Antineoplaston Therapy in Treating Patients With Primary Malignant Brain Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Antineoplaston Therapy in Treating Patients With Primary Malignant Brain Tumors (NCT00003475), a na phase 2 study. The primary outcome is Number of Participants With Objective Response.

2. Clinical Question

The registry describes the study as a phase II investigation of the effects, both good and bad, of antineoplaston therapy in adults whose primary malignant brain tumors had not responded to standard therapy. That stated purpose includes response and safety; it does not, by itself, establish that the therapy is beneficial or harmful.

Because the design has one group and no listed comparator, the clinical question is about outcomes among participants receiving the therapy, not a randomized estimate of the difference between treatments. The registry lists percentage of participants who survived as a secondary outcome, but the survival result is not reported in the registry record. The primary response result is also absent, so the recorded question can be described, but its answer cannot be quantified from this record.

3. Trial Design

The registry classifies this as a phase II, single-group study. It lists enrollment of 40, allocation as not applicable, and masking as none. The study status is completed. Its recorded start is 1996-02, and the primary completion date is 2011-05; an overall completion date is not reported in the registry record.

The intervention is Antineoplaston therapy, named as Atengenal and Astugenal. The arm description specifies intravenous infusion every four hours for at least 12 months, with increasing doses until the maximum tolerated dose is reached. The registry does not describe a separate control arm, randomized assignment, or masking procedure. The record therefore does not support a treatment-versus-control comparison.

The primary outcome is the number of participants with objective response at 12 months. Response is described using MRI assessment of target lesions under RANO criteria. The record also lists percentage of participants who survived as a secondary outcome. Although two outcome measures are listed, no outcome analyses are listed in the registry record, and no numerical outcome results are included in the registry record for interpretation.

The registry’s rationale says that standard therapies for the stated population provide very limited benefit and that the properties attributed to antineoplaston therapy motivated its study. This is the study rationale, not an observed finding from this trial. The registry record does not report the protocol’s sample-size justification, an interim-analysis plan, or a detailed statistical analysis plan. Those omissions limit what can be concluded about how the study was designed to estimate effects or assess uncertainty.

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:

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 Participants With Objective Response, measured over 12 months.

The primary endpoint is the number of participants with an objective response at 12 months. The registry defines response using RANO criteria for target lesions assessed by MRI. A complete response means disappearance of all disease sustained for at least four weeks. A partial response means at least a 50% decrease in the sum of the products of the greatest perpendicular diameters of all measurable enhancing lesions, sustained for at least four weeks.

In general, a response endpoint turns imaging observations into a defined outcome that can be counted. Explicit criteria help make the meaning of response more consistent than an informal judgment alone. Requiring a response to persist for the stated duration also distinguishes a sustained change from a transient observation. The endpoint is time-specific: the registry identifies 12 months as its timeframe, so the question concerns response at that assessment horizon, rather than response at any time or survival over an unspecified period.

A count is meaningful alongside the number of participants assessed. The registry lists enrollment of 40, but it does not report the number assessed for this endpoint, the number responding, or how missing assessments were handled. Consequently, the response count and the uncertainty around it cannot be evaluated from the registry record. The endpoint definition is available; its observed result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study and a primary endpoint recorded as a participant count. These features shape which statistical interpretations are possible. The record does not list outcome analyses, and a detailed statistical analysis plan is not reported in the registry record. The concepts below are general explanations of how such data are often considered; they are not claims about analyses performed in this study.

What does a count endpoint represent?

A count of participants with an event records how many people met a defined outcome. For a response endpoint, the event is meeting the specified response criteria within the stated timeframe. A count should be interpreted with its denominator: the number of participants who were eligible for the assessment and whose outcome could be determined. Enrollment alone does not establish that every participant had an observed outcome at the endpoint assessment. Here, the response count, assessment denominator, and handling of unavailable assessments are not reported in the registry record.

In general, analysts may express a binary outcome as a proportion as well as a count. Such a proportion is the observed frequency of the event in the group under study. It is descriptive of that group and depends on the outcome definition, follow-up, and participants included in the analysis. No response proportion can be reconstructed from the registry information because the response count and endpoint denominator are absent. No recalculated analysis is available to compare with a sponsor analysis.

Why does the design matter?

A single-group study can document outcomes among participants receiving an intervention, but it does not estimate a contrast against a concurrent control group. General changes over time, characteristics of enrolled participants, and other influences cannot be separated from the intervention effect using a one-group outcome alone. Randomization, when used in a suitable comparative design, is a method for balancing known and unknown factors between groups on average. This study is not recorded as randomized and has no comparator listed, so that type of between-group inference is not available from the registry record.

