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 Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma (NCT00554788), a non-randomized phase 3 study. The primary outcome is Event-free Survival (EFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00554788 |
| Phase | Phase 3 |
| Condition | Extraocular Retinoblastoma |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 60 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Children's Oncology Group |
| Results posted | Yes |
2. Clinical Question
Population
Young patients with extraocular retinoblastoma. The registry record lists enrollment of 60 and says ineligible patients were excluded from the primary endpoint analysis; the number excluded is not reported in the registry record.
Intervention
A treatment pathway involving combination chemotherapy and, depending on disease stage and treatment course, autologous stem cell transplantation and/or radiation therapy. The record describes induction chemotherapy and consolidation for stage 4a or 4b disease.
Comparator
No concurrent comparator is registered. The trial is described as non-randomized and single-group, so it does not provide a randomized, like-for-like control comparison.
Primary question
What is the probability of event-free survival at 1 year after enrollment? An event is defined as relapse, second malignancy, or death from any cause.
The clinical question is about the outcome observed after an intensive, multi-modality treatment approach, rather than about a treatment effect estimated by comparing randomized groups. The registry describes the study as examining both side effects and how well chemotherapy with autologous stem cell transplantation and/or radiation therapy works. Treatment components may differ by disease stage: consolidation is specified for stage 4a or 4b disease, while the treatment description also refers to induction and autologous stem cell infusion.
The record does not provide a primary endpoint estimate, confidence interval, or outcome analysis. It therefore does not permit a numerical description of the event-free survival observed at the stated follow-up time. Nor does the single-group design establish how outcomes would compare with a different treatment or with no treatment. The registered question is clinically specific, but the available result information is insufficient to quantify the observed outcome or isolate the contribution of any particular treatment component.
3. Trial Design
This is a completed Phase III trial with non-randomized allocation, no masking, and a single-group model. The registry lists enrollment of 60. These design features mean that the record describes a treatment cohort, not a randomized comparison between treatment arms. A comparator group is not registered, and no like-for-like control comparison is available from the design details.
The study concerns extraocular retinoblastoma and evaluates an intensive treatment approach that can include combination chemotherapy, autologous stem cell transplantation, and radiation therapy. The registry description gives an induction phase involving vincristine, cisplatin, cyclophosphamide, and G-CSF. It also describes consolidation with carboplatin, thiotepa, and etoposide for stage 4a or 4b disease. The treatment summary describes radiation as a possible component after chemotherapy and/or transplantation. The complete treatment schedule and the criteria governing each component are not reported in the registry record.
The registry lists a start date of 2008-05-06, primary completion on 2018-06-30, and status as completed. These dates describe the record’s study timeline; they do not supply the duration of follow-up for each participant. The primary endpoint is event-free survival at 1 year after enrollment. Ineligible patients were excluded from its analysis, but the number excluded and other details of the analysis population are not reported in the registry record.
