Academic Stress and Proinflammatory Cytokines: Omega-3 Intervention: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Academic Stress and Proinflammatory Cytokines: Omega-3 Intervention (NCT00519779), a randomized phase 2 study. The primary outcome is Serum ln(IL-6).

2. Clinical Question

The primary endpoint was serum ln(IL-6), an inflammation-related measure, reported as an average outcome across assessments every 3 weeks for 3 months after supplementation began. The registry also lists ln(Beck Anxiety Score) and ln(CES-D) as secondary outcomes. These measures address mood-related outcomes and complement, rather than replace, the primary inflammatory endpoint.

The central statistical question is about the difference between randomized groups in the recorded outcome, not whether an individual participant improved or whether any observed change has clinical importance. The registry record does not report a clinical threshold for interpreting the size of a difference. It also does not report detailed eligibility criteria, the omega-3 dose, or the intended sample-size justification.

3. Trial Design

The registry describes a randomized, triple-masked, parallel-group phase 2 study with an enrollment of 68. Participants were assigned to oral omega-3 fish oil supplementation or oral omega-3 fish oil placebo. Each arm has 34 participants in the posted primary outcome results. The trial status is completed. Its recorded start was 2007-07, and primary completion was 2008-12.

A parallel design compares groups assigned to different interventions during the same study period. Random allocation is intended, in general, to make the groups comparable on average at the start of a trial. Masking is intended, in general, to limit the influence of knowledge about assignment on participant experience, study conduct, or outcome assessment. The registry identifies the masking as triple, but does not specify which groups of people were masked or describe the masking procedures.

The study summary says it was designed to examine fish oil effects on immune function and mood in medical students. The condition is recorded as stress-related changes in inflammation. The sponsor is the National Center for Complementary and Integrative Health (NCCIH). Details of recruitment, eligibility, treatment duration beyond the outcome timeframe, adherence, and any protocol deviations are not reported in the registry record.

The primary outcome is described as serum ln(IL-6), with assessments every 3 weeks for 3 months after supplementation began; the posted outcome is the average across all 4 time points. The primary population is intention to treat. The record also lists ln(Beck Anxiety Score) and ln(CES-D) as secondary outcomes, with the same stated assessment schedule. The original sample-size assumptions and the basis for the planned enrollment 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: intention to treat

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 Serum ln(IL-6), measured over every 3 weeks for 3 months after initiating supplementation (outcome reported is the average outcome across all 4 time points).

The primary endpoint is serum ln(IL-6), a log-transformed measure of circulating interleukin-6. The registry describes serum cytokine levels as an assessment of systemic inflammation: cytokine levels circulating throughout the body. It notes that higher levels are typically interpreted as worse unless an individual is acutely ill. This is the registry's general framing of the measure, not a claim that the endpoint alone establishes a person's health status.

The outcome is reported as the average across assessments scheduled every 3 weeks for 3 months after supplementation began. Repeated measurements can describe the outcome over the assessment period rather than at only one occasion. Averaging across the 4 time points is the outcome definition recorded for this result. The registry does not provide separate results for each time point in the posted primary outcome data.

The endpoint was selected to address the study's question about immune function and inflammation. The registry also mentions stimulated cytokine production as reflecting the inflammatory cytokine production capacity of monocytes, but the primary endpoint presented is serum ln(IL-6), not a reported stimulated-production result. No clinical threshold, minimally important difference, or decision rule for interpreting changes in ln(IL-6) is reported in the registry record. Consequently, the group comparison can describe the direction and precision of the recorded average difference, but its clinical meaning cannot be established from the endpoint result alone.

7. Results Posted in the Registry

• Omega-3 Fish Oil Supplement: mean 0.05 versus 0.05 on control; difference -0.00 (95% CI -0.20 to 0.19), standardized effect d = -0.01; z-test p = 0.976.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

ln(Beck Anxiety Score)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Omega-3 Fish Oil Supplement: mean 0.93 versus 1.20 on control; difference -0.27 (95% CI -0.48 to -0.06), standardized effect d = -0.61; z-test p = 0.011.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Omega-3 Fish Oil Supplement than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

ln(CES-D)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Omega-3 Fish Oil Supplement: mean 1.60 versus 1.60 on control; difference 0.00 (95% CI -0.27 to 0.27), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Omega-3 Fish Oil Supplement and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes give a mixed overall pattern. The anxiety measure has a reported group difference in the direction of a lower score in the omega-3 arm, whereas the depressive-symptom measure has similar arm summaries. This does not form a consistent pattern across all reported mood-related outcomes. Neither secondary result changes the primary finding for serum ln(IL-6), because the outcomes address different measures and questions.

