This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Temozolomide in Concomitant Radiochemotherapy Followed by Sequential Temozolomide Chemotherapy - Observational Program (Study P04816) (NCT00725010), a registered phase not stated study. The primary outcome is Safety: Number of Adverse Events in the Indicated Categories.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00725010 |
| Phase | Phase not stated |
| Condition | Glioblastoma |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 64 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants had newly diagnosed glioblastoma multiforme and received care in a routine-care setting. The registry record lists enrollment of 64 participants. The characteristics of the participants and the criteria used to determine eligibility are not reported in the registry record.
Intervention
The program concerned temozolomide given with radiotherapy during concomitant treatment, followed by sequential temozolomide chemotherapy. These therapies were described as standard care prescribed to participants. The record lists temozolomide as a drug and radiotherapy as radiation.
Comparator
The posted adverse-event results distinguish a temozolomide plus radiotherapy group from a temozolomide-alone group. This was not a randomized comparison, and allocation is not stated. The groups therefore should not be read as like-for-like control groups: the record does not establish that participants in them were comparable or that the groups represent treatment strategies assigned under the same conditions.
Primary question
The primary measure was safety, expressed as the number of adverse events in indicated categories. Events were to be assessed weekly during concomitant treatment and monthly during the monotherapy phase. The registry describes the program as evaluating safety, tolerability, and efficacy in routine care, but the posted primary outcome is an adverse-event measure. The record does not post an analysis estimating a causal treatment effect or a statistical comparison between the groups.
3. Trial Design
This completed program was observational rather than a randomized controlled trial. The registry describes participants with newly diagnosed glioblastoma multiforme who were prescribed temozolomide and radiotherapy as standard care. Its purpose was to evaluate the safety, tolerability, and efficacy of concomitant radiochemotherapy followed by sequential temozolomide chemotherapy in a routine-care setting. The record lists enrollment of 64 participants.
The record gives a start date of 2007-04 and a primary completion date of 2009-04. It lists temozolomide and radiotherapy as interventions. The reported group labels are Temozolomide+Radiotherapy and Temozolomide Alone. They describe different treatment contexts, not randomized arms. Allocation is not stated, and the registry explicitly cautions that the arms are not a like-for-like control comparison. Differences between their posted counts could reflect differences in who entered each group or in the circumstances and duration of treatment, as well as any differences in adverse events.
The primary outcome is a safety measure: number of adverse events in indicated categories, assessed weekly during the concomitant phase and monthly during the monotherapy phase. The record lists two outcome measures, but does not provide a detailed description of the other measure in the available results. It lists zero analyses. Therefore, the record does not give an inferential comparison, an adjusted estimate, or a statistical test for the reported groups. A protocol, allocation process, and detailed analysis plan are not reported in the registry record.
The group counts in the safety results should not be assumed to account for every enrolled participant. The registry lists 44 at risk in the combined-treatment group and 6 at risk in the temozolomide-alone group for both serious and other adverse events. The reason these counts differ from the enrollment figure is not reported in the registry record. No explanation should be inferred from the observational design alone.
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
| Stage | Planned Temozolomide+Radiotherapy |
|---|---|
| STARTED | 50 |
| COMPLETED | 25 |
| NOT COMPLETED | 25 |
Reasons for not completing this period:
| Reason | Planned Temozolomide+Radiotherapy |
|---|---|
| Toxicity | 9 |
| Tumor Progression | 7 |
| Withdrawal by Subject | 2 |
| Death | 1 |
| Lost to Follow-up | 1 |
| Hepatopathy probably not Temodal-related | 1 |
| Suspect lymph nodes neck thorax abdomen | 1 |
| No further documentation | 1 |
| Intensified treatment scheme: 3 on 1 off | 2 |
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.
