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 EGb761 in Maintaining Mental Clarity in Women Receiving Chemotherapy for Newly Diagnosed Breast Cancer (NCT00046891), a randomized phase 3 study. The primary outcome is The Level of Cognitive Dysfunction as Measured by the High Sensitivity Cognitive Screen (HSCS) Overall Score..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00046891 |
| Phase | Phase 3 |
| Condition | Breast Cancer, Neurotoxicity |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 226 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alliance for Clinical Trials in Oncology |
| Results posted | Yes |
2. Clinical Question
Population
Women receiving chemotherapy for newly diagnosed breast cancer. The registry record lists breast cancer and neurotoxicity as conditions and describes the trial as addressing possible chemotherapy-related cognitive dysfunction. It does not report further eligibility details in the information available for this analysis.
Intervention
Ginkgo Biloba, identified as EGb761 in the trial description, at 120 mg per day (60 mg BID). The trial rationale concerns whether this intervention might help maintain mental clarity during chemotherapy. A rationale is not evidence of an observed treatment effect.
Comparator
Placebo, described as 1 tablet BID. The trial used randomized allocation and double masking, with a parallel design. Further details about how the placebo was matched or how masking was maintained are not reported in the registry record.
Primary question
The primary endpoint concerned the level of cognitive dysfunction, measured using the High Sensitivity Cognitive Screen (HSCS) overall score and summarized as an area under the curve from baseline to 12 months after starting chemotherapy. Lower HSCS scores are better. The registry record does not report the comparative endpoint values, an effect estimate, or a statistical test, so the direction and precision of any between-group difference cannot be assessed.
3. Trial Design
The registry describes a completed, randomized, double-masked, parallel-group phase 3 trial sponsored by the Alliance for Clinical Trials in Oncology. Enrollment was 226. The trial began in 2002-12, and primary completion was recorded in 2006-10. The study compared Ginkgo Biloba with placebo among women receiving chemotherapy for newly diagnosed breast cancer.
The intervention is listed as Ginkgo Biloba, with an arm description of 120 mg per day (60 mg BID). The comparator is listed as placebo, described as 1 tablet BID. These entries identify the assigned treatments but do not establish the extent to which participants adhered to the assigned regimen. Adherence results are not reported in the registry record.
Randomization is intended to make treatment groups comparable on average at the point of assignment, including for characteristics that may not be measured. It does not guarantee that the groups will be identical, especially in a particular trial. Double masking is intended to limit the influence of treatment knowledge on participant experience, reporting, and assessment. The registry does not describe who was masked, how allocation was concealed, or whether masking was assessed.
The listed efficacy population includes patients who reported a baseline value and one value after baseline. This definition is narrower than a statement that every enrolled participant contributed to the primary analysis, and the number meeting the definition is not reported in the registry record. The record does not report the randomization ratio, site details, eligibility criteria, treatment duration, or follow-up procedures beyond the primary endpoint timeframe.
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 | Ginkgo Biloba | Placebo |
|---|---|---|
| STARTED | 113 | 113 |
| COMPLETED | 84 | 83 |
| NOT COMPLETED | 29 | 30 |
Reasons for not completing this period:
| Reason | Ginkgo Biloba | Placebo |
|---|---|---|
| Cancels | 5 | 9 |
| Ineligible | 1 | 1 |
| Withdrawal by Subject | 18 | 15 |
| Adverse Event | 5 | 5 |
Analysis population for the primary outcome, as defined in the registry: Efficacy analyses uses all patients that reported baseline and one value after baseline.
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 | Ginkgo Biloba | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 113 | 113 | 226 | |
| Age, Customized: Age < 50 | participants | 55 | 54 | 109 |
| Age, Customized: Age >= 50 | participants | 58 | 59 | 117 |
| Sex: Female, Male: Female | Participants | 113 | 113 | 226 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 113 | 113 | 226 |
6. Primary Endpoint
The registry lists the primary outcome as The Level of Cognitive Dysfunction as Measured by the High Sensitivity Cognitive Screen (HSCS) Overall Score., measured over Baseline, 12 months after starting Chemotherapy..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale*months |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the HSCS overall score, described as a measure of cognitive dysfunction. The primary analysis combined HSCS scores into area-under-the-curve (AUC) scores for data points from baseline to the 12 month data point. The unit is stated as units on a scale*months. Lower scores are better. The registry describes the endpoint parameter as a mean and its dispersion as a standard deviation.
