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 Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma (NCT00602667), a non-randomized phase 2 study. The primary outcome is Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00602667 |
| Phase | Phase 2 |
| Condition | Brain and Central Nervous System Tumors |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 293 |
| Arms in the primary outcome | n/a |
| Lead sponsor | St. Jude Children's Research Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The primary endpoint population consists of eligible medulloblastoma patients who started methotrexate. The registry record reports n=81 for this analysis. The broader trial concerns young children with newly diagnosed central nervous system tumors, including embryonal brain tumors, choroid plexus carcinoma, high grade glioma, and ependymoma.
Intervention
Patients received induction chemotherapy followed by therapy assigned according to risk group. The registry lists low-risk, intermediate-risk, and high-risk therapy, alongside induction chemotherapy. The study rationale describes chemotherapy that includes methotrexate and says most patients will also receive radiation, including focal conformal or proton beam radiotherapy.
Comparator
This is a non-randomized study. Its risk groups receive different risk-adapted regimens and are not like-for-like randomized treatment arms. The primary endpoint description reports PFS estimates by risk group, but a controlled comparison between those groups is not established by the design.
Primary question
The primary endpoint is the percent probability of progression-free survival for medulloblastoma patients, estimated at 1 year after treatment and reported by risk group. It concerns the time from treatment start to progression, relapse, medulloblastoma-related death, or last contact for patients without an event. Numerical PFS estimates are not reported in the registry record.
The broader clinical question is how risk-adapted chemotherapy and radiation are associated with disease control in young patients with several types of central nervous system tumors. The registry rationale describes chemotherapy as a way to allow more time for brain development before radiation, and notes a rationale for targeting radiation to the tumor area. Those statements explain the study’s motivation; they are not findings about benefit or cognitive outcomes from the posted results.
Because the population includes different diagnoses and risk groups, the primary endpoint is narrower than the full study population. Its stated analysis includes eligible medulloblastoma patients who received any methotrexate. Other secondary outcomes address survival compared with historical controls, response to induction chemotherapy, tumor molecular characteristics, sample collection, and toxicity-related delays. Numerical results for those secondary outcomes are not reported in the registry record.
3. Trial Design
This is a phase 2, non-randomized, parallel study with no masking. The registry lists enrollment of 293 and identifies St. Jude Children's Research Hospital as the sponsor. The study began on 2007-12-17, reached primary completion on 2017-09-27, and has a status of active, not recruiting.
Risk assignment determines which regimen patients receive. The low-risk description includes patients with GTR/M0 medulloblastoma, nodular desmoplastic histology, or high grade glioma histology; those patients receive induction chemotherapy and low-risk therapy. The record notes that accrual to the low-risk medulloblastoma cohort closed as of 12/2/2015, while accrual to the low-risk high grade glioma cohort remained open. Patients with CNS metastatic disease are described as receiving induction chemotherapy and high-risk therapy. The intermediate-risk description includes M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, as well as other histologic diagnoses without metastatic disease.
These groups reflect clinical risk categories and treatment pathways, not randomly allocated alternatives. Consequently, outcomes across groups may reflect differences in diagnosis, disease extent, and other characteristics as well as differences in regimen. The record does not describe a randomized treatment contrast, and the group outcomes should not be interpreted as if patients had been assigned to otherwise comparable arms.
The registry lists 82 outcome measures and 4 analyses. It does not report the protocol’s full statistical analysis plan, the details of risk assignment, or whether the stated enrollment is a target or a final enrollment figure. The primary endpoint population is specifically described as eligible medulloblastoma patients who started methotrexate, n=81; that endpoint population is not interchangeable with the broader trial enrollment.
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.
Before assignment: Of the 293 participants enrolled, 3 were ineligible and removed from study, leaving 290 eligible patients. Eighty-one (81) of the 290 eligible patients enrolled had histologically confirmed medulloblastoma; medulloblastoma patients are the focus of the primary study objectives.
