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 An Open-label Extended Clinical Protocol of Ranibizumab to Evaluate Safety and Efficacy in Rare VEGF Driven Ocular Diseases. (NCT01908816), a na phase 3 study. The primary outcome is Number of Participants With Adverse Events as a Measure of Safety and Tolerability.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01908816 |
| Phase | Phase 3 |
| Condition | Choroidal Neovascularization, Macular Edema, Glaucoma, Neovascular |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 270 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
The study asked whether ranibizumab’s safety and efficacy could be evaluated in people with rare VEGF-driven ocular diseases. Its primary outcome concerned the number of participants with adverse events as a measure of safety and tolerability. The record describes the safety outcome over 24 months, while noting that early termination led to descriptive analysis only.
Population
The study covered people with choroidal neovascularization, macular edema, neovascular glaucoma, or diabetic retinopathy. The registry lists an enrollment of 270. The safety population was defined as patients who received at least one application of study treatment and had at least one post-baseline safety assessment; a statement that a patient had no adverse events also counted as a safety assessment.
Intervention
The intervention was ranibizumab, described as 0.5 mg administered as an intravitreal injection of 0.05 mL. The regimen was individualized. The record does not give a uniform injection schedule, so the intervention should not be read as a fixed schedule shared by every participant.
Comparator
There was no randomized control comparison in the registry record. The study is classified as single-group, with allocation listed as not applicable and masking listed as none. The different disease groups are not a like-for-like control comparison; they represent different clinical conditions rather than randomized treatment arms.
Primary question
The primary question was descriptive: how many participants experienced adverse events, including serious adverse events, during the safety observation period? The record does not describe a comparative primary efficacy test. It lists secondary outcomes concerning visual acuity, disease-specific ocular measures, vitreous cavity hemorrhage, angiographic leakage, and ranibizumab injections, but the registry record does not report analyses for those outcomes.
Accordingly, the results address the recorded safety experience in the study population. They do not establish what would have happened under a different treatment or without ranibizumab, and they do not provide a randomized estimate of treatment effect.
3. Trial Design
This was a phase 3, open-label, single-group clinical study sponsored by Novartis Pharmaceuticals. The registry lists the study start as 2013-09-26, primary completion as 2016-01-08, and status as completed. Enrollment is listed as 270. Those are registry-level study details; they should not be interpreted as the number of people included in every outcome analysis.
Masking was listed as none, and allocation was listed as not applicable. The study therefore did not use a randomized, masked comparison as recorded in the registry. Ranibizumab was administered using an individualized regimen, described as 0.5 mg in 0.05 mL by intravitreal injection. The record does not report a common injection schedule or explain how individual regimens were selected.
The conditions included choroidal neovascularization, macular edema, glaucoma of neovascular origin, and diabetic retinopathy. The adverse-event results are presented under condition-specific group labels, including choroidal neovascularization, macular edema, rubeosis iridis/neovascular glaucoma, and proliferative diabetic retinopathy requiring vitrectomy. The record does not report whether participants could appear in more than one condition group, so these groups should not be treated as confirmed mutually exclusive cohorts.
The primary outcome was the number of participants with adverse events as a measure of safety and tolerability, with a timeframe of 24 months. The description states that the study terminated early and that only descriptive analysis was conducted. The registry record does not report a reason for early termination or provide a formal statistical analysis plan. It also does not report the intended sample-size justification, any interim analyses, or a prespecified comparative hypothesis.
Seven outcome measures are listed in the record. The secondary outcomes concern best corrected visual acuity for participants with choroidal neovascularization and macular edema, neovascularization extension in neovascular glaucoma, vitreous cavity hemorrhage in proliferative retinopathy, central retinal thickness, angiographic leakage, and ranibizumab injection. Although these measures are listed, the registry record does not report analyses for them.
