12 Month Open Extension of TNS for ADHD.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 12 Month Open Extension of TNS for ADHD. (NCT03888391), a na na study. The primary outcome is ADHD-IV Rating Scale (ADHD-RS).

2. Clinical Question

The registry describes an open extension for participants who had shown sufficient ADHD symptom improvement in a prior study of active trigeminal nerve stimulation. Its stated purpose was to collect additional information on long-term response and tolerability while participants continued treatment. The record does not include numerical results for the primary symptom outcome, so it does not establish the size or precision of any change during the extension.

The design is suited to collecting follow-up information among participants continuing treatment, but it cannot separate change during the extension from the effects of time, expectations, continued participation, or other influences. It also does not provide a like-for-like comparison with an untreated or alternative-treatment group.

3. Trial Design

This completed study is titled “12 Month Open Extension of TNS for ADHD.” It is registered as a single-group study, with allocation and phase listed as not applicable and masking listed as none. The sponsor is James McGough. The registry lists a start date of 2014-12-01 and a primary completion date of 2018-05-30. The enrollment was 18.

Participants who exhibited sufficient ADHD symptom improvement in a prior study of active TNS were to be invited into the extension. In the extension, the active TNS intervention was administered nightly during sleep with the Monarch eTNS System, for up to 12 months. The study was intended to collect additional data on long-term response and tolerability and to provide participants ongoing clinical benefit from treatment. These statements describe the study’s purpose; they are not evidence that a particular benefit or tolerability outcome was achieved.

Because the study had one group and no masking, participants and study personnel were not blinded to treatment assignment. The registry record does not describe a concurrent comparator or randomized allocation. The listed primary outcome was ADHD-IV Rating Scale score, with change assessed over baseline and at Month 3, Month 6, Month 9, and Month 12. The record also lists Clinical Global Impression - Improvement, height, weight, systolic and diastolic blood pressure, and pulse as secondary outcomes.

The record does not report detailed eligibility criteria, the number of people invited, the number who declined, or the treatment and assessment procedures used in the prior study. It also does not report the actual duration of exposure for each participant. These omissions limit how fully the extension cohort and its follow-up can be characterized from the registry record alone.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants lost to follow up over time.

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 ADHD-IV Rating Scale (ADHD-RS), measured over Change over baseline, Month 3, Month 6, Month 9, Month 12.

The primary endpoint is the ADHD-IV Rating Scale (ADHD-RS), a dimensional measure of ADHD symptoms. The registry describes scores ranging from 0 to 54, with higher scores signifying worse severity. It identifies the outcome as a continuous measure and specifies a least-squares mean with standard error as the measure of summary. The time frame is change over baseline, with follow-up at Month 3, Month 6, Month 9, and Month 12.

A symptom rating scale is used to represent severity in a consistent numerical form. Tracking scores at multiple visits can describe the course of scores during follow-up, rather than relying on a single end-of-study observation. In general, a change-from-baseline measure expresses follow-up values relative to the starting assessment; the registry record does not provide the numerical change estimates for this outcome.

The record identifies the primary outcome population as “Participants lost to follow up over time.” That wording does not clarify whether it refers to an analysis population, a data-handling approach, or something else. The precise analysis population and the handling of observations after participants leave follow-up are not reported in the registry record. Without the posted estimates and their uncertainty, the scale description and assessment schedule alone do not show the amount or precision of change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a continuous outcome summarized using a least-squares mean and standard error. The following explains these statistical terms in general; it does not establish which model or analysis procedures were actually used in this study.

What does a least-squares mean represent?

In general, a least-squares mean is an estimate obtained from a statistical model. It can represent an estimated average under the model rather than a simple arithmetic average of the observed values. The model may account for specified features of the data, but which features are included depends on the analysis. The registry record does not specify the fitted model, its covariates, or other adjustment terms. It is therefore not possible to determine from the record whether, or how, the reported measure would adjust for participant characteristics or repeated observations.

The record describes the endpoint as change over baseline and lists follow-up at Month 3, Month 6, Month 9, and Month 12. In general, repeated measurements can be analyzed to describe how an outcome changes across visits. Such analyses require decisions about how to represent time, how to account for measurements from the same participant, and how to handle observations that are missing. The registry record does not report those decisions or the numerical results of the primary analysis.

How should a standard error be read?

In general, a standard error describes the sampling variability of an estimate: smaller standard errors indicate greater precision, while larger standard errors indicate less precision. A standard error is not the same as the spread of individual participant scores. It also does not, by itself, communicate the range of values compatible with the data as directly as a confidence interval. The registry names standard error as the dispersion measure but does not report its value for the primary endpoint in the registry record. No confidence interval should be inferred without the estimate and analysis details.

