A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM) (NCT00735436), a non-randomized phase 2 study. The primary outcome is 24-week Overall Survival.

2. Clinical Question

The study asked whether the combination of Gliadel followed by Avastin and irinotecan could be assessed using survival 24 weeks after treatment began in patients with grade IV malignant glioma following surgical resection. The primary endpoint was the percentage of participants alive at that time. The study also listed progression-free survival and toxicity as secondary objectives.

This is therefore a question about the observed outcome in one treated group, not a randomized comparison of treatment strategies. Without a reported primary estimate, the record cannot establish what the 24-week survival percentage was. Nor can a single-group result by itself separate any treatment contribution from other influences on survival.

3. Trial Design

This was a phase 2 study sponsored by Duke University. The registry lists a planned enrollment of 18 and describes the design as non-randomized, with no masking and a single-group model. The only intervention group is named Gliadel/Avastin/CPT-11. Its description repeats that name without adding a dosing schedule or further treatment details.

The record lists a start date of 2008-12 and a primary completion date of 2011-07. The overall status is terminated. The reason for termination is not reported in the registry record, so the status alone does not explain whether recruitment, follow-up, or another aspect of the study ended earlier than intended. The record does not provide a fuller recruitment history.

The primary endpoint was 24-week overall survival, defined as the percentage of participants surviving 24 weeks from the start of study treatment. The stated analysis population is intent-to-treat. Secondary outcomes include 24-week progression-free survival, median progression-free survival, median overall survival, central nervous system hemorrhage, and specified hematologic and non-hematologic toxicities. The brief summary also names progression-free survival and toxicity as secondary objectives.

Because there is only one group and no masking, the design does not support a randomized, blinded comparison with another treatment. A control group, randomization procedure, masking procedure, and reasons for their absence are not reported beyond the design labels. Further details about eligibility, treatment delivery, follow-up, and how the endpoint was analyzed are not reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: intent-to-treat

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 24-week Overall Survival, measured over 24 weeks.

The primary endpoint is the percentage of participants who survived 24 weeks from the start of study treatment. It is defined as a proportion at a specified follow-up time, rather than as a median survival time or a rate of events over person-time. The registry states that the intended population for this endpoint is intent-to-treat and that the result should be accompanied by a 95% confidence interval.

A fixed-time survival percentage offers a direct description of the share of the study population alive at a clinically specified point. It can be easier to interpret than a time-to-event summary when the question is specifically about status at that time. It does not, by itself, describe when deaths occurred before or after the assessment point, and it does not summarize the full survival experience.

As a general statistical explanation, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the method used. A wider interval indicates less precision than a narrower interval, while neither the estimate nor its interval establishes a causal effect in a single-group design. The method used to calculate the interval is not reported in the registry record.

The registry identifies the endpoint and timeframe, but does not report the observed survival percentage or its confidence interval. Consequently, the endpoint definition can be described, but the result and its precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a binary-percentage primary endpoint: the share of participants alive at 24 weeks after treatment began. It also specifies a 95% confidence interval. It does not report the estimate, interval, calculation method, or any hypothesis test. The explanations below describe general statistical ideas and should not be read as a description of unreported trial procedures.

What does a percentage endpoint represent?

A percentage for a fixed-time endpoint describes the fraction of an analysis population meeting a stated condition at the chosen assessment time. Here, the condition is survival at 24 weeks. This differs from a median, which is a point in a time-to-event distribution, and from a hazard, which describes event occurrence over time under a particular model. A fixed-time percentage answers a focused question, but leaves other aspects of the event history outside that single summary.

For interpretation, the population definition and the handling of participants whose status is unknown at the assessment time are important. The primary population is labeled intent-to-treat, but the number analyzed and the method for handling missing vital status are not reported in the registry record. A population label alone does not reveal how incomplete follow-up was treated.

How should a confidence interval be understood?

In general, a confidence interval communicates the uncertainty associated with an estimate under a specified statistical procedure. Its width depends on factors including the amount of information and the method's assumptions. A narrow interval indicates greater precision than a wide interval, but interval width is not itself a test of clinical importance. A 95% confidence interval is a repeated-sampling property of a procedure under its assumptions; it is not a direct probability statement that the particular interval contains the true value.

The registry names a 95% confidence interval but does not identify the method used to calculate it. It also does not post the estimate and interval. Thus, neither the interval's width nor the degree of uncertainty around the endpoint can be evaluated from the registry record.

What can a single-group design estimate?

A single-group design can describe outcomes observed among its participants. It does not, on its own, establish what would have happened to the same participants under an alternative treatment. Randomized concurrent comparisons help address that counterfactual question by allocating participants to different groups. This study is listed as non-randomized and single-group, so no randomized between-group treatment contrast is specified.

