COGNUTRIN in Breast Cancer Survivors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for COGNUTRIN in Breast Cancer Survivors (NCT01823991), a randomized early/phase 1 study. The primary outcome is Change in Cognitive Function Scores With Intervention - HVLT and COWA.

2. Clinical Question

The clinical question concerns a nutritional-supplement combination and cognitive test performance in breast cancer survivors after chemotherapy. It is not a single-score question: the registry describes two tests and group scores at two time points. The primary outcome title refers to change in scores, while the description also says scores were reported by group and compared by testing time. The registry record does not identify one summary contrast or provide numerical estimates that would resolve how those elements were combined.

The record describes the study as an early-phase pilot clinical trial. Its stated purpose includes examining safety and influence on cognitive performance. The listed secondary outcomes concern adverse events, adverse-event causality, grade 3 or higher adverse events, and MRI changes. These outcomes describe additional questions, but no numerical results for them are reported as outcome analyses in the registry record. The question can therefore be described from the trial record, but the degree or direction of any cognitive change cannot be determined from the posted information.

3. Trial Design

The registry record describes a randomized, triple-masked, parallel-group early-phase 1 trial. The study is marked completed. It lists 36 participants enrolled and gives the condition as breast cancer. The record identifies H. Lee Moffitt Cancer Center and Research Institute as sponsor. The recorded start date is 2014-07-30, and primary completion is recorded as 2017-04-05.

The intervention arm combined VitaBlue and n-3 fatty acids. The arm description specifies one tablet of Lovaza twice a day and one tablet of VitaBlue three times a day. Participants in the placebo arm received two placebo products, with one taken twice a day and the other three times a day. The intervention list names VitaBlue™, Placebo, and Lovaza®. The arm titles use the wording “twice a day,” while the detailed intervention description distinguishes the schedules of the two components.

Randomized means that assignment to study groups was intended to use a random process. Triple masking indicates that the record classifies the trial as masked at three levels, but the identities of the masked groups or individuals are not reported in the registry record. A parallel design means participants were assigned to a group and assessed within that group, rather than crossing from one treatment condition to another. These are general descriptions of the design labels; the detailed procedures are not reported in the registry record.

The safety entries list 18 participants at risk in each arm. Those safety denominators describe the groups in the adverse-event record and do not establish the number included in each cognitive-outcome analysis. The primary-outcome population is described only as all evaluable participants at the time of analysis. The number evaluable, the allocation ratio, and the number completing each assessment are not reported in the registry record. The trial's own sample-size justification and detailed statistical analysis plan are also not reported.

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: Participants were randomized to receive Cognutrin (n-3 fatty acids + anthocyanins) or placebo for a period of 3 months.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All evaluable participants at time of 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.

Population: All Participants.

6. Primary Endpoint

The registry lists the primary outcome as Change in Cognitive Function Scores With Intervention - HVLT and COWA, measured over Baseline (Time 1) and at 3 months +/- 7 days (Time 2).

The primary outcome is change in cognitive-function scores from baseline to post-intervention, with the later assessment scheduled at 3 months +/- 7 days. The record names the HVLT and COWA. The HVLT assesses verbal learning and memory: participants hear a list of words and are asked to recall as many as possible across repeated attempts. The COWA is a verbal-fluency test that counts spontaneous word production within a category or beginning with a designated letter.

The registry describes HVLT results as age-adjusted T-scores, with an average score of 50 and a standard deviation of 10. Scores under 50 indicate performance under population averages, while scores over 50 indicate performance over those averages. COWA results are converted to z-scores; the record says a z-score of -1 is one standard deviation under the mean, and that lower z-scores indicate poorer fluency. It also gives possible extremes as <= -3.0 and >=3.0.

Using both measures addresses different aspects of cognition named in the record: verbal learning and memory, and verbal fluency. Comparing baseline with the later assessment is intended to describe change over the intervention period, while comparing groups can describe whether their score patterns differed. These are general reasons to measure domains separately and compare change over time; they do not establish that the tests capture every aspect of cognition.