For a continuous symptom score, the scale’s direction matters. The registry states that ADHD-RS scores range from 0 to 54 and that higher scores signify worse severity. If a numerical change estimate were available, its sign and magnitude would need to be interpreted using that direction and the stated baseline reference. Since the numerical change estimates are not reported in the registry record, the direction and size of observed change cannot be assessed from the endpoint definition alone.

What can a single-group design estimate?

In general, a single-group follow-up can describe outcomes observed among participants who receive the same intervention, subject to the analysis and missing-data approach. It does not furnish a concurrent estimate of what would have happened to a comparable group under another condition. This distinction matters because changes can arise from influences other than the intervention, including time, expectations, measurement variation, and changes in who remains under observation. These are general design considerations, not claims that any one influence occurred in this study.

The extension was open and had no masking. In general, knowledge of treatment can affect participants’ reports, study conduct, and outcome assessments, depending on how outcomes are measured. The record does not describe safeguards or the roles of assessors, so the potential influence of awareness cannot be assessed in detail.

How do planning illustrations differ from trial results?

General sample-size planning estimates describe how many participants might be needed under specified assumptions to detect a target effect with a chosen statistical procedure. The registry’s accompanying planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not a description of this trial’s single-group design. The record states that the illustration is not the trial’s own design calculation.

Planning estimates are not observed power and do not show whether the study found an effect. They depend on the assumptions used, including the target effect and design. The numerical sample-size illustrations are not included in the registry entries, and the trial’s own sample-size justification is not reported in the registry record. No conclusion about the study’s power or adequacy can be drawn from the enrollment count alone.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability in count data is greater than a model assumes. If present and ignored, uncertainty estimates for a count outcome may be too small. This is a general statistical issue, not a reported feature of this study’s continuous primary endpoint. The registry identifies the primary outcome as a continuous score and does not report an over-dispersion assessment.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures and 6 analyses. Multiple outcomes and analyses raise a general multiplicity question: when many statistical claims are examined, the chance of at least one apparently notable result can increase if no adjustment or other interpretive strategy is used. The record does not report whether multiplicity was addressed, which analyses were confirmatory, or how the listed outcomes relate to any prespecified hierarchy. The counts alone do not establish that a particular correction was required or applied.

The record identifies ADHD-RS as the primary outcome and lists Clinical Global Impression - Improvement, height, weight, systolic blood pressure, diastolic blood pressure, and pulse as secondary outcomes. It does not provide a complete analysis plan or clarify the status of each analysis. Interim analyses and any rules for stopping or changing analyses are not reported in the registry record.

Missing data are especially relevant to a study with repeated follow-up visits. The primary outcome population is described as “Participants lost to follow up over time,” but the meaning of that phrase is unclear. The registry record does not state how many participants contributed measurements at each visit, why observations were missing, or how missing values were handled. It also does not describe sensitivity analyses assessing how conclusions might change under alternative assumptions about missing outcomes.

In general, analyses restricted to participants with observed measurements can differ from analyses using a model or imputation approach, particularly when the likelihood of missingness is related to outcome values or participant characteristics. Without the analysis population and missing-data methods, the influence of attrition on any estimated change cannot be assessed. No particular missing-data mechanism can be inferred from the 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.

Most frequent non-serious adverse event terms

The registry lists 18 participants at risk for serious adverse events in the Active TNS group, with zero affected, and zero deaths. It separately lists 18 participants at risk for other adverse events, with 11 affected. These figures are counts of participants recorded as affected, not a rate or an estimate of comparative risk. No comparison group is present.

Zero serious adverse events in the recorded group means that none were listed as affected in the registry’s serious-event count. It does not demonstrate that serious events cannot occur, nor does it quantify how the count would compare with another treatment or with no treatment. The record does not list serious adverse-event terms.

The 11 affected for other adverse events should not be read as 11 distinct event types or as a count of all event episodes; the record does not clarify the counting convention or give the specific terms. It also does not report severity, timing, duration, or whether events led to treatment changes or withdrawal. Exposure was planned for up to 12 months, but each participant’s actual exposure and time under safety observation are not reported in the registry record.

These counts provide a limited descriptive safety summary. They do not, on their own, establish the presence or absence of a treatment-related safety effect.

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

The registry record establishes that this was a completed, open extension study of active TNS in a selected group of participants with ADHD. It specifies the ADHD-RS as the primary continuous symptom measure, describes its score direction and range, and lists repeated follow-up assessments through Month 12. It also records the group’s serious and other adverse-event counts.

The record does not include numerical ADHD-RS changes, standard errors, confidence intervals, or test results. Consequently, it does not show how much scores changed, how precisely any change was estimated, or whether a particular statistical comparison was conducted. The study’s stated objective of collecting long-term response and tolerability information is a purpose, not a result. Neither that objective nor the completion status can substitute for outcome estimates.

