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 Effects of Sensory Flicker and Electrical Flicker Stimulation (NCT04188834), a non-randomized na study. The primary outcome is Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04188834 |
| Phase | NA |
| Condition | Brain Diseases |
| Allocation | Non-Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 23 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Emory University |
| Results posted | Yes |
2. Clinical Question
The study asks whether sensory flicker can modulate neural activity in deep brain regions and whether it is associated with behavioral effects. It also describes an aim to compare sensory flicker with direct electrical brain stimulation. The primary outcome, however, focuses on sensory flicker: power at the frequency of the presented flicker is compared between flicker and baseline periods.
Population
The registry lists participants with Brain Diseases. The primary-outcome population is described as participants who completed study procedures and had valid data points for each frequency and region. The enrolled population was 23; the number meeting the primary-outcome criteria is not reported in the registry record.
Intervention
Sensory flicker stimulation used a customized version of the DAVID device. The arm description refers to sequences of sensory flicker trials, with participants’ eyes open or closed; the full set of modalities and other procedural details is not reported in the registry record.
Comparator
For the primary measure, the comparator is the baseline period, not a randomized parallel control group. The study also included direct electrical brain stimulation using Blackrock CereStim, but the primary outcome description does not specify an electrical-stimulation comparison for its reported measure.
Primary question
Among recorded locations with a significant response to sensory stimulation compared with baseline, how does power at the flicker frequency change during sensory flicker relative to baseline, across the specified brain regions and stimulus conditions?
The study is registered as nonrandomized and crossover, so it is not a randomized comparison between independent groups. The registry explicitly cautions that its arms are not a like-for-like control comparison. The record does not report a behavioral primary outcome result.
3. Trial Design
The registry describes a completed, nonrandomized crossover study sponsored by Emory University. Enrollment is listed as 23. The record gives the study start as 2020-01-10 and primary completion as 2022-11-22. It lists no masking. The phase is recorded as NA, and the study type is listed as other.
Two device interventions are named: a customized version of the DAVID device for sensory flicker stimulation and Blackrock CereStim for electrical flicker stimulation. The study summary describes an aim to evaluate sensory flicker’s effects on neural activity and behavior and to compare those effects with direct electrical brain stimulation. The registry record’s primary outcome description is specifically a sensory flicker measure comparing flicker and baseline periods.
The sensory-stimulation arm description refers to repeated flicker trials lasting from a few seconds to 5 minutes, with an exposure period of about 10 to 60 minutes at a time. It mentions auditory-only and visual-on modalities, but the description is incomplete. The electrical-stimulation description refers to low-amplitude current at frequencies ranging from 5-100Hz, for up to 10 seconds at a time, and says that 5.5Hz and 40Hz would initially be tested. Further procedural detail is not reported in the registry record.
The record labels the design crossover but does not report the order of conditions, whether order was balanced, or how periods were separated. Allocation is nonrandomized and masking is none. Consequently, any comparison across conditions should be read with those design features in mind rather than as evidence from a randomized, blinded, parallel-group control design. The registry does not report a protocol-level sample-size justification or details of the statistical plan.
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: Participants only had the Sensory Flicker Stimulation. In the initial IRB protocol submission, the research team intended to potentially do electrical flicker experiments as further exploration of their project but ended up opting not to pursue this avenue.
Overall Study
| Stage | Sensory Flicker Stimulation |
|---|---|
| STARTED | 23 |
| COMPLETED | 19 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Sensory Flicker Stimulation |
|---|---|
| Participants did not complete enough proportion of experiment(s) to be included in analysis | 4 |
Analysis population for the primary outcome, as defined in the registry: Participants who completed study procedures and had valid data points for each frequency and region are included.
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 | Sensory Flicker Stimulation |
|---|---|---|
| Participants analysed | 23 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 23 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 33.7 (SD 11.7) |
| Sex: Female, Male: Female | Participants | 14 |
| Sex: Female, Male: Male | Participants | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 22 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 |
| Race (NIH/OMB): White | Participants | 16 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 23 |
6. Primary Endpoint
The registry lists the primary outcome as Fold-change in Oscillatory Activity (Power Spectral Density) in Response to Exposure to Sensory Flicker: Comparing Mean Power Spectral Density at the Frequency of Flicker Being Presented Between Flicker and Baseline Periods, measured over During experiment session (up to 2 hours) during hospital admission (up to 2 weeks).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | Fold-change in power |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is a fold-change in power spectral density at the frequency of the sensory flicker being presented, comparing flicker periods with baseline periods. Power spectral density describes how signal power is distributed across frequencies. In this study, it is used to characterize oscillatory activity in local field potential recordings from visual areas, auditory areas, the hippocampus, and prefrontal cortex.