Although the record labels the trial Phase III, the non-randomized, single-group design remains important when interpreting outcomes. A cohort outcome can describe what happened among the analyzed participants, but without a registered control group it cannot by itself estimate a comparative treatment effect. The reasons for the non-randomized design and the protocol’s sample-size justification are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Stage 2/3 Patients | Stage 4a Patients | Stage 4b Patients |
|---|---|---|---|
| STARTED | 21 | 18 | 21 |
| COMPLETED | 14 | 12 | 7 |
| NOT COMPLETED | 7 | 6 | 14 |
Reasons for not completing this period:
| Reason | Stage 2/3 Patients | Stage 4a Patients | Stage 4b Patients |
|---|---|---|---|
| Adverse Event | 0 | 1 | 2 |
| Lost to Follow-up | 4 | 3 | 3 |
| Physician Decision | 1 | 1 | 3 |
| Withdrawal by Subject | 0 | 0 | 1 |
| Refusal of further protocol therapy | 0 | 1 | 1 |
| Progressive disease | 0 | 0 | 3 |
| Ineligible | 2 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Ineligible patients were excluded from analysis
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Stage 2/3 Patients | Stage 4a Patients | Stage 4b Patients | Total |
|---|---|---|---|---|---|
| Participants analysed | 21 | 18 | 21 | 60 | |
| Age, Continuous | years | 3.24 (SD 1.36) | 3.96 (SD 2.27) | 2.91 (SD 1.83) | 3.34 (SD 1.85) |
| Sex: Female, Male: Female | Participants | 4 | 9 | 14 | 27 |
| Sex: Female, Male: Male | Participants | 17 | 9 | 7 | 33 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 8 | 7 | 8 | 23 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 13 | 10 | 13 | 36 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 0 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 2 | 0 | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 2 | 5 | 10 |
| Race (NIH/OMB): White | Participants | 11 | 11 | 12 | 34 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 6 | 3 | 4 | 13 |
| Region of Enrollment: United States | Participants | 14 | 14 | 13 | 41 |
| Region of Enrollment: Canada | Participants | 1 | 0 | 0 | 1 |
| Region of Enrollment: Argentina | Participants | 3 | 4 | 2 | 9 |
| Region of Enrollment: Egypt | Participants | 3 | 0 | 4 | 7 |
| Region of Enrollment: Brazil | Participants | 0 | 0 | 1 | 1 |
| Region of Enrollment: Chile | Participants | 0 | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Event-free Survival (EFS), measured over At 1 year.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Probability |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is event-free survival at 1 year after enrollment. The registry describes it as the probability of surviving without experiencing an event during that period. Events are defined as relapse, second malignancy, or death from any cause. Thus, the endpoint combines several clinically important outcomes: a participant is not event-free if any one of the defined events occurs.
Event-free survival is used in trials where a treatment goal includes avoiding disease relapse and other specified events, as well as remaining alive. It captures more than survival alone, because an event can occur even when a participant is still alive. The endpoint’s interpretation depends on its event definition and the specified time point; it should not be read as a measure of overall survival alone.
The registry identifies a 95% confidence interval as the endpoint’s dispersion measure, but the event-free survival estimate and interval bounds are not reported in the registry record. The record also says ineligible patients were excluded from the analysis. How eligibility was determined, how participants with incomplete follow-up were handled, and how the estimate was calculated are not reported in the registry record. Consequently, the endpoint’s definition is available, but its numerical result and precision cannot be assessed from the posted result information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry specifies a meaningful and clearly defined primary outcome: event-free survival at 1 year after enrollment, with relapse, second malignancy, and death from any cause counted as events. However, it does not report the numerical event-free survival probability or the bounds of its 95% confidence interval. Without those values, the posted record does not allow readers to quantify the outcome or assess its statistical precision.
The listed enrollment is 60, but this is not necessarily the number included in the primary endpoint analysis. The registry explicitly says ineligible patients were excluded, and does not report how many were excluded or the final analyzed population. Enrollment alone therefore cannot establish the denominator underlying the endpoint. The record also does not provide event counts for the primary endpoint, follow-up completeness, or the number of participants at risk at 1 year.
The trial is non-randomized and single-group, with no registered comparator. Even if an event-free survival estimate were available, it would describe the outcome in the analyzed cohort rather than establish a difference from another treatment. Outcomes can reflect patient characteristics, disease stage, treatment selection, and other influences in addition to the treatment approach. Without a concurrent control and an appropriate comparative analysis, the effect attributable to treatment cannot be separated from these influences.
The record lists secondary outcomes for response to induction and adverse events, but it does not provide analysis results for the primary endpoint or a count of analyses. It does include adverse-event counts by disease stage. Those safety entries are descriptive and do not substitute for an event-free survival result. Death counts in the adverse-event data should also not be treated as the primary endpoint’s death count without a matching analysis definition and follow-up context.
Accordingly, the available registry information supports a description of the trial’s design, treatment approach, endpoint definition, and selected adverse-event entries. It does not support a numerical conclusion about 1-year event-free survival, a comparison with an alternative treatment, or an attribution of outcomes to any individual component of the multi-modality approach. The endpoint result and its uncertainty are not reported in the registry record.
