This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for The Impacts of Theta-burst Stimulation on Children and Adolescents With Autism Spectrum Disorder (NCT03621189), a randomized na study. The primary outcome is Changes of Total Scores of Social Responsiveness Scale.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03621189 |
| Phase | NA |
| Condition | Autism Spectrum Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 80 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Chang Gung Memorial Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Children and adolescents with autism spectrum disorder. The registry record does not report further details about the enrolled participants, such as an age range or baseline clinical characteristics.
Intervention
Real intermittent theta-burst stimulation over the posterior superior temporal sulcus. The Active-Active group received real stimulation for 8 weeks, 2 days per week.
Comparator
The Sham-Active group received sham stimulation for 4 weeks, 2 days per week, followed by real stimulation for 4 weeks, 2 days per week. The sham procedure used a coil tilted one-wing 90° off the head.
Primary question
The trial planned to assess changes in total Social Responsiveness Scale scores at baseline, during treatment, after treatment, and at follow-up. The registry record does not report numerical results for these scores or a single comparison between the groups.
The central statistical question is whether the two treatment sequences were associated with different patterns of Social Responsiveness Scale scores over the specified assessment times. The intervention was delivered over the posterior superior temporal sulcus, and the comparator was not a sham-only group throughout the full study period: participants in the Sham-Active group later received real stimulation. Consequently, the trial's design concerns the sequence of sham and real stimulation as described in the registry, rather than a comparison of real stimulation with no treatment over the entire period.
The record identifies the Social Responsiveness Scale as a measure of autism clinical severity, with lower scores described as indicating better social responsiveness. It lists additional behavioral and imaging outcomes, including accuracy on the Frith-Happe Animation and Eyes tasks, functional MRI, resting-state fMRI, and diffusion tensor imaging. Those outcomes provide other planned perspectives on the intervention, but their numerical results are not reported in the registry record either.
3. Trial Design
The registry describes a randomized, double-masked, parallel-group trial with an enrollment of 80. Its status is completed. The record lists the study start as 2016-11-02 and primary completion as 2019-04-17. It identifies Chang Gung Memorial Hospital as the sponsor and autism spectrum disorder as the condition under study. The phase is recorded as NA.
The two groups differed in the sequence of stimulation. Participants in Active-Active received real intermittent theta-burst stimulation over the posterior superior temporal sulcus for 8 weeks, 2 days per week. Participants in Sham-Active received sham stimulation at that site for 4 weeks, 2 days per week, then real stimulation for 4 weeks, 2 days per week. The record describes the sham procedure as use of a coil tilted one-wing 90° off the head. It does not provide additional details about implementation of randomization or masking, including which roles were masked.
The primary outcome was change in total Social Responsiveness Scale scores. Assessments were listed at baseline, during treatment at 4 weeks after baseline, after treatment at 8 weeks after baseline, and at a follow-up 4 weeks after post-treatment. The registry identifies the outcome as a mean with standard deviation, but does not provide numerical outcome values or a reported comparison of the groups.
The record also lists secondary outcomes involving behavioral task accuracy and brain imaging. Although it reports seven outcome measures, it lists no analyses. The specific analysis plan, allocation ratio, eligibility criteria, and sample-size justification are not reported in the registry record. The record's enrollment figure is not enough by itself to establish how many participants contributed data to each outcome or assessment.
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: Of the total 80 patients, 5 withdrew from the study.
Overall Study
| Stage | Active-Active | Sham-Active |
|---|---|---|
| STARTED | 40 | 40 |
| COMPLETED | 40 | 35 |
| NOT COMPLETED | 0 | 5 |
Reasons for not completing this period:
| Reason | Active-Active | Sham-Active |
|---|---|---|
| Withdrawal by Subject | 0 | 3 |
| Physician Decision | 0 | 2 |
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.
