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 Standard Temodal (Temozolomide) Regimen Versus Standard Regimen Plus Early Postsurgery Temodal for Newly Diagnosed Glioblastoma Multiforme (Study P05572) (NCT00686725), a randomized phase 4 study. The primary outcome is Overall Survival (OS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00686725 |
| Phase | Phase 4 |
| Condition | Glioblastoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 99 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Patients with newly diagnosed glioblastoma multiforme were eligible for the study described in the registry record. The record reports an enrollment of 99. It does not report baseline demographic or clinical characteristics, eligibility criteria in detail, or the size of the population included in the primary analysis.
Intervention
The experimental strategy began with temozolomide alone after surgery, followed by temozolomide with radiotherapy and then the standard temozolomide regimen. The arm description states that the early course began 2 weeks after surgery and used 75 mg/m^2/day orally for 14 days. It describes standard treatment as beginning on Day 29 after surgery.
Comparator
The comparator was standard temozolomide with radiotherapy, followed by additional temozolomide cycles. The description says treatment began 4 weeks after surgery, with temozolomide administered concomitantly with radiotherapy at 75 mg/m^2/day orally for 42 days. The registry record also describes further temozolomide treatment after radiotherapy.
Primary question
The primary question was whether overall survival differed between the standard regimen alone and the early postsurgery temozolomide strategy followed by standard treatment. Overall survival was defined as time from randomization to death and assessed up to 2 years. The posted results give a median and 95% confidence interval for each arm, but do not report a hazard ratio or a direct statistical test of the between-arm difference.
3. Trial Design
This was a randomized, parallel-group phase 4 study with no masking. The registry record reports an enrollment of 99 and a completed status. The study start date was 2008-06-24, and the primary completion date was 2011-09-28. Merck Sharp & Dohme LLC is identified as the sponsor. The condition listed is glioblastoma.
The comparison was between two treatment strategies. One arm received temozolomide with radiotherapy and then additional temozolomide. The other began with an early postsurgery course of temozolomide alone, then proceeded to temozolomide with radiotherapy and the later standard treatment. The arm descriptions include timing and daily dosing for parts of the regimens, but the descriptions are truncated in the registry record; additional regimen details are not reported in the registry record.
Randomization means assignment to study arms was intended to be determined by chance, which can help balance measured and unmeasured prognostic factors across groups. The record does not report the randomization sequence method, allocation concealment, or whether any stratification factors were used. It also does not report the intended allocation ratio. The observed primary-outcome groups contain 47 participants in the standard temozolomide plus radiotherapy arm and 52 in the early temozolomide arm.
Because the study was unmasked, participants and study personnel were not blinded to assignment according to the registry description. This can matter for outcomes influenced by treatment awareness, decisions about care, or subjective assessments. Overall survival is based on death and is less dependent on subjective rating than many outcomes, but the registry record does not describe how outcome ascertainment or follow-up was conducted. Further information about trial conduct and deviations from the planned regimen is 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
| Stage | Temozolomide + Radiation | Temozolomide Alone, Then Temozolomide + Radiation |
|---|---|---|
| STARTED | 47 | 52 |
| COMPLETED | 1 | 10 |
| NOT COMPLETED | 46 | 42 |
Reasons for not completing this period:
| Reason | Temozolomide + Radiation | Temozolomide Alone, Then Temozolomide + Radiation |
|---|---|---|
| Adverse Event | 1 | 1 |
| Progressive Disease | 17 | 23 |
| Lost to Follow-up | 7 | 5 |
| Death | 6 | 3 |
| Withdrawal by Subject | 13 | 4 |
| Protocol Violation | 1 | 3 |
| Other | 1 | 3 |
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 | Temozolomide + Radiation | Temozolomide Alone, Then Temozolomide + Radiation | Total |
|---|---|---|---|---|
| Participants analysed | 47 | 52 | 99 | |
| Age, Continuous | years | 52.1 (SD 10.12) | 48.5 (SD 13.04) | 50.2 (SD 11.82) |
| Sex: Female, Male: Female | Participants | 13 | 20 | 33 |
| Sex: Female, Male: Male | Participants | 34 | 32 | 66 |
| Region of Enrollment: China | participants | 47 | 52 | 99 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival (OS), measured over Up to 2 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint was overall survival, measured from randomization to death and analyzed with the Kaplan–Meier method. The reported timeframe was up to 2 years. The result for each arm is a median survival time in months accompanied by a 95% confidence interval.
