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 Safety Study of 2.0mg Lucentis to Treat Polypoidal Choroidal Vasculopathy (NCT01469156), a randomized phase 1, phase 2 study. The primary outcome is Incidence and Severity of Ocular and Systemic Adverse Events Will be Compared Between the 2.0mg or 1.0mg (HIGH DOSE) and 0.5 mg Groups..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01469156 |
| Phase | Phase 1, Phase 2 |
| Condition | Polypoidal Choroidal Vasculopathy |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | Double |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Southeast Retina Center, Georgia |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns subjects with exudative polypoidal choroidal vasculopathy, a condition listed in the registry as polypoidal choroidal vasculopathy. The registry describes a planned total enrollment of 20. The posted adverse-event groups include 5 people in the 0.5 mg group and 15 in the group described as receiving 1.0 mg or 2.0 mg. The registry does not report further population characteristics.
Intervention
The intervention is intravitreal ranibizumab. The study summary describes three monthly doses of 0.5 mg and 1.0 or 2.0 mg, followed by a 9 month period of criteria-based, as-needed retreatment and 12 month of drug safety follow up. The higher-dose description groups 1.0 mg and 2.0 mg together, so the posted safety figures do not distinguish those doses.
Comparator
The registry describes a 0.5 mg ranibizumab group as the comparison for the 1.0 mg or 2.0 mg group. It also lists photodynamic therapy, laser photocoagulation, or intravitreal steroids as options that may be considered at the investigator's discretion if rescue criteria are met. The record does not give details about how often these additional options were used.
Primary question
The primary question is whether the incidence and severity of ocular and systemic adverse events differ between the higher-dose group and the 0.5 mg group over 2 years. The registry names examples including 30 letter loss, major subretinal hemorrhage involving 75% or more clinical macula, injection-related endophthalmitis, retinal detachment, and other adverse events. Posted counts are available, but the primary outcome has several categories or time points and is not reduced in the registry record to one comparison. The record therefore does not supply a single estimate of the overall group difference or its precision.
3. Trial Design
The registry lists this as a Phase I/II study, with randomized allocation and double masking. It also labels the study model as single group, while the intervention descriptions and adverse-event results show a 0.5 mg group and a group receiving 1.0 mg or 2.0 mg. These entries do not explain how the single-group label relates to the randomized group descriptions, so the record does not resolve that apparent inconsistency.
The planned enrollment was 20. The study summary describes intravitreal ranibizumab at 0.5 mg and 1.0 or 2.0 mg, given in three monthly doses, followed by a 9 month period of criteria-based, as-needed retreatment and 12 month of drug safety follow up, for a total of 24 months. The primary outcome timeframe is listed as 2 years. The registry describes rescue options that could be considered at investigator discretion if criteria were met; it does not report their use in the posted results.
The record lists the study as completed. The posted adverse-event groups comprise 5 in the 0.5 mg group and 15 in the 1.0 mg or 2.0 mg group. Those group sizes sum to the planned enrollment, but the registry does not provide additional participant-flow details. The sponsor is Southeast Retina Center, Georgia. The study start is listed as 2011-09 and primary completion as 2015-02. Specific details about the randomization procedure, masking implementation, and allocation concealment are not reported in the registry record.
The intervention description also mentions photodynamic therapy with visudyne, laser photocoagulation, or intravitreal steroids as possible rescue options, alone or in combination with ranibizumab. Their availability is part of the described study context, but the registry does not state how these options affected individual treatment exposure or the group comparisons.
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 | Ranibizumab 1.0 or 2.0 mg (HIGH DOSE) | Ranibizumab 0.5 mg |
|---|---|---|
| STARTED | 15 | 5 |
| COMPLETED | 15 | 5 |
| NOT COMPLETED | 0 | 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 | Ranibizumab 1.0 or 2.0 mg (HIGH DOSE) | Ranibizumab 0.5 mg | Total |
|---|---|---|---|---|
| Participants analysed | 15 | 5 | 20 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 12 | 4 | 16 |
| Age, Categorical: >=65 years | Participants | 3 | 1 | 4 |
| Sex: Female, Male: Female | Participants | 7 | 2 | 9 |
| Sex: Female, Male: Male | Participants | 8 | 3 | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 15 | 5 | 20 |
| 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 | 1 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 7 | 1 | 8 |
| Race (NIH/OMB): White | Participants | 7 | 4 | 11 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 15 | 5 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence and Severity of Ocular and Systemic Adverse Events Will be Compared Between the 2.0mg or 1.0mg (HIGH DOSE) and 0.5 mg Groups., measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the incidence and severity of ocular and systemic adverse events, compared between the 1.0 mg or 2.0 mg group and the 0.5 mg group over 2 years. Incidence concerns whether adverse events are recorded; severity distinguishes the seriousness of those events. The registry names examples such as 30 letter loss, major subretinal hemorrhage involving 75% or more clinical macula, disease related vitreous hemorrhage, injection-related endophthalmitis, retinal detachment, vitreous hemorrhage, study drug or procedure-related uveitis, and other events identified through physical examination, subject reporting, and changes in vital signs.