| Characteristic | Unit | Active-Active | Sham-Active | Total |
|---|---|---|---|---|
| Participants analysed | 40 | 35 | 75 | |
| Age, Continuous | years | 13 (SD 2.8) | 12.5 (SD 2.9) | 12.8 (SD 2.9) |
| Sex: Female, Male: Female | Participants | 5 | 5 | 10 |
| Sex: Female, Male: Male | Participants | 35 | 30 | 65 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Full scale intelligence | units on a scale | 88.2 (SD 16.7) | 90 (SD 14.7) | 89 (SD 15.8) |
| Social Responsiveness Scale | units on a scale | 107.3 (SD 24) | 102.1 (SD 23.2) | 104.9 (SD 23.8) |
| Repetitive Behavior Scale-Revised | units on a scale | 32.2 (SD 18.9) | 33.5 (SD 20.6) | 32.8 (SD 19.7) |
| Eye task | units on a scale | 20.8 (SD 8) | 24.8 (SD 6.9) | 22.7 (SD 7.8) |
| Frith-Happe Animation (Total) | units on a scale | 5.5 (SD 2.1) | 5.6 (SD 1.9) | 5.5 (SD 2) |
| Comorbidity with ADHD | Participants | 22 | 14 | 36 |
| Medication (Methylphenidate) | Participants | 14 | 10 | 24 |
| Medication (Atomoxetine) | Participants | 1 | 1 | 2 |
| Medication (Antipsychotics) | Participants | 5 | 5 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Changes of Total Scores of Social Responsiveness Scale, measured over baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in total score on the Social Responsiveness Scale. The registry describes the scale as measuring autism clinical severity and gives its range as 65-260. It states that lower scores indicate better social responsiveness. The recorded outcome type is a mean, with standard deviation as the measure of dispersion.
Repeated assessments were planned: baseline, during treatment at 4 weeks after baseline, post-treatment at 8 weeks after baseline, and one-month follow-up, described as 4 weeks after post-treatment. These time points can help characterize how scores vary during and after the treatment sequence. However, the registry record does not report the scores at any of these assessments, changes from baseline, between-group contrasts, confidence intervals, or p-values. It also does not identify one time point or one contrast as the sole comparison for a numerical result.
In general, a standardized clinical scale can make changes in a complex clinical concept easier to describe consistently. A mean conveys the average score in a group, while a standard deviation describes the spread of individual scores around that average. Those summaries do not, by themselves, show the uncertainty in a group comparison or the distribution of individual responses. Because numerical outcome results are not reported in the registry record, the endpoint's direction and precision cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study's question and design, but it does not report the numerical results needed to interpret the primary outcome. It names changes in total Social Responsiveness Scale scores as the primary outcome and specifies multiple assessment times. However, the record provides no group means, standard deviations, changes from baseline, treatment contrast, confidence interval, or p-value for that outcome. The registry record therefore does not establish the size, direction, or precision of a difference between the treatment sequences.
This distinction matters because an outcome definition is not an outcome result. The fact that the scale was planned for use, and that lower scores were described as better social responsiveness, does not indicate what scores participants actually had or whether they changed. Without numerical results, it is not possible to assess whether scores in either group moved in a particular direction, whether the groups differed, or how compatible the data would be with a range of possible effects.
The assessment schedule also complicates any attempt to reduce the primary outcome to a single comparison. Measurements were planned at baseline, during treatment, after treatment, and at follow-up. The registry explicitly indicates that the primary outcome has several categories or time points and was not reduced to one comparison. A trajectory across repeated measurements and a contrast at one selected time point are different statistical questions. The record does not report which analysis, if any, was used to address the repeated assessments.
The design compares two treatment sequences rather than a full-period real-stimulation group against a full-period sham group. Active-Active received real stimulation throughout its scheduled 8 weeks, while Sham-Active received sham for the initial 4 weeks and real stimulation for the later 4 weeks. Therefore, any interpretation would need to take account of the timing and sequence of treatment. The registry does not report a numerical result that would support such an interpretation.
The completed status and enrollment of 80 describe trial conduct at a high level; they do not substitute for outcome reporting. Nor do the safety counts establish the primary endpoint's effect. The posted adverse-event figures are a separate part of the record and have their own limits, including the lack of event descriptions and other context. Overall, the record permits a description of the planned comparison and reported safety counts, but not an estimate of the primary outcome effect.
9. Statistical Methods Explained
The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. These are descriptive statistics: a mean locates the center of observed scores, and a standard deviation describes how spread out those scores are. To evaluate a treatment comparison, researchers generally also need an estimate of the difference between groups and a measure of uncertainty around that estimate. Numerical estimates and uncertainty measures for the primary outcome are not reported in the registry record.
What does a confidence interval describe?
In general, a confidence interval expresses the statistical uncertainty around an estimated quantity, such as a difference between group means. A narrow interval indicates greater precision than a wide interval, given the method used. An interval can also help readers judge which effect sizes remain reasonably compatible with the observed data. It is not a guarantee that the true effect lies inside the interval. The registry record does not report a confidence interval for the primary outcome, so precision cannot be evaluated from the posted primary-outcome information.
What does a p-value answer?
