A Response Modulation Hypothesis of Socioemotional Processing Associated With Alcohol Use Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Response Modulation Hypothesis of Socioemotional Processing Associated With Alcohol Use Disorder (NCT03535129), a randomized na study. The primary outcome is Alcohol Attention Bias Signal - Stage 1.

2. Clinical Question

3. Trial Design

The registry identifies NCT03535129 as a randomized, double-masked, parallel study. It lists the phase as not applicable. Enrollment was 101, and the record gives the status as completed. The listed study dates are 2018-09-20 for start and 2025-03-23 for primary completion. These registry-level design labels do not, by themselves, describe how randomization was carried out, who was masked, or whether masking was maintained.

The study description separates the work into a pilot Stage 1 and a Stage 2 involving neurofeedback and sham groups. In Stage 1, participants with alcohol use disorder and healthy control volunteers underwent a single fMRI scan while performing a socioemotional processing task. The arm descriptions state that these scans occurred before real-time active neurofeedback. Stage 2 included participants with alcohol use disorder assigned to neurofeedback or sham groups; the descriptions report two fMRI scans, in week 1 and week 4. The registry record does not fully describe the sequence or content of the Stage 2 procedures because the arm descriptions are incomplete.

The study’s stated objectives concern brain responses to social and alcohol-related pictures and whether participants can regulate brain activity in an MRI scanner. The brief description also lists screening, questionnaires, behavioral tasks, and MRI procedures. It does not provide a complete visit schedule or a full account of all procedures in each group. The primary endpoint is specifically labeled as a Stage 1 measure. Its analysis population was limited to Stage 1 participants who completed the scan, had good-quality imaging data, and met a further criterion whose description is truncated. The registry record does not report a primary endpoint analysis for Stage 2.

There are five outcome measures listed, but no analysis records are listed. The record therefore distinguishes between planned or registered outcomes and reported statistical comparisons: an endpoint description is available, but an analyzed treatment contrast is not. Details such as the allocation ratio, randomization method, masking roles, and the rationale for 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.

Stage 1 - Pilot

Reasons for not completing this period:

Stage 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis included participants enrolled in Stage 1 of the protocol only, as it was pre-specified that Stage 1 participants would complete a single scan only. Furthermore, analysis included only those participants who completed the fMRI brain scan, had good quality imaging data, and who successfully completed the socio-emotional processing behavioral task in the pilot study.

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 Alcohol Attention Bias Signal - Stage 1, measured over On day of fMRI scan.

The primary endpoint is titled “Alcohol Attention Bias Signal - Stage 1” and is measured in arbitrary units (A.U). It is the mean contrast in estimated blood-oxygen-level-dependent (BOLD) response between two conditions during an fMRI scan: a negative socioemotional cue paired with an alcohol cue, and a negative socioemotional cue paired with a neutral cue. The registry description defines the contrast by subtracting the response for the alcohol-cue condition from the response for the neutral-cue condition. The timeframe is the day of the fMRI scan.

In general, a contrast expresses the difference between responses under specified task conditions. Here, the conditions differ in whether the negative socioemotional cue is paired with an alcohol cue or a neutral cue. The endpoint is intended to capture a brain-response pattern relevant to attention to alcohol-related material during socioemotional processing. It is an imaging measure, not a direct measure of drinking behavior or a clinical outcome.

The registry says that the Stage 1 analysis was restricted to participants who completed the fMRI scan and had good-quality imaging data, with another eligibility criterion described only in part. That makes the analyzed group narrower than all enrolled participants. The registry record does not report the endpoint’s observed mean, standard deviation, number analyzed, or any group comparison. Consequently, the direction and magnitude of the recorded signal, and its statistical precision, cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods should be read in relation to the question, endpoint, analysis population, and comparison being made. For this study, the listed primary endpoint is a continuous imaging measure: a mean contrast in estimated BOLD response, reported in arbitrary units. The registry labels the endpoint parameter as a mean and its dispersion as a standard deviation. The results record does not give the endpoint’s mean, standard deviation, or an associated analysis. Thus, the method labels describe the type of measure, not a completed or reported statistical comparison.

