Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin (NCT01175356), a na phase 1 study. The primary outcome is Percentage of MIBG Avid Patients Treated With Meta-iodobenxylguanide (MIBG) Labeled With Iodine-131.

2. Clinical Question

3. Trial Design

This is a completed phase 1 pilot study sponsored by the Children’s Oncology Group. The registry lists a single-group model, no masking, and allocation as NA. Enrollment is 99. The recorded start date is 2011-12-21, and primary completion is recorded as 2016-09-28. The current status is completed.

The treatment approach combines induction chemotherapy with 131I-MIBG and includes later intensive chemotherapy, autologous hematopoietic stem cell transplantation, radiation therapy, and maintenance therapy with isotretinoin. The registry lists radiation approaches and transplant among the interventions, along with chemotherapy agents. Its brief summary describes radioisotope therapy, chemotherapy, transplant, radiation, and isotretinoin as components of the overall treatment strategy. The arm description refers readers to a detailed description, so the full treatment schedule is not reported in the registry record excerpt.

Because the study has a single group, the primary feasibility percentage is descriptive rather than a between-group treatment effect. The design can describe whether eligible, evaluable patients received 131I-MIBG under the study’s treatment pathway. It cannot, on its own, separate the contribution of 131I-MIBG from the other treatment components or provide a randomized estimate comparing this regimen with an alternative.

The registry identifies three outcome measures and lists a secondary outcome concerning unacceptable toxicity and sinusoidal obstruction syndrome. It does not list analysis records. The registry record does not report a detailed statistical analysis plan, sample-size justification, interim-analysis plan, or further allocation procedures.

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: Includes patients who met criteria to receive 131I-MIBG but went off protocol therapy before receiving a dose assignment, but excludes patients that could not continue onto 131I-MIBG therapy due to lack of an open treatment slot. The definition of receiving MIBG labeled with iodine-131 is receiving 131I-MIBG.

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 Percentage of MIBG Avid Patients Treated With Meta-iodobenxylguanide (MIBG) Labeled With Iodine-131, measured over Up to 6 weeks after course 5 of induction.

The primary endpoint is the percentage of MIBG-avid patients treated with 131I-MIBG. Its stated timeframe is up to 6 weeks after course 5 of induction. The endpoint description defines the calculation as the number of MIBG-avid patients who receive 131I-MIBG divided by the number evaluable for the feasibility endpoint, multiplied by 100%. It also describes an analysis population that includes patients who met criteria to receive 131I-MIBG but went off protocol therapy before receiving a dose assignment, while excluding patients unable to continue to 131I-MIBG because no treatment slot was open.

This endpoint addresses whether the planned treatment could be delivered to the population defined for feasibility assessment. In a pilot study, such a process measure can describe treatment delivery, distinct from measuring tumor response, survival, or comparative benefit. The registry record does not report the endpoint’s observed percentage or its 95% confidence interval. The endpoint description is also cut off after beginning to define what counts as receiving 131I-MIBG, so the complete operational definition is not reported in the registry record.

A percentage is interpreted together with its denominator: the same numerator can imply different precision depending on how many participants were evaluable. A confidence interval describes uncertainty around the estimated percentage under the statistical model used. Without the observed estimate, interval, and underlying counts, the precision of this feasibility result cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a percentage as the primary outcome and a 95% confidence interval as its dispersion measure. The concepts below are general statistical explanations; the registry record does not report the primary endpoint estimate or its interval.

What does a percentage estimate?

A percentage expresses the share of a defined population that meets an outcome definition. For this study, the stated numerator is the number of MIBG-avid patients who receive 131I-MIBG, and the denominator is the number evaluable for the feasibility endpoint. The endpoint description gives the percentage calculation as the numerator divided by that denominator and multiplied by 100%. This is a treatment-delivery measure: it summarizes receipt of the planned treatment under the study’s feasibility rules.

The denominator definition is part of the outcome, not a minor technical detail. The registry says the evaluable population includes patients who met criteria but left protocol therapy before receiving a dose assignment. It excludes patients who could not continue to 131I-MIBG therapy because a treatment slot was unavailable. A different eligibility or evaluability rule could yield a different percentage, even if the treatment receipts themselves were unchanged. Since the full definition of receipt is cut off in the registry record excerpt, the endpoint cannot be reconstructed completely.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with the observed data under a statistical procedure and its assumptions. It communicates precision: a narrower interval indicates less sampling uncertainty than a wider interval, while neither width nor location alone resolves possible bias or limitations in outcome measurement. A 95% confidence interval is listed as the planned way to express dispersion for this endpoint. The actual interval is not reported in the registry record, so its width and the precision of the observed percentage cannot be evaluated.