9. Statistical Methods Explained
The statistical information in the registry record is limited. The primary endpoint is identified as a probability with a 95% confidence interval, but the estimate and interval limits are not reported. The record also indicates no analyses for the listed outcome measures. The statistical method used to produce an event-free survival estimate, if one was calculated, is not reported in the registry record.
What does the confidence interval describe?
In general, a confidence interval expresses uncertainty around an estimated quantity. A point estimate gives a single value; the interval indicates the range of values compatible with the data under the method’s assumptions. A narrower interval indicates greater precision than a wider interval, while the interval’s position also matters for interpretation. Here, the registry names a 95% confidence interval but gives neither the event-free survival estimate nor the interval bounds. Its precision and substantive implications therefore cannot be evaluated.
How is event-free survival generally analyzed?
In general, time-to-event methods account for the time until a defined event and can accommodate participants whose event status is not observed through the full follow-up period. Participants without a recorded event may be censored at the last time their status is known, depending on the analysis plan. These methods rely on definitions and assumptions about event ascertainment, follow-up, and censoring. The registry record does not report the method used, censoring rules, how incomplete follow-up was handled, or whether the 1-year probability came from a time-to-event estimate or another approach. No particular method should be inferred from the endpoint label alone.
What does the design allow?
The design is registered as non-randomized and single-group. In general, a single-group outcome estimate describes the observed cohort; it does not provide a randomized estimate of the difference between treatment strategies. Randomization can help balance measured and unmeasured prognostic factors across treatment groups, whereas a non-randomized design may be subject to differences in who receives particular components or enters the analysis. No adjustment method, covariate model, or comparative analysis is reported in the registry record.
The multi-modality treatment approach also complicates component-specific interpretation. The record describes chemotherapy and possible transplantation and radiation, with consolidation specified for stage 4a or 4b disease. Since there is no registered treatment arm for each component, an outcome cannot be attributed separately to chemotherapy, transplantation, or radiation on the basis of this design description. The criteria for treatment selection and the protocol’s detailed statistical plan are not reported in the registry record.
How should planning illustrations be read?
Planning illustrations based on an observed effect are not the trial’s own prospective sample-size justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event planning, the stated quantity is the total number of events; for other outcomes, it is participants per arm. These assumptions describe hypothetical planning scenarios and do not alter the registered single-group design. They are not observed power and cannot show that the completed trial had a particular probability of detecting an effect. The protocol’s own sample-size rationale is not reported in the registry record.
In general, over-dispersion matters when outcome variability exceeds what a statistical model assumes: standard errors may then be understated and intervals too narrow if the extra variability is ignored. The registry record does not identify a count model, provide a dispersion estimate, or report an adjustment for over-dispersion. This general issue should not be mistaken for a method known to have been used in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures, including event-free survival, response to the induction phase, and adverse events assessed using CTCAE Version 4.0. It reports no analyses for those outcome measures. A plan for prioritizing outcomes beyond the designated primary endpoint, or for controlling multiplicity across outcomes or analyses, is not reported in the registry record.
Multiplicity matters when several outcomes or repeated tests are considered: the chance of at least one apparently notable result can increase as the number of tests grows. In general, a prespecified strategy may control that risk or clarify which results are confirmatory and which are exploratory. No such strategy is described in the registry record, so the inferential status of any secondary findings cannot be assessed from the record.
The primary endpoint population excludes ineligible patients. The number excluded, the eligibility criteria applied to the analysis, and the resulting analysis population are not reported in the registry record. Missing-data procedures are also not reported. The record does not state how participants without complete follow-up were handled, whether any imputation was used, or how withdrawals and censoring were treated.
These omissions limit reproducibility and interpretation. The stated enrollment cannot be assumed to equal the primary analysis population, and the endpoint’s precision cannot be reconstructed from the available information. The registry record also does not report a statistical analysis plan or explain whether outcome definitions or analyses changed during the study.
