalcitrant Age Related Macular Degeneration (NCT01543568), a na phase 4 study. The primary outcome is The Number of Patients With no Fluid on OCT.

2. Clinical Question

In plain terms, the study asked whether participants who still had retinal or subretinal fluid after prior ranibizumab treatment would have no fluid visible on OCT during follow-up after receiving aflibercept. OCT is an imaging method used to assess retinal structure and fluid. The primary endpoint is a participant count rather than a mean change, a rate, or a comparison between treatment groups.

The question is limited to the enrolled study group and its follow-up. Because the design is single-group and open label, it does not directly compare aflibercept with continued ranibizumab, another treatment, or no treatment. The record also does not report the number of participants who met the primary endpoint, the analysis population used for that endpoint, or an uncertainty estimate. Consequently, the clinical question can be described from the protocol information, but the posted record does not establish how often the endpoint occurred.

3. Trial Design

The TURF study is listed as a Phase 4, completed, single-group study of aflibercept 2.0 mg in people with age-related macular degeneration. The registry lists an enrollment of 46. The brief summary, however, begins by describing 50 patients. The reason for the difference between these figures is not reported in the registry record, so they should not be treated as interchangeable descriptions of the number enrolled or analyzed.

The study is described as open label, with masking listed as none. Participants were seen monthly. The treatment description specifies mandatory aflibercept injections at baseline and months 1, 2 and 4, and possible pro re nata retreatment at months 3 and 5 if spectral domain OCT indicated disease. This schedule describes the planned treatment approach, not the extent to which each participant followed it; treatment received by individual participants is not reported in the registry record.

The listed primary endpoint was the number of participants with no fluid on OCT at six months. Secondary outcomes included mean change in OCT central foveal thickness, average time to resolution of intraretinal cysts and subretinal fluid, the percentage losing > 15 letters of visual acuity, mean change in visual acuity, change in choroidal neovascular lesion area or size, and mean number of aflibercept injections administered. The registry lists seven outcome measures, but the reported information does not give the results for those measures.

There is no randomized allocation or concurrent control group described. As a result, the design can describe outcomes observed among participants treated in the study, if those results are available, but cannot by itself separate treatment-associated changes from changes over time or other influences. The registry record does not report a statistical analysis plan, a sample-size justification for the original study, or an explanation of how participants were selected for analysis.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as The Number of Patients With no Fluid on OCT, measured over 6 months.

The primary endpoint is titled “The Number of Patients With no Fluid on OCT.” It is a count of participants meeting a condition at the six-month timeframe: no fluid detected on OCT. OCT is a structural imaging approach that can identify fluid in or beneath the retina. In this study, absence of visible fluid is a binary participant-level status: each assessed participant either meets the endpoint definition or does not.

A count can be clinically and statistically straightforward to interpret because it describes how many participants reached a specified imaging state. It is distinct from a mean change in retinal thickness, a time-to-resolution measure, or visual acuity change, all of which appear among the secondary outcomes. Those outcomes address different aspects of disease status and should not be substituted for the primary endpoint.

In general, an imaging endpoint requires a defined assessment time and consistent criteria for classifying scans. The registry names the six-month timeframe and OCT, but a more detailed definition of how fluid was assessed, how borderline scans were classified, or how missing scans were handled is not reported in the registry record. The endpoint result itself is also not reported in the registry record. Therefore, the endpoint can be explained, but its observed frequency and precision cannot be interpreted from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry lists a primary endpoint that is a participant count: the number with no fluid on OCT at six months. It also lists seven outcome measures and zero analyses. These entries describe the endpoint and the presence or absence of registry-posted analyses; they do not provide numerical study findings. The primary result and analysis details are not reported in the registry record.

What does a count endpoint represent?

In general, a binary endpoint classifies each assessed participant into one of two categories, such as meeting or not meeting an endpoint definition. A count adds the participants who meet that definition. To interpret a count, a reader also needs to know the relevant denominator: for example, whether it includes everyone enrolled, everyone treated, or only participants with an assessment at the specified visit. That denominator is not reported in the registry record for the primary outcome.

A count alone does not show how precise an estimate is. In general, a confidence interval expresses a range of values compatible with the data and a specified statistical procedure. It helps convey the uncertainty around an estimate; it does not guarantee that the true value lies within the interval. Neither a primary endpoint estimate nor a confidence interval is reported in the registry record.

What would a comparison show?

In general, a comparative treatment analysis uses outcomes in one group in relation to outcomes in another group. Random allocation can help make groups comparable on average, while a concurrent control can help distinguish changes associated with treatment from changes that might occur over time or under other care. This registry describes a single-group study and lists allocation as not applicable. It therefore does not provide a randomized between-group treatment contrast. No comparative effect estimate is reported in the registry record.

