Medical Treatment of "High-Risk" Neurofibromas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Medical Treatment of "High-Risk" Neurofibromas (NCT00846430), a na phase 2 study. The primary outcome is Improvement of Symptoms and Pain.

2. Clinical Question

3. Trial Design

This is a phase II, completed, open-label, single-group clinical study registered as NCT00846430. The registry lists enrollment of 9 participants and identifies neurofibromatosis type 1 as the condition. Because the study has no randomized comparison group, the treatment experience is described within a single study group rather than as a head-to-head comparison of assigned arms. The record lists allocation as not applicable.

The study description concerns sequential medical therapies for high-risk plexiform neurofibromas. It states that all participants began treatment with celecoxib and interferon alpha-2b, described as the first treatment combination. Response to that treatment was to be assessed at six months using clinical and radiographic evaluations. The registry summary describes evaluation of two treatment combinations, and the intervention list also includes temozolomide and vincristine sulfate. The subsequent treatment sequence and the rules governing any change in therapy are not reported in the registry record.

Masking is listed as none, so the study was open-label. That design means treatment assignment was not concealed from participants and study personnel as it would be in a masked trial. The registry gives a start date of 2008-10, a primary completion date of 2017-04, and a completed status. The sponsor is Corewell Health West.

The primary outcome is titled “Improvement of Symptoms and Pain.” Its description refers to pain and quality-of-life scores, with physical examinations scheduled monthly during the first three months and then every three months for up to 36 months. The record lists four outcome measures, but it does not provide a numerical primary-outcome result or analysis. The sample-size planning assumptions describe a hypothetical two-arm comparison; they do not change the registered single-group design or constitute a trial comparison.

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: Period 1: Baseline to 6 months", "Period 2: After 6 month evaluation for addition of vincristine and temozolomide", if accurate and appropriate

Overall Study

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 Improvement of Symptoms and Pain, measured over Monthly physical exam first three months and then every three months after, for up to 36 months.

The primary outcome is titled “Improvement of Symptoms and Pain.” The registry describes evaluation of pain and quality-of-life scores, alongside physical examinations. Assessments were scheduled monthly during the first three months and then every three months for up to 36 months. The endpoint is therefore intended to capture whether participants experienced symptom or pain improvement over follow-up, rather than focusing only on tumor measurements.

Patient symptoms and quality of life can matter in a condition where tumors may be associated with pain, disability, organ dysfunction, or serious risk. A clinical assessment that includes pain and quality of life can reflect aspects of participants’ experience that imaging alone may not capture. In general, repeated assessments can describe changes over time, but interpretation depends on how improvement is defined, which assessment is used, how missing observations are handled, and whether the analysis accounts for repeated measurements. Those details are not reported in the registry record.

The endpoint’s title does not by itself specify a numerical threshold for improvement or identify whether the reported outcome was a score change, a categorized response, or another measure. The record supplies no numerical result for this primary outcome. It therefore does not support a conclusion about the number of participants who improved, the size of any symptom change, or the precision of an estimated effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in this record needs to be interpreted in light of the design and the level of outcome reporting. The study is registered as a single-group, open-label phase II study. It is not a randomized comparison, and the allocation field is not applicable. These features determine which statistical contrasts are available: a within-group description may be possible when outcome data are reported, but a randomized between-group treatment contrast is not part of this design.

What does a single-group design tell readers?

In general, a single-group study follows participants who receive the study intervention and describes outcomes in that group. It can document what was observed during the study, but it lacks a concurrent randomized control group for comparison. If symptoms change, the study alone cannot determine whether the change was caused by treatment, reflected the condition’s natural course, followed other care, or arose from measurement variation or other factors. Randomization is useful because it aims to balance known and unknown influences between groups; this record does not have that design feature.

The study is also open-label. In general, knowledge of treatment can influence behavior, care decisions, reports of subjective symptoms, and assessment. This is particularly relevant when an outcome includes pain or quality-of-life scores, which may involve participant reporting or judgment. The registry does not describe any masking procedures, and masking is explicitly listed as none. The absence of masking does not invalidate observations, but it is relevant when considering how objectively the outcome may have been assessed.

How should a count outcome be read?

The primary outcome is described as improvement of symptoms and pain, with evaluation of pain and quality-of-life scores. The registry classifies the outcome information as counts of participants with an event, but it does not report a primary-outcome count or define the event threshold in the record. In general, a count tells how many participants met a specified outcome definition. To interpret that count, readers need to know the denominator, the outcome definition, the assessment time, and how unavailable observations were treated. Those details cannot be reconstructed from a title alone.

For a binary outcome, a confidence interval can communicate uncertainty around an estimated event proportion. In general, the interval reflects both the observed data and the statistical method used; it is not a guarantee that the true value lies within a particular range. Small datasets often produce imprecise estimates, and a count without an interval does not fully convey that uncertainty. No confidence interval or primary-outcome estimate is reported in the registry record.