Overall survival is a time-to-event outcome: both whether the event occurs and how long participants remain alive after randomization contribute to the outcome. A median summarizes the time by which half of the participants in the estimated survival distribution have experienced the event. The Kaplan–Meier method estimates survival over time and can account for participants whose event time is not observed during follow-up by incorporating their available follow-up up to censoring. This is a general description of the method; the registry record does not describe censoring rules, follow-up completeness, or the handling of participants lost to follow-up.
Overall survival is used in trials because it has a clear event definition and is directly relevant to the duration of survival. Its interpretation still depends on follow-up, event ascertainment, and the analysis population. The registry record reports arm-specific median estimates, but not a hazard ratio, a confidence interval for a between-arm contrast, or a p-value for the comparison. The medians therefore describe the posted results in each arm; by themselves, they do not quantify the uncertainty in the difference between treatment strategies.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results are median overall survival of 13.17 months (95% confidence interval 11.14 to 18.76) for temozolomide plus radiation, based on 47 participants, and 17.58 months (95% confidence interval 15.18 to 23.03) for temozolomide alone followed by temozolomide plus radiation, based on 52 participants. These are arm-specific Kaplan–Meier estimates for overall survival, defined as time from randomization to death, with a reported timeframe of up to 2 years.
The confidence interval describes statistical uncertainty around each arm’s estimated median under the analysis. It is not a range containing most participants’ survival times, and it does not represent a prediction for an individual. The intervals are also not a confidence interval for the difference between arms. Comparing two arm-specific estimates is not equivalent to a formal test of the treatment contrast.
A hazard ratio, direct confidence interval for the between-arm effect, and p-value are not reported in the registry record. The record therefore does not provide the relative-effect estimate needed to describe how the instantaneous event rates compared over follow-up, nor does it give a reported test of the primary comparison. The posted medians can be described as estimates in their respective randomized groups, but a claim about statistical evidence for a between-arm effect cannot be established from these summaries alone.
The confidence intervals show that each estimated median has uncertainty. They do not resolve other questions about validity, such as whether follow-up was complete, whether treatment adherence differed, or whether the analysis population preserved the randomized comparison. Those details are not reported in the registry record. The enrolled sample was 99, and the primary outcome group sizes were 47 and 52; these observed group sizes do not establish how many participants had complete follow-up or were included in every analysis.
The registry also lists secondary outcomes involving progression-free survival, overall response, and analyses by MGMT status. Eight secondary outcomes are listed, while four analyses are reported. The outcomes and analysis counts indicate that the record includes more than the primary survival question, but their numeric results are not included in the stated details. Results for those outcomes, subgroup estimates, and any conclusions based on them are not reported in the registry record.
The most precise reading is therefore limited to the reported arm-specific medians and their confidence intervals. They describe estimated survival in the two groups; they do not, on their own, establish the size or statistical significance of a treatment effect. Interpretation should also keep in view the open-label design, the missing details about follow-up and analysis populations, and the absence of a reported direct comparison estimate.
9. Statistical Methods Explained
The primary outcome is a time-to-event measure. In this study, the event was death, and the time origin was randomization. The registry record states that overall survival was calculated with the Kaplan–Meier method and reported as a median with a 95% confidence interval. Those choices summarize survival experience while retaining information about the timing of events, rather than reducing the outcome to a simple event count at one time point.
What does the Kaplan–Meier method estimate?
In general, the Kaplan–Meier method estimates the probability of remaining free of the event over time. It updates that estimate as events occur, using the participants still under observation at each event time. A participant whose event is not observed before the end of available follow-up may contribute information until the point follow-up ends; this is called censoring. The method relies on assumptions about censoring and the quality of event-time information. The registry record does not report the censoring rules, follow-up schedule, completeness of follow-up, or how deaths were confirmed.
The median is obtained from the estimated survival curve: it is the time at which the estimated probability of survival reaches one half. It is a summary of the estimated distribution, not the mean survival time and not a statement about the survival time of each participant. If follow-up does not extend far enough, a median may be difficult or impossible to estimate. In this record, a median is reported for each arm, but the registry entries do not describe the curve’s shape or the number at risk at particular follow-up times.
How should the confidence intervals be read?