What does a continuous endpoint mean?

General explanation: a continuous measure can take values across a scale rather than being limited to categories such as yes or no. A group mean describes the average value for the participants included in that group. A standard deviation describes how spread out individual values are around that mean. It is not the same as the standard error, which describes uncertainty in an estimated mean. A mean and standard deviation alone would not show the precision of a group difference unless the analysis also accounts for the group sizes and design.

The endpoint is a contrast between two task conditions. In general, a contrast is formed by comparing measurements under distinct conditions according to a defined direction. The registry defines the subtraction direction: the BOLD response for the negative socioemotional cue paired with an alcohol cue is subtracted from the response for the negative socioemotional cue paired with a neutral cue. The sign of a contrast depends on that definition. Without a reported estimate, its sign and size cannot be interpreted.

What would an estimate and confidence interval tell a reader?

General explanation: an estimated group difference describes the observed separation between groups on the outcome scale. A confidence interval conveys uncertainty around that estimate under the statistical model and assumptions used. A narrow interval indicates greater precision than a wide interval, but the interval’s meaning depends on how the analysis was performed and which participants were included. A confidence interval does not establish clinical importance, and an interval containing a null value does not prove that groups are identical.

No primary endpoint estimate or confidence interval is reported in this registry record. No p-value or test statistic is listed either. It is therefore not possible to distinguish a small estimated contrast measured precisely from a similar contrast measured imprecisely, or to determine whether the posted data are compatible with a broad range of values.

Why does the analysis population matter?

The primary endpoint description says the Stage 1 analysis included participants who completed the fMRI scan, had good-quality imaging data, and met an additional criterion that is not fully described. This is an analysis population defined by scan completion and data suitability, rather than a clear statement that every enrolled participant contributed to the endpoint. General explanation: excluding participants can affect both the number of observations and the interpretation of the result. If the likelihood of having usable data is related to participant characteristics or outcome values, an analysis restricted to usable scans may not represent all enrolled participants. The registry record does not report the number excluded, reasons for exclusion, or a comparison of included and excluded participants.

For a randomized comparison, the analysis population is also relevant to preserving the balance created by random assignment. General explanation: an intention-to-treat approach typically analyzes participants according to assigned group, while other approaches can use different inclusion rules. The registry record does not identify an intention-to-treat analysis or another named analysis population for the primary endpoint. It would be inappropriate to assign one based only on the study’s randomized design label.

How should the planning illustrations be understood?

The record describes sample-size illustrations as planning exercises based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For non-time-to-event outcomes, those illustrations are expressed as participants per arm. General explanation: such calculations explore how many participants might be needed under specified assumptions about an effect and statistical procedure. They are not observed outcomes, and they are not the same as the trial’s actual enrollment or analysis sample. They should not be described as observed power.

The record does not give a trial-specific sample-size justification or enough detail to establish that the planning assumptions were the assumptions used to design or conduct the study. It also does not report the numerical planning outputs in the registry record for this explanation. Therefore, the illustrations cannot be used to infer the study’s planned enrollment, actual allocation, or ability to detect a particular effect.

What role does over-dispersion play?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. It can make standard errors too small if the model fails to account for that extra variability, which can make confidence intervals too narrow and tests too optimistic. It is especially relevant to count outcomes in some models. The registered primary endpoint is a continuous mean contrast, and the registry record does not report an analysis model or evidence about over-dispersion. It should not be assumed to be a feature of this study’s endpoint.

The record lists five outcome measures but no analysis records. It does not identify a model for the primary measure, covariate adjustments, handling of repeated observations, or the standard-error method. Those methods are not reported in the registry record. A reader should therefore avoid treating any unreported calculation or model as part of the trial’s documented analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures. The primary endpoint description refers to a Stage 1 signal, while the brief study description gives broader aims concerning socioemotional and alcohol-related brain responses and neurofeedback. The registry record does not report a multiplicity procedure, such as a hierarchy among outcomes or an adjustment for testing several outcomes. It also does not report a statistical analysis plan that would clarify how the multiple measures were intended to be interpreted. Without that information, it is not possible to assess how the overall chance of false-positive findings was handled.

