Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex (NCT00411619), a na phase 1, phase 2 study. The primary outcome is Number With Observed Adverse Side Effects.

2. Clinical Question

The study was intended to evaluate safety and potential side effects in people with tuberous sclerosis complex and astrocytoma, while also considering possible tumor-volume change. Its single-group structure makes the safety counts descriptive: they show what was recorded among participants receiving everolimus, not how those counts compare with an untreated or differently treated group. The registry record does not report a randomized comparison or an estimate of the difference between treatment strategies.

3. Trial Design

This was a Phase 1 and Phase 2 study of everolimus (RAD001) in people with tuberous sclerosis complex and subependymal giant cell astrocytoma. The registry lists an enrollment of 28, the sponsor as Children's Hospital Medical Center, Cincinnati, and the study status as completed. The recorded study start is 2007-01, and the primary completion is 2014-01.

The design is listed as single group, with allocation not applicable and no masking. The arm description says the study was non-randomized and open-label, and that all patients received everolimus. Accordingly, the observed safety outcomes are outcomes recorded in one treated group. There is no concurrent control arm in the registry record against which to distinguish effects associated with treatment from events that might also occur in the underlying clinical setting.

The primary outcome is titled Number With Observed Adverse Side Effects and has a timeframe of the entire study. Overall Reduction in SEGA Tumor Volume is listed as a secondary outcome. The registry record lists two outcome measures, but numerical results for tumor-volume change are not reported in the record information available for this analysis. The listed adverse-event counts are therefore the main numerical results addressed below.

The record does not report a detailed protocol, treatment schedule, dose, eligibility criteria, follow-up schedule, or reasons for participant withdrawal. Those details should not be inferred from the Phase 1 and Phase 2 designation or from the study duration. The record also does not report a statistical analysis plan or analysis entries. As a result, the design can be described from its listed features, but the planned handling of outcomes and analysis populations cannot be reconstructed.

Because there is no randomized comparison, the study is not a like-for-like test of everolimus against another intervention. The trial can describe what occurred among the participants included in the reported safety counts, but its structure does not by itself support a causal comparison of treatment strategies.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number With Observed Adverse Side Effects, measured over During the entire study.

The primary outcome is the number of participants with observed adverse side effects during the entire study. It is a binary participant-level outcome: each participant is counted according to whether an adverse side effect was observed, rather than by the total number of separate events. This kind of count is useful for describing how many participants in a treated group had a recorded safety event over the stated observation period.

The registry’s safety results distinguish serious adverse events from other adverse events. In the everolimus group, the serious-event count is 9 of 28 participants, while the count for other adverse events is 28 of 28. These are descriptive counts for the group; they are not a comparison with a control group. The registry record does not report a confidence interval or a comparative effect estimate for the primary outcome.

As a general statistical point, a participant-level count avoids treating multiple events in the same person as though they came from separate people. It does not, by itself, describe how many events each participant had, how long each event lasted, or how severe events were beyond the serious-versus-other classification. The outcome title does not specify a more detailed event definition, and such a definition is not reported in the registry record.

The overall reduction in SEGA tumor volume is listed as a secondary outcome, but numerical results for that outcome are not reported in the registry record. The safety endpoint and the tumor-volume outcome answer different questions; the safety counts cannot be used as evidence of tumor-volume change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study and reports participant counts for adverse events. The key statistical distinction is between describing outcomes in one group and comparing outcomes between groups. The listed safety counts address the first task only. Because there is no randomized control group, there is no between-group contrast to interpret.

What does a participant count represent?

A binary participant-level outcome records whether each participant had at least one event of the specified type during the stated observation period. The serious adverse-event result is reported as 9 affected participants among 28 at risk. The other adverse-event result is reported as 28 affected participants among 28 at risk. These counts do not give the total number of events: a participant with several events still contributes one affected participant to a participant-level count.

As a general statistical concept, a proportion is a way to summarize a binary outcome by relating the number of participants with the event to the number assessed. The registry record supplies the affected and at-risk counts, but no confidence intervals for these outcomes. A confidence interval is a range expressing uncertainty around an estimate under a specified model and method. Its absence means the precision of the reported counts is not quantified by an interval in the record.

Why does the design matter?

In a randomized comparison, groups are assigned by chance, supporting a structured comparison of outcomes between treatment strategies. This study is listed as non-randomized, open-label, and single arm. All participants received everolimus, so the observed counts cannot be contrasted with a concurrent control group. The study design therefore supports a descriptive account of recorded outcomes but not a controlled estimate of the difference attributable to treatment.

Open-label means the record lists no masking. As a general consideration, knowledge of treatment assignment can affect how symptoms are reported, assessed, or recorded. The registry record does not describe outcome-assessment procedures, so the extent to which assessment might have been influenced cannot be determined. This possibility is a methodological consideration, not evidence that reporting was biased in this study.

