A Study Using Transorbital Alternating Current Stimulation for People With Glaucoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Using Transorbital Alternating Current Stimulation for People With Glaucoma (NCT03188042), a randomized na study. The primary outcome is Change in Peripapillary RNFL Thickness.

2. Clinical Question

The broader study question was whether the intervention protocol merited further evaluation, both in terms of preliminary effects and whether the methods could be implemented in a larger multi-site trial. The record also describes intended assessment of visual function, functional ability, and quality of life. Those aims do not mean that every outcome has a posted result: the registry record lists 20 outcome measures but no posted secondary results. The primary endpoint therefore addresses a structural eye measure, not all of the functional, quality-of-life, or feasibility questions. The available summaries are descriptive and do not establish whether any observed difference between groups is compatible with chance, nor how precise a treatment contrast would be.

3. Trial Design

The registry record describes a prospective, randomized, controlled, double-masked pilot study using a parallel-group design. Participants were assigned to rtACS stimulation or sham intervention. The study is marked completed, with 18 participants enrolled. The start date is 2017-12-14 and the primary completion date is 2022-10-20. The listed phase is NA.

A pilot study can be used to examine whether procedures are workable and whether outcome measures can be collected as planned, alongside estimating preliminary outcome patterns. The record explicitly frames this study as assessing the protocol for a possible larger multi-site randomized controlled trial. That framing matters when interpreting a small set of posted outcome summaries: descriptive results from a pilot do not automatically answer a definitive efficacy question or establish the performance of a future trial.

For the primary endpoint, the posted summaries list 7 participants in the rtACS group and 9 in the sham group. These are the counts attached to the outcome summaries; they are not the same as the total enrollment of 18. The registry record does not explain the difference between enrollment and the endpoint counts, so reasons for the smaller outcome counts should not be inferred.

The sham intervention is described as resembling rtACS without being active rtACS. Double masking is recorded, but the record does not specify which study roles were masked or how masking was maintained. Allocation concealment procedures, the randomization sequence method, treatment duration or schedule, and details of follow-up beyond the primary endpoint timeframe are not reported in the registry record. The primary outcome timeframe is baseline and Week 4. The record lists NYU Langone Health as sponsor.

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:

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 Change in Peripapillary RNFL Thickness, measured over Baseline, Week 4.

The primary endpoint is change in peripapillary retinal nerve fiber layer thickness, measured in micrometers (μm) with optical coherence tomography (OCT). The registry record identifies the summary measure as the mean and the dispersion measure as the standard deviation. Measurements are described at baseline and Week 4. The posted arm results are mean changes over that timeframe.

RNFL thickness is a structural measure of tissue around the optic nerve. In general, a structural endpoint can provide information about an anatomical feature relevant to the condition being studied. OCT is an imaging method used to measure retinal structures. This endpoint is distinct from measures of visual performance, independence, or quality of life, which the study summary also identifies as areas of interest.

Using change from baseline expresses how the measured value shifted over the specified follow-up interval within each group. It does not, by itself, show whether the groups differ statistically. The clinically relevant comparison in a randomized parallel-group study would generally be the difference in change between the intervention and comparator groups, interpreted with an estimate of uncertainty and a suitable analysis. The registry record does not report that comparison or its uncertainty for this endpoint.

The choice of a structural measure also sets a boundary on interpretation. A posted RNFL result cannot alone describe every aspect of vision or functional ability. The registry record does not report a primary endpoint result for those broader domains.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. The groups are parallel: one received rtACS stimulation and one received sham intervention. The outcome is a change score between baseline and Week 4. No two-arm analysis is reported for this endpoint, so the interpretation is limited to the posted descriptive summaries.

What do the mean and standard deviation describe?

In general, the mean is an average across participants with an available outcome summary. It condenses the group’s observed changes into a single value, but it does not show the full distribution of individual responses. The standard deviation describes how much those values vary around the mean. A larger standard deviation indicates more spread in the observations, not necessarily a larger treatment effect or less accurate measurement. The two posted standard deviations describe within-group variability; neither is an estimate of uncertainty for the difference between group means.

The mean change is not the same as the change for every participant. A mean can reflect a mixture of individual increases and decreases. Without individual-level data, distributional plots, or additional summaries, the registry record does not show the range of participant-level changes or whether unusual values influenced the means.

What would a randomized comparison estimate?