Safety outcomes are used to characterize harms and tolerability during the study, rather than to quantify visual benefit. A comparison of event counts can be informative, but interpretation also depends on the number of people observed, follow-up completeness, event definitions, and how severity is classified. The registry does not reduce this outcome, which has several categories or time points, to one comparison. A single overall effect estimate, confidence interval, or inferential test for the primary endpoint is therefore not reported in the registry record. The posted adverse-event figures should be read as component counts, not as a complete statistical summary of the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results show no serious adverse events in either listed group: the registry records 0 affected among 5 at risk in the 0.5 mg group and 0 affected among 15 at risk in the 1.0 mg or 2.0 mg group. For other adverse events, it records 2 affected among 5 at risk in the 0.5 mg group and 9 affected among 15 at risk in the higher-dose group. These are the counts as posted; they do not by themselves establish a difference between groups.
The group sizes are limited, and the serious-event counts are zero in both groups. In general, zero observed events does not establish that the underlying event risk is zero. A small set of observations can be compatible with a wide range of underlying risks, and the precision of a comparison depends on the event counts and study size. The registry does not post confidence intervals or a primary statistical comparison that would quantify that uncertainty for these adverse-event results.
The group labelled 1.0 mg or 2.0 mg combines two doses. The posted counts therefore cannot show whether the adverse-event pattern differed between those doses. The record also does not state the actual distribution of participants between 1.0 mg and 2.0 mg, or report how often the described rescue interventions were used. These details constrain interpretation of what exposure the combined group represents.
The registry names several additional outcomes, including visual acuity changes, central foveal thickness, fluorescein angiography leakage, and visual acuity gain thresholds at specified visits. Results for those outcomes are not reported in the registry record. In particular, the safety counts do not answer questions about visual outcomes.
The study is marked completed, but completion status does not replace a reported analysis. The primary outcome is not reduced to one comparison, and the registry does not provide a single estimate with a measure of precision. The counts are descriptive evidence from this study record; they should not be read as a definitive comparison of safety or as evidence about how treatment would perform in other populations or settings.
9. Statistical Methods Explained
The registry describes a primary outcome based on counts of adverse events, rather than a continuous measurement. For a count outcome, a basic descriptive summary is the number of people or events observed in each group, together with the relevant group size and observation period. Here, the adverse-event display lists the number at risk and the number affected. Keeping those quantities visible helps readers distinguish the observed count from the amount of exposure represented by each group.
In general, a group comparison may be expressed as an absolute difference in risk, a relative measure, or a model-based estimate. These approaches answer related but distinct questions and rely on particular definitions of the outcome and denominator. No such comparison is posted as the primary result. The registry record does not report the statistical method used for the primary endpoint, a confidence interval, or a p-value. It is not appropriate to infer a test or an adjusted analysis from the descriptive counts alone.
A confidence interval is a way to express statistical uncertainty around an estimate. Its width depends on the data and the method used; a broad interval indicates that the estimate is not very precise. This is especially important for uncommon events and small groups. When few events are observed, methods that rely on large-sample approximations may behave poorly. General alternatives for sparse count data include exact procedures or carefully specified models, but the registry does not report which, if any, were used for this study. These are general statistical considerations, not claims about the study's analysis.
Counts may also be summarized as rates when participants have different amounts of time under observation. That requires person-time or another suitable exposure measure. Although the study describes follow-up over 2 years, the registry figures give people at risk and affected counts, not person-time. The registry record does not report enough detail to reconstruct exposure-adjusted rates or determine whether every participant completed the same follow-up.
Over-dispersion is a general issue for count models: it occurs when observed variability exceeds what a chosen model assumes. If present, it can make standard errors too small and confidence intervals too narrow when the model does not account for it. The registry does not report whether a count model was used or whether over-dispersion was assessed. Given the small group sizes and the nature of the posted counts, any model choice would need to be justified by the analysis plan and data structure; neither is described in enough detail in the registry record to evaluate that choice.
