Temporal Interference Brain Stimulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Temporal Interference Brain Stimulation (NCT03747601), a na na study. The primary outcome is Participants With a Change in Their Visual Field.

2. Clinical Question

The study’s broader aims were to assess the safety and feasibility of TI stimulation and investigate its focality and steerability. The protocol description focuses on selectively modulating activity in subregions of the calcarine cortex and on whether stimulation could affect different regions of the visual field represented there. It also describes an aim of exploring selective targeting of deep brain structures without exciting overlaying cortex.

The registry record describes hypotheses that TI stimulation could affect different visual-field regions and would be well tolerated, with side effects consistent with other forms of transcranial electric current stimulation. These are stated hypotheses, not posted findings. Because there is no comparator group, the study does not make a controlled comparison between TI stimulation and another intervention or a control condition. The primary question is therefore descriptive: the endpoint counts participants with a specified visual-field change after intervention. The registry record does not report the count for that endpoint, so the primary question cannot be answered from the posted results.

3. Trial Design

This was a single-group study of Temporal Interference (TI) Stimulation, listed as a device intervention. The intervention description says stimulation was applied to the head via standard electrodes. The study is listed as phase NA, with allocation NA and no masking. Its status is TERMINATED. Enrollment was 8. The registry record lists Visual Acuity as the condition.

The study record gives a start date of 2019-09-19 and a primary completion date of 2023-06-30. It describes an early phase human experiment intended to translate TI stimulation methodology to humans and examine safety, feasibility, steerability, and focality. The specific aims included assessing safety and examining whether activity in subregions of the calcarine cortex could be selectively modulated. The record also describes an overall goal of advancing TI methodology and its translation to humans.

There is no like-for-like control group described. The single-group structure means that the posted record does not support a randomized treatment comparison. Masking is listed as NONE. The registry record does not report further details about allocation procedures, a comparator, or the statistical plan. The trial’s termination status does not, by itself, establish why the study ended; a reason for termination is not reported in the registry record.

The record notes that 4 other participants were not able to complete visits due to Covid. It does not explain how this affected the primary endpoint analysis or identify an analysis population. The enrollment count should therefore be read as the recorded enrollment, not as evidence that every enrolled participant contributed data to the primary endpoint.

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: 4 enrolled participants did not receive the intervention due to early termination of the study due to COVID.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Other 4 were not able to complete visits due to Covid

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: number of participants enrolled in the study

6. Primary Endpoint

The registry lists the primary outcome as Participants With a Change in Their Visual Field, measured over Immediately after intervention.

The primary endpoint is titled “Participants With a Change in Their Visual Field.” It is a count of participants, and its description specifies a visual-field change (scitoma) assessed by a neurophthalmologist. The stated assessment time is immediately after intervention. The endpoint is therefore a participant-level event count at a specified post-intervention time, rather than a continuous measurement of the size of a visual-field change.

This kind of endpoint can address whether any participants met a defined criterion for change after the intervention. A count is direct to interpret as the number of participants meeting that criterion, provided the number assessed and the outcome definition are clear. The registry record does not provide further operational detail about how a change was defined, how visual fields were tested, or how assessors determined whether the criterion was met. It also does not report the primary endpoint count.

As a result, the endpoint’s purpose can be described, but the observed primary outcome cannot be interpreted from the registry record. The study’s stated aims include safety and the feasibility, focality, and steerability of stimulation; the primary endpoint addresses a visual-field change, not all of those aims. No primary endpoint estimate, uncertainty measure, or analysis is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a single-group study with a participant-count endpoint. No statistical analysis is listed, and no primary outcome count is reported. Statistical concepts can still clarify what the endpoint and the posted safety counts would mean, but they should not be mistaken for methods documented as having been used in this study.

What does a participant count represent?

In general, a count endpoint records how many participants meet a specified outcome definition. Here, that definition is a change in visual field (scitoma), assessed by a neurophthalmologist immediately after intervention. A count is meaningful only in relation to the number of participants whose outcome was actually assessed. A proportion can sometimes help readers compare event frequency across groups or studies, but no primary endpoint count or analysis denominator is reported in the registry record. No such proportion can be interpreted from the posted primary outcome information.

The count also depends on the outcome definition and assessment process. In general, clear criteria help distinguish a true event from measurement variability or differences in judgment. The registry record does not report the operational criteria for “a change,” detailed visual-field testing procedures, or assessor training. It states who assessed the outcome and when, but does not provide those additional measurement details.

