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 Gliadel Wafer and Fluorescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma (NCT01310868), a na phase 2 study. The primary outcome is Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01310868 |
| Phase | Phase 2 |
| Condition | Glioblastoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 59 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University College, London |
| Results posted | Yes |
2. Clinical Question
Population
Patients with primary glioblastoma undergoing surgical management. The registry describes 72 patients as recruited, 62 as having received 5-ALA and carmustine wafers, and 59 of those patients as eligible for the final analysis.
Intervention
Fluorescence-guided surgery using 5-ALA with Gliadel, or carmustine, wafers, followed by radiotherapy and chemotherapy with temozolomide. The record describes radiotherapy and concomitant and adjuvant chemotherapy as following standard clinical protocols determined by the neuro-oncologist.
Comparator
There was no comparator arm. This was a single-group feasibility study, and the registry lists allocation as not applicable and masking as none.
Primary question
Could the combination of intra-operative 5-ALA and Gliadel wafers be used with acceptable tolerability and feasibility before adjuvant radiotherapy plus temozolomide? The primary outcome describes procedure compliance and postoperative and treatment-course events, rather than a randomized comparison of treatment effects.
The question is about the practical and safety experience of combining two surgical technologies in a defined clinical pathway. The registry’s primary outcome description includes whether patients who underwent 5-ALA resection received carmustine wafer implants, postoperative deficits or surgical complications, delays in starting chemoradiotherapy due to surgical complications, failure to start or complete chemoradiotherapy, and a lower WHO performance status after surgery with wafers.
The record also lists time to clinical progression and survival at 24 months as secondary outcomes. Their results are not reported in the registry record. Because there is no control group, the study is not designed to establish how these outcomes compare with another surgical strategy or with care without one or both technologies.
3. Trial Design
This is a phase II, completed, single-group study of patients with primary glioblastoma. Its official title describes an evaluation of tolerability and feasibility when combining 5-ALA and carmustine wafers in surgical management. The stated treatment pathway includes fluorescence-guided surgery with 5-ALA, Gliadel wafers, and subsequent radiotherapy and temozolomide.
The registry lists an enrollment of 59. Separately, its primary outcome population description says that 72 patients were recruited, 62 received 5-ALA and carmustine wafers, and 59 of those 62 were eligible and included in the final analysis. These are distinct figures with different descriptions; the record does not explain the difference between the enrollment field and the narrative recruitment count.
Allocation is listed as not applicable, masking as none, and the model as single group. There is therefore no randomized control arm and no masked treatment assignment described. The study started in 2011-05, had primary completion in 2015-03, and is listed as completed.
The primary outcome is described over the period from surgery to the end of temozolomide and radiotherapy treatment, up to 34 weeks. It is a collection of feasibility and safety measures expressed in terms of participants or proportions, not a single time-to-event or continuous measure. The record lists three outcome measures in total and names time to clinical progression and survival at 24 months as secondary outcomes. Outcome estimates and analysis results are not reported in the registry record.
The sponsor is University College, London. The registry does not report the protocol’s sample-size justification, detailed statistical analysis plan, or whether interim analyses were planned. Those details cannot be inferred from the phase or the single-group design.
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: Study entry was based on imaging that has been judged to have typical appearances of a primary glioblastoma multiforme (GBM). Patients would have neurosurgery and GBM would be confirmed peri/post-operatively. If not GBM patients OR wafers+ 5-ala not administered then remain in the trial for follow up but were not included in the final analysis.
