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 Pilot Study of Lucentis Combined With Proton Beam Irradiation in Treating Wet Age-related Macular Degeneration (NCT00517010), a na early/phase 1 study. The primary outcome is Incidence and Severity of Ocular Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00517010 |
| Phase | EARLY/Phase 1 |
| Condition | Age-related Macular Degeneration |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, Davis |
| Results posted | Yes |
2. Clinical Question
Population
People with wet, also described in the record as exudative, age-related macular degeneration. The registry record reports an enrollment of 6 participants.
Intervention
Proton beam irradiation combined with intravitreal ranibizumab, marketed as Lucentis. The record describes 24Gy of proton radiation in 2 fractions, with radiation given within 6 weeks of the first ranibizumab dose. Treatment also included four monthly ranibizumab doses and monthly prn ranibizumab thereafter.
Comparator
There was no separate comparator group. The study is recorded as single-group, with allocation listed as NA and masking as none.
Primary question
What incidence and severity of ocular adverse events would be recorded during 24 months of follow-up after treatment with the combination? The primary outcome description says events identified by eye examination would be recorded and assessed for a possible or probable relation to study treatment.
The study is a pilot focused on safety and tolerability, not a randomized test of whether combination treatment is more effective than ranibizumab alone. The registry summary says the motivation was to evaluate the combination before considering a larger study of comparative effectiveness, if no major safety issues were associated with it. That statement describes the rationale, not a result from this trial.
A secondary outcome is change in best-corrected visual acuity from baseline. However, results for that outcome are not reported in the registry record. The record also does not report numerical results for the primary ocular adverse-event outcome. The available adverse-event counts can therefore be described, but they do not establish the full incidence or severity profile of ocular events over the stated follow-up.
3. Trial Design
The registry record identifies this as an early phase 1 pilot study, with a completed status. Its official title describes a phase 1, pilot, open-label, prospective observational study of safety and tolerability. The design entries list a single group, no masking, and allocation as NA. Enrollment was 6 participants. The recorded condition is age-related macular degeneration.
All participants were assigned to the combined-treatment group in the record: proton beam irradiation with ranibizumab. The intervention description specifies 24Gy of proton radiation in 2 fractions, administered within 6 weeks of the first intravitreal ranibizumab dose. It also specifies four monthly doses of intravitreal Lucentis and monthly prn Lucentis thereafter. There is no listed monotherapy group or untreated group.
The primary outcome is incidence and severity of ocular adverse events over 24 months. Events identified by eye examination were to be recorded and assessed for possible or probable relation to study treatment. Change in best-corrected visual acuity from baseline is listed as a secondary outcome. Numerical results for these outcomes are not reported in the registry record.
The registry records a start of 2007-05 and primary completion of 2010-06. These dates describe the study record, but they do not supply details about the timing of individual participants’ visits or duration of their actual follow-up. The rationale describes this as an initial safety study that could inform whether a larger comparative study might be conducted. The registry record does not report a sample-size justification, a protocol for a later study, or further details of how the pilot was intended to inform one.
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 | Lucentis Combined With Proton Beam |
|---|---|
| STARTED | 6 |
| COMPLETED | 5 |
| NOT COMPLETED | 1 |
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 | Lucentis Combined With Proton Beam |
|---|---|---|
| Participants analysed | 6 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 6 |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 4 |
| Best corrected visual acuity | logMAR best corrected visual acuity | 0.58 (SD 0.26) |
| Optical coherence tomography central macular thickness | microns | 335 (SD 67) |
6. Primary Endpoint
The registry lists the primary outcome as Incidence and Severity of Ocular Adverse Events, measured over 24 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | number of adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled incidence and severity of ocular adverse events. The record describes it as a number of adverse events, with a 24-month timeframe. Ocular events identified by eye examination were to be recorded, then assessed for a possible or probable relation to study treatment. Thus, the endpoint is intended to capture safety events observed during follow-up, rather than a direct measure of visual benefit.
General statistical context: safety outcomes matter in early-phase studies because an intervention may produce harms that need to be characterized before larger or comparative research is considered. Recording events and assessing their possible relation to treatment are separate tasks: the event count describes what was observed, while a relation assessment is an attribution judgment. Such an assessment does not by itself prove that treatment caused an event or rule out other explanations.
The posted registry record does not include a numerical result for the primary endpoint, a breakdown of ocular event types, or severity categories. It does include adverse-event figures indicating that no participants were recorded as affected by serious adverse events or by other adverse events. Those participant counts do not supply the missing event-level description or a severity distribution for ocular events over 24 months. The endpoint’s stated purpose and its available results therefore need to be distinguished.