For a percentage, precision is influenced by the number of evaluable participants and by how common the event is in that population. The registry record does not state the primary endpoint’s observed numerator or evaluable denominator. The enrollment figure is not interchangeable with the endpoint denominator, because the endpoint uses specific eligibility and evaluability rules.

Why does the single-group design matter?

A single-group study can describe outcomes among participants receiving the study regimen, but it does not estimate a randomized contrast against a concurrent control. The primary outcome is feasibility of receiving 131I-MIBG, not a treatment difference. It therefore should not be read as evidence of comparative efficacy. The regimen includes multiple treatment components, so a descriptive result would not isolate the effect of 131I-MIBG from chemotherapy, transplant, radiation, or maintenance therapy.

The study is listed as unmasked. General statistical interpretation should recognize that unmasked outcome assessment can be vulnerable to differences in observation or classification, depending on how an outcome is defined and measured. The primary endpoint is receipt of treatment, but the registry excerpt does not describe procedures for adjudicating eligibility, receipt, or missing outcome information. Whether any such procedures were used is not reported in the registry record.

What can recalculation or planning illustrations show?

Recalculation from posted summary statistics, when available, is an unadjusted check based on those summaries. It is not a replacement for the sponsor’s analysis when a discrepancy is present. In this record, the primary endpoint’s numerical summary is not reported, so no endpoint recalculation can be interpreted. The record lists no analysis records.

Planning illustrations based on an observed effect are hypothetical design calculations, not observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Those assumptions do not match the registered single-group design. They should be understood as a separate planning framework, not as a feature of this trial’s allocation or evidence about its realized power. The observed endpoint effect needed to interpret such illustrations is not reported in the registry record.

Finally, statistical precision does not address every source of uncertainty. A confidence interval, even if reported, would quantify sampling uncertainty under a method, not resolve limitations arising from selection into the evaluable population, incomplete outcome definitions, missing observations, or the absence of a comparator. Those issues require reporting about conduct and analysis that is not available in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment (131I-MIBG, Chemotherapy)")
n      <- c(68)
events <- c(59)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment (131I-MIBG, Chemotherapy)  68  59  86.8  76.4  93.8  76.7  92.9  76.7  92.8

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies three outcome measures, but it does not provide a complete account of how multiple outcomes were handled statistically. A multiplicity strategy specifies how interpretation is adjusted when investigators assess several outcomes or make several statistical claims. Without a reported strategy, the chance of false-positive findings across multiple tests cannot be evaluated. No analysis records are listed, and the registry record does not report a statistical analysis plan or whether adjustment for multiplicity was used.

The primary feasibility outcome has a defined eligibility and evaluability rule, but the record does not give the observed numerator, denominator, or percentage. It also does not describe the handling of missing endpoint data beyond the stated population rules. Whether additional participants had missing, indeterminate, or unclassifiable endpoint information is not reported in the registry record.

Analysis populations are important because the same study can produce different estimates depending on whether the analysis includes all enrolled participants, only those meeting eligibility criteria, or only those with an evaluable endpoint. The registry’s primary outcome description specifies a feasibility population, including some patients who left protocol therapy before dose assignment and excluding patients who could not continue because of an unavailable treatment slot. The complete operational definition is not reported in the registry record excerpt. The record also does not report a separate intention-to-treat or per-protocol analysis population for this outcome.

These omissions do not establish that missing-data or multiplicity procedures were absent; they mean those procedures are not reported in the registry record. Without them, the robustness of the outcome analysis and the interpretation of any nominal statistical findings cannot be assessed.

12. 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: 24600-death nos (13.3%), 17400-blood bilirubin increased (8.2%), 14900-ascites (6.1%), 88200-weight gain (5.1%), 43900-hypoxia (5.1%).

The registry reports adverse-event information for the treatment group. It lists 98 participants at risk for serious adverse events and 27 affected, and 98 at risk for other adverse events and 86 affected. These counts describe participants recorded as affected, not the total number of event episodes. The record does not report a separate deaths count.

The listed serious adverse-event terms include Death NOS at 13.3%, blood bilirubin increased at 8.2%, ascites at 6.1%, weight gain at 5.1%, hypoxia at 5.1%, and alanine aminotransferase increased at 4.1%. These are event-term percentages in the registry listing. The record does not explain the relationship between these term percentages and the participant-level affected count, nor whether participants could appear under more than one term. Categories may overlap in general adverse-event reporting, so term percentages should not be added together.

Seriousness is a reporting classification and does not by itself establish causation. The record does not report whether listed events were judged treatment-related, their duration, their resolution, or the clinical context of individual events. Death NOS is a term in the serious-event list; it should not be treated as a separate confirmed count of deaths or as evidence about cause.

