Omega-3 Fatty Acids as Adjunct Treatment for Major Depressive Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Omega-3 Fatty Acids as Adjunct Treatment for Major Depressive Disorder (NCT00511810), a randomized phase 2, phase 3 study. The primary outcome is Mood Symptoms Ratings.

2. Clinical Question

The clinical question therefore combines a mechanistic objective—changes in cortical activity and biochemical measures—with a symptom-rating outcome. The record describes a population selected for ongoing symptoms despite SSRI medication, and the fish oil is characterized as adjunctive rather than as a replacement treatment. Its design can address contrasts between the two assigned dose groups, but a randomized two-arm dose comparison alone does not establish what would have happened without fish oil.

For the symptom outcome, the available values do not answer whether either group changed during the treatment period, whether the groups differed at 10 weeks, or whether symptom changes were associated with the proposed cortical measures. Those treatment-period results are not reported in the registry record. The baseline scores describe participants before the endpoint time frame, and should not be read as evidence for or against the study's prediction.

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. It lists both Phase 2 and Phase 3, an enrollment of 20, and a completed status. The sponsor is the University of Cincinnati. The registered study dates are start 2007-08 and primary completion 2011-03. These record details describe the trial's administrative and design features; they do not establish that all planned outcomes or analyses were posted.

Participants were assigned to one of two fish-oil regimens. The low-dose group received capsule omega-3 fatty acids at 2.4g/day, described as four capsules per day. The high-dose group received liquid omega-3 fatty acid at 15 g/day, described as two tablespoons per day. The record identifies the interventions as drugs and describes supplementation as adjunctive to SSRI medications. A separate placebo or usual-care-only arm is not listed among the posted interventions.

The outcome record gives baseline CDRS-R means and standard deviations for the two arms: the high-dose group had 8 participants, with a mean of 33.0 and standard deviation of 1.5; the low-dose group had 12 participants, with a mean of 33.1 and standard deviation of 1.7. These are baseline measurements, not follow-up results. The endpoint's timeframe is listed as 10 weeks, but treatment-period arm values are not reported in the registry record.

The record does not report how the random sequence was generated, whether allocation was concealed, the exact schedule of assessments, adherence, or the statistical analysis plan. The absence of masking is explicit; its practical implications include the possibility that participants and study personnel knew which dose was assigned. The record does not report whether outcome assessors were masked. Enrollment and the listed baseline data alone do not establish whether all randomized participants completed follow-up or entered an analysis.

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: A total of 24 patients were screened and 20 patients met inclusion criteria.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Mood Symptoms Ratings, measured over 10 weeks.

The posted primary outcome is titled Mood Symptoms Ratings and is measured with the Children's Depression Rating Scale-Revised (CDRS-R). The record describes it as an observer-rated instrument based on a semi-structured interview with the child. It contains 17 symptom areas, each rated on a 6- or 7-point scale, with a total score ranging from a low of 17, described as not depressed, to a maximum of 108, described as very depressed. Higher scores therefore indicate greater symptom severity under the scale description in the record.

The record defines remission as a CDRS-R score <28. That threshold is an interpretation criterion stated in the outcome description; the posted primary outcome is nevertheless a continuous score summarized by a mean and standard deviation. A continuous measure retains information across the score range, whereas a threshold classifies scores according to a specified cutoff. Neither form should be confused with a diagnosis made independently of the scale.

Rating depressive symptoms is relevant to the trial's stated interest in symptom reductions accompanying changes in cortical measures. The endpoint timeframe is 10 weeks. However, the arm values posted for this outcome are explicitly labeled as baseline CDRS-R values. No 10-week means, changes from baseline, between-group estimate, or uncertainty interval for the treatment-period outcome are reported in the registry record. Consequently, the available endpoint information describes how symptom scores were summarized and participants' baseline scores, but not the symptom response during treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods translate measurements from participants into estimates that address a study question. For this trial, the key distinction is between baseline description and treatment-period comparison. A mean summarizes the central value of a continuous measure, while a standard deviation describes how spread out individual measurements are around that mean. The posted CDRS-R numbers are means and standard deviations at baseline. They do not, by themselves, estimate what changed over 10 weeks or whether the two assigned dose groups differed after treatment.

