Pegylated Interferon ALFA-2b in Children With Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pegylated Interferon ALFA-2b in Children With Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas (NCT02343224), a na phase 2 study. The primary outcome is Number of Children Responding to Treatment.

2. Clinical Question

The trial was intended to characterize tumor response to pegylated interferon alfa-2b in a pediatric population with progressive disease. Its stated purposes also included learning about side effects, MRI images, and quality of life. The available record identifies event-free survival and overall survival as secondary outcomes, but does not provide their results or assessment details in the information available for this analysis.

Because this was a single-group study, its primary question is descriptive: what response category did study participants meet after treatment, under the study's specified assessment approach? It is not a randomized comparison of pegylated interferon alfa-2b against another treatment or a control condition. As a result, the registry design cannot by itself distinguish a treatment-associated response pattern from outcomes that might have occurred without this intervention.

The record gives an enrollment of 9 and marks the study completed. It does not report the number of enrolled participants included in the Month 12 response assessment, the primary response count, or reasons participants may not have contributed an assessment. Those omissions limit how fully the primary question can be answered from the posted information.

3. Trial Design

This was a phase II study with a single-group model. The registry lists allocation as not applicable and masking as none. The enrollment was 9, and the study status is completed. The record gives a start date of 2014-11 and a primary completion date of 2020-11-11.

The intervention was pegylated interferon alfa-2b. The planned administration described in the registry was PEG-Intron based on body weight at 1 mcg/kg/dose once a week. That describes the intended regimen; information about actual treatment exposure, dose changes, adherence, or treatment duration is not reported in the registry record available for this analysis.

The official study title specifies children with recurrent or refractory and radiographically or clinically progressive juvenile pilocytic astrocytomas and optic pathway gliomas. The primary outcome was the number of children responding to treatment at Month 12. The record describes response categories and their imaging-based criteria. Event-free survival and overall survival appear among the secondary outcomes, but the available record does not give their timeframes or results.

Without a concurrent comparator, observed outcomes can describe what happened among participants in this study, but they cannot establish how those outcomes compare with an alternative treatment or with no study intervention. Lack of masking also means the registry does not describe a blinded outcome-assessment process. Whether the imaging reviewers were independent or masked is not reported in the registry record.

The record does not report a sample-size justification, a recruitment target rationale, or a protocol-based statistical analysis plan. Any planning calculations associated with the posted displays are illustrations based on stated assumptions, not a description of how this study was designed. The sponsor's own design rationale, if any, is not reported in the registry record.

The registry describes study purposes beyond tumor response, including side effects, MRI images, and quality of life. However, the information does not specify the measurement instruments, assessment schedules, or analysis methods for those purposes. Those details would be needed to understand how consistently such measures were collected and how they were intended to inform the study.

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

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 Number of Children Responding to Treatment, measured over Month 12.

The primary endpoint is the number of children responding to treatment at Month 12. The registry defines the response assessment using complete response, partial response, or stable disease. The classification is anchored to the pre-study baseline scan closest to study entry and considers target and non-target lesions, as well as the appearance of new lesions.

Complete response requires disappearance of all target and non-target lesions and no new lesions. Partial response requires a ≥ 65% decrease in the sum of the products of the three perpendicular diameters of all target lesions, with no new lesions. Stable disease is defined as neither enough decrease to qualify as partial response nor enough increase in a single target lesion to qualify as progressive disease, and with no new lesions.

As a general statistical concept, a categorical response endpoint can summarize the proportion or number of participants meeting a prespecified clinical and imaging definition at a chosen assessment time. The registry's primary outcome is expressed as a count of participants, not as a continuous measure of tumor size. This approach makes the endpoint interpretable against explicit response categories, while its meaning depends on the criteria and the completeness and consistency of assessments.

The Month 12 response count itself is not reported in the registry record available for this analysis. The record also does not report how many participants had an evaluable Month 12 scan or how missing or indeterminate scans were handled. Consequently, the endpoint definition can be described, but the observed primary response result and its precision cannot be assessed from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help translate trial observations into estimates and clarify how much uncertainty surrounds them. In this study, the registry identifies a participant-count endpoint and a single-group design, but the available record does not report the primary response count, a confidence interval, or a detailed statistical analysis plan. The concepts below explain how such information is generally interpreted; they do not describe methods that the registry confirms were used.