In general, a p-value is calculated under a specified statistical model and a null hypothesis. It describes how unusual data at least as incompatible with that null hypothesis would be under the model. It does not measure the probability that a treatment is effective, the size of an effect, or its practical importance. A p-value should be interpreted alongside an effect estimate and its uncertainty. No primary-outcome p-value or analysis result is reported in the registry record.
Why do repeated measurements matter?
Measurements from the same participant over time are generally related rather than independent. An analysis of repeated assessments may account for that within-participant relationship and may estimate either changes over time or differences between groups at particular times. The choice depends on the research question and analysis plan. Here, the listed primary outcome spans baseline, the assessment during treatment, post-treatment, and follow-up. The registry indicates that the outcome has several categories or time points and was not reduced to one comparison. The statistical model, handling of repeated measurements, and planned contrast are not reported in the registry record.
What do planning sample sizes mean?
Sample-size calculations are planning tools, not results about the participants who actually enrolled. The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm for 80% power or another stated power level. Such calculations are conditional on their assumptions and do not show the probability that this completed trial found a real effect. They are not observed power. The record does not report a sample-size justification from the trial's own design, and numerical planning results are not included in the registry record.
Why can over-dispersion matter?
In general, over-dispersion means that observed variability exceeds what a statistical model assumes. If a model understates variability, its uncertainty estimates can be too optimistic. The relevance of this issue depends on the outcome type and chosen model. The primary endpoint is described as a continuous score summarized by a mean and standard deviation, but the analysis model and diagnostics are not reported. It is therefore not possible to say whether over-dispersion was considered or relevant to the reported analysis.
Finally, an unadjusted re-calculation from summary statistics, when available, is not the same as the sponsor's prespecified analysis. The registry record does not report a sponsor analysis for the primary outcome or summary statistics from which an unadjusted re-calculation could be made. No new effect estimate can be reconstructed from the information reported.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is listed across several assessment times, and the record notes that it was not reduced to one comparison. Assessing several time points can create a multiplicity issue: when many statistical comparisons are made, the chance of at least one apparently notable result can increase. In general, an analysis plan may address this by defining a primary contrast in advance, adjusting for multiple comparisons, or interpreting a set of results as exploratory. The registry record does not report a multiplicity strategy or a specific primary contrast.
The record lists secondary outcomes involving Frith-Happe Animation accuracy, Eyes Task accuracy, functional MRI during a biological motion task, resting-state fMRI, and diffusion tensor imaging. It reports seven outcome measures in total, but no analyses. It is not possible to determine from the record how these outcomes were prioritized, whether hypotheses were prespecified for each, or how multiplicity across outcomes was handled.
Information about missing data is also limited. The registry gives an enrollment of 80, while the safety figures list 40 participants at risk in Active-Active and 35 in Sham-Active. These figures do not establish how many participants posted primary-outcome data at each assessment. The number missing, reasons for missingness, imputation methods, and sensitivity analyses are not reported in the registry record.
The analysis populations are not reported either. The record does not say whether the primary outcome was analyzed according to randomized assignment, among participants who completed treatment, or under another definition. Without those details and the outcome results, readers cannot assess the extent to which missingness, exclusions, or analytic choices might affect the estimated treatment contrast.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Active-Active | 0 | 40 | 0.0% |
| Sham-Active | 0 | 35 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Active-Active | 0 of 40 |
| Sham-Active | 0 of 35 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Active-Active | 4 of 40 |
| Sham-Active | 10 of 35 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Active-Active | Sham-Active |
|---|---|---|---|
| Pain at application site | Nervous system disorders | 4 of 40 | 10 of 35 |
| Pain at application site | Nervous system disorders | 4 of 40 | 0 of 35 |
The safety record reports zero serious adverse events in both groups. For other adverse events, it reports 4 affected participants among 40 at risk in Active-Active and 10 affected participants among 35 at risk in Sham-Active. No deaths are reported in either group. These are the posted counts; they do not describe the nature, timing, severity, or duration of the events.
The registry separates serious events from other adverse events. These categories should not be treated as interchangeable, and the other-event counts do not indicate that all events were clinically similar. The record does not identify the event terms, and its list of top serious-event terms is empty. It also does not report whether events were judged related to the intervention, whether participants experienced more than one event, or how events were collected and classified.
The at-risk totals differ between the groups in the safety record. Those counts should not be assumed to represent the number analyzed for the primary outcome. Safety counts are descriptive and, without further definitions and context, do not establish a comparative safety effect. The record also does not provide a broader follow-up description for adverse events.
