Intranasal Oxytocin for Infants With Prader-Willi Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intranasal Oxytocin for Infants With Prader-Willi Syndrome (NCT03245762), a randomized phase 1, phase 2 study. The primary outcome is Suck and Swallow Competency in Infants/Children With PWS Who Are in Nutritional Phase 1a.

2. Clinical Question

The clinical question is narrowly framed around swallowing function during a short treatment period in a specific nutritional phase. It is not a question about all infants or children with Prader-Willi Syndrome, all stages of the condition, or outcomes beyond the stated study period. Videofluoroscopic swallow studies were planned on treatment day 1 and on the day following the treatment morning of day 6, according to the brief summary. The primary-outcome timeframe is separately labeled baseline to day 5. These descriptions do not align exactly, and the registry record does not explain the difference.

The comparison is between assigned study treatments, rather than a comparison with no treatment. The record identifies randomization, masking, and parallel groups, but gives no further detail on how treatment assignment was generated or concealed. The question is whether the recorded swallow-study assessment indicates overall improvement, and whether the pattern differs between the treatment groups. The posted record does not establish that an observed difference is clinically important, nor does it provide enough outcome data to judge the size or precision of any difference.

3. Trial Design

The registry identifies this as a randomized, double-masked, parallel-group study in phase 1 and phase 2. Its title and brief description focus on infants and children with Prader-Willi Syndrome who are in nutritional phase 1a. The listed enrollment is 15. The study began on 2017-08-01, had a primary completion date of 2018-01-04, and is marked completed.

Participants were assigned to intranasal oxytocin or placebo. The arm descriptions specify 4 IU/day of the assigned spray each morning. A parallel design means the assigned groups receive their respective treatments during the study rather than switching between them. Randomization is intended, in general, to reduce systematic differences between groups at assignment. Masking is intended to limit the influence of treatment knowledge on participant care, assessments, or reporting. The record says the study was double-masked, but does not identify exactly who was masked or describe the procedures used to maintain masking.

The brief summary says videofluoroscopic swallow studies were to be performed on treatment day 1 and on the day following the treatment morning of day 6. The primary-outcome record labels the timeframe baseline to day 5 and describes the outcome as overall improvement on a swallow study. Because the timing descriptions differ, the precise analysis visit cannot be established from the registry record alone.

The registry record does not report the randomization method, allocation concealment, planned treatment duration in more detail, adherence information, or protocol deviations. It also does not report the analysis population or explain whether all randomized participants were included in the outcome analysis. Those omissions limit assessment of how closely the observed data, if available, would represent the planned randomized comparison.

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

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 Suck and Swallow Competency in Infants/Children With PWS Who Are in Nutritional Phase 1a, measured over baseline to day 5.

The primary endpoint is labeled “Suck and Swallow Competency in Infants/Children With PWS Who Are in Nutritional Phase 1a.” The record describes the measure as overall improvement on a swallow study and uses participants as the unit. It is therefore a participant-count outcome: the intended observation is whether a participant is classified as having improved, rather than a continuous score or a time-to-event measurement.

Swallow competency is relevant to the stated question because the study concerns feeding-related function in infants and children at this nutritional phase. A swallow study provides an assessment tied to swallowing, while comparing baseline with a later assessment gives a way to evaluate change during the treatment period. The registry brief summary specifically mentions videofluoroscopic swallow studies at treatment day 1 and around day 6.

The record does not define the criteria for “overall improvement,” identify the categories underlying the outcome, or report how disagreements in classification would be handled. It also does not provide a numerical result for this endpoint that can be expressed as one comparison. The timeframe label, baseline to day 5, differs from the brief-summary description of the day following the treatment morning of day 6. The registry record does not clarify the endpoint definition or timing further. These details matter because interpretation depends on what counts as improvement and when that judgment is made.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help frame the registry information, even though it does not report enough primary-outcome data for a numerical comparison.

What does randomization contribute?

In general, randomization assigns participants to study groups using a chance-based process. Its purpose is to reduce systematic differences in measured and unmeasured characteristics at the start of a trial. It does not guarantee that groups will be identical, particularly in a small study, and it does not remove the need to report group characteristics and outcome data. The registry identifies the study as randomized but does not report the sequence-generation method, allocation concealment, or other implementation details. The success of those procedures therefore cannot be assessed from the record.

What does masking contribute?

In general, masking can reduce the chance that expectations influence treatment delivery, outcome assessment, or participant reporting. The record labels this study double-masked, but does not say which people were masked or how the masking was maintained. The presence of a masking label is useful design information, but it is not a substitute for details about implementation or assessment procedures.

How should a participant-count endpoint be understood?

The primary outcome is described as a count of participants with overall improvement on a swallow study. For a binary outcome, each participant is classified into one of two states for a particular analysis, such as improvement or no improvement. However, the registry analysis information says that the primary outcome involved several categories or time points and was not reduced to one comparison. Thus, the simple binary framing does not supply a single outcome count or contrast for interpretation. The record does not define the categories or say how they were combined.

