Intranasal Vasopressin Treatment in Children With Autism: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intranasal Vasopressin Treatment in Children With Autism (NCT03204786), a randomized phase 2, phase 3 study. The primary outcome is Change From Baseline in Parent Rated Social Responsiveness Scale, Second Edition (SRS-2) Total Scores During Treatment..

2. Clinical Question

3. Trial Design

The registry classifies this as a randomized, quadruple-masked, parallel trial in Phase 2 and Phase 3. It records an enrollment of 157 and a completed status. The recorded start date is 2018-02-20, and the primary completion date is 2024-03-18. The registry identifies Stanford University as the sponsor. Further details about how randomization was conducted, who was included in quadruple masking, or how the sample size was justified are not reported in the registry record.

The arm descriptions specify different treatment sequences. The Vasopressin-Vasopressin group received vasopressin nasal spray for 8 weeks. The Placebo-Vasopressin group received placebo nasal spray for 4 weeks, followed by vasopressin nasal spray for 4 weeks. The Placebo-Placebo group received placebo nasal spray for 8 weeks, followed by a 4-week open-label extension of vasopressin. The active-treatment descriptions specify 16 international units twice daily. Because treatment changes over time in some groups, the sequence and the time point matter when interpreting any comparison.

The primary outcome timeframe is baseline, 4-week, and 8-week assessment. The listed changes are 4-week minus baseline and 8-week minus 4-week; the latter is an interval change, not a change from baseline to the end of 8 weeks. The baseline score is defined as the average of screening and baseline visits, with the average taken approximately 2 to 3 weeks after screening. The registry does not report the allocation ratio, adherence, treatment discontinuation, or the exact analysis model.

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: 323 participants were screened. 157 participants signed informed consent, and 108 were randomized.

Treatment Period 1 (4 Weeks)

Treatment Period 2 (4 Weeks)

Open-label Extension (4 Weeks)

Analysis population for the primary outcome, as defined in the registry: Participants with available data at the respective time point

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: Participants who were randomized and treated (received intervention)

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Parent Rated Social Responsiveness Scale, Second Edition (SRS-2) Total Scores During Treatment., measured over baseline, 4-week, 8-week.

The primary endpoint is change in the parent-rated Social Responsiveness Scale, Second Edition (SRS-2) total score, expressed as a T-score. The measure is intended to quantify social abilities and symptom levels. The registry states that lower scores mean better social abilities and higher scores correspond to greater symptom levels. It also describes the scale’s population reference: a T-score of 50 indicates the population mean, with a standard deviation of 10. The total-score range is described as 37 to above 90.

The registry places scores of 59 or lower within normal limits, scores from 60 to 65 in the mild range, scores from 66 to 75 in the moderate range, and scores of 76 or higher in the severe range. These categories help give scale values a clinical reference, but the primary analysis concerns change in the continuous total score rather than a change in category. A continuous outcome retains information about the size and direction of score changes instead of reducing them to category shifts.

The endpoint is reported as a least-squares mean with a standard error. The registry defines change at 4 weeks as the 4-week score minus baseline and change at 8 weeks as the 8-week score minus the 4-week score. Thus the two reported intervals answer different questions. The registry record does not report numerical estimates for either interval, so the magnitude and precision of the observed change cannot be assessed from the recorded primary outcome results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports the primary outcome as a least-squares mean with a standard error. It does not report the model used to obtain the least-squares mean, a treatment contrast, a confidence interval, or a p-value. The statistical concepts below are general explanations; they do not establish which procedures the trial team used.

What does a least-squares mean represent?

In general, a least-squares mean is a model-based estimate of a group mean. It can account for terms included in the fitted model and can therefore differ from a simple arithmetic average of observed values. The estimate is interpretable only in the context of the model, the analysis population, and the comparison being made. The model specification, included covariates, and contrast definitions are not reported in the registry record, so those details cannot be assessed.

What does the standard error describe?

In general, a standard error describes the sampling uncertainty of an estimated quantity. It is not the same as the spread of individual participant scores. A smaller standard error indicates a more precisely estimated mean under the model and its assumptions; a larger standard error indicates greater uncertainty. The registry names the standard error as the dispersion measure but does not give numerical estimates for the primary outcome. Without those values, precision cannot be judged.

How would a confidence interval help?

