Evaluation of Pain and Inflammation After Injection of Lucentis vs Eylea for Treatment of Wet Macular Degeneration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Pain and Inflammation After Injection of Lucentis vs Eylea for Treatment of Wet Macular Degeneration (NCT01926977), a non-randomized phase 1, phase 2 study. The primary outcome is Evidence of Anterior Chamber Inflammation.

2. Clinical Question

3. Trial Design

The registry record describes a Phase 1 and Phase 2, parallel, single-masked, non-randomized study. Its stated purpose was to compare post-injection inflammation and pain after intravitreal ranibizumab versus aflibercept. The record lists a planned enrollment of 100 and identifies neovascular age-related macular degeneration as the condition under study. The status is completed, with a start date of 2013-09 and primary completion in 2014-05.

The two listed arms received a single injection: ranibizumab 0.5mg or aflibercept 2.0mg. Since allocation was non-randomized, differences in participant characteristics, clinical circumstances, or other factors could be associated with arm membership. The registry record does not explain how allocation was determined, whether the groups were balanced at baseline, or whether any adjustment was planned to address differences. It therefore does not establish that observed arm differences, if results were available, would reflect the injections alone.

Masking is recorded as single, but the identity of the masked group and the practical masking procedures are not reported in the registry record. The record lists the study model as parallel, meaning the listed arms represent separate groups, but additional details of study conduct are not reported. The registry also does not report the rationale for the planned enrollment, a sample-size justification, or whether any interim analyses were planned.

The study has two outcome measures listed and no analyses recorded. The primary outcome concerns anterior chamber inflammation; the secondary outcome concerns post-injection pain. The record does not provide results for either outcome or identify analysis populations. Safety counts are reported separately for the two arms, but they do not supply the missing primary endpoint comparison.

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 Evidence of Anterior Chamber Inflammation, measured over 24 to 48 hours (visit #1) and 5 to 7 days (visit #2).

The primary endpoint is the number of participants with evidence of anterior chamber inflammation. The record specifies assessment using Standardization of Uveitis Nomenclature at 24 to 48 hours (visit #1) and 5 to 7 days (visit #2). This is a participant-count outcome: it is intended to describe how many participants met the recorded inflammation criterion at the stated visits. The registry record does not give the criterion details beyond the named standard, nor does it report the number meeting the endpoint at either visit.

In general, a clinical endpoint should correspond to an outcome relevant to the study question and be defined consistently enough to measure across participants. A standardized assessment framework can support consistency in how a clinical finding is classified. However, the registry description does not explain who assessed inflammation, whether assessments were masked, how findings at the two visits were combined, or whether the primary endpoint was evaluated separately at each visit. Those details are not reported in the registry record.

The endpoint is distinct from the secondary pain outcome. Pain was recorded as the number of patients with a post-injection pain score of one or higher on the pain scale, but its results are also not reported in the registry record. Without endpoint counts, there is no reported basis for describing the frequency of inflammation or comparing the arms on the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant-count endpoint represent?

As a general statistical concept, a binary endpoint classifies each participant according to whether a defined event or finding is present. A count then records the number classified as having that finding. To interpret such a count, readers need both the number with the finding and the number assessed. The primary endpoint in this study is described as the number of participants with evidence of anterior chamber inflammation at the stated visits. The registry record does not report the endpoint counts, denominators, or analysis results.

The endpoint is named as a participant count, but the record does not specify whether the two assessments were analyzed separately or whether any combined rule was used. It also does not report how participants with missing visits were handled. These details matter because a count at one visit and a count across a follow-up period answer different questions. The record supplies the visit windows but does not explain the endpoint construction beyond that description.

What can a comparison between arms establish?

In general, a comparative analysis estimates how outcomes differ between groups under a defined analysis plan. Random allocation can help make groups comparable with respect to both observed and unobserved characteristics, on average. This study is recorded as non-randomized, and the registry specifically cautions that the arms are not a like-for-like control comparison. A difference, if reported, could therefore reflect characteristics associated with assignment as well as the injections. The registry record does not describe an adjustment strategy or provide baseline information with which to assess comparability.

A confidence interval is a statistical range that expresses uncertainty around an estimated effect under the assumptions of the analysis. Narrower intervals generally indicate greater precision, while wider intervals indicate less precision. The registry record does not report an effect estimate or confidence interval for the primary endpoint or pain outcome, so their magnitude and precision cannot be assessed. It also does not report a hypothesis test or p-value for these outcomes.

How should the safety counts be read?