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 |
|---|---|---|---|
| Stage 2/3 Patients | 1 | 18 | 5.6% |
| Stage 4a Patients | 2 | 18 | 11.1% |
| Stage 4b Patients | 0 | 19 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Stage 2/3 Patients | 2 of 18 |
| Stage 4a Patients | 5 of 18 |
| Stage 4b Patients | 15 of 19 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Stage 2/3 Patients | 13 of 18 |
| Stage 4a Patients | 12 of 18 |
| Stage 4b Patients | 10 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Stage 2/3 Patients | Stage 4a Patients | Stage 4b Patients |
|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 1 of 18 | 1 of 18 | 0 of 19 |
| Sepsis | Infections and infestations | 0 of 18 | 1 of 18 | 0 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Stage 2/3 Patients | Stage 4a Patients | Stage 4b Patients |
|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 9 of 18 | 9 of 18 | 7 of 19 |
| Infections and infestations - Other, specify | Infections and infestations | 5 of 18 | 6 of 18 | 4 of 19 |
| Hypokalemia | Metabolism and nutrition disorders | 5 of 18 | 3 of 18 | 4 of 19 |
| Anorexia | Metabolism and nutrition disorders | 2 of 18 | 6 of 18 | 3 of 19 |
| Mucositis oral | Gastrointestinal disorders | 1 of 18 | 5 of 18 | 1 of 19 |
| Vomiting | Gastrointestinal disorders | 2 of 18 | 4 of 18 | 1 of 19 |
| Hypophosphatemia | Metabolism and nutrition disorders | 4 of 18 | 0 of 18 | 2 of 19 |
| Nausea | Gastrointestinal disorders | 3 of 18 | 2 of 18 | 1 of 19 |
| Hyponatremia | Metabolism and nutrition disorders | 2 of 18 | 0 of 18 | 3 of 19 |
| Alanine aminotransferase increased | Investigations | 0 of 18 | 3 of 18 | 1 of 19 |
Serious events with the highest arm-level rate: febrile neutropenia (5.6%), sepsis (5.6%).
The safety entries are reported by disease-stage group. For serious adverse events, the record lists 1 affected among 18 at risk in the Stage 2/3 group, 2 among 18 in Stage 4a, and 0 among 19 in Stage 4b. For other adverse events, it lists 13 among 18, 12 among 18, and 10 among 19, respectively. These are group-specific counts, not a randomized comparison. The record does not provide an adjusted comparison or indicate that the groups are equivalent in baseline risk.
The registry lists febrile neutropenia and sepsis as serious adverse event terms, each with a reported percentage of 5.6%. The denominator and method used for those percentages are not reported in the registry record, so they should not be reverse-engineered or treated as group-specific estimates.
The registry also lists death counts of 2 for Stage 2/3, 5 for Stage 4a, and 15 for Stage 4b in the adverse-event data. The relationship of these entries to the primary endpoint analysis and their event timing are not reported in the registry record. They should not be treated as the event-free survival result or assumed to represent treatment-related deaths. Adverse-event categories and endpoint events have distinct definitions, and the record does not provide the detail needed to reconcile them.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed, single-group Phase III trial evaluated an intensive treatment approach for young patients with extraocular retinoblastoma. It specifies the primary endpoint as event-free survival at 1 year and defines events as relapse, second malignancy, or death from any cause. It also identifies an analysis population that excludes ineligible patients and reports selected adverse-event entries by stage.
The record does not report the primary endpoint estimate or its 95% confidence interval. It therefore does not show the observed 1-year event-free survival probability or how precisely that probability was estimated. It also does not report the final endpoint analysis population, the primary endpoint event count, or how incomplete follow-up was handled. These gaps prevent a quantitative reading of the primary outcome.