A confidence interval expresses uncertainty in an estimated quantity under the statistical procedure used. The reported 95% confidence intervals are 11.14 to 18.76 months for the standard temozolomide plus radiation arm and 15.18 to 23.03 months for the early temozolomide strategy. These intervals apply to the corresponding arm-specific median estimates. They are not intervals for individual outcomes, and they do not directly provide uncertainty for the difference or ratio between arms.
A direct comparison usually requires an estimate of the treatment contrast and its uncertainty, such as a hazard ratio with a confidence interval, or another specified comparison measure. Such a contrast and a p-value are not reported in the registry record. The posted medians should therefore be read as descriptive estimates for each randomized group rather than as a complete inferential comparison.
Why can time-to-event analyses use information from participants with incomplete follow-up?
In general, time-to-event methods can retain participants who have not experienced the event by the time their follow-up ends. Their observed time contributes up to the point at which they are censored. This differs from treating every participant without an observed event as though the event never occurred. The method does not remove the need to describe follow-up or assess whether censoring could be related to prognosis. The registry record does not report how many participants were censored, how many were lost to follow-up, or whether censoring differed by arm.
The endpoint description says the analysis covered up to 2 years. This identifies the stated timeframe, but does not by itself show that every participant was followed for the full period or clarify whether results after that period were collected. Detailed follow-up and censoring information is not reported in the registry record.
What do the design features imply for analysis?
The study is described as randomized and parallel-group, with no masking. Randomization is generally intended to make treatment groups comparable at assignment, while a parallel design assigns participants to one strategy rather than crossing them between strategies. The registry record does not provide the randomization method, allocation concealment, stratification details, or planned allocation ratio. The observed primary-outcome group sizes are 47 and 52.
No masking can allow awareness of assignment to influence behavior, co-interventions, or assessments. Overall survival is an event-based outcome, but the record does not report whether death ascertainment was independent of treatment knowledge. The consequences of unmasked conduct cannot be determined from the reported medians alone.
What is not established by planning calculations?
General sample-size illustrations can show how a hypothetical study might be planned under stated assumptions. Such calculations are planning exercises, not estimates of observed power and not evidence that the trial was designed around its eventual results. The stated illustration assumptions refer to a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. Time-to-event illustrations use a total number of events, while other illustrations use participants per arm. The trial’s own sample-size justification and design assumptions are not reported in the registry record. No planning illustration should be interpreted as an observed result or as proof that the study was adequately powered.
The registry record identifies Kaplan–Meier estimation for the primary outcome, but does not report the model or test intended for a formal comparison, adjustment variables, handling of protocol deviations, missing-data methods, or analysis populations. These omissions limit evaluation of how the posted arm-specific summaries relate to a prespecified treatment-effect analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists eight secondary outcomes in addition to overall survival. They include progression-free survival, overall response after surgery, and overall survival or progression-free survival analyses within MGMT-positive and MGMT-negative groups. Four analyses are reported. Numeric results for these listed secondary outcomes are not reported in the registry record.
When a study evaluates several outcomes or subgroups, the chance of finding at least one apparently notable result can increase if each is tested separately. Statistical approaches can address this multiplicity, for example by prioritizing a primary endpoint or adjusting inference across a family of tests. The registry record does not report a multiplicity procedure, a hierarchy for secondary outcomes, or a plan for subgroup inference. It is therefore not possible to determine how the secondary comparisons were intended to affect confirmatory conclusions.
The primary outcome population is not specified in the record. The number of participants analyzed under an intention-to-treat approach, a per-protocol approach, or another analysis population is not reported. The registry gives an enrollment of 99 and arm-specific primary outcome counts of 47 and 52, but does not explain whether these counts represent all randomized participants or a defined analysis set.
Missing outcome data, loss to follow-up, censoring by arm, and methods for handling missing information are not reported in the registry record. The record also does not state whether interim analyses were planned or conducted, or describe a statistical analysis plan. These omissions make it difficult to assess the extent to which the reported estimates follow a prespecified approach and whether incomplete data could affect interpretation.
