A Pharmaco-imaging Approach to Predicting Social Functioning and Clinical Responses to Oxytocin Administration in Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pharmaco-imaging Approach to Predicting Social Functioning and Clinical Responses to Oxytocin Administration in Schizophrenia (NCT03900754), a randomized phase 2 study. The primary outcome is Social Functioning Score.

2. Clinical Question

The registry’s rationale is that social-functioning deficits are important in schizophrenia and are not necessarily addressed by improvement in other symptom domains. That rationale explains why the investigators chose a functional measure and a brain-imaging approach; it is not itself evidence of an effect. The posted record gives a study question and design, but the outcome results needed to answer that question are not reported in the registry record.

3. Trial Design

This was a Phase 2 randomized, double-masked, parallel trial sponsored by the VA Office of Research and Development. The registry lists an enrollment of 26 and the condition as schizophrenia. The recorded study start was 2020-01-13, and the primary completion date was 2024-01-31. The status is terminated. The reason for termination and whether the planned enrollment was reached are not reported in the registry record.

The intervention listings include oxytocin and placebo. The arm descriptions specify intranasal oxytocin at 20IU or 40IU and saline as placebo. The record’s adverse-event groups use four arm labels for each of two phases, but it does not map those labels to the listed doses and comparator. The actual allocation ratio, sequence-generation method, and concealment procedures are not reported. “Double” masking is recorded, but the identities of the masked parties and the procedures used to maintain masking are not described.

The study description distinguishes an fMRI phase and a chronic phase. The primary outcome’s timeframe says the full baseline assessment occurred before treatment, that assessment was not collected during the fMRI phase, and that a partial assessment was collected before the start and at the end of three weeks of daily administration in the chronic phase. The record does not explain how participation or treatment proceeded between phases, or whether the same participants contributed to both phases.

The study aimed to examine brain activation in relation to behavioral effects and to predict individual clinical response. Specific imaging tasks, acquisition details, predictive modeling procedures, and the planned statistical comparisons are not reported in the registry record. The trial’s status and the existence of a stated study objective do not establish that all planned procedures or analyses were completed.

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

Analysis population for the primary outcome, as defined in the registry: Data for an individual was only included if both assessment timepoints were completed in full (i.e. no missing values)

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.

Population: Only individuals who completed all outcome assessment timepoints were included in the results calculation

6. Primary Endpoint

The registry lists the primary outcome as Social Functioning Score, measured over Baseline visit: Full assessment is collected prior to any treatments fMRI phase: assessment not collected Chronic phase: partial assessment collected before the start (A1) and at end (A2) of 3 weeks of daily administration.

The primary endpoint was the Social Functioning Scale global summary score. The registry describes this as a 79-item semi-structured interview-based assessment, with a scale from 0 for lower functioning to 90 for higher functioning. It identifies the global summary score as the primary outcome. The record does not report observed scores, changes, group summaries, or a treatment-effect estimate.

The endpoint is relevant to the stated research question because the study focuses on social functioning rather than only on symptoms such as hallucinations or delusions. The registry’s rationale highlights motivation, emotional expression, and understanding other people’s mental states as challenges that can affect interpersonal interactions and community relationships. These statements explain the clinical motivation for measuring social functioning; they should not be read as trial findings.

The registry expected the social-engagement, interpersonal-communication, and prosocial subscales to change over three weeks, while other subscales, such as employment, were not expected to change and were not collected during the chronic period. The description says the full assessment was collected at baseline, but a partial assessment was used at the chronic-phase assessments. No outcome values for either the global score or the subscales are reported in the registry record, so the scale’s direction and intended use can be described, but the observed pattern cannot.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies randomization, double masking, and a parallel design. It does not report the specific statistical analysis plan. The methods used for the primary comparison, adjustment for baseline scores, handling of repeated measurements, or modeling of imaging and behavioral data are not reported in the registry record. The statistical concepts below are general explanations, not descriptions of analyses confirmed for this trial.

What does randomization contribute?

General: randomization assigns participants to study groups using a chance-based process. When implemented as planned, it is intended to reduce systematic differences between groups at the start of a trial, including differences that may not have been measured. Randomization does not guarantee that every characteristic will be balanced in a small study, and it does not remove the need to report group sizes, baseline information, and the analysis used. Although this trial is recorded as randomized, the sequence-generation and allocation-concealment methods are not reported in the registry record.

What does a parallel design mean?

General: in a parallel design, participants are assigned to a group and comparisons are made across groups rather than each participant receiving every study condition in a crossover sequence. The registry identifies this trial as parallel and lists oxytocin and saline placebo. The record does not describe the exact group structure in enough detail to map all listed doses to the four arm labels used in the safety listings. It also does not report the allocation ratio. Equal allocation appears among the assumptions for planning illustrations, but that assumption is not evidence of the actual trial allocation.

How should the primary scale be understood?