The registry lists zero analysis records. It therefore does not report which outcomes were analyzed, which comparisons were made, or whether any analysis was exploratory. The reason no analyses are listed is not reported in the registry record. The absence of analysis results should not be interpreted as evidence that there was no effect, nor as evidence that all possible effects were null.

Missing-data methods are also not reported. The primary outcome population is described as participants who completed the Stage 1 scan, had good-quality imaging data, and met an additional criterion whose wording is incomplete. The registry does not report how many participants failed those criteria, why data were unusable, whether missing data were imputed, or whether sensitivity analyses were performed. General explanation: missingness can affect an estimate when the chance that an observation is missing is related to participant characteristics or the unobserved outcome. The registry information is insufficient to assess that possibility.

The analysis population for the primary endpoint is not fully specified, and no participant flow for that analysis is available in the registry record. The number enrolled cannot establish how many contributed usable primary endpoint data. The record also does not state whether Stage 2 analyses used all randomized participants or another population. These omissions limit interpretation of both the results and the risk of bias from outcome availability.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The adverse-event figures are reported separately for four groups. The Stage 1 alcohol-use-disorder group lists 30 participants at risk for serious adverse events and 0 serious events; its other adverse event count is 0 among 30 at risk. The Stage 1 healthy control group likewise lists 30 at risk for serious adverse events and 0 serious events, with 0 other adverse events among 30 at risk.

The Stage 2 neurofeedback group lists 20 participants at risk for serious adverse events and 0 serious events. It reports 1 other adverse event among 20 at risk. The Stage 2 sham group lists 21 at risk for serious adverse events and 0 serious events, and reports 1 other adverse event among 21 at risk. The registry lists 0 deaths in each of the first three groups and 1 death in the Stage 2 sham group.

These are descriptive counts. The record does not report the event descriptions, timing, severity details beyond the serious-versus-other categories, or whether events were judged related to study procedures. The listed death should therefore not be attributed to the sham condition on the basis of this record. The counts also do not establish that groups had equivalent safety experience: the record does not report a statistical comparison, and the group sizes are limited. No serious adverse event terms are listed among the top serious terms.

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

The study addresses a question about socioemotional processing, alcohol-related cues, and the potential use of real-time fMRI neurofeedback. It includes both participants with alcohol use disorder and healthy control volunteers, and Stage 2 includes neurofeedback and sham groups. The primary endpoint is a specified imaging contrast measured during a task in the scanner. These elements establish the subject and broad structure of the research, but they do not establish an outcome.

The registry record does not report a numerical result for the primary endpoint or a comparison between the Stage 2 neurofeedback and sham groups. It provides no estimate of effect, confidence interval, p-value, or analysis population size for the primary endpoint. Consequently, the posted results do not show whether the measured BOLD contrast differed between groups, how large any difference might have been, or how precisely it was estimated.

General explanation: a study’s objective is a question to be investigated, not a finding. An intervention description indicates what was intended or assigned, not whether it changed the endpoint. Likewise, the presence of a randomized design label does not allow a treatment effect to be inferred without the analyzed outcomes and the methods used to compare groups. The completed status does not fill in those missing results.

The endpoint is an imaging signal in arbitrary units. Even if an estimate were available, interpreting its practical or clinical relevance would require context about the scale, its variability, and how it relates to outcomes meaningful to participants. The registry record does not report such a relationship. The signal should not be treated as a direct measure of alcohol consumption or as evidence of a clinical benefit.

The safety figures report event counts but not causal attribution or a comparative analysis. They can be read as reported counts within the listed groups, not as proof that an intervention caused or prevented an event. Overall, the record documents a research program and limited descriptive safety information, while leaving the principal statistical question unresolved in the posted results.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a registered scientific question and a reported result. The record describes a randomized, double-masked, parallel study and defines an imaging endpoint, but lists no analysis records. That makes it important to separate design information from evidence about an effect. Knowing the intended contrast does not reveal its observed value or uncertainty.