What a treatment contrast would describe

In a randomized parallel-group design, an analysis might compare an outcome measured after assignment between the groups, compare change from baseline, or use a model that accounts for baseline scores. Each approach has a different estimand and assumptions. The registry record does not report which approach was planned or used. It also does not post the follow-up values or a calculated treatment contrast for the CDRS-R outcome. It is therefore not possible to describe a treatment estimate or determine how much uncertainty surrounds one.

A confidence interval, in general, expresses the range of values compatible with the observed data and the chosen statistical procedure, under its assumptions. It can convey precision as well as the direction and size of an estimate. A narrow interval generally indicates greater precision than a wide interval, but precision is not the same as clinical importance. No confidence interval for a 10-week symptom contrast is reported in the registry record. A p-value, in general, evaluates how compatible data are with a specified null model; it is not the probability that a treatment works, nor does it measure the size or importance of an effect. No p-value for the treatment-period CDRS-R comparison is reported.

Why the baseline summaries are not an efficacy test

Randomization is intended to support a fair comparison by assigning participants independently of their measured and unmeasured characteristics. It does not make every baseline characteristic identical across groups, especially in a small study. Baseline summaries can describe the enrolled groups and reveal observed starting values, but a baseline comparison does not test the effect of receiving one dose rather than the other. Here, the CDRS-R summaries are explicitly labeled baseline, while the outcome timeframe is 10 weeks. Treating those baseline values as follow-up results would answer a different question from the one stated in the trial objective.

The high-dose and low-dose baseline summaries include group-specific sample sizes, means, and standard deviations. Those quantities are descriptive. A standard deviation reflects variation among observed scores; it is not a confidence interval for the mean and should not be read as a measure of how precisely the group mean estimates a population value. The registry does not post standard errors or confidence intervals for these baseline means.

Analysis populations and missing observations

Clinical trials can define analysis populations in different ways. For example, an analysis may include all randomized participants, only participants who received assigned treatment, or participants who meet specified adherence and follow-up criteria. These choices can affect interpretation, and the registry record does not state which analysis population was planned or used. The baseline arm counts do not establish the number with a 10-week outcome. Participant flow, withdrawals, and reasons for missing data are not reported in the registry record.

Missing-data methods depend on the amount and pattern of missingness and on assumptions about why observations are absent. General approaches may use complete cases, likelihood-based models, or imputation, but their suitability depends on the study context and analysis plan. No missing-data method is reported for the primary outcome. It is therefore not possible to assess whether follow-up data were incomplete, how any incompleteness was addressed, or how sensitive a result might be to those choices.

Multiplicity and secondary measures

Multiplicity arises when a study evaluates several outcomes, time points, doses, or statistical contrasts. Repeated testing can increase the chance of a nominally unusual result, so protocols may prespecify a primary comparison or use an adjustment strategy. The brief study description refers to cortical functional activity, biochemical indices, and depressive symptoms. The registry record does not report a multiplicity strategy or a detailed statistical plan. It lists one posted outcome measure and no posted secondary outcomes. That does not establish which measures were collected or whether additional analyses were conducted; those details are not reported in the registry record.

The study's prediction concerned dose-related changes, but the record does not specify the formal test, contrast, or model used to evaluate a dose relationship. With two assigned dose groups, a direct comparison could address differences between the regimens, but it would not alone estimate the effect relative to no supplementation. No comparison against a placebo arm is listed. The statistical interpretation must therefore remain tied to the two-arm design and the results actually posted.

Planning estimates and precision

Sample-size calculations are planning tools based on assumptions about the effect to detect, variability, significance level, allocation, and analysis. They do not report what was observed, and an observed power calculation is not a substitute for an estimate and its confidence interval. The registry record does not report the trial's own sample-size justification. The stated planning illustration assumptions refer to a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. However, no usable treatment-period effect or participant-per-arm planning result is reported in the record described for this analysis. These assumptions cannot supply the missing efficacy result or establish the trial's original design rationale.

In general, over-dispersion means that observed variability is greater than a model assumes. When that occurs, standard errors and intervals based on the narrower variance assumption can be too optimistic. This concept is relevant when selecting a model for outcomes whose variability exceeds a simple model's expectations, but the posted CDRS-R summaries do not report an over-dispersion assessment or an outcome model. The endpoint is recorded as a continuous measure summarized by a mean and standard deviation; the registry record does not provide enough analysis detail to assess model fit or alternative assumptions.