Masking can reduce the potential influence of knowledge about assigned treatment on assessment or reporting. The record lists masking as none. The endpoint uses specified MRI criteria, which make the response definition explicit, but the registry does not describe who assessed scans or whether assessments were independently reviewed. Those details are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the observed data under a statistical model and its assumptions. It communicates uncertainty around an estimate; it does not guarantee that the true value lies in the interval. For a binary response outcome, uncertainty depends on the number of observed responses and the denominator, as well as the method used to calculate the interval. Since the response result and denominator are absent, neither an estimate nor an interval can be discussed for this trial.

Statistical tests and confidence intervals answer related but different questions. A test evaluates data against a specified null hypothesis under its assumptions; a confidence interval conveys the range of effect sizes reasonably compatible with the data. Neither substitutes for a clearly defined estimand, outcome, population, and follow-up period. The registry record does not report a test, interval, or detailed analysis plan for the primary endpoint.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability exceeds what a particular statistical model assumes. It matters for outcomes whose model relies on a specified variance structure, because underestimated variability can make uncertainty appear too small. The primary endpoint is a binary participant outcome summarized as a count, not a repeated event count per participant. The registry does not report a model or analysis that would permit an assessment of over-dispersion, so it would be inappropriate to claim that it was present or addressed.

How do the planning assumptions relate to this study?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, not the trial’s own design. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it considers detecting a stated fraction of the observed effect. For non-time-to-event outcomes, the stated planning convention is participants per arm. These are assumptions for a hypothetical planning exercise, not evidence that this single-group study used two arms or those design choices.

Planning sample sizes are not observed power. They are illustrations conditional on assumptions about an effect and a statistical method. The registry record does not report a sample-size justification for the trial, and no planning values are included in the registry record for this interpretation. Such illustrations cannot supply the missing response result, establish precision, or be treated as a retrospective evaluation of study success.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of number of participants with objective response and a secondary outcome of percentage of participants who survived. It does not report a testing hierarchy, a multiplicity adjustment, or a plan for interpreting several outcome tests. When multiple outcomes are tested, the chance of at least one apparently notable result can increase; in general, a prespecified hierarchy or adjustment can help address that issue. No such approach is reported in the registry record, and no outcome analyses are listed.

Missing-data handling for the primary response endpoint is also not reported. The record does not state how participants without an MRI assessment at 12 months were treated, whether assessments outside that timeframe were included, or what analysis population was used. Enrollment of 40 does not establish the number with an observed primary outcome. These details matter because an outcome count and its denominator must be interpreted together.

The population field for the primary outcome is blank, and the registry record does not identify an intention-to-treat, per-protocol, or other analysis population. It also does not report a method for handling missing survival information. These omissions do not show that a particular method was or was not used; they mean the method is not reported in the registry record. Without analysis populations and missing-data procedures, it is not possible to assess how participant availability may have affected the posted outcome estimates. No numerical outcome analyses are listed in the record.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: seizure (12.5%), somnolence/depressed level of consciousness (12.5%), infection (documented clinically): lung (pneumonia) (10.0%), thrombosis/thrombus/embolism (7.5%), central venous catheter infection (5.0%).

The safety record lists 40 participants at risk for serious adverse events and 21 participants affected. It separately lists 40 at risk and 40 affected for another adverse-event category. The registry fields do not explain that second category in the information available for interpretation, so the figures should be read as separate recorded categories rather than combined or reclassified.

Selected serious adverse-event terms are reported with percentages: seizure, 12.5%; somnolence/depressed level of consciousness, 12.5%; lung infection (pneumonia), 10.0%; thrombosis/thrombus/embolism, 7.5%; central venous catheter infection, 5.0%; and pain involving the head/headache, 5.0%. The registry does not specify the denominator or counting convention for these term percentages in the registry record. They should not be converted into participant counts or added together; people may have more than one event, and the categories need not be mutually exclusive.

These figures describe safety reporting within the single therapy group. They do not show whether event frequency was higher or lower than it would have been under another treatment. Deaths are not reported in the registry safety fields. The figures therefore do not provide a complete comparative safety assessment.

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

The record establishes that a completed phase II, single-group study was registered to evaluate antineoplaston therapy in adults with primary malignant brain tumors that had not responded to standard therapy. It identifies the treatment components and schedule, the 12-month MRI-based response endpoint, and a secondary survival outcome. It also contains safety-event reporting for the therapy group.