Even if an outcome percentage were available, differences between a study result and results from another population or time period could reflect differences in eligibility, care, follow-up, or other factors. The registry record does not report a comparison strategy that would account for such differences. The trial's design should therefore guide interpretation of any eventual outcome estimate.

How do the secondary outcomes differ?

Progression-free survival and overall survival are time-to-event outcomes. Their interpretation generally depends on the event definition, timing of assessments, censoring rules, and analysis method. A median time-to-event result describes the time by which half of the event distribution has occurred, when that summary can be estimated. The record lists 24-week progression-free survival, median progression-free survival, and median overall survival, but does not report their values or analytic details.

The registry also lists central nervous system hemorrhage and specified hematologic and non-hematologic toxicities. Incidence summaries describe whether an event was recorded in participants, while severity classifications describe the recorded level of harm. The exact ascertainment procedures, observation period, coding rules, and handling of repeat events are not reported in the registry record. The posted adverse-event summaries should therefore be read as descriptive registry figures, not as a complete account of each participant's safety course.

What do the planning assumptions mean?

The sample-size planning illustration is described as a calculation based on an observed effect, not as the trial's own design. It assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; its target effect is a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is a total number of events, while other illustrations use participants per arm.

These are planning assumptions for hypothetical sample-size calculations. They do not change the actual study design, which is single-group and non-randomized, and they are not an account of the protocol's sample-size justification. The registry does not report the trial's own sample-size rationale. Planning illustrations are not observed power, do not show that the study achieved a particular power, and cannot substitute for an outcome estimate. Because the registry does not report the primary effect estimate or its analysis, the planning assumptions should not be mistaken for trial findings.

Finally, the record lists 0 analyses. It does not report whether an analysis plan specified statistical models, interim analyses, covariate adjustment, or sensitivity analyses. The absence of these details should not be interpreted as evidence that a method was or was not used outside the registry record.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("Gliadel/Avastin/CPT-11")
n      <- c(18)
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  Gliadel/Avastin/CPT-11  18  14  77.8  52.4  93.6  54.8  91.0  54.4  90.9

11. Multiplicity, Missing Data and Analysis Populations

The registry names a primary endpoint and several secondary outcomes. The primary endpoint is 24-week overall survival; the secondary outcomes cover progression-free survival, median survival measures, central nervous system hemorrhage, and specified toxicity categories. With multiple outcomes, interpretation often depends on which analyses were designated as primary, how claims across outcomes were controlled, and whether outcomes were added or changed during the study. The registry record does not report a multiplicity strategy, hierarchy of secondary hypotheses, or adjustment procedure.

The record lists 0 analyses. It therefore does not provide a set of outcome estimates or tests from which to assess the extent of statistical testing or the handling of multiple comparisons. The presence of several registered outcomes does not establish that each was tested, nor does it indicate how any findings would have been interpreted together.

The primary endpoint population is described as intent-to-treat. The registry does not report the analyzed population size, participant flow, missing-data amount, reasons for missingness, or methods for handling missing survival status. It also does not describe censoring rules for time-to-event outcomes, or whether sensitivity analyses addressed incomplete follow-up. These details matter because outcome estimates can depend on who is included and how incomplete observations are treated.

As a general matter, a missing-data method should be aligned with the outcome and with assumptions about why observations are missing. No particular method or assumption can be attributed to this study from the registry record. Likewise, no interim-analysis schedule, stopping rule, or statistical analysis plan is reported. The terminated status does not reveal whether an interim analysis occurred or why the study ended.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: wound infection (16.7%), peripheral motor neuropathy (16.7%), seizure (16.7%), cognitive disturbance (11.1%), lung infection (5.6%).

The registry lists 18 participants at risk for serious adverse events in the Gliadel/Avastin/CPT-11 group and 8 affected. For other adverse events, it lists 18 at risk and 14 affected. These are group-level participant counts as recorded; the registry record does not provide further detail about the observation period or the criteria used to classify each event.

The listed serious adverse-event terms include wound infection, peripheral motor neuropathy, and seizure, each at 16.7%; cognitive disturbance at 11.1%; and lung infection and wound dihiscence, each at 5.6%. These percentages are reported registry figures. The terms may not represent mutually exclusive groups of participants, and the record does not state that they can be added to obtain a total. A death count is not reported in the registry record.

These summaries describe events recorded in the study group; they do not establish that the intervention caused an event or show how risk compares with another treatment. The record does not report event-level timing, duration, recurrence, management, or a detailed attribution method. The listed figures should therefore be read as descriptive safety information rather than as a complete participant-level safety profile.

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

The registry record defines a focused primary question: the percentage of participants alive 24 weeks after the start of study treatment. It also identifies the intended primary population as intent-to-treat and specifies a 95% confidence interval. Those details clarify what the trial set out to summarize. However, the registry record does not report the survival percentage, its interval, or a primary analysis. The intended question can be described, but its observed answer cannot be recovered from the posted record.

