Enhancement of Behavioral and Cognitive Outcomes in Autism Spectrum Disorder Via Neurostimulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Enhancement of Behavioral and Cognitive Outcomes in Autism Spectrum Disorder Via Neurostimulation (NCT05371912), a randomized na study. The primary outcome is The Effects of rTMS on Reciprocal Social Awareness.

2. Clinical Question

3. Trial Design

The study is a randomized, triple-masked, parallel-group trial of transcranial magnetic stimulation in autism spectrum disorder. The registry lists an enrollment of 16 and describes two arms: left inferior parietal lobule stimulation and right inferior parietal lobule stimulation. Each arm description says that half of the subjects would receive stimulation at its named location. The record does not explain who was masked or how masking was maintained.

The comparison is between stimulation locations. It is therefore important not to interpret it as a test of stimulation against no stimulation, unless other information establishes such a comparator; no such comparator is described in the registry record. The listed phase is NA. The sponsor is Christiana Care Health Services.

The study start date is 2022-03-15, the primary completion date is 2023-10-31, and the status is completed. These administrative details describe the registry timeline and status; they do not establish that outcome data were posted or that a particular analysis was conducted.

The primary outcome is described as a continuous measure, with the mean as its summary parameter and standard deviation as its dispersion measure. The registry gives a baseline and 5-week timeframe. It also lists secondary outcomes concerning verbal fluency and executive function, including measures using a Flanker task. Specific procedures for allocation, follow-up, adherence, and analysis 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.

Before assignment: All patients met the diagnostic criteria for autism spectrum disorder. We excluded all patients with history of seizures or metallic devices in the hedonic area.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects were randomized to receive right or left IPL stimulation.

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 The Effects of rTMS on Reciprocal Social Awareness, measured over at baseline and 5 weeks of rTMS.

The primary endpoint is reciprocal social awareness assessed using the Social Responsiveness Scale, Second Edition, Parent/Caregiver form. The registry describes a total raw score based on 65 items, each scored 0-3, with a total range of 0-195. Higher scores indicate greater social impairment, so a higher raw total represents a less favorable score on this instrument. The study reports raw totals rather than T-scores.

This type of measure is used to quantify social responsiveness and impairment through caregiver or parent ratings. A continuous score can describe variation across participants rather than reducing the outcome to a simple event category. Comparing scores at baseline and after 5 weeks of rTMS could describe change over the study period, while comparing change between the randomized groups could address whether the observed pattern differed by stimulation location.

However, the registry record does not report the group means, standard deviations, changes from baseline, or an inferential comparison for this endpoint. It also does not report whether the analysis used endpoint scores, change scores, or an adjusted model. The direction of the scale is clear, but the magnitude and precision of any group difference are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as continuous and names the mean as its summary parameter, with standard deviation as the dispersion measure. In general, a mean describes the central level of a continuous measurement across participants. A standard deviation describes how spread out individual measurements are around that mean. Together, these summaries can characterize a group's observed scores, but they do not by themselves establish whether groups differ reliably.

For this endpoint, the scale is a raw total from the Social Responsiveness Scale, Second Edition, Parent/Caregiver form. The record states that the total is built from 65 items scored 0-3 and ranges from 0-195. The direction is also specified: higher scores mean greater social impairment. Those properties help interpret a reported mean, but the registry does not give the actual means or standard deviations at baseline or after treatment.

A comparison could be expressed in more than one way. An analysis might compare scores at the later assessment, compare change from baseline, or model the repeated measurements while accounting for baseline values. These approaches can answer related but not identical questions. The registry record does not report which approach was used, nor does it present an estimate from any of them. The notation that the outcome was measured at baseline and 5 weeks of rTMS is a timeframe, not a description of the statistical model.

In general, a confidence interval gives a range of values compatible with the observed data under the assumptions of the analysis. It conveys uncertainty around an estimate, whereas a p-value addresses how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions held. Neither quantity is reported for the primary comparison in the registry record. Without an effect estimate and an uncertainty measure, the size and precision of a possible difference cannot be evaluated.

The trial is described as randomized, triple-masked, and parallel. In general, randomization is intended to make assigned groups comparable on average, while masking can limit some forms of expectation or assessment bias. A parallel design assigns participants to a group whose intervention is followed over the study period, rather than having each participant receive both study interventions in sequence. These design labels do not disclose the randomization procedure, the identities of masked parties, or the success of masking; those details are not reported in the registry record.