The registry specifies the primary outcome as a mean Social Functioning Scale score and describes its dispersion as the full range. General: a mean is a measure of the center of a set of values. A full range describes the lowest and highest observed values, so it can show the overall spread but may be strongly influenced by extreme observations. The registry does not report observed means or ranges, and no analysis estimate is available to interpret. The stated scale runs from 0 for lower functioning to 90 for higher functioning; that direction is needed to interpret the sign of a change if results are reported.

Why do repeated assessments matter?

The primary outcome timeframe distinguishes baseline, an fMRI phase, and a chronic phase. It says the assessment was not collected during the fMRI phase, while a partial assessment was collected before and at the end of three weeks of daily administration in the chronic phase. General: repeated measurements can be analyzed by comparing changes over time, by adjusting a later measurement for baseline, or by using a model that represents multiple observations per participant. These approaches answer related but not identical questions and rely on different assumptions. The registry does not state which approach was planned or used, so no specific analysis method should be attributed to the investigators.

What do estimates and uncertainty convey?

General: an effect estimate quantifies a contrast, such as a difference between groups or a difference in change over time. Its interpretation depends on the outcome scale, the direction of the contrast, and which participants and timepoints are included. A confidence interval indicates the range of values compatible with the data and model at a chosen confidence level. It helps communicate precision, but it does not correct for bias, missing observations, or an inappropriate model. The registry reports no primary-outcome estimate or confidence interval, so the size and precision of a treatment contrast cannot be assessed.

General: a p-value is calculated under a statistical model and a null hypothesis. It is not the probability that the null hypothesis is true, and it does not measure the size of an effect. When multiple outcomes, timepoints, or comparisons are examined, the chance of at least one apparently unusual result can increase unless the analysis plan addresses multiplicity. The registry lists four outcome measures and identifies a primary outcome, but it does not report the planned testing hierarchy or any completed analyses.

What do the planning assumptions tell the reader?

The registry describes sample-size illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. General: such calculations illustrate how a hypothetical target effect and design assumptions relate to a sample size under a chosen model. They are not the number of participants observed in an analysis, do not establish the original trial’s sample-size justification, and are not observed power. The original sample-size rationale is not reported in the registry record. The illustrations cannot substitute for an effect estimate and uncertainty interval based on the trial data.

For time-to-event outcomes, the registry’s general planning note describes event totals; the primary endpoint is a score, not a time-to-event measure. No primary result or analysis is reported, so the available statistical information supports a description of the intended design and measurement, rather than a quantitative treatment-effect interpretation.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome, the Social Functioning Scale global summary score, and lists the Clinical Assessment Interview for Negative Symptoms score as a secondary outcome. It also reports four outcome measures overall, but does not detail all of them in the available record. The primary outcome description distinguishes multiple subscales and different assessment periods. The registry notes that the primary outcome has several categories or timepoints and does not reduce it to one comparison. The statistical plan for choosing or prioritizing comparisons is not reported in the registry record.

General: multiplicity arises when several outcomes, timepoints, subscales, or treatment contrasts are tested. Considering many tests can increase the chance of a nominally notable finding occurring by chance. A prespecified hierarchy or adjustment can help define how those tests should be interpreted. The registry does not report whether such a plan was specified or used. It also lists zero analyses, so no multiplicity-adjusted or unadjusted outcome findings are reported.

The primary outcome description says data for an individual were included only if both assessment timepoints were completed in full. This is a complete-assessment requirement for those data. The number of participants excluded under that rule, the amount and pattern of missing data, and any sensitivity analyses are not reported in the registry record. Whether imputation or another missing-data method was used is also not reported.

The analysis populations are not reported. In particular, the registry does not say how many randomized participants were included in the primary analysis or whether analysis followed assignment regardless of treatment received. The enrollment of 26 should not be treated as the denominator for every outcome, phase, or safety group. Without analysis populations and denominators, outcome estimates and missing-data sensitivity cannot be evaluated.

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 listing separates fMRI-phase and chronic-phase groups, using four arm labels in each phase. For each phase, the listed numbers at risk are 2, 2, 6, and 3 across Arm 1 through Arm 4. No serious adverse events are listed in any of these groups, and deaths are listed as 0 throughout. In both phases, one other adverse event is listed in Arm 3; the other groups have 0. The specific non-serious event term is not reported in the registry record, and the top serious-event terms list is empty.

These counts should be read as registry-reported group counts, not as evidence about comparative risk. The arm labels are not mapped in the record to oxytocin dose or placebo, so the counts cannot be attributed to a particular treatment from this listing. The small numbers at risk also mean that counts alone provide limited information about how frequently events occurred in a broader population. No event rates, comparative safety estimates, or uncertainty intervals are reported.

The fMRI and chronic-phase listings are presented separately. The registry does not explain whether the same people could appear in both phases, so the counts should not be added or treated as distinct participants. Zero serious events in these listings means that none were recorded in those groups; it does not establish that serious events are impossible or rule out uncommon risks. The cause of termination is not reported, and no connection between termination and safety can be inferred.

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

The registry record describes a trial designed to investigate oxytocin, social functioning, and brain activation in schizophrenia. It specifies a randomized, double-masked, parallel Phase 2 design, oxytocin dosages of 20IU or 40IU, saline placebo, and a primary social-functioning score. These details establish the study’s intended question and measurement framework.