| Characteristic | Unit | Planned Temozolomide+Radiotherapy |
|---|---|---|
| Participants analysed | 50 | |
| Age, Continuous | years | 57 (SD 12.06) |
| Sex: Female, Male: Female | Participants | 23 |
| Sex: Female, Male: Male | Participants | 27 |
| Region of Enrollment: Austria | participants | 50 |
6. Primary Endpoint
The registry lists the primary outcome as Safety: Number of Adverse Events in the Indicated Categories, measured over Weekly during the concomitant treatment phase, and then monthly during the monotherapy phase.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Adverse Events |
| Endpoint classification | not reduced to a single comparison |
The primary measure concerns the number of adverse events in indicated categories. The record specifies repeated assessment: weekly during concomitant treatment and monthly during the monotherapy phase. This timing reflects the program’s focus on documenting safety across different treatment phases. An adverse-event count can describe the burden of recorded events, while category-specific counts can make particular types of events visible.
Counts require careful interpretation. A total event count is not necessarily the same as the number of participants who experienced an event: one participant may have more than one event. The posted serious and other adverse-event summaries list participants at risk and participants affected, but do not provide a complete event-level account or a detailed definition of each category. The registry record does not report the primary endpoint’s overall result as a single total number of events, nor does it provide an inferential analysis for that endpoint.
In general, safety measures are used to describe events observed during care and to identify patterns that may warrant further study. Their interpretation depends on how events were defined, collected, classified, and followed over time. Those procedural details are not reported in the registry record. The posted outcome therefore supports a descriptive reading of the listed counts; it does not, by itself, establish how treatment caused or changed the occurrence of adverse events.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry’s safety summaries list 44 participants at risk and 8 affected by serious adverse events in the Temozolomide+Radiotherapy group. For the Temozolomide Alone group, the corresponding figures are 6 at risk and 1 affected. For other adverse events, the record lists 44 at risk and 12 affected in the combined-treatment group, and 6 at risk and 1 affected in the temozolomide-alone group. These are descriptive figures from groups formed in routine care, not results from randomized assignment.
The counts do not estimate what would have happened to the same participants under an alternative treatment. The registry states that allocation is not stated and that the arms are not a like-for-like control comparison. The groups may differ in participant characteristics, treatment phase, observation time, or other aspects of care; whether and how they differ is not reported in the registry record. As a result, contrasts between the group counts cannot be attributed to treatment alone.
The serious adverse-event terms listed include Pancytopenia at 16.7%, Thrombocytopenia at 4.5%, General physical health deterioration at 2.3%, Metastases to lymph nodes at 2.3%, Dural fistula at 2.3%, and Status epilepticus at 2.3%. The record does not give the denominators or event counts underlying each percentage, nor does it explain whether a participant could be represented in more than one term. These percentages should therefore be read as registry-listed descriptive values, not as directly comparable risks between groups.
No confidence intervals, p-values, adjusted estimates, or group-comparison analyses are posted; the registry lists zero analyses. This means the precision of a treatment contrast cannot be assessed from the posted results. The absence of an analysis in the registry record does not establish that no analysis was conducted elsewhere; it means an analysis is not reported in this record.
The enrollment figure is 64, while the safety summaries list 44 and 6 participants at risk across the two groups. The record does not explain the difference, so those figures should not be combined or reconciled by assumption. It also does not report death counts in these safety summaries. Overall, the record offers a limited descriptive account of adverse events and does not support a causal or comparative efficacy conclusion.
9. Statistical Methods Explained
The posted results are descriptive. They list counts of participants at risk and affected by serious and other adverse events, and list selected serious-event terms with percentages. They do not report a fitted statistical model, a comparison estimate, or an inferential test. The registry record lists zero analyses. Consequently, the methods used to produce the adverse-event summaries beyond their stated assessment schedule are not reported in the registry record.
What does a count measure?