For the reported safety categories, the registry gives counts and numbers at risk. Those counts can be read descriptively within each arm, but they do not alone establish a causal difference. In general, a formal comparison would need an analysis method suited to the outcome and study design, along with attention to the number assessed and the process by which groups were formed. No such comparison is recorded for these safety entries. The record gives no serious adverse events in either arm, while the other adverse-event counts differ. No inference about why the counts differ is justified from these entries alone.

When event counts are small, statistical estimates may be imprecise. More generally, sparse data can make some methods unstable or require methods tailored to small counts. This is a general consideration, not a claim about an analysis performed in this study: no safety analysis is reported in the registry record. Nor does the record provide details about event timing, event definitions, completeness of follow-up, or causal attribution.

What do the sample-size illustrations mean?

As a general concept, a sample-size calculation estimates the number of participants needed under specified assumptions to detect a chosen effect with a chosen error rate and power. The registry record notes that its sample-size illustrations are based on the observed effect, use a two-sided significance level of 0.05, assume equal allocation, and use a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning illustrations, not evidence of the study's original design rationale or a report of observed power.

The registry record does not report the trial's own sample-size justification. It also does not report a primary endpoint effect estimate from which to understand such planning illustrations. The illustrations should not be interpreted as observed power, as a guarantee that the study could detect a particular effect, or as proof that the intended enrollment was adequate. Sample-size calculations depend on assumptions, and the record does not report whether the trial used these assumptions when it was designed.

In general, statistical interpretation also depends on the analysis population, missing-data handling, endpoint definition, and analysis plan. Here, the record lists no analyses. It does not report whether analysis was by assigned arm, whether participants with incomplete assessments were excluded or otherwise handled, or whether any covariates were included. Without those details and outcome results, the study's primary comparison cannot be reconstructed from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures: anterior chamber inflammation as the primary outcome and post-injection pain as a secondary outcome. When several outcomes or repeated assessments are analyzed, general statistical practice considers multiplicity: testing multiple questions can increase the chance of finding a nominally unusual result by chance. An analysis plan may specify which outcome is primary, how repeated time points are handled, and whether any adjustment or hierarchy is used. Although the record labels the inflammation outcome primary, it does not report a multiplicity strategy or statistical analysis plan. No analyses are recorded.

The primary outcome is assessed at 24 to 48 hours and 5 to 7 days. The record does not say whether those visits constitute separate endpoint tests or contribute to one combined endpoint. It does not report outcome counts at either visit, so missing assessments and the denominator at each visit cannot be evaluated. Handling of missing data is not reported in the registry record.

The record does not identify the primary analysis population or state whether all enrolled participants were included in each analysis. It gives a planned enrollment of 100 and separate safety risk counts, but those details do not establish outcome-specific denominators. Whether participants were excluded, whether deviations from the intended treatment were handled, and whether analyses were adjusted for any participant characteristics are not reported in the registry record.

These omissions limit reproducibility and interpretation. They do not establish that any particular analysis or data-handling method was used. The registry record does not report interim analyses, and no conclusion about whether they occurred can be drawn from the record.

11. 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 non-serious adverse event terms

The registry reports serious adverse events for 47 participants at risk in the ranibizumab 0.5mg arm and 53 participants at risk in the aflibercept 2.0mg arm. The recorded serious adverse-event count is 0 in each arm. For other adverse events, the record lists 1 among 47 at risk in the ranibizumab arm and 10 among 53 at risk in the aflibercept arm. These are the counts as recorded; the registry does not provide a statistical comparison of them.

These entries should be read as safety descriptions rather than as evidence about the primary inflammation endpoint or the pain outcome. The record does not define the other-adverse-event category in further detail, report event types, or say whether events were considered related to an injection. It also does not give event timing or explain how safety follow-up was conducted. The entries therefore cannot establish the cause of an event or explain why counts differed between arms.

Deaths are not reported in the registry record. No serious adverse-event terms are listed. The risk counts describe the denominators attached to the safety entries; they do not establish the denominators used for the unreported primary and secondary outcome analyses.

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

The registry record establishes that a completed, non-randomized study was designed to compare inflammation and pain after single intravitreal injections of ranibizumab 0.5mg and aflibercept 2.0mg. It identifies anterior chamber inflammation as the primary outcome, names the assessment standard, and gives two visit windows. It also identifies a secondary pain outcome and reports safety counts for each arm. These details describe the study question and some aspects of its conduct.