The record also does not report interim analyses, stopping rules, adjustment for baseline values, or a protocol-defined hierarchy of outcomes. These omissions are not evidence that a particular method was or was not used outside the registry record. They limit the ability to evaluate whether the posted results, if later added, would correspond to prespecified analyses or to exploratory decisions. At present, the primary statistical conclusion is limited: baseline distributions are described, but the treatment-period estimate and its uncertainty are not reported in the registry record.

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.

R code and output

arm <- c("Baseline CDRS-R: High Dose Fish Oil", "Baseline CDRS-R: Low Dose Fish Oil")
n   <- c(8, 12)
m   <- c(33, 33.1)
sp  <- c(1.5, 1.7)
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  Baseline CDRS-R: High Dose Fish Oil  8  33.000  1.500  31.746  34.254
CARM  Baseline CDRS-R: Low Dose Fish Oil  12  33.100  1.700  32.020  34.180

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one posted outcome measure and no posted secondary outcomes. At the same time, the study description identifies cortical functional activity, biochemical indices, and depressive symptoms as areas of interest. The record does not explain how these outcomes were prioritized for statistical testing, whether a hierarchy was prespecified, or whether any adjustment for multiple comparisons was planned. A multiplicity strategy is therefore not reported in the registry record. The absence of posted secondary outcomes should not be taken to mean that no additional measures were collected or analyzed.

The record also does not report the statistical analysis plan, analysis populations, or interim analyses. It gives baseline CDRS-R summaries but no 10-week arm values or analysis of change. Thus, it is not possible to identify a complete-case population, an intention-to-treat analysis set, or another defined group for the primary endpoint. The enrollment count and baseline group counts do not establish who completed follow-up or contributed to an endpoint analysis.

Missing-data handling is not reported in the registry record. There is no description of the amount, timing, or reasons for any missing outcome data, nor of methods used to address missingness. Without participant flow and follow-up outcome availability, the impact of missing observations on a treatment estimate cannot be assessed. The record's lack of an outcome comparison is not equivalent to a result showing no difference; it means that the treatment-period analysis is not available in the registry record.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: worsening of depressive symptoms (16.7%).

The serious adverse-event listing gives the number at risk and number affected in each group. In the high-dose fish-oil group, 8 participants were at risk and 0 had a recorded serious adverse event. In the low-dose fish-oil group, 12 participants were at risk and 2 had a recorded serious adverse event. The top serious-event term is “Worsening of depressive symptoms,” listed at 16.7%. The record does not give event-level descriptions, timing, duration, or an assessment of relatedness to the intervention.

The listing also records 0 participants with other adverse events in either group. Death counts are not reported in the registry record. These categories should be read separately: serious adverse events are not the same as all adverse events, and neither category is a substitute for the CDRS-R symptom endpoint. A serious-event count does not describe the full course of depressive symptoms for every participant.

These are small group counts from the posted record, and they are descriptive rather than a causal comparison. The record does not provide an uncertainty estimate or a formal between-group safety analysis. The serious-event information therefore identifies what was listed and the group counts, but does not establish why events occurred or whether their occurrence differed reliably between regimens.

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

The record establishes that a randomized, open-label, parallel trial compared two adjunctive fish-oil regimens in adolescents with major depressive disorder who exhibited a partial response to SSRI medications. It also establishes that the primary symptom measure was the CDRS-R, with a 10-week timeframe, and that baseline means and standard deviations were posted for both arms. These details describe the design and starting symptom scores.

They do not establish whether CDRS-R scores improved, worsened, or remained similar during the treatment period. No 10-week outcome values, change estimates, or between-group treatment estimate are reported in the registry record. The record also does not post results for the cortical activity and biochemical outcomes central to the study's stated objective. Accordingly, the available information cannot resolve the trial's primary prediction about dose-related changes or symptom reductions.

The baseline mean scores should not be interpreted as evidence of treatment effect. Nor does the lack of a posted treatment-period result mean that the two regimens had identical outcomes. A result that is absent from the registry record is not a null finding. The serious adverse-event listings are a separate descriptive record and do not supply the missing symptom comparison.

The two-arm design can, in principle, estimate a contrast between the assigned dose regimens if appropriate follow-up data and analyses are available. It does not include a listed placebo or no-fish-oil group, so a difference between doses would not by itself establish the effect of supplementation relative to no supplementation. The open-label design also means masking was absent; the record does not state whether outcome assessors were masked. Those features matter when considering the potential for expectations or assessment practices to influence subjective outcomes, but they do not determine the direction or size of any bias.

