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 Pilot rTMS for AUD+mTBI (NCT03995173), a randomized phase 2 study. The primary outcome is Total Adverse Event Frequency.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03995173 |
| Phase | Phase 2 |
| Condition | Alcohol Use Disorder, Mild Traumatic Brain Injury, Post-traumatic Stress Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 2 |
| Arms in the primary outcome | 2 |
| Lead sponsor | VA Office of Research and Development |
| Results posted | Yes |
2. Clinical Question
Population
Veteran participants with alcohol use disorder and co-occurring mild traumatic brain injury and/or post-traumatic stress disorder were the intended population. The record lists all three conditions. Although its brief summary describes a plan to enroll 20 participants, the enrollment recorded in the registry is 2; the primary outcome description says only 1 was randomized.
Intervention
The active intervention was repetitive transcranial magnetic stimulation (rTMS). The study summary describes 10 treatment sessions, scheduled once every weekday for 2 weeks, followed by phone follow-up to assess craving and other symptoms. These are the described study procedures; the record does not establish that every planned procedure was completed.
Comparator
The comparator was placebo rTMS. The primary outcome description states that the single randomized participant was assigned to placebo. The posted primary outcome therefore has no active-arm participants and cannot support a comparison between active and placebo treatment.
Primary question
The registered primary outcome asks for the total frequency of adverse events recorded across rTMS treatment sessions, assessed after the last, or 10th, session within a timeframe of up to 2 weeks. The study summary emphasizes alcohol craving as a goal, and the Penn Alcohol Craving Scale is listed as a secondary outcome. The posted primary endpoint is safety-related event frequency, not a direct estimate of change in craving.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group Phase 2 study sponsored by the VA Office of Research and Development. The listed intervention was repetitive transcranial magnetic stimulation, with active rTMS and placebo rTMS as the two arms. The study concerned veterans with alcohol use disorder and co-occurring mild traumatic brain injury and/or post-traumatic stress disorder.
The record lists a start date of 2019-03-21, a primary completion date of 2020-03-31, and a status of terminated. It records enrollment of 2. The brief summary describes an intended enrollment of 20, divided equally between real and placebo rTMS, and describes 10 weekday sessions over 2 weeks followed by phone follow-up. Those details describe the study plan; the record does not show that the intended enrollment or full treatment schedule was achieved.
The primary outcome was total adverse-event frequency after the treatment course. The primary outcome description explains that an adverse-event log would be kept for each participant and session, with the total frequency assessed after all 10 sessions. Its population note says only 1 participant was randomized, to placebo. The posted primary outcome has no active-arm participants and one placebo participant. The randomized design therefore did not yield a usable treatment contrast in the posted outcome data.
The Penn Alcohol Craving Scale is listed as a secondary outcome. The record reports three outcome measures, while one secondary outcome name is listed. It does not report outcome analyses. The reason for termination, the number of completed treatment sessions, and whether follow-up calls were completed are not reported in the registry record.
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: Research participants will be randomly assigned to receive sham or active rTMS using a double blind (participant and researcher) design. Two participants were enrolled, one was randomized.
Overall Study
| Stage | Active | Placebo |
|---|---|---|
| STARTED | 0 | 1 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Though 2 people were enrolled in the study, only 1 was randomized and they were randomized to the placebo arm. That is why outcome measures for all of the active arm are zero.
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: Two participants were enrolled, one was randomized and had baseline data collected.
| Characteristic | Unit | Active | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 1 | 1 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 1 | 1 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | — | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Total Adverse Event Frequency, measured over immediately after last/10th rTMS session - up to 2 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Count of Adverse Events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the total count of adverse events recorded during rTMS treatment, assessed immediately after the last, or 10th, session within a timeframe of up to 2 weeks. The record describes an event log for each participant and session, with counts accumulated across the treatment course. This is a count outcome: it represents the frequency of recorded events, rather than a measure of symptom change or the proportion of participants experiencing improvement.
