Sunitinib Malate to Treat Advanced Eye Disease in Patients With Von Hippel-Lindau Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sunitinib Malate to Treat Advanced Eye Disease in Patients With Von Hippel-Lindau Syndrome (NCT00673816), a na phase 1, phase 2 study. The primary outcome is Change in Best Corrected Visual Acuity (BCVA) From Baseline to Week 36.

2. Clinical Question

This was a pilot investigation of a systemic treatment for retinal angiomas associated with Von Hippel-Lindau syndrome. The clinical question focused on visual acuity, while secondary ocular assessments concerned retinal thickness, angioma leakage, and visual field changes. The record also lists changes in non-ocular Von Hippel-Lindau lesion status among the secondary outcomes. These measures address different aspects of disease status; they are not interchangeable ways of measuring the primary visual-acuity endpoint.

Because the design had a single group and no control condition, any recorded change over time would describe participants during the study rather than establish what would have happened without treatment. In general, a control group helps distinguish treatment-associated change from other influences, including the natural course of a condition and measurement variability. The registry record does not provide an outcome analysis that could answer even the within-group question for the primary endpoint.

3. Trial Design

The registry describes a Phase 1 and Phase 2 study with a single-group model and no masking. It was open-label, meaning that treatment was not masked from participants or study personnel in the registered design. Allocation was listed as not applicable. There was no randomized comparison and no like-for-like control arm. The study was sponsored by the National Eye Institute (NEI).

The study description characterizes the project as a pilot of systemic sunitinib malate in participants with Von Hippel-Lindau syndrome and retinal angiomas. The intended enrollment in the brief summary was five participants; the registry enrollment field reports 2. These are different pieces of information: the former is the planned number in the study description, while the latter is the enrollment recorded by the registry. The record does not state why enrollment was lower than the intended number.

The treatment plan described 9 months of therapy in 6 cycles. Each cycle consisted of 50 mg taken orally once daily for 4 weeks, followed by a 2-week rest period. The arm description says participants were expected to receive this regimen; the registry does not provide participant-level information about treatment received, adherence, dose changes, or exposure.

The study start is recorded as 2008-05 and primary completion as 2011-02. Its status is terminated. The reason for termination, the date of termination, and whether the intended follow-up was completed are not reported in the registry record. A terminated status alone does not explain why the study stopped or establish what happened to participants.

The primary outcome was change in best-corrected visual acuity from baseline to Week 36. Secondary outcomes included retinal thickness, leakage intensity and area by fluorescein angiography, visual field changes documented by microperimetry, and non-ocular lesion status. The registry lists 6 outcome measures but does not report an outcome analysis. With a single group and limited enrollment, the design is best read as exploratory; it cannot provide a randomized estimate of comparative treatment effect.

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

Reasons for not completing this period:

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 Change in Best Corrected Visual Acuity (BCVA) From Baseline to Week 36, measured over Baseline and 36 Weeks.

The primary endpoint is change in best-corrected visual acuity from baseline to Week 36, measured in ETDRS letters. The ETDRS protocol uses letters read on a standardized eye chart as a measure of visual acuity. The registry description notes that the letter score corresponds to Snellen measurements and gives an example in which reading between 84 and 88 letters is equivalent to 20/20 vision.

The study summary identifies a change of at least 15 letters from baseline to Week 36 as the primary threshold of interest. This threshold defines the change the study planned to focus on; it does not tell whether any participant reached it. The posted registry results do not give an observed change, a participant-level count meeting the threshold, a group summary, or an uncertainty interval for this endpoint. The endpoint result is therefore not reported in the registry record.

In general, a standardized measure can make assessments more consistent and interpretable across visits. A baseline-to-follow-up change focuses on how a measured value differs over time for participants assessed at both time points. Such a change does not, by itself, show that an intervention caused the change, especially in a single-group study without a concurrent control. Visual acuity is only one aspect of ocular status; the registered secondary outcomes were intended to describe other aspects, including retinal structure, angioma leakage, and visual field. Those outcomes also lack reported analyses in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes this as a single-group, open-label study, with Phase 1 and Phase 2 listed. These features describe different parts of the design. A phase label indicates the registered development stage, while the model and masking fields describe the structure of the study and whether treatment was masked. None of these labels supplies an outcome result. The registry does not report a statistical analysis plan, so the intended statistical tests, models, covariate adjustments, and handling of incomplete measurements are not reported in the registry record.