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 Radiation | 11 | 42 | 26.2% |
| Temozolomide Alone, Then Temozolomide Radiation | 11 | 52 | 21.2% |
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 Radiation | 24 of 42 |
| Temozolomide Alone, Then Temozolomide Radiation | 22 of 52 |
Most frequent serious adverse event terms
| Event term | Organ system | Temozolomide Radiation | Temozolomide Alone, Then Temozolomide Radiation |
|---|---|---|---|
| NEOPLASM RECURRENCE | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 4 of 42 | 5 of 52 |
| DISEASE PROGRESSION | General disorders | 3 of 42 | 2 of 52 |
| RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | 1 of 42 | 1 of 52 |
| NAUSEA | Gastrointestinal disorders | 1 of 42 | 0 of 52 |
| VOMITING | Gastrointestinal disorders | 1 of 42 | 0 of 52 |
| DISEASE RECURRENCE | General disorders | 1 of 42 | 0 of 52 |
| HEPATIC FAILURE | Hepatobiliary disorders | 1 of 42 | 0 of 52 |
| CENTRAL NERVOUS SYSTEM INFECTION | Infections and infestations | 0 of 42 | 1 of 52 |
| LUNG INFECTION | Infections and infestations | 0 of 42 | 1 of 52 |
| BRAIN HERNIATION | Injury, poisoning and procedural complications | 0 of 42 | 1 of 52 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Temozolomide Radiation | Temozolomide Alone, Then Temozolomide Radiation |
|---|---|---|---|
| NAUSEA | Gastrointestinal disorders | 13 of 42 | 7 of 52 |
| VOMITING | Gastrointestinal disorders | 12 of 42 | 4 of 52 |
| HEADACHE | Nervous system disorders | 10 of 42 | 2 of 52 |
| PYREXIA | General disorders | 5 of 42 | 3 of 52 |
| DECREASED APPETITE | Metabolism and nutrition disorders | 4 of 42 | 2 of 52 |
| EPILEPSY | Nervous system disorders | 1 of 42 | 4 of 52 |
| DIZZINESS | Nervous system disorders | 0 of 42 | 4 of 52 |
| ALOPECIA | Skin and subcutaneous tissue disorders | 1 of 42 | 3 of 52 |
| CONSTIPATION | Gastrointestinal disorders | 0 of 42 | 3 of 52 |
| GAIT DISTURBANCE | General disorders | 3 of 42 | 0 of 52 |
Serious events with the highest arm-level rate: neoplasm recurrence (9.6%), disease progression (7.1%), nausea (2.4%), vomiting (2.4%), disease recurrence (2.4%).
The registry reports serious adverse events and other adverse events separately by treatment group. For the standard temozolomide radiation group, 11 of 42 participants at risk were reported as affected by serious adverse events, and 24 of 42 were affected by other adverse events. For the temozolomide-alone-then-temozolomide-radiation group, the corresponding counts were 11 of 52 for serious adverse events and 22 of 52 for other adverse events.
These are participant counts within the stated at-risk groups. They should not be read as counts of distinct event episodes: one participant may have experienced more than one event. The registry record does not explain why the serious-event at-risk group for the first arm is 42 when the primary outcome group contains 47, or provide details about event collection, severity grading, duration, or attribution to treatment. Death counts in the adverse-event information are not reported.
The listed serious adverse-event terms include NEOPLASM RECURRENCE at 9.6%, DISEASE PROGRESSION at 7.1%, NAUSEA at 2.4%, VOMITING at 2.4%, DISEASE RECURRENCE at 2.4%, and HEPATIC FAILURE at 2.4%. These terms and percentages are the registry’s reported serious-event entries; the record does not provide enough information to infer a causal relationship or compare risk between arms from those entries alone. The counts describe reported safety data, not a recommendation about treatment.
12. What the Result Does, and Does Not, Mean
The primary results provide arm-specific estimates of median overall survival in a randomized comparison. The reported median was 13.17 months in the standard temozolomide plus radiation group and 17.58 months in the group that began with early postsurgery temozolomide and then received the standard strategy. The corresponding 95% confidence intervals were 11.14 to 18.76 months and 15.18 to 23.03 months. The registry record defines overall survival as time from randomization to death and names Kaplan–Meier estimation as the analysis method.
These summaries do not establish the size or statistical significance of the contrast between treatment strategies. There is no reported hazard ratio, confidence interval for a between-arm effect, or p-value in the registry record. The separate confidence intervals describe uncertainty around each median, not uncertainty around a treatment effect. The results should therefore be described as the observed posted summaries, without turning them into a definitive comparative conclusion.
The record also does not provide results for the eight listed secondary outcomes, detailed survival follow-up, analysis-population definitions, or missing-data methods. It is not possible from these registry entries to judge whether the secondary findings would support, qualify, or conflict with the primary summaries. Nor can the reported safety counts establish that an event was caused by a study treatment.
