Safety of Transcranial Direct Current Stimulation in Pediatric Hemiparesis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety of Transcranial Direct Current Stimulation in Pediatric Hemiparesis (NCT01636661), a randomized early/phase 1 study. The primary outcome is Adverse Events/Safety Assessment..

2. Clinical Question

The primary outcome was an adverse-events and safety assessment. It counted participants meeting specified criteria based on vital signs, physician evaluation, or reported symptoms. The assessment timeframe included baseline, posttest, and a follow-up session at one-week. The registry also lists hand-function decline as a secondary outcome.

This is a safety-focused question, not a test of whether active stimulation improves function. The hypotheses concerned absence of major safety events and absence of changes in hand function or cognitive status. The registry record does not report a single combined estimate for those questions: the primary endpoint includes several criteria and time points, and it is not reduced to one comparison. The posted adverse-event counts therefore need to be read as descriptive information about participants in the study, rather than as a definitive answer about safety in children generally.

3. Trial Design

The registry describes NCT01636661 as a randomized, triple-masked, parallel-group, early-phase one study. It was conducted by the University of Minnesota and is recorded as completed. Enrollment was 13. The study compared active transcranial direct current stimulation with sham tDCS. The sham arm used equipment set to a placebo setting.

Random allocation means that assignment to a study group is determined by a chance-based process, rather than being selected solely by participants or investigators. In general, randomization is intended to reduce systematic differences between groups at the start of a study. The registry does not report details of the randomization procedure or allocation concealment. It identifies the masking as triple, but does not state which groups of people were masked or how masking was maintained.

A parallel-group design assigns participants to a group and compares the groups over the study period. The registry’s primary safety assessment covered baseline, posttest, and a follow-up session at one-week. It describes assessment through vital signs, physician evaluation, and subject reports of symptoms. Detailed adverse events are recorded in the adverse-events module.

The record calls the study a pilot and states that there was no sample-size analysis and that it was completed per protocol. The protocol, the meaning of “completed per protocol” in operational terms, and details of participant flow are not reported in the registry record. The record does not report a formal efficacy phase or an intended confirmatory comparison. The listed design and enrollment therefore provide context for a preliminary safety assessment, but do not establish that the study was designed to estimate rare harms precisely or to support broad conclusions beyond the participants studied.

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: If a child did not exhibit a motor evoked potential from the ipsilesional cortex, they were excluded from the trial after enrollment but before assignment to a group.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Pilot study therefore no sample size analysis. Completed per protocol.

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: Pilot study estimating a sample of children with hemiparesis. No formal sample size nor power analysis was performed.

6. Primary Endpoint

The registry lists the primary outcome as Adverse Events/Safety Assessment., measured over Baseline, Posttest, Follow-Up Session at One-Week.

The primary endpoint is titled “Adverse Events/Safety Assessment.” It measures the number of participants who met specified safety criteria. The criteria include a change in resting blood pressure or heart rate greater than 2SD from pretest to posttest; a physician assessment that a child declined in function from pretest to posttest; or a subject report of serious adverse events or symptoms from pretest to posttest. The assessment timeframe also includes baseline, posttest, and a follow-up session at one-week. Detailed adverse events are reported in the adverse-events module.

A participant-count endpoint gives a direct description of how many people met the recorded criteria. It can be useful in a pilot safety study because it helps identify signals that merit attention in subsequent research. It does not, by itself, show the severity, timing, or cause of each event, and it does not quantify how precisely the underlying risk is known. Those interpretations require event details and suitable statistical estimates.

The primary endpoint combines different kinds of observations: vital-sign changes, physician-rated functional decline, and reported serious events or symptoms. These are not interchangeable outcomes. The registry record does not provide a single disaggregated estimate for each criterion at each assessment time, nor a single primary comparison that combines them. The posted counts should therefore be interpreted alongside this definition rather than as a complete account of every safety dimension.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, triple-masked, parallel-group study. Each of these design features addresses a different source of potential bias, but the record does not provide enough procedural detail to assess how fully each feature was implemented. The study is identified as early phase one and as a pilot, with enrollment of 13.

What does randomization contribute?

In general, randomization assigns participants to study groups using chance. Its purpose is to make systematic differences between groups less likely at the outset, including differences that investigators may not have measured. Randomization does not guarantee that groups will be identical, particularly in a pilot study, and it does not remove uncertainty from a small body of observations. The specific randomization method and allocation concealment are not reported in the registry record.

What does masking mean?

Masking is intended to limit the influence of knowing a participant’s assignment on expectations, assessments, or reporting. The registry labels the study triple-masked but does not identify the masked roles or describe how masking was maintained. The sham equipment was set to a placebo setting. The record does not report whether participants or assessors could distinguish active from sham stimulation.

How should participant counts be understood?