They do not establish an answer to the treatment question. No primary outcome values, group comparisons, effect estimates, confidence intervals, or p-values are reported in the registry record. The record also lists zero analyses. It is therefore not possible to determine whether scores changed, whether groups differed, or how uncertain an estimated difference would be. The absence of reported outcome estimates is not evidence that there was no effect, and it is not evidence that an effect occurred.

The enrollment entry of 26 is not a substitute for analysis denominators. The endpoint description requires both assessment timepoints to be complete for an individual’s data to be included, but the number meeting that requirement is not reported. The terminated status does not explain whether the planned sample size or analyses were completed, or why the study ended.

The safety listings record no serious adverse events and no deaths in the listed groups, along with one other event in Arm 3 in each phase. These counts are limited to the registry’s listed groups and do not identify the treatment corresponding to each arm. They cannot establish comparative safety or exclude events not captured in the record.

General: clinical interpretation depends on both the estimated effect and its precision, as well as the quality and completeness of the underlying data. A design and rationale can explain why a trial was undertaken, but they cannot replace results. The defensible conclusion from the registry is that the study question and endpoint are described while the evidence needed to judge the primary comparison is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining a functional clinical outcome with a stated interest in brain activation and individual response prediction. The primary measure is a global social-functioning score, while the rationale also describes social engagement, interpersonal communication, and prosocial behavior. The registry’s stated aim is to examine whether brain activation can help explain behavioral effects and predict response. Those aims raise questions about how clinical outcomes, imaging measures, timepoints, and predictive analyses are connected.

That complexity makes a prespecified analysis plan important. Multiple subscales and assessment periods can support different comparisons, and a prediction objective requires clear definitions of the predictors, outcome, and evaluation approach. The registry record does not report the analysis plan or predictive modeling methods. It also lists zero analyses, so no conclusion about prediction or associations between brain activation and clinical response is available.

The complete-assessment rule for the primary outcome is also relevant. Requiring both timepoints can make the analysis depend on who completed both assessments. The registry does not report how many participants met the requirement or how missing observations were handled. Those details matter for understanding the analysis population and the extent to which reported results, if available, would represent all randomized participants.

Finally, the terminated status and enrollment of 26 frame the scale of the study record, but do not explain what was completed or why the trial ended. The sample-size illustrations use stated assumptions, but they do not establish the original design rationale or observed statistical power. In statistical terms, the registry captures a scientifically specific question, yet does not report the estimates needed to judge effect size, precision, or the relationship between the imaging and clinical aims.

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 most important limitation for interpreting the trial is that the registry record does not report primary-outcome results or analyses. It gives no observed Social Functioning Scale scores, treatment contrasts, uncertainty intervals, or analysis denominators. The stated enrollment of 26 cannot resolve these gaps, particularly because the outcome description says that both assessment timepoints had to be completed in full for an individual’s data to be included.

The record describes different assessment procedures across baseline, the fMRI phase, and the chronic phase. The fMRI-phase assessment was not collected, and the chronic-phase measure was partial. The timing and role of the fMRI phase relative to the chronic phase, and whether the same participants contributed to both, are not explained. This limits interpretation of how the measurements were intended to connect.

The arm descriptions list two oxytocin dosages and saline placebo, but the four arm labels in the adverse-event record are not mapped to those conditions. The allocation ratio, masking procedures, and details of dose assignment are not reported. The reason for termination and whether planned enrollment or analyses were completed are also not reported.

The registry lists four outcome measures, but does not provide a full account of all measures, the intended testing hierarchy, or the statistical methods. It does not report how missing data beyond the complete-assessment rule were handled, or define the analysis populations. These omissions prevent assessment of multiplicity, missing-data sensitivity, and the robustness of any treatment comparison. No assumption about those procedures should be made from the design label or study rationale.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Pharmaco-imaging Approach to Predicting Social Functioning and Clinical Responses to Oxytocin Administration in Schizophrenia — NCT03900754.
• Registry record last updated 2026-01-20; status last verified 2025-12.
• Results first posted 2026-01-20.
• 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 describes NCT03900754, a randomized, double-masked, parallel Phase 2 study sponsored by the VA Office of Research and Development. The condition is schizophrenia, the listed enrollment is 26, and the status is terminated. The recorded start date is 2020-01-13, with primary completion on 2024-01-31. Intranasal oxytocin at 20IU or 40IU was compared with saline placebo.

The primary outcome was the Social Functioning Scale global summary score, described as a 79-item assessment with a range from 0 for lower functioning to 90 for higher functioning. The registry also lists the Clinical Assessment Interview for Negative Symptoms score as a secondary outcome. It describes a baseline assessment and a partial assessment before and after three weeks of daily administration in the chronic phase.

Outcome analyses and primary results are not reported in the registry record. The termination reason, analysis populations, missing-data methods, and statistical plan are also not reported. The safety listings record no serious adverse events or deaths in the listed groups.