The HSCS contains questions concerning memory, language, visual-motor function, spatial function, attention and concentration, and self-regulation and planning. The registry gives the component ranges as Memory (0-39), Language (0-30), Visual-motor (0-10), Spatial (0-8), Attention and Concentration (0-25), and Self-Regulation and Planning (0-6). The total is calculated by summing these subscales, with values ranging from 0 to 125.
In general, an AUC summarizes measurements across a defined period rather than relying only on a single assessment. It can reflect the combined level of scores over that interval, but its interpretation depends on the measurement schedule and calculation. The registry does not provide the individual observations, the resulting group means, or the between-group comparison. It therefore does not establish whether the groups differed or how precisely any difference was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The trial addresses a clinically relevant measurement question: how cognitive-function scores changed over the period from baseline to 12 months after starting chemotherapy, and whether the summarized scores differed between randomized treatment groups. The registry describes the endpoint and the direction of its scale, but it does not report the primary endpoint results. No group means, standard deviations, treatment contrast, confidence interval, or primary-outcome p-value are included in the information available for this analysis.
Without a comparative estimate, the size and direction of the observed treatment difference cannot be described. Without an interval estimate, its precision cannot be assessed. Without a reported test result and analysis details, it is not possible to characterize the evidence against a null hypothesis from the registry record. The absence of reported results in this record should not be interpreted as evidence that the groups were equal, nor as evidence that one treatment was better.
The outcome description says that lower HSCS scores are better. That direction is useful for interpreting a reported score, but it does not reveal what happened in the trial. The endpoint uses an AUC summary across time, so a comparison would concern that summary rather than a single score at one isolated assessment. The available information does not show whether scores were similar at baseline, how they changed during follow-up, or whether any difference was concentrated at a particular time.
The registry lists median scores for Trail Making Tests A and B, cognitive-function measures using those tests, self-reported symptoms or side effects using the Symptom Experience Diary, and associations involving self-reported cognition, HSCS, and Trail Making Test results among secondary outcomes. These outcomes could provide additional perspectives on cognitive performance and reported experience. Their listed presence alone does not establish their findings. Numerical results and comparative estimates for those measures are not reported in the registry record.
The safety entries report serious adverse events among participants at risk as 4 for Ginkgo Biloba and 3 for placebo; the corresponding at-risk counts are 104 and 101. The record also lists other adverse events as 89 and 94 among the respective at-risk groups. These counts describe recorded events in the registry categories, but do not by themselves provide a complete account of event timing, duration, severity distribution, or relationship to treatment. The record's serious-event terms include neutrophil count decreased, leukocyte count decreased, febrile neutropenia, infection with grade 3 or 4 neutropenia, and platelet count decreased, with percentages listed for those terms.
Overall, the design features and endpoint definition can be described, but the comparative efficacy findings cannot. A statistically careful reading separates what the record says about the planned measurement from what it reports as observed results. In this case, the primary comparison and its uncertainty are not reported in the registry record, so no conclusion about the treatment contrast can be drawn from these registry entries.
9. Statistical Methods Explained
Random allocation is a method for assigning participants to treatment groups by chance. In general, it helps reduce systematic differences between groups at enrollment, including differences in measured and unmeasured characteristics. Randomization does not ensure identical groups in the realized sample. It also does not, by itself, resolve problems caused by missing outcomes, non-adherence, or departures from the planned analysis. The registry identifies the trial as randomized but does not report the allocation sequence, concealment procedures, or randomization ratio.
What does double masking contribute?
Masking is intended to reduce bias that could arise if participants or study personnel know the assigned treatment. Knowledge of assignment can influence symptom reporting, care, assessment, or decisions about follow-up. The registry labels the trial double-masked, but does not identify which roles were masked, describe the practical masking procedures, or report whether participants or assessors correctly guessed assignment. The label therefore records a design feature without allowing a detailed evaluation of how masking operated.
What does the endpoint summary represent?
