Improving Hallucinations by Targeting the rSTS With tES: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Improving Hallucinations by Targeting the rSTS With tES (NCT05165654), a randomized na study. The primary outcome is Positive and Negative Syndrome Scale (PANSS).

2. Clinical Question

The trial asks whether noninvasive electrical stimulation targeted to the right superior temporal sulcus (rSTS) can change brain activity, sensory integration, and hallucinations. The registry rationale describes the rSTS as a site involved in multimodal sensory integration and refers to lesion network mapping as evidence linking lesions connected to this region with hallucinations. The trial compares active stimulation with a passive sham condition; the listed primary measure is change in Positive and Negative Syndrome Scale (PANSS) scores from baseline to day 5.

3. Trial Design

The registry describes a randomized, double-masked, parallel-group trial with an enrollment of 12. Its status is completed. The record lists the sponsor as Beth Israel Deaconess Medical Center. The study start is recorded as 2021-11-01 and primary completion as 2025-06-01. The phase is listed as NA.

Participants were assigned to active tDCS or passive sham stimulation. The active arm description specifies stimulation to the rSTS in two, twenty-minute sessions for 5 days, with 10 total sessions. The sham description specifies passive stimulation with a 30 second ramped up and down at the beginning and end of the 20 min period, also for 5 days and 10 total sessions. Both descriptions therefore refer to a repeated treatment schedule, but the registry record does not describe adherence or the actual number of sessions received by participants.

In general, randomization is intended to make treatment groups comparable at assignment, while masking is intended to reduce the influence of treatment knowledge on participant experience, care, or outcome assessment. The record labels the study randomized and double-masked, but does not state which people were masked, how assignment was generated or concealed, or whether masking was assessed. Those implementation details are not reported in the registry record.

The record lists auditory hallucinations and psychosis as conditions and describes hallucinations across psychiatric and neurological conditions in its rationale. Specific eligibility criteria, diagnostic composition, baseline severity, recruitment setting, and participant characteristics are not reported in the registry record. The enrollment figure describes the recorded study enrollment, not the number contributing data to any particular endpoint; endpoint-specific analysis populations are not reported.

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: Individuals performed a full clinical assessment including a structured clinical interview and medical history review to confirm diagnosis. Individuals were required to have a history or current hallucinations (visual, auditory, tactile, etc.) to participate in the study. Participants were then randomized to one of the two arms of the study (active tDCS or sham) targeting the right superior temporal sulcus.

Overall Study

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 Positive and Negative Syndrome Scale (PANSS), measured over Change from baseline to day 5.

The listed primary endpoint is the Positive and Negative Syndrome Scale (PANSS), assessed as change from baseline to day 5. The registry describes a total psychosis-symptom score, General symptoms, Negative Symptoms, and Positive Symptoms. Higher scores represent higher symptom severity. The total score has a stated minimum of 30 and maximum of 210; each listed symptom subscale has a stated minimum score of 16 and maximum score of 112.

The endpoint is intended to capture symptom severity over the trial period. A change measure compares a participant's later score with their baseline score, so the direction and magnitude of change can be considered in relation to the scale's stated meaning. In general, using a symptom scale can provide a structured way to assess clinical features, but interpretation depends on the definition of the score, timing, completeness of assessments, and the analysis used.

The registry record specifies the summary measure as the median and the dispersion as the inter-quartile range. It does not give the observed medians, inter-quartile ranges, changes, or a treatment-group comparison. It also indicates that the primary outcome was not reduced to one comparison because it has several categories or time points. Thus, the endpoint's measurement framework is described, but its numerical findings and the precise primary contrast are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-masked, parallel-group design. It names a primary PANSS outcome, gives a baseline-to-day-5 timeframe, and specifies median and inter-quartile range as the summary approach. The posted record contains 0 analyses and does not report primary-outcome estimates. The distinctions below explain how these methods are generally interpreted and which implementation details remain unavailable in the registry record.

What does randomization contribute?

