Effects of Omegas 3 and 6 on Alcohol Dependence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Omegas 3 and 6 on Alcohol Dependence (NCT01211769), a randomized phase 3 study. The primary outcome is "Drinking Days" in the Previous Month.

2. Clinical Question

The study asks whether supplementation with polyunsaturated fatty acids (PUFAs), alone or alongside naltrexone, is associated with a change in drinking among people with alcohol dependence. The stated objective is to assess the effectiveness of PUFA supplementation in treating alcohol-dependent patients. The registry lists drinking days in the previous month as the primary outcome, with measurement at the 3-month timeframe.

The question is clinically framed around drinking behavior, while the posted primary measure is a count of days assessed retrospectively with the Alcohol Timeline Followback method. The record also lists the Short Alcohol Dependence Data Questionnaire and the Obsessive Compulsive Drinking Scale as secondary outcomes. Their results are not reported in the registry record. Thus, the research question can be described from the planned outcome and interventions, but the posted information does not establish how the groups compared on drinking or on the secondary measures.

3. Trial Design

The registry identifies this as a randomized, double-masked, parallel-group phase 3 trial, with an enrollment of 80. It is marked completed. The listed study condition is alcohol dependence, and the objective concerns PUFA supplementation in treatment. The registry lists placebo, naltrexone, PUFAs, and naltrexone plus PUFAs as intervention arms. This arrangement makes it possible to ask about the listed treatments and their combinations, but the registry information does not state which contrasts were prespecified as primary or how treatment effects were to be separated statistically.

The intervention descriptions distinguish active and matching preparations. Naltrexone is described as naltrexone chlorhydrate 50 mg. The PUFA preparation is borage oil, rich in omega 6, at a dosage of 1 gram, together with 1 gram of fish oil, rich in omega 3. The placebo descriptions include talcum powder in a pill identical to the naltrexone pill and yellow liquid paraffin described as identical to the borage seed and fish oil pills. The combined active arm is described as containing both naltrexone and PUFAs.

Randomization is a design feature intended to support fair comparisons by allocating participants to groups through a chance-based process. Double masking means the registry classifies the study as masked for two roles, but the record does not identify those roles or explain how masking was maintained. The parallel model indicates that participants were assigned to a treatment group rather than being described as crossing between treatments; further protocol details are not reported in the registry record.

The registry gives a start date of 2006-02 and a primary completion date of 2008-06. These dates describe the record's study timeline; they do not provide evidence about the timing of analyses or results. The study sponsor is the Federal University of São Paulo. The registry record does not report a sample-size justification, detailed allocation procedures, treatment duration, adherence measures, or the full statistical analysis plan. Those absences limit how much can be inferred about conduct and analysis beyond the design labels and intervention descriptions.

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: 645 individuals contacted; 325 were excluded after answering the questionnaire by phone. Most of the remaining 320 patients did not meet the inclusion criteria. 80 patients participated in the study.

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 "Drinking Days" in the Previous Month, measured over 3 months.

The primary endpoint is “Drinking Days” in the Previous Month, measured in days and summarized as a mean with standard deviation. The stated timeframe is 3 months. The registry describes the Alcohol Timeline Followback (TLFB) as a method for estimating daily drinking retrospectively: a participant uses a calendar to report drinking day by day over a specified period that can vary up to 12 months from the interview date. This approach turns a behavioral history into a quantitative outcome that can be compared across treatment groups.

Counting drinking days captures the frequency of drinking occasions across the assessment period, rather than directly describing the amount consumed on each occasion. It can therefore address a particular aspect of drinking behavior, but it does not by itself summarize every clinically relevant dimension of alcohol use. The record does not report whether the primary analysis used the endpoint as a raw count, adjusted for baseline values, or handled any special distributional features.

The distinction between outcome timeframe and recall period matters for interpretation. The registry names a 3-month timeframe while the endpoint title refers to the previous month; the record does not give additional detail explaining the timing of the interview in relation to treatment or clarifying the assessment schedule. The posted record also does not report the observed means, standard deviations, or a comparison estimate. Consequently, the measure and its intended meaning can be described, but the primary outcome's observed pattern cannot be reconstructed from this registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. The outcome is drinking days in the previous month, measured in days. In general, a mean describes the average value within a group, while the standard deviation describes how dispersed individual observations are around that average. These summaries can help characterize a continuous outcome, but they do not on their own show the difference between treatment groups or the uncertainty around that difference. The registry record does not report the arm-specific primary-outcome summaries.

What would a treatment contrast describe?

In general, a treatment contrast expresses how an outcome in one group compares with an outcome in another group. For a mean-based endpoint, the contrast may be expressed as a difference in group means. Its direction depends on which group is placed first, and its scale remains the scale of the outcome. For drinking days, that scale is days. A contrast is most informative when interpreted alongside an uncertainty interval and the analysis definition, including the population analyzed and any adjustment for baseline or other variables. Those details and the contrast itself are not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval communicates the precision of an estimated effect under the statistical model and assumptions used. A narrower interval indicates greater precision than a wider interval, but width alone does not establish clinical importance. An interval that includes values compatible with no difference may still include effects that matter in either direction; interpretation depends on the interval's endpoints and relevant context. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated.

