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 Flavanol Augmentation for Antidepressant Non-Responsive Late Life Depression (NCT02943096), a randomized na study. The primary outcome is Hamilton Rating Scale of Depression (HRSD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02943096 |
| Phase | NA |
| Condition | Depression, Major Depressive Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 6 |
| Arms in the primary outcome | 2 |
| Lead sponsor | New York State Psychiatric Institute |
| Results posted | Yes |
2. Clinical Question
Population
The study focused on older adults with Major Depressive Disorder whose depressive symptoms remained above a specified threshold despite an adequate antidepressant trial. The proposed population also had significant cognitive complaints without a dementia diagnosis. The summary describes a plan to recruit adults aged 60 years or older; the registry record reports enrollment of 6.
Intervention
The intervention of interest was cocoa-derived flavanol supplementation alongside continued antidepressant medication. The brief summary describes an 8-week augmentation period. The intervention list names CocoaVia, and the arm description refers to blinded treatment with either CocoaVia 500mg or placebo.
Comparator
The comparison was placebo capsules alongside continued antidepressant medication. The arm descriptions use the same wording for the Flavanol and Placebo groups, stating that blinded treatment could be either CocoaVia 500mg or placebo. The record does not provide further detail about capsule assignment or adherence.
Primary question
The primary outcome was depressive symptom severity on the Hamilton Rating Scale of Depression at Week 8. The study’s central question was whether adding flavanols to ongoing antidepressant treatment would be associated with a different Week 8 mean HRSD score than adding placebo. The registry reports arm-level means and standard deviations, but no inferential comparison.
3. Trial Design
The registry identifies this as a randomized, parallel-group trial with quadruple masking. Its stated purpose was to pilot whether flavanol supplements could augment cognitive and mood benefits of antidepressant medication in older adults with late-life depression. The brief summary describes an intended 8-week treatment period, with participants continuing their antidepressant while receiving flavanol capsules or capsules without flavanols.
The listed arms are Flavanol and Placebo. Their descriptions are identical: blinded treatment with either CocoaVia 500mg or placebo. The intervention list also names CocoaVia and Placebo. The record therefore identifies the intended comparison, but does not resolve the repeated, nonspecific arm wording with additional allocation details.
The summary describes a proposed recruitment target of 50 adults aged 60 years or older with Major Depressive Disorder, persistent depressive symptoms despite an adequate antidepressant trial, and significant cognitive complaints without a dementia diagnosis. The registry reports enrollment of 6, and the trial status is TERMINATED. The recorded start is 2016-11, and primary completion is 2018-02-06. These registry entries describe the trial record; they do not establish why recruitment ended or whether all planned assessments were completed.
The brief summary mentions pre- and post-treatment brain MRI and comprehensive assessments, but the available text ends before fully describing those procedures. Further protocol details, including the reason for termination and the planned statistical analysis, are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Every subject evaluated for this protocol will receive a clinical interview by a psychiatrist or psychologist, be administered the 24-item Hamilton Rating Scale for Depression (HRSD) and Antidepressant Treatment History Form, and have a SCID performed by a trained rater. They will be educated about appropriate treatments available for depression.
Overall Study
| Stage | Flavanol | Placebo |
|---|---|---|
| STARTED | 3 | 3 |
| COMPLETED | 3 | 2 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Flavanol | Placebo |
|---|---|---|
| Lack of Efficacy | 0 | 1 |
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 | Flavanol | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 3 | 6 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 0 | 1 |
| Age, Categorical: >=65 years | Participants | 2 | 3 | 5 |
| Age, Continuous | years | 71.8 (SD 5.72) | 75.2 (SD 8.93) | 73.5 (SD 6.95) |
| Sex: Female, Male: Female | Participants | 2 | 0 | 2 |
| Sex: Female, Male: Male | Participants | 1 | 3 | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 3 | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 2 | 3 | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 3 | 3 | 6 |
| Hamilton Rating Scale for Depression | units on a scale | 20 (SD 1.73) | 17 (SD 8.72) | 18.5 (SD 5.86) |
6. Primary Endpoint
The registry lists the primary outcome as Hamilton Rating Scale of Depression (HRSD), measured over Week 8.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the Hamilton Rating Scale of Depression (HRSD) score at Week 8. The record describes it as a clinician-administered scale for depressive symptoms, assessed by a trained rater. It states that higher scores indicate a worse outcome and gives a possible score range from 0 to 74.