In general, a count is a non-negative quantity, such as the number of recorded events. It differs from a participant count: a person can experience multiple events, so counting events and counting people affected answer different questions. A count of affected participants describes how many people had at least one event in a category, if that is how the category is defined. A total event count can instead include repeat events in the same person. The record’s primary measure is described as number of adverse events, while the group summaries identify participants at risk and affected. The event-level definitions and counting rules are not reported in the registry record, so these summaries should not be treated as interchangeable.
Why does observation time matter?
In general, counts depend on the amount of time during which events can be observed. A group followed longer may accumulate more events even if the underlying event rate is similar. Rates can account for exposure time when an appropriate denominator is available, but the registry does not report person-time or a rate analysis for these results. The stated schedule is weekly during the concomitant treatment phase and monthly during the monotherapy phase. The record does not state how many assessments each participant completed, how long each participant was followed, or whether the schedule was fully observed.
Why can count data be statistically challenging?
In general, count outcomes are often unevenly distributed, with many small values and a smaller number of larger values. Some count models assume that the variability is closely tied to the average count. If the observed variability is greater than that assumption allows, called over-dispersion, standard errors and confidence intervals from an unsuitable model can be misleading. Other approaches may be considered depending on the data structure, including repeated events within participants and differences in observation time. These are general methodological considerations, not claims about methods used in this program. The registry record does not report a count model, an over-dispersion assessment, or any corresponding diagnostics.
What would a comparison require?
In general, a comparative analysis needs a clearly defined outcome, groups that can be meaningfully compared, and an approach to differences in follow-up and participant characteristics. Randomization can support comparability by balancing factors on average, but this program is identified as observational and the allocation process is not stated. Statistical adjustment can address measured differences under appropriate assumptions, but it cannot guarantee that unmeasured differences have been removed. The registry lists no adjusted comparison and does not describe covariates or an adjustment strategy. A causal interpretation is therefore not justified by these posted counts.
How should estimates and uncertainty be read?
In general, a confidence interval describes uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater statistical precision than a wide interval, but does not remove bias from study design or measurement. The registry record does not post confidence intervals for the adverse-event summaries or an estimate comparing the groups. It is therefore not possible to assess the statistical precision of a comparative effect from this record. The listed percentages for serious-event terms are descriptive; their underlying denominators are not reported in the registry record.
What do planning illustrations mean?
The accompanying sample-size illustrations are planning exercises based on the observed effect, not the program’s own design justification and not observed power. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. In general, such illustrations ask how many participants per arm would be needed to detect a specified effect under those assumptions. They do not show that the observational groups were assigned equally, that a particular number was enrolled for that reason, or that the analysis had a particular probability of finding a result. A sample-size justification for the program is not reported in the registry record. Because the groups are not a like-for-like control comparison, a planning illustration based on their observed contrast also inherits the limitations of that contrast.
Time-to-event methods are not described for the primary safety measure. In general, those methods account for the timing of an event and differing follow-up, while a simple count does not inherently do so. The registry record does not report a time-to-event analysis, event dates, or censoring rules. The suitable interpretation is thus limited to the posted descriptive counts and listed terms.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures, but the available record identifies the primary measure as the number of adverse events in indicated categories. It does not describe a complete hierarchy of outcomes, the role of the other measure, or which outcomes were formally tested. No statistical analyses are listed. The record therefore does not show a testing plan or explain whether any adjustment for multiple outcomes or repeated comparisons was intended.
In general, when many outcomes or categories are examined, the chance of finding an apparently unusual result can increase if each is assessed separately. A prespecified analysis plan can clarify which findings are primary and how multiple comparisons are handled. Such a plan is not reported in the registry record. The serious-event terms and their percentages should be understood as descriptive listings, not as findings established through a documented multiplicity-controlled analysis.
Missing-data procedures are not reported in the registry record. It does not state how missed assessments, incomplete event reports, or participants with partial follow-up were handled. The safety summaries give at-risk and affected counts, but do not specify the observation completeness behind them. The relationship between the enrollment figure of 64 and the at-risk counts of 44 and 6 is not explained.