What can be said about event categories?

The record lists serious adverse-event terms with percentages. It does not provide enough detail to determine whether the listed categories overlap at the participant level, whether each percentage represents people or events, or whether all event types are included in the list. For that reason, the percentages should be read as reported for their individual terms and not combined. The serious and other adverse-event participant counts are separate summaries, not a breakdown that can be used to infer the number of unique events.

As a general statistical point, over-dispersion matters when event counts vary more between participants than a simple count model assumes. A participant-level yes-or-no outcome does not report repeated-event counts, so over-dispersion cannot be assessed from these figures. The registry record does not report a model for recurrent events or a method for accounting for within-participant clustering.

What do the planning assumptions mean?

The study record includes planning assumptions for an illustrative sample-size calculation: two-sided significance level 0.05, equal allocation between two arms, normal approximation, and an effect defined as a stated fraction of the observed effect. These assumptions describe a planning illustration, not the design of this single-group study. The registry record does not report a trial-specific sample-size justification, and no calculated planning sample sizes are stated in the registry record for this analysis.

As a general statistical concept, a sample-size calculation asks how many participants might be needed to detect an effect under chosen assumptions. It does not measure the probability that a completed study’s finding is correct, and a planning illustration based on an observed effect is not observed power. The two-arm equal-allocation assumption does not match the recorded single-arm design, so it should not be interpreted as a description of how participants were assigned in this trial.

What analysis details are absent?

The registry record does not report an analysis plan, confidence intervals, hypothesis tests, adjustment methods, or analysis populations. It lists zero analysis entries. The record also does not report how missing observations were handled or whether any participants were excluded from particular outcomes. Without those details, it is not possible to assess whether the reported counts followed a prespecified analysis or how sensitive they might be to missing data or analytic choices.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures: the primary count of participants with observed adverse side effects and the secondary outcome of overall reduction in SEGA tumor volume. It does not report a detailed statistical analysis plan, a hierarchy for testing outcomes, or a multiplicity adjustment. Therefore, it is not possible to determine whether any formal adjustment for examining more than one outcome was planned or used. The presence of multiple outcomes alone does not establish that multiple hypothesis tests were performed.

The record lists zero analysis entries. No test statistics, p-values, confidence intervals, or model-based estimates are reported for the outcomes described in the registry record for this analysis. Numerical tumor-volume results are not reported in the registry record, so the secondary outcome cannot be evaluated from the posted information.

The safety counts include 28 participants at risk for serious adverse events and 28 at risk for other adverse events. These denominators do not supply a missing-data method or establish the completeness of every measurement. The registry record does not report the number of participants with missing outcome data, how missingness was defined, whether participants withdrew, or whether any imputation or other missing-data procedure was used.

The record also does not specify an analysis population, such as whether outcome summaries were based on all enrolled participants or another defined set. It does not state how participants who did not complete follow-up were handled. These omissions make it difficult to judge whether the reported safety counts represent a complete follow-up assessment for the enrolled group. No particular handling of missing observations or analysis population should be inferred from the counts alone.

As a general statistical consideration, multiplicity can increase the chance of at least one apparently notable result when several hypotheses are tested. Whether that concern applies in a specific way depends on the tests and analysis plan, which are not reported in the registry record. The appropriate conclusion is limited to the available descriptive safety counts and the absence of numerical results for tumor-volume change.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abscess limb (7.1%), cellulitis (7.1%), convulsion (7.1%), bronchitis viral (3.6%), gastroenteritis (3.6%).

The registry reports serious adverse events in 9 of 28 participants at risk in the everolimus group. It reports other adverse events in 28 of 28 participants at risk. These are counts of participants affected, not totals of separate event episodes. The record lists Abscess Limb, Cellulitis, and Convulsion at 7.1% each among the serious adverse-event terms, and Bronchitis Viral, Gastroenteritis, and Leukocytosis at 3.6% each.

The event-term percentages should be read individually. The registry record does not establish that the categories are mutually exclusive, so the percentages should not be summed. Nor does the list necessarily describe every adverse event experienced by participants. The record does not report a death count.

As a general statistical point, a safety count describes what was observed and recorded under the study’s ascertainment procedures. It does not, without a comparison group and further information, show how many events were caused by treatment or how the frequency would differ under another treatment. The single-group, open-label design makes these results descriptive. The record does not report a detailed event definition, attribution procedure, or analysis of event timing and duration, so those features cannot be assessed from the counts.

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

The registry record supports a limited, descriptive conclusion about safety: it reports serious adverse events affecting 9 of 28 participants and other adverse events affecting 28 of 28 participants in the everolimus group. It also lists several serious-event terms with their reported percentages. These observations describe the recorded experience of participants in this single-group study.

