Temozolomide in Treating Patients With Low-Grade Glioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Temozolomide in Treating Patients With Low-Grade Glioma (NCT00313729), a na phase 2 study. The primary outcome is Response Rate (Complete and Partial Response).

2. Clinical Question

The trial was designed to study treatment in adult patients with supratentorial low-grade glioma. Its primary outcome names response rate and defines the response categories using MRI together with neurological examination and steroid requirements. The registry record does not report the number of participants who achieved complete or partial response, so the observed response rate cannot be described from this record.

The record also lists time to tumor progression and safety profile as secondary outcomes. It does not provide numerical results for those outcomes. The study enrolled 120 participants, but the record does not state how many were included in an analysis of the primary endpoint or how many had evaluable response assessments.

Because the study is single group and has no listed comparator, the primary question is descriptive: what response was recorded in the treated group under the stated assessment criteria? The record cannot answer a comparative question about temozolomide versus another treatment or no treatment.

3. Trial Design

This was a phase II study of temozolomide in adult patients with supratentorial low-grade glioma. The registry identifies the study model as single group, lists allocation as not applicable, and records masking as none. The only listed intervention is temozolomide, and the arm description names a temozolomide group. Enrollment was 120.

The study began in 1999-05, reached primary completion on 2014-09-25, and is recorded as completed. The sponsor is University of California, San Francisco. The registry describes the study purpose as assessing how well temozolomide works in this patient population. It gives no further detail on treatment dose, schedule, treatment duration, eligibility criteria, or follow-up beyond the endpoint timeframes stated in the record; those details are not reported in the registry record.

The absence of a comparator is central to interpreting the design. A single-group study can describe outcomes among participants receiving the study treatment, but it does not provide a concurrent control group for estimating a treatment contrast. The record therefore supports a description of the planned question and reported safety counts, but it does not establish how outcomes compare with another treatment or with the course participants would have experienced without temozolomide.

The study lists three outcome measures, including response rate, time to tumor progression, and safety profile. The primary outcome is specified for 12 months. The registry record does not provide analysis results or a detailed statistical analysis plan. In particular, the rationale for the enrollment target, the intended analysis population, and any prespecified handling of missing assessments 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

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 Response Rate (Complete and Partial Response), measured over 12 months.

The primary endpoint is titled Response Rate (Complete and Partial Response), is measured as a count of participants, and has a timeframe of 12 months. The registry says response was assessed using MRI alongside neurological examination and steroid requirements, drawing on Macdonald's criteria. A complete response required complete disappearance of the lesion on consecutive MRI scans with stable or improved neurological examination and steroid status. A partial response required a 50% reduction in lesion size, or a tumor burden judged definitely better than on the prior scan, with stable or improved neurological examination and steroid status.

This endpoint combines imaging findings with clinical assessment and steroid use. In general, such a composite assessment can capture more than a change in lesion size alone, while requiring its components to be considered together according to the stated criteria. The count of participants meeting the response definition would describe the frequency of response in the study group over the specified timeframe.

The registry record does not report the response count, the number assessed, or a response-rate estimate. It also does not report a confidence interval or a statistical test for this endpoint. Consequently, the criteria and timeframe can be described, but the degree of observed response and its precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry record is limited. It identifies a phase II, single-group study with no masking, a participant-count primary endpoint, and a 12-month timeframe. It describes how response categories were assessed, but does not report a statistical analysis plan, response results, confidence intervals, or hypothesis tests. The explanations below distinguish general statistical concepts from what the record actually states.

What does a participant count measure?

The primary outcome is a count of participants meeting the complete or partial response definition. In general, a count tells readers how many observations met a stated criterion. To interpret a response proportion, the count must be considered with the number of participants assessed under the same definition. Although enrollment was 120, the record does not state how many participants had an evaluable response assessment, and it does not provide the response count. A response proportion cannot be recovered from enrollment alone.

The endpoint definition uses several forms of assessment: MRI findings, neurological examination, and steroid requirements. The record describes the criteria for complete and partial response, including the requirement for stable or improved examination and steroid status. In general, clear and consistently applied criteria help make endpoint classification more reproducible. The registry does not provide details about assessment timing beyond the 12-month timeframe, independent review, or how disagreements between assessments were handled.

What would a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity. For a response proportion, it would help readers understand how precisely the observed study-group response frequency is estimated. A narrow interval generally indicates greater precision than a wide interval, given the method and assumptions used. No response estimate or interval is reported in the registry record, so its precision cannot be assessed.