In general, a treatment comparison for a binary outcome can be expressed in multiple ways, including a difference in event proportions or a relative measure. Those measures answer related but distinct questions. The choice should follow the analysis plan and outcome definition. No such comparative measure is reported in the registry information, so none should be inferred.

What would a confidence interval tell a reader?

In general, a confidence interval conveys the statistical uncertainty around an estimated effect. A narrower interval indicates greater precision under the statistical model, while a wider interval indicates more uncertainty. A confidence interval does not by itself establish clinical importance, eliminate bias, or prove that a result is true. For this study, the registry record does not report an effect estimate or confidence interval for the primary outcome, so precision cannot be evaluated.

What does a p-value contribute?

In general, a p-value summarizes how incompatible the observed data are with a specified null hypothesis under the assumptions of the analysis. It does not measure the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The record does not report a primary-outcome p-value or the statistical test used. No significance judgment can therefore be made from the available outcome description.

How should sample-size planning illustrations be read?

The planning assumptions described for the sample-size illustration are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is based on the observed effect, with the effect to detect expressed as a stated fraction of that effect. It is a planning exercise, not the trial's own design justification, and it is not observed power. The registry record does not report the protocol's sample-size justification or any calculated participant requirements in the registry record used for this analysis. A planning illustration cannot replace reporting of the trial's actual outcome estimates and uncertainty.

In general, planning calculations depend on assumptions about the effect size, variability or event rate, allocation, and analysis method. If an observed effect is used as the starting point, the illustration is conditional on that estimate and its uncertainty. It should not be interpreted as a retrospective measure of whether the completed study had a meaningful chance of detecting an effect.

Why does endpoint timing matter?

A change-from-baseline analysis depends on a clear definition of baseline and follow-up. The brief summary refers to change from baseline to the morning of day 6 and describes swallow assessments on treatment day 1 and the day following the treatment morning of day 6. The endpoint timeframe is labeled baseline to day 5. The registry record does not reconcile those descriptions. This leaves uncertainty about the exact visit and contrast represented by the endpoint label.

In general, a statistical analysis should follow a prespecified endpoint definition and account for the data structure, including repeated assessments when relevant. The record does not report whether the outcome was analyzed as a single follow-up classification, as change across assessments, or using another method. Without that information and the underlying results, a reader cannot reproduce or fully evaluate the primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was addressed. Multiplicity arises when several outcomes, categories, time points, or comparisons are assessed. In general, making many statistical tests can increase the chance of obtaining an apparently notable result by chance if the testing strategy is not accounted for. Whether any adjustment or hierarchy was planned for this study is not reported in the registry record.

The primary outcome is described as having several categories or time points and was not reduced to one comparison. The registry record does not identify which categories or time points were included in the analysis, how they were ordered, or whether one was designated as the principal contrast. It also does not report an analysis plan that would clarify how such choices were made. A single p-value or effect estimate should not be reconstructed from an outcome description that does not specify the comparison.

Missing-data handling is also not reported in the registry record. The record does not state how many participants had an assessable primary outcome, whether any observations were missing, or how missing observations were handled. In general, missingness can affect interpretation when the chance of having an observed outcome is related to group assignment or participant outcome. Different assumptions and methods can lead to different estimates, so transparent reporting is important.

The analysis populations are not reported in the registry record. It is not stated whether the primary analysis included all randomized participants, only participants who completed treatment, or another defined group. The total enrollment does not establish the endpoint denominator. These omissions prevent assessment of the analysis set, missingness, and robustness of the primary comparison.

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.

The safety record lists serious adverse events for the intranasal oxytocin group with 10 participants at risk and 0 affected, and for the IN-placebo group with 5 participants at risk and 0 affected. It also lists other adverse events with 10 at risk and 0 affected in the intranasal oxytocin group, and 5 at risk and 0 affected in the IN-placebo group. Deaths are listed as 0 in each group.

These are descriptive registry counts. “At risk” indicates the denominator used in the safety listing; it should not be substituted for the primary-outcome analysis population. The record does not explain the safety observation window or provide event-level detail. The listed zeros mean that no events of those types were reported in these group entries, not that the possibility of such events has been ruled out. In general, a lack of reported events in a small study can leave substantial uncertainty about uncommon harms. The safety counts also do not answer the primary question about swallow competency.

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

The study is relevant as a randomized comparison of intranasal oxytocin and placebo in infants and children with Prader-Willi Syndrome who were in nutritional phase 1a. It focuses on a defined functional outcome, suck and swallow competency, assessed by swallow study during a short period. Its design features—randomization, masking, and parallel groups—are pertinent to interpreting a treatment comparison, although the registry does not report implementation details.