The analysis populations are also not reported in the registry record. It is not stated whether the summaries include all enrolled participants, only those who began a particular treatment phase, or another defined subset. The group summaries should therefore be interpreted as the counts listed, without assuming a particular population rule or missing-data approach.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Temozolomide+Radiotherapy | 8 | 44 | 18.2% |
| Temozolomide Alone | 1 | 6 | 16.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Temozolomide+Radiotherapy | 12 of 44 |
| Temozolomide Alone | 1 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Temozolomide+Radiotherapy | Temozolomide Alone |
|---|---|---|---|
| Pancytopenia | Blood and lymphatic system disorders | 2 of 44 | 1 of 6 |
| Thrombocytopenia | Blood and lymphatic system disorders | 2 of 44 | 0 of 6 |
| General physical health deterioration | General disorders | 1 of 44 | 0 of 6 |
| Metastases to lymph nodes | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 44 | 0 of 6 |
| Dural fistula | Nervous system disorders | 1 of 44 | 0 of 6 |
| Status epilepticus | Nervous system disorders | 1 of 44 | 0 of 6 |
| Deep vein thrombosis | Vascular disorders | 1 of 44 | 0 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Temozolomide+Radiotherapy | Temozolomide Alone |
|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | 7 of 44 | 0 of 6 |
| Leukopenia | Blood and lymphatic system disorders | 5 of 44 | 0 of 6 |
| Rash | Skin and subcutaneous tissue disorders | 3 of 44 | 0 of 6 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 44 | 1 of 6 |
Serious events with the highest arm-level rate: pancytopenia (16.7%), thrombocytopenia (4.5%), general physical health deterioration (2.3%), metastases to lymph nodes (2.3%), dural fistula (2.3%).
For serious adverse events, the registry lists 44 participants at risk and 8 affected in the Temozolomide+Radiotherapy group, and 6 at risk and 1 affected in the Temozolomide Alone group. For other adverse events, the corresponding listed figures are 44 and 12, and 6 and 1. These are the registry’s group-specific safety counts; they are not a randomized comparison and should not be interpreted as evidence that one regimen caused more or fewer events.
The listed serious-event terms are Pancytopenia (16.7%), Thrombocytopenia (4.5%), General physical health deterioration (2.3%), Metastases to lymph nodes (2.3%), Dural fistula (2.3%), and Status epilepticus (2.3%). The record does not state the denominator for these percentages or whether categories overlap. They should not be summed or treated as mutually exclusive estimates. Death counts are not reported in the registry record.
In general, safety summaries depend on consistent event definitions, event collection, and follow-up. Those details are not reported in the registry record. The figures are best read as descriptive reporting, not as a complete account of event frequency or a comparison of risk.
12. What the Result Does, and Does Not, Mean
The record describes an observational routine-care program involving temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme. Its primary measure concerns adverse-event counts across concomitant treatment and monotherapy phases. The posted safety summaries give the numbers at risk and affected in two treatment groups and list selected serious-event terms with percentages. This provides a descriptive record of reported safety information.
It does not establish a treatment effect. Participants were not randomized, allocation is not stated, and the record explicitly warns that the arms are not a like-for-like control comparison. The group counts cannot show what would have happened to the same participants under a different treatment strategy. They also do not account, in the posted results, for potential differences in participant characteristics, follow-up duration, event ascertainment, or treatment phase.
The record does not post an inferential analysis, confidence intervals, p-values, adjusted estimates, or a detailed analysis plan. It does not report the event-level definitions or the denominator behind the serious-event term percentages. The outcome summaries therefore do not establish the precision of a treatment contrast or the completeness of event capture. The registry’s zero listed analyses means that an analysis is not reported in this record; it does not establish what analyses may exist elsewhere.
The program description says its purpose was to evaluate safety, tolerability, and efficacy, but the posted primary outcome is safety-focused. The registry record does not provide a comparative efficacy result in the available information. Nor do the listed adverse-event figures alone establish whether a treatment is effective or ineffective. Their appropriate meaning is narrower: they describe counts and terms recorded for the groups in this observational program, subject to the reporting and design limitations stated above.