A p-value, in general, evaluates how compatible observed data are with a specified statistical hypothesis under the assumptions of a test. Its meaning depends on the hypothesis and analysis plan. The registry record lists no analyses and reports no p-value for the primary endpoint. No testing strategy or hypothesis for the primary outcome is reported in the registry record. A p-value should not be inferred from the study phase or from the enrollment count.

Why does the single-group design matter?

In general, a concurrent comparison group can help distinguish outcomes associated with one treatment strategy from outcomes under another strategy, subject to the design and analysis. This study is recorded as single group, with allocation not applicable and no masking. It therefore does not provide a randomized comparison. The study can be described in terms of outcomes among its treated participants if those outcomes are reported, but it cannot directly estimate a between-group treatment difference. No adjustment can create a randomized control group when one is absent.

Masking is recorded as none. In general, masking can reduce the influence of knowledge about treatment assignment on some aspects of assessment or reporting. The record does not describe safeguards that may have been used for outcome assessment, so none should be assumed. The response definition includes MRI and clinical assessments, but the registry does not state whether image assessments were reviewed independently or without knowledge of treatment.

What do the planning assumptions mean?

The record describes a sample-size planning illustration as based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These assumptions describe a hypothetical planning exercise, not the design of this single-group trial. In general, a sample-size calculation estimates the number of participants or events needed under specified assumptions; it does not describe how many participants were observed to have an outcome.

The registry does not report the trial's own sample-size justification. The planning assumptions do not establish that the trial was designed with those methods, that the hypothetical two-arm comparison was conducted, or that an observed effect was confirmed. Sample-size illustrations are planning quantities, not observed power. Since the registry record does not report a numerical primary response result, it also does not provide a response effect that can be interpreted from the record.

What can be concluded from the posted methods?

The record allows readers to identify the study model, endpoint definition, and timeframe, and to note the listed adverse-event counts. It does not give enough information to reproduce a primary endpoint analysis. The analysis population, response denominator, missing-data approach, statistical tests, interval-estimation method, and any sensitivity analyses are not reported in the registry record. General statistical principles can clarify why those details matter, but cannot replace the missing results or establish what methods were actually used.

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("Temozolomide")
n      <- c(120)
events <- c(7)
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  Temozolomide  120  7  5.8  2.4  11.6  2.9  11.6  2.9  11.6

11. Multiplicity, Missing Data and Analysis Populations

The registry names three outcome measures: response rate, time to tumor progression, and safety profile. Response rate is identified as the primary outcome; time to tumor progression and safety profile are listed as secondary outcomes. The registry record lists no analyses and does not report a statistical analysis plan, a testing hierarchy, or a method for controlling multiplicity.

In general, multiplicity arises when several outcomes or hypotheses are examined. If multiple statistical tests are conducted, the chance of at least one apparently notable finding can change, depending on the tests and their relationship. A prespecified testing strategy can clarify how results should be interpreted. The record does not establish whether formal tests were planned or performed, so no multiplicity adjustment or testing sequence can be described.

Missing-data methods are also not reported in the registry record. The primary endpoint requires response assessments, but the record does not say how missing scans, incomplete examinations, withdrawals, or participants without an evaluable response were handled. It does not give the number assessed for the endpoint. The enrolled total therefore cannot be treated as the endpoint denominator.

The analysis populations are not reported in the registry record. It is not stated whether analyses used all enrolled participants, participants who received treatment, or a subset with available outcome assessments. These omissions limit interpretation of both the primary endpoint and the secondary outcomes. They do not show that particular procedures were or were not used; they mean the registry record does not describe them.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: seizure (5.0%), headache (2.5%), neutropenia (1.7%), neutrophils/granulocytes (anc) (0.8%), thrombocytopenia (platelets) (0.8%).

The registry lists 120 participants at risk for serious adverse events in the temozolomide group, with 17 recorded as affected. For other adverse events, it lists 120 at risk and 31 affected. These are registry counts. The record does not give further detail about how events were collected, their timing, or whether individual participants could contribute to more than one event category.

Listed serious adverse event terms include seizure at 5.0%, headache at 2.5%, neutropenia at 1.7%, neutrophils/granulocytes (ANC) at 0.8%, thrombocytopenia (platelets) at 0.8%, and infection with unknown ANC at 0.8%. These are the percentages reported in the registry. The record does not specify in the listed information how the percentages were calculated or whether the terms overlap. They should not be added together to infer a total.

In general, an adverse event recorded during a study is not, by itself, proof that the study treatment caused it. A serious adverse event is a separate category from other adverse events, and the counts should not be combined or treated as interchangeable. The registry record does not report deaths. The safety entries describe reported events in the study group, not a comparison with an untreated or alternative-treatment group.