Secondary outcomes can help describe other aspects of a study, but they commonly have less evidential weight than a prespecified primary outcome. When several outcomes are tested, the chance of obtaining at least one apparently notable result can increase, even if there are no true effects. In general, adjustment procedures or a prespecified testing hierarchy can address aspects of this multiplicity problem. The registry record does not report whether any such procedure or hierarchy was used.

The posted unadjusted secondary results should therefore be treated as exploratory evidence rather than independent confirmation of an overall effect. The registry records a mixed models analysis for the secondary measures, while the simple recalculations are unadjusted comparisons based on posted summaries. Those approaches need not produce identical estimates or uncertainty. Interpretation should prioritize the reported analysis and consider the full pattern of outcomes rather than selecting a single secondary result.

The record lists 6 outcome measures and 6 analyses, but only 2 secondary outcomes are posted in the results data. The status and results of any other measures are not reported in the registry record. The record also does not provide the original statistical analysis plan, so the prespecified status of each secondary measure and the intended approach to multiple testing are not reported.

These limitations do not make the secondary outcomes irrelevant. They indicate that their results are best viewed as supporting context for the study's broader questions about mood, rather than as a replacement for the primary endpoint or as conclusive evidence in isolation.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• ln(Beck Anxiety Score)
• ln(CES-D)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: serum ln(IL-6). Continuous outcomes are measured on a scale where differences between values can be expressed as a mean difference. The recorded arm summaries are least-squares means, accompanied by standard errors. A least-squares mean is a model-based group mean; the registry does not give enough detail to explain which covariates or model terms were used to obtain these particular summaries.

What does a mean difference describe?

The mean difference compares the outcome in the omega-3 arm with the outcome in the placebo arm. A negative estimate indicates that the recorded average is lower in the omega-3 arm on the outcome scale; a positive estimate would indicate a higher average. For the primary endpoint, the reported mixed models estimate is -0.003. The estimate is close to zero on the recorded scale. This describes a difference between group averages, not a change experienced by every participant.

The registry reports a Mixed Models Analysis with a parameter described as mean difference (final values). A mixed model is generally used to analyze data with related observations, such as repeated measurements from the same participant. In general, accounting for the correlation among repeated measurements can be important because observations from one person are not necessarily independent. The registry does not report the model specification, covariance structure, covariates, or exact handling of incomplete repeated measurements. No further details should be inferred from the method label alone.

What does the confidence interval add?

A confidence interval gives a range of estimates compatible with the observed data under the analysis assumptions. It conveys statistical uncertainty around the estimated group difference. The reported primary 95% interval runs from -0.18 to 0.18. Since the interval includes zero, the data do not distinguish a difference from no difference at conventional significance levels. The interval should not be interpreted as a guarantee that the true effect lies within it, and it does not answer whether any value in the range is clinically important.

What does the p-value describe?

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that null and the analysis assumptions held. It is not the probability that the null is true, and it is not a measure of effect size. The sponsor's reported primary p-value is 0.97. The recalculation gives p = 0.976. Both are consistent with the interval's inclusion of no difference. A large p-value does not demonstrate equivalence; an equivalence conclusion would require a stated margin and an analysis designed for that question, neither of which is reported in the registry record.

The recalculation is an unadjusted comparison derived from the posted means and standard errors. The posted comparison notes that the pooled standard deviation is approximate. In general, a standard error describes uncertainty in an estimated mean, while a standard deviation describes variability among individual observations. Converting between them requires assumptions about the data and sample. The simple recalculation is therefore useful as a transparent check against the posted summaries, but it is not a substitute for the sponsor's model-based analysis.

Why can repeated measurements and variability matter?

Repeated outcome assessments can improve the description of an outcome over time, but they require an analysis that accounts for within-participant dependence. In general, a model that treats correlated observations as independent may give misleading uncertainty. The registry identifies a mixed-model approach for the reported analysis, but does not state its detailed implementation. Variability also affects precision: more variability relative to the group difference generally makes a difference harder to estimate precisely. The record reports standard errors for arm means, not individual-level data from which to inspect distributions or outliers.