What does a participant count represent?

The primary outcome is the number of children classified as having complete response, partial response, or stable disease at Month 12. A count is an absolute number, and its interpretation depends on knowing the population assessed. For example, a count among all enrolled participants answers a different descriptive question from a count among only those with an evaluable scan. The record gives an enrollment of 9, but does not report the number assessed at Month 12 or the primary analysis population. Therefore, the denominator and the handling of participants without an assessment are not reported in the registry record.

As general statistical context, a proportion can be useful when both the number meeting an endpoint and the number assessed are known. The proportion makes the endpoint count interpretable relative to the assessed group, while a confidence interval expresses uncertainty around that estimate. Neither a proportion nor a confidence interval for the primary endpoint can be recovered from the registry information without adding or deriving information that is not reported.

Why does the endpoint definition matter?

The registry specifies response categories tied to imaging criteria and the appearance of new lesions. Complete response, partial response, and stable disease are not interchangeable labels: they reflect different patterns under the stated rules. The partial response criterion uses a decrease in the sum of the products of three perpendicular diameters, and stable disease is defined relative to the thresholds for partial response and progressive disease. This makes the classification dependent on a baseline scan and subsequent assessment.

As a general measurement principle, an endpoint is more interpretable when the assessment rules, timing, and data collection procedures are clear. The registry identifies the baseline reference scan and the Month 12 timeframe, but the available record does not report details such as assessor training, independent review, adjudication, or handling of scans that could not be classified. Without those details, the reproducibility of the assessment cannot be evaluated from this record.

What can a single-group study estimate?

A single-group study can describe observed outcomes among participants who receive the study intervention. It does not contain a concurrent control arm for estimating a treatment contrast. In general, random allocation to concurrent groups helps balance known and unknown prognostic factors on average, whereas an uncontrolled design cannot separate treatment-associated outcomes from other influences with the same degree of protection. Here, allocation is listed as not applicable and the model as single group.

The design therefore matters when interpreting any apparent response. The primary outcome could describe participants meeting the registry's response criteria, if the result and assessment denominator were available. It would not, by itself, quantify the difference that would have occurred under a comparator condition. The record does not report a historical control analysis or another strategy for constructing a comparison.

How should uncertainty be understood?

As general statistical context, a confidence interval gives a range of values compatible with the observed data under specified assumptions. A wide interval indicates limited precision, while a narrower interval indicates more precision. For a small study, estimates can be sensitive to the outcome of individual participants; nevertheless, the exact uncertainty depends on the outcome counts and the analysis method. Because the primary count and its interval are not reported, the precision of the response estimate cannot be assessed.

Statistical significance, if reported, would not resolve the design limitations. A significance test generally assesses data relative to a specified null hypothesis and depends on the analysis plan. The registry information available does not report a primary hypothesis test, its null value, or the statistical model. No p-value for the primary endpoint is reported in the registry record.

What do the planning illustrations mean?

Sample-size illustrations are planning calculations, not observed outcomes and not a measure of the study's achieved power. The stated assumptions for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. Those assumptions do not match the recorded single-group design, which has no two-arm allocation. Thus, such illustrations should not be read as the design or analysis used for this trial.

As general statistical context, a sample-size calculation asks how many participants or events might be needed under specified assumptions to detect a chosen effect with a chosen error rate and power. It does not show what the trial actually observed, and it does not establish that an effect exists. In this case, no sample-size justification for the actual study is reported in the registry record. The assumptions attached to planning illustrations should be distinguished from a protocol's original design rationale.

Why can over-dispersion matter?

As general statistical context, over-dispersion occurs when observed variation is greater than expected under a statistical model. If a model assumes less variation than the data contain, estimated uncertainty can be too small, making results appear more precise than warranted. This concept is relevant to some count outcomes, but the registry record does not identify an over-dispersion model or provide a dispersion estimate for this study. The primary outcome is a participant count, and no model-based primary analysis is reported.