What does a single-group design estimate?

In general, a single-group study can describe outcomes observed among participants over time. For a baseline-to-follow-up endpoint, an analysis might summarize changes among those with measurements at both visits. Such a summary is not a randomized comparison: there is no untreated or alternative-treatment group measured over the same period to provide a counterfactual comparison. A counterfactual is the outcome that would have occurred for the same participants under a different treatment condition; it cannot be directly observed for an individual. Randomized control groups help estimate that contrast at the group level.

For this trial, the registry identifies a baseline-to-Week-36 visual-acuity outcome but provides no corresponding analysis. It does not specify whether the planned analysis would use individual change scores, a model comparing visits, or another method. Those details are not reported in the registry record. It would therefore be inappropriate to attribute any particular statistical procedure to the investigators.

What is the role of the outcome threshold?

The study summary states that the primary outcome of interest was a change of at least 15 ETDRS letters from baseline to Week 36. In general, a threshold can define a clinically or scientifically meaningful response criterion, while the underlying measurement can also be summarized as a continuous value. A threshold-based result might report how many participants meet the criterion; a continuous summary might describe the magnitude and spread of change. The registry does not report either form of primary result. It also does not report a rationale for selecting the threshold.

Thresholds can simplify interpretation but discard information about how far an observation lies from the cutoff. A person just short of a threshold and a person with little change can be placed in the same non-responder category, even though their measured changes differ. Conversely, a threshold classification does not reveal the distribution of values within the group meeting it. These are general properties of threshold-based analyses, not findings from this study.

How should uncertainty be understood?

In general, a point estimate describes the value calculated from observed data, while a confidence interval describes uncertainty around that estimate under the assumptions of the analysis. A narrow interval is usually more precise than a wide interval, but precision does not by itself guarantee that an estimate is unbiased or that a causal interpretation is justified. The registry record does not report a primary outcome estimate or confidence interval, so neither the magnitude nor the statistical precision of visual-acuity change can be assessed.

A small sample typically offers limited information for estimating a population pattern, and individual observations can strongly influence a group summary. That general concern is particularly relevant when interpreting an enrollment of 2. However, no outcome values are available to determine the influence of any participant's measurement. No uncertainty interval can be reconstructed from the registry information without inventing or deriving unreported data.

What do the planning illustrations mean?

In general, sample-size calculations are planning exercises based on assumptions about the effect to detect, variability, significance level, power, and allocation. The registry's stated assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. These are described as planning assumptions, not as the original design of this single-group trial. They should not be read as observed power or as evidence that the study had a particular probability of detecting an effect.

Power is a design property calculated under specified assumptions. It is not a probability that a result is true, nor is a retrospective calculation based on an observed estimate a substitute for the outcome analysis. Planning illustrations can help show how required sample size would vary under assumptions, but they do not change the actual design or supply a control group. The record does not report the trial's own sample-size justification. The primary outcome result is also not reported, so the observed effect on which an illustration would be based cannot be independently evaluated from the posted results.

Why do multiple outcomes matter?

The registry lists a primary outcome and secondary outcomes spanning retinal thickness, leakage intensity and area, visual fields, and non-ocular lesion status. In general, analyzing multiple outcomes can increase the chance of finding at least one apparently notable result by chance, especially when many hypotheses are tested. Multiplicity refers to this family of related statistical questions. Methods such as prespecifying a primary endpoint, adjusting significance thresholds, or using hierarchical testing can address multiplicity in different ways. The registry record does not report whether any such approach was planned or used.

The presence of multiple listed outcomes does not establish that all were measured, completed, or analyzed. No analysis results are reported for these outcomes. Thus, there is no basis to compare their results, assess consistency across measures, or determine whether a multiplicity adjustment affected interpretation.

What can the safety counts tell readers?