The registry says the HRSD was selected because it is a standard measure of depression severity in antidepressant clinical trials. It also explains that the choice was intended to support compatibility with the investigators’ meta-analyses and ongoing studies of expectancy. These are the rationale stated in the record, not evidence that the measure captures every aspect of depression or cognitive functioning.
The endpoint is reported as a mean, with standard deviation as the measure of spread. The posted results give a Week 8 mean HRSD score of 18.3 with standard deviation 6.43 in the Flavanol arm, and a mean of 20.3 with standard deviation 2.08 in the Placebo arm. These are descriptive arm-level results. The registry does not report a confidence interval or a statistical test comparing the arms.
The outcome description says the HRSD list contains 21 items, while also saying scoring is based on the first 24 items. Those statements are inconsistent in the registry description, and the record does not clarify the discrepancy.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome is a continuous measure, reported as a mean and standard deviation for each arm at Week 8. The Flavanol arm has a mean HRSD score of 18.3 and standard deviation 6.43; the Placebo arm has a mean of 20.3 and standard deviation 2.08. Because the registry defines higher HRSD scores as worse, the arm means can be read in that direction. They remain descriptive summaries, not a demonstrated treatment effect.
The posted arm sizes are 3.0 for Flavanol and 3.0 for Placebo. With such limited reported group information, the means and standard deviations cannot by themselves establish how precisely the difference between treatment strategies is estimated. The registry record gives no confidence interval, p-value, adjusted estimate, or other inferential result for the primary endpoint. It also reports zero analyses. The record therefore does not establish whether the observed arm-level pattern is compatible with a meaningful difference, no difference, or a range of possibilities.
The result should be read in the context of the registry’s stated enrollment of 6 and TERMINATED status, alongside a summary that describes a plan to recruit 50 adults. The record does not state why the study terminated, whether the planned recruitment target changed, or whether the posted outcome represents every participant enrolled. Those details are not reported in the registry record, so the results should not be interpreted as if they came from a completed, adequately sized confirmatory trial.
These scores also do not answer the full set of questions in the study summary. The stated aims included cognitive outcomes, and the summary mentions MRI and pre- and post-treatment assessments. Secondary outcome names are listed, but results for them are not present in the registry record reported for this analysis. No conclusion about cognitive outcomes or brain imaging follows from the HRSD means.
Overall, the posted data describe Week 8 HRSD scores in the two arms. They do not provide a formal comparison, quantify its uncertainty, or support a causal conclusion about flavanol augmentation. Interpreting the numerical separation between arm means as proof of benefit or lack of benefit would go beyond the registry results.
9. Statistical Methods Explained
The registry identifies the study as randomized, quadruple masked, and parallel. Randomization is a method for assigning participants to study arms by chance; in general, its purpose is to reduce systematic differences between groups at the time of assignment. Masking is intended to limit the influence of knowing the assigned treatment on care, assessment, or interpretation. The record does not describe which specific roles were masked or how masking was maintained, so those operational details are not reported in the registry record.
What do the reported means and standard deviations convey?
The primary endpoint is continuous, and the registry reports a mean HRSD score and standard deviation for each arm. In general, a mean describes the center of observed scores, while a standard deviation describes how dispersed those scores are around the mean. They answer different questions: the mean characterizes the group’s average score, and the standard deviation characterizes variation among scores. Neither measure alone gives the uncertainty in an estimated between-arm effect.
The reported Flavanol mean is 18.3 with standard deviation 6.43; the Placebo mean is 20.3 with standard deviation 2.08. These values are arm summaries at Week 8, not adjusted estimates. The registry does not report baseline HRSD scores or an analysis of change from baseline. It is therefore not possible to tell from these summaries whether the posted comparison accounts for baseline values or other participant characteristics.
Why is a confidence interval useful?
In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the statistical method used. For a treatment comparison, it can show which effect sizes are reasonably compatible with the observed data and model. A point estimate alone gives no such range. The registry record does not report a confidence interval for the primary comparison, so its precision cannot be assessed from an interval estimate.
A p-value, in general, measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It does not measure the probability that a treatment works, nor does it show the size or clinical importance of an effect. No primary-outcome p-value is reported in the registry record. The absence of a reported test means the arm means should not be described as statistically significant or nonsignificant.
What does over-dispersion mean for a continuous outcome?
In general, over-dispersion refers to more variability in the data than a model expects. For a continuous outcome, unusually broad variation can make standard errors based on a restrictive model unreliable. Here the registry reports standard deviations, but the small arm sizes and absence of participant-level data do not allow a robust assessment of the distribution of scores or whether a particular model’s assumptions were appropriate. No modeling approach or variance adjustment is reported in the registry record.