The study lists randomized allocation and double masking. Randomization, in general, aims to make groups comparable in expectation, while masking can limit some forms of bias in care or assessment. Those design labels do not reveal the specific methods used. The sequence-generation process, concealment procedures, masking details, and handling of deviations are not reported in the registry record. The additional single-group model label also sits alongside descriptions of two dose groups, and the record does not explain that classification.
The registry lists 13 outcome measures and one analysis, but does not supply a complete statistical analysis plan. The primary endpoint includes multiple event categories or time points and has not been reduced to a single comparison. A planning illustration elsewhere on the page is based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; it considers an effect that is a stated fraction of the observed effect. Such an illustration is not the trial's own design justification, does not establish the original enrollment target, and is not observed power. The sample-size justification for the trial is not reported in the registry record.
Finally, a results analysis needs explicit definitions of the analysis population, missing-data handling, and follow-up rules. For example, the interpretation can change depending on whether participants are analyzed according to randomized group, whether incomplete follow-up is included, and how an event occurring after withdrawal is handled. Those details are not reported in the registry record. This limits independent assessment of how the posted counts were assembled and how directly they represent the planned 2-year comparison.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures. The secondary outcomes cover visual acuity change, central foveal thickness, fluorescein angiography leakage, and counts of participants reaching visual acuity gain thresholds at several visits. Considering many outcomes or visits creates a multiplicity issue: even when each individual analysis is reasonable, the chance of at least one apparently notable result can increase when many results are examined. General approaches include defining a primary comparison in advance, adjusting for multiple testing, or interpreting secondary results as exploratory. The registry record does not report a multiplicity strategy.
The primary endpoint itself includes several adverse-event categories or time points and is not reduced to one comparison in the registry record. The record lists one analysis, but does not explain how that analysis relates to the multiple components of the primary outcome. Statistical methods for combining or separately analyzing those components are not reported in the registry record.
Missing-data details are also not reported in the registry record. There is no description of how incomplete follow-up, withdrawals, missing outcome assessments, or different exposure durations were handled. The analysis population is not specified. The listed groups and at-risk counts describe the posted adverse-event data, but do not establish the full set of rules used to include participants in each analysis. These gaps limit assessment of the potential for missingness or analysis choices to affect interpretation.
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 |
|---|---|---|---|
| Control Group: Ranibizumab 0.5mg | 0 | 5 | 0.0% |
| Ranibizumab 1.0mg or 2.0mg | 0 | 15 | 0.0% |
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 |
|---|---|
| Control Group: Ranibizumab 0.5mg | 2 of 5 |
| Ranibizumab 1.0mg or 2.0mg | 9 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Control Group: Ranibizumab 0.5mg | Ranibizumab 1.0mg or 2.0mg |
|---|---|---|---|
| Affected vision | Eye disorders | 1 of 5 | 6 of 15 |
| Intravitreal injection side effects | Eye disorders | 0 of 5 | 2 of 15 |
| Increased cataract | Eye disorders | 0 of 5 | 2 of 15 |
| Superior hemorrhage | Eye disorders | 0 of 5 | 1 of 15 |
| Increased Choroidal neovascularization | Eye disorders | 0 of 5 | 1 of 15 |
| Corneal Abrasion | Eye disorders | 0 of 5 | 1 of 15 |
| Trace epiretinal membrane | Eye disorders | 0 of 5 | 1 of 15 |
| Progression of edema | Cardiac disorders | 0 of 5 | 1 of 15 |
| Elevated Blood pressure | Cardiac disorders | 1 of 5 | 0 of 15 |
The registry lists the 0.5 mg group with 5 at risk and 0 affected by serious adverse events. It lists the 1.0 mg or 2.0 mg group with 15 at risk and 0 affected by serious adverse events. For other adverse events, the corresponding posted counts are 2 affected among 5 at risk and 9 affected among 15 at risk. These are raw counts; no percentages or comparative estimates are added.
The serious-event entries show that none were recorded in these groups in the posted results. That is not equivalent to proof that serious events cannot occur, particularly when the groups are small. The non-serious or other-event counts likewise need context about event definitions, follow-up, and exposure. The registry record does not provide an event-by-event breakdown for the other adverse events in this display, or a statistical comparison of these counts. Death information is not reported in the registry record. The figures are best read as descriptive summaries of the posted safety data, not as a complete evaluation of the primary endpoint.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry records 0 serious adverse events in each of the listed groups, alongside other adverse-event counts of 2 in the 0.5 mg group and 9 in the 1.0 mg or 2.0 mg group. They do not provide a precision estimate for the difference, a test of the primary comparison, or a complete analysis across the primary endpoint's categories. The data therefore describe what was recorded, but do not quantify how uncertain a group contrast is.