Overall Study
| Stage | 5-ALA and Gliadel Wafers |
|---|---|
| STARTED | 72 |
| COMPLETED | 59 |
| NOT COMPLETED | 13 |
Reasons for not completing this period:
| Reason | 5-ALA and Gliadel Wafers |
|---|---|
| Do not have histologically confirmed GBM | 13 |
Analysis population for the primary outcome, as defined in the registry: of 72 patients recruited, 62 received 5-ALA and carmustine wafers. Of these 62 patients, 59 were found to be eligible and included in the final analysis
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 | 5-ALA and Gliadel Wafers |
|---|---|---|
| Participants analysed | 72 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 54 |
| Age, Categorical: >=65 years | Participants | 18 |
| Sex: Female, Male: Female | Participants | 23 |
| Sex: Female, Male: Male | Participants | 49 |
| Region of Enrollment: United Kingdom | participants | 72 |
6. Primary Endpoint
The registry lists the primary outcome as Safety, Tolerability, and Feasibility of Combination Intra-operative 5-ALA and Gliadel Wafers Prior to Adjuvant Radiotherapy Plus Temozolomide, measured over Date of surgery to end of temozolomide and radiotherapy treatment (up to 34 weeks).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint description brings together several aspects of safety, tolerability, and feasibility during the surgical and postoperative treatment pathway. It includes procedure compliance among patients with 5-ALA resection, specifically whether carmustine wafer implants were received. It also describes postoperative deficits and surgical complications, including wound infection, cerebrospinal fluid leakage, and intracranial hypertension.
Other listed components concern whether surgical complications delayed the start of chemoradiotherapy, prevented it from starting, or interrupted completion of treatment. A further measure is the proportion of patients whose WHO performance status was lower after surgery with carmustine wafers, assessed at the first postoperative clinic visit. The stated timeframe runs from surgery to the end of temozolomide and radiotherapy treatment, up to 34 weeks.
These measures are useful for a feasibility question because they describe whether the combined procedure and subsequent treatment could be carried out and what complications or disruptions were recorded. They do not, by themselves, estimate a comparative treatment effect. The record describes the measures but does not report their observed values, component-specific denominators, or uncertainty estimates. Consequently, the endpoint’s intended scope can be described, but its results cannot be quantified from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study addresses a single-group feasibility question: whether 5-ALA and Gliadel wafers could be combined in surgical management and followed by radiotherapy and temozolomide. The posted design information identifies the intervention pathway and a final analysis population of 59 eligible patients. It does not provide observed results for the primary safety and feasibility measures, so the extent of procedure compliance, postoperative complications, or treatment disruption cannot be assessed from the registry record.
The record’s population description distinguishes recruitment, treatment receipt, and eligibility for final analysis: 72 patients were recruited, 62 received both 5-ALA and carmustine wafers, and 59 were eligible and included in the final analysis. These counts indicate that the analysis population was not simply described as everyone recruited. The record does not explain why individuals were not included at each stage, or provide outcomes for those who were not included in the final analysis. The registry enrollment field itself is 59, which is not the same figure as the narrative recruitment count.
Safety information is posted for a group of 59. The record lists 26 participants affected by serious adverse events and 23 affected by other adverse events. Among the serious-event terms listed, seizure is reported as 13.6%, thromboembolic event as 5.1%, and cerebral spinal fluid leak, infections other (not specified), sepsis, and wound infection as 3.4% each. These entries describe safety reporting in the study group; they do not establish that the intervention caused an event, and the registry does not provide a comparison group for interpreting event rates relative to another approach.
There is no randomized comparator, so observed outcomes cannot separate the effects of the combined intervention from the underlying disease, surgery, subsequent treatment, or other clinical circumstances. The design also does not support a direct estimate of what would have happened to the same patients under an alternative strategy. Descriptive safety and feasibility information can still be relevant to understanding the experience recorded in this cohort, but it should not be read as a comparative estimate.
The registry lists time to clinical progression and survival at 24 months as secondary outcomes, but their results are not reported in the registry record. It also lists three outcome measures and zero analyses. As a result, there are no posted analysis estimates, confidence intervals, or hypothesis tests on which to base conclusions about efficacy or precision. Planning illustrations based on an observed effect, where presented, are not observed power and do not replace missing trial results.
9. Statistical Methods Explained
What the design can estimate
In a single-group study, outcomes are described within the participants who received the study intervention. For a binary outcome, the basic summary is a count of participants with the event and the number of participants assessed. A proportion can be informative about how often an event or procedure outcome was recorded in that group. It does not show how that frequency differs from a control strategy, because no control group is present.
The primary outcome description includes several distinct events and process measures. These should not be treated as one interchangeable endpoint: receipt of a wafer implant, a postoperative complication, a delay in starting treatment, and a lower postoperative performance status represent different aspects of the pathway. The registry describes the measures but does not provide their separate results or specify a single combined rule that would define an overall primary outcome. Component estimates and their denominators are not reported in the registry record.