The primary endpoint is a continuous measure: the HSCS overall score summarized as an AUC from baseline to the 12 month data point. A continuous outcome can take a range of values rather than representing only whether an event occurred. The registry identifies the mean as the endpoint parameter and the standard deviation as its dispersion. In general, a mean describes the central level of a set of values, while a standard deviation describes how spread out individual values are around that mean. Neither statistic is reported for the trial's treatment groups in the information.
An AUC is a summary of measurements over time. It differs from comparing only the starting or ending score because it incorporates the score trajectory over the defined interval, according to the calculation used. The scale is expressed in units on a scale*months. Interpretation depends on how observations were scheduled and how values between observations were handled. Those calculation details are not reported in the registry record beyond the description that data points from baseline to the 12 month data point were compiled into AUC scores.
The record notes that the HSCS total sums the listed domains and that lower scores are better. A combined score can provide an overall summary, while also potentially obscuring variation among its component domains. The registry lists domain ranges but does not report domain-specific primary comparisons in the registry record for this analysis. The AUC total should therefore be read as the designated overall cognitive-function summary, not as proof that every component changed in the same way.
How should uncertainty be assessed?
In general, a confidence interval gives a range of effect estimates that are compatible with the data and the method used to calculate the interval. Its width conveys precision: narrower intervals indicate greater precision, while wider intervals indicate less precision. A p-value addresses compatibility of the data with a specified null model and assumptions; it does not measure the probability that a treatment works, and it does not describe the size or clinical importance of an effect. The registry record does not report a confidence interval or primary-outcome p-value, so neither precision nor statistical evidence for the primary comparison can be evaluated.
For a continuous endpoint, a treatment contrast might be expressed as a difference between group means, with its uncertainty estimated using an analysis appropriate to the design and data. That is a general description, not a statement about the method used in this trial. The registry does not report the fitted model, covariate adjustment, handling of repeated measurements, variance assumptions, or the exact contrast used for the primary analysis. Those details are needed to reproduce or fully evaluate an analysis.
Why do distribution and model assumptions matter?
Statistical procedures rely on assumptions about how the observations and errors behave. For example, a model for a mean contrast may rely on assumptions about residual variation and independence, while longitudinal analyses must account for the relationship between measurements from the same participant. If the data do not fit the assumptions well, estimates or standard errors may be unreliable. The record's summary of a mean and standard deviation does not specify which model was used, whether assumptions were checked, or whether alternative analyses were conducted.
Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. In that circumstance, standard errors can be too small if the extra variability is ignored, leading to intervals that are too narrow or tests that appear more decisive than warranted. This is a general statistical consideration, not a reported feature of this trial. The registry does not report whether over-dispersion was assessed or whether it was relevant to the HSCS analysis.
What do planning calculations mean?
Sample-size calculations are design illustrations: they estimate how much information a future study might need under stated assumptions. They depend on the target effect, variability, significance level, allocation, and analysis approach. A calculation based on an observed effect is especially dependent on that estimate, which can be imprecise. Such a planning value is not observed power and cannot replace a confidence interval for the actual trial estimate. The registry describes planning assumptions based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It does not report the trial's own design justification in the information available for this analysis. The planned-assumption description should not be treated as proof that those methods were used for the primary analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes, including Trail Making Test A and B measures, self-reported symptoms or side effects using the Symptom Experience Diary, and associations among self-reported cognition, HSCS, and Trail Making Test results. It also reports six outcome measures and one analysis in its summary of posted outcomes. When a study examines multiple outcomes or comparisons, the chance of obtaining at least one apparently notable result by chance can increase. Statistical methods such as prespecifying a primary outcome, adjusting for multiple comparisons, or treating secondary analyses as exploratory can address different aspects of this issue. The registry record does not report a multiplicity adjustment or a detailed statistical plan for secondary analyses.
The registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. As a result, the primary endpoint description does not provide a single reported contrast that can be interpreted as the trial's overall primary result. Which comparisons were prespecified, how time points or categories were handled, and whether any adjustment was made are not reported in the registry record.
The described efficacy population consists of patients who reported a baseline value and one value after baseline. This indicates that the stated analysis population depended on having outcome data at baseline and after baseline. The number included under that definition is not reported in the registry record. The record does not explain how missing measurements were handled, whether additional observations were imputed, or whether sensitivity analyses examined departures from assumptions about missingness.