Over-dispersion is a general concern when observed variability exceeds what an assumed statistical model allows. In that circumstance, standard errors can be too small if the extra variability is ignored. The posted record does not describe an over-dispersion assessment, and the outcome is continuous rather than a count result for which that issue is often discussed. No claim about whether it occurred in this trial can be made.

What does intention to treat mean?

In general, an intention-to-treat analysis compares participants according to their randomized assignment, regardless of whether they followed the assigned regimen. This preserves the comparison created by randomization. The primary population is identified as intention to treat, but the registry does not report how missing measurements, discontinuation, or deviations from assigned supplementation were handled. The label alone cannot establish that all randomized participants contributed complete outcome data.

Finally, statistical significance and clinical importance are different questions. The reported p-value and interval describe evidence and precision under a statistical analysis. The registry does not report a threshold for a meaningful change in serum ln(IL-6), nor does it provide enough clinical context to translate the estimate into a health outcome. Interpretation should therefore focus on the measured endpoint and the uncertainty around its group difference.

11. Confidence Intervals and Precision

The sponsor's primary estimate is -0.003, with a 95% confidence interval from -0.18 to 0.18. The unadjusted recalculation gives -0.003, with an interval from -0.196 to 0.190. These intervals include zero and allow values on either side of no group difference. The results therefore do not precisely establish the direction of the underlying difference.

In general, a confidence interval expresses the uncertainty of an estimate under the statistical model and its assumptions. A narrower interval indicates greater precision than a wider interval, but precision alone does not establish clinical importance. The registry does not provide a clinically meaningful threshold for serum ln(IL-6), so the interval cannot be divided into clinically important and unimportant values using the posted information.

The interval is also not proof of equivalence. To show equivalence, a study would ordinarily need a prespecified margin defining differences small enough to count as equivalent, along with an appropriate analysis. Such a margin is not reported in the registry record. Likewise, the confidence interval does not indicate the probability that the true effect is within its bounds.

The recalculated interval is close to, but not identical to, the sponsor's reported interval. The former is derived from posted summary statistics and is unadjusted; the latter is from the registry's mixed models analysis of final values. The sponsor's analysis is the reported trial analysis. The modest difference between interval endpoints should be understood in light of the distinct calculation methods, not as evidence that one result can be substituted for the other.

The enrollment and arm sizes are relevant context for precision, but the record does not report the original planning assumptions or a sample-size justification. Thus, the observed interval is the direct indication of uncertainty for the reported primary estimate; planned power cannot be reconstructed from the record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size material gives planning illustrations based on the observed effect, not the original trial design. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row considers an effect equal to a stated fraction of the observed effect. The listed figures are participants per arm, not total events. This is not observed power.

The 80% power column describes the number of participants per arm in a hypothetical study that, under the stated assumptions and effect size, would have an 80% chance of detecting a difference at the specified significance level. The 90% power column uses a higher chance of detection under those same planning conditions. These are prospective planning concepts; they do not tell whether the completed trial had an 80% or 90% chance of finding its actual result.

The rows for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect illustrate how the assumed target changes the planning requirement. Smaller effects need more participants because they are harder to distinguish from random variation. The displayed figures are conditional on the assumptions and the observed effect used for illustration. They are not a recommendation for a future study and do not establish the appropriate target for a new research question.

The registry does not report the original sample-size justification or the assumptions used when the trial was designed. The planning illustrations should therefore be read separately from the actual enrollment of 68 and the 34 participants per arm in the posted primary results. They are not a retrospective explanation of why that enrollment was selected.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.003; pooled standard deviation σ = 0.405.
2. n = 2 × (1.96 + 0.842)² × 0.405² / -0.003² = 286,461.4, rounded up to 286,462 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.003                      # observed difference in means
sigma <- 0.405261643879605                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(519779)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 286,462 (80% power), 383,491 (90% power)
 75% of observed effect: n per arm = 509,265 (80% power), 681,762 (90% power)
 50% of observed effect: n per arm = 1,145,846 (80% power), 1,533,963 (90% power)
power.t.test: 286462.4 
Simulated power at n = 286,462 per arm: 0.803 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry's reported primary analysis is a mixed models analysis of final values. It gives a mean difference of -0.003, a 95% confidence interval from -0.18 to 0.18, and p = 0.97. The unadjusted recalculation from the posted arm summaries gives a mean difference of -0.003, a 95% interval from -0.196 to 0.190, and p = 0.976.