A before-and-after description, if available, would still be different from a randomized comparison. In general, changes between baseline and follow-up can reflect several influences, including the course of the condition, measurement variability, and other care. The posted record does not include the primary outcome values at baseline or follow-up, nor a reported analysis of change.

What does the treatment schedule imply for analysis?

The study describes mandatory aflibercept at baseline and months 1, 2 and 4, with possible retreatment at months 3 and 5 based on OCT evidence of disease. This is a treatment schedule, not a statistical method. Participants could have different actual injection histories under a schedule that includes PRN decisions. The registry does not report the individual treatment histories, adherence, or how additional treatment was incorporated into outcome analyses.

In general, outcome timing matters when participants are assessed repeatedly. A prespecified primary time point can focus interpretation, while other time points or endpoints may support additional descriptions. The registry identifies six months for the primary endpoint but does not report the detailed visit window, assessment rules, or analysis approach.

How should planning illustrations be understood?

In general, a sample-size planning illustration asks how many participants per arm might be needed under stated assumptions to detect a chosen effect with a chosen error rate and power. It is a design calculation, not an observed study outcome and not evidence that a study had a particular probability of success. The registry's planning-assumption description refers to a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of an observed effect. It also distinguishes total events for time-to-event planning from participants per arm for other outcomes.

These are planning assumptions, not evidence that the original study used them. The record does not report the study's own sample-size justification or a power calculation. Since no observed primary effect is reported in the registry record, planning illustrations based on an observed effect should not be read as a substitute for the missing result, nor as observed power.

What can be concluded from the posted analysis information?

The registry lists zero analyses, and it does not provide an inferential method, model, test statistic, p-value, confidence interval, or adjusted estimate for the primary endpoint. Those items are not reported in the registry record. In general, statistical methods should be interpreted alongside the endpoint definition, analysis population, missing-data approach, and assumptions. Without those details and the outcome data, the available information supports a description of study design rather than a statistical conclusion about the treatment outcome.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("2.0 mg Intravitreal Aflibercept")
n      <- c(46)
events <- c(10)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  2.0 mg Intravitreal Aflibercept  46  10  21.7  10.9  36.4  12.3  35.6  12.3  35.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, including OCT thickness, time to resolution of retinal fluid, visual acuity, lesion characteristics and injection count. When a study assesses multiple outcomes, there is a general statistical issue called multiplicity: the more separate hypotheses or comparisons examined, the greater the chance that some result may appear noteworthy by chance. Methods such as prespecifying a hierarchy or adjusting inference can address this issue, but the registry does not report whether any such approach was planned or used.

The record lists seven outcome measures and zero analyses. Results for the primary and secondary outcomes are not reported in the registry record. A statistical analysis plan, outcome hierarchy, multiplicity adjustment, and explanation of which analyses were considered confirmatory are not reported in the registry record. It is therefore not possible to determine how multiple outcomes were handled or whether any reported analysis was selected after examining the data.

Missing data also affect interpretation. For this OCT endpoint, participants might not have an assessable scan at the target time, but the record does not state whether this occurred or how missing assessments were handled. The numbers assessed at six months, reasons for missingness, rules for excluding participants, and any imputation or sensitivity analyses are not reported in the registry record. In general, missingness can affect a result if the participants with observed outcomes differ systematically from those without observed outcomes.

The analysis population is likewise not reported in the registry record. The registry gives enrollment of 46 and a brief-summary description of 50 patients, without explaining the difference. It does not identify an intention-to-treat, treated, or evaluable population for the primary outcome. Without the population definition and denominator, a future reported count would need context before it could be interpreted as representative of all enrolled participants.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: upper respiratory tract infection (11.1%), urinary tract infection (4.4%), squamous cell carcinoma (4.4%), death (2.2%), atrial fibrillation (2.2%).

The registry lists 45 participants at risk for serious adverse events, with 9 affected, and 45 at risk for other adverse events, with 6 affected. These are separate categories in the safety record. They describe counts in the group titled 2.0 mg Intravitreal Aflibercept; they do not, by themselves, establish whether an event was caused by treatment. The registry does not report participant-level overlap between the categories, so the figures should not be added together.

The listed top serious-event terms include upper respiratory tract infection at 11.1%, urinary tract infection at 4.4%, squamous cell carcinoma at 4.4%, death at 2.2%, and atrial fibrillation at 2.2%. These entries are event-term percentages in the registry listing. The record does not give the detailed event narratives, timing, recurrence, relatedness assessment, or severity information for each listed term. Deaths in the group-level summary are listed as null, while “Death” appears among the serious-event terms; the relationship between those entries is not reported in the registry record.

In general, adverse-event counts are descriptive safety observations. In a single-group study without a control arm, they cannot establish comparative risk. The listed figures should be read as registry-reported events, not as proof that aflibercept caused or prevented any event.