Overall, the posted information supports a description of the endpoint definition and study design, but does not report the primary outcome result or the methods needed to reconstruct an estimate and its uncertainty. General statistical explanations should not be mistaken for confirmation of the trial's own analysis procedures.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response outcome and secondary outcomes for event-free survival and overall survival. It also describes broader study purposes involving side effects, MRI images, and quality of life. The available record does not report a hierarchy among secondary outcomes, a multiplicity adjustment, or an analysis plan specifying how multiple outcomes or tests were to be interpreted. Therefore, it is not possible to determine whether the study prespecified any procedure to control the chance of false-positive findings across multiple analyses.

As general statistical context, examining several outcomes or several analyses can increase the chance that at least one result appears unusual by chance. Methods for addressing multiplicity can include prespecified testing sequences or adjusted significance thresholds, but the registry does not say whether any such approach was planned or used in this study. The number of analyses listed in the record does not substitute for a description of the methods used.

Missing-data handling is also not reported in the registry record available for this analysis. In particular, the record does not state how participants without a Month 12 scan, with an indeterminate scan, or with incomplete follow-up were treated in the primary response analysis. It does not report the primary analysis population or whether participants were analyzed according to enrollment, treatment received, or endpoint evaluability.

As general statistical context, missing outcome data can affect both the denominator and the interpretation of an estimate. The direction and magnitude of any effect depend on why data are missing and on the analysis assumptions; they cannot be inferred from the enrollment figure alone. The registry record does not provide enough information to assess whether missing data could have influenced the endpoint findings.

Likewise, no details are reported about interim analyses, stopping rules, or adjustments to the planned analysis. These features should not be assumed either way. The absence of a reported plan limits assessment of how outcome selection, repeated testing, and incomplete observations were handled.

11. 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: anorexia, grade 3 (11.1%).

The serious adverse event summary lists 9 participants at risk and 1 affected. The other adverse event summary lists 9 participants at risk and 9 affected. The registry also records 2 deaths. These are separate fields in the posted safety record; the record does not explain how the event categories overlap or how the deaths relate to the affected-participant counts.

The top serious term is anorexia, grade 3, listed at 11.1%. This identifies a reported serious adverse event term and its registry percentage. It should not be interpreted as the frequency of every serious event, or as an estimate of treatment-attributable risk, without further information about event definitions and attribution. The available record does not provide additional detail about timing, duration, seriousness criteria, relatedness to treatment, or whether events occurred in the same participant.

As general statistical context, safety summaries are descriptive unless the design and analysis support a comparison. Here, there is no control group, so these counts cannot establish a comparative excess or reduction in adverse events. The deaths are recorded, but their causes and relationship to treatment are not reported in the registry record. The counts therefore describe the posted safety information without establishing causation.

The at-risk counts should not be assumed to equal the number with complete safety follow-up for every event type unless the registry defines them that way. The information available does not report event-level detail or the duration over which participants were monitored. These limitations matter when comparing safety profiles across studies or interpreting the counts as risks over a defined period.

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

The registry record documents a completed phase II study of pegylated interferon alfa-2b in children with progressive juvenile pilocytic astrocytomas or optic pathway gliomas. It defines a Month 12 response endpoint using imaging-based categories and lists event-free survival and overall survival among secondary outcomes. It also reports selected safety summaries. These details establish what the study set out to examine and identify the information posted about design and safety.

The record does not report the primary response count, the number assessed for response, or a confidence interval. Consequently, it does not allow readers to quantify the observed response result or judge its precision. The endpoint definition alone is not an outcome result. The names of secondary outcomes likewise do not establish what participants experienced, since their results are not reported in the information available for this analysis.

The single-group design is central to interpretation. It can describe outcomes among participants receiving the study intervention, but it cannot provide a concurrent randomized comparison. Even a reported response count would not, on its own, establish what would have happened under a different treatment or without the study intervention. This is a design limitation, not a claim about the direction of any observed outcome.

The safety counts and the anorexia, grade 3, term should also be read as descriptive registry summaries. The record does not establish that the deaths were caused by treatment, and does not report sufficient event-level information to assess causation. A finding recorded during a study is not automatically attributable to the intervention.

As general statistical context, a result is most informative when its endpoint definition, analysis population, missing-data handling, and uncertainty are all available. Here, key elements needed to evaluate the primary endpoint are not reported in the registry record. The posted information therefore supports understanding the trial's question and some aspects of its conduct, but not a conclusion that the intervention did or did not produce a particular response or comparative benefit.