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 | CNV (Choroidal Neovascularization) | ME (Macular Edema) | RI/NVG (Rubeosis Iridis and Neovacular Glaucoma) | PDR/V |
|---|---|---|---|---|
| STARTED | 93 | 84 | 58 | 35 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 93 | 84 | 58 | 35 |
Reasons for not completing this period:
| Reason | CNV (Choroidal Neovascularization) | ME (Macular Edema) | RI/NVG (Rubeosis Iridis and Neovacular Glaucoma) | PDR/V |
|---|---|---|---|---|
| Subject's no longer requires study drug | 0 | 0 | 0 | 1 |
| Protocol deviation | 1 | 2 | 1 | 1 |
| Withdrawal by Subject | 0 | 4 | 2 | 2 |
| Lost to Follow-up | 3 | 5 | 4 | 2 |
| Death | 1 | 0 | 7 | 1 |
| Unsatisfactory therapeutic effect | 1 | 13 | 1 | 0 |
| Early termination | 87 | 60 | 43 | 28 |
Analysis population for the primary outcome, as defined in the registry: Safety population: all patients who received at least one application of study treatment and had at least one post-baseline safety assessment. The statement that a patient had no adverse events also constituted a safety assessment. All safety evaluations were carried out on the safety population.
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.
Population: A total of 267 patients who received ranibizumab and had at least one post-baseline efficacy assessment were included in the ITT population.
| Characteristic | Unit | CNV (Choroidal Neovascularization) | ME (Macular Edema) | RI/NVG (Rubeosis Iridis and Neovacular Glaucoma) | PDR/V | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 93 | 84 | 56 | 34 | 267 | |
| Age, Continuous | Years | 49.7 (SD 16.85) | 64.5 (SD 13.99) | 70.9 (SD 13.02) | 56.5 (SD 9.86) | 59.7 (SD 16.62) |
| Sex: Female, Male: Female | Participants | 48 | 35 | 26 | 17 | 126 |
| Sex: Female, Male: Male | Participants | 45 | 49 | 30 | 17 | 141 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events as a Measure of Safety and Tolerability, measured over 24 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adverse events, used as a measure of safety and tolerability. Its description includes the frequency of adverse events and serious adverse events for ocular and non-ocular events. The stated timeframe is 24 months. The endpoint is a participant count: it records whether participants experienced events, rather than measuring the severity of a symptom on a continuous scale or the change in a laboratory measurement.
Safety outcomes are used to characterize the harms observed during treatment and follow-up. Looking at both serious and other adverse events can describe different levels of clinical seriousness, but the counts alone do not establish why an event occurred. The registry record does not state that the listed events were caused by ranibizumab, nor does it give a causal adjudication method.
The safety population includes patients who received at least one application of study treatment and had at least one post-baseline safety assessment. The description explicitly counts a statement that a patient had no adverse events as a safety assessment. This defines who was included in the safety evaluations; it is not necessarily identical to the enrollment figure or to the number represented in each condition-specific adverse-event listing.
The record states that early termination meant only descriptive analysis was conducted. Thus, the endpoint is presented as a summary of observed safety experience, not as a formal test against a control group. The record does not report an inferential estimate, confidence interval, or adjusted comparison for the primary endpoint. The endpoint can describe events recorded in the study, but it cannot by itself determine comparative risk or prove that treatment caused or prevented an event.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The adverse-event results should be read as descriptive counts within the condition-specific groups listed in the registry. For choroidal neovascularization, the record lists 11 participants with serious adverse events among 93 at risk, and 46 with other adverse events among 93 at risk; it lists 1 death. For macular edema, it lists 15 with serious adverse events among 84 at risk, and 66 with other adverse events among 84 at risk; it lists 0 deaths. For rubeosis iridis/neovascular glaucoma, it lists 31 with serious adverse events among 58 at risk, and 40 with other adverse events among 58 at risk; it lists 7 deaths. For proliferative diabetic retinopathy requiring vitrectomy, it lists 14 with serious adverse events among 35 at risk, and 21 with other adverse events among 35 at risk; it lists 1 death.
These are separate listings by condition. They should not be added together or interpreted as a single overall participant total: the registry record does not establish that the condition groups are mutually exclusive, and the reported at-risk counts differ by group. The serious-event and other-event counts are also distinct reported categories. The record does not specify whether a participant could contribute to both categories, nor does it provide event-level counts or a rule for handling repeated events. The counts therefore should not be treated as the number of unique events.
The registry lists ocular hypertension in the study eye as a serious adverse-event term at 12.1%, diabetes mellitus inadequate control at 8.6%, cardiac failure at 6.9%, retinal detachment in the study eye at 5.2%, glaucoma in the study eye at 3.4%, and vitreous haemorrhage in the contralateral eye at 3.4%. These are reported terms and percentages. The record does not specify their denominators or provide an attribution assessment for these terms, so they should not be converted into a broader causal claim about treatment.