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

The registry record establishes that a completed, open-label, single-group study evaluated aflibercept 2.0 mg in people described as incomplete responders to ranibizumab for recalcitrant exudative age-related macular degeneration. It identifies a primary OCT endpoint at six months and a treatment schedule that included mandatory injections and PRN retreatment. It also lists secondary imaging, visual-acuity and treatment-use outcomes.

The record does not report the primary endpoint count or results for the secondary outcomes. It also does not report a statistical analysis, confidence interval, p-value, analysis population, or missing-data approach. Thus, the available record cannot show how often participants had no fluid on OCT, how uncertain such an estimate would be, or whether any observed change differed from what might have happened under another approach.

The design is single group, so any reported outcomes would describe participants in that group rather than establish a treatment contrast against a control. In general, an observed change during follow-up can have more than one explanation. Without a concurrent randomized comparator, the effect attributable specifically to treatment cannot be separated from other influences using this design alone.

The safety listing reports serious and other adverse event counts and names several serious-event terms. These are descriptive entries, not comparative risk estimates. The information does not provide enough detail to resolve the relationship between the group-level death entry and the listed serious-event term “Death.”

Accordingly, the study's registry entry is informative about its population description, intervention schedule, endpoint choices and design. It does not provide the outcome data required to determine what the primary endpoint showed. Completion status should not be interpreted as evidence of a favorable, unfavorable, or otherwise specific treatment result.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a well-defined clinical question and an answer that is not present in the registry record. The primary endpoint is concrete: a participant count based on fluid status on OCT at six months. Yet a named endpoint without its observed count, denominator, or analysis does not yield an estimate of the outcome. Readers need results and context, not just a protocol description, to assess the evidence.

The single-group design also makes the interpretation boundary important. In general, an uncontrolled study can describe what happened among participants receiving the study regimen, but it cannot provide the same direct comparative inference as a randomized trial with a control group. This is particularly relevant for outcomes followed over time, where the observed course may reflect more than the intervention alone.

The registry's combination of mandatory and PRN injections illustrates why treatment exposure and outcome analysis are related but distinct. A schedule states what was intended; actual exposure and how it was handled analytically are separate questions. The record does not report participant-level treatment histories or an analysis of injection use.

Finally, the discrepancy between the enrollment figure of 46 and the brief summary's description of 50 patients, together with the absence of analysis populations and missing-data methods, highlights how record completeness affects statistical interpretation. The safety entries provide counts and event terms, but do not create a controlled comparison. These points make the registry useful for identifying what was planned and recorded, while also showing why no efficacy conclusion can be drawn from the posted information.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this record constrain interpretation. First, the primary endpoint result is not reported in the registry record. Without the count, denominator, or uncertainty estimate, the frequency of participants with no fluid on OCT cannot be assessed. Results for the listed secondary outcomes are likewise not reported in the registry record.

Second, the registry gives enrollment of 46, while the brief summary describes 50 patients. It does not explain whether these figures refer to different stages or definitions. The number treated, the number completing the study, and the number included in each outcome analysis are not reported in the registry record.

Third, the study is single group and open label, with no comparator arm described. That limits causal interpretation and prevents a direct treatment contrast. The record does not report masking of image assessment or the detailed OCT classification rules. Nor does it report the statistical analysis plan, analysis population, missing-data handling, or a trial-specific sample-size justification.

Fourth, the arm description lists aflibercept 2.0 mg, while one secondary outcome is worded as the mean number of 0.2 mg aflibercept injections administered. The reason for this difference in dose wording is not reported in the registry record. It should not be resolved by assumption.

Finally, safety entries lack detailed event timing, relatedness, recurrence and participant-level overlap. The summary lists deaths as null while “Death” appears as a serious-event term; the relationship between those entries is not reported in the registry record. These limitations describe gaps in the posted information and do not establish what occurred in the study beyond the stated entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study for Recalcitrant Age Related Macular Degeneration — NCT01543568.
• Registry record last updated 2017-01-02; status last verified 2016-11.
• Results first posted 2017-01-02.
• 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.

19. Record Summary

NCT01543568 is a completed Phase 4, single-group, open-label study of intravitreal aflibercept 2.0 mg for people with age-related macular degeneration described as incomplete responders to ranibizumab. The registry lists enrollment of 46 and a brief-summary description of 50 patients; the difference is not explained. Treatment was scheduled monthly, with mandatory doses at baseline and months 1, 2 and 4 and PRN retreatment at months 3 and 5 based on OCT evidence of disease.

The primary endpoint was the number of participants with no fluid on OCT at six months. Secondary outcomes concerned OCT thickness, fluid resolution, visual acuity, lesion characteristics and injection count. The primary and secondary outcome results, analysis population, missing-data approach and statistical analysis are not reported in the registry record. The safety entry lists 9 of 45 participants with serious adverse events and 6 of 45 with other adverse events.