The registry describes a response-based summary: researchers considered recorded locations that showed a significant response to sensory stimulation compared with baseline, then summarized the fold-change in oscillatory activity within a region of interest. If a condition was repeated across experimental sessions and a location showed a significant response in multiple sessions, the registry says the data point with the highest response was retained. The stated timeframe is during an experiment session of up to 2 hours during a hospital admission of up to 2 weeks.
The outcome is listed as a median with inter-quartile range. Its narrative also refers to an average increase and to reporting the average fold-change and 25th and 75th percentiles. This wording does not make fully clear whether the reported central summary is a median or an average; the measure is formally listed as a median with inter-quartile range. The endpoint can describe the size and spread of recorded neural responses, but the registry record does not report its observed values. It is therefore not possible to assess the magnitude or precision of the primary result from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes what the primary outcome was intended to measure, but it does not report the numerical primary outcome results. No fold-change estimate, inter-quartile range, confidence interval, or test result is included in the available record. The number of analyses is listed as 0. These omissions mean that the record does not support a conclusion about the size, direction, or statistical uncertainty of the primary outcome.
The endpoint is not described as a summary of every recorded site. It is defined around locations that showed a significant response compared with baseline. In addition, where a location responded in multiple sessions, the largest response was retained. These choices make the endpoint conditional on detecting a response and on which repeated-session value was selected. General statistical interpretation: selecting observations based on statistical significance or retaining the largest of repeated observations can make reported response summaries look more pronounced than summaries that include all measurements under a prespecified rule. The record does not provide enough detail to determine the size of any such influence.
There is an important distinction between the study’s broad aims and the primary measure. The summary refers to neural and behavioral effects and to a comparison with electrical stimulation. The primary outcome described in the registry addresses sensory flicker versus baseline for oscillatory power. A primary result for behavior, or a direct primary comparison of sensory and electrical stimulation, is not reported in the registry record. The registry lists a secondary outcome concerning the rate of interictal epileptiform discharges, but its result is also not reported in the registry record.
The study is classified as nonrandomized and crossover, with no masking. A crossover structure can allow measurements under more than one condition within a participant, which can reduce some between-person variability in a well-specified analysis. That general advantage does not itself remove effects of condition order, time, measurement context, or other sources of bias. The order and handling of conditions are not reported in the registry record. The registry also warns that the arms are not a like-for-like control comparison, so differences between arm summaries should not be treated as though they arose from randomized, equivalent groups.
For the adverse-event figures, the record lists no serious adverse events among the 23 at risk in the sensory flicker group and lists 16 other adverse events among 23 at risk. These counts do not establish that stimulation caused, or did not cause, any event. Event descriptions and further context are not reported in the registry record.
Any sample-size calculations associated with the record are planning illustrations based on fractions of an observed effect, not observed power and not a substitute for the study’s own design justification. The registry record does not report a sample-size justification. The available information therefore supports a description of the design and endpoint, but not a quantitative assessment of the primary finding or its precision.
9. Statistical Methods Explained
The primary endpoint uses power spectral density, a way to describe the strength of a signal across frequencies. Here the question is whether power at the frequency being presented during sensory flicker differs from power during a baseline period. This is a measure of neural activity, not a direct measure of behavior or clinical benefit. The registry names visual areas, auditory areas, the hippocampus, and prefrontal cortex as regions in which local field potential power would be measured.
What does fold-change express?
Fold-change expresses a measurement relative to a reference condition. In this endpoint, the reference is the baseline period. It gives a relative description of power rather than an absolute description of the signal. The registry identifies the unit as fold-change in power, but the observed fold-change values are not reported in the registry record. Without those values and their spread, the magnitude and precision of the measured responses cannot be evaluated.
Why report a median and inter-quartile range?
The outcome is formally specified as a median with an inter-quartile range. The median is the middle value in an ordered set of observations. The inter-quartile range describes the spread from the 25th to the 75th percentile. These summaries can be useful when data are skewed or when unusually large values make the mean less representative of a typical observation. General statistical explanation: the median is less affected by extreme values than the mean, while the inter-quartile range focuses on the central part of the distribution rather than its full range.
The narrative description also uses the words average increase and average fold-change. Because the formal outcome listing specifies a median and inter-quartile range, while the narrative uses average wording, the intended central summary is not entirely clear from the registry record. The record does not report numerical summaries that would resolve this wording ambiguity.
How does response-based selection affect interpretation?
The registry states that the summary concerns recording locations with a significant response to sensory stimulation compared with baseline. It also says that if a location showed a significant response across repeated sessions, the data point with the highest response was retained. Thus, the described summary is not simply an average across all recorded locations and sessions. It is conditional on a location meeting a response criterion, and repeated-session values are handled by retaining the highest response when that criterion is met more than once.