The figures also do not separate the 1.0 mg and 2.0 mg exposures. Nor do they report the use of optional rescue treatments, participant-level follow-up, missingness, or the analysis population. Those omissions matter when deciding how closely the posted counts correspond to the planned comparison. The registry lists other visual and anatomical outcomes, but their results are not reported, so these safety counts cannot answer questions about those outcomes.
In general, results from a clinical study should be interpreted in light of the study design, the amount and completeness of follow-up, the outcome definitions, and the precision of estimates. Here, the planned enrollment was 20 and the adverse-event groups are small. The posted data do not support a definitive claim about comparative safety beyond describing the counts recorded in this registry entry. They also do not establish what would happen in a broader population or under different treatment and follow-up conditions.
The study is marked completed, but the registry record does not supply a single primary-outcome estimate or the statistical details needed to assess that estimate. The absence of a reported comparison should not be interpreted as evidence that the groups are equivalent. It means the posted record does not resolve the primary statistical question in a single comparative result.
13. Why This Trial Matters Statistically
This study illustrates a recurring statistical challenge in early-phase safety research: clinically important adverse events may be uncommon, while the number of participants available to observe them is limited. With planned enrollment of 20 and posted groups of 5 and 15, a count of zero serious events can be described, but it offers limited information about the precision of an underlying risk estimate. Reporting uncertainty is important alongside raw counts.
It also shows why an outcome definition matters. The primary endpoint includes incidence and severity across ocular and systemic adverse events, with several named examples and other events identified through examinations, subject reporting, and vital-sign changes. A collection of event types cannot automatically be interpreted as one coherent numerical comparison. The registry record does not reduce these components to a single result, so readers should keep the outcome's breadth in view.
The combined 1.0 mg or 2.0 mg group is another statistical consideration. A grouped result can summarize the record, but it cannot show dose-specific patterns. The record's single-group model label alongside descriptions of randomized dose groups further emphasizes the importance of transparent design and analysis reporting. These features are not reasons to infer an unreported result; they are reasons to interpret the displayed counts cautiously.
Finally, completed status and posted counts are not substitutes for a clear statistical analysis plan, defined analysis population, missing-data account, and interval estimates. This trial is useful as an example of how much can and cannot be learned from descriptive safety figures when the primary comparison is not reported in a reduced, uncertainty-aware form.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
A key limitation is the small planned enrollment of 20, reflected in the posted adverse-event groups of 5 and 15. The serious-event count is zero in both groups, and the registry does not provide confidence intervals or another estimate of precision. This makes it difficult to assess the range of risks compatible with the observations.
The higher-dose group combines participants receiving 1.0 mg or 2.0 mg. The registry does not report how many received each dose, so its adverse-event counts cannot be interpreted as separate dose-specific results. The intervention descriptions also permit rescue options at investigator discretion if criteria are met, but use of those options is not reported in the registry record.
The registry lists randomized allocation and double masking, but does not describe the allocation procedure or how masking was maintained. It also labels the model as single group despite presenting two dose groups, and does not explain the classification. These reporting details limit the ability to reconstruct the design from the record alone.
The primary outcome is not reduced to one comparison, and the registry does not report an inferential result, analysis population, missing-data method, or multiplicity strategy. The listed secondary outcomes do not have results. Follow-up completion and participant flow beyond the group counts are not reported in the registry record. These limitations restrict both statistical interpretation of the safety findings and assessment of how completely the posted results address the study's planned outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety Study of 2.0mg Lucentis to Treat Polypoidal Choroidal Vasculopathy — NCT01469156.
- Registry record last updated 2022-12-12; status last verified 2022-11.
- Results first posted 2022-12-12.
- 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
This completed Phase I/II study examined intravitreal ranibizumab for polypoidal choroidal vasculopathy. The registry lists randomized allocation, double masking, a planned enrollment of 20, and a primary safety outcome comparing the 1.0 mg or 2.0 mg group with the 0.5 mg group over 2 years. The study summary describes three monthly doses, a 9 month period of criteria-based, as-needed retreatment, and 12 month of drug safety follow up.
The posted serious adverse-event counts are 0 affected among 5 at risk in the 0.5 mg group and 0 among 15 at risk in the higher-dose group. Other adverse-event counts are 2 among 5 and 9 among 15, respectively. The primary outcome is not reduced to one comparison, and statistical methods, precision estimates, missing-data handling, and results for the listed secondary outcomes are not reported in the registry record. The higher-dose group combines 1.0 mg and 2.0 mg, so the posted figures do not distinguish those doses.