Best-corrected visual acuity change from baseline is listed separately as a secondary outcome. The registry record does not report its numerical result. Without those results, the listed secondary endpoint cannot be used to characterize the observed visual-acuity course.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study enrolled 6 participants in a single group receiving proton beam irradiation combined with ranibizumab. In the adverse-event figures, 0 of 6 participants were affected by serious adverse events, and 0 of 6 were affected by other adverse events. These counts describe the participants recorded in those categories; they do not establish that no ocular events of any kind occurred, because the registry record does not give event-level results for the primary ocular endpoint.
The primary outcome was intended to capture incidence and severity of ocular adverse events over 24 months, but its numerical result is not reported in the registry record. Neither the types of ocular events nor their severity distribution are reported. The adverse-event summary therefore offers a limited safety description rather than a complete report of the prespecified primary outcome. The count of participants affected in the broad adverse-event categories should not be treated as an event count for every ocular outcome.
The design also limits comparative interpretation. Because there was no separate comparator group, the record cannot estimate how the observed outcomes compare with ranibizumab alone or with another treatment. With no masking and no random allocation, the study was not structured to provide a like-for-like comparison. These design features are consistent with a small pilot focused on safety and tolerability, but they prevent a causal comparative interpretation of outcomes.
The registry lists change in best-corrected visual acuity from baseline as a secondary outcome, but does not report its result. Consequently, the available record does not permit a numerical account of visual acuity change or a comparison of such change with another group. The study rationale mentions the possibility of a later larger study to evaluate comparative effectiveness; that motivation is not evidence that effectiveness was established in this pilot.
General statistical context: a count of zero affected participants in a small group is compatible with several underlying levels of risk. When few participants are observed, a rare event may simply not occur in that group, and the estimate is imprecise. The observed count is still worth reporting accurately, but it should not be interpreted as proof that risk is absent. A registry result also depends on what was defined and captured; a missing event breakdown cannot be reconstructed from the participant-level counts.
The registry record lists 0 analyses. This means the record does not report analysis results through that entry; it does not establish that no analyses were conducted outside the registry. No confidence interval, statistical test, or adjusted estimate is reported in the record. Accordingly, interpretation rests on the design description and the limited adverse-event counts, not on a comparative treatment-effect estimate.
9. Statistical Methods Explained
The design determines what statistical conclusions the study can support. This record describes a single-group, open-label study with allocation listed as NA and masking listed as none. Participants received the combination of proton beam irradiation and ranibizumab; no parallel control group is recorded. Results can therefore describe outcomes within the treated group, but cannot provide a randomized estimate of how those outcomes differ from outcomes under another treatment.
What does a single-group design estimate?
General statistical context: a single-group study can describe the outcomes observed among its participants, such as event counts or changes over follow-up. It does not directly identify what would have happened to those same participants under a different treatment. That unobserved alternative is the counterfactual comparison needed to estimate a treatment effect. Without a comparison group, observed outcomes may reflect treatment, the underlying course of the condition, participant characteristics, co-interventions, or other factors. The registry record does not report a design intended to separate those influences.
Open-label status means that masking is recorded as none. General statistical context: knowledge of treatment can influence reporting, clinical assessment, or decisions about whether an event is considered related to treatment. An eye examination is the stated way ocular events were identified, but the record does not describe masking of outcome assessors or other procedures that might limit assessment bias. Further details are not reported in the registry record.
How should the adverse-event counts be understood?
The registry adverse-event figures report participant counts: 6 participants at risk and 0 affected in the serious-event category, and 6 at risk and 0 affected in the other-event category. These are not the same as a full listing of event episodes. A participant may experience more than one event, and a participant-level count does not show event type, timing, severity, or attribution. The primary endpoint calls for ocular events to be recorded and assessed for possible or probable relation to treatment, but event-level results and those assessments are not reported in the registry record.
General statistical context: an observed zero is a sample result, not proof that the underlying risk equals zero. In a small group, uncommon events may not appear during observation. Precision depends on the amount and completeness of information, and no confidence interval for adverse-event risk is reported. Nor does the record supply the event-level detail needed to assess how the adverse-event figures correspond to the primary ocular endpoint.
What do the planning assumptions mean?
The record describes sample-size calculations as planning illustrations based on an observed effect, not as the trial’s own design. It states assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the stated calculation convention is total events, while other outcomes are expressed as participants per arm.
These assumptions do not describe the actual single-group study, which has no two-arm allocation. Any two-arm planning illustration is therefore a hypothetical framework, not evidence that the pilot used that design. The calculations are explicitly planning illustrations, not observed power. General statistical context: power is a design property tied to assumptions about a future study, including its target effect, variability, allocation, and analysis. It cannot be inferred from whether a result is statistically significant, and a planning calculation based on an observed effect should not be presented as the probability that this completed study detected an effect. The calculation outputs and specific effect values are not reported in the registry record.