Even if outcome changes were available, the single-group, open design would limit causal interpretation. Without a concurrent comparator, observed changes could not be distinguished from time-related changes, expectations, selection of participants based on prior improvement, or other influences. These are general limitations of the design, not evidence that any specific influence determined the results.

The safety counts show zero participants affected by serious adverse events and 11 affected by other adverse events among 18 at risk, as recorded. They do not provide event descriptions or a comparative assessment. The registry record also leaves the meaning of the primary outcome’s population wording and the handling of missing follow-up unclear.

Thus, the record supports an account of the study’s design, intended assessments, and limited safety counts. It does not support a quantitative conclusion about the primary symptom outcome or a causal conclusion about treatment effects. The absence of reported numerical outcome results should be distinguished from evidence that no change occurred.

13. Why This Trial Matters Statistically

Open extensions address a different statistical question from randomized comparisons. They can document follow-up among participants who continue after an earlier study, including repeated symptom assessments and safety observations over time. Such information can be useful for understanding what was recorded in a continuing-treatment cohort, while remaining distinct from evidence that attributes changes to treatment.

This record makes several interpretive challenges visible. The extension cohort was selected from participants who had exhibited sufficient improvement in a prior active-TNS study. The study was open and single-group, so it had no concurrent control for separating intervention-related change from other influences. Follow-up was planned for up to 12 months, but actual participant-level exposure and visit completion are not reported in the registry record.

Statistically, the primary outcome is a repeated continuous measure summarized as a least-squares mean with standard error. Those terms convey the kind of summary intended, but without the model specification and numerical estimates they do not permit evaluation of the endpoint’s magnitude or precision. The unclear description of the primary outcome population further limits interpretation of how participants lost to follow-up entered the analysis.

The safety counts are also useful to read in context. The registry records no serious adverse events among 18 at risk and other adverse events affecting 11 of 18 at risk, but it supplies no event-level detail in the registry record described. Counts without event descriptions, follow-up time, or a comparator cannot establish comparative safety.

The statistical lesson is to separate study purpose, design, outcome definitions, and observed results. The record gives substantial context about the intended extension and its measures, but the numerical primary findings and key analysis details are not reported. Recognizing that boundary prevents a study description from being mistaken for an estimate of effect.

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 principal limitation for interpreting the primary endpoint is that numerical ADHD-RS results are not reported in the registry record. The scale range, direction, assessment schedule, and intended summary statistic do not reveal the observed changes or their uncertainty. The model used to obtain the least-squares mean and standard error is also not described.

The single-group, unmasked design does not include a concurrent control. Consequently, the study cannot distinguish changes over follow-up from influences unrelated to the intervention. The cohort was drawn from participants who had exhibited sufficient improvement in a prior active-TNS study; further selection criteria and details of that earlier study are not reported in the registry record.

The primary outcome population is described as “Participants lost to follow up over time,” but the meaning is not clear. Participant counts at each assessment, reasons for missingness, actual follow-up duration, and methods for handling missing measurements are not reported. These gaps make it difficult to understand which observations contributed to the primary analysis and how attrition may have affected any estimate.

The registry lists 16 outcome measures and 6 analyses but does not report a detailed statistical analysis plan or how multiplicity was considered. The sample-size justification for the trial, interim analyses, and the basis for its enrollment target are not reported in the registry record. The sample-size planning assumptions described for an illustration do not establish the design rationale for this single-group extension.

Safety interpretation is limited by the lack of non-serious event terms, severity, timing, duration, and participant-level exposure information. With 18 enrolled and no comparison group, the posted counts are descriptive and cannot quantify comparative risks.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: 12 Month Open Extension of TNS for ADHD. — NCT03888391.
• Registry record last updated 2019-05-29; status last verified 2019-05.
• Results first posted 2019-04-29.
• 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

NCT03888391 is a completed, open, single-group extension study titled “12 Month Open Extension of TNS for ADHD.” The registry lists 18 enrolled participants and describes nightly active TNS with the Monarch eTNS System for up to 12 months. Participants were invited after exhibiting sufficient ADHD symptom improvement in a prior active-TNS study.

The primary outcome was ADHD-RS score, described as ranging from 0 to 54, with higher scores indicating worse severity. Change was scheduled for assessment over baseline and at Month 3, Month 6, Month 9, and Month 12. Numerical primary outcome estimates and analysis details are not reported in the registry record. Secondary outcomes include Clinical Global Impression - Improvement, height, weight, systolic and diastolic blood pressure, and pulse.

The registry records zero participants affected by serious adverse events among 18 at risk, zero deaths, and 11 participants affected by other adverse events among 18 at risk. Specific other-event terms are not reported in the registry record.