In general, a confidence interval gives a range of values compatible with the data and the statistical model at a stated confidence level. It conveys uncertainty about an estimate and is often more informative than a significance test alone. The registry record does not report a confidence interval or its confidence level for the primary outcome. It is therefore not possible to describe a plausible range for the treatment effect from the recorded outcome information.

Why do the change definitions matter?

The registry defines the first change as the 4-week score minus the baseline score, and the next change as the 8-week score minus the 4-week score. In general, a difference between successive visits describes change during that interval. It is not interchangeable with the total change from the original baseline. The second interval also follows different assigned treatment sequences across groups. Interpretation of any contrast would need to match the interval and treatment sequence being compared; the record does not provide the numerical contrasts.

What does randomization contribute?

In general, random assignment is intended to make treatment groups comparable, on average, with respect to factors measured and unmeasured at the time of assignment. It does not guarantee identical groups, and it does not correct for every later source of bias, such as missing outcome data or departures from assigned treatment. The registry classifies the trial as randomized but does not describe the randomization procedure, concealment, or analysis according to assignment. Those implementation details are not reported in the registry record.

How should masking be understood?

The registry labels the trial quadruple-masked. In general, masking can reduce the influence of treatment knowledge on participant reports, clinician assessments, and other trial processes. The record does not identify which four roles were masked or whether masking was maintained across the open-label extension. The open-label extension is explicitly described as open label, so results from that period would need to be considered separately from masked treatment periods.

What is the role of the planning illustration?

The planning illustration is based on the observed effect and assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes participants per arm for a stated fraction of the observed effect. In general, such calculations illustrate the sample size associated with specified assumptions; they are not observed power and do not show the probability that the completed trial detected an effect. The registry record does not report the trial’s own sample-size justification or the assumptions used in its original design.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 48 outcome measures and zero analyses in the results record. The primary outcome itself involves more than one time interval: change from baseline to 4 weeks and change from 4 weeks to 8 weeks. The record identifies multiple secondary outcomes, including clinical global impression, social-cognition tasks, parent-rated behavior and anxiety scales, and electrocardiogram measures. Considering several outcomes or time points raises a general multiplicity issue: the more statistical comparisons made, the greater the chance of at least one apparently unusual result by chance alone. The registry does not report a multiplicity adjustment, a hierarchy of outcomes, or which comparisons were considered confirmatory.

For the primary outcome, the registry record does not report a numerical result for either interval or a statistical comparison. It therefore does not support an assessment of how multiple comparisons were handled in the analysis. A multiplicity plan is not reported in the registry record.

The primary outcome population is described as participants with available data at the respective time point. The number of participants contributing to each estimate, reasons for missing data, and methods for handling missing observations are not reported in the registry record. In general, missing data can affect both precision and the interpretation of group comparisons, particularly if availability is related to participants’ characteristics or outcomes. The record does not specify whether any imputation, likelihood-based method, or sensitivity analysis was used.

The analysis population and whether participants were analyzed according to their randomized assignment are not reported in the registry record. The sample-size illustration uses equal allocation between two arms, but that planning assumption does not establish the allocation ratio or analysis population in the completed trial.

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 registry reports serious adverse events by treatment group and treatment period. The listed serious-event counts are zero for the Vasopressin-Vasopressin group in Treatment Period 1, with 22 at risk; the Placebo-Vasopressin group in Treatment Period 1, with 42 at risk; and the Placebo-Placebo group in Treatment Period 1, with 39 at risk. For Treatment Period 2, the serious-event counts are zero for the Vasopressin-Vasopressin group, with 21 at risk; the Placebo-Vasopressin group, with 38 at risk; and the Placebo-Placebo group, with 39 at risk. The open-label vasopressin group lists zero serious events, with 32 at risk. No deaths are listed in these groups.

These figures describe the recorded counts within each listed period; the groups and periods should not be combined into a single count. The record separately lists other adverse events, but does not provide event terms in the serious-event list. A zero count of serious events in a listed group does not establish that no adverse events occurred, nor does it by itself establish comparative safety. The registry record does not report detailed event descriptions, attribution, or the statistical method used for safety comparisons.

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

The available registry information establishes the trial’s randomized, quadruple-masked, parallel classification, its treatment sequences, and its primary endpoint definition. It also records serious adverse-event counts by group and period. These details help readers understand what the trial set out to measure and how the treatment schedules differed.