What can a confidence interval tell a reader?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. It gives information about precision that a point estimate alone cannot provide. A confidence interval is not reported for the primary endpoint in the registry record. Because the event count itself is also not reported, neither the size nor the precision of the primary result can be evaluated.

For a single-group event count, an interval could describe uncertainty in an event frequency if the count, denominator, and analysis method were known. It would not create a control group or remove uncertainty about missing outcomes. It would also not establish that an event was caused by the intervention. Those distinctions matter particularly in a study without a randomized comparison.

What does the study design permit?

In general, a single-group study can describe outcomes observed among participants who received the intervention. Without a comparator, it cannot directly estimate how outcomes would have differed under another intervention or a control condition. This is a design limitation, not a statistical adjustment that can be resolved by analyzing the same group differently. The allocation field is NA, the model is single group, and no like-for-like control comparison is described in the registry record.

Masking is listed as NONE. In general, masking can reduce the influence of expectations on outcome assessment or reporting, depending on who is masked and how the outcome is measured. The registry record does not describe masking procedures beyond listing none. It does not report a detailed statistical plan, adjustment methods, or an inferential analysis. The record lists 0 analyses, so no specific analysis method should be attributed to the study.

How should planning illustrations be understood?

In general, sample-size planning estimates how much information a proposed study may need to detect a chosen effect under specified assumptions. The planning illustration described for this study is not the trial’s own design and is based on the observed effect. Its assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Time-to-event illustrations use a total event count; other illustrations use participants per arm.

Those assumptions do not match the reported single-group design, and a planning illustration is not observed power. The registry record does not report the trial’s own sample-size justification. A planning calculation also cannot replace the missing primary endpoint result or show whether the study answered its stated question. No planning output should be read as an observed result or as evidence about precision in this trial.

Why do missing outcomes matter?

In general, missing outcome data can change how a count should be interpreted because the observed participants may not represent everyone enrolled. It is important to know how many people were assessed, why assessments were missing, and what analysis handled the missing values. The record notes that 4 other participants were not able to complete visits due to Covid, but does not report how missing primary endpoint data were handled or specify the analysis population. It is therefore not possible to determine from the registry record how incomplete visits affected the primary endpoint estimate.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Temporal Interference (TI) Stimulation")
n      <- c(4)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Temporal Interference (TI) Stimulation  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome measure: the count of participants with a change in visual field (scitoma), assessed immediately after intervention. It lists 0 analyses and does not report an inferential analysis or statistical analysis plan. The record does not describe whether multiple hypotheses or outcome assessments were formally tested, or whether any multiplicity adjustment was planned. A multiplicity strategy is therefore not reported in the registry record; it should not be inferred from the stated study aims alone.

The record notes that 4 other participants were not able to complete visits due to Covid. It does not specify how many participants had an evaluable primary endpoint, whether the inability to complete visits resulted in missing endpoint data, or how any missing data were handled. It also does not report imputation, a sensitivity analysis, or a rule for treating missing outcomes. These details are not reported in the registry record.

The analysis population is also not defined. The enrollment count is 8, but the record does not state whether the primary outcome was analyzed among all enrolled participants, only participants who completed visits, or another group. Without that information and the endpoint count, the primary outcome cannot be reconstructed or evaluated. The study’s single-group design does not involve a reported comparison between treatment arms, and no control-group analysis population is described.

12. 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 record lists 8 participants at risk for serious adverse events, with 0 serious adverse events reported. It also lists 8 participants at risk for other adverse events, with 0 other adverse events reported, and records 0 deaths. No serious adverse-event terms are listed.

These figures are counts from the study’s single group. They are not a comparison with an untreated group or another intervention. In general, a zero observed count means no event of that category was recorded among the participants included in the stated at-risk group; it does not demonstrate that the event cannot occur. The registry record does not provide further detail about adverse-event monitoring, event definitions, or the observation period for these safety counts.

The primary endpoint is a visual-field change, while the safety fields report serious adverse events, other adverse events, and deaths. The record does not report the primary endpoint result, and the safety counts do not fill that gap. The recorded zeros should be read as the posted safety counts, not as a complete account of every possible symptom or as proof of safety.

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

The registry record describes a study intended to translate temporal interference stimulation into humans and examine safety, feasibility, steerability, and focality. Its primary outcome is a count of participants with a visual-field change immediately after intervention. The record does not report that count, so it does not show whether any participants met the endpoint or how many were assessed. The stated hypotheses about visual-field effects and tolerability remain hypotheses in the absence of the corresponding posted results.

