Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas (NCT00782626), a na phase 2 study. The primary outcome is Overall Response.

2. Clinical Question

This is a question about observed disease status during treatment, rather than a comparison of outcomes between assigned treatments. The response classification used MRI evaluations and specified lesion-based criteria. Without the response counts, analysis estimates, or uncertainty measures, the posted information does not establish how often each response category occurred or how precise any estimate was. The record also does not report a comparator against which the observed disease course could be evaluated.

3. Trial Design

The registry describes a phase II study sponsored by Dana-Farber Cancer Institute. It was a single-group, non-masked study of everolimus in children with chemotherapy- and/or radiation-refractory progressive or recurrent low-grade gliomas. Allocation is listed as NA, and the study is not a randomized comparison. Enrollment is recorded as 23. The study status is completed; its recorded start was 2009-06 and its primary completion was 2012-08.

Participants received oral everolimus. The stated course was 5.0 mg/m2/day for a 28-day treatment course, with treatment permitted for up to 12 courses (48 weeks) if disease was stable, unless toxicity was unacceptable. Dose reductions were permitted. The registry does not report how many participants received each dose, how long participants remained on treatment, or how many completed the planned courses.

Disease evaluations used brain MRI, including volumetric analysis. They were scheduled at baseline, at the end of course 1, every 3 courses during treatment up to 12 courses, and at early treatment discontinuation. This schedule describes intended assessment times; the record does not provide attendance, evaluability by visit, or the timing of individual participants’ recorded responses.

The primary endpoint was overall response, categorized as complete response, partial response, stable disease, or progressive disease. The analysis population is described as all evaluable patients, with all treated patients considered evaluable. The record does not report a separate control arm, masking, a statistical analysis plan, or analysis entries. As a single-group study, its observed outcomes would describe participants treated in this study; the design alone cannot separate treatment effects from other explanations for observed disease status.

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:

Analysis population for the primary outcome, as defined in the registry: The analysis dataset is comprised of all evaluable patients. All treated patients were evaluable.

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 Overall Response, measured over Disease evaluations (MRI brain, including volumetric analysis) occurred at baseline, at the end of course 1, every 3 courses during treatment up to 12 courses and at early treatment discontinuation..

The primary endpoint, overall response, classifies participants’ disease status on therapy as complete response, partial response, stable disease, or progressive disease. It is based on brain MRI evaluations, including volumetric assessment. The registry defines target-lesion volume using an elliptical model based on three dimensions and allows assessment of up to 5 target lesions.

In the registry definition, complete response requires disappearance of all target and non-target lesions and no new lesions. Partial response requires at least 65% decrease in the sum of the products relative to baseline. Progressive disease requires a 40% or greater increase in any target lesion relative to the smallest product observed on therapy. Stable disease is defined as meeting none of those response or progression criteria. Partial response and stable disease classification also require no new lesions and no unequivocal progression of non-target lesions; otherwise, the classification is progressive disease.

A categorical endpoint can distinguish degrees of observed disease status rather than reducing the assessment to a single continuous measurement. It is useful for describing whether imaging assessments meet prespecified response or progression definitions. However, the categories do not by themselves show the magnitude or durability of change for each participant. The registry record does not report the counts in each category, an overall response estimate, or uncertainty around an estimate. Thus, the endpoint definition is available, but its observed result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies overall response as a binary-kind outcome with participants as the unit and counts as the intended meaning. The response definition itself has four possible categories: complete response, partial response, stable disease, and progressive disease. The presence of a defined endpoint does not mean its observed distribution is available. The registry record contains no analysis entries and does not report category counts or an overall response estimate.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimate. A narrow interval indicates greater precision under the assumptions used for the analysis; a wide interval indicates less precision. An interval does not resolve limitations in study design, measurement, or missing reporting, and it cannot create a comparison group where none exists. No confidence interval for overall response is reported in the registry record, so the precision of a response estimate cannot be assessed.

What can a single-group design estimate?

In general, a single-group study can describe outcomes observed among participants who received the study treatment. It does not directly estimate a randomized contrast with a concurrent control group. An observed response proportion, if reported, would be a description of this study population and its assessment process. It would not by itself establish what would have happened to comparable participants under another treatment or without the study treatment. Here, even a descriptive response proportion is not reported in the registry record.

How should the response categories be understood?