The adverse-events module reports the number of participants at risk and the number affected in each group, separately for serious and other adverse events. These are counts, not rates or adjusted treatment effects. A count reflects events recorded under the registry’s definitions and observation period. It should not be converted into a general risk estimate without considering the study design, follow-up, completeness of ascertainment, and uncertainty. No such conversion or adjusted analysis is reported in the registry record.

The primary outcome is defined through several safety criteria and time points rather than as a single measure. It includes vital-sign change, physician evaluation of functional decline, and participant reports of serious adverse events or symptoms. The registry indicates that this outcome was not reduced to one comparison. A composite endpoint can simplify reporting when it combines prespecified components, but its interpretation depends on how the components are defined and whether each component is reported separately. Here, a single composite estimate and the component-level results for the primary endpoint are not reported in the registry record.

What can a confidence interval tell a reader?

In general, a confidence interval expresses the uncertainty around an estimate under a statistical model and method. A narrow interval indicates greater precision than a wide interval, while an interval spanning a broad range of plausible values signals substantial uncertainty. The registry record does not report confidence intervals for the adverse-event counts. Without interval estimates, the precision of a comparison cannot be judged from the counts alone.

Why do event definitions and follow-up matter?

Safety results depend on what qualifies as an event, how it is assessed, and when observations are collected. The primary assessment refers to baseline, posttest, and follow-up at one-week. The registry mentions that detailed adverse events appear in the adverse-events module, but the terms for serious events are not listed there. The other-event descriptions, event timing, and participant-level detail are not reported in the registry record. These omissions limit evaluation of consistency, clinical importance, and whether event ascertainment was comparable across groups.

Over-dispersion is a general statistical concern when count variation is greater than expected under a simple count model. If a model assumes less variability than the data have, uncertainty can be understated and inferential results may be too confident. The registry does not report a count model, model diagnostics, or an analysis of over-dispersion. Given that the posted information consists of participant counts and no recorded analyses, it is not possible to assess whether such modeling was used or appropriate.

The record states that no sample-size analysis was performed because this was a pilot. A sample-size calculation is generally a planning exercise based on a target effect, a chosen error rate, and assumptions about variability or event frequency. It is not an observed result and cannot demonstrate that a study had adequate power after the fact. The registry describes a planning-illustration framework using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. Those assumptions do not constitute the trial’s own design justification, which the registry says was not performed. The record does not report a prospective sample-size rationale or an inferential analysis of the observed safety counts.

10. Multiplicity, Missing Data and Analysis Populations

The primary safety endpoint includes multiple criteria: vital-sign changes, physician evaluation of functional decline, and participant reports of serious adverse events or symptoms. The assessment also refers to baseline, posttest, and a follow-up session at one-week. When a study examines multiple outcomes or time points, the chance of obtaining an apparently notable result can increase if many comparisons are tested. In general, multiplicity procedures can control that risk, but they require a defined analysis plan and a clear account of which comparisons were made.

The registry record states that the primary outcome has several categories or time points and is not reduced to one comparison. It lists zero analyses. A multiplicity strategy, a hierarchy of outcomes, and an analysis plan are not reported in the registry record. It is therefore not possible to determine whether adjustment was planned or applied. No p-values for a primary comparison are reported.

Missing-data handling is also not reported in the registry record. The enrollment entry and the adverse-event module’s group-specific at-risk counts do not describe participant flow, missed assessments, withdrawals, or how incomplete observations were handled. The record does not state whether all participants had evaluable data at every assessment time.

The analysis populations are not described. Although the primary outcome includes assessment time points and the primary population description says the study was completed per protocol, the registry does not define an intention-to-treat population, a per-protocol analysis set, or a safety population. Without these details, the relationship between enrollment, assessment completion, and the posted counts cannot be fully evaluated. These reporting gaps limit inference; they do not establish that data were missing or that an analysis was conducted incorrectly.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 serious adverse-event figures are zero affected participants in the active tDCS group, with 5 at risk, and zero affected participants in the sham group, with 6 at risk. The adverse-events module lists no top serious-event terms. These figures indicate that the registry recorded no serious adverse events in either group in the reported data.

A zero count is not proof that serious events cannot occur. It is an observation from the participants and follow-up represented in the registry, and the record does not report confidence intervals or enough detail to quantify how precisely the underlying risk is estimated. The figures should not be generalized beyond the study without additional evidence.

The module also reports other adverse events: 1 affected participant among 5 at risk in the active group and 4 among 6 at risk in the sham group. These are separate from the serious-event counts. Event descriptions, timing, and a statistical comparison are not reported in the registry record. The difference in the raw counts should not be interpreted as evidence that active stimulation caused fewer events or that sham caused more. The primary safety assessment has additional criteria and time points, and its results are not reduced to one comparison in the registry record.

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

The posted results give a limited descriptive account of adverse events in a randomized pilot comparison of active and sham tDCS. No serious adverse events were recorded in either group in the adverse-events module. Other adverse events were recorded in both groups, with different participant counts. Those observations summarize what the registry reports; they are not a causal estimate of the effect of active stimulation.