The study was open-label and single-group, and the registry states that it was not a randomized comparison. As a result, the observed counts cannot be contrasted with a concurrent randomized control group to estimate how safety outcomes differed under another treatment or no treatment. Differences across the disease-specific listings are not treatment comparisons: the groups have different underlying conditions, and their composition and overlap are not reported.
The description says that early termination led to descriptive analysis only. No inferential analysis of the primary safety outcome is reported. The data can therefore be used to describe which adverse events and deaths were recorded in the listed groups, but they do not establish a comparative safety effect or explain the reasons for the observed events. The registry record does not report event timing, duration, severity grading beyond the serious/other distinction, or a causal assessment.
9. Statistical Methods Explained
What does a descriptive analysis tell the reader?
General explanation: a descriptive analysis organizes observed data without using a statistical test to decide whether a treatment differs from a comparator. Counts and percentages can show what was recorded in a study population. They do not, on their own, estimate what would have happened to the same participants under an alternative treatment. In this study, the registry explicitly says early termination led to descriptive analysis only. The listed safety counts should therefore be read as descriptions of the recorded experience, not as estimates from a randomized comparison.
The primary outcome is a participant count for adverse events. A participant-level count and an event-level count answer different questions. A participant-level count concerns how many people had an event, while an event-level count can include repeated events in the same person. The record identifies the primary outcome as the number of participants with adverse events, but does not provide event-level totals or a rule for repeated events. The posted counts should not be reinterpreted as counts of every separate event.
Why does the study design matter?
General explanation: randomization helps make groups comparable at the start of a study, on average, and a concurrent control group provides a reference for comparing outcomes. Masking can reduce the influence of expectations on reporting or assessment. This trial is listed as single-group, with allocation not applicable and masking none. It therefore does not provide the structure needed for a randomized treatment-versus-control estimate. The distinct disease groups cannot serve as substitutes for randomized controls because they are defined by different conditions rather than by assigned treatment.
Open-label status is relevant when interpreting adverse-event reporting. Knowledge of treatment can affect how symptoms are noticed, described, or assessed. That general possibility does not show that reporting was biased in this trial; the registry record does not report whether or how such effects were evaluated. The absence of masking should be understood as a design feature, not as proof that any specific result is inaccurate.
What is the role of the safety population?
The registry defines the safety population as patients who received at least one application of study treatment and had at least one post-baseline safety assessment. A statement that a patient had no adverse events counted as a safety assessment. This rule clarifies which patients were eligible for safety evaluation under the registry’s definition. The enrollment figure is a separate study-level detail, and the record does not say that every enrolled participant necessarily met the safety-population definition or contributed to every condition-specific listing.
General explanation: an analysis population is a stated set of participants used for an outcome analysis. Clear population definitions help readers understand which observations are included and how missing follow-up may affect interpretation. Here, the safety population is described, but the registry record does not report a participant flow, reasons for exclusion from safety evaluation, or the amount and pattern of missing safety assessments.
Why do denominators and condition groups need care?
The adverse-event listings provide a count at risk for each condition group. Those denominators are useful context for the associated participant counts, but they are not evidence that the groups are independent or non-overlapping. The record does not state whether a patient with more than one condition could appear in multiple groups. Accordingly, group-specific results should remain attached to their own labels rather than being combined into a study-wide total.
General explanation: a denominator defines the population against which a count or percentage is interpreted. If populations differ, direct comparisons can be misleading even when the numbers are presented in the same format. Differences among these condition-specific counts may reflect differences in the groups, their underlying diseases, or follow-up; the record does not provide the detail needed to separate such explanations.
What can significance tests and confidence intervals add?
General explanation: a significance test evaluates how compatible observed data are with a specified statistical hypothesis, under the assumptions of the model. A confidence interval describes the range of values compatible with the data and method, and can communicate precision. Neither automatically resolves bias, confounding, poor measurement, or lack of a suitable comparator. The registry record does not report inferential tests or confidence intervals for the primary safety outcome, and it says only descriptive analysis was conducted.
