A Study of PD 0332991 in Patients With Recurrent Rb Positive Glioblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of PD 0332991 in Patients With Recurrent Rb Positive Glioblastoma (NCT01227434), a non-randomized phase 2 study. The primary outcome is Progression Free Survival.

2. Clinical Question

This study was designed around a treatment strategy that differed according to whether a participant was expected to undergo resection as clinical care. The surgical group had a pre-surgery drug period and resumed treatment after recovery; the other group received drug without a planned surgical procedure. Those clinical pathways define the comparison, but they do not create randomized treatment groups. Participants needing surgery may differ from those not needing it in ways that also relate to their subsequent outcomes.

The registry describes an intended total of 30 participants, with up to 15 in each pathway, and records enrollment of 23. The difference between an intended enrollment and the recorded enrollment does not by itself explain why recruitment ended or how many participants contributed to each efficacy analysis. The reason the study was terminated and detailed analysis populations are not reported in the registry record.

3. Trial Design

This was a phase II, non-randomized, parallel-group study sponsored by the University of California, San Francisco. The record lists enrollment of 23 and a terminated status. It identifies no masking. The study began in 2010-09, and primary completion is recorded as 2013-12. The reason for termination is not reported in the registry record.

The two groups represented different care pathways rather than randomized alternatives. Participants in the Surgical Group were to receive PD 0332991 before an intended resection and resume the drug after recovery. The registry describes the preoperative dose as 125 mg daily for 7 days. The postoperative schedule is described as 21 consecutive days of treatment followed by a 7-day break, repeating on a 28-day cycle. Resection is identified as clinical care, not as a randomized study intervention.

The Non-surgical group was described as receiving PD 0332991 at 125 mg daily for 21 consecutive days followed by a 7-day break, with treatment repeated every 28 days. The record says participants without disease progression may receive treatment for 12 cycles. These schedules give context for the study arms but do not establish how long each participant actually received treatment.

The registry's brief summary describes a plan for 30 participants, divided between the planned-surgery and non-surgical pathways. Enrollment is recorded as 23. The number who completed treatment, underwent resection, or entered each primary-outcome analysis is not reported in the registry record. Nor is a detailed account of the recruitment and follow-up of the enrolled participants.

Since treatment pathway was not randomized, any observed difference between groups would combine possible treatment-related differences with differences in the participants selected for each pathway. The registry record itself warns that the arms are not a like-for-like control comparison. A randomized comparison, allocation concealment, and masking are not part of the design described in the 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.

Before assignment: Of 23 participants consented, 1 was found ineligible prior to randomization

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 Progression Free Survival, measured over up to 142 weeks.

The primary endpoint is progression-free survival, reported in the registry as a mean measured in weeks, with full range. Progression-free survival captures the time participants remain alive without recorded disease progression under the endpoint definition used in the study. It is often used in oncology research because it describes disease-control duration without requiring death to be the only event of interest. The endpoint definition and assessment procedures beyond the registry description are not reported in the registry record.

The registry gives a timeframe of up to 142 weeks. This describes the stated observation window, not the mean result or the duration of follow-up for every participant. Although the endpoint is described as a mean with full range, the numerical mean and range are not reported in the registry record. The record also does not report a confidence interval, group-specific endpoint estimates, or a statistical comparison of the groups.

Interpretation of a time-to-event outcome depends on how progression is assessed, how events are dated, and how participants without a recorded event are handled. Those details are not reported in the registry record. Without them and without numerical outcome results, the endpoint's precision and the degree of uncertainty around any group estimate cannot be evaluated from the registry entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial statistics depend on both the design and the way outcomes are recorded and analyzed. In this study, the registry describes a non-randomized, parallel-group design. The groups received the same named drug but followed different pathways based on planned surgery. That distinction is important: statistical comparisons between groups can describe their observed outcomes, but the design does not ensure that the groups were comparable at the start.

What does non-randomized allocation mean?

In a randomized study, chance assignment is used to make treatment groups comparable, on average, with respect to both known and unknown participant characteristics. In a non-randomized study, group membership may be related to clinical circumstances or other participant characteristics. Here, the surgical pathway was intended for participants undergoing resection as clinical care, while the other pathway was for those not in need of surgery. This can create differences between groups apart from their treatment schedules.

Statistical adjustment can sometimes account for measured differences between groups, but it cannot automatically remove bias from unmeasured differences. The registry record does not report a covariate-adjustment plan or an adjusted primary-outcome analysis. Any causal interpretation would therefore need to be especially cautious, and the record itself warns that the arms are not a like-for-like control comparison.

What does a mean with full range describe?

A mean is a measure of the center of a set of observations. The full range describes the lowest and highest observed values. Together they offer a compact account of the spread, but they do not reveal the full shape of the data. For a time-to-event outcome such as progression-free survival, some participants may not have had a recorded progression by the end of observation. A standard mean and range alone may not describe how such incomplete event times were handled.