What the registry record does not establish is whether competency improved more in one group, how large any difference was, or how uncertain that difference may be. The primary-outcome information is not reported as a single comparison, and no group-specific efficacy results, effect estimate, confidence interval, or p-value are available in the record summarized for this analysis. Thus, neither a positive nor a null efficacy conclusion is supported by these registry entries.

The safety listing records no serious adverse events, other adverse events, or deaths in either group. Those entries describe what was reported in the registry, rather than proving that no risk exists. The study's listed enrollment and safety denominators also do not establish how many participants contributed to the primary outcome.

The endpoint timeframe is not entirely consistent across the registry descriptions: one refers to baseline to day 5, while the brief summary describes change to the morning of day 6 and assessments around that time. The record does not resolve this discrepancy. Interpretation of a change outcome depends on knowing exactly when measurements were made and how improvement was defined.

The appropriate reading is therefore limited: the record documents a trial design and a planned clinical question, together with descriptive safety counts, but it does not provide a usable primary efficacy comparison. This is not evidence that the treatment does or does not affect the endpoint; it is a limit on what can be inferred from the registry information reported.

13. Why This Trial Matters Statistically

This trial illustrates how a focused clinical question can be paired with an outcome that is directly tied to the population and treatment period under study. Suck and swallow competency is the stated functional focus for infants and children with Prader-Willi Syndrome in nutritional phase 1a. The randomized, double-masked, parallel design is intended to support a comparison between oxytocin and placebo rather than relying on change in one group alone.

It also demonstrates why outcome reporting must go beyond naming an endpoint. Readers need the operational definition of improvement, the assessment timing, the number of participants contributing data, and the group-specific results. In this record, the endpoint description does not specify the improvement criteria, the outcome information involves several categories or time points, and no single comparative result is reported. The difference between the baseline-to-day-5 label and the day-6 description further complicates interpretation.

These are not merely technical details. A treatment effect estimate and its uncertainty are necessary to distinguish a potentially important signal from a result that remains compatible with a wide range of effects. Without those, the clinical question remains unanswered by the reported primary-outcome information. The safety entries are useful as descriptive data, but cannot substitute for efficacy results or establish the absence of risk.

The example also highlights the distinction between a trial's results and a planning illustration. Sample-size illustrations rely on stated assumptions and are not observed power. They cannot repair missing outcome reporting or establish what the completed trial found. Clear reporting of the analysis plan, outcome definitions, timing, missing-data handling, and estimates with uncertainty is essential for readers to evaluate evidence accurately.

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 limitations affect interpretation of the registry record. Most importantly, no single primary-outcome comparison is reported. The outcome information is described as involving several categories or time points, and the record does not provide the underlying group counts, a comparative estimate, or an uncertainty interval. The endpoint therefore cannot be evaluated for direction, magnitude, or precision.

The outcome definition is also incomplete. “Overall improvement” is not accompanied by criteria explaining how improvement was determined or how categories were assigned. The registry gives different timing descriptions: the primary outcome is labeled baseline to day 5, while the brief summary refers to the morning of day 6 and describes assessments on treatment day 1 and around day 6. The registry record does not clarify which timing was used for the primary analysis.

Although the study is identified as randomized and double-masked, the record does not report the randomization procedure, allocation concealment, who was masked, or how masking was maintained. The analysis population, primary-outcome denominators, missing-data methods, and handling of protocol deviations are also not reported in the registry record. These gaps make it difficult to assess risk of bias and the relevance of any unreported outcome data.

The listed enrollment is 15, but it does not reveal the number with an assessable primary endpoint or how participants were distributed for efficacy analysis. Safety denominators are reported separately and should not be treated as outcome denominators. Finally, the registry record does not report the trial's statistical analysis plan or sample-size justification. The planning assumptions described for an illustration do not supply those missing design details.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Intranasal Oxytocin for Infants With Prader-Willi Syndrome — NCT03245762.
• Registry record last updated 2020-03-26; status last verified 2020-03.
• Results first posted 2019-06-25.
• 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 identifies NCT03245762, “Intranasal Oxytocin for Infants With Prader-Willi Syndrome,” as a completed randomized, double-masked, parallel-group study in phase 1 and phase 2. It lists University of Florida as sponsor, enrollment of 15, a start date of 2017-08-01, and a primary completion date of 2018-01-04.

The study compared intranasal oxytocin, 4 IU/day by nasal spray each morning, with placebo by nasal spray at the same stated daily dose. Its primary outcome concerns suck and swallow competency in infants and children with Prader-Willi Syndrome in nutritional phase 1a. The record describes overall improvement on a swallow study but does not report a single comparative primary-outcome result. Its timing descriptions differ between baseline to day 5 and an assessment around day 6.

The safety entries report 0 serious adverse events, 0 other adverse events, and 0 deaths in each listed group. Analysis populations, missing-data methods, and further statistical-plan details are not reported in the registry record.