Molecular Guided Therapy for Refractory or Recurrent Neuroblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Molecular Guided Therapy for Refractory or Recurrent Neuroblastoma (NCT01355679), a na na study. The primary outcome is Percentage of Participants That Are Able to Meet Feasibility Parameters..

2. Clinical Question

The clinical question is about whether this testing and treatment-planning pathway could be carried through, not whether the proposed treatment combinations were effective. The registry’s brief summary explicitly says the study was not designed to study the effectiveness of those combinations. Secondary outcomes included adverse events, overall response rate using RECIST criteria, and treatment activity using progression-free survival. Those outcomes describe other questions, but they do not replace the feasibility question as the primary endpoint.

3. Trial Design

This was a completed, single-group feasibility trial registered as NCT01355679, with the title “Molecular Guided Therapy for Refractory or Recurrent Neuroblastoma.” The listed phase and allocation are NA. Masking was none, and the study model was single group. The registry records enrollment of 16 participants. The arm description states that a total of 14 eligible patients with refractory or relapsed neuroblastoma on conventional therapy would be treated. The primary endpoint description says two subjects were deemed ineligible after biopsy because their tumor type was benign.

The study evaluated a pathway that began with biopsy or surgical resection and molecular testing of the tumor. The registry describes gene expression profiling using the experimental technology OncInsights. Guided therapy could use a combination of up to 4 agents, if the agents were included in the study report. The feasibility criteria also required a tumor board, review and approval by a medical monitor, timely treatment initiation, and completion of 1 cycle of therapy.

The listed intervention is Guided Therapy, categorized as a device. There was no randomized treatment assignment and no like-for-like control arm. Any outcome observed in the single group would therefore describe participants who went through this pathway; it would not by itself establish how the same participants would have fared under an alternative process or treatment strategy.

The registry lists the study as completed, with a start date of 2011-05 and primary completion date of 2013-09. Its purpose was to assess feasibility rather than the effectiveness of treatment combinations selected using the profiling process. The experimental technology had not been approved by the U.S. Food and Drug Administration, according to the brief summary.

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: All subjects had soft tissue disease in which biopsy was possible. Two subjects were deemed ineligible due to benign tumor type after biopsy.

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: Multiply relapsed or refractory neuroblastoma.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants That Are Able to Meet Feasibility Parameters., measured over 1 year.

The primary endpoint is the percentage of participants able to meet the study’s feasibility parameters over a timeframe of 1 year. The parameters describe a sequence of process requirements: enrollment, obtaining quality mRNA, completing the gene chip, holding a tumor board, medical monitor review and approval, starting treatment by 21 days after biopsy or surgical resection, and completing 1 cycle of therapy.

A percentage endpoint can express how often a defined process succeeds within the evaluated group. For a feasibility study, that kind of measure can help characterize whether the steps of a proposed research pathway can be completed. It is distinct from a clinical efficacy endpoint: completing the process does not establish that the selected treatment improves a health outcome.

The registry record does not report the primary endpoint’s observed numerator, denominator, or percentage. Although the record reports enrollment of 16 and describes 14 eligible patients in the arm, those counts alone do not establish how many participants met every feasibility criterion. The information about two subjects found ineligible after biopsy also means the analyzed population and handling of those subjects need to be specified to interpret a final percentage. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What the primary measure represents. The primary endpoint is a binary participant-level outcome: a participant either meets the complete set of feasibility parameters or does not, under the registry’s definition. The reported summary is intended to be a percentage of participants meeting that definition. The criteria span testing, review, treatment initiation, and completion of a therapy cycle. This makes the endpoint a measure of whether the entire pathway was carried through, rather than a measure of only whether molecular testing produced a profile.

General explanation of a binary percentage. For a binary outcome, the percentage is calculated from the number meeting the specified condition relative to the defined analysis population. The population definition matters because exclusions, missing assessments, or incomplete follow-up can change which participants belong in the denominator. The registry record identifies 16 enrolled participants and describes 14 eligible patients in the treatment arm, while also noting two subjects were ineligible after biopsy because their tumors were benign. It does not report the final endpoint numerator, denominator, or rules for handling participants without all assessments. Therefore, no primary percentage can be interpreted from these counts alone.

Precision and uncertainty. General statistical interpretation of a percentage should consider its uncertainty, often expressed with a confidence interval. A confidence interval describes a range of values compatible with the observed data under a specified statistical method; it does not guarantee that the true value lies in that range. With a small study group, an estimate may be imprecise, but the registry record does not report a confidence interval or enough primary endpoint results to assess precision. No uncertainty estimate should be inferred from enrollment alone.