Overall Study
| Stage | Low-Risk Group | Intermediate-Risk Group | High-Risk Group |
|---|---|---|---|
| STARTED | 57 | 156 | 77 |
| COMPLETED | 38 | 75 | 14 |
| NOT COMPLETED | 19 | 81 | 63 |
Reasons for not completing this period:
| Reason | Low-Risk Group | Intermediate-Risk Group | High-Risk Group |
|---|---|---|---|
| Still on Therapy | 0 | 2 | 2 |
| Death | 0 | 1 | 1 |
| Family request | 3 | 25 | 6 |
| Excessive toxicity | 1 | 1 | 0 |
| Second malignancy | 0 | 1 | 0 |
| Physician Decision | 2 | 3 | 8 |
| Progressive disease | 13 | 48 | 45 |
| Progressive disease prior to therapy | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All eligible medulloblastoma patients started methotrexate and were included (n=81). PFS estimates are reported by risk group.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Participants were patients with newly diagnosed tumors of the CNS, including medulloblastoma, supratentorial primitive neuroectodermal tumor (PNET), pineoblastoma, atypical teratoid rhabdoid tumor (ATRT), choroid plexus carcinoma, ependymoma, and high-grade glioma. All eligible patients enrolled were included in the baseline characteristics.
| Characteristic | Unit | Low-Risk Group | Intermediate-Risk Group | High-Risk Group | Total |
|---|---|---|---|---|---|
| Participants analysed | 57 | 156 | 77 | 290 | |
| Age, Continuous | months | 17.0 (SD 10.0) | 22.9 (SD 12.8) | 19.3 (SD 10.4) | 20.8 (SD 11.9) |
| Age, Continuous | months | 16.1 (0.2 to 35.2) | 21.9 (1.8 to 60.6) | 20.0 (0.9 to 36.9) | 20.1 (0.2 to 60.6) |
| Sex: Female, Male: Female | Participants | 22 | 66 | 43 | 131 |
| Sex: Female, Male: Male | Participants | 35 | 90 | 34 | 159 |
| Race/Ethnicity, Customized: Ethnicity – Mexican/Chicano | Participants | 0 | 5 | 2 | 7 |
| Race/Ethnicity, Customized: Ethnicity – NOS Spanish, Hispanic, Latino | Participants | 7 | 16 | 7 | 30 |
| Race/Ethnicity, Customized: Ethnicity – Non Spanish speaking, Non Hispanic | Participants | 47 | 120 | 64 | 231 |
| Race/Ethnicity, Customized: Ethnicity – Puerto Rican | Participants | 1 | 2 | 1 | 4 |
| Race/Ethnicity, Customized: Ethnicity – South or Central American | Participants | 0 | 2 | 0 | 2 |
| Race/Ethnicity, Customized: Ethnicity – Unknown | Participants | 2 | 11 | 3 | 16 |
| Race/Ethnicity, Customized: Race – American Indian/Alaskan/White | Participants | 1 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Race – American Indian/Alaskan Native | Participants | 0 | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Race – Asian | Participants | 3 | 6 | 1 | 10 |
| Race/Ethnicity, Customized: Race – Asian and White | Participants | 0 | 2 | 2 | 4 |
| Race/Ethnicity, Customized: Race – Black | Participants | 6 | 14 | 10 | 30 |
| Race/Ethnicity, Customized: Race – Black and White | Participants | 0 | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Race – Multiple Race (NOS) | Participants | 1 | 7 | 1 | 9 |
| Race/Ethnicity, Customized: Race – Other | Participants | 2 | 4 | 1 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients, measured over From date on treatment until date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percent Probability |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percent probability of progression-free survival (PFS) for medulloblastoma patients. The registry defines the interval from the date on treatment to the first progression, medulloblastoma-related death, or last contact for patients who have not experienced an event. Progression includes a 25% increase in the size of any measurable lesion, appearance of a new lesion, or a change from negative to positive cerebrospinal fluid cytology. The stated timeframe is an estimate at 1 year after treatment.
PFS is a time-to-event measure: it reflects how long patients remain free of the events specified in the endpoint definition. General statistical context: survival methods can use information from participants whose event has not been observed by their last contact, rather than treating their follow-up as if an event had occurred. Such observations are commonly described as censored. The registry definition refers to last contact for patients without an event, but the details of the estimation method and censoring rules are not reported in the registry record.
The endpoint is reported by risk group, which allows the registry to describe disease-course estimates in the distinct treatment pathways. It does not by itself establish a comparative treatment effect between groups. The numerical PFS estimates and their confidence limits are not reported in the registry record, so the magnitude and precision of the observed PFS cannot be assessed from the stated endpoint information alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome description specifies what is to be estimated, the patient population, and the event definition, but it does not give numerical PFS results. The record says that estimates are reported by risk group and identifies the analysis population as eligible medulloblastoma patients who started methotrexate (n=81). It does not report the group-specific probabilities or their 95% confidence intervals. Therefore, the posted information does not support a numerical description of PFS or a comparison of its magnitude across risk groups.