In general, randomization assigns participants to study groups using an assignment process intended to avoid systematic selection of one group over another. It supports a fair comparison by making known and unknown participant characteristics less likely to be deliberately aligned with treatment assignment. Randomization does not guarantee that groups will have identical characteristics, particularly in a study with limited enrollment. The record labels the trial randomized, but does not report the sequence-generation method, allocation concealment procedures, or any baseline group characteristics.

In general, a parallel-group design assigns participants to one study arm and compares outcomes across arms. Here the described arms are active tDCS and passive sham stimulation, both targeting the rSTS. The registry calls the trial double-masked, but does not specify the masked roles or provide information on whether masking was maintained. The sham procedure is described, but the record does not report participants' or assessors' guesses about assignment.

What do median and inter-quartile range convey?

In general, the median is the middle of an ordered set of observations. It can describe the center of a distribution without requiring the values to be symmetrically distributed. The inter-quartile range describes the spread of the middle portion of the observations. Together, these summaries can be useful when scores are skewed or when a few observations are far from the center. They do not, by themselves, provide a treatment-group contrast or quantify uncertainty in that contrast.

The registry specifies median and inter-quartile range for PANSS, but does not report those values for either arm. It also does not clarify in the posted results whether summaries refer to endpoint scores, changes, or each of the listed symptom categories. The outcome timeframe is change from baseline to day 5, while the registry's note says several categories or time points prevented reduction to one comparison. The full statistical definition of the primary analysis is not reported in the registry record.

How should a between-group effect be interpreted?

In general, a treatment effect estimate describes the difference between groups for a defined outcome and analysis population. A confidence interval expresses the range of estimates that are compatible with the observed data and the assumptions of the method. A narrow interval indicates greater statistical precision than a wide interval, while an interval that includes values on both sides of no difference may be compatible with a range of interpretations. The actual estimate and confidence interval are not reported for PANSS in the registry record, so these concepts cannot be applied to a numerical result from this trial.

A comparison of changes from baseline is not necessarily equivalent to a comparison of endpoint scores, and statistical adjustment can affect an estimate. In general, the analysis should specify which measure is compared and how baseline values are used. The record provides the change timeframe but does not report the analysis model, adjustment variables, contrast definition, or handling of repeated observations.

Why do over-dispersion and distributional assumptions matter?

In general, over-dispersion means observed variability is greater than a statistical model assumes. When a model underestimates variability, uncertainty may be understated and tests can appear more decisive than warranted. The relevance of this issue depends on the outcome type and model. The registry does not report a model for the PANSS comparison, distributional diagnostics, or any assessment of over-dispersion; no conclusion about those features can be drawn from the record.

The record's sample-size assumptions describe planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such illustrations are planning quantities, not observed power and not a substitute for the trial's actual outcome estimates. Their numerical values and the underlying observed effect are not reported in the registry record. The trial's design justification and sample-size calculation are also not reported.

What can be inferred from the analysis record?

The registry lists 0 analyses. It does not report p-values, confidence intervals, adjusted or unadjusted comparisons, model results, or subgroup results. No statistical analysis plan, interim analysis information, stopping rule, or multiplicity procedure is reported. The primary endpoint includes multiple score categories, and the record lists secondary measures across several physiological domains. In general, when multiple outcomes or contrasts are examined, the analysis plan should define which comparisons are confirmatory and how the risk of chance findings is addressed. The registry record does not explain how that was done, if at all.

Missing-data methods and analysis populations are likewise not described in the posted results. In general, incomplete outcome measurement can affect both the number of observations available and the comparability of groups; the implications depend on why data are missing and how the analysis handles them. Without participant flow, endpoint-specific denominators, and a stated method, the completeness and representativeness of the PANSS summaries cannot be assessed. These unknowns do not establish that the analysis was inadequate; they mark the limits of what the registry record reports.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description includes several PANSS categories: total psychosis symptoms, General symptoms, Negative Symptoms, and Positive Symptoms. The registry also records a note that the primary outcome has several categories or time points and was not reduced to one comparison. This matters because a study with multiple outcome definitions can support several possible comparisons, and the interpretation depends on which one was prespecified as primary or how the comparisons were handled.