Missing data can affect a treatment comparison if availability of measurements is related to health, treatment assignment, or the outcome itself. In general, complete-case analyses can be biased when the participants with observed values differ systematically from those without them. The registry population definition alone is not enough to determine whether that concern applied or how it was addressed. Reasons for missing data, participant flow by group, and analysis-population details beyond the stated efficacy criterion are not reported in the registry record.
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 |
|---|---|---|---|
| Ginkgo Biloba | 4 | 104 | 3.8% |
| Placebo | 3 | 101 | 3.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ginkgo Biloba | 89 of 104 |
| Placebo | 94 of 101 |
Most frequent serious adverse event terms
| Event term | Organ system | Ginkgo Biloba | Placebo |
|---|---|---|---|
| Neutrophil count decreased | Investigations | 4 of 104 | 2 of 101 |
| Leukocyte count decreased | Investigations | 1 of 104 | 2 of 101 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 104 | 1 of 101 |
| Infection with grade 3 or 4 neutropenia | Infections and infestations | 1 of 104 | 0 of 101 |
| Platelet count decreased | Investigations | 1 of 104 | 0 of 101 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ginkgo Biloba | Placebo |
|---|---|---|---|
| Hemoglobin decreased | Blood and lymphatic system disorders | 66 of 104 | 72 of 101 |
| Nausea | Gastrointestinal disorders | 68 of 104 | 66 of 101 |
| Leukocyte count decreased | Investigations | 56 of 104 | 60 of 101 |
| Vomiting | Gastrointestinal disorders | 32 of 104 | 37 of 101 |
| Platelet count decreased | Investigations | 25 of 104 | 32 of 101 |
| Hemorrhage | Vascular disorders | 19 of 104 | 17 of 101 |
| Neutrophil count decreased | Investigations | 15 of 104 | 13 of 101 |
| Fatigue | General disorders | 6 of 104 | 5 of 101 |
| Headache | Nervous system disorders | 4 of 104 | 2 of 101 |
| Thrombosis | Vascular disorders | 1 of 104 | 4 of 101 |
Serious events with the highest arm-level rate: neutrophil count decreased (3.8%), leukocyte count decreased (2.0%), febrile neutropenia (1.0%), infection with grade 3 or 4 neutropenia (1.0%), platelet count decreased (1.0%).
The registry separates serious adverse events from other adverse events. For serious adverse events, it reports 4 affected participants among 104 at risk in the Ginkgo Biloba group, and 3 among 101 at risk in the placebo group. For other adverse events, it reports 89 affected among 104 at risk for Ginkgo Biloba and 94 among 101 at risk for placebo. These are the posted counts and denominators; they are not adjusted comparisons, and no statistical uncertainty for the group contrast is reported.
The registry lists the following serious adverse-event terms with their recorded percentages: neutrophil count decreased, 3.8%; leukocyte count decreased, 2.0%; febrile neutropenia, 1.0%; infection with grade 3 or 4 neutropenia, 1.0%; and platelet count decreased, 1.0%. The entries identify events, but the record does not provide enough detail to interpret duration, recurrence, timing relative to treatment, or attribution to the assigned intervention. Death counts are not reported in the registry record.
These safety figures should be read as descriptive registry entries rather than as a complete causal comparison. A numerical difference in counts alone does not establish whether treatment caused an event or whether groups differed beyond chance. The record does not report a formal safety analysis or confidence intervals for these figures.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a randomized, double-masked, parallel-group phase 3 trial comparing Ginkgo Biloba with placebo in women receiving chemotherapy for newly diagnosed breast cancer. It also identifies the HSCS overall score, summarized as an AUC from baseline to the 12 month data point, as the primary cognitive-function measure. Lower scores are better, and the stated efficacy population required a baseline report and one value after baseline.
Those design and measurement details clarify what the study was intended to assess. They do not reveal the outcome. The registry information available for this analysis does not report the primary group summaries, a treatment-effect estimate, a confidence interval, or a p-value. It is therefore not possible to determine the direction, magnitude, or precision of the primary comparison from the registry record. The absence of those results should not be converted into a claim of benefit, lack of benefit, or equivalence.
The listed secondary outcomes and safety entries add context about what the registry tracked, but listing an outcome is not the same as reporting its comparative result. The serious and other adverse-event counts are descriptive and cannot by themselves establish causation or a statistically reliable difference. Nor can the HSCS endpoint alone represent every dimension of cognition or every aspect of participants' experience during chemotherapy.