Time-to-event analyses commonly use methods that account for participants whose event time is not observed during follow-up. Such methods distinguish the time an event is observed from a time beyond which the participant's outcome is unknown. The registry lists a mean and full range, but does not report whether censoring occurred, how it was handled, or whether a survival-curve or other time-to-event method was used. These details are not reported in the registry record.

How should a confidence interval be understood?

A confidence interval is a range of values that expresses the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not account for every source of uncertainty, such as selection bias or outcome misclassification. No confidence interval for progression-free survival is reported in the registry record, so its precision cannot be judged from the entry.

A p-value, if reported, would describe how compatible the data are with a specified null hypothesis under a statistical model. It would not measure the probability that a treatment works, nor would it correct for the non-randomized design. The registry record does not report a primary-outcome p-value or a stated inferential comparison. A result cannot be reconstructed from the endpoint label alone.

Why do sample-size assumptions matter?

Sample-size planning depends on the effect a study is designed to detect, the variability or event pattern expected, the significance level, the desired power, and the analysis method. A planning illustration based on an observed effect is not the same as the original trial's design justification. It is also not observed power. The registry record does not report the study's own sample-size justification, target effect, or statistical assumptions for the primary analysis.

Any planning illustrations associated with the posted results should be interpreted as hypothetical scenarios under their stated assumptions, rather than as evidence about the reliability of the observed findings. The registry entry gives no numerical efficacy estimate from which to assess such a scenario. The assumptions for the planning illustration are described as a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect defined as a stated fraction of the observed effect. Those assumptions do not establish that the original study used the same design or analysis.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability in data is greater than a statistical model assumes. If a model fails to account for extra variability, estimated standard errors can be too small and statistical evidence can appear more precise than it is. This concept is relevant to some count-data analyses, but the registry does not describe a count-data primary analysis or report a model in which over-dispersion was evaluated. It should not be assumed to have affected this study's endpoint.

What can be inferred from the safety counts?

Counts of participants affected summarize how many people had an event within the recorded category, but do not describe the number of event episodes or their timing unless those details are reported. A participant may experience more than one event, and a listing of event terms may use a different denominator from a participant-level count. The registry gives group-specific at-risk and affected counts, alongside percentages for selected serious-event terms, but does not specify the percentage denominator in the entry. Those values should be kept distinct rather than combined into a new rate.

For these reasons, the strongest statistical reading is descriptive. The record states the intended question and records some safety counts, but it does not provide the numerical primary efficacy results, confidence intervals, p-values, or a detailed analysis plan. General statistical concepts can clarify what such measures would mean, but cannot substitute for trial-specific results that are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, groups, time points, or statistical contrasts. Testing many questions can increase the chance that at least one result appears statistically notable by chance. Researchers may address this through a prespecified hierarchy, adjustment procedures, or a clearly identified primary endpoint. The registry lists progression-free survival as the primary outcome and identifies an adverse-event outcome as secondary, but a detailed multiplicity strategy is not reported in the registry record.

The registry reports two outcome measures and one analysis, but does not explain the analysis structure or whether more than one comparison was planned for the primary endpoint. It also does not report interim analyses, stopping rules, or whether the primary analysis was prespecified before results were examined. These elements should not be inferred from the phase or status of the study.

Missing-data handling is also important. Participants may have incomplete follow-up, may withdraw, or may have an outcome that is not observed before the observation window ends. The record does not describe missing-data procedures, censoring rules, or sensitivity analyses. It does not state whether the primary analysis included all enrolled participants, only treated participants, or another defined analysis population. These details are not reported in the registry record.

Without a documented analysis population and missing-data approach, it is difficult to judge how representative an endpoint estimate would be of all enrolled participants. The registry's recorded enrollment does not establish how many contributed to the endpoint analysis. Nor does the endpoint timeframe specify the follow-up actually achieved by each participant. These limitations affect interpretation even if a numerical estimate were available.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: headache (33.3%), seizure (33.3%), death nos (16.7%), meningitis (16.7%), wound infection (16.7%).

The safety summary separates the number of participants at risk from the number affected. In the Surgical Group, 6 participants were at risk for serious adverse events and 5 were affected; for other adverse events, 6 were at risk and 4 were affected. In the Non-surgical group, 16 were at risk for serious adverse events and 4 were affected; for other adverse events, 16 were at risk and 15 were affected. These are descriptive counts within the registry's group summaries.

The listed serious-event terms are Headache and Seizure, both reported at 33.3%; Death NOS, Meningitis, Wound Infection, and Muscle Weakness are each reported at 16.7%. The registry does not identify the denominator behind those percentages in this entry. The percentages should not be converted into participant counts or treated as incidence estimates without that information.

The safety summaries do not show whether an event was judged related to treatment, when it occurred, how severe it was, or whether an individual had more than one event. The registry also gives no deaths value for either group in the group-level summary. The term Death NOS appears in the serious-event listing, but the entry does not clarify its relationship to the separate death field. No causal conclusion about PD 0332991 can be made from these summaries alone.