The record does not report a sample-size justification for enrolling 6 participants, the method used to select the target enrollment, or assumptions used in the original study design. Those omissions matter because enrollment size affects the precision of estimates. The trial’s 6 participants are the observed enrollment, whereas hypothetical sample sizes for a future comparison would be planning quantities and must not be confused with observed enrollment or outcome evidence.
What can be inferred from the listed outcomes?
The primary outcome is a number of ocular adverse events within 24 months. A count outcome is naturally expressed as event counts, but interpretation requires knowing what events were counted, how observation time was handled, and whether each participant contributed the same follow-up. The registry record does not report those details or the primary numerical result. The secondary outcome, change in best-corrected visual acuity from baseline, would describe a within-participant change if results were reported. No numerical result, variability estimate, or analysis method for that outcome is reported.
General statistical context: a confidence interval communicates the range of estimates that are reasonably compatible with the observed data under a specified statistical model. It conveys precision as well as direction and magnitude; a point estimate alone does not show how uncertain an estimate is. No confidence interval for the listed outcomes is reported in the registry record. A p-value, if available, would address compatibility with a specified null model, not prove that a treatment caused an outcome. The record reports no such test result, and no comparative treatment-effect estimate can be derived from the single-group design.
Why can event variability matter?
General statistical context: event-count data can be more variable than a simple model assumes, especially when event rates differ across participants or follow-up conditions. Over-dispersion means the observed variability exceeds that expected under the chosen count model; ignoring it can make uncertainty appear smaller than it is. Assessing over-dispersion requires event counts and an analysis model. The registry record does not report such a model or the detailed data needed to assess it, so no conclusion about over-dispersion is warranted.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary outcome of incidence and severity of ocular adverse events and a secondary outcome of change in best-corrected visual acuity from baseline. It also reports 2 outcome measures, but numerical results for the listed outcomes are not reported in the registry record. The record lists 0 analyses. This does not establish that no analyses were performed; it means analysis results are not reported through that registry entry.
Multiplicity concerns arise when several outcomes or statistical tests are examined. General statistical context: testing multiple outcomes can increase the chance of at least one apparently notable result by chance, so a prespecified hierarchy or adjustment may be used to guide interpretation. The registry record does not report a multiplicity strategy, a hierarchy beyond the primary and secondary labels, or details of which statistical tests were planned. No inference about adjustment should be made from the outcome labels alone.
Missing-data handling is not reported in the registry record. In particular, the record does not explain whether all enrolled participants completed follow-up, how incomplete visits were handled, or whether any outcome observations were missing. The adverse-event figures list 6 participants at risk, but do not establish completeness of every scheduled assessment or outcome measure. The record also does not describe imputation, exclusion rules, or sensitivity analyses for missing observations.
Analysis populations are not reported in the registry record. There is no description of an intention-to-treat population, a per-protocol population, or another analysis set. The enrollment count alone should not be taken as proof that every participant contributed to every outcome analysis. Without the population definitions and outcome-specific denominators, the relationship between enrollment, follow-up, and analysis cannot be fully assessed.
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 |
|---|---|---|---|
| Lucentis Combined With Proton Beam | 0 | 6 | 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 |
|---|---|
| Lucentis Combined With Proton Beam | 0 of 6 |
The registry adverse-event figures report 0 participants affected by serious adverse events among 6 at risk, and 0 participants affected by other adverse events among 6 at risk. These figures are participant counts, not a detailed enumeration of every event episode. The record lists no serious adverse-event terms. Deaths are not reported in the registry record.
These figures should be read narrowly. They describe no affected participants in the reported categories for this enrolled group; they do not establish that the risk of an adverse event is absent. The registry’s primary endpoint specifically concerns ocular adverse-event incidence and severity over 24 months, but its numerical results, event types, and severity breakdown are not reported in the registry record. It is therefore not possible to determine from these figures alone whether all ocular events were captured in the adverse-event categories or how events were assessed for possible or probable relation to treatment.
General statistical context: a zero count in a small study can coexist with nonzero underlying risk, particularly for uncommon events. The count is an observation from 6 participants, not a precise estimate of risk. No confidence interval or event-level analysis is reported. The safety figures are useful as a limited description of what was recorded, but they cannot support a broad claim about safety beyond this group and the reported categories.
12. What the Result Does, and Does Not, Mean
The record documents a completed early phase 1 pilot with 6 participants receiving ranibizumab combined with proton beam irradiation. Its stated primary purpose was to assess safety and tolerability, with ocular adverse events as the primary outcome over 24 months. The adverse-event summary records 0 participants affected by serious events and 0 affected by other events among 6 at risk. These are the available participant-level counts, not a complete account of ocular event types or severity.
The primary endpoint’s numerical result is not reported in the registry record, and the secondary result for change in best-corrected visual acuity from baseline is also not reported. The record therefore cannot establish the observed incidence and severity of ocular events across the stated follow-up or describe visual-acuity change. The listed outcome definitions are not substitutes for outcome results.