General statistical explanation: restricting a summary to observations that first pass a significance threshold can yield a selected set whose apparent responses are larger than the underlying average response across all observations. Choosing the largest response from repeated measurements can also favor larger values. These are reasons to interpret a response-conditioned summary differently from an estimate based on all eligible measurements under a fixed analysis rule. The registry does not report the exact response-testing procedure, its threshold, or how uncertainty was calculated.
What does the crossover label contribute?
The study is classified as crossover, meaning the design involves conditions considered within a crossover framework rather than only independent parallel groups. In general, within-participant comparisons can account for stable differences between people. They can still be affected by condition sequence, time trends, carryover, or differences in measurement opportunities. The registry does not report condition order, whether it was randomized, or the analytical handling of repeated measurements. Allocation is explicitly nonrandomized and masking is listed as none. The registry further states that the arms are not a like-for-like control comparison.
How should planning calculations be read?
The planning assumptions describe a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. General statistical explanation: a planning calculation estimates the sample size that a hypothetical future study might need under specified assumptions. It is not a measure of the probability that the completed study found a true effect, and it is not observed power. The record describes the calculations as planning illustrations, not as the trial’s own design. It does not report a protocol-based sample-size justification.
The planning assumptions also distinguish event-count calculations for time-to-event settings from participant-per-arm calculations for other settings. These are methodological conventions, not findings from this study. No numerical planning results are reported in the registry record in the information available for this analysis, so they cannot be used to quantify the size of a future study.
The registry lists the number of outcome measures as 2 and the number of analyses as 0. Those listings do not provide analysis methods, effect estimates, uncertainty intervals, or test results. Specific inferential methods, including any model for repeated measurements, adjustment for covariates, and procedure for handling multiple comparisons, are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome spans stimulus frequencies, modalities, and several named brain regions. Considering multiple frequencies, modalities, regions, or recording locations can create multiplicity: the more comparisons examined, the greater the chance that some may appear noteworthy by chance if statistical testing is repeated without an appropriate strategy. General statistical explanation: multiplicity procedures can control the overall false-positive risk or otherwise make the exploratory nature of many comparisons clear.
The registry record does not report how many comparisons were tested, whether a multiplicity adjustment was used, or which outcome analyses were prespecified. It lists 2 outcome measures and 0 analyses, but those entries do not describe a testing strategy. The response-based selection of locations that showed a significant change also makes the selection process relevant to interpretation. The statistical threshold and any adjustment associated with that selection are not reported in the registry record.
The primary-outcome population is described as participants who completed study procedures and had valid data points for each frequency and region. This defines an eligibility condition for the reported outcome, but the number of participants meeting it is not reported in the registry record. The record does not explain how missing or invalid recordings were handled, why data might be unavailable, or whether participants with incomplete data contributed to any other analyses. The analysis populations for the secondary outcome and behavioral aims are also not reported in the registry record.
Details about exclusion rules, imputation, sensitivity analyses, and the treatment of repeated-session observations beyond retaining the highest response when a location repeatedly met the response criterion are not reported in the registry record. Without these details, the impact of missing data and analytic selection cannot be quantified.
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 |
|---|---|---|---|
| Sensory Flicker Stimulation | 0 | 23 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sensory Flicker Stimulation | 0 of 23 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sensory Flicker Stimulation | 16 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sensory Flicker Stimulation |
|---|---|---|
| Headache or discomfort | Nervous system disorders | 8 of 23 |
| Fatigue | General disorders | 8 of 23 |
| Miscellaneous | General disorders | 8 of 23 |
| Seizure likely unrelated to experiment | Nervous system disorders | 3 of 23 |
For the sensory flicker stimulation group, the registry lists 23 participants at risk for serious adverse events and 0 serious adverse events. It separately lists 23 participants at risk for other adverse events and 16 participants with other adverse events. The record does not list serious adverse-event terms.
These are registry counts, not a comparison of event rates between randomized groups. The study is nonrandomized, and the registry warns that the arms are not a like-for-like control comparison. The event categories, definitions, timing, severity details for the other events, and assessment of whether events were related to stimulation are not reported in the registry record. The record also does not provide a detailed account of adverse events for the electrical flicker group in the information.
Zero recorded serious adverse events should be read as a count in this registry entry, not as proof that serious events are impossible or that the intervention is risk-free. Likewise, the listed other adverse events do not establish that sensory flicker caused them. These figures are descriptive and do not by themselves provide a comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The registry record describes a study designed to examine neural responses during sensory flicker, with a primary measure based on power at the presented flicker frequency relative to baseline. It also describes broader interests in behavior and comparison with direct electrical brain stimulation. These aims provide context for what the investigators sought to study, but they are not a substitute for results.