More generally, a trial result applies to the participants, care settings, outcome definitions, and follow-up represented in the study. The registry record identifies newly diagnosed glioblastoma and the two strategies, but does not report enough participant characteristics to assess how closely the enrolled group represents any other population. Overall, the posted data describe two median survival estimates and their uncertainty; they do not supply all the information needed for a full assessment of comparative efficacy, safety, or generalizability.
13. Why This Trial Matters Statistically
This trial illustrates why an arm-specific outcome summary and a treatment-effect estimate answer different statistical questions. A median overall survival describes one feature of the estimated survival distribution in a group. A hazard ratio or another direct contrast would address the comparison between randomized groups and would need its own uncertainty estimate. The registry record reports the medians and their confidence intervals but does not report a direct comparative estimate or test.
It also shows why time-to-event outcomes require attention to follow-up and censoring. Kaplan–Meier methods can use partial follow-up, but interpretation depends on how participants leave observation and whether censoring is informative. The registry identifies the endpoint and method, yet does not report censoring details, numbers lost to follow-up, or numbers at risk over time. Those omissions matter when judging precision and robustness.
The study’s open-label design is another useful teaching point. Randomization supports a fair comparison at assignment, while lack of masking can affect conduct or outcome assessment. The primary outcome is an objectively defined event, but that does not remove questions about follow-up or ascertainment. Statistical interpretation depends on design, implementation, and reporting together.
Finally, the listed secondary outcomes and MGMT subgroup analyses raise the issue of multiplicity. Multiple questions may be useful for exploration, but interpretation requires knowing which were prespecified and how inference across them was handled. Those details are not reported in the registry record. This trial therefore demonstrates how to separate what the numerical summaries directly describe from what remains uncertain because comparative estimates, analysis details, and secondary results are not reported.
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 registry record contains limited information for assessing the primary comparison beyond the arm-specific medians and confidence intervals. A hazard ratio, direct confidence interval for the treatment contrast, and p-value are not reported. The primary outcome population is not specified, and the record does not state whether the analysis followed an intention-to-treat principle or another approach.
Important details of survival follow-up are not reported, including numbers at risk over time, censoring patterns, completeness of follow-up, and handling of participants lost to follow-up. Although the outcome timeframe is listed as up to 2 years, the record does not clarify how long each participant was followed or whether outcome ascertainment was complete. The primary endpoint description names Kaplan–Meier estimation but does not provide the comparison method.
The study is described as randomized and unmasked, but the randomization procedure, allocation concealment, stratification, and intended allocation ratio are not reported. The arm descriptions are truncated, so the full treatment schedules are not available in this record. Baseline characteristics and detailed eligibility criteria are also not reported, limiting assessment of group comparability and applicability to other populations.
Eight secondary outcomes are listed, but their numeric results and the four reported analyses are not detailed in the registry record. A multiplicity strategy and subgroup-analysis plan are not reported. Missing-data procedures, interim analyses, and the trial’s own sample-size justification are likewise not reported.
Safety information has separate at-risk group sizes, including 42 for serious adverse events in the standard arm, while the primary outcome group contains 47. The record does not explain the difference. Details about event definitions, grading, attribution, and death counts are not reported, which limits interpretation of the safety summaries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Standard Temodal (Temozolomide) Regimen Versus Standard Regimen Plus Early Postsurgery Temodal for Newly Diagnosed Glioblastoma Multiforme (Study P05572) — NCT00686725.
- Registry record last updated 2017-06-14; status last verified 2017-05.
- Results first posted 2013-04-04.
- 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.
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18. Record Summary
NCT00686725 is a completed randomized, parallel-group phase 4 study with no masking, sponsored by Merck Sharp & Dohme LLC. It enrolled 99 participants with glioblastoma. The study began on 2008-06-24, and primary completion was recorded on 2011-09-28.
The comparison was standard temozolomide with radiotherapy versus early postsurgery temozolomide followed by the standard regimen. The primary outcome was overall survival, defined as time from randomization to death and estimated using Kaplan–Meier methods, with a timeframe of up to 2 years. Median survival was 13.17 months (95% confidence interval 11.14 to 18.76) in the standard arm and 17.58 months (95% confidence interval 15.18 to 23.03) in the early-treatment arm.
The record lists eight secondary outcomes and reports adverse-event counts by group. A direct primary comparison estimate, secondary outcome results, analysis-population definitions, and several details about follow-up and statistical procedures are not reported in the registry record.