The record does not report the primary endpoint counts, the pain results, or statistical analyses. It therefore does not show the frequency of inflammation or pain in either arm, the size or direction of a difference between arms, or the precision of any estimated difference. No conclusion about comparative effectiveness or the presence or absence of a treatment effect can be drawn from the unreported outcome results.

The safety entries show recorded counts of serious and other adverse events among the participants at risk. They do not establish that the injections caused or prevented an event, and they are not a substitute for the missing primary endpoint results. The record does not provide a statistical safety comparison, event details, or attribution information.

Even if outcome comparisons were available, the non-randomized allocation would require careful interpretation. Without information on how participants were assigned, baseline comparability, and any adjusted analyses, differences could be associated with factors other than the injection. The study record itself cautions against treating the arms as a like-for-like control comparison.

Accordingly, the record supports a description of the planned question, design, endpoint schedule, and limited safety counts. It does not support claims that one injection produced more or less inflammation or pain than the other. Missing results should not be interpreted as evidence of no difference.

13. Why This Trial Matters Statistically

This study illustrates why a clearly named endpoint is not enough to support a statistical conclusion. The record identifies anterior chamber inflammation, the assessment framework, and the visit windows, but does not report the endpoint counts or analysis. Without outcome data, readers cannot assess the observed frequency, compare groups, or judge precision.

The non-randomized design is also central to interpretation. Group assignment can be associated with participant or clinical characteristics, so a comparison may not isolate the effect of the injection. The registry explicitly warns that the arms are not a like-for-like control comparison. This is not a minor technical qualification: it affects what a between-arm contrast could mean, even if numerical outcome results were available.

The record also distinguishes planned enrollment from safety denominators. It lists planned enrollment of 100 and reports safety risk counts of 47 and 53, while outcome-specific analysis populations are not reported. This makes it important not to assume that safety and efficacy denominators are interchangeable.

Finally, the record lists two outcomes but no analyses. A statistical plan would ordinarily help readers understand how the primary outcome and the two assessment visits were handled, what populations were analyzed, and how missing observations or multiple outcome questions were addressed. Those details are not reported. The case therefore demonstrates the value of complete registry results and transparent analysis descriptions: design details and safety counts cannot replace outcome estimates and their uncertainty.

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 most consequential limitation of the available record is that it does not report results for either listed outcome. The primary endpoint counts at 24 to 48 hours and 5 to 7 days are absent, as are the secondary pain results. No effect estimate, confidence interval, or statistical test is reported. The primary comparison therefore cannot be quantified or evaluated for precision.

Non-randomized allocation limits causal interpretation. The registry does not report how assignment was made or whether the arms differed at baseline. It also does not report adjusted analyses. The record warns that the arms are not a like-for-like control comparison, so any apparent contrast, if results were available, could reflect differences between groups beyond the intervention.

Important operational details are not reported in the registry record. These include who was masked, how masking was implemented, endpoint-specific denominators, analysis populations, missing-data handling, and the definition used to combine or distinguish the two primary assessment visits. A sample-size justification for the trial and a statistical analysis plan are also not reported.

The safety information is limited to counts and numbers at risk. The record does not provide event descriptions for other adverse events, timing, attribution, or a statistical comparison. Deaths are not reported in the registry record. The safety entries should not be used to fill gaps in the unreported inflammation and pain outcomes.

Finally, planned enrollment and safety counts do not establish how many participants contributed to each outcome analysis. The registry reports no analyses, so it is not possible to assess exclusions, deviations, or completeness of endpoint follow-up.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of Pain and Inflammation After Injection of Lucentis vs Eylea for Treatment of Wet Macular Degeneration — NCT01926977.
• Registry record last updated 2016-03-03; status last verified 2016-02.
• Results first posted 2016-03-03.
• 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.

18. Record Summary

The registry describes a completed, Phase 1 and Phase 2, parallel, single-masked, non-randomized study of post-injection inflammation and pain in neovascular age-related macular degeneration. The listed arms received a single intravitreal injection of ranibizumab 0.5mg or aflibercept 2.0mg. Planned enrollment was 100.

The primary outcome was the number of participants with anterior chamber inflammation assessed at 24 to 48 hours and 5 to 7 days using Standardization of Uveitis Nomenclature. Pain was listed as a secondary outcome. Neither outcome's results nor statistical analyses are reported in the registry record.

Safety entries record 0 serious adverse events among 47 at risk in the ranibizumab arm and 0 among 53 at risk in the aflibercept arm. Other adverse-event counts are 1 and 10, respectively. Allocation was non-randomized, and the registry cautions that the arms are not a like-for-like control comparison.