13. Why This Trial Matters Statistically
This record is statistically instructive because it shows how clinical data gathered in routine care differ from results of randomized assignment. Observational groups can describe what was recorded during care, but the treatment groups may not be comparable at the outset. Here, allocation is not stated, and the registry cautions that the groups are not a like-for-like control comparison. A numerical contrast between them would therefore be difficult to interpret as a treatment effect.
It also illustrates why the outcome’s definition matters. The primary measure is described as the number of adverse events, while the posted group summaries report participants at risk and affected. Event counts and counts of affected participants describe different features of safety data. Clear definitions, exposure time, and follow-up information are important for judging whether the summaries capture comparable opportunities to experience and report events; those details are not reported in the registry record.
Finally, the record distinguishes descriptive reporting from statistical inference. It lists no analyses and provides no uncertainty interval or adjusted comparison. The serious-event percentages are useful as reported categories, but their denominators and overlap are not specified. Sample-size illustrations based on an observed effect can help frame hypothetical future planning, but they are not the study’s design justification or observed power, and they do not correct limitations in the underlying comparison.
For biostatistical interpretation, the key lesson is to match the claim to the design and reporting. These data can be read as a limited description of adverse events in the recorded groups. Stronger claims would require information and analyses that the registry record does not report.
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 nonrandomized design is a central limitation. The record does not state how participants entered the Temozolomide+Radiotherapy and Temozolomide Alone groups. Since allocation is not stated and the arms are not a like-for-like control comparison, baseline differences and treatment-context differences may affect the observed safety counts. The record does not report participant characteristics that would allow those differences to be assessed.
The posted enrollment is 64, while the safety summaries list 44 at risk in one group and 6 in the other. The record does not explain the relationship between these figures, including whether the group summaries involve different eligibility, follow-up, or assessment criteria. The analysis population is not reported in the registry record. These counts should not be reconciled through assumptions about enrollment or treatment exposure.
The safety outcome is described broadly as number of adverse events in indicated categories. The registry does not report detailed event definitions, severity grading rules, coding procedures, or the handling of repeat events in the available record. The schedule is described as weekly during concomitant treatment and monthly during monotherapy, but the duration and completeness of participant follow-up are not reported. Without exposure time and consistent observation details, raw counts may not represent comparable event opportunities.
The serious-event term percentages lack reported denominators, and the record does not state whether categories can overlap. Death counts are not reported in the registry record. Missing-data handling and the reasons for any incomplete observations are also not described. Finally, no statistical analyses are listed, and no comparative uncertainty estimates are posted. These limitations restrict interpretation to the descriptive information in the registry record and preclude a confident comparative or causal reading.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Temozolomide in Concomitant Radiochemotherapy Followed by Sequential Temozolomide Chemotherapy - Observational Program (Study P04816) — NCT00725010.
- Registry record last updated 2015-09-09; status last verified 2015-09.
- Results first posted 2010-11-18.
- 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.
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18. Record Summary
NCT00725010 is a completed observational program sponsored by Merck Sharp & Dohme LLC. It enrolled 64 participants with newly diagnosed glioblastoma multiforme and concerned temozolomide with radiotherapy followed by sequential temozolomide chemotherapy in routine care. The record lists a start date of 2007-04 and a primary completion date of 2009-04.
The primary measure is the number of adverse events in indicated categories, assessed weekly during concomitant treatment and monthly during monotherapy. Safety summaries distinguish Temozolomide+Radiotherapy from Temozolomide Alone and list selected serious-event terms. Allocation is not stated, the groups are not a like-for-like control comparison, and zero analyses are listed. The registry record does not report a comparative statistical analysis, analysis populations, missing-data procedures, or the detailed denominator information needed to interpret the listed serious-event percentages.