No medical decision should be based on this registry summary alone. It is a limited account of one single-group study, and the available information does not establish comparative effectiveness or causation.

13. Why This Trial Matters Statistically

This trial raises several statistical issues that are important in small, single-group clinical studies. The first is the distinction between defining an outcome and reporting its result. The registry gives detailed criteria for complete response, partial response, and stable disease at Month 12, but the response count is not reported in the record available for this analysis. Clear criteria are necessary for interpreting a result, but they cannot replace the result itself.

A second issue is the denominator. The record reports enrollment of 9, yet it does not report the number of participants with an evaluable Month 12 assessment or identify the primary analysis population. Counts are most interpretable when readers know who was included and how participants with missing or indeterminate assessments were handled. Without this information, the endpoint result and its precision cannot be evaluated.

The single-group design also illustrates the difference between describing outcomes and estimating a comparative effect. Outcomes among treated participants may be important to document, but without a concurrent control group they do not provide a like-for-like estimate of what would have occurred under an alternative condition. That distinction should remain clear even when an endpoint is defined precisely.

The safety summaries offer another useful statistical lesson: counts, event terms, and causal interpretation are not the same thing. The registry reports affected participants, deaths, and a serious event term, but does not provide the detail needed to connect these observations causally to treatment. Reporting the safety figures without overstating their meaning preserves what the record can support.

Finally, the record underscores why statistical plans and missing-data procedures matter. The availability of an outcome name is not enough to assess multiplicity, analysis choices, or uncertainty. Reporting these details allows readers to understand how observed data became a result and what conclusions are warranted. In this case, several such methods are not reported in the registry record.

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 primary limitation for interpreting this trial is that the registry information available does not report the primary Month 12 response count. It also does not report the number of participants with an evaluable response assessment. Although enrollment was 9, enrollment should not be treated as the endpoint denominator without a reported analysis population.

The study was single group, with allocation listed as not applicable and masking listed as none. There was no concurrent control arm for a direct comparison. The record does not report independent or blinded imaging review, so the process used to reduce assessment bias cannot be evaluated from the available information.

The registry describes the response criteria and baseline scan reference, but additional operational details are not reported, including how indeterminate scans or participants without a Month 12 assessment were handled. The analysis plan, confidence intervals, hypothesis tests, and methods for missing data are also not reported in the registry record. These omissions restrict assessment of the reliability and precision of the primary outcome.

The secondary outcomes are named, but their results, timeframes, and analysis details are not available in the information used for this analysis. The study's stated purposes also include side effects, MRI images, and quality of life, without measurement and analysis details. For safety, the posted summaries do not give event-level timing or establish relationships between adverse events, deaths, and treatment.

Finally, the study's enrollment is limited, and a study of this size can offer only limited precision in descriptive estimates. The exact uncertainty cannot be assessed without the endpoint result and its analysis. The registry record does not report a sample-size rationale or statistical plan, so the enrollment target's original basis cannot be evaluated.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pegylated Interferon ALFA-2b in Children With Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas — NCT02343224.
• Registry record last updated 2022-01-24; status last verified 2022-01.
• Results first posted 2022-01-24.
• 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.

18. Record Summary

This is a completed phase II, single-group study of pegylated interferon alfa-2b in children with recurrent or refractory and progressive juvenile pilocytic astrocytomas or optic pathway gliomas. The registry lists enrollment of 9, a start date of 2014-11, and a primary completion date of 2020-11-11. The planned regimen was PEG-Intron at 1 mcg/kg/dose once a week.

The primary outcome was the number of children meeting response criteria at Month 12, including complete response, partial response, or stable disease. The primary response count and the evaluable assessment denominator are not reported in the registry record available for this analysis. Event-free survival and overall survival are listed as secondary outcomes, without results in the available record.

The safety summary lists 1 affected among 9 at risk for serious adverse events, 9 affected among 9 at risk for other adverse events, and 2 deaths. Anorexia, grade 3, is listed among the top serious terms at 11.1%. The design has no concurrent comparator, and the available record does not report the primary endpoint analysis plan or handling of missing data.