Study design and comparison. This is a single-group study with no randomized allocation and no masking. General statistical principle: without a concurrent comparator, observed outcomes describe the group that received the study pathway, but do not isolate the effect of the pathway from other influences. In particular, the design cannot provide a randomized comparison of molecular-guided planning against another treatment-planning approach. The registry explicitly frames the study as a feasibility assessment and says it was not studying the effectiveness of the proposed therapy combinations.

Secondary outcomes. The registry lists adverse events, overall response rate using RECIST criteria, and treatment activity using progression-free survival as secondary outcomes. Each asks a different question from the primary feasibility endpoint. General explanation: response outcomes describe tumor response under a stated assessment framework, while progression-free survival concerns time until a defined event or censoring. Their interpretation depends on outcome definitions, assessment timing, follow-up, and analysis methods. Those details and numerical results are not reported in the registry record, so no effect estimate or precision can be described for these outcomes.

Analysis plans and multiplicity. The record lists 4 outcome measures and no analysis records. The presence of multiple outcomes can raise a general statistical concern about multiplicity: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a detailed statistical analysis plan. It is not possible to determine whether such methods were planned or used.

Planning illustrations. Any sample-size figures based on an observed effect are planning illustrations, not observed power. General explanation: power calculations explore the sample size that might be required under stated assumptions; they do not show the probability that a completed study has established a result. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. These assumptions do not describe this single-group trial’s design, and the registry does not report the trial’s own sample-size justification. Numerical planning estimates and an observed primary effect are not reported in the registry record.

Distributional assumptions. General explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. It can make standard errors too small if the model does not account for the extra variability. The primary endpoint is described as a participant percentage, but the registry record does not report a model for its analysis or any over-dispersion assessment. No claim about a model fit or correction can be made.

Recalculation and sponsor analysis. A recalculated estimate from summary statistics, when available, is an unadjusted check and may not reproduce a sponsor’s analysis if methods or populations differ. The registry record does not report a primary endpoint estimate to recalculate, and no sponsor analysis result is included in the registry record described. There is consequently no recalculated primary result to compare with a sponsor analysis.

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("Guided Therapy")
n      <- c(14)
events <- c(14)
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  Guided Therapy  14  14  100.0  76.8  100.0  78.5  100.0  78.2  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures, including the primary feasibility endpoint and secondary outcomes concerning adverse events, RECIST overall response rate, and treatment activity using progression-free survival. It also lists no analysis records. These registry entries do not reveal whether outcomes were tested formally, which outcomes were prioritized beyond their primary or secondary labels, or whether any adjustment for multiple testing was used. The statistical plan and multiplicity procedures are not reported in the registry record.

Missing data handling is also not described. The primary endpoint requires completion of several steps, so an incomplete assessment could affect whether a participant is classified as meeting the full feasibility definition. The record does not state how missing mRNA results, incomplete gene-chip procedures, absent reviews, delayed treatment starts, or incomplete therapy cycles were handled. It also does not provide a participant flow accounting for these possibilities.

The population description notes that all subjects had soft tissue disease in which biopsy was possible, and that two subjects were deemed ineligible after biopsy because their tumor type was benign. The record does not specify how those participants were treated in the primary endpoint analysis or give the final analysis denominator. It also does not report whether the primary endpoint used an intention-to-treat, eligible-participant, or other analysis population. Those analysis population details are not reported in the registry record.

These omissions limit assessment of selection, missingness, and the robustness of the endpoint estimate. They do not establish that data were missing or that any particular handling method was used; they mean the registry record does not describe those details.

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 non-serious adverse event terms

The registry’s serious adverse event figures list 14 participants at risk and 0 affected in the Guided Therapy group. For other adverse events, it lists 14 participants at risk and 12 affected. These counts should be read as separate registry summaries. The record does not provide serious adverse event terms, and no top serious event terms are listed.

The counts do not convey event timing, duration, severity grading, recurrence, or whether an event was considered related to the study intervention. Those details are not reported in the registry record. The field for deaths is null; this is not a reported numerical death count and should not be interpreted as a stated count of zero.

The group is small and there is no comparator arm, so these figures do not support a comparative estimate of safety. They also do not describe the safety of every treatment combination that might be selected after testing. The trial’s stated focus was feasibility, and its brief summary says the effectiveness of the proposed combinations was not under study. The posted adverse-event counts are therefore limited descriptive information, not a complete account of risk or a basis for comparing treatment strategies.

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

The main statistical question is whether the molecular-testing and treatment-planning pathway could be completed according to prespecified feasibility steps. The registry defines those steps but does not report how many participants met all of them or the resulting percentage. Consequently, the posted information does not quantify the primary feasibility outcome or its precision.