What is stated about sample-size planning?
The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is specified as a proportion of the observed effect. The record also distinguishes participant counts per arm for ordinary outcomes from total event counts for time-to-event outcomes. The numerical planning results are not reported in the registry record. Such calculations are planning illustrations, not observed power and not evidence that the study was adequately sized.
The registry’s enrollment of 6 is not the same as a sample-size justification. The rationale for the intended recruitment target, the assumptions used in the original design, and any planned interim analyses are not reported in the registry record. It would be inappropriate to infer these from the posted means or from the planning description.
What does the absence of a recalculated comparison mean?
The record does not report a recalculated unadjusted comparison for the continuous endpoint. It also does not give an adjusted treatment estimate. The posted group means and standard deviations are not enough to establish which analysis was prespecified or to reconstruct a sponsor analysis that is absent from the record. There is no reported discrepancy between a sponsor analysis and a recalculation, but there is also no comparative analysis to interpret. The arm-level descriptive results are the extent of the primary outcome evidence reported in the registry record for this analysis.
10. Confidence Intervals for Each Arm
No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| Flavanol | 3 | 18.300 | 6.430 | 2.327 to 34.273 |
| Placebo | 3 | 20.300 | 2.080 | 15.133 to 25.467 |
R code and output
arm <- c("Flavanol", "Placebo")
n <- c(3, 3)
m <- c(18.3, 20.3)
sp <- c(6.43, 2.08)
sd <- sp # posted standard deviations
for (i in seq_along(n)) {
se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}
CARM Flavanol 3 18.300 6.430 2.327 34.273
CARM Placebo 3 20.300 2.080 15.133 25.46711. Multiplicity, Missing Data and Analysis Populations
The registry lists four secondary outcome entries: Mnemonic Similarity Task (MST) and Modified-Benton Task (ModBent), each appearing twice. It reports five outcome measures overall and zero analyses. The record does not explain why the secondary outcome names are repeated, which results correspond to distinct time points or measures, or whether any secondary results were analyzed.
When a study assesses multiple outcomes or performs multiple tests, the chance of at least one apparently notable result can increase. In general, statistical plans may address this issue by defining a primary outcome, specifying a testing order, or adjusting inference across tests. The registry record does not report a multiplicity strategy, a hierarchy for secondary outcomes, or any secondary-outcome estimates. No multiplicity-adjusted interpretation can therefore be made.
Missing-data handling is also not reported in the registry record. The record does not explain whether participants with incomplete Week 8 assessments were included, how missing scores were handled, or whether any imputation method was used. Analysis populations, such as an intention-to-treat or per-protocol population, are not reported either. The posted arm sizes and outcome summaries do not resolve those questions.
These gaps matter because the enrollment was 6 and the trial status is TERMINATED, while the brief summary describes a planned recruitment of 50 adults. The registry does not say whether all enrolled participants contributed the endpoint data, why recruitment ended, or whether the intended analysis changed. The HRSD summaries should thus be read without assuming a particular missing-data strategy, analysis population, or correction for multiple comparisons.
12. 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 |
|---|---|---|---|
| Flavanol | 0 | 3 | 0.0% |
| Placebo | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Flavanol | 0 of 3 |
| Placebo | 0 of 3 |
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 |
|---|---|
| Flavanol | 0 of 3 |
| Placebo | 0 of 3 |
The adverse-event record reports serious adverse events in 0 participants in the Flavanol arm and 0 in the Placebo arm. The number at risk for this measure is 3 in each arm. The record also reports 0 participants with other adverse events in each arm, with 3 at risk in each arm, and 0 deaths in either arm. No top serious-event terms are listed.
These figures describe what is recorded for the groups and event categories. A recorded count of zero means that no event of that category is reported for the stated group in this registry entry; it does not establish that the intervention has no safety risks. With limited enrollment, absence of a recorded event provides little information about uncommon harms. The registry does not report further details about how adverse events were collected, their duration of observation, or whether event ascertainment differed between groups.
The serious-event figures should therefore be read as limited descriptive safety information, not as a comparison capable of ruling out risk. The record does not provide a formal statistical comparison of adverse events.
13. What the Result Does, and Does Not, Mean
The posted results show Week 8 HRSD means of 18.3 in the Flavanol arm and 20.3 in the Placebo arm, with standard deviations of 6.43 and 2.08, respectively. The registry defines higher HRSD scores as worse. These summaries describe the participants whose results are represented in the record, but do not quantify an adjusted or inferential treatment contrast.