General explanation: over-dispersion matters when data vary more than a statistical model expects; using a model that assumes too little variability can make uncertainty appear smaller than it is. This is relevant to some count-data analyses, but the registry record does not report a count model or a dispersion assessment for this study. No model-based conclusion should be inferred from the adverse-event counts alone.
How should planning illustrations be distinguished from observed findings?
General explanation: sample-size planning calculations describe what a future study might require under stated assumptions. They are not evidence about how much power the completed study actually had. The planning assumptions associated with the posted illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of an observed effect. Those are planning assumptions, not the design of this single-group trial. The registry record does not report the trial’s sample-size justification, and the planning illustrations should not be presented as observed power or as proof that a treatment effect was detected.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures, including the primary safety outcome and secondary measures concerning visual acuity, neovascularization extension, vitreous cavity hemorrhage, central retinal thickness, angiographic leakage, and injections. Considering multiple outcomes can increase the chance that at least one result appears noteworthy by chance when formal testing is performed. General explanation: multiplicity procedures are methods for controlling or describing that issue, such as adjusting testing thresholds or identifying outcomes as exploratory.
The registry record does not report a multiplicity strategy, a hierarchy for testing secondary outcomes, or an inferential analysis of those outcomes. The primary outcome description says that early termination led to descriptive analysis only. No unreported adjustment or formal hypothesis-testing plan should be assumed. The secondary outcomes are listed, but the registry record does not report their analyses.
The safety population is defined as patients who received at least one application of study treatment and had at least one post-baseline safety assessment. The record says that an explicit statement of no adverse events counted as a safety assessment. It does not report details about missing data, the number of participants with incomplete assessments, reasons for missingness, or any imputation method. General explanation: missingness can affect descriptive summaries if the chance of having an observed assessment is related to health status or adverse events. Without further reporting, the direction or size of any such influence cannot be determined.
The record also does not report how participants who stopped treatment early were handled in each listed outcome, whether all participants were followed for the full stated timeframe, or how death affected other safety summaries. These omissions limit interpretation of the completeness and comparability of follow-up. They do not justify assuming either that data were complete or that a particular missing-data method was used.
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 |
|---|---|---|---|
| Choroidal Neovascularization | 11 | 93 | 11.8% |
| Macular Edema | 15 | 84 | 17.9% |
| Rubeosis Iridis/ Neovascular Glaucoma | 31 | 58 | 53.4% |
| Proliferative Diabetic Retinopathy Requiring Vitrectomy | 14 | 35 | 40.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Choroidal Neovascularization | 1 of 93 |
| Macular Edema | 0 of 84 |
| Rubeosis Iridis/ Neovascular Glaucoma | 7 of 58 |
| Proliferative Diabetic Retinopathy Requiring Vitrectomy | 1 of 35 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Choroidal Neovascularization | 46 of 93 |
| Macular Edema | 66 of 84 |
| Rubeosis Iridis/ Neovascular Glaucoma | 40 of 58 |
| Proliferative Diabetic Retinopathy Requiring Vitrectomy | 21 of 35 |
Most frequent serious adverse event terms
| Event term | Organ system | Choroidal Neovascularization | Macular Edema | Rubeosis Iridis/ Neovascular Glaucoma | Proliferative Diabetic Retinopathy Requiring Vitrectomy |
|---|---|---|---|---|---|
| Ocular hypertension (Study eye) | Eye disorders | 1 of 93 | 1 of 84 | 7 of 58 | 0 of 35 |
| Vitreous haemorrhage (Study eye) | Eye disorders | 0 of 93 | 2 of 84 | 2 of 58 | 1 of 35 |
| Cardiac failure | Cardiac disorders | 0 of 93 | 0 of 84 | 4 of 58 | 0 of 35 |
| Retinal detachment (Study eye) | Eye disorders | 0 of 93 | 0 of 84 | 3 of 58 | 1 of 35 |
| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | 0 of 93 | 0 of 84 | 1 of 58 | 3 of 35 |
| Cataract (Contralateral eye) | Eye disorders | 0 of 93 | 2 of 84 | 1 of 58 | 0 of 35 |
| Glaucoma (Study eye) | Eye disorders | 0 of 93 | 0 of 84 | 2 of 58 | 1 of 35 |
| Visual acuity reduced (Study eye) | Eye disorders | 1 of 93 | 0 of 84 | 1 of 58 | 1 of 35 |
| Intraocular pressure increased (Study eye) | Investigations | 0 of 93 | 1 of 84 | 2 of 58 | 0 of 35 |
| Renal failure | Renal and urinary disorders | 0 of 93 | 0 of 84 | 2 of 58 | 1 of 35 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Choroidal Neovascularization | Macular Edema | Rubeosis Iridis/ Neovascular Glaucoma | Proliferative Diabetic Retinopathy Requiring Vitrectomy |
|---|---|---|---|---|---|
| Inappropriate schedule of drug administration (Study eye) | Injury, poisoning and procedural complications | 11 of 93 | 21 of 84 | 4 of 58 | 1 of 35 |
| Drug ineffective (Study eye) | General disorders | 3 of 93 | 27 of 84 | 1 of 58 | 0 of 35 |
| Eye pain (Study eye) | Eye disorders | 6 of 93 | 5 of 84 | 7 of 58 | 3 of 35 |
| Headache | Nervous system disorders | 7 of 93 | 4 of 84 | 2 of 58 | 0 of 35 |
| Incorrect product storage (Study eye) | Injury, poisoning and procedural complications | 4 of 93 | 6 of 84 | 1 of 58 | 0 of 35 |
| Fatigue | General disorders | 2 of 93 | 3 of 84 | 4 of 58 | 0 of 35 |
| Visual acuity reduced (Study eye) | Eye disorders | 3 of 93 | 3 of 84 | 0 of 58 | 1 of 35 |
| Conjunctival haemorrhage (Study eye) | Eye disorders | 0 of 93 | 4 of 84 | 0 of 58 | 1 of 35 |
| Ocular hypertension (Study eye) | Eye disorders | 0 of 93 | 0 of 84 | 2 of 58 | 3 of 35 |
| Ulcerative keratitis (Study eye) | Eye disorders | 0 of 93 | 1 of 84 | 2 of 58 | 2 of 35 |
Serious events with the highest arm-level rate: ocular hypertension (study eye) (12.1%), diabetes mellitus inadequate control (8.6%), cardiac failure (6.9%), retinal detachment (study eye) (5.2%), glaucoma (study eye) (3.4%).
Each condition-specific listing gives the number at risk, the number of participants with serious adverse events, the number with other adverse events, and the recorded deaths. For choroidal neovascularization, the figures are 93 at risk, 11 with serious events, 46 with other events, and 1 death. For macular edema, they are 84 at risk, 15 with serious events, 66 with other events, and 0 deaths. For rubeosis iridis/neovascular glaucoma, they are 58 at risk, 31 with serious events, 40 with other events, and 7 deaths. For proliferative diabetic retinopathy requiring vitrectomy, they are 35 at risk, 14 with serious events, 21 with other events, and 1 death.
These are group-specific descriptive figures, not randomized comparisons. The registry record does not establish whether the groups overlap, whether the adverse-event categories can overlap, or whether the deaths were related to treatment. Deaths should not be added to the serious-event counts or interpreted as treatment-caused deaths: the record does not provide that relationship.
The listed serious-event terms include ocular and non-ocular events. Their percentages are recorded as reported, but the registry record does not specify their denominators in the presented summary. They describe reported event terms and do not, by themselves, show causation or comparative risk.
12. What the Result Does, and Does Not, Mean
The results mean that the registry records adverse-event counts and deaths for condition-specific groups in an open-label, single-group study of ranibizumab. The primary safety outcome was intended to describe the number of participants with adverse events, and the registry states that only descriptive analysis was conducted after early termination. The figures offer a record of observed safety events within the listed groups.
They do not show how these counts compare with a randomized control group, because the study did not have a randomized comparison. The condition groups are not equivalent treatment arms. Differences between their counts cannot be attributed to treatment, nor can they establish that one disease group had greater or lesser treatment-related risk than another. The record does not state that the listed adverse events or deaths were caused by ranibizumab.
The results also do not establish efficacy. The study’s stated purpose included evaluating safety and efficacy, and secondary outcome measures are listed, but the registry record does not report analyses for those secondary outcomes. The posted safety counts cannot substitute for results on visual acuity, retinal thickness, angiographic leakage, or the other listed measures.