The record also describes a phase 2, non-randomized, single-group study of Gliadel followed by Avastin and irinotecan. That design can provide descriptive experience in the treated group, but it does not furnish a randomized comparator. Even a reported outcome from a single group would not, by itself, identify the effect of the treatment relative to an alternative. There is no basis in this record to claim that the treatment works or does not work.

The adverse-event figures provide some additional descriptive information: the record lists affected participants and selected serious-event terms with percentages. They do not establish causation, comparative safety, or the full course of events. No death count is reported, and further methods for safety collection and analysis are not reported in the registry record.

More broadly, the endpoint definitions and outcome labels should not be confused with outcome results. The record lists progression-free survival and toxicity outcomes, but does not report their analyses. It also lists 0 analyses. The reason for termination is not reported, so the study status cannot be used to infer a particular outcome, safety concern, or operational cause.

The defensible reading is therefore limited but useful: the registry documents the design, intended outcomes, enrollment figure, status, and some adverse-event summaries. It does not provide the numerical primary endpoint result or enough analysis detail to judge its precision, comparative meaning, or robustness. Those absences constrain what can be concluded from the registry record.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction in clinical research reporting: registering an endpoint is not the same as reporting its result. The primary question is clearly framed around 24-week overall survival, and the registry specifies a confidence interval. Yet the record does not post the estimate, the interval, or a primary analysis. Without those values, readers cannot assess the endpoint's observed level or precision.

The design also matters to interpretation. A non-randomized, single-group study can describe outcomes among participants receiving the listed intervention. It cannot, on its own, provide a randomized estimate of the difference between that intervention and a comparator. Recognizing the distinction between a within-group outcome and a between-group treatment effect prevents a descriptive result from being overstated.

The record offers a further lesson about registered secondary outcomes and safety summaries. Naming outcomes creates a map of questions the study intended to address, but it does not establish that analyses were completed or posted. Adverse-event counts and selected terms can add context, yet they do not replace the missing primary estimate or establish causality and comparative risk.

Finally, the record is marked terminated, while the reason for termination and the statistical analysis details are not reported. This makes clear why outcome availability, participant flow, missing-data handling, and analysis plans are important parts of an interpretable clinical-trial record. The statistical significance of a trial depends not only on which endpoint was chosen, but also on the evidence reported and the design that supports the intended inference.

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 specific to this record constrain interpretation. First, the primary endpoint is defined, but its observed percentage and 95% confidence interval are not reported in the registry record. The record lists 0 analyses, so no primary analysis result is available to assess. The listed enrollment of 18 does not establish how many participants were treated, observed at 24 weeks, or included in an analysis.

Second, the design is non-randomized and single-group, without masking. No concurrent comparator is listed. This limits the study's ability to support a comparative treatment-effect interpretation, even if within-group outcomes were available. The registry does not provide details of a comparison with external or historical data.

Third, the status is terminated, but the reason is not reported in the registry record. The start and primary-completion dates are listed, but the record does not explain the relationship between those dates, participant follow-up, or the termination. It does not report recruitment flow, follow-up completeness, or the number of participants with missing endpoint status.

Fourth, analysis methods are sparsely documented. The record does not report the interval calculation method, any statistical analysis plan, the handling of missing outcomes, censoring rules, multiplicity procedures, interim analyses, or sensitivity analyses. It also does not report detailed treatment schedules or safety ascertainment methods. These omissions prevent a fuller assessment of precision, robustness, and potential sources of bias.

Finally, the adverse-event summaries are limited to group counts and selected terms with percentages. The record does not report a death count or enough detail to determine timing, recurrence, attribution, or comparison with another group. These limitations do not negate the descriptive information that is recorded, but they restrict the conclusions that can be drawn from it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM) — NCT00735436.
• Registry record last updated 2013-02-11; status last verified 2012-12.
• Results first posted 2013-02-04.
• 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

The registry record describes a phase 2, non-randomized, unmasked, single-group study sponsored by Duke University, with enrollment listed as 18. It evaluates Gliadel followed by Avastin and irinotecan in patients with grade IV malignant glioma following surgical resection. The study is marked terminated; its reason for termination is not reported in the registry record.

The primary endpoint is the percentage surviving 24 weeks from the start of study treatment, with a stated 95% confidence interval and an intent-to-treat population. The registry record does not report the primary estimate or interval and lists 0 analyses. Secondary outcomes address progression-free survival, median survival, and safety. Some group-level adverse-event counts and selected serious-event terms are listed, but the record does not report a death count or detailed safety methods.

The available record supports description of the trial's design and intended questions, but not a conclusion about its primary survival result or a comparative treatment effect.