The estimates are close and lead to the same broad statistical reading: the interval includes zero, and the reported p-values do not indicate a clear difference between groups in the primary outcome. The recalculation is based on posted summary statistics and is not a reproduction of the mixed model. The model may use information or assumptions not represented in a simple summary-statistic calculation; its details are not reported in the registry record.

The sponsor's analysis is the primary reported trial analysis. Small differences between the sponsor's estimate and the unadjusted recalculation should not be treated as a contradiction or resolved by selecting whichever number appears more favorable. The trial's analysis is the relevant reported result, while the recalculation serves as a straightforward check using the posted summaries.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates more than one outcome, time point, comparison, or analysis. In general, conducting multiple tests can increase the chance that at least one result appears statistically notable by chance. Common approaches include prespecifying a primary outcome, setting a testing hierarchy, or adjusting the interpretation for multiple comparisons. The registry identifies serum ln(IL-6) as the primary outcome and lists ln(Beck Anxiety Score) and ln(CES-D) as secondary outcomes. Whether the original protocol prespecified an order or a multiplicity adjustment is not reported in the registry record.

The record states 6 outcome measures and 6 analyses, while 2 secondary outcome results are posted alongside the primary result. It does not give enough information to determine the status or findings for any outcome measures not posted in these results. A complete accounting of all planned and conducted analyses is important when considering selective reporting, but the registry information does not establish whether any outcome was omitted or why.

The primary population is described as intention to treat. In general, this approach aims to retain participants in the groups to which they were randomized. The registry does not report the number of participants with observed measurements at each assessment, missing-data patterns, reasons for missingness, or the methods used to handle missing outcomes. It is therefore not possible to assess from the record whether missing data could have affected the estimates.

The registry identifies a mixed models analysis, but details such as the model specification and assumptions about missing data are not reported. Such assumptions can matter because an analysis may rely on conditions about why measurements are missing. No conclusions about the validity of those assumptions can be drawn from the method label alone.

The record also does not report interim analyses, stopping rules, a detailed statistical analysis plan, or the original sample-size justification. These matters are not necessarily evidence of a problem; they are information gaps that limit evaluation of how the analyses were planned and carried out. The reported primary analysis remains the central result, while interpretation of secondary tests and the completeness of the analysis process must remain cautious.

16. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 34 participants in the placebo arm and zero among 34 participants in the omega-3 fish oil arm. These are the serious-event figures posted for the groups. The registry does not list serious adverse event terms in the results data.

Other adverse events are listed for 18 participants in the placebo arm and 20 participants in the omega-3 arm. These counts are distinct from the serious adverse event figures. The registry record does not provide event descriptions, severity details, timing, or a causal assessment in the information. The counts alone do not show whether events were related to the assigned supplementation or whether participants experienced more than one event.

Deaths are not reported in the registry record. A count of zero serious events in the posted results should not be read as proof that no harm is possible, particularly without detail about event definitions, follow-up, and ascertainment. These figures describe the safety results recorded for this trial and do not provide medical advice or a complete assessment of safety.

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

The primary data describe average serum ln(IL-6) in the omega-3 and placebo groups over the scheduled assessment period. The estimated group difference is close to zero, and the reported confidence interval includes no difference. The trial therefore does not provide clear statistical evidence of a difference in this primary endpoint. The interval still allows differences in either direction, so the result is not proof that the groups are identical.

That conclusion is specific to the endpoint, population, intervention, comparison, and assessment schedule recorded for this study. The primary outcome is a log-transformed serum cytokine measure, not a direct measure of every aspect of immune function, mood, or health. The registry's broad study aim does not mean that one biomarker result can answer all questions about fish oil or inflammatory processes.

The secondary outcomes add information about the mood measures included in the study, but their overall pattern is mixed and the registry does not report a multiplicity approach. Those results should not be treated as definitive confirmation of a broader effect. In general, secondary outcomes are most informative when their planned role and interpretation are clear and when the full set of outcomes is considered.

The record does not report a clinically meaningful threshold for the primary measure, the original sample-size assumptions, detailed missing-data methods, or a full account of the analysis plan. Without those details, the statistical result cannot establish whether a difference of any particular size would matter in practice or whether the study was designed to detect such a difference.