In general, interpreting a trial requires considering the estimated effect, its uncertainty, the analysis population, missing data, and the relevance of the measure to the question. Here, key efficacy statistics and several analysis details are not reported in the registry record. The defensible conclusion is limited to the trial design, endpoint definition, and posted safety counts. No treatment recommendation or conclusion about clinical effectiveness follows from those details.
13. Why This Trial Matters Statistically
This trial is statistically notable for connecting a clinical question about cognitive function during chemotherapy to a repeated-measure summary rather than a single endpoint observation. The HSCS overall score combines domains that include memory, language, visual-motor function, spatial function, attention and concentration, and self-regulation and planning. The AUC description indicates that the primary measure was intended to represent scores over time, from baseline to the 12 month data point.
That choice illustrates a broader design issue: a summary across time answers a different question from a comparison at a single follow-up visit. AUC can combine the level and duration of scores over the defined interval, while an endpoint-only comparison focuses on a particular assessment. In general, the summary must be interpreted in light of the measurement schedule, score direction, and handling of missing observations. The registry offers the general endpoint definition but does not provide enough calculation or analysis detail to evaluate those choices fully.
The randomized, double-masked design also highlights how study conduct can support a fair comparison, while leaving important questions about analysis and reporting. Randomization and masking do not eliminate the need to understand who contributed data, how missing outcomes were treated, and how multiple outcomes were handled. The registry identifies an efficacy population requiring baseline and postbaseline information, but does not report its size or the missing-data methods.
Finally, the record illustrates a limit of registry-based interpretation: methodological details and outcome definitions do not substitute for comparative estimates and uncertainty. Without the primary results, the statistical question remains unresolved in the available record. This distinction is important for clinical researchers reading trial registrations and posted results: what was measured, how a trial was designed, and what the observed comparison showed are separate kinds of evidence.
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 central limitation for interpreting this trial is that the primary comparative result is not reported in the registry record available for this analysis. There are no group means or standard deviations for the HSCS AUC, no treatment contrast, and no confidence interval or p-value. Consequently, neither the direction nor the precision of the primary finding can be assessed. The record's description of lower scores as better does not fill this gap.
The primary outcome is described as an AUC using data points from baseline to the 12 month data point, but the detailed calculation procedure is not reported. The timing and completeness of assessments, treatment of measurements between observed time points, and analysis model are not specified. These omissions limit the ability to reproduce the endpoint or judge how well its construction reflects the intended cognitive-function question.
The stated efficacy population includes patients with baseline and one postbaseline value, but the number meeting that definition and participant flow by treatment group are not reported. Missing-data reasons and methods, including any sensitivity analyses, are also not reported in the registry record. This matters because outcome availability can influence a comparison if it is related to treatment or participant status.
The record lists secondary outcomes but does not report their results or a multiplicity strategy. It does not provide detailed eligibility criteria, site information, adherence, treatment discontinuation, allocation concealment, masking procedures, or the statistical analysis plan. Safety entries lack detailed timing, event-level follow-up, and a reported formal comparison. These limitations constrain interpretation without establishing that any particular bias or problem occurred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: EGb761 in Maintaining Mental Clarity in Women Receiving Chemotherapy for Newly Diagnosed Breast Cancer — NCT00046891.
- Registry record last updated 2016-07-06; status last verified 2016-07.
- Results first posted 2015-04-15.
- 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
The registry record describes NCT00046891, a completed, randomized, double-masked, parallel phase 3 trial sponsored by the Alliance for Clinical Trials in Oncology. Enrollment was 226. The trial began in 2002-12 and primary completion was recorded in 2006-10. It compared Ginkgo Biloba, described as 120 mg per day (60 mg BID), with placebo, described as 1 tablet BID, in women receiving chemotherapy for newly diagnosed breast cancer.
The primary endpoint was the HSCS overall score summarized as an AUC from baseline to the 12 month data point. Lower scores are better. The registry record does not report the primary comparative results, so the treatment contrast and its precision cannot be evaluated from the information available for this analysis. Safety counts and selected serious adverse-event terms are recorded, but a formal safety comparison is not reported.