12. What the Result Does, and Does Not, Mean
The record shows that a randomized, double-masked, parallel-group trial was conducted to study theta-burst stimulation in children and adolescents with autism spectrum disorder. It describes two treatment sequences, an 8-week schedule, a primary scale, several assessment times, secondary behavioral and imaging outcomes, and posted adverse-event counts. These details clarify what the trial set out to examine and what categories of results were registered.
The record does not report numerical results for the Social Responsiveness Scale. It therefore cannot show whether scores changed, how the groups compared, or how precisely a treatment contrast was estimated. No conclusion about the primary outcome can be drawn from a stated endpoint, a completed status, or the enrollment figure alone. The listed adverse-event counts are not a substitute for primary-outcome results and do not by themselves establish a causal relationship between treatment and events.
The treatment sequence is important to interpretation. One group received real stimulation across the scheduled treatment period, while the other began with sham and later received real stimulation. That design differs from maintaining a sham comparison throughout. In the absence of reported outcome estimates and a described analysis, the record does not establish how the sequences compared at any particular assessment or over time.
These limits do not mean that the trial had no findings; they mean that the registry record does not report the numerical findings needed to evaluate them. The record also does not provide details about the analysis populations, missing data, multiplicity, or the statistical model. Readers can describe the registered design and the posted safety counts, but should not interpret unreported outcomes as evidence in either direction.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why a registered outcome and a reported result are not the same thing. The record gives a named primary measure, its interpretation, and several planned assessment times. Without group-level values and a comparison estimate, however, the statistical questions that matter most—effect direction, magnitude, and precision—remain unanswered in the registry record.
The treatment schedule also makes clear why design details matter. The groups received different sequences of sham and real stimulation, and one group transitioned from sham to real stimulation. A comparison needs to be interpreted in light of that sequence and the time at which outcomes were measured. A single label such as “active versus sham” would not fully describe the design registered.
The presence of multiple time points and secondary outcomes raises further statistical questions about the planned contrast, multiplicity, and handling of repeated measurements. Those questions are not technical details separate from interpretation: they affect what a reported estimate would mean and how confidently readers could distinguish a prespecified result from a post hoc selection.
The record also demonstrates the value of transparent reporting beyond an enrollment total and a completed status. Reporting participant counts at each assessment, analysis populations, missing-data methods, outcome estimates, and uncertainty would allow readers to assess both the strength and limitations of the evidence. Until numerical primary-outcome results and those analytic details are available in the registry record, the trial can be characterized by its design and registered measures, but its primary statistical result cannot be evaluated.
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 results are not reported in the registry record. These include eligibility criteria, participant characteristics, the age range, baseline outcome values, the allocation ratio, and the procedures used to implement randomization and masking. The record labels the trial double-masked but does not say which participants or study personnel were masked or how masking was maintained.
The primary outcome is identified at several time points, but the record does not report numerical results or a selected between-group contrast. It also does not describe the statistical model, whether baseline scores were adjusted for, or how within-participant correlations across time were handled. Although seven outcome measures are reported and multiple secondary outcomes are named, the analysis results and approach to multiplicity are not included.
Participant flow and missing-data information are also absent. The record does not state how many participants completed each assessment, why data may have been unavailable, or which analysis population was used. The safety at-risk counts cannot fill this gap because they are not identified as primary-outcome analysis counts. A sample-size justification from the trial's own design is not reported in the registry record.
The safety information is limited to counts in serious and other adverse-event categories and deaths. Event descriptions, timing, severity, attribution, and collection methods are not reported. These omissions limit assessment of both outcome precision and possible sources of bias; they do not, on their own, show that any particular problem occurred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Impacts of Theta-burst Stimulation on Children and Adolescents With Autism Spectrum Disorder — NCT03621189.
- Registry record last updated 2024-01-23; status last verified 2018-08.
- Results first posted 2021-08-27.
- 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.
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18. Record Summary
The registry record describes a completed randomized, double-masked, parallel-group trial sponsored by Chang Gung Memorial Hospital. It enrolled 80 children and adolescents with autism spectrum disorder. The two groups received different sequences of real and sham theta-burst stimulation over the posterior superior temporal sulcus.
The primary outcome was change in total Social Responsiveness Scale scores, assessed at baseline, during treatment, post-treatment, and follow-up. The record lists behavioral and imaging secondary outcomes but reports no analyses. Numerical primary-outcome results, the statistical analysis plan, missing-data methods, and analysis populations are not reported in the registry record.
Safety reporting lists zero serious adverse events and zero deaths in each group, with other adverse events reported for 4 of 40 at risk in Active-Active and 10 of 35 at risk in Sham-Active. Event descriptions and further context are not reported.