Even if group-specific estimates are available elsewhere in the registry, the design matters for interpretation. Treatment was not randomized, and risk groups correspond to different clinical profiles and treatment pathways. A difference between risk-group estimates would not isolate the effect of one regimen from differences in disease severity, histology, metastatic status, or other group characteristics. There is no like-for-like randomized control comparison in this trial.
The registry also lists event-free survival and overall survival compared with historical controls as secondary outcomes. Such comparisons can be informative descriptions, but historical controls are not concurrent randomized controls. The record does not report the specific historical cohorts, their comparability, or numerical results for those outcomes. Those details are not reported in the registry record.
Safety figures are given by low-, intermediate-, and high-risk groups. The record lists patients at risk and affected for serious events and other adverse events, and also lists deaths. These are descriptive counts within groups; they do not establish that treatment caused an event or death. The registry does not give the context needed to attribute deaths to disease, treatment, or another cause, and does not report comparative safety estimates adjusted for group differences.
Confidence intervals are listed as the dispersion measure for the primary endpoint, but their endpoints are absent from the registry record. General statistical context: a confidence interval communicates the uncertainty around an estimated quantity, and wider intervals generally indicate less precision. Without the actual estimates and intervals, it is not possible to judge whether the data are compatible with a broad range of PFS values or are relatively precise. No conclusion about efficacy, comparative benefit, or treatment effect should be inferred from the design description or the existence of a planned endpoint alone.
9. Statistical Methods Explained
The following statistical explanations are general; the registry record does not report all analysis details for this trial.
What does the primary endpoint represent?
PFS is a time-to-event outcome. Each eligible patient contributes follow-up beginning at the date on treatment. Follow-up ends at the first event specified by the endpoint definition, or at last contact for a patient without a recorded event. The specified events include progression, relapse, or medulloblastoma-related death in the timeframe description; the endpoint definition further describes progression and uses medulloblastoma-related death as an event. The exact operational handling of relapse and any other event distinctions is not reported in the registry record.
General statistical context: time-to-event analysis preserves information about how long patients were followed, including when an event has not occurred by the end of observation. A patient with no event at last contact is not necessarily known to remain event-free indefinitely. Their record is censored at last contact, and the estimation method accounts for this incomplete follow-up under assumptions. The specific censoring assumptions and estimator are not reported in the registry record.
How should the 1-year estimate be read?
The endpoint is described as a percent probability of PFS, estimated at 1 year after treatment. In general, a survival probability at a specified time represents the estimated proportion of the population remaining free of the defined event up to that time, accounting for censoring according to the chosen method. The registry record does not provide the numerical estimate, its confidence limits, or the group-specific number of events. It is therefore not possible to describe the size or precision of the PFS estimate from the record.
The registry names a 95% confidence interval as the uncertainty measure. General statistical context: a confidence interval gives a range of values compatible with the data and the method under repeated sampling. Its width conveys precision; it is not a guarantee that the true value lies within a particular interval. Because the interval limits are not reported in the registry record, neither precision nor the uncertainty around a risk-group estimate can be evaluated.
What does risk-group reporting allow?
Risk-group estimates describe outcomes in populations receiving the corresponding risk-adapted therapy. They are not automatically estimates of comparative treatment effects. In this study, allocation is non-randomized, and the risk groups have differing eligibility descriptions. General statistical context: randomization helps balance measured and unmeasured prognostic factors on average; without it, group differences may reflect both treatment and patient or disease characteristics. Statistical adjustment can address measured differences only when suitable data and methods are available, and it cannot guarantee removal of unmeasured confounding. The registry record does not report an adjusted primary analysis or the covariates used in any adjustment.
The study is described as parallel, but that label does not make the groups exchangeable. It indicates concurrent treatment pathways rather than a crossover sequence. The record does not report a randomized allocation procedure, and it explicitly identifies the study as non-randomized. Comparisons across risk groups should therefore be treated as descriptive unless a separate, appropriately justified analysis is documented.
How do event definitions affect interpretation?