The registry lists 28 outcome measures, including auditory, visual, and cross-modal evoked-potential measures and resting-state EEG measures. Some outcome labels appear more than once in the record, but the record does not explain the structure or analysis of each measure. It reports 0 analyses and does not describe a multiplicity adjustment, hierarchy of outcomes, or distinction between confirmatory and exploratory analyses. In general, examining multiple outcomes can increase the chance of observing an apparently notable result by chance unless the analysis strategy addresses that issue. No specific multiplicity method is reported in the registry record.

Missing-data handling is not reported. The record does not provide participant flow, endpoint-specific numbers assessed, reasons for missing measurements, or methods for dealing with missing observations. Analysis populations, such as whether participants were analyzed according to assigned group or according to treatment received, are not reported either. In general, these details help readers judge how closely the analysis represents the randomized comparison and whether missing observations could alter interpretation.

No numerical primary or secondary outcome analyses are posted, so these uncertainties cannot be resolved by examining reported estimates. The absence of detail should be understood as a limitation of the registry record, not proof that the trial did or did not use a particular method.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports safety figures separately for active stimulation and sham. In the active stimulation arm, 6 were at risk for serious adverse events and 0 serious adverse events were reported; 6 were at risk for other adverse events and 0 other adverse events were reported. In the sham arm, 6 were at risk for serious adverse events and 0 serious adverse events were reported; 6 were at risk for other adverse events and 2 other adverse events were reported. The record reports 0 deaths in each arm. No serious adverse-event terms are listed.

These are the entries reported for this study, not estimates of comparative risk over a wider population. The figures for participants at risk describe the registry's safety denominators; the record does not explain safety-event ascertainment, definitions, follow-up completeness, or whether the other adverse-event entries represent unique participants or events. The event descriptions and severity details for the other adverse events are not reported in the registry record.

In general, an absence of recorded serious events in a small trial does not establish that such events cannot occur. Safety interpretation depends on the duration and completeness of observation, event definitions, and the amount of exposure. The record supports a narrow description of what was reported during this study, not a broad risk comparison or a conclusion about safety in other settings.

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

The registry record establishes that this was a completed randomized, double-masked, parallel-group study of active tDCS targeted to the rSTS versus passive sham stimulation. It describes the treatment schedules and identifies PANSS change from baseline to day 5 as the primary outcome. It also describes physiological secondary outcomes. These details clarify the intended comparison and the outcomes the study set out to assess.

The record does not, however, report numerical PANSS findings, a group contrast, or an uncertainty estimate. It lists 0 analyses and does not give numerical results for the secondary outcomes. Therefore, the posted record does not show how symptom scores changed, whether the arms differed, how large any difference was, or how precisely an effect was estimated. No treatment-effect conclusion can be drawn from the outcome information in this record alone.

The enrollment is 12, and the registry reports no serious adverse events or deaths in either arm, along with 2 other adverse events in the sham arm and none in the active arm. These safety observations are specific to the registry entries and the study; they cannot establish comparative safety in broader populations. The record does not provide the event descriptions or detail how events were collected.

In general, a completed trial status indicates that the registry marks the study as completed; it does not by itself mean that all outcomes have been reported or that the study answered its research question. Likewise, a planning illustration based on an observed effect is not observed power and does not replace an actual effect estimate with a confidence interval. The numerical inputs and any such planning values are not reported in the registry record.

The appropriate interpretation is limited: the trial's design and measurement aims are documented, while its numerical symptom and physiological results are not. This does not show that stimulation had no effect, nor does it show that it improved outcomes. It means the posted results are insufficient to determine the direction, magnitude, or precision of the outcome comparisons.