In general, the central randomized comparison for a continuous endpoint is a contrast between outcomes in the assigned groups. Depending on the prespecified analysis, that may compare mean changes or use a model that adjusts for baseline measurements. Such an estimate should normally be accompanied by an uncertainty interval and a statistical test when those are part of the analysis plan. The registry record does not report an analysis model, an estimated contrast, a confidence interval, or a p-value for the primary endpoint. It also does not report whether the analysis used change scores, baseline adjustment, or another approach.

Random assignment can support a causal comparison when the allocation and analysis procedures are appropriate and follow-up is adequately handled. But the existence of randomization does not turn separate group means into a complete treatment-effect analysis. In particular, the registry record does not describe random sequence generation, allocation concealment, the analysis population, or handling of missing outcomes. Those omissions make it impossible to assess the planned and executed comparison in detail.

How should uncertainty be understood?

In general, a confidence interval communicates statistical uncertainty around an estimate under the model and assumptions used to calculate it. It does not guarantee that the interval contains the true value, and it does not represent the spread of individual observations. A p-value, when reported, is a measure tied to a specified null hypothesis and analysis; it is not a direct measure of clinical importance. Neither type of inferential result is posted for this two-arm continuous comparison.

The outcome counts are small: 7 participants in the rtACS group and 9 in the sham group. With limited observations, estimates can be sensitive to individual values, and uncertainty may be substantial. This is a general consideration, not a claim about the unreported analysis. The posted standard deviations indicate observed variability, but they are not enough to establish the precision of a group contrast.

What do the planning illustrations mean?

The registry record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The assumed effect to detect is a stated fraction of the observed effect. For outcomes other than time-to-event measures, the illustrations are expressed as participants per arm. These are hypothetical planning calculations, not the study’s observed power and not evidence that a future study will achieve a particular result.

In general, a sample-size planning calculation asks how many participants would be needed under stated assumptions to detect a specified effect with a chosen probability and significance threshold. Its output depends on those assumptions, including the target effect and variability. Because the assumptions are tied to an observed pilot effect, estimates can be unstable when the pilot data are limited. The registry record does not report its own sample-size justification, so the planning illustrations should not be mistaken for the original enrollment target or design rationale.

Why can over-dispersion matter?

General explanation: over-dispersion means the observed variability is greater than a statistical model expects. It can affect standard errors and confidence intervals, making analyses that assume less variability appear more precise than they should. It is especially discussed for count outcomes, but the general lesson is that the assumed data distribution and variability need to be appropriate. The primary endpoint is continuous, and the registry record does not report an analysis model or an assessment of model fit. There is therefore no basis for saying that over-dispersion was present or affected this result.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("rtACS Stimulation Group", "Sham Intervention Group")
n   <- c(7, 9)
m   <- c(-0.13, -1.8)
sp  <- c(2.3, 3.91)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  rtACS Stimulation Group  7  -0.130  2.300  -2.257  1.997
CARM  Sham Intervention Group  9  -1.800  3.910  -4.805  1.205

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 20 outcome measures, but no secondary outcome results are posted. It reports no posted analyses. The record does not describe a prespecified multiplicity strategy, such as prioritizing outcomes, adjusting significance thresholds, or controlling a family-wise error rate. Without that information and without the secondary results, the overall pattern across outcomes cannot be evaluated.

Multiplicity is a general statistical concern when many hypotheses are tested: the more comparisons made, the greater the chance of at least one apparently notable result arising by chance if each is interpreted in isolation. Methods for addressing this depend on the research questions and analysis plan. No adjustment or unadjusted secondary testing should be inferred from the count of outcome measures alone.

Missing data are also not described for the primary endpoint. The registry record does not report how many enrolled participants lacked a Week 4 measure, why any measurements were unavailable, or how missing outcomes were handled. It does not state whether the posted summaries include all randomized participants or only those with outcome measurements. The primary endpoint group counts are 7 and 9, whereas enrollment is 18; the record does not explain that difference.

The analysis population is not reported in the registry record. In general, an intention-to-treat analysis retains participants in their assigned groups regardless of adherence, while a complete-case summary uses participants with observed outcomes. The posted group counts alone do not identify which approach was used. The record also does not report sensitivity analyses to examine how assumptions about missing outcomes might affect an estimated treatment contrast. As a result, the potential influence of missingness on the primary result cannot be assessed.

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

The posted result establishes that the registry record contains descriptive mean changes and standard deviations for peripapillary RNFL thickness in the rtACS and sham groups over baseline to Week 4. It also establishes that the outcome summaries include 7 participants in the rtACS group and 9 in the sham group. These registry entries describe the recorded endpoint values; they do not establish a treatment effect.