What the registry does not establish is the observed primary response result. The number of participants who met the RANO response definition, the number assessed at 12 months, and an estimate of uncertainty are not reported in the registry record. The survival result is likewise not reported. The study’s registered enrollment cannot be substituted for these outcome data, and the endpoint definition alone cannot reveal how participants fared.

Even if one-group response results were available, they would describe outcomes in that study group rather than provide a randomized comparison. The record lists no comparator, allocation is not applicable, and masking is none. A one-group result cannot by itself establish what would have happened to similar participants under another treatment or without the intervention. Nor does a completed study status mean that its primary outcome was positive or that a treatment effect was demonstrated.

The adverse-event figures describe reported events in the study group, but there is no comparator with which to estimate a relative safety difference. The record also does not report deaths in the safety fields or explain all event-category details. Thus, the information supports a description of the registered design and selected safety reporting, but not a balanced estimate of treatment benefit and harm.

In short, the registry record supplies the question and some design and safety information, but not the numerical primary or secondary outcome findings needed to characterize efficacy or survival. No conclusion that the therapy works or does not work follows from the missing results.

13. Why This Trial Matters Statistically

This trial is statistically instructive because its design and its endpoint need to be kept distinct from the result. The study is registered as a single-group phase II study, while its primary outcome is a count of participants meeting a defined MRI response criterion at 12 months. A clear endpoint makes the intended measurement understandable, but it does not replace the observed count, denominator, or an uncertainty estimate.

The record also illustrates why enrollment is not an outcome. Enrollment is listed as 40, but the registry does not report how many participants had an evaluable 12-month assessment or how many met response criteria. Without those details, neither response frequency nor precision can be assessed. This distinction is central when interpreting clinical trial registries: design and planned measurement can be available even when analyzed results are not.

The lack of a comparator is equally important. A one-group study can describe outcomes and adverse events in the treated group, but it does not make a like-for-like treatment comparison. The registry’s safety figures should therefore be read as within-group reporting rather than evidence of relative risk versus another option.

Finally, the registry includes planning assumptions for a sample-size illustration. Those assumptions concern a hypothetical equal-allocation, two-arm planning exercise and are not the design of this single-group trial. Recognizing that distinction prevents a planning calculation from being mistaken for an observed result, an actual protocol choice, or observed power. The statistical lesson is to match every interpretation to the design and the reported data, while treating unreported results as unknown rather than as evidence in either direction.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most consequential limitation of the registry record for statistical interpretation is that it does not report the primary response result. The record specifies the 12-month response definition but gives no observed responder count, endpoint denominator, confidence interval, or analysis. The secondary survival outcome is listed without a numerical result or a reported analysis. As a result, the magnitude and precision of either outcome cannot be evaluated.

The single-group design and absence of a comparator limit causal interpretation even if descriptive outcomes were available. The record also lists no masking. It does not describe who reviewed MRI assessments, how missing endpoint assessments were handled, or which participants were included in the analysis population. These details are not reported in the registry record and should not be inferred from the endpoint definition.

The safety information is limited to figures for the therapy group and selected serious adverse-event terms. The record does not provide a comparative safety analysis, does not report deaths in the safety fields, and does not explain the counting conventions for the listed term percentages in the available information. It is therefore not possible to interpret these figures as comparative risks or to combine categories into an overall event burden.

The registry does not report the trial’s sample-size justification, interim-analysis plan, detailed statistical analysis plan, multiplicity strategy, or missing-data procedures. A planning illustration based on an observed effect is not a substitute for these protocol details and is not evidence of the study’s original design. These limitations concern what the record reports; they do not establish that unreported procedures were absent from the trial.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Antineoplaston Therapy in Treating Patients With Primary Malignant Brain Tumors — NCT00003475.
• Registry record last updated 2017-08-24; status last verified 2017-07.
• Results first posted 2016-12-19.
• 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

The registry records NCT00003475 as a completed phase II, single-group study sponsored by Burzynski Research Institute. It lists enrollment of 40, a start date of 1996-02, and a primary completion date of 2011-05. The intervention is Antineoplaston therapy, named as Atengenal and Astugenal, administered by intravenous infusion every four hours for at least 12 months with increasing doses until the maximum tolerated dose was reached.

The primary outcome is the number of participants with objective response at 12 months, assessed by MRI using RANO criteria. Percentage of participants who survived is listed as a secondary outcome. Numerical results and outcome analyses are not reported in the registry record. Safety fields list 21 participants with a serious adverse event among 40 at risk and 40 participants affected in a separate adverse-event category among 40 at risk, along with selected serious-event terms. No comparator group is listed, and deaths are not reported in the safety fields.