The safety fields report 0 serious adverse events, 0 other adverse events, and 0 deaths, with 8 participants at risk for each adverse-event category. These counts describe what was recorded in the study. They do not establish that no risk exists, and they do not compare TI stimulation with another condition.

The single-group design is important to interpretation. Even if the primary outcome result were available, a change observed after intervention would not, by itself, establish that the intervention caused the change. There is no comparator group described that could help distinguish an intervention-associated outcome from other influences. The record also lists no masking.

The enrollment was 8, and the record notes that 4 other participants were not able to complete visits due to Covid. The effect of those incomplete visits on the endpoint analysis is not reported. The number assessed, treatment of missing data, and analysis population are also not reported. These gaps prevent a complete assessment of the primary outcome and its precision.

Accordingly, the record supports a description of the study’s aims, design, endpoint definition, and posted safety counts. It does not support a conclusion about the frequency of visual-field changes, the precision of the primary result, or a causal claim about stimulation. The study’s TERMINATED status does not explain why it ended; a reason is not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because it asks an early human translation question using a single-group design and a participant-level visual-field endpoint. The stated aims involve safety and the feasibility, focality, and steerability of temporal interference stimulation. Those aims concern distinct aspects of a new methodology, while the primary endpoint is specifically a count of participants with a visual-field change after intervention. Keeping the endpoint distinct from the broader aims helps prevent a result on one measure from being treated as an answer to every study question.

The design also illustrates the difference between describing an outcome and estimating a comparative effect. A single-group study can record what happened among participants who received the intervention, but it does not include a like-for-like control comparison in the registry record. That means the design cannot, on its own, separate an observed change from other explanations. This limitation remains even if the outcome is measured carefully.

Missing outcome information matters as much as the choice of statistical method. The record reports enrollment of 8 and notes that 4 other participants were unable to complete visits due to Covid, but does not explain the impact on endpoint assessment or analysis. It also does not report the primary outcome count. Without the count, denominator, and missing-data approach, readers cannot judge the observed event frequency or its precision.

The posted safety counts offer a limited descriptive snapshot: no serious adverse events, other adverse events, or deaths are recorded in the listed at-risk group. Such counts are informative as recorded observations, but they do not demonstrate absence of risk. Together, these features show why transparent outcome reporting, clear analysis populations, and a design aligned with the question are central to statistical interpretation in early human research.

15. 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 primary limitation for interpretation is the absence of a reported result for the primary endpoint. Although the registry record defines a count of participants with a visual-field change and gives the assessment time, it does not report the count or the number of participants evaluated. Consequently, the primary outcome cannot be summarized or assessed for precision.

The study is single group, with allocation listed as NA and masking listed as NONE. There is no comparator group described, so the design does not provide a controlled estimate of an intervention effect. The registry record also does not report the statistical analysis plan, an inferential analysis, or a trial-specific sample-size justification.

The record notes that 4 other participants were not able to complete visits due to Covid. It does not clarify the effect of this on the primary endpoint, how missing data were handled, or which participants were included in the analysis population. It does not provide detailed criteria for defining visual-field change or further information about the assessment process beyond naming the assessor and the immediate post-intervention timeframe.

The posted safety counts are limited to the recorded categories and at-risk groups. No serious adverse-event terms are listed, and the record does not provide additional monitoring or event-definition details. Finally, the study is marked TERMINATED, but the reason for termination is not reported in the registry record. These limitations constrain interpretation without establishing why results or other details are absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Temporal Interference Brain Stimulation — NCT03747601.
• Registry record last updated 2025-05-25; status last verified 2025-05.
• Results first posted 2025-05-25.
• 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.

19. Record Summary

The registry record describes NCT03747601, “Temporal Interference Brain Stimulation,” sponsored by Beth Israel Deaconess Medical Center. The official title is “The Development and Human Translation of Temporal Interference Brain Stimulation.” The study is listed as phase NA, single group, with allocation NA and masking NONE. Its status is TERMINATED. Enrollment was 8; the start date was 2019-09-19, and the primary completion date was 2023-06-30.

The intervention was Temporal Interference (TI) Stimulation applied to the head via standard electrodes. The primary endpoint was the count of participants with a visual-field change assessed immediately after intervention. The registry record does not report the primary endpoint result. It reports 0 serious adverse events among 8 at risk, 0 other adverse events among 8 at risk, and 0 deaths. It also notes that 4 other participants were not able to complete visits due to Covid. The analysis population, handling of missing outcomes, and reason for termination are not reported in the registry record.