General explanation: a treatment effect is a comparison between outcomes under alternative treatment conditions. A single-group description observes outcomes under the treatment regimen used, without observing a randomized concurrent alternative for the same study context. It therefore cannot separate treatment effects from the underlying disease course, other care, participant characteristics, or chance. This is a limitation of what the design can answer, not a claim that the recorded events are uninformative.
The record’s early-termination statement also matters: it says descriptive analysis only was conducted, but does not report the reason for termination or the completeness of follow-up. Taken together, the posted data are best understood as a descriptive account of safety observations and not as proof of benefit, proof of harm, or a comparative estimate of risk.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its stated goal spans safety and efficacy across rare VEGF-driven ocular diseases, while its primary reported outcome is a safety count. The conditions named in the record are clinically distinct, and the adverse-event results are organized by condition. That makes population definition and denominator discipline especially important: a count should be interpreted within its labeled group, and group totals should not be combined without knowing whether participants overlap.
The study also demonstrates why design labels shape interpretation. Open-label, single-group data can describe observed events, but they do not provide a randomized comparator for estimating a treatment contrast. When the registry further states that early termination led to descriptive analysis only, readers should distinguish the actual reported safety summaries from any inferential conclusion that the data do not support.
The participant-level endpoint is another useful statistical distinction. Counting participants with adverse events differs from counting every event, because a participant may experience more than one event. The registry identifies a participant count as the primary outcome but does not provide event-level totals or repeated-event handling. This illustrates why the unit of analysis and the population definition should be explicit when reading safety results.
Finally, the record lists secondary efficacy and disease-specific outcomes without reporting their analyses. A registered outcome list is not itself a result. Keeping the distinction between planned or listed measures and reported findings helps avoid treating an outcome’s presence in a registry as evidence that it was measured successfully or that a particular result was obtained.
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 registry record says the study terminated early and that only descriptive analysis was conducted, but does not report why termination occurred. It does not provide a formal statistical analysis plan, interim-analysis details, or a sample-size justification. Consequently, the timing and rationale for the descriptive approach cannot be evaluated from the registry entry.
The open-label, single-group design has no randomized comparator. The adverse-event listings therefore cannot estimate a comparative treatment effect. The record also does not report masking, independent event adjudication, or a method for attributing events to treatment. The listed deaths and serious adverse events should not be interpreted as treatment-caused without such information.
The condition-specific denominators differ, and the registry record does not state whether participants could appear in more than one group. It does not report whether serious and other adverse-event categories overlap, how repeated events were handled, or the denominators used for the listed serious-event percentages. These gaps prevent some broader summaries or cross-group comparisons from being justified.
Although the safety population is defined, the record does not report participant flow, the number with incomplete safety follow-up, reasons for missing assessments, or missing-data methods. It also does not say whether every participant was observed for the full 24 months. The effect of incomplete or unequal follow-up on the descriptive results therefore cannot be assessed from the registry record.
The registry lists secondary outcomes but does not report their analyses. It also does not report a multiplicity strategy. Thus, the posted safety data do not support conclusions about the secondary efficacy measures, and no unreported statistical testing should be inferred. These are limits of the available registry information, not evidence that a particular result or analysis did or did not occur outside the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Open-label Extended Clinical Protocol of Ranibizumab to Evaluate Safety and Efficacy in Rare VEGF Driven Ocular Diseases. — NCT01908816.
- Registry record last updated 2019-08-12; status last verified 2019-07.
- Results first posted 2019-08-12.
- 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
NCT01908816 is a completed phase 3, open-label, single-group study sponsored by Novartis Pharmaceuticals. The registry lists enrollment of 270 and identifies choroidal neovascularization, macular edema, neovascular glaucoma, and diabetic retinopathy among the conditions studied. Ranibizumab was administered as 0.5 mg in 0.05 mL by intravitreal injection using an individualized regimen.
The primary outcome was the number of participants with adverse events as a measure of safety and tolerability over 24 months. The record defines the safety population and lists serious and other adverse-event counts, along with deaths, by condition-specific group. It states that early termination meant only descriptive analysis was conducted.
The registry does not report a randomized comparison, inferential results for the primary safety outcome, analyses of the listed secondary outcomes, or details needed to establish causation. The findings therefore describe recorded safety events in this single-group study, rather than comparative treatment effects.