The registry record does not report group means, mean changes, standard errors, confidence intervals, or test results for either measure. It also does not report a single combined endpoint or clarify how the multiple tests and time points were reduced to one primary comparison. Thus, the endpoint's intended content and timing are described, but its observed magnitude and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure reported as a mean, with standard error named as the dispersion measure. A mean describes the center of a set of scores. For a clinical trial, group means can be presented at each assessment, and mean change can describe how scores differ between baseline and follow-up. The registry record describes these quantities conceptually but does not report their values for HVLT or COWA.

A standard error describes the statistical precision of an estimated mean, not the spread of individual participants' scores. General distinction: standard deviation describes variability among observations, whereas standard error describes uncertainty in an estimate such as a sample mean. Smaller standard errors usually indicate more precise estimates, though precision also depends on the design and the observations available. The record names standard error but gives no numerical standard errors, so precision cannot be assessed for the cognitive outcomes.

A confidence interval is a range constructed by a statistical method to express uncertainty around an estimate. General interpretation: a wider interval indicates less precision, and an interval can help readers assess which effect sizes remain compatible with the data under the method's assumptions. No confidence intervals for the primary outcome are reported in the registry record. A confidence interval cannot be reconstructed without outcome estimates and their uncertainty information.

The outcome description has two distinct cognitive tests and two assessment times. One general approach in a repeated-measure setting is to compare changes between groups; another is to model scores across time and estimate a group-by-time pattern. The registry record does not identify a model or state which contrast was prespecified. These examples describe general analysis possibilities, not the analysis used in this trial. The record's note that the primary outcome has several categories or time points and was not reduced to one comparison reinforces that a single result should not be inferred from the outcome title alone.

Multiple outcomes and comparisons raise a general multiplicity issue. If many tests are examined, the chance of at least one apparently notable result can increase when each is interpreted separately. Possible responses in statistical practice include prespecifying a primary contrast, controlling error across a family of tests, or interpreting secondary findings as exploratory. The registry record does not report a multiplicity adjustment, a hierarchy among the cognitive measures, or an analysis plan that would clarify how the multiple measures were handled. No adjustment should be assumed.

Randomization is intended to make treatment-group assignment independent of participants' measured and unmeasured characteristics on average, though chance imbalances can still occur. Masking can reduce the influence of expectations on care, assessment, or reporting, depending on who is masked and how masking is maintained. These are general purposes of randomization and masking. The record labels this study randomized and triple-masked but does not report the randomization sequence, concealment procedures, identities of masked parties, or checks of masking.

The parallel-group label indicates that the intervention and comparator groups are followed as separate groups. A between-group comparison is generally important because change within one group alone does not distinguish intervention effects from time-related changes or other influences. This is a general statistical point, not a claim about the trial's findings. The record describes comparison with placebo but does not post the group-specific cognitive results or a numerical between-group estimate.

The sample-size assumptions described for planning illustrations are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of an observed effect. These are assumptions for a planning illustration, not evidence of the trial's original design rationale. A sample-size illustration based on an observed effect is not observed power and does not establish the probability that the trial detected a true effect. The trial's own sample-size justification is not reported in the registry record, and no numerical cognitive effect is available in the record to interpret as an observed effect.

Over-dispersion is a general concern when outcome variability is greater than a statistical model assumes. It can make standard errors too small if the model does not account for the extra variability. The registry record does not report a model, a dispersion assessment, or any indication that over-dispersion was relevant to the cognitive scores. It should not be asserted as a feature of this trial.

Recalculation from posted summaries can sometimes check a simple unadjusted contrast, but it cannot reproduce an adjusted model or account for participant-level data that are not reported. Here, cognitive summaries are absent, so no unadjusted recalculation can be made. The registry record lists no analyses. It also does not report an analysis method, adjustment variables, interim analyses, or a statistical analysis plan. These missing details limit the ability to assess how the investigators intended to estimate uncertainty and address the multiple outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome covers two cognitive measures, HVLT and COWA, assessed at baseline and at 3 months +/- 7 days. Its description refers to mean change and to group scores compared by testing time. The registry record notes that the primary outcome has several categories or time points and was not reduced to one comparison. It does not identify one primary contrast, a testing hierarchy, or a multiplicity adjustment. These omissions matter because results from several measures or comparisons cannot be interpreted as though only one test had been conducted unless the analysis plan supports that interpretation.