The registry defines progression using lesion enlargement, a new lesion, or conversion of cerebrospinal fluid cytology from negative to positive. General statistical context: clear event definitions are important because changing the threshold or assessment process can change when an event is counted. Timing and ascertainment can also affect estimates. The registry record does not describe review procedures, imaging schedules, blinded outcome assessment, or adjudication of events.
The timeframe states that PFS runs from treatment start until progression, relapse, disease-related death, or last contact, while the detailed definition refers to first progression, medulloblastoma-related death, or last contact. The record does not explain any difference in wording between these descriptions. The precise event coding and handling of relapse are not reported in the registry record.
What can the planning illustrations tell readers?
The sample-size assumptions describe planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. For time-to-event tables, the stated quantity is the total number of events; for other outcomes, it is participants per arm. General statistical context: such illustrations explore what a future comparison might require under chosen assumptions. They are not observed power, do not show that the trial was designed around those assumptions, and do not establish that the required conditions were met in this non-randomized study. The actual illustration values are not reported in the registry record.
The registry does not report a sample-size justification for the primary endpoint, the assumed PFS rate, an interim-monitoring plan, or the exact statistical model and software used. These details are not reported in the registry record. A stated enrollment figure alone cannot establish whether the study had adequate precision for a particular risk-group estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 82 outcome measures and 4 analyses, spanning survival, response, tumor characteristics, specimen collection, and treatment feasibility or toxicity. When many outcomes or subgroup analyses are considered, the chance of at least one apparently notable result can increase. General statistical context: multiplicity procedures, such as prespecified hierarchies or adjustments to significance thresholds, can be used to control some forms of this risk. Whether any such approach was planned or used is not reported in the registry record.
The primary endpoint is defined for eligible medulloblastoma patients who started methotrexate (n=81), with estimates by risk group. The record does not state how missing endpoint data were handled, how many patients were censored, whether follow-up was complete, or whether analysis populations differed from the stated eligible population. These details are not reported in the registry record. General statistical context: missingness and loss to follow-up can affect estimates when the chance of incomplete observation is related to prognosis or outcome.
The record does not describe sensitivity analyses for missing data, a protocol-defined intention-to-treat population, or rules for excluding patients from the primary analysis. Those details are not reported in the registry record. The endpoint description says that patients who received any methotrexate are included, but does not provide further eligibility or analysis-set rules.
The trial’s non-randomized risk groups and multiple tumor diagnoses also make the scope of each analysis important. The record does not report whether risk-group analyses were prespecified, whether subgroup findings were adjusted for baseline differences, or how outcomes across tumor types were handled. Those details are not reported in the registry record. Without the analysis plan and numerical results, the influence of multiplicity, missing observations, and population definitions cannot be 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 |
|---|---|---|---|
| Low-Risk Group | 3 | 57 | 5.3% |
| Intermediate-Risk Group | 7 | 156 | 4.5% |
| High-Risk Group | 5 | 76 | 6.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Low-Risk Group | 10 of 57 |
| Intermediate-Risk Group | 58 of 156 |
| High-Risk Group | 49 of 77 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Low-Risk Group | 55 of 57 |
| Intermediate-Risk Group | 145 of 156 |
| High-Risk Group | 70 of 76 |
Most frequent serious adverse event terms
| Event term | Organ system | Low-Risk Group | Intermediate-Risk Group | High-Risk Group |
|---|---|---|---|---|
| Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | General disorders | 1 of 57 | 3 of 156 | 0 of 76 |
| Vomiting | Gastrointestinal disorders | 1 of 57 | 2 of 156 | 1 of 76 |
| Infection with normal ANC or Grade 1 or 2 neutrophils, Catheter-related | Infections and infestations | 1 of 57 | 1 of 156 | 1 of 76 |
| Seizure | Nervous system disorders | 1 of 57 | 1 of 156 | 1 of 76 |
| Hypotension | Cardiac disorders | 0 of 57 | 2 of 156 | 0 of 76 |
| Fatigue (asthenia, lethargy, malaise) | General disorders | 1 of 57 | 0 of 156 | 1 of 76 |