Why do repeated assessments need clear analysis rules?

The outcome schedule includes monthly physical examinations during the first three months, followed by assessments every three months for up to 36 months. Repeated observations from the same participant are related, rather than independent measurements. In general, an analysis of repeated measurements needs to specify how it represents change over time, handles correlations among observations, and defines the time point or summary used for the main result. If participants have different amounts of follow-up or miss assessments, analysis choices can also affect the result. The registry record does not report the statistical approach for these repeated assessments.

The six-month response assessment is described as a point for evaluating response to the initial combination. Since treatment is sequential, outcome interpretation could also depend on whether later therapy was initiated according to response or other criteria. The available registry description is incomplete about the later sequence and its decision rules. A statistical analysis would need to clarify which treatment exposure and follow-up period are represented in each estimate. Those methods are not reported in the registry record.

What do the planning assumptions represent?

The registry’s sample-size assumptions describe a planning illustration, not the trial’s own design or an observed analysis. They refer to a two-sided significance level of 0.05, equal allocation between two hypothetical arms, a normal approximation, and effects expressed as fractions of an observed effect. The assumptions also distinguish between time-to-event planning, which uses a total number of events, and other planning, which uses participants per arm. These are generic inputs for planning illustrations; they do not imply that this single-group study randomized participants, used those methods for its analysis, or demonstrated a particular level of power.

In general, a sample-size calculation estimates the amount of information a planned study might need under specified assumptions. Its result depends on the assumed effect, variability or event rate, statistical threshold, and design. A planning illustration based on an observed effect is not an observed-power calculation and does not demonstrate that the study found an effect. The registry record does not report the values of any resulting planning estimates in the registry record for this account.

What is known about the analysis?

The registry lists four outcome measures and zero analyses. That indicates that the record does not contain a reported analysis entry for those measures. It does not establish that no analyses were conducted outside the registry, nor does it explain why results are absent. The primary outcome’s numerical findings, statistical model, estimate of uncertainty, analysis population, and missing-data strategy are not reported in the registry record. Therefore, readers should distinguish the registered outcome plan from reported statistical evidence.

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("Open-Label Intervention")
n      <- c(9)
events <- c(9)
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  Open-Label Intervention  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and zero analyses. It identifies “Improvement of Symptoms and Pain” as the primary outcome and lists a secondary outcome concerning no reported psychological toxicity based on psychological evaluations. The record does not describe a multiplicity strategy, such as whether statistical testing across outcomes was planned, how any family of tests would be defined, or whether adjustment would be used. It also does not report numerical primary-outcome analyses. Without reported analyses and a stated approach, it is not possible to assess how multiple outcomes or repeated assessments were handled.

Missing-data methods are not reported in the registry record. The outcome schedule calls for repeated assessments during follow-up, but the record does not say how missed visits, incomplete scores, withdrawal, or incomplete follow-up were handled. In general, missing observations can affect an estimate when the availability of data is related to participants’ health, treatment, or outcome. Statistical approaches make assumptions about those missing observations, and those assumptions should be described for readers to judge the results. No such approach is available in this record.

The analysis population is also not reported in the registry record. It is not specified whether the primary analysis was intended to include all enrolled participants, only participants with available outcome measurements, or another defined population. The record does not state how participants who changed treatment or stopped treatment would be represented in an analysis. These omissions do not prove how the study was conducted; they mean that the registry entry does not document these analytic choices.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: suicidal ideation (11.1%).

For the open-label intervention group, the registry lists 9 participants at risk for serious adverse events and 1 affected. It also lists 9 at risk for other adverse events and 1 affected, with deaths reported as 0. Suicidal ideation is listed as a top serious adverse-event term at 11.1%. These are the safety figures recorded for the study group; they are not a comparison with an untreated or randomized control group.

Counts and percentages answer different descriptive questions. A count indicates the number of participants recorded as affected, while a percentage expresses a frequency relative to a denominator. The record’s percentage should be read as the registry-reported figure, not as an independently calculated estimate. The information does not state whether the serious and other adverse-event categories refer to the same participant, nor does it provide event timing, duration, severity details beyond the serious classification, or attribution to a particular treatment in the sequence. Those details are not reported in the registry record.

With no comparative arm, these figures cannot estimate how safety outcomes differ under another treatment or no study treatment. They describe observed safety reporting in this study group and should not be interpreted as a causal comparison.

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

The registry entry establishes that a completed phase II, open-label, single-group study evaluated sequential medical therapies for high-risk plexiform neurofibromas in people with neurofibromatosis type 1. It documents an intended primary focus on symptom and pain improvement, assessment of pain and quality-of-life scores, and a schedule of repeated physical examinations. It also records limited safety counts for the open-label intervention group.

The entry does not report numerical results for the primary outcome. It does not state how many participants met a defined improvement threshold, how scores changed, or how uncertain an estimated change might be. Without those results, the registry record cannot quantify the magnitude or consistency of symptom improvement. The outcome title and assessment plan describe what the study sought to measure; they are not results in themselves.