Nine outcome measures are listed in total. The secondary outcomes include adverse events, adverse-event causality, grade 3 or higher adverse events, and MRI changes. The record does not report a full statistical analysis plan, adjustment approach, or outcome-by-outcome analysis results. It is therefore not possible to tell which outcomes were considered confirmatory and which, if any, were exploratory.

The primary-outcome population is described as all evaluable participants at analysis. The number evaluable for each measure and time point is not reported in the registry record. The record does not describe missing-data reasons, the number lacking follow-up scores, imputation, or sensitivity analyses. General concern: when participants lack follow-up measurements, estimates can be affected if missingness is related to observed or unobserved outcomes. Without the extent and handling of missing data, the direction or size of any such influence cannot be assessed.

Interim analyses are not reported in the registry record. The analysis populations beyond the description of all evaluable participants are also not reported. The available record therefore does not establish whether the results, if any, were analyzed by randomized assignment, by treatment received, or under another population definition.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: psychosis (5.6%).

The adverse-event record lists 18 participants at risk in each group. It records 1 participant with a serious adverse event in the COGNUTRIN group and 0 in the matching-placebo group. The record lists Psychosis as a top serious term, with 5.6%. It also records 10 participants with other adverse events in the COGNUTRIN group and 4 in the placebo group. Deaths are listed as 0 in both groups.

These are descriptive counts in the registry record. They do not, on their own, establish whether an event was caused by the intervention, whether the groups differed statistically, or how event timing and severity were distributed beyond the listed categories. Although occurrence of adverse events by causality is named as a secondary outcome, a causality breakdown is not reported in the registry record. The detailed event narratives, exposure-adjusted comparisons, and statistical analysis of safety are also not reported.

The listed term and percentage should be read in the context of the small safety denominators and the registry's event coding. The record does not explain the basis or denominator for the 5.6% term entry. A single serious-event count cannot be generalized into a stable estimate of uncommon risks. The counts also do not address the primary cognitive outcome.

General interpretation: safety counts can identify events recorded during a trial, but a comparison requires attention to the number exposed, follow-up, event definitions, and uncertainty. The posted record gives group denominators and selected counts but not enough detail for a broader safety estimate or causal conclusion.

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

The record establishes that a randomized, triple-masked, parallel-group early-phase 1 pilot trial was conducted to examine COGNUTRIN in breast cancer survivors following chemotherapy. It describes a combination of VitaBlue and n-3 fatty acids, a placebo comparator, and cognitive testing at baseline and at 3 months +/- 7 days. It also describes safety and MRI outcomes as additional study interests.

That information does not establish the size or direction of a cognitive effect. No group means, mean changes, standard errors, confidence intervals, or p-values for HVLT or COWA are reported in the registry record. It is therefore not possible to state that cognitive scores increased, decreased, or differed between groups. Nor is it possible to judge whether any difference was precise, clinically important, or compatible with a range of possible effects.

The record's T-score and z-score descriptions explain how the cognitive measures are scaled and interpreted in general. They do not provide actual participant scores. The stated population average for HVLT and the definitions of COWA z-scores are measurement context, not trial findings. The registry record also does not report a single combined cognitive score or a single comparison that resolves the multiple measures and time points.

The safety entries provide limited descriptive counts: serious events are recorded for 1 participant in the COGNUTRIN group and none in placebo, other adverse events for 10 and 4 participants respectively, and no deaths in either group. These entries do not establish causality or quantify all safety risks. The record does not report the requested causality breakdown or numerical MRI results.

General statistical interpretation distinguishes absence of a posted result from evidence of no effect. With no numerical cognitive results, neither an effect nor a lack of effect can be inferred. The registry record can support a description of the trial's intended question and some safety counts, but it cannot support a quantitative conclusion about cognitive outcomes or their uncertainty.