| Hydrocephalus | Nervous system disorders | 1 of 57 | 0 of 156 | 1 of 76 |
| Pulmonary/Upper Respiratory - Other | Respiratory, thoracic and mediastinal disorders | 0 of 57 | 0 of 156 | 2 of 76 |
| Hearing: patients with/without baseline audiogram and enrolled in a monitoring program | Ear and labyrinth disorders | 0 of 57 | 1 of 156 | 0 of 76 |
| Hemoglobin | Blood and lymphatic system disorders | 0 of 57 | 1 of 156 | 0 of 76 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Low-Risk Group | Intermediate-Risk Group | High-Risk Group |
|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 36 of 57 | 92 of 156 | 48 of 76 |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | 32 of 57 | 57 of 156 | 10 of 76 |
| Leukocytes (total WBC) | Blood and lymphatic system disorders | 24 of 57 | 45 of 156 | 6 of 76 |
| Vomiting | Gastrointestinal disorders | 10 of 57 | 25 of 156 | 22 of 76 |
| Infection, Catheter-related | Infections and infestations | 11 of 57 | 17 of 156 | 8 of 76 |
| Anorexia | Gastrointestinal disorders | 6 of 57 | 15 of 156 | 12 of 76 |
| Infection with normal ANC or Grade 1 or 2 neutrophils, Catheter-related | Infections and infestations | 8 of 57 | 19 of 156 | 5 of 76 |
| Diarrhea | Gastrointestinal disorders | 6 of 57 | 13 of 156 | 8 of 76 |
| Hemoglobin | Blood and lymphatic system disorders | 13 of 57 | 9 of 156 | 3 of 76 |
| Platelets | Blood and lymphatic system disorders | 7 of 57 | 8 of 156 | 4 of 76 |
Serious events with the highest arm-level rate: pulmonary/upper respiratory - other (2.6%), fever (in the absence of neutropenia, where neutropenia is defined as anc <1.0 x 10e9/l) (1.9%), fatigue (asthenia, lethargy, malaise) (1.8%), vomiting (1.8%), hemorrhage/bleeding - other (1.8%).
The safety record reports figures by low-, intermediate-, and high-risk group. For serious adverse events, it lists 3 affected among 57 at risk in the low-risk group, 7 among 156 in the intermediate-risk group, and 5 among 76 in the high-risk group. For other adverse events, it lists 55 among 57, 145 among 156, and 70 among 76, respectively. Death counts are listed as 10, 58, and 49 for those groups. These are group-specific registry counts, not comparisons adjusted for differences between the groups.
The most frequently listed serious-event terms include pulmonary/upper respiratory - other (2.6%), fever in the absence of neutropenia (1.9%), fatigue (1.8%), vomiting (1.8%), hemorrhage/bleeding - other (1.8%), and catheter-related infection with normal ANC or Grade 1 or 2 neutrophils (1.8%). The registry defines neutropenia in the fever term using ANC <1.0 x 10e9/L.
General statistical context: an affected count records that an event was reported for a participant, while event totals can also depend on whether repeated events are counted. The record does not describe that counting convention, severity grading for all events, exposure time, or causal attribution. The listed death counts should not be read as treatment-related deaths; cause and attribution are not reported in the registry record. Differences between groups also cannot be interpreted as regimen effects because group assignment was non-randomized and eligibility differed.
12. What the Result Does, and Does Not, Mean
The registry record describes a risk-adapted treatment study and defines a medulloblastoma PFS endpoint. It identifies an analysis population of eligible medulloblastoma patients who started methotrexate (n=81), with PFS estimated by risk group at 1 year after treatment. However, numerical PFS estimates and confidence limits are not reported in the registry record. Readers therefore cannot determine the observed PFS probabilities or their precision from the information recorded for this endpoint.
The study design also limits comparative interpretation. Patients were not randomized, and the risk groups reflect different clinical circumstances and treatment regimens. Any differences in outcome between risk groups could arise from prognosis, tumor characteristics, treatment, or other factors. The registry record does not report an analysis that separates these influences. The risk-group descriptions are useful for understanding the study’s treatment pathways, but they do not create a controlled comparison.
The safety counts describe events recorded in each risk group, and the registry lists some serious-event terms with percentages. These data do not establish that a treatment caused an event. Nor do the death counts identify cause or treatment attribution. Group differences should be interpreted cautiously because the groups are not randomized and can differ in underlying risk.
The record lists secondary outcomes comparing event-free survival and overall survival with historical controls, as well as response, molecular findings, specimen collection, and treatment feasibility. Numerical results for those outcomes are not reported in the registry record. The rationale discusses potential motivations for chemotherapy and targeted radiation, but rationale is not outcome evidence.