How should a p-value be understood?

In general, a p-value describes the compatibility of data with a statistical null hypothesis under a specified model. It is not the probability that the null hypothesis is true, and it does not measure the size of an effect. A small p-value does not establish that a difference is important, while a larger p-value does not establish equivalence. The registry record does not report a p-value for the primary endpoint or identify the test used. No statistical-significance conclusion can therefore be drawn from the registry information.

Why can count outcomes need care?

Although the endpoint is summarized as a mean, drinking days are recorded as a count over a recall period. In general, count data may have features such as skewness or over-dispersion, where variation is greater than a simple model assumes. Over-dispersion matters because a model that understates variation can produce uncertainty estimates that are too narrow. Other modeling choices may be appropriate depending on the outcome distribution, study design, and analysis objective. The registry record does not report a distributional assessment, model choice, or method for addressing over-dispersion, so it would be speculative to attribute any particular method to this trial.

What do randomization and masking contribute?

In general, random allocation can reduce systematic differences between groups at the point of assignment, while masking can limit the influence of expectations on behavior, care, and outcome assessment. These design features do not guarantee that groups remain comparable in every respect, eliminate missing data, or prevent bias from deviations after allocation. Their strengths depend on implementation. The registry labels this study randomized and double-masked, but does not report the sequence-generation method, concealment process, identities of masked roles, or any assessment of masking success.

How should planning illustrations be read?

In general, a sample-size planning illustration translates assumptions about an effect, variability, significance level, allocation, and statistical model into a planned number of participants. It is conditional on those assumptions and is not an observed trial result. A calculation based on an observed effect is especially dependent on that effect estimate and should not be described as observed power. The registry record describes planning assumptions involving a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of an observed effect. It also specifies that time-to-event calculations use total events, while other calculations use participants per arm. The record does not report the numerical planning outputs or the trial's own sample-size justification. Such illustrations cannot establish what the trial was designed to detect or the precision of its actual findings.

What is not known about the analysis?

The statistical analysis plan is not reported in the registry record. In particular, the record does not specify the primary comparison, whether the analysis was adjusted, the analysis population, how repeated or missing observations were handled, or how multiplicity was addressed. These are not minor details: the contrast definition determines which groups are compared, the analysis population affects who contributes data, and missing-data assumptions can influence estimates. Without the plan and results, the design labels and endpoint description do not identify the statistical procedure used or validate a particular interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The record lists a primary outcome and two secondary outcome measures: the Short Alcohol Dependence Data Questionnaire (SADD) and the Obsessive Compulsive Drinking Scale (OCDS). It also lists several treatment arms. When a study evaluates multiple outcomes or comparisons, the chance of at least one apparently notable result can increase if each is assessed separately without an appropriate plan. In general, multiplicity procedures or a clear hierarchy of outcomes can help control how results are interpreted. The registry record does not report a multiplicity strategy, the planned hierarchy of comparisons, or which arm contrasts were considered primary.

The primary outcome is not reduced in the registry information to a reported single comparison. The record does not report a treatment-effect estimate or results by arm for the primary or secondary measures. As a result, there is no basis for judging whether the reported conclusions, if any, accounted for multiple outcomes or comparisons. Nor can it be determined whether secondary results were exploratory or confirmatory from the available information.

Missing-data handling is also not reported in the registry record. The record does not say how many participants contributed outcome data, whether the analysis followed the randomized assignment, how missing assessments were handled, or whether sensitivity analyses were conducted. These details matter because observed outcomes may differ from missing outcomes, and methods for addressing missingness rely on assumptions. The enrolled number and safety at-risk counts do not establish the number with primary-endpoint observations. Analysis-population definitions, protocol deviations, and adherence information are not reported in the registry record. These gaps prevent a complete assessment of the analysis and its vulnerability to missing-data or selection effects.

11. 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 lists serious adverse events by arm and reports zero serious events for the placebo, naltrexone, PUFAs, and naltrexone plus PUFAs groups. Each entry lists 20 participants at risk for serious events. The registry's separate entries for other adverse events list zero in placebo and one in each of the naltrexone, PUFAs, and naltrexone plus PUFAs groups, with 20 at risk in each entry. These figures describe the entries recorded in the registry, not a complete account of every symptom or event experienced during the study.

The record does not list serious adverse-event terms, and it does not report deaths. A zero in the serious-event field means that no serious event is recorded in that entry; it does not establish that a treatment has no risk. The registry does not provide descriptions of the other adverse events, their timing, severity, relatedness to treatment, or whether an individual could contribute more than one event. It also does not describe safety surveillance or the criteria used to classify events.

Safety counts should be read alongside the amount and completeness of follow-up and the methods used to collect events. Those details are not reported in the registry record. The posted counts alone are not a formal comparative analysis of safety and do not support conclusions about differences in adverse-event risk.