13. Why This Trial Matters Statistically

This trial raises a statistical question that is important for interpreting small, mechanism-oriented clinical studies: whether a targeted intervention changes a defined clinical measure and whether accompanying physiological measures provide interpretable evidence about the proposed process. The registry describes stimulation aimed at the rSTS, a region presented in the rationale as involved in multimodal sensory integration, and identifies PANSS and several evoked-potential and EEG measures.

The design combines a randomized comparison with masking and a sham condition. In general, these features are intended to make group comparisons less vulnerable to systematic differences in assignment and expectations. The record does not report enough implementation detail to evaluate how randomization and masking were carried out, and the absence of numerical outcome analyses prevents evaluation of whether the comparison yielded a precise estimate.

Statistically, the primary outcome definition is consequential. PANSS is described through total and symptom-category scores, while the registry notes that the outcome was not reduced to one comparison because it has several categories or time points. A prespecified primary contrast is important for clarifying which result carries the main inferential weight, particularly when the study also lists many secondary measures. That contrast and any strategy for handling multiplicity are not reported.

The trial also illustrates the distinction between a study's rationale and evidence from its posted results. A biological or clinical rationale can motivate measurement, but the proposed relationship between stimulation, brain activity, sensory integration, and hallucinations must be evaluated using reported estimates and their uncertainty. Those numerical findings are absent from the registry record. The record therefore documents a question and design, but does not permit a statistical assessment of whether the data support the proposed chain of effects.

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.

Important limitations of interpretation arise from what the registry record does not report. The enrollment is 12, but the numbers contributing to the primary or secondary outcome analyses are not given. Participant flow, withdrawal information, endpoint-specific denominators, and reasons for missing observations are not reported. This prevents assessment of outcome completeness and of how much information contributed to each comparison.

Participant characteristics and specific eligibility criteria are also absent. Although auditory hallucinations and psychosis are listed as conditions, the record does not give the diagnostic composition, baseline symptom severity, or other clinical characteristics needed to understand how closely participants resemble any intended population. Recruitment setting and details of concomitant care are not reported.

The statistical analysis is not described in sufficient detail to identify a single primary contrast. The outcome includes several PANSS categories, and the registry notes that it was not reduced to one comparison. The record does not provide model specifications, adjustment variables, analysis populations, missing-data methods, or a multiplicity strategy. It also reports 0 analyses, so no numerical estimates or uncertainty measures are available to help resolve these questions.

The trial is labeled double-masked, but the masked roles, allocation concealment, and any assessment of masking are not reported. The record describes the active and sham procedures but does not report adherence, delivered stimulation details beyond the arm descriptions, or treatment fidelity. Safety-event definitions, descriptions of other adverse events, and the completeness of safety follow-up are also not reported.

Finally, the registry offers planning assumptions but does not report the design justification or numerical planning inputs. In general, planning illustrations cannot establish what precision the completed study achieved. Without posted outcome estimates and confidence intervals, the clinical and statistical importance of the study's findings cannot be assessed from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Improving Hallucinations by Targeting the rSTS With tES — NCT05165654.
• Registry record last updated 2025-09-17; status last verified 2025-09.
• Results first posted 2025-09-17.
• 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

The registry record for NCT05165654 describes a completed randomized, double-masked, parallel-group study sponsored by Beth Israel Deaconess Medical Center. It lists an enrollment of 12 and compares active tDCS targeted to the rSTS with passive sham stimulation. The primary outcome is PANSS change from baseline to day 5, summarized by median and inter-quartile range.

The record describes PANSS total and symptom-category scores and lists secondary physiological measures involving auditory, visual, cross-modal evoked potentials, and resting-state EEG. It reports 28 outcome measures and 0 analyses. Numerical primary and secondary outcome results, a defined primary contrast, and confidence intervals are not reported in the registry record.

Safety entries report no serious adverse events or deaths in either arm, and report 2 other adverse events in the sham arm and none in the active arm. The record documents the study question and design, but the absence of numerical outcome analyses means the magnitude, direction, and precision of clinical and physiological effects cannot be evaluated from the posted results.