Adverse-event counts are descriptive registry entries. In general, an event count indicates how many participants are recorded as having an event, while an at-risk count gives the denominator used for that listing. These counts do not necessarily describe how many individual events occurred: one participant can have more than one event. They also do not establish causation. The record's serious-event and other-event counts are reported separately, but event terms and detailed timing are not provided. A count without event descriptions cannot characterize the clinical nature or severity of the experiences.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary visual-acuity endpoint and secondary ocular and non-ocular outcomes. It does not report how the investigators planned to address multiple statistical comparisons. In general, testing several outcomes can make chance findings more likely across the collection of tests. A statistical plan may define a primary endpoint, specify an order of testing, or use an adjustment, but whether any such strategy was used is not reported in the registry record. The lack of posted analyses means there are no results with which to assess multiplicity in practice.

Missing-data handling is also not described. The registry does not report whether all enrolled participants had Week 36 assessments, how missing measurements were treated, or whether any imputation or sensitivity analysis was performed. These details matter because the participants with observed follow-up may differ from those without it. In general, an analysis based only on available measurements can be biased if missingness is related to outcome or treatment experience; the direction and magnitude of any such bias depend on circumstances not given.

Analysis populations are not described. The record does not specify whether analyses were intended to include all enrolled participants, only those who received treatment, or only those with an endpoint assessment. There is no reported participant flow, outcome-specific denominator, or analysis set definition. It is therefore not possible to determine which participants would have contributed to an endpoint estimate or whether the analyzed population would have matched the enrolled population.

The registry lists zero analyses, and outcome results are not reported. Accordingly, multiplicity procedures, missing-data assumptions, and analysis-population choices cannot be evaluated. The absence of these details is not evidence that a particular method was or was not used; it means these methods are not reported in the registry 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events affecting 0 of 2 participants at risk in the Sunitinib Malate group. It lists other adverse events affecting 2 of 2 participants at risk. These are participant counts in separate categories, not counts of all event episodes. The record does not list the serious adverse-event terms, and it does not provide descriptions or severity details for the other adverse events.

The deaths field is not populated with a number, so deaths are not reported in the registry record. A blank or unavailable death entry should not be interpreted as a reported count of zero. The record also does not provide timing, duration, attribution to treatment, or information about how adverse events were collected. The counts therefore cannot establish whether events were caused by sunitinib malate.

In general, adverse-event counts describe what was recorded within a study's reporting system and depend on the definitions, observation period, and completeness of reporting. A count of participants with an event does not indicate how many events each participant had. With enrollment of 2, the safety figures are limited descriptive observations and do not establish a comparative safety profile. They should be read separately from the missing primary efficacy result.

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

The registry establishes that an open-label, single-group pilot study of sunitinib malate for advanced ocular disease associated with Von Hippel-Lindau syndrome was conducted and terminated. It records enrollment of 2, a planned primary assessment of best-corrected visual acuity at Week 36, and safety counts. It does not report the primary outcome result, secondary outcome analyses, or estimates of uncertainty.

As a result, the posted information does not show the direction or magnitude of visual-acuity change. It does not state whether any participant met the study summary's threshold of at least 15 ETDRS letters. It also does not report changes in retinal thickness, angioma leakage, visual fields, or non-ocular lesion status. No numerical conclusion about these outcomes can be drawn from the registry record.

Even if within-group changes had been reported, the design would not provide a randomized comparison with an alternative or no treatment. In general, an observed change from baseline can be consistent with several explanations, and a single-group study cannot separate treatment effects from other changes over time. The open-label design also means there was no masking as registered. These limitations do not negate the value of an exploratory pilot, but they constrain what it can establish.

The study description intended enrollment of five participants, while the registry enrollment field reports 2. The reason for the difference and the reason the study was terminated are not reported in the registry record. Neither the status nor the enrollment information explains the missing outcome data. The safety entries report no serious adverse events affecting the listed participants and other adverse events affecting both participants, but event details are not provided and the death count is not reported.

The appropriate conclusion is therefore limited: the registry documents the study's question, planned measures, design, enrollment, and sparse safety counts, but does not provide outcome analyses to answer its primary question. The record cannot establish that treatment did or did not change vision, nor can it support a comparative estimate of benefit or harm.