Denominators and analysis populations
A proportion depends on which participants are eligible for its denominator. The record describes 72 recruited patients, 62 who received 5-ALA and carmustine wafers, and 59 eligible participants included in the final analysis. It also describes procedure compliance among 5-ALA resected patients. Those descriptions imply that the relevant denominator may differ across measures, but the component-specific denominators are not reported in the registry record. Without them, readers cannot determine precisely which participants contributed to each endpoint.
The enrollment figure is 59, while the population narrative gives a recruitment count of 72. The record does not reconcile these figures. It also does not state how missing outcome observations were handled, whether participants were excluded after treatment receipt for particular analyses, or whether analyses followed an intention-to-treat, per-protocol, or other population definition. These are important distinctions when interpreting a study in which eligibility and treatment receipt are described separately.
Precision and uncertainty
A confidence interval is a statistical range that expresses uncertainty around an estimate under the assumptions of the analysis. For a proportion, its width depends in part on the number of participants assessed and the observed event frequency. A single-group estimate can therefore have uncertainty even when the count is fully observed. A confidence interval does not address bias from selection, missing data, measurement, or the lack of a comparator.
No confidence intervals or inferential analyses are reported in the registry record. The reported safety counts and percentages can be read descriptively, but the precision of those estimates cannot be evaluated from the registry results alone. Nor can a statistical test of a between-group difference be made when no comparison group is described.
Safety-event summaries
Adverse-event records commonly distinguish serious events from other events, and may also list event terms separately. A participant can experience more than one event, so event terms should not be assumed to represent distinct people or mutually exclusive categories unless the reporting definition says so. The record gives counts of affected participants for serious and other adverse events, alongside percentages for selected serious-event terms. It does not explain the event-term counting convention or whether individuals could appear under more than one term. The term percentages therefore should be read as posted registry summaries, not added together to create a total.
Planning illustrations and power
Sample-size calculations are planning tools that ask how many participants might be needed to detect a specified effect under stated assumptions. The registry’s planning illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is defined as a stated fraction of an observed effect. These are illustration assumptions, not a description of this single-group study’s allocation or its own design justification. The registry record does not report the original sample-size justification.
Any sample sizes calculated under such assumptions are planning illustrations, not observed power. Observed power should not be used to interpret a result after the fact; precision is better understood from the estimate and its confidence interval. In this record, no primary outcome estimates or confidence intervals are reported, so these planning assumptions cannot establish the precision or evidential strength of the trial results.
Time-to-event outcomes
Time-to-event methods account for both the time until an event and participants whose event time is not observed during follow-up. A survival estimate at a specified time point and a time-to-progression analysis require details about follow-up, censoring, event definitions, and the analysis population. The registry names time to clinical progression and survival at 24 months as secondary outcomes, but does not report their results or the associated analysis methods. No event counts, estimates, or uncertainty measures for these outcomes can therefore be interpreted from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures, with safety, tolerability, and feasibility as the primary outcome and time to clinical progression and survival at 24 months as secondary outcomes. When a study evaluates several outcomes or multiple components, the chance of at least one apparently unusual result can increase if each is tested separately. Statistical plans may address this multiplicity through a hierarchy, adjustment, or a clearly descriptive interpretation. The registry record does not report such a plan, and it lists zero analyses. No multiplicity adjustment or testing strategy should be assumed.
The primary outcome description itself contains multiple measures, including wafer implantation, complications, treatment delays or failures, treatment completion, and postoperative performance status. The record does not specify whether these were intended as separate outcomes, a composite, or a set of descriptive measures. Component-level results are not reported in the registry record, so no conclusion can be drawn about which component occurred most often or drove any overall finding.
The record identifies 59 eligible patients in the final analysis, but does not explain the handling of missing values or incomplete follow-up. It does not state whether all participants contributed to every measure, how missing outcome data were treated, or whether sensitivity analyses were performed. Missingness may affect estimates if participants with unavailable outcomes differ from those assessed; the direction and magnitude of any such effect cannot be determined without further reporting.
Analysis-population definitions are also not reported in detail. The narrative distinguishes recruited patients, patients who received both technologies, and those eligible for final analysis, but does not describe a formal analysis-set rule. The registry record does not report whether an intention-to-treat or per-protocol approach was used. These omissions limit assessment of selection, missing-data handling, and the relationship between the analyzed group and all recruited patients.