The appropriate conclusion is narrow: the registry record describes the intended question and baseline CDRS-R data, while treatment-period efficacy results and key analysis details are not reported. No conclusion about benefit, lack of benefit, or relative dose performance can be drawn from the posted primary outcome values alone.

14. Why This Trial Matters Statistically

This trial raises several important statistical distinctions. First, a study objective, a registered endpoint, and a posted result are different things. The objective describes what the investigators sought to evaluate, while the outcome record defines a measure and timeframe. The posted CDRS-R values are labeled baseline, so they cannot stand in for the stated 10-week assessment. Keeping those roles separate prevents descriptive starting values from being mistaken for evidence about treatment response.

Second, randomization supports a comparison between assigned groups, but only when outcomes and an analysis are available. The two dose arms could address a relative dose question, yet no treatment-period contrast is reported. Randomization cannot compensate for absent follow-up results, and similar baseline means do not answer a post-treatment question. This is a useful reminder that a trial's design may be informative even when its registry record does not contain enough results to estimate the outcome of interest.

Third, precision matters alongside the direction of an estimate. A treatment contrast without an uncertainty interval can be difficult to interpret; in this case neither the contrast nor an interval is reported. The group sizes and baseline standard deviations describe the starting data, but they do not establish the precision of a 10-week treatment effect. Planning calculations, if available, would be prospective illustrations based on assumptions rather than observed efficacy evidence.

Finally, the trial's stated mechanistic and symptom objectives raise multiplicity and reporting questions. The record does not provide a statistical plan or a strategy for handling multiple outcomes, and it lists no secondary outcomes. These omissions do not prove selective reporting, but they limit evaluation of how the outcomes were prioritized and analyzed. The case illustrates why complete reporting of prespecified outcomes, analysis populations, missing-data methods, and estimates with uncertainty is essential for readers to assess clinical trial evidence.

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 most consequential limitation for interpretation is that the posted primary outcome values are baseline summaries, while the registered timeframe is 10 weeks. No treatment-period CDRS-R means, changes, or between-group estimate are reported in the registry record. Without these, the primary symptom question cannot be assessed statistically. The record also lacks results for the cortical functional and biochemical measures described in the study objective.

The study enrolled 20 participants, with baseline summaries for 8 in the high-dose group and 12 in the low-dose group. The record does not report why the group counts differ, whether all randomized participants are represented, or how many participants completed the 10-week assessment. The listed baseline counts therefore do not establish follow-up completeness. Missing-data reasons and methods are not reported.

The trial was open-label, and masking was listed as none. The record does not say whether outcome assessors were masked. Because CDRS-R is observer-rated and based on an interview, the lack of masking is relevant to potential measurement and expectation effects, though the registry record does not establish that such effects occurred. The absence of a listed placebo or no-fish-oil arm also limits the causal question to the comparison between two dose regimens.

Other important details are not reported in the registry record: the random-sequence method, allocation concealment, adherence, protocol-level sample-size justification, statistical analysis plan, analysis populations, interim analyses, and multiplicity procedures. No conclusion about how these elements were handled outside the registry record is warranted. The serious adverse-event listing is also limited: event timing, relatedness, participant-level details, and uncertainty estimates are not provided. Together, these limitations mean that the posted record supports a design and baseline description, but not a complete evaluation of efficacy or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Omega-3 Fatty Acids as Adjunct Treatment for Major Depressive Disorder — NCT00511810.
• Registry record last updated 2016-05-27; status last verified 2016-04.
• Results first posted 2014-12-04.
• 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.

19. Record Summary

NCT00511810 is a completed randomized, open-label, parallel trial sponsored by the University of Cincinnati, with enrollment of 20. It studied adjunctive low-dose capsule fish oil at 2.4g/day and high-dose liquid fish oil at 15 g/day in adolescents with major depressive disorder exhibiting a partial response to SSRI medications. The listed primary outcome is Mood Symptoms Ratings, measured using the CDRS-R at 10 weeks.

The posted primary outcome values are baseline means and standard deviations: 33.0 (SD 1.5) for 8 high-dose participants and 33.1 (SD 1.7) for 12 low-dose participants. A 10-week treatment comparison, secondary outcome results, statistical analysis plan, and missing-data methods are not reported in the registry record. Serious adverse events are listed for 0 of 8 high-dose participants and 2 of 12 low-dose participants; worsening of depressive symptoms is the top serious-event term at 16.7%.