The numerical primary-outcome estimate and its inter-quartile range are not reported in the registry record. Therefore, the record does not establish whether the measured power was higher or lower during flicker, how large any change was, how variable the response was, or how precise an estimate might be. The same limitation applies to the secondary outcome on interictal epileptiform discharges and to behavioral effects: results are not reported in the registry record.
The primary summary concerns locations selected for significant responses, and the described repeated-session rule retains the highest qualifying response. This makes the endpoint a response-focused description rather than an unselected summary of all recording locations and measurements. General statistical interpretation: such summaries can help characterize detected responses, but they should not be treated as an unbiased estimate of the average response across every possible recording or stimulus condition without further information.
The crossover classification does not make this a randomized comparison. The allocation is nonrandomized, masking is none, and the registry cautions that the arms are not a like-for-like control comparison. The record does not explain the condition sequence or provide an inferential analysis that addresses possible order or period effects. Accordingly, the design description alone cannot establish that differences between conditions are attributable to stimulation.
The adverse-event counts are also descriptive. They report no serious adverse events in the sensory flicker group and 16 other adverse events among those at risk, but they do not establish causation or comparative safety. Overall, the registry record documents the study’s aims, design labels, and planned outcome definition; without reported outcome estimates and analysis details, it does not support a quantitative conclusion about the effects measured.
13. Why This Trial Matters Statistically
This study is statistically interesting because it combines within-participant crossover features with neurophysiological measurements across stimulus conditions and brain regions. In general, within-participant designs can reduce the influence of stable differences between individuals when the same person contributes measurements under multiple conditions. They also require careful handling of repeated observations and condition order. The registry classifies the study as crossover but does not report the order or analysis methods needed to assess those issues.
The endpoint also raises an important distinction between a broad measurement plan and a response-selected summary. Power is considered across frequencies and regions, but the outcome description focuses on locations that showed significant responses and retains the highest response across repeated sessions when a location qualifies more than once. This makes the estimand—the precise quantity being summarized—central to interpretation. A summary among selected responsive locations answers a different question from an average across all recorded locations.
Multiplicity matters because examining several regions, frequencies, and modalities can produce many opportunities to identify apparent changes. The registry record does not report a multiple-comparison strategy or numerical results, so it is not possible to assess how such choices affected inference. The explicit distinction between a median and inter-quartile range in the formal listing and average wording in the narrative is another reason to attend closely to how outcomes are defined.
Finally, the record illustrates why design labels, outcome definitions, and results must be read separately. A completed status does not supply an effect estimate, and a planning illustration does not establish observed power. Because the primary results are not reported in the registry record, the main statistical contribution available for evaluation is the structure of the measurement question and the limitations of the analysis information.
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 registry record does not report the primary outcome values, their inter-quartile range, confidence intervals, or statistical tests. The number of analyses is listed as 0, and inferential methods are not described. As a result, the magnitude and precision of the primary outcome cannot be assessed from the registry record.
The primary outcome population is restricted to participants who completed procedures and had valid data points for each frequency and region, but the size of that analysis population is not reported. Missing-data reasons, handling of invalid or incomplete measurements, and sensitivity analyses are not reported in the registry record.
The response-based endpoint selects locations with significant sensory responses and keeps the highest response when a location qualifies across multiple sessions. The record does not report the statistical threshold, the method used to determine significance, or whether uncertainty calculations account for this selection. The description also uses both median and average language for its central summary, without numerical results to clarify the intended reporting.
The design is nonrandomized, unmasked, and classified as crossover. Condition order, balancing, and handling of possible period or carryover effects are not reported in the registry record. The record itself warns that the arms are not a like-for-like control comparison. The sensory flicker arm description is incomplete, and the registry does not provide results for the electrical-stimulation comparison, behavioral aims, or secondary outcome. These gaps limit both reproducibility and interpretation of the study’s broader aims.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effects of Sensory Flicker and Electrical Flicker Stimulation — NCT04188834.
- Registry record last updated 2024-03-26; status last verified 2024-02.
- Results first posted 2024-03-26.
- 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
NCT04188834 is a completed, nonrandomized crossover study sponsored by Emory University, with enrollment listed as 23 and masking listed as none. It evaluates sensory flicker and electrical flicker stimulation. The primary outcome is a fold-change in oscillatory power at the presented sensory flicker frequency, comparing flicker with baseline and summarizing responses across specified brain regions.
The registry describes a response-selected analysis and lists the primary measure as a median with inter-quartile range, while its narrative also uses average wording. It does not report numerical primary or secondary outcome results, inferential methods, or a sample-size justification. The sensory flicker safety entry lists 0 serious adverse events and 16 other adverse events among 23 at risk. These counts are descriptive and do not establish causality or comparative safety.