The record also includes a sample-size planning description. It states that the planning illustration uses a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. It distinguishes participant-per-arm planning for non-time-to-event outcomes from total-event planning for time-to-event outcomes. This is a planning framework, not evidence of observed power and not a report of the original trial's design justification. The numerical planning results and the trial's own sample-size justification are not reported in the registry record. Because the primary outcome is not reduced to a single comparison and no observed effect estimate is reported, the record does not permit a reader to evaluate a numerical planning illustration for this endpoint.

In general, a confidence interval can also be used to consider whether an estimate is compatible with a range of effects that would matter scientifically. Statistical significance alone would not establish importance, and a nonsignificant result would not establish equivalence. Such interpretation requires an estimate, its uncertainty, and a context for judging meaningful differences. The registry record does not provide a threshold for a meaningful change on this measure or the outcome results needed for that assessment.

Repeated assessments can create analytic choices about how to represent time and how to handle participants without complete measurements. In general, a model that uses repeated observations may account for within-participant correlation, but its appropriateness depends on the design and assumptions. No repeated-measures model, covariance structure, adjustment strategy, or missing-data method is reported in the registry record. These details should not be inferred from the fact that baseline and 5-week assessments were specified.

The registry lists five outcome measures and zero analyses. It names secondary outcomes involving verbal fluency and executive function, including a Flanker task, but does not give their numerical results or analysis details. The registry record also does not report an analysis population, a prespecified hierarchy of outcomes, or adjustment for multiple comparisons. These absences limit the ability to reconstruct the statistical analysis or assess how uncertainty was handled across outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies reciprocal social awareness as the primary outcome and lists secondary outcomes concerning verbal fluency and executive function. It reports five outcome measures overall and zero analyses. The primary outcome is flagged as involving several categories or time points and not being reduced to one comparison. The record therefore does not specify a single reported primary contrast on which to base an inference.

When a study evaluates multiple outcomes, time points, or contrasts, the chance of obtaining at least one apparently unusual result can increase. In general, a statistical plan may address this through a prespecified hierarchy or a multiplicity adjustment. Whether either approach was planned or used is not reported in the registry record. No adjusted or unadjusted outcome tests are presented, so no multiplicity strategy can be assessed from the posted results.

The registry record does not report how missing measurements were handled, whether all randomized participants were included in the analysis, or how the analysis population was defined. It also does not report numbers of participants with available measurements at each assessment. These details matter because missingness and exclusions can affect both the interpretation and the precision of a group comparison.

Without an analysis population, missing-data approach, and specified comparison, it is not possible to determine whether the intended randomized comparison was preserved in the outcome analysis. These omissions do not establish that data were missing or that a particular analysis was inappropriate; they mean the relevant information is not reported in the registry record.

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 registry reports serious adverse events for each stimulation group with 8 participants at risk and 0 affected. For other adverse events, it likewise reports 8 participants at risk and 0 affected in each group. The reported death count is 0 in each group. These are the safety figures recorded for the left and right inferior parietal lobule stimulation arms.

These counts should be read as registry-reported observations, not as proof that no adverse events of any kind occurred. The record does not describe the event collection procedures, observation window, severity definitions for other events, or completeness of safety follow-up. It also does not give event descriptions because no serious-event terms are listed. A zero count in the posted fields is distinct from evidence that a treatment has no risk.

The safety entries do not answer the primary social-awareness question. They also do not provide a detailed comparison of event timing or participant-level experience. The registry record supports the limited statement that the listed affected counts and deaths are zero in both groups; broader safety conclusions are not established by these figures alone.

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

The record does establish that a randomized, triple-masked, parallel-group study compared stimulation at the left and right inferior parietal lobule in autism spectrum disorder. It specifies a primary measure of reciprocal social awareness, the instrument used, the direction of scoring, and the baseline and 5-week assessment timeframe. These details make the intended research question understandable.

The record does not establish whether the groups differed on the primary outcome. It contains no reported group scores, change estimates, effect estimate, confidence interval, or test result for that comparison. A completed study status cannot fill that gap. Nor does the scale's range or score direction indicate what happened to participants' measured scores.