13. Why This Trial Matters Statistically

This study illustrates why design and reporting details are essential when reading a clinical trial record. The primary question concerns change in visual acuity, but the registry does not report the value or analysis. A named endpoint and a specified visit do not substitute for a result. Without the observed measurements and an account of who contributed them, readers cannot judge the direction, size, or precision of change.

The single-group structure is also statistically important. A baseline comparison may describe how measurements changed among participants, but it does not provide a randomized estimate of what would have happened under a different treatment condition. This distinction is central to causal interpretation. The open-label design and the absence of a control group limit what the design could establish, regardless of the statistical method used to summarize any available data.

The registry's enrollment of 2 highlights how little information a very small study can contribute to a population-level estimate. In general, small studies produce imprecise estimates and may be sensitive to individual observations. Here, the absence of outcome data prevents even a descriptive assessment of how the observed results varied. This is different from concluding that no effect occurred: the relevant outcome analysis is not reported.

The record also presents a useful distinction between a planned clinical threshold and an observed result. The threshold of at least 15 ETDRS letters defines an outcome criterion in the study summary; it does not tell how many participants met it. Likewise, planning calculations are not trial results or observed power. They depend on assumptions and cannot replace reported estimates with uncertainty measures.

Finally, the record shows why safety counts need context. Participant counts do not describe event types, timing, or causal attribution. With no event terms or detailed safety analyses reported, the figures remain limited descriptions. Together, these features make the study statistically informative as an example of the constraints imposed by missing results and a non-comparative design, rather than as a basis for a quantified treatment-effect conclusion.

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 outcome reporting is the most immediate limitation: no primary visual-acuity result or secondary outcome analysis is reported in the registry record. There are no numerical endpoint estimates, measures of variability, confidence intervals, or outcome-specific participant counts. The registry therefore does not permit assessment of the magnitude or precision of change, or whether the stated primary threshold was reached.

The recorded enrollment is 2, compared with the intended enrollment of five in the study summary. Reasons for the difference are not reported. The registry also does not state how many participants completed follow-up, whether participants discontinued treatment, or which measurements were available at Week 36. These omissions prevent evaluation of follow-up completeness and the population included in any potential analysis.

The study was open-label and single-group, with no concurrent control. A within-group change, if reported, would not by itself isolate an intervention effect from other influences over time. The registry does not describe masking of outcome assessors or other procedures to reduce assessment bias. The allocation field is listed as not applicable, consistent with the absence of a randomized comparison.

Other important details are not reported in the registry record, including the statistical analysis plan, sample-size justification, multiplicity strategy, missing-data methods, analysis populations, and reason for termination. The record also does not describe treatment adherence, dose modification, or participant-level exposure. Safety reporting lacks event terms and details, and deaths are not reported as a number. These are reporting gaps; they should not be filled by assumptions about what happened in the study.

Finally, the registered measures span visual function, retinal structure, leakage, and lesion status. Without outcome analyses, readers cannot evaluate whether these measures agreed or differed. The single-group design and limited enrollment would constrain interpretation even if results were available; the missing results make that interpretation impossible from the posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sunitinib Malate to Treat Advanced Eye Disease in Patients With Von Hippel-Lindau Syndrome — NCT00673816.
• Registry record last updated 2024-01-05; status last verified 2011-11.
• Results first posted 2011-12-19.
• 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

NCT00673816 is registered as a Phase 1 and Phase 2, open-label, single-group pilot study of systemic sunitinib malate for advanced ocular disease in people with Von Hippel-Lindau syndrome. The National Eye Institute (NEI) is listed as sponsor. The study start is recorded as 2008-05, primary completion as 2011-02, and status as terminated.

The brief summary describes intended enrollment of five participants, while the registry enrollment field reports 2. The planned regimen was 9 months, in 6 cycles of 50 mg orally once daily for 4 weeks followed by a 2-week rest period. The primary outcome was change in best-corrected visual acuity from baseline to Week 36, with secondary measures covering retinal and other disease outcomes.

The registry reports no outcome analyses. Serious adverse events affected 0 of 2 participants at risk; other adverse events affected 2 of 2. Event details and a death count are not reported in the registry record. The reason for termination is also not reported.