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

The record establishes that a phase II study evaluated PD 0332991 in a population described as having recurrent Rb-positive glioblastoma multiforme or gliosarcoma. Its primary endpoint was progression-free survival, expressed as a mean in weeks with full range and a timeframe of up to 142 weeks. The study used two parallel, non-randomized pathways, one involving an intended surgical resection and one without planned surgery.

The record does not report the numerical progression-free survival result, a group comparison, or uncertainty estimates. It therefore cannot establish the observed duration of progression-free survival or whether outcomes differed between pathways. The stated timeframe is a measurement window, not a result. Enrollment of 23 and the intended total of 30 describe study size, not the number analyzed for the primary outcome.

The non-randomized design also limits what a group comparison could mean. Participants were in the surgical group because they were expected to undergo surgery as clinical care; those in the other group were not in need of surgery. Differences in clinical status or other characteristics could affect outcomes. Since there was no randomized assignment and no untreated control group described, the design cannot by itself separate the effect of the drug from these differences or estimate how outcomes compare with no drug.

The adverse-event counts and selected serious-event terms offer limited descriptive safety information. They do not establish causation, event rates with a clearly specified denominator, or the full severity and timing of events. Missing details about analysis populations, follow-up, and event handling further constrain interpretation.

Thus, the registry record documents the research question, treatment pathways, and selected safety summaries, but does not report the efficacy results needed to quantify the primary outcome. This is a limitation of what can be concluded from the record, not evidence that the study did or did not observe a particular result.

13. Why This Trial Matters Statistically

This study illustrates why trial design must be considered before interpreting an apparent difference between groups. The parallel structure may invite a direct comparison, but the pathways were non-randomized and were defined by planned surgery. Participants in the two groups were therefore selected under different clinical circumstances. A numerical contrast, even if reported, would not automatically have the interpretation of a randomized treatment effect.

It also highlights the difference between an endpoint definition and an endpoint result. Naming progression-free survival, its unit, and its follow-up timeframe does not tell readers the observed outcome or its precision. The registry lists the endpoint as a mean in weeks with full range, but does not report those values. Statistical interpretation must stop short of conclusions that require the missing estimates.

The safety information demonstrates another practical issue: counts and percentages are meaningful only when their denominators and definitions are clear. Group-level affected counts are reported alongside selected event terms with percentages, but the denominator for those percentages is not reported in the registry record. Keeping the summaries separate avoids treating them as directly interchangeable measures.

Finally, the record shows why enrollment, treatment schedules, and analysis populations should not be conflated. Enrollment is recorded as 23, while the study description states an intended total of 30. The number contributing to the primary outcome analysis is not reported in the registry record. Those details describe different aspects of the study and cannot substitute for one another. Careful statistical reading preserves these distinctions and avoids turning a sparse registry entry into a stronger efficacy claim than its reported results support.

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 main limitation for interpreting this study from the registry record is that numerical results for the primary endpoint are not reported. The registry names progression-free survival and describes its measurement, but gives no mean, range, group-specific estimate, or confidence interval. The statistical evidence for the primary question therefore cannot be assessed.

The non-randomized allocation limits comparability between the groups. The record states that the surgical group was planned around resection as clinical care and that the non-surgical group comprised patients not in need of surgery. Any outcome difference could reflect underlying differences between these populations, as well as differences in their treatment pathways.

The record lists enrollment of 23, while the study description gives an intended total of 30. The reason for termination is not reported in the registry record. It is also not stated how many participants were treated, completed the planned schedule, underwent resection, or contributed to the primary analysis. The analysis population, endpoint follow-up completeness, and handling of missing observations are not reported.

The endpoint description does not provide the detailed progression criteria, assessment schedule, censoring rules, or statistical method. The registry does not report a prespecified analysis plan, a sample-size justification, an interim-analysis plan, or adjustments for multiple testing. None of these details can be inferred from the endpoint label or study phase.

Safety interpretation is constrained by the lack of detail on event timing, severity, attribution, and the denominator behind the listed serious-event percentages. The record does not explain how the selected event terms relate to participant-level counts. These limitations mean the safety summaries should be treated as descriptive rather than as evidence of comparative risk or causation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of PD 0332991 in Patients With Recurrent Rb Positive Glioblastoma — NCT01227434.
• Registry record last updated 2015-07-17; status last verified 2015-06.
• Results first posted 2015-06-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

This phase II study evaluated PD 0332991 in patients with recurrent Rb-positive glioblastoma or related tumors. It used a non-randomized parallel design without masking, with a surgical pathway involving preoperative treatment and a non-surgical pathway. The registry records enrollment of 23, a terminated status, and an intended total of 30 participants.

Progression-free survival was the primary endpoint, described as a mean in weeks with full range over a timeframe of up to 142 weeks. Numerical primary-outcome results and detailed analysis methods are not reported in the registry record. The safety record includes group-level counts of participants affected and selected serious-event terms, but does not report the denominator for the term percentages in this entry.

Because allocation was non-randomized and the groups followed different clinical pathways, they are not a like-for-like control comparison. The record supports a description of the study design and its reported safety summaries, but not a numerical conclusion about efficacy or a causal comparison between groups.