The results also cannot establish whether stimulation at either location is better than no stimulation, because the described comparison is between two active stimulation locations and no sham or no-stimulation arm is reported. The registry does not provide results for the listed secondary outcomes, so their contribution to the study's cognitive questions cannot be assessed either.

In general, a trial's estimate addresses the participants and procedures studied and is interpreted alongside its uncertainty, design, and limitations. Here, the missing outcome comparison prevents even a basic description of the direction or precision of the primary result. That absence is not evidence of no difference; it is an absence of a reported comparison in the registry record.

Accordingly, the statistical meaning of the posted information is chiefly about the study's design and measurement plan, not a demonstrated comparative outcome. The safety counts are also limited to the adverse-event fields. Any broader conclusion about efficacy, equivalence, clinical importance, or safety would go beyond what the registry record reports.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it illustrates the distinction between a well-defined research question and a reported answer. The registry gives a randomized comparison, identifies the two stimulation locations, and specifies a continuous primary measure with an interpretable direction. Those features provide a framework for understanding what an eventual analysis would need to compare.

At the same time, a design description cannot substitute for an outcome estimate. For a continuous measure, a reader needs the observed group summaries or a direct estimate of the between-group contrast, together with information about uncertainty. The registry record does not report these for reciprocal social awareness. Without them, there is no basis for judging the magnitude, direction, or precision of a difference.

The record also makes clear why a prespecified comparison matters when measurements are collected at more than one time point and multiple outcomes are included. A focused analysis plan can identify the primary contrast and explain how secondary results and missing measurements are handled. The registry does not report those details, and it flags the primary outcome as not reduced to a single comparison. This limits reproducibility and the reader's ability to interpret any analysis beyond the registry record.

The listed sample-size assumptions are another reason to separate planning from evidence. A planning illustration based on an observed effect is not the trial's own justification and is not observed power. Without the primary estimate and the numerical planning outputs in the registry record, that description cannot establish whether the study was designed to detect a particular difference.

The central statistical lesson is that registration details describe intended methods, while outcome estimates and their uncertainty are needed to evaluate comparative findings. Here, the former are more fully documented than the latter.

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 direct limitation for interpretation is that the registry record does not report the primary outcome values or a single comparison between the randomized groups. The record explicitly notes that the primary outcome has several categories or time points and is not reduced to one comparison. This prevents a reader from determining the observed direction, magnitude, or precision of the primary result.

The record describes a baseline and 5-week measurement but does not report the number of participants with measurements at each time, the amount of missing data, or how missing observations were handled. It does not identify the analysis population or specify whether the primary analysis compared follow-up scores, changes from baseline, or repeated measurements. These omissions make the analysis difficult to reconstruct.

Although the trial is described as triple-masked, the registry does not state which parties were masked or how masking was implemented. It also does not give detailed randomization procedures, intervention parameters, adherence information, or participant characteristics beyond the condition and group descriptions. These details are relevant to assessing design implementation and the context of any future results.

Secondary outcome names are listed, but numerical findings and analysis methods are not reported. The registry does not describe a multiplicity plan, a threshold for meaningful change on the primary scale, or the sample-size justification for the trial. Its planning assumptions do not replace these details and do not establish observed power.

Finally, the safety fields report zero affected counts, but event ascertainment and follow-up procedures are not described. These limitations concern what can be concluded from the registry record; they do not establish that the study lacked procedures or that its unreported analyses were not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Enhancement of Behavioral and Cognitive Outcomes in Autism Spectrum Disorder Via Neurostimulation — NCT05371912.
• Registry record last updated 2025-11-26; status last verified 2025-11.
• Results first posted 2025-11-26.
• 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

NCT05371912 is a completed, randomized, triple-masked, parallel-group study sponsored by Christiana Care Health Services. It enrolled 16 participants with autism spectrum disorder and compared transcranial magnetic stimulation at the left versus right inferior parietal lobule. The listed phase is NA.

The primary outcome was reciprocal social awareness measured with the Social Responsiveness Scale, Second Edition, Parent/Caregiver form, at baseline and 5 weeks of rTMS. Higher raw totals indicate greater social impairment. Secondary outcomes address verbal fluency and executive function.

The registry record does not report a primary outcome comparison or numerical results for the secondary outcomes. It reports zero affected participants for serious and other adverse events in each group and zero deaths. The record describes sample-size planning assumptions but does not report the study's own sample-size justification.