They do not show how the same participants would have fared without everolimus or with another treatment. Since the study had no concurrent control group and was not randomized, the recorded counts cannot estimate a comparative increase or decrease in risk. They also cannot establish that everolimus caused any specific event. A causal interpretation would require evidence beyond a one-group event count.

The study description presents a hypothesis that tumor size could decrease, and the registry lists overall reduction in SEGA tumor volume as a secondary outcome. However, a numerical result for tumor-volume change is not reported in the registry record. The safety findings therefore do not answer whether tumor volume changed, nor do they establish the size or precision of any such change.

The record does not report confidence intervals or other measures of uncertainty for the safety counts. As a general statistical principle, uncertainty matters because an observed count is an estimate of outcomes in the group under observation, not a guarantee of the frequency that would be seen in another group or setting. Without reported uncertainty intervals, the precision of these findings cannot be quantified from the registry record.

The absence of reported analysis details also limits interpretation. The record does not describe missing-data procedures, analysis populations, or a prespecified statistical plan. Those omissions do not invalidate the counts, but they limit assessment of completeness and analytic choices. The results should be understood as registry-reported observations, not as a controlled demonstration of benefit or harm.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a safety description and a comparative treatment estimate. A single-group study can record the number of participants who experience adverse events during observation. It cannot, by design alone, tell whether that number is higher or lower than it would have been under another treatment strategy. The lack of a concurrent control group is therefore central to interpreting the registry’s safety counts.

The record also illustrates why an outcome’s label and measurement matter. The primary outcome is a participant count for observed adverse side effects over the entire study. The secondary outcome concerns overall reduction in SEGA tumor volume, a distinct question for which numerical results are not reported in the registry record. Safety summaries cannot substitute for an efficacy outcome, and a stated tumor-response hypothesis is not a reported result.

Precision and transparency are important alongside the counts themselves. The record gives affected and at-risk participant numbers, but no confidence intervals, analysis entries, or detailed missing-data and analysis-population information. Readers can identify what was counted, but cannot fully assess uncertainty or the analysis choices behind the results.

The planning assumptions included in the record also highlight the distinction between a hypothetical sample-size illustration and the study’s actual design. The listed illustration assumes two equally allocated arms, while the trial is recorded as single group. Planning calculations should not be read as observed evidence or as proof that a study had adequate precision. These design and reporting distinctions help keep conclusions aligned with what the registry actually reports.

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 limitation for interpretation is the single-group, non-randomized, open-label design. All participants received everolimus, and the registry record does not provide a concurrent control arm. The adverse-event counts therefore cannot support a like-for-like treatment comparison or isolate treatment effects from other possible explanations.

The reported safety summaries are participant counts, not detailed event histories. The registry record does not report event onset, duration, recurrence, severity beyond the serious-versus-other classification, or attribution to treatment. The listed serious-event terms may overlap, and the record does not specify whether the displayed terms represent all serious events. A death count is not reported in the registry record.

The numerical information available for the primary safety outcome does not include confidence intervals or a detailed analysis. The registry record lists zero analysis entries and does not report a statistical analysis plan, missing-data methods, or analysis populations. Although both safety categories have 28 participants at risk, the record does not establish that all participants completed the same follow-up or had complete data for every outcome.

The secondary outcome of overall reduction in SEGA tumor volume is listed without a numerical result in the registry record. No conclusion about tumor-volume change or its precision can therefore be drawn from the posted information. The record also does not report details such as treatment schedule, dose, eligibility criteria, or follow-up procedures. These omissions restrict assessment of how the results were generated and to whom they may apply.

Finally, the planning illustration assumes equal allocation between two arms, unlike the recorded single-group study. It should not be used to characterize the trial’s design, observed precision, or statistical power. A trial-specific sample-size justification is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex — NCT00411619.
• Registry record last updated 2014-10-20; status last verified 2014-10.
• Results first posted 2014-10-20.
• 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

NCT00411619 is a completed Phase 1 and Phase 2, non-randomized, open-label, single-group study of everolimus (RAD001) in people with tuberous sclerosis complex and subependymal giant cell astrocytoma. The registry lists 28 participants enrolled and identifies Children's Hospital Medical Center, Cincinnati as the sponsor.

The primary outcome is the number of participants with observed adverse side effects during the entire study. Serious adverse events affected 9 of 28 participants, and other adverse events affected 28 of 28. The record lists several serious-event terms with percentages. Overall reduction in SEGA tumor volume is listed as a secondary outcome, but its numerical result is not reported in the registry record.

Because there is no concurrent control group, the safety counts are descriptive and do not estimate a comparative treatment effect. The record does not report confidence intervals, an analysis plan, analysis populations, or missing-data methods.