Enrollment and eligibility information provides context but cannot substitute for an endpoint result. The registry records enrollment of 16 and describes 14 eligible patients in the arm; it also reports two subjects deemed ineligible after biopsy because the tumor was benign. The final analysis population and endpoint denominator are not reported in the registry record. No primary endpoint confidence interval is reported either.

The information also does not establish whether treatment combinations chosen through molecular profiling improve response, prolong progression-free survival, or are superior to another approach. The study had a single group and no concurrent comparator, and the brief summary says treatment effectiveness was not the purpose of the study. Although response and progression-free survival are listed as secondary outcomes, their numerical results are not reported in the registry record.

The safety counts describe participants recorded as affected by serious or other adverse events, but event details and a death count are unavailable in the registry record. Those counts should not be interpreted as a complete safety profile or as comparative evidence.

In practical statistical terms, the registry record documents the feasibility objective, the process definition, design, enrollment, and limited adverse-event counts. It does not include the central primary outcome estimate, associated uncertainty, or enough analysis detail to evaluate missing data and endpoint classification. The appropriate interpretation is therefore constrained to what is documented: the study was designed to assess feasibility, while the reported record does not quantify whether its feasibility criteria were achieved.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary question concerns feasibility of a multi-step research pathway rather than treatment effectiveness. The endpoint combines successful enrollment, molecular testing, clinical review, treatment initiation within a defined period, and completion of therapy. Such an endpoint can capture whether the full process is workable, but it also makes the outcome dependent on several distinct steps and on how incomplete cases are classified.

The distinction between process success and clinical benefit is important. A pathway may be feasible without demonstrating that its treatment choices improve patient outcomes. The registry’s brief summary explicitly separates the feasibility objective from the effectiveness of therapy combinations. The single-group design also means that there is no concurrent control against which to assess comparative outcomes.

The trial further illustrates why a defined endpoint is not enough on its own for statistical interpretation. A reader also needs the observed number meeting the definition, the analysis denominator, a measure of uncertainty, and information about missing data and analysis populations. Those primary-result and analysis details are not reported in the registry record, limiting what can be concluded even though the feasibility criteria are described.

The listed secondary outcomes broaden the questions the study intended to address, but the record does not provide numerical results for them. Separating feasibility, safety, response, and progression-free survival prevents one type of evidence from being mistaken for another. In this record, the design and endpoint definition can be described, but results for the primary and listed secondary outcomes cannot be quantified.

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 limitation for interpretation is that the registry record does not report the observed primary endpoint count or percentage. It also does not provide a confidence interval or other measure of precision. Without the numerator, denominator, and uncertainty estimate, the frequency of meeting the feasibility definition cannot be evaluated.

The registry describes enrollment of 16, 14 eligible patients in the arm, and two subjects deemed ineligible after biopsy because of benign tumor type. It does not state how those subjects were handled in the primary analysis or identify the final analysis population. The criteria involve multiple sequential requirements, but the record does not describe the status of each step, reasons for noncompletion, or missing-data procedures.

The design was single group, without randomized allocation, masking, or a concurrent comparator. Therefore, the record cannot support a comparative estimate of the pathway’s effect. The stated purpose was feasibility rather than effectiveness, and the registry does not report numerical results for the listed response and progression-free survival outcomes.

Safety reporting is limited to participant counts. Serious event terms are not listed, and the death field is null rather than a numerical count. Event timing, severity, attribution, and follow-up are not reported in the registry record.

The statistical analysis plan, sample-size justification, interim analyses, and multiplicity handling are not reported in the registry record. The record also lists no analysis records. These absences limit assessment of how outcomes were analyzed; they do not establish which methods were or were not used in practice.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Molecular Guided Therapy for Refractory or Recurrent Neuroblastoma — NCT01355679.
• Registry record last updated 2024-08-06; status last verified 2024-08.
• Results first posted 2016-07-28.
• 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

NCT01355679 is a completed single-group feasibility trial of molecular-guided therapy planning for refractory or recurrent neuroblastoma. The registry lists enrollment of 16, while the arm description refers to 14 eligible patients; the primary endpoint description notes two subjects were deemed ineligible after biopsy because their tumor type was benign.

The primary endpoint was the percentage meeting a set of feasibility parameters over 1 year, including molecular testing, clinical review, timely treatment initiation, and completion of 1 cycle of therapy. The observed endpoint result and its precision are not reported in the registry record.

Listed secondary outcomes include adverse events, RECIST overall response rate, and treatment activity using progression-free survival. The posted safety counts are 0 serious adverse events among 14 at risk and 12 participants with other adverse events among 14 at risk. The record does not report numerical results for the secondary efficacy outcomes or detailed analysis methods.