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 |
|---|---|---|---|
| 5-ALA and Gliadel Wafers | 26 | 59 | 44.1% |
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 |
|---|---|
| 5-ALA and Gliadel Wafers | 23 of 59 |
Most frequent serious adverse event terms
| Event term | Organ system | 5-ALA and Gliadel Wafers |
|---|---|---|
| seizure | Nervous system disorders | 8 of 59 |
| thromboembolic event | Vascular disorders | 3 of 59 |
| cerebral spinal fluid leak | Nervous system disorders | 2 of 59 |
| infections other (not specified) | Infections and infestations | 2 of 59 |
| sepsis | Infections and infestations | 2 of 59 |
| wound infection | Infections and infestations | 2 of 59 |
| Wound dehiscence | Injury, poisoning and procedural complications | 1 of 59 |
| hematoma | Vascular disorders | 1 of 59 |
| pulmonary edema | Respiratory, thoracic and mediastinal disorders | 1 of 59 |
| headache | Nervous system disorders | 1 of 59 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 5-ALA and Gliadel Wafers |
|---|---|---|
| seizure | Nervous system disorders | 5 of 59 |
| muscle weakness | Musculoskeletal and connective tissue disorders | 5 of 59 |
| thrombolytic event | Vascular disorders | 4 of 59 |
| neutrophil count decreased | Investigations | 4 of 59 |
| platelet count decreased | Investigations | 4 of 59 |
| nausea | Gastrointestinal disorders | 4 of 59 |
| wound infection | Injury, poisoning and procedural complications | 3 of 59 |
| white blood cell decreased | Investigations | 3 of 59 |
| lethargy | Nervous system disorders | 3 of 59 |
| vomiting | Gastrointestinal disorders | 3 of 59 |
Serious events with the highest arm-level rate: seizure (13.6%), thromboembolic event (5.1%), cerebral spinal fluid leak (3.4%), infections other (not specified) (3.4%), sepsis (3.4%).
For the 5-ALA and Gliadel wafers group, the registry records 59 participants at risk for serious adverse events and 26 participants affected. It records 59 at risk for other adverse events and 23 affected. These are safety summaries for the study group, not a comparison with an untreated or alternative-treatment group.
The listed serious-event terms include seizure at 13.6%, thromboembolic event at 5.1%, and cerebral spinal fluid leak, infections other (not specified), sepsis, and wound infection at 3.4% each. The record does not provide the event-term counting rules, so the terms should not be assumed to represent separate participants. A participant may be represented in more than one event category; the percentages should not be summed to infer a total.
These figures describe events recorded during the study and do not establish causation. A serious event occurring during a trial is not necessarily caused by the study intervention. The registry does not report comparative safety estimates, detailed event timing, or a causal attribution analysis. The posted summaries therefore characterize recorded safety experience but do not quantify how that experience differs from another clinical approach.
12. What the Result Does, and Does Not, Mean
The registry describes a phase II, single-group feasibility study involving fluorescence-guided surgery with 5-ALA and Gliadel wafers, followed by radiotherapy and temozolomide. The primary outcome was intended to capture whether the combined surgical approach and subsequent treatment pathway could be carried out, alongside postoperative complications and treatment disruptions. The population narrative identifies 59 eligible participants in the final analysis.
That design can support descriptive reporting about the study group, such as how many participants experienced a specified event or completed a specified step, if those outcome results are available. The registry record does not report the primary outcome results, however. It also does not report results for the listed secondary outcomes of time to clinical progression and survival at 24 months. Thus the registry information does not establish the observed feasibility rate, the frequency of each primary outcome component, or the progression and survival outcomes.
The safety summaries report 26 participants affected by serious adverse events and 23 affected by other adverse events among 59 at risk in each category. These figures describe events recorded in the group. Without a comparator, they cannot show whether the frequency is greater or lower than under another strategy, and they do not establish that the intervention caused the events.
The single-group design also cannot isolate the contribution of 5-ALA, Gliadel wafers, surgery, radiotherapy, or temozolomide from one another. It cannot determine what the same patients’ outcomes would have been under a different treatment pathway. The registry does not report an analysis plan, confidence intervals, or detailed missing-data methods that would allow readers to assess the statistical precision and robustness of outcome estimates.