The record does not report a statistical comparison between groups, an uncertainty interval, or a p-value for the primary endpoint. Therefore, the available summaries cannot determine whether the observed group pattern is compatible with a meaningful difference, whether the groups are similar, or how precise a randomized comparison would be. Absence of a reported comparison is not evidence that the groups are equivalent, and it is not evidence that the intervention has no effect.

The endpoint is structural, measured by OCT. It cannot, by itself, establish changes in visual function, quality of life, independence, or other outcomes described in the study aims. The registry record lists 20 outcome measures but posts no secondary results, so those broader questions cannot be answered from the available results.

The study is identified as a pilot focused on preliminary efficacy and feasibility. Its posted outcome summaries may describe a preliminary pattern, but the record does not report enough information to determine whether the procedures were feasible, how participants experienced them, or what criteria would be used to progress to a larger trial. The registry record also does not report the statistical plan or sample-size justification.

These findings should be read as a limited registry result rather than a complete analysis of the study. The entries do not support a clinical recommendation or a conclusion that either intervention should be used or avoided. They show only the recorded primary endpoint summaries and the absence of a reported inferential two-group analysis.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a pilot’s descriptive outcome summaries and a complete estimate of a randomized treatment contrast. The registry record identifies randomization, masking, a sham comparator, and a defined structural endpoint. Yet the posted primary result gives group means and standard deviations without an inferential comparison. Readers need the distinction between describing each group and estimating how the groups differ.

The design also links a clinical question to a measurable endpoint. Peripapillary RNFL thickness is a structural measure taken with OCT at baseline and Week 4. The study summary describes wider aims involving visual function, functional ability, and quality of life, but no secondary results are posted. This highlights why outcome domains should not be treated as interchangeable: a structural measurement does not itself answer a functional question.

The pilot framing is relevant to planning, but should not be confused with proof of efficacy or with observed power. The registry record describes planning illustrations based on an observed effect under stated assumptions. Such illustrations can help explore the scale of a future study, but they do not substitute for a reported analysis plan, a justification of the original enrollment, or evidence about the performance of a future trial.

Finally, the difference between total enrollment and the primary endpoint counts, together with missing information about analysis populations and missing data, shows how registry reporting details affect interpretation. Clear reporting of participant flow, outcome availability, analysis methods, and uncertainty would make the treatment comparison easier to assess. Those details are not reported in the registry record.

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 of these trial-specific results is that the registry record does not report a statistical comparison for the primary continuous endpoint. The group means and standard deviations cannot supply the missing estimate of the between-group effect or its precision. No confidence interval or p-value for that comparison is reported.

The primary endpoint summaries include 7 participants in the rtACS group and 9 in the sham group, while enrollment is 18. The registry record does not explain the participant flow leading to these endpoint counts. It does not report whether participants were excluded from the endpoint summary, whether Week 4 measurements were missing, or why any measurements were unavailable.

Important design and analysis details are also absent. Randomization and double masking are recorded, but the record does not describe sequence generation, concealment, who was masked, or how masking was maintained. The statistical analysis plan, analysis population, missing-data method, and sample-size justification are not reported in the registry record. No sensitivity analyses or prespecified multiplicity procedures are reported.

The record lists 20 outcome measures but no posted secondary results and no posted analyses. This limits the ability to evaluate outcomes beyond the primary structural measure or understand how the findings fit together. Adverse-event entries list zero participants at risk and zero affected in each group, which does not establish the completeness of safety reporting across the enrolled participants.

These limitations are specific to the registry information available. They do not show that analyses or assessments were not conducted; they show that those details and results are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study Using Transorbital Alternating Current Stimulation for People With Glaucoma — NCT03188042.
• Registry record last updated 2024-02-09; status last verified 2024-02.
• Results first posted 2024-02-09.
• 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

NCT03188042 is a completed, randomized, double-masked, parallel pilot study sponsored by NYU Langone Health. The registry record lists 18 enrolled participants and compares rtACS stimulation with a sham intervention in people with glaucoma.

The primary endpoint is mean change in peripapillary RNFL thickness, measured in micrometers by OCT from baseline to Week 4. The posted mean change is -0.13 μm (standard deviation 2.3 μm; 7 participants) for rtACS and -1.8 μm (standard deviation 3.91 μm; 9 participants) for sham. The registry record does not report a two-arm statistical comparison for this endpoint.

The study aimed to examine preliminary efficacy and feasibility, including procedures for assessing functional ability and quality of life. Although 20 outcome measures are listed, no secondary results are posted. The registry record does not report the statistical plan, analysis population, missing-data handling, or sample-size justification.