13. Why This Trial Matters Statistically

This trial matters statistically because its primary question involves several related measurements rather than one uncomplicated outcome. HVLT and COWA assess different named cognitive domains, and the registry describes scores at baseline and follow-up. A clear distinction among individual measures, time points, and the primary contrast is important for understanding what an estimate represents and how many comparisons informed interpretation.

The record illustrates why an endpoint description is not the same as a result. Knowing the tests, their scales, the intended assessment time, and the planned comparison helps define the scientific question. It does not reveal observed changes or uncertainty. Without the numerical estimates and their precision, readers cannot assess the data's compatibility with different effect sizes or determine whether apparent patterns might reflect sampling variation.

The trial is identified as a pilot and early-phase 1 study, and its enrollment is 36. General statistical context: pilot studies can be useful for studying feasibility and informing later research, but their scale alone does not determine the reliability of an effect estimate. Interpretation depends on the outcomes, analysis, and uncertainty. The registry record does not report a sample-size justification or numerical cognitive results, so it cannot show whether the study was designed to estimate a particular effect with a target precision.

The safety record also demonstrates the limits of small descriptive counts. Counts can document events, but they cannot independently establish causality or provide a precise estimate of uncommon outcomes. A complete reading requires event definitions, follow-up information, and the planned safety analyses, which are not reported in the registry record.

Finally, the record's multiple measures make transparent reporting of analysis choices especially important. A prespecified contrast, missing-data approach, and multiplicity strategy would help readers distinguish the principal question from additional comparisons. Those details are not reported, and no analyses are listed. The statistical significance of the trial's question therefore lies in both the measurement design and the limits of what can be inferred from the registry entry.

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 principal limitation for interpretation is that numerical results for the primary cognitive outcome are not reported in the registry record. The record names HVLT and COWA and describes the timing and scales, but it gives no group means, change estimates, standard errors, confidence intervals, or p-values. The cognitive effect and its precision cannot be evaluated.

The primary-outcome description refers to multiple measures and time points without identifying a single numerical comparison. The record says the outcome was not reduced to one comparison, and it does not report how multiplicity was handled. This prevents a clear reading of which cognitive estimate would answer the primary question.

Although the study enrolled 36 participants, the number evaluable for each cognitive measure and assessment time is not reported. The record does not describe missing measurements, reasons for loss of follow-up, or methods for handling missing data. The safety denominators of 18 participants per group should not be taken as the cognitive analysis denominators.

The record labels the study randomized and triple-masked but does not report the randomization procedure, allocation concealment, the identities of masked parties, or whether masking was assessed. The trial's own sample-size justification, statistical analysis plan, analysis populations, adjustment variables, and interim analyses are not reported. No numerical MRI results or adverse-event causality breakdown are reported either.

These limitations concern the information available in the registry record. They do not show that a procedure was absent from trial conduct; they mean that the relevant details are not reported in the registry record. As a result, the design can be described more confidently than the outcome estimates or their statistical interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: COGNUTRIN in Breast Cancer Survivors — NCT01823991.
• Registry record last updated 2020-07-14; status last verified 2020-06.
• Results first posted 2019-08-29.
• 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

The registry record describes a completed, randomized, triple-masked, parallel-group early-phase 1 pilot trial with 36 participants enrolled. The population was breast cancer survivors following chemotherapy. COGNUTRIN combined VitaBlue and n-3 fatty acids and was compared with placebo. The primary outcome was change in HVLT and COWA cognitive-function scores from baseline to 3 months +/- 7 days.

The primary-outcome description gives test characteristics and score scales, but numerical cognitive results are not reported in the registry record. The number evaluable for those outcomes, missing-data methods, multiplicity handling, analysis plan, and sample-size justification are also not reported. The safety entries list 18 participants at risk in each group, with 1 serious adverse event in the COGNUTRIN group and 0 in placebo; other adverse events are listed for 10 and 4 participants, respectively, and deaths for 0 in both groups. The record does not provide a causality breakdown or numerical MRI results.