The evidence does not establish that tDCS is safe in all children with hemiparesis, nor does it establish that it is unsafe. The study is a pilot, enrollment was 13, and the registry states that no sample-size analysis was conducted. A study of this kind can identify observations worth examining and help inform further research, but the absence of a recorded serious event does not rule out uncommon harms. The record does not provide interval estimates that would quantify uncertainty.

The primary question also included changes in vital signs, functional decline, and reported symptoms, with assessment at baseline, posttest, and follow-up at one-week. Those elements are broader than the serious adverse-event count. The primary outcome is not reported as a single comparison, and the registry lists zero analyses. The posted module counts therefore cannot be treated as a complete statistical answer to every stated safety hypothesis.

The registry’s hypotheses included no major adverse event, including seizure activity, and no change in paretic or nonparetic hand function or cognitive status. The adverse-event counts alone do not establish those hypotheses. The registry lists hand-function decline as a secondary outcome, but detailed results for that outcome are not reported in the record summarized by these safety counts. Cognitive-status results are also not reported in the registry record. Conclusions should remain confined to the recorded observations and the study’s limited scope.

13. Why This Trial Matters Statistically

This trial is statistically useful as an example of the distinction between a safety question and a definitive safety conclusion. A pilot study can collect structured observations, but a low number of participants offers limited information about events that may be uncommon. A zero count can be important to report while still leaving substantial uncertainty about the range of risks compatible with the data.

The endpoint also illustrates the challenge of interpreting a safety outcome made up of different components. A change in vital signs, a physician’s assessment of function, and a reported serious event or symptom represent distinct kinds of evidence. Combining or comparing them requires clear definitions and an analysis plan. The registry notes that the primary outcome has several categories or time points and is not reduced to one comparison, so the reader should not infer a single primary effect from the adverse-event module.

The randomized, triple-masked design is relevant because allocation and masking can reduce certain forms of bias in general. At the same time, the registry does not specify the randomization procedure, which roles were masked, or how masking was maintained. Statistical interpretation depends not only on the design label but also on the methods used in practice and the transparency of reporting.

Finally, this record illustrates why counts, uncertainty estimates, and analysis populations all matter. Counts communicate what was recorded; confidence intervals would help convey precision; and participant-flow and missing-data information would clarify what observations support the results. The registry reports neither inferential analyses nor a sample-size analysis. These limitations make the findings best understood as preliminary descriptive evidence rather than a precise group comparison.

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 main limitation is the pilot scale: enrollment was 13, and the registry explicitly states that no sample-size analysis was performed. The record does not provide a prospective sample-size justification, so it is not possible to determine what precision or effect the design was intended to support. The absence of a serious adverse event in the posted counts should not be read as evidence that rare events are excluded.

The primary endpoint is heterogeneous, covering vital signs, physician evaluation, and symptom reports across several assessment times. The registry says it is not reduced to one comparison. Component-level primary outcome results are not reported in the registry record, which limits interpretation of the endpoint as defined. The secondary outcome listed is hand-function decline, but detailed results for that outcome are not included in the safety counts.

Reporting of the analysis is sparse. The registry lists zero analyses and does not report p-values, confidence intervals, a statistical model, missing-data handling, or defined analysis populations. Participant flow and completeness of assessments are not described. The protocol, detailed randomization procedure, allocation concealment, and the specific roles included in triple masking are also not reported in the registry record.

The adverse-events module gives group counts, but detailed event descriptions and timing for other adverse events are not reported; no top serious-event terms are listed. Without those details, the clinical context and comparability of events across groups cannot be assessed. These limitations qualify the interpretation of the posted results and do not imply that unreported procedures or analyses were absent from the conduct of the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety of Transcranial Direct Current Stimulation in Pediatric Hemiparesis — NCT01636661.
• Registry record last updated 2015-11-09; status last verified 2015-10.
• Results first posted 2015-07-20.
• 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

NCT01636661 is a completed, randomized, triple-masked, parallel-group, early-phase one pilot study sponsored by the University of Minnesota. It enrolled 13 and compared active tDCS with sham tDCS in children with hemiparesis. The stated research question concerned the safety of tDCS in children with congenital hemiparesis.

The primary endpoint assessed participant counts meeting safety criteria involving vital signs, physician evaluation, or subject-reported symptoms. Its timeframe included baseline, posttest, and follow-up at one-week. The adverse-events module reports no serious adverse events in either group and reports other adverse events affecting 1 participant in the active group and 4 in the sham group. The registry states that the study was a pilot with no sample-size analysis, and it lists zero analyses. The primary outcome has several categories or time points and is not reduced to one comparison. The record supports descriptive interpretation of the posted counts, but does not report the analyses or precision estimates needed for a definitive statistical comparison.