In general, a trial’s design, endpoint definitions, analysis population, and uncertainty estimates all matter alongside an outcome point estimate. Here, the endpoint definition and selected safety counts are available, while key numerical efficacy estimates and analysis details are not. The record therefore supports a description of the study and the kinds of outcomes assessed, but not a conclusion about whether a regimen improved survival or was superior to another approach.
13. Why This Trial Matters Statistically
This trial is statistically notable for examining a complex, risk-adapted treatment strategy across several central nervous system tumor diagnoses in young children. Rather than assigning a single regimen to all participants, the protocol descriptions link treatment intensity to risk and disease characteristics. That structure makes the clinical context essential to statistical interpretation: the groups are not interchangeable treatment arms, and outcome differences would not be a clean measure of regimen effects.
The primary endpoint also illustrates why the analysis population must be distinguished from overall enrollment. The registry lists enrollment of 293, while the primary PFS analysis is described for eligible medulloblastoma patients who started methotrexate (n=81). These figures refer to different scopes and should not be combined or treated as if they described the same population.
Time-to-event outcomes can make use of follow-up information from patients who have not experienced an event by last contact, but the resulting estimate depends on the event definition, censoring, and follow-up. The registry describes the event criteria and names a 95% confidence interval, but numerical estimates and interval limits are not reported in the registry record. This means that statistical precision cannot be evaluated from the endpoint description alone.
There is also a broad set of secondary outcomes and analyses. Such breadth can be valuable for characterizing a multi-diagnosis trial, but it raises questions about which analyses were prespecified and how multiplicity was handled. Those details are not reported in the registry record. The record’s limited numerical efficacy information means that the study’s statistical contribution cannot be judged from endpoint labels or design alone.
Overall, this trial highlights the distinction between describing risk-group outcomes and estimating causal treatment effects. That distinction is important in clinical research, especially when patients with different prognoses follow different treatment pathways.
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 most important trial-specific limitation in the registry record is the absence of numerical results for the primary PFS endpoint. The record describes the population, event criteria, timeframe, and intended reporting by risk group, but does not report the estimates or their 95% confidence intervals. Consequently, neither the observed PFS level nor its precision can be assessed.
The non-randomized design prevents a straightforward causal comparison across risk groups. The eligibility descriptions indicate that groups differ by disease extent and histology, and the treatment pathways differ accordingly. The registry record does not report adjusted estimates or sufficient baseline information to assess how group characteristics relate to outcomes.
The endpoint descriptions use related but not identical wording about progression, relapse, and disease-related death. The record does not explain how these terms were reconciled for analysis. It also does not report the assessment schedule, event adjudication procedures, follow-up completeness, censoring details, or handling of missing data. These details are not reported in the registry record.
The registry lists numerous outcomes and analyses but does not report the statistical analysis plan, prespecification of subgroup analyses, or multiplicity strategy. Those details are not reported in the registry record. The safety data are descriptive and do not include the context needed to attribute adverse events or deaths to treatment, compare exposure-adjusted risks, or account for differing group characteristics.
Finally, historical-control comparisons are listed among secondary outcomes, but the registry record does not identify the historical cohorts or provide numerical results. Without those details, comparability and the influence of changes in care or measurement cannot be evaluated.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma — NCT00602667.
- Registry record last updated 2026-10-16; status last verified 2026-10.
- Results first posted 2019-01-30.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT00602667 is a non-randomized, open-label, parallel phase 2 study of risk-adapted therapy for young children with central nervous system tumors. The registry lists enrollment of 293 and status as active, not recruiting. Treatment descriptions assign induction chemotherapy and low-, intermediate-, or high-risk therapy according to clinical group.
The primary outcome is the percent probability of PFS for eligible medulloblastoma patients who started methotrexate (n=81), estimated at 1 year after treatment and reported by risk group. The endpoint definition includes progression and medulloblastoma-related death, with last contact used for patients without an event. Numerical PFS estimates and confidence limits are not reported in the registry record.
Safety counts and selected serious adverse-event terms are listed by risk group. Since allocation is non-randomized and risk groups differ clinically, neither efficacy nor safety differences across groups establish comparative treatment effects. The registry also lists secondary survival, response, molecular, specimen, and feasibility outcomes, but their numerical results and many analysis details are not reported in the registry record.