The results do not establish that flavanol supplementation improves depressive symptoms, nor do they establish that it has no effect. No confidence interval, p-value, or comparative analysis is reported. The available summaries do not show how uncertain a difference between arms may be, and do not address whether any score difference is clinically important.
The study summary presents a broader research question involving cognitive outcomes and brain imaging. The primary HRSD summaries cannot answer those questions. Although the registry lists secondary outcome names and mentions MRI assessments in the summary, results for those measures are not reported in the registry record for this analysis. Claims about cognition or imaging would therefore exceed the recorded results.
Nor should the results be treated as a completed confirmatory test of the treatment strategy. The registry reports enrollment of 6, a TERMINATED status, and a planned recruitment target of 50 in the study summary. The reason for termination and the relationship between the planned assessments and the posted outcome are not reported in the registry record. The trial’s small reported group sizes and missing inferential details limit what can be learned from its arm summaries.
The most defensible reading is narrow: the registry records descriptive Week 8 HRSD scores and adverse-event counts for the Flavanol and Placebo arms. It does not report enough comparative analysis to support a conclusion about the effectiveness, lack of effectiveness, or overall safety of flavanol augmentation.
14. Why This Trial Matters Statistically
This trial illustrates the difference between an outcome summary and an estimate of a treatment effect. Group means and standard deviations describe observed scores, but they do not supply a comparative estimate with uncertainty. Without a reported confidence interval or statistical test, readers cannot assess the precision of the apparent separation in HRSD means from the registry results alone.
It also highlights why enrollment and study status belong in the statistical interpretation. The record reports enrollment of 6 and TERMINATED status, while its summary describes an intended recruitment target of 50. This context cautions against treating the posted summaries as though they came from a large, completed confirmatory comparison. The record does not explain the termination or provide a sample-size justification.
The registry names several cognitive outcomes in addition to the primary depression scale, and its summary mentions MRI and pre- and post-treatment assessments. Yet no analyses are posted. This distinction matters: listing a measure or a planned assessment does not show its result, establish that it was collected, or demonstrate that it was analyzed. Nor does the number of listed outcomes reveal how multiplicity was handled.
From a biostatistical perspective, the record is useful as an example of how to separate descriptive reporting, inferential evidence, and planning assumptions. The planning description is not observed power, and the arm-level summaries are not a substitute for a transparent analysis plan and treatment estimate. Readers can identify what was recorded while recognizing that the central comparative question remains unresolved by the posted statistics.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record has substantial gaps for interpreting the primary outcome. It reports arm-level Week 8 means and standard deviations but no comparison estimate, confidence interval, p-value, or analysis method. Baseline HRSD values and change-from-baseline results are not reported. The analysis population, handling of missing outcome data, and any adjustment for covariates are also not reported in the registry record.
The reported enrollment of 6 is limited in relation to the planned recruitment of 50 described in the summary. The trial is marked TERMINATED, but the reason for termination and the extent to which planned assessments were completed are not reported. The record does not explain whether the posted endpoint includes all enrolled participants.
The intervention descriptions leave uncertainty about implementation. Both arm descriptions say participants received blinded treatment with either CocoaVia 500mg or placebo, without clarifying the assignment within each arm. The record does not report adherence or additional details about treatment delivery. The outcome description also contains an internal inconsistency: it says the HRSD list contains 21 items but that scoring is based on the first 24 items. No clarification is reported.
Finally, the registry lists secondary outcomes but reports zero analyses, and it does not state a multiplicity approach. These limitations do not show that a particular analysis or procedure was absent; they mean the relevant details are not reported in the registry record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Flavanol Augmentation for Antidepressant Non-Responsive Late Life Depression — NCT02943096.
- Registry record last updated 2019-09-06; status last verified 2019-09.
- Results first posted 2019-09-06.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry record describes a randomized, quadruple-masked, parallel study of flavanol supplementation as an addition to antidepressant medication for older adults with late-life depression. The primary outcome is the Week 8 Hamilton Rating Scale of Depression score. The study summary describes an 8-week intervention and a planned recruitment target of 50; the record reports enrollment of 6 and status TERMINATED.
Posted HRSD results are a mean of 18.3 with standard deviation 6.43 for Flavanol, and a mean of 20.3 with standard deviation 2.08 for Placebo. No comparative statistical analysis is reported. The adverse-event record lists 0 serious events and 0 other events in each arm, and 0 deaths in either arm.
The registry lists secondary outcomes but reports zero analyses. Details on the reason for termination, missing-data handling, analysis populations, and the statistical plan are not reported in the registry record. The results are descriptive and do not settle the treatment comparison.