The primary outcome is also specific to Stage 1, where participants were assessed during a single scan before real-time active neurofeedback. The record separately describes Stage 2 neurofeedback and sham groups. Keeping those stages distinct avoids treating a pilot imaging measure as though it were a reported treatment comparison. It also highlights why an endpoint’s population and timing are central to interpreting any estimate.

Imaging endpoints can be technically dependent on data quality and scan completion. The registry’s restriction to participants with good-quality imaging data makes the analysis population especially relevant. Without counts of exclusions or information about missing scans, readers cannot assess how much the analyzed group may differ from everyone enrolled. This is a general concern in studies where an outcome depends on obtaining usable technical measurements.

The safety counts further illustrate the limits of descriptive data. A small number of recorded events, without event details or attribution, cannot establish a comparative safety pattern. Statistical interpretation requires more than comparing the appearance of counts; it requires attention to denominators, uncertainty, definitions, and study procedures.

For clinical researchers and biostatisticians, the central lesson is that transparent endpoint definitions and trial labels are useful but incomplete. Results need an estimate, a clearly described analysis population, an analysis method, and an account of missing data and multiplicity. Those details are not reported for the primary outcome in this registry record, so its statistical contribution cannot be evaluated from the posted results alone.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpreting this study from its registry record is the absence of a reported primary endpoint analysis. Although the endpoint is defined, the record gives no observed mean or standard deviation, analysis sample size, effect estimate, confidence interval, or test result. It also lists no analysis records. The direction, magnitude, and precision of the primary signal are therefore unknown from the posted results.

The endpoint description is restricted to Stage 1 participants who completed the fMRI scan and had good-quality imaging data, plus an additional criterion that is not fully described. The record does not report how many participants met these conditions or how many were excluded. It also does not give a complete account of missing or unusable imaging data. This makes it difficult to judge the representativeness of the analysis population.

The trial design labels identify randomization, masking, and a parallel model, but the registry does not describe the randomization method, allocation ratio, masking roles, or procedures for maintaining masking. Arm descriptions are truncated, leaving details of the feedback and sham procedures incomplete. The record does not report the trial’s statistical analysis plan, model specification, covariate adjustments, or handling of repeated measurements.

There are five registered outcome measures, but no reported multiplicity strategy or analysis results. The record does not state whether analyses were prespecified beyond the available endpoint wording, or how multiple outcomes were to be interpreted. Sample-size planning illustrations are described in general terms, but a trial-specific justification and numerical outputs are not reported in the registry record.

Safety reporting is limited to group counts. Event descriptions, timing, attribution, and comparative analyses are not reported. These limitations do not show that the study was poorly conducted; they describe what cannot be evaluated from the registry information available.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Response Modulation Hypothesis of Socioemotional Processing Associated With Alcohol Use Disorder — NCT03535129.
• Registry record last updated 2026-04-23; status last verified 2026-04.
• Results first posted 2026-04-23.
• 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

NCT03535129 is a completed, randomized, double-masked, parallel study listed as not applicable for phase, with enrollment of 101. The registry gives a start date of 2018-09-20 and a primary completion date of 2025-03-23. The study concerns socioemotional processing associated with alcohol use disorder and real-time fMRI neurofeedback.

The record describes a Stage 1 pilot scan in participants with alcohol use disorder and healthy control volunteers, and a Stage 2 comparison involving neurofeedback and sham groups among participants with alcohol use disorder. The primary endpoint is a Stage 1 mean BOLD contrast between negative socioemotional cues paired with alcohol versus neutral cues. The registry lists five outcome measures but zero analysis records.

Adverse-event counts are reported for four groups, including no serious adverse events and one death in the Stage 2 sham group. Event attribution and details are not reported. Because the primary endpoint results and analysis methods are absent, the posted record does not provide an estimate of the primary signal or a treatment-effect comparison.