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

This trial record is useful for identifying the study's population, treatment arms, primary endpoint, and design labels. It documents a randomized, double-masked, parallel-group phase 3 study of naltrexone and PUFAs for alcohol dependence, with drinking days in the previous month named as the primary outcome. It also records the TLFB as the assessment method and lists SADD and OCDS as secondary measures. These details explain what the study set out to investigate.

They do not establish what the study found. The registry record does not report primary-outcome means, standard deviations, effect estimates, confidence intervals, or p-values. It does not report the secondary-outcome results either. Therefore, the direction, magnitude, and precision of treatment contrasts cannot be assessed from this record. Completion status is not a substitute for results, and intervention descriptions are not evidence that a treatment changed drinking behavior.

The safety entries report no serious adverse events in the listed groups and some other adverse-event counts, but provide little detail about event types, follow-up, or collection. Those counts should not be treated as a comprehensive safety evaluation. Similarly, the sample-size planning assumptions described in the record are not observed outcomes and do not provide evidence of efficacy or safety.

In general, assessing a treatment comparison requires an interpretable estimate, its uncertainty, and enough information about analysis methods and missing observations to judge how the estimate was obtained. A registry record can support an account of the study's design and registered measures while leaving the treatment effect unresolved. For this study, the central result needed to answer the primary question is not reported in the registry record. No treatment recommendation or conclusion about effectiveness follows from the information available.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of why a registered design and an interpretable result are different kinds of evidence. Randomization, masking, a defined primary endpoint, and a stated measurement method describe how a comparison was intended to be organized. They do not supply the observed effect or its uncertainty. For clinical researchers and biostatisticians, that distinction is essential when reading registry records: design features help frame the question, while outcome estimates are needed to evaluate the answer.

The endpoint also illustrates how operational definitions shape interpretation. “Drinking Days” in the Previous Month is a behavioral measure based on retrospective calendar reports using the TLFB. It addresses drinking frequency over a recall period, not every feature of alcohol dependence or alcohol-related harm. The choice of outcome determines what a treatment contrast would mean and what it would leave unmeasured.

The listed arms include naltrexone, PUFAs, their combination, and placebo. Such a layout raises questions about which treatment comparisons are of greatest interest and how multiple comparisons should be interpreted. The registry record does not report those analysis priorities or an adjustment plan. This underscores the value of explicit prespecification when several treatments, outcomes, or contrasts are studied.

Finally, the record shows why the absence of results must be made visible in interpretation. Without group summaries and an effect estimate, statistical significance, precision, and clinical relevance cannot be assessed. A completed status, safety counts, or planning assumptions cannot fill that gap. The appropriate statistical conclusion is limited: the study question and design are documented, but the posted record does not report the primary findings required to resolve the question.

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 registry information leaves important limitations for interpreting the study. It does not report the primary outcome results, including arm means, standard deviations, or a treatment contrast. There is no reported uncertainty interval or p-value, and no secondary-outcome results are reported. Consequently, the size and precision of any observed differences cannot be evaluated.

Although the record labels the study randomized and double-masked, it does not report the randomization procedure, allocation concealment, who was masked, or whether masking was maintained. The registry also does not report eligibility criteria in the available study description, treatment duration, adherence, co-interventions, or the timing of outcome assessments beyond the stated timeframe. These omissions constrain assessment of how the design was implemented and how broadly the results might apply.

The primary outcome description combines the title “Drinking Days” in the Previous Month with a 3-month timeframe, but the registry does not further explain the assessment schedule. It does not report the analysis model, prespecified comparisons, adjustment strategy, analysis population, missing-data methods, or multiplicity handling. The record therefore does not establish how observations were analyzed or how incomplete follow-up was addressed.

The safety entries have limited detail: serious-event terms are not listed, deaths are not reported, and the other adverse events lack descriptions and context. The planning assumptions are described, but the numerical illustrations and the trial's own sample-size justification are not reported in the registry record. Taken together, these limitations mean that the record supports a description of the study's intent and design, but not a full appraisal of its results, conduct, or treatment effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of Omegas 3 and 6 on Alcohol Dependence — NCT01211769.
• Registry record last updated 2010-09-29; status last verified 2010-09.
• Results first posted 2010-09-29.
• 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, double-masked, parallel-group phase 3 study sponsored by the Federal University of São Paulo. Enrollment is listed as 80, and the condition is alcohol dependence. The study evaluates naltrexone and PUFAs, individually and in combination, with placebo comparators listed among the arms. The PUFA preparation is described as borage oil and fish oil.

The primary endpoint is drinking days in the previous month, summarized as a mean with standard deviation and associated with a 3-month timeframe. The registry describes the Alcohol Timeline Followback method for retrospective daily drinking estimates. SADD and OCDS are listed as secondary outcomes.

Outcome estimates for the primary and secondary measures are not reported in the registry record. Safety entries list zero serious adverse events in each arm and other adverse-event counts of zero or one, while deaths are not reported. The record does not provide enough statistical results or analysis details to assess treatment effects or their precision.