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

The study addresses whether a complex treatment pathway including 131I-MIBG could be delivered to the intended feasibility population. Its registered primary endpoint is a percentage of MIBG-avid, evaluable patients who received 131I-MIBG, within the stated timeframe of up to 6 weeks after course 5 of induction. The registry record does not report the observed percentage or confidence interval. It therefore does not permit a conclusion about the measured level of feasibility or its precision.

Even if the percentage were available, it would describe treatment delivery under the study’s rules, not establish a comparative treatment effect. There is no randomized control group, and the trial is listed as single group. Its treatment strategy combines 131I-MIBG with chemotherapy and other components, so an outcome cannot be attributed to any single component using this design alone.

The record’s safety listings describe adverse events recorded in the treatment group. They do not establish that treatment caused those events, and they do not include enough detail to characterize event timing, duration, or clinical course. The serious-event term Death NOS is not a standalone mortality result.

The registry identifies the study as completed, with enrollment of 99, and records the study’s primary completion date as 2016-09-28. Completion status and enrollment do not supply the missing primary endpoint estimate. The interpretation must remain bounded by the information actually reported: the study design, endpoint definition, and adverse-event summaries are available, while the numerical feasibility result and detailed statistical procedures are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of a pilot study whose central question is treatment feasibility rather than a randomized comparison. Its primary endpoint focuses on whether MIBG-avid patients in a defined evaluable population received 131I-MIBG. That focus makes the denominator and eligibility rules central to interpretation. The registry describes some inclusions and exclusions, but the endpoint definition is incomplete in the record excerpt.

The single-group design also clarifies the limits of inference. A descriptive percentage can characterize delivery within the study pathway, but it cannot supply a concurrent comparative estimate. Because the regimen combines several forms of treatment, the design cannot identify the separate contribution of each component. These distinctions matter when reading a percentage that might otherwise be mistaken for an effectiveness comparison.

The record also demonstrates why outcome estimates and their uncertainty need to be reported together. A percentage without its numerator, denominator, and confidence interval cannot show how precise the feasibility estimate is. Here, the numerical primary result is not reported, so the statistical question remains unresolved despite the registration of a defined endpoint.

Finally, trial completion, enrollment, and adverse-event listings answer different questions from the primary outcome. They describe aspects of study status and safety reporting, but they do not replace the feasibility estimate. Keeping these roles separate prevents registry information from being interpreted as stronger evidence than it contains.

15. 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 primary endpoint result is not reported in the registry record. The observed percentage, confidence interval, numerator, and evaluable denominator are all unavailable, so neither the size nor the precision of the feasibility estimate can be assessed. The endpoint definition is also incomplete in the record excerpt, which ends while specifying what counts as receiving 131I-MIBG.

The study has a single-group, unmasked design and no concurrent comparator. Its results therefore cannot provide a randomized treatment contrast. The intervention is a multicomponent strategy involving 131I-MIBG and chemotherapy along with transplant, radiation, and maintenance therapy; the design does not isolate the contribution of any one component.

The registry record lists three outcome measures but no analysis records. A full statistical analysis plan, multiplicity procedures, sample-size justification, interim-analysis plan, and detailed missing-data handling are not reported in the registry record. The record also does not describe further analysis populations beyond the primary endpoint’s feasibility rules.

The adverse-event summary supplies participant counts and selected term percentages, but does not report event-level timing, duration, attribution, or outcomes. The deaths field is not populated, and the Death NOS term should not be interpreted as a separate death count. These gaps limit safety interpretation as well as interpretation of the primary feasibility endpoint.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin — NCT01175356.
• Registry record last updated 2026-01-23; status last verified 2026-01.
• Results first posted 2017-09-28.
• 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.

19. Record Summary

NCT01175356 is a completed phase 1 pilot study sponsored by the Children’s Oncology Group. It is listed as single group, with no masking and allocation recorded as NA. Enrollment is 99. The registry records a start date of 2011-12-21 and primary completion on 2016-09-28.

The treatment strategy includes induction therapy with 131I-MIBG and chemotherapy, followed by transplant, radiation therapy, and maintenance therapy with isotretinoin. The primary endpoint is the percentage of MIBG-avid patients who received 131I-MIBG, assessed up to 6 weeks after course 5 of induction. Its numerical result and 95% confidence interval are not reported in the registry record. The registry lists three outcome measures and no analysis records.

For adverse events, 27 of 98 participants at risk are listed as affected by serious events, and 86 of 98 as affected by other events. The record does not report a separate deaths count or establish event causation.