However, the registry record does not report numerical results for the primary SRS-2 outcome. It does not provide estimated changes, a treatment contrast, a confidence interval, or a p-value. As a result, the posted information cannot quantify the difference between vasopressin and placebo, indicate the precision of an estimate, or establish whether a statistical comparison met a criterion for significance. Missing results should not be interpreted as evidence of no difference.

The outcome is a parent-rated scale, and the registry explains how its T-scores correspond to social abilities and symptom levels. That information describes the meaning of the measure, not a result from the trial. The record also specifies two successive change intervals, which are not equivalent to a single baseline-to-endpoint change. The different treatment sequences and the open-label extension further limit any interpretation that ignores timing and assignment.

The adverse-event counts are descriptive. They report no serious events in the listed groups, but counts alone do not characterize all event types or establish the comparative safety of the treatment sequences. The registry does report other adverse-event counts, yet details about those events are not reported in the registry record.

Accordingly, the posted information supports a careful account of design, measurement, and recorded safety counts. It does not support a conclusion about the size or certainty of the primary treatment effect, nor a clinical recommendation.

13. Why This Trial Matters Statistically

This trial is statistically notable for its repeated outcome assessments and changing treatment sequences. The primary outcome is defined across two successive intervals, so a result for the first interval would address a different period from a result for the second. The placebo-then-vasopressin sequence and the placebo-only sequence also make it important to identify which groups and time points are being compared. Without clearly defined contrasts, a change estimate can be difficult to interpret as a treatment effect.

The endpoint is a parent-rated continuous measure with a stated direction and reference scale. Reporting a model-based mean alongside its uncertainty would help readers distinguish the estimated change from its precision. In the registry information recorded for this analysis, those numerical outcome results are absent. This makes the gap between a detailed endpoint definition and an interpretable treatment estimate especially important.

The trial also illustrates why outcome multiplicity, missing data, and analysis populations matter. The registry lists 48 outcome measures, while the primary endpoint has more than one interval. A clear analysis plan would help readers understand which comparisons were primary and how uncertainty from multiple testing was handled. Information about time-point-specific availability and missing-data methods would also help readers assess the robustness of estimates.

Finally, the safety record separates serious adverse events by treatment period and sequence. That structure is more informative than collapsing events across different exposure periods, but event counts alone do not provide a full safety analysis. Together, these design features show why transparent reporting of estimates, contrasts, uncertainty, and analysis methods is central to evaluating a clinical trial statistically.

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.

Several trial-specific details needed to interpret the primary outcome are not reported in the registry record. These include numerical estimates for the SRS-2 changes, group contrasts, confidence intervals, p-values, the fitted model, covariate adjustment, and the number of participants contributing at each time point. The record defines the endpoint and its time intervals but does not provide the inferential results needed to evaluate the comparative effect or its precision.

The record does not describe the randomization procedure, allocation ratio, masking roles, adherence, or treatment discontinuations. It does not report the age range or further participant characteristics in the information recorded for this analysis. These omissions limit assessment of how closely the participants and trial conduct can be characterized.

The registry lists multiple outcome measures, but a multiplicity plan and missing-data methods are not reported. The primary outcome population is defined by data availability at each time point; the consequences of that availability for the estimates cannot be assessed without participant counts and information about missing observations. The record also does not report the trial’s own sample-size justification or interim analyses.

The treatment sequences differ over time, and one arm includes an open-label extension. Findings from that period would not have the same masking conditions as findings from the earlier masked periods. The registry does not report a specific primary contrast that resolves these distinctions. Safety reporting is also limited: serious-event counts are given by group and period, but detailed event descriptions and attribution are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Intranasal Vasopressin Treatment in Children With Autism — NCT03204786.
• Registry record last updated 2026-06-04; status last verified 2026-05.
• Results first posted 2025-09-19.
• 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, quadruple-masked, parallel trial in Phase 2 and Phase 3, sponsored by Stanford University. It records an enrollment of 157, a start date of 2018-02-20, and a primary completion date of 2024-03-18. The listed sequences include vasopressin, placebo followed by vasopressin, and placebo followed by an open-label vasopressin extension.

The primary outcome is parent-rated SRS-2 total T-score change, defined for baseline to 4 weeks and for 4 weeks to 8 weeks. Lower scores indicate better social abilities. The registry record does not report numerical primary-outcome estimates or an inferential comparison. It lists serious adverse-event counts by group and period, with zero serious events in each listed group. Statistical-plan details, missing-data methods, and the trial’s own sample-size justification are not reported in the registry record.