The single-group design also means that any reported before-and-after change would not, by itself, establish that treatment caused that change. Participants were not randomized against a concurrent control group, and the study was open-label. Other explanations for observed changes cannot be separated from a treatment effect using this design alone. The registry does not provide a treatment-effect estimate or a statistical comparison.

The safety entries document reported events, including the listed serious adverse-event count and the serious term of suicidal ideation. They do not provide comparative safety estimates, detailed event narratives, or attribution across the sequence of treatments. The count for deaths is reported as 0, but that figure is limited to the registry’s recorded study group and does not answer questions beyond this study record.

Accordingly, this entry is informative about the study’s registered design, treatment sequence as far as described, outcome schedule, and selected safety reporting. It is not a complete statistical report of efficacy or a basis for causal conclusions. Details such as the primary analysis, definitions of response, missing-data handling, later-treatment rules, and uncertainty estimates are not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises a central statistical issue in clinical research: a clinically important question can be difficult to answer when the design and result reporting do not support a clear comparison. The registry describes treatment for high-risk plexiform neurofibromas and identifies pain and quality of life as important outcome domains. It also records a single-group, open-label design. That combination makes careful separation of descriptive observations from causal claims especially important.

In general, a single-group study can contribute information about feasibility, follow-up, observed experiences, and events recorded during treatment. It cannot provide the same protection against confounding as a randomized comparison. With symptoms such as pain, the possibility that reporting or assessment is influenced by knowledge of treatment is also relevant. Those design considerations do not make the observations meaningless; they define what the observations can support.

The outcome schedule extends over time and includes repeated evaluations. That makes clear definitions of improvement, analysis time points, handling of repeated measurements, and missing-data rules important for interpretation. The registry record does not report those analysis details or numerical primary-outcome findings. Consequently, readers cannot assess the estimated size of any change or its statistical precision from this entry.

The record also illustrates why planning calculations must be kept separate from evidence. Its stated planning assumptions describe hypothetical two-arm calculations, whereas the registered study is a single-group study. Those assumptions do not establish that the trial used a two-arm design, and planning illustrations do not substitute for observed outcomes. Statistical interpretation depends on the study actually conducted and the analyses reported, not on a planning scenario.

Finally, the safety counts are useful as descriptive registry information but cannot be compared against a concurrent control group. Taken together, these features show why design, outcome definitions, analysis reporting, and uncertainty estimates are essential parts of a clinical trial record, not optional details surrounding the result.

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.

Several limitations are specific to the information recorded for this study. The registry identifies a single-group, open-label design, with allocation listed as not applicable. There is no randomized concurrent control group, so the study cannot make a like-for-like comparison that would help distinguish treatment effects from other causes of change. Open-label assessment is also relevant because the primary outcome includes pain and quality-of-life measures.

The primary outcome’s numerical results are not reported in the registry record. Although its description identifies pain and quality-of-life evaluation, the record does not define the threshold or rule for classifying an improvement. It also does not report an effect estimate, confidence interval, or statistical test. The complete statistical analysis plan, analysis population, and missing-data approach are not reported in the registry record.

The treatment description is incomplete for later stages. The record says participants began with celecoxib and interferon alpha-2b and that response would be assessed at six months. It also lists temozolomide and vincristine sulfate, but the subsequent sequence and the rules for moving between treatments are not reported in the registry record. This limits interpretation of treatment exposure and any outcome attributed to a particular stage.

The registry lists 9 participants enrolled, but it does not provide the participant flow or a numerical description of baseline characteristics in the registry entries. It lists four outcome measures and zero analyses, leaving the relationship between registered measures and any conducted analyses unclear. Safety reporting is limited to the listed counts and term; event details, timing, and treatment attribution are not reported. These reporting gaps do not establish what was or was not done outside the registry, but they limit what can be concluded from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Medical Treatment of "High-Risk" Neurofibromas — NCT00846430.
• Registry record last updated 2023-08-30; status last verified 2023-08.
• Results first posted 2023-08-30.
• 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.

19. Record Summary

NCT00846430 is a completed phase II study sponsored by Corewell Health West, with a start date of 2008-10 and a primary completion date of 2017-04. It enrolled 9 participants and is registered as an open-label, single-group study of sequential medical therapies for high-risk plexiform neurofibromas in people with neurofibromatosis type 1.

The registry says participants began with celecoxib and interferon alpha-2b and describes response assessment at six months. Temozolomide and vincristine sulfate are also listed, but the later sequence is not reported in the registry record. The primary outcome concerns improvement of symptoms and pain, assessed through pain and quality-of-life evaluations and scheduled physical examinations. Numerical results for that outcome and the statistical analysis are not reported in the registry record.

The record reports 1 participant affected by a serious adverse event, 1 affected by another adverse event, 0 deaths, and suicidal ideation as a top serious term at 11.1%. These are descriptive safety figures from the single study group, not comparative treatment estimates.