The trial design does not include a registered comparator and is not randomized. As a result, the record cannot establish a relative treatment effect against another approach. Nor can the contribution of each treatment component be isolated: the described approach may include chemotherapy, transplantation, and radiation, with treatment components varying by stage. Observed outcomes in a single cohort can be influenced by factors other than the treatment itself.
The adverse-event counts provide descriptive information, but they do not resolve those limitations. They are organized by stage, not by randomized assignment, and they do not provide a controlled estimate of risk. The record does not establish whether listed deaths correspond to primary endpoint events or provide enough detail to interpret them as treatment-related.
Thus, the available information describes the clinical question, design, endpoint definition, and selected safety data, but it does not support a numerical conclusion about the primary outcome or a causal claim about treatment benefit or harm. Those results and analyses are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial raises several statistical issues common to studies of intensive treatment for uncommon or clinically complex conditions. Its endpoint is time-specific and event-based: event-free survival at 1 year includes relapse, second malignancy, and death from any cause. That definition matters because a participant may experience an endpoint event without dying, and the result is not interchangeable with overall survival.
The treatment approach also has multiple components and is described as varying according to disease stage. This makes clear endpoint definitions and transparent reporting of treatment exposure especially important. A single-group design can describe outcomes in the enrolled cohort, but it cannot separate the influence of the treatment approach from the influence of patient characteristics, disease stage, or other factors. Nor can it identify the effect of one component apart from the others.
Precision is central to interpreting a survival probability. The registry identifies a 95% confidence interval, but does not report its bounds or the point estimate. Without those values, readers cannot judge whether the estimate is precise or uncertain. The stated enrollment of 60 does not resolve this issue because ineligible participants were excluded from the primary analysis and the analyzed population is not reported.
The record also illustrates why transparent reporting of analysis populations, missing follow-up, event counts, and statistical methods matters. Without these details, the primary result cannot be reproduced or fully assessed. The design and outcome definitions are useful context, but they do not replace a reported estimate with its uncertainty and the methods needed to interpret it.
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 the primary endpoint result. Although event-free survival at 1 year and a 95% confidence interval are specified, neither the estimate nor the interval bounds are reported. Primary endpoint event counts and follow-up completeness are also not reported, preventing assessment of precision and outcome ascertainment.
The analysis population is incompletely described. Ineligible patients were excluded, but the number excluded, eligibility criteria, and number analyzed are not reported in the registry record. The listed enrollment of 60 therefore cannot be treated as the endpoint denominator. Missing-data procedures, censoring rules, and details of participant follow-up are also not reported.
The single-group, non-randomized design limits causal interpretation. No concurrent comparator is registered, and treatment components can vary by stage. The registry does not report methods for adjusting for differences in patient characteristics or for assessing the separate contribution of chemotherapy, transplantation, or radiation. The protocol’s sample-size justification and detailed statistical analysis plan are not reported in the registry record.
Safety information is also limited in interpretability. The record lists affected and at-risk counts by stage, serious adverse event terms with percentages, and death counts, but does not report the denominator for the term percentages or clarify how the death entries relate to the primary endpoint. No randomized comparison or adjusted safety analysis is reported. These limitations mean the entries should be read descriptively rather than as estimates of comparative treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma — NCT00554788.
- Registry record last updated 2025-01-13; status last verified 2025-01.
- Results first posted 2019-06-26.
- 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
The registry record describes a completed Phase III, non-randomized, single-group trial of multi-modality treatment for extraocular retinoblastoma, with enrollment listed as 60. Treatment descriptions include induction chemotherapy, consolidation for stage 4a or 4b disease, and possible autologous stem cell transplantation and/or radiation therapy.
The primary endpoint is event-free survival at 1 year after enrollment, defined by relapse, second malignancy, or death from any cause. Ineligible patients were excluded from the analysis. The endpoint estimate, 95% confidence interval, final analysis population, and statistical methods are not reported in the registry record.
Selected adverse-event counts are listed by disease stage, but the trial has no registered comparator and does not provide a randomized treatment comparison. The record therefore describes the study design and selected outcomes without establishing a comparative treatment effect.