This study also does not compare the combination with ranibizumab alone. There is no separate comparator group, and the design is recorded as single-group, open-label, and without masking. As a result, the outcomes cannot establish a comparative treatment effect or distinguish treatment effects from other explanations. The rationale refers to a possible larger study of comparative effectiveness, but this pilot’s registry information does not show that such a comparison occurred.
General statistical context: small studies are often useful for describing feasibility or identifying signals that merit further study, but estimates from small groups are imprecise, especially for uncommon events. Absence of recorded events in a small sample does not prove that an event cannot occur. Conversely, the limited adverse-event counts do not imply that an unreported event occurred. The appropriate conclusion is constrained by what the registry reports, not by assumptions about missing outcome details.
The record does not report confidence intervals, statistical tests, or analysis methods for the outcomes. No numerical effectiveness estimate can be obtained from the listed information. The planning assumptions associated with sample-size illustrations are not the trial’s actual design and are not observed power. Overall, the registry supports a description of the pilot’s design and its reported adverse-event counts, while leaving important outcome results and analysis details unreported.
13. Why This Trial Matters Statistically
This trial is statistically notable because its safety question and its design are aligned more closely than a comparative effectiveness question would be. A single-group pilot can record what happened among participants exposed to a combination treatment. It cannot, without a comparator, determine how those outcomes differ from what would have occurred under ranibizumab alone or another strategy. Keeping those questions distinct is essential when interpreting early-phase evidence.
The small enrollment of 6 also makes precision a central issue. General statistical context: rare events may not appear in a small study even when they remain possible, and an observed zero does not show that the underlying risk is zero. Event-level information and uncertainty estimates are needed to understand how informative a zero count is. Those details are not reported for the primary ocular endpoint in the registry record.
The difference between a prespecified outcome and a reported result matters as well. The registry defines incidence and severity of ocular adverse events over 24 months, yet the primary numerical result, event types, and severity details are not reported. The secondary visual-acuity outcome is listed but also has no numerical result. Readers should not treat an outcome’s presence in a registry as evidence that its result is available or interpretable.
Finally, planning calculations must be separated from the observed study. The record describes hypothetical sample-size illustrations using two-arm assumptions, while the actual design is single-group. Those illustrations can concern future planning, but they do not alter the study design, demonstrate observed power, or supply evidence of a treatment effect. This distinction helps prevent a planning framework from being mistaken for a result from the pilot.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation is the absence of a comparator group. Outcomes in the combined-treatment group cannot be contrasted with outcomes under ranibizumab alone, so comparative effects are not estimable from this design. The record also lists no masking. For an outcome involving eye examinations and judgments about possible or probable treatment relation, lack of masking may leave room for assessment or attribution influences; additional safeguards are not reported in the registry record.
Enrollment was 6 participants. This is a limited basis for characterizing uncommon safety events, and the record provides no confidence intervals or other uncertainty estimates. The adverse-event figures report no affected participants in the serious and other categories, but do not give event-level descriptions, ocular event severity, or a numerical result for the primary endpoint. Deaths are not reported in the registry record.
The registry lists change in best-corrected visual acuity from baseline as a secondary outcome, but its result is not reported. Follow-up completion and outcome-specific denominators are not described, nor are missing-data procedures or analysis populations. The record therefore does not clarify whether every enrolled participant contributed complete data to each outcome.
The registry record also does not report a sample-size justification, detailed statistical analysis methods, a multiplicity approach, or a confidence interval for any outcome. Its sample-size illustrations use planning assumptions for a hypothetical two-arm framework, unlike the actual single-group design. These gaps limit assessment of precision, analysis choices, and the relationship between planned and reported outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pilot Study of Lucentis Combined With Proton Beam Irradiation in Treating Wet Age-related Macular Degeneration — NCT00517010.
- Registry record last updated 2016-07-11; status last verified 2016-06.
- Results first posted 2016-07-11.
- 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
NCT00517010 is a completed early phase 1 pilot study sponsored by the University of California, Davis. It enrolled 6 participants with age-related macular degeneration and recorded a single-group, open-label design, with allocation listed as NA and no masking. The intervention combined proton beam irradiation with intravitreal ranibizumab.
The primary outcome was incidence and severity of ocular adverse events over 24 months. Change in best-corrected visual acuity from baseline was listed as a secondary outcome. Numerical results for these outcomes are not reported in the registry record. The adverse-event figures record 0 participants affected by serious adverse events and 0 affected by other adverse events among 6 at risk.
With no comparator group, the study does not provide a randomized comparative estimate. The record does not report confidence intervals, outcome analysis methods, missing-data handling, or analysis populations. The reported adverse-event counts should therefore be read as limited descriptive information, not as a complete account of the primary endpoint or a general estimate of risk.