The findings also do not establish that supplementation works or does not work as a treatment. They describe the posted comparison in a completed randomized phase 2 study with 68 enrolled participants. Generalization to other populations, formulations, doses, durations, or outcomes is not established by this record. The most defensible reading is limited: the posted primary analysis found no clear group difference in average serum ln(IL-6), with uncertainty remaining around the size and direction of any underlying difference.

18. Why This Trial Matters Statistically

This trial illustrates why a result should be read through its estimate and confidence interval, not through a p-value alone. The primary estimate is close to zero, while its interval spans values below and above zero. Together, those statistics show that the data do not clearly distinguish a group difference from no difference, but they also do not prove equivalence. The distinction is central to interpreting trials with modest enrollment and continuous outcomes.

It also shows how a registry-reported model-based analysis can be compared with a simple recalculation from posted group summaries. The two primary estimates are close, but they are not identical because the recalculation is unadjusted and does not reproduce the mixed models analysis. Understanding what each calculation represents helps avoid treating a summary-statistic check as if it were the full trial analysis.

The study's repeated outcome schedule raises another general statistical issue: measurements from the same participant may be related. A mixed model is a broad class of methods used for such data, but a method label alone is not enough to evaluate model assumptions or missing-data handling. The registry record does not report those implementation details, making the distinction between known results and unknown analytic choices especially important.

Finally, the secondary outcome pattern and the absence of a reported multiplicity approach demonstrate why several outcomes should be considered together. An isolated secondary finding can be less persuasive when multiple measures are evaluated and the analysis plan is not available. The trial is therefore useful as an example of disciplined interpretation: focus on the primary result, describe uncertainty, and avoid turning statistical evidence into a broader clinical conclusion that the record cannot support.

19. 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.

Several trial-specific information gaps constrain interpretation. The registry does not report the omega-3 dose, detailed formulation, duration of supplementation, adherence, or the characteristics and eligibility criteria of the enrolled medical students. These details would help readers understand the intervention and the population to which the findings apply.

The primary endpoint is an average across assessments every 3 weeks for 3 months after supplementation began. The registry does not post separate results by time point, so the pattern of measurements over the assessment period cannot be evaluated from these results. The model specification and details of how repeated measurements were handled are also not reported beyond the mixed models label.

The primary population is intention to treat, but the registry does not report the number of participants contributing data at each time point, missing-data patterns, reasons for missingness, or the approach used for incomplete observations. Information about adherence and protocol deviations is not reported either. These omissions limit assessment of how the analyzed data relate to the randomized groups.

The original sample-size justification, prespecified clinically meaningful difference, and trial-specific planning assumptions are not reported in the registry record. Planning illustrations based on the observed effect cannot fill that gap. The record also does not describe a multiplicity strategy, a testing hierarchy for secondary outcomes, interim analyses, or a full statistical analysis plan. These absences limit assessment of the intended analysis and the strength of secondary findings.

Safety information is limited to the posted counts: zero serious adverse events in each arm and other adverse events recorded for 18 participants in the placebo arm and 20 participants in the omega-3 arm. Event details and deaths are not reported in the registry record. The trial's enrollment and the available outcome information also limit the breadth of conclusions; results from this study do not by themselves establish effects in other populations or on other outcomes.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Academic Stress and Proinflammatory Cytokines: Omega-3 Intervention — NCT00519779.
• Registry record last updated 2012-03-27; status last verified 2012-02.
• Results first posted 2012-03-22.
• 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.

23. Record Summary

This completed phase 2 study was randomized, triple-masked, and parallel-group, with enrollment of 68. It compared oral omega-3 fish oil supplementation with oral omega-3 fish oil placebo in a study designed to examine immune function and mood in medical students. The primary endpoint was average serum ln(IL-6) across assessments every 3 weeks for 3 months after supplementation began.

The sponsor's mixed models analysis reported a mean difference (final values) of -0.003, with a 95% confidence interval from -0.18 to 0.18 and p = 0.97. The interval includes no difference, and the result does not provide clear evidence of a group difference in the primary endpoint. Secondary mood-related outcomes show a mixed overall pattern and should be interpreted cautiously because a multiplicity approach is not reported.

The registry record does not report the original sample-size justification, detailed missing-data methods, or a full statistical analysis plan. The findings describe the posted results for this study and do not establish equivalence or a broader clinical effect.