Accordingly, the record supports a description of the study’s aim, design, population accounting, and posted safety counts. It does not support a comparative claim about benefit or harm, or a conclusion about treatment efficacy. Those boundaries reflect both the single-group design and the absence of posted outcome analyses.
13. Why This Trial Matters Statistically
Feasibility studies address practical questions that can arise before a larger comparative evaluation: whether a procedure can be implemented, whether participants can proceed through the intended treatment pathway, and what safety events are recorded. The primary outcome description for this study is aligned with those questions. It includes procedure compliance, postoperative complications, delays or failures in starting treatment, treatment completion, and postoperative performance status.
Statistically, the study illustrates why endpoint definitions and denominators matter. The registry describes different population stages: patients recruited, patients who received both technologies, and patients eligible for final analysis. It also defines procedure compliance with reference to patients who had 5-ALA resection. Different measures may therefore use different analysis populations. Clear reporting of each numerator, denominator, and eligibility rule is needed for readers to interpret a proportion and compare it with other studies.
The single-group design is appropriate for descriptive feasibility questions but has a limited role in comparative inference. Counts can describe experience in the study group; they cannot show whether outcomes are better or worse than under another approach. The posted adverse-event information can therefore be read as a record of observed safety experience, not as a causal estimate.
The distinction between a registered outcome and a reported result also matters. The registry names progression and survival outcomes, but their estimates are not reported in the registry record. A named endpoint alone does not reveal how it was measured, how much follow-up was available, or how precise an estimate would be. Reporting those details is necessary for readers to assess evidence about outcomes beyond feasibility.
Finally, planning calculations should be kept separate from results. A sample-size illustration based on assumptions does not show how much power the completed study had, nor does it substitute for an observed effect estimate and uncertainty interval. For this trial, the lack of posted outcome analyses means that the most defensible statistical reading is focused on design, population accounting, and the limited safety summaries that are recorded.
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 the trial is that it is a single-group study with no comparator. Its design can describe outcomes in the treated group but cannot estimate a contrast with another strategy or distinguish treatment effects from other influences on outcomes. Masking is listed as none, and the registry provides no account of blinded outcome assessment.
The population counts are not fully reconciled. The registry enrollment field is 59, while the primary outcome narrative describes 72 patients recruited, 62 receiving 5-ALA and carmustine wafers, and 59 eligible for final analysis. The reasons for these differences and the outcomes of people not included in the final analysis are not reported in the registry record. This limits evaluation of selection and of how representative the final analysis population is of everyone recruited.
The registry describes several primary outcome components but does not report their observed results, component-specific denominators, or confidence intervals. It also names time to clinical progression and survival at 24 months without reporting their results. The absence of posted analyses prevents assessment of outcome magnitude and precision.
Details about missing-data handling, analysis populations, endpoint definitions beyond the brief descriptions, and the statistical analysis plan are not reported in the registry record. The registry also does not explain the adverse-event term counting convention or provide a comparator for safety interpretation. These reporting gaps make it difficult to assess the robustness and completeness of the outcome summaries, beyond the descriptive safety counts that are posted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Gliadel Wafer and Fluorescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma — NCT01310868.
- Registry record last updated 2017-10-05; status last verified 2017-09.
- Results first posted 2017-08-14.
- 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
NCT01310868 is a completed phase II, single-group study of fluorescence-guided surgery with 5-ALA and Gliadel wafers in primary glioblastoma, followed by radiotherapy and temozolomide. Allocation is listed as not applicable and masking as none. The study started in 2011-05 and reached primary completion in 2015-03.
The registry enrollment field is 59. The primary outcome population description says 72 patients were recruited, 62 received both 5-ALA and carmustine wafers, and 59 were eligible and included in the final analysis. The primary outcome concerns safety, tolerability, and feasibility through the end of temozolomide and radiotherapy treatment, up to 34 weeks.
The registry lists time to clinical progression and survival at 24 months as secondary outcomes. It records serious adverse events in 26 of 59 participants at risk and other adverse events in 23 of 59 at risk. Primary and secondary outcome analyses are not reported in the registry record.