The endpoint uses lesion measurements and prespecified classification rules. Complete response, partial response, stable disease, and progressive disease are not interchangeable outcomes: each represents a different imaging classification. The partial-response rule uses a decrease in the summed products relative to baseline, while the progression rule uses an increase in any target lesion relative to the smallest product observed on therapy. Stable disease is the category for assessments meeting none of the response or progression criteria, subject to the stated conditions concerning new lesions and non-target lesions. These are endpoint definitions, not reported findings about participants.

Repeated imaging assessments can characterize disease status over treatment, but the registry gives no participant-level trajectories, response duration, or analysis of change over time. The listed assessment schedule specifies baseline, the end of course 1, assessments every 3 courses up to 12 courses, and assessment at early discontinuation. It does not report whether every scheduled assessment was completed or how measurements were handled when assessments were unavailable.

What do the planning assumptions mean?

The registry describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. These are planning conventions, not evidence that this single-group trial was designed with two randomized arms. The record does not report numerical sample-size illustrations or the observed effect on which such illustrations would depend. The illustrations therefore cannot be interpreted as the trial’s enrollment target, observed power, or a post hoc demonstration that the study could detect an effect.

In general, a planning calculation asks how much information a future design might need under specified assumptions. Its output depends on the assumed effect and design, and does not demonstrate that a study had a particular probability of detecting an effect after its results are known. No observed power should be inferred from a planning illustration. No trial-specific sample-size justification or further statistical design rationale is reported in the registry record.

What does over-dispersion mean in general?

Over-dispersion is a general concern for count outcomes when variability exceeds what a chosen statistical model assumes. In such cases, a model that understates variability can produce uncertainty estimates that are too narrow. This concept does not establish that over-dispersion occurred in this study. The primary outcome is described as participants with an event, and the registry does not report a model-based count analysis or an over-dispersion assessment.

More broadly, the registry record does not report a statistical model, adjustment variables, hypothesis tests, or a method for estimating uncertainty for the primary response endpoint. No inferential method should be attributed to the study beyond the information recorded. The methods needed to evaluate whether response classifications differed by participant characteristics, or whether outcomes changed across assessments, are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, overall response, and no analysis entries. It does not report a multiplicity procedure or explain how multiple analyses, endpoints, or time points were handled. The assessment schedule includes repeated MRI evaluations, but the registry record does not specify how those repeated assessments were incorporated into a single primary result. It would be inappropriate to assume a particular adjustment, hierarchy, or selection rule.

The analysis population is described as all evaluable patients, and the record states that all treated patients were evaluable. This is the only population rule reported for the primary outcome. The record does not describe how missing imaging assessments, incomplete measurements, or early discontinuations were handled for analysis. It does not report imputation, sensitivity analyses, or a missing-data assumption. The assessment schedule includes evaluation at early treatment discontinuation, but that schedule does not establish that all such evaluations were available or how absent measurements were treated.

Missingness matters because the interpretation of a response summary can depend on whether participants without an assessment are excluded, classified in a particular category, or handled with another method. Those approaches can lead to different summaries. Since no response counts or missing-data method are reported in the registry record, readers cannot assess the impact of missing assessments on the primary outcome.

The record does not report an analysis plan, interim analyses, or a sample-size justification. These items are not inferable from a phase II label or from the fact that a primary endpoint is named. Their absence from the registry record limits assessment of how the outcome analyses were planned and whether reported analyses, if any, followed prespecified methods.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: muco/stomatitis by exam, oral cavity (8.7%), vomiting (8.7%), fatigue (4.3%), infection-other (4.3%), vascular access,thrombosis/embolism (4.3%).

For the everolimus group, the registry records 23 participants at risk for serious adverse events and 6 affected. For other adverse events, it records 23 at risk and 22 affected. These are participant counts, not counts of every event episode, and they do not indicate how many events each affected participant experienced. The registry does not report a deaths value.

The listed serious adverse-event terms include muco/stomatitis by exam, oral cavity and vomiting, each recorded as 8.7%; fatigue, infection-other, vascular access, thrombosis/embolism, and neutrophils, each recorded as 4.3%. These percentages are reproduced as listed. The terms should be read as registry categories; they do not provide details about onset, duration, severity grading, recurrence, or whether an event was judged related to treatment. The list does not establish that unlisted events did not occur.

There is no control group, so the counts do not support a comparative safety estimate. The registry record also does not report a complete narrative of adverse events or the rules used to determine attribution. These figures describe the recorded safety information, not a full comparison of treatment risks.

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

The record establishes that a phase II, single-group study examined everolimus in children with chemotherapy- and/or radiation-refractory progressive or recurrent low-grade gliomas. It specifies an imaging-based overall-response endpoint and records selected safety counts. It does not report the primary response results. Therefore, the record does not show how many participants had complete response, partial response, stable disease, or progressive disease.