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

The record establishes that a phase II, single-group study of temozolomide in adult patients with supratentorial low-grade glioma was completed, with enrollment of 120. It specifies a primary response endpoint assessed within 12 months and describes the criteria used to classify complete and partial response. It also lists time to tumor progression and safety profile as secondary outcomes.

The key limitation for interpreting efficacy is that the registry record does not report the primary response count or estimate. It also does not report the numerical results for the listed secondary outcomes. Without those outcome results, the record cannot show the frequency of response, the time-to-progression experience, or the precision of either. Enrollment alone does not reveal how many participants were assessed or what their outcomes were.

The reported safety counts and event terms describe observations in the study group. They do not establish causation and do not provide a comparative estimate of harm, because there is no concurrent comparator. The registry also does not report deaths. These entries should be read as descriptive registry data rather than as evidence of a difference between treatment strategies.

More generally, an uncontrolled study can document outcomes in its participants but cannot, on its own, separate treatment effects from other factors that may influence outcomes. This is a design limitation, not a finding that any particular effect did or did not occur. The absence of reported response results is an additional limitation: it prevents a quantitative account of the primary endpoint from this record.

The registry record therefore supports statements about the trial's design, the response criteria, and the listed safety counts. It does not support a conclusion about whether temozolomide improved outcomes, how its outcomes compared with another approach, or how precisely the primary response outcome was estimated.

14. Why This Trial Matters Statistically

This trial illustrates why study design and outcome reporting must be considered together. The registry identifies a phase II study of temozolomide, but its single-group model means it has no concurrent control group. That design permits descriptive reporting of outcomes in the treated group, but does not provide a randomized treatment contrast. Readers need the design information to understand what kind of question the study can answer.

The response endpoint also illustrates the importance of a clearly stated outcome definition. It combines MRI findings with neurological examination and steroid requirements, and distinguishes complete from partial response. The registry gives the timeframe and assessment criteria, but does not provide the response count or an analysis denominator. A well-described endpoint cannot be interpreted quantitatively without the corresponding results.

The safety entries show why counts, percentages, and causal claims should be distinguished. The record lists participants at risk and affected, alongside selected serious adverse event terms and their percentages. Those descriptions are useful for understanding what the registry recorded, but they do not establish that temozolomide caused an event or how the event frequency compares with another treatment.

Finally, the record separates a study's stated outcomes from its statistical analyses. It lists a primary outcome and secondary outcomes but no analyses. It also does not report a statistical analysis plan or the trial's sample-size justification. This makes clear that outcome names, enrollment, and planning assumptions do not substitute for estimates and uncertainty measures. For biostatisticians and clinical researchers, these distinctions are essential when deciding what conclusions the registry record can support.

15. Limitations

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

The available registry record leaves important details about eligibility and treatment implementation unspecified. It identifies adult patients with supratentorial low-grade glioma and lists the condition as CNS Tumor, Adult, but detailed inclusion and exclusion criteria are not reported in the registry record. Dose, schedule, treatment duration, adherence, and co-interventions are not reported in the registry record either.

The single-group design and lack of masking limit what can be inferred from outcomes. There is no concurrent control group, and the record lists masking as none. These features matter when interpreting descriptive outcomes and assessments, particularly because the primary endpoint includes clinical judgments alongside MRI findings. Independent assessment procedures are not reported in the registry record.

Most importantly, the response outcome is not numerically reported. The record does not state the count of complete or partial responses, the response denominator, or an interval estimate. Results for time to tumor progression and the safety profile are also not reported as numerical outcome analyses. The analysis population, missing-data handling, and endpoint assessment completeness are not reported in the registry record.

The safety information is limited to the listed counts and selected serious adverse event terms. The record does not describe event collection procedures, timing, attribution, or overlap among terms. Deaths are not reported in the record. The trial's sample-size justification and statistical analysis plan are also not reported in the registry record, so the analysis methods and intended precision cannot be evaluated.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Temozolomide in Treating Patients With Low-Grade Glioma — NCT00313729.
• Registry record last updated 2019-02-07; status last verified 2019-01.
• Results first posted 2019-01-23.
• 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

This completed phase II study evaluated temozolomide in adult patients with supratentorial low-grade glioma. It used a single-group design, had no masking, and enrolled 120 participants. The primary endpoint was complete or partial response within 12 months, assessed using MRI together with neurological examination and steroid requirements. The record also lists time to tumor progression and safety profile as secondary outcomes.

The registry record does not report the numerical primary response result, secondary outcome analyses, confidence intervals, or a statistical analysis plan. It lists 120 participants at risk for serious and other adverse events, with 17 and 31 affected, respectively, and gives selected serious adverse event terms and percentages. The study began in 1999-05 and reached primary completion on 2014-09-25. Its sponsor is University of California, San Francisco.