That absence is not evidence that the treatment produced no responses, nor is it evidence that responses occurred. It means the registry record does not provide the outcome values needed to describe the primary result. No estimate or uncertainty interval is reported, so the size and precision of any response estimate cannot be assessed from this information.

The study also lacks a comparison arm. As a result, the design cannot supply a randomized treatment contrast. In general, outcomes recorded during treatment in a single group may reflect several influences, and a treated-group outcome alone cannot identify the effect attributable to treatment. This design limitation remains even if outcome counts are available; in this record, the primary outcome counts are unavailable as well.

The safety data indicate that adverse events were recorded among participants in the everolimus group, including the serious-event counts and listed terms. Those figures do not establish comparative safety or explain each event’s clinical course. The record does not report a deaths value, so no conclusion about deaths should be drawn from that field.

Accordingly, the defensible interpretation is narrow: the registry describes a treatment regimen, an imaging-based response definition, and selected adverse-event figures, but it does not report the primary response result or the statistical analyses needed to quantify it. Conclusions about treatment benefit, comparative effects, or the precision of a response estimate are not supported by the registry record.

13. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported endpoint result are both necessary for statistical interpretation. The registry gives detailed criteria for complete response, partial response, stable disease, and progressive disease, along with an MRI assessment schedule. These details help explain what the investigators intended to measure. Without category counts or an analysis estimate, however, readers cannot determine the observed distribution of outcomes or its precision.

The single-group design is also important. It can provide a description of outcomes among treated participants, but it does not create a concurrent control comparison. This distinction matters whenever the scientific question concerns whether an intervention changed outcomes relative to an alternative. The design and the registry’s absence of primary outcome results together leave no basis for estimating a comparative response effect from the posted information.

The record separates several kinds of information that should not be conflated: enrollment, the stated analysis population, outcome definitions, and observed outcomes. Enrollment of 23 and the statement that all treated patients were evaluable do not reveal how many participants met each response category. Similarly, a detailed assessment schedule does not reveal whether all scheduled measurements were obtained or how missing measurements were handled.

The safety information shows why participant counts and adverse-event terms need context. Counts describe participants recorded as affected, while the listed terms and percentages offer selected category-level information. Without a comparator and fuller details of timing, severity, and attribution, these figures cannot answer comparative safety questions.

For biostatistical reading, the key lesson is to distinguish a protocol-like endpoint definition from a posted result, and a planning convention from a trial’s observed analysis. A study can have an informative design description while leaving the central outcome and its uncertainty unreported in the registry record.

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 that the registry record does not report the primary response counts or any analysis entries. The endpoint is described, but no observed distribution across complete response, partial response, stable disease, or progressive disease is available. No response estimate or confidence interval is reported. This prevents assessment of the primary outcome’s magnitude and precision.

The single-group design has no like-for-like control comparison. It can describe outcomes in the treated group but cannot, by itself, distinguish treatment-associated outcomes from other influences on disease status. The absence of a comparator also limits interpretation of the safety counts as comparative risks.

The record states that all treated patients were evaluable, but it does not explain how missing imaging data or incomplete assessments were handled. Nor does it report participant-level response timing, response duration, treatment completion, or the number of assessments available at each scheduled evaluation. These omissions limit evaluation of the endpoint’s measurement and follow-up.

The registry provides selected adverse-event counts and terms, but does not report event timing, duration, severity grading beyond the serious-event grouping, attribution, or a deaths value. The listed serious terms are not a complete account of all safety experience. The record also does not report a statistical analysis plan, multiplicity method, or interim analysis details. These elements should be treated as not reported in the registry record, rather than inferred from the study phase or design.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas — NCT00782626.
• Registry record last updated 2018-08-15; status last verified 2018-07.
• Results first posted 2016-02-02.
• 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

The registry describes a completed phase II, single-group study of oral everolimus for children with chemotherapy- and/or radiation-refractory progressive or recurrent low-grade gliomas. Enrollment is recorded as 23. The primary endpoint is overall response by MRI-based criteria, with all treated patients described as evaluable. The registry record does not report response-category counts or analysis entries, so the primary response result and its precision cannot be determined from the posted information.

Safety information records 6 participants affected by serious adverse events and 22 affected by other adverse events, each among 23 at risk. Selected serious-event terms and percentages are listed, while the deaths value is not reported in the registry record. Because the study has no comparison group, these safety figures are descriptive rather than comparative.