Recording adverse events is one way to describe the safety experience during a treatment study. A count can capture repeated events, so it is not necessarily interchangeable with the number of participants who had at least one event. In this record, the placebo arm has a posted primary-outcome value of 1.0 among one participant, while the active arm has no participants and no posted value. The estimate therefore describes only the placebo observation; it cannot establish a difference in event frequency between treatment arms.
Although the brief summary identifies reducing alcohol craving as the study goal, the posted primary endpoint is adverse-event frequency. The Penn Alcohol Craving Scale is listed as a secondary outcome, but the registry record does not report a result for it.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome contains a value of 1.0 for the placebo arm, with one participant, and no value for the active arm, which has zero participants. The outcome description confirms that only one participant was randomized and that assignment was to placebo. Consequently, there is no active-versus-placebo estimate for adverse-event frequency. A treatment effect, uncertainty interval, or meaningful between-arm test cannot be interpreted from these arm results.
The placebo value is a descriptive observation from the participant represented in that arm, not evidence about what would happen across a larger population. It does not provide a stable estimate of typical event frequency, and it does not describe variation among participants. The record supplies no spread measure or confidence interval for the endpoint. With no active-arm observations, the outcome cannot indicate whether active rTMS would have a different event count.
The safety record separately lists one participant at risk in the placebo group and reports one other adverse event affecting one participant, with no serious adverse events or deaths in that group. The active group has no participants at risk. These entries should be read as a very limited account of events in the enrolled study, not as evidence that the active intervention has no adverse events or that the placebo condition is safer. Zero participants in an arm means there was no exposure from which to characterize that arm's safety.
The registry status is terminated, and the recorded enrollment is 2, despite the brief summary's intended enrollment of 20. The record does not state why the study ended or whether the planned treatment and follow-up were completed. It also reports no outcome analyses. Those omissions prevent readers from assessing whether the endpoint was collected as planned, whether any craving findings were observed, or whether an analysis addressed the original clinical question.
In practical statistical terms, the results are descriptive rather than comparative. Random assignment is part of the design, but randomization alone does not produce a treatment-effect estimate when the posted primary outcome contains observations in only one arm. The record supports reporting what was recorded for the placebo participant; it does not support a conclusion about relative efficacy or safety.
9. Statistical Methods Explained
Clinical trial statistics distinguish the study design from the evidence available for analysis. A randomized parallel-group design assigns participants to separate treatment arms, intending to compare outcomes across those arms. Here the record identifies a randomized, quadruple-masked, parallel-group study, but its primary outcome description says only one participant was randomized and assigned to placebo. The active arm therefore has no posted participants for this endpoint. A randomized design cannot by itself compensate for the absence of observations in one arm.
What does a count endpoint measure?
The primary outcome is a count of adverse events, accumulated from logs across treatment sessions and assessed after the treatment course. Counts differ from continuous measurements such as a scale score: a count records how many events occurred, rather than how far a measurement lies along a scale. Counts can also differ from participant-level indicators. One participant may experience repeated events, so a total event count and the number of participants with any event answer different questions. The registry describes both event frequency and the number of participants affected in its safety entries, and those quantities should not be treated as interchangeable.
In general, count data may vary more than a simple statistical model expects, particularly when events cluster in some participants or observation periods. This is called over-dispersion. Accounting for it can affect uncertainty estimates in a sufficiently informative analysis. In this trial record, however, there is no two-arm outcome dataset from which to assess such variation. The record does not report a model for the count endpoint or a statistical analysis plan, so the method intended for handling count variation is not reported in the registry record.
Why is there no treatment contrast?
A two-arm comparison needs outcome information from both arms. The posted active-arm sample size is zero and its outcome value is missing; the placebo arm has one participant and a value of 1.0. A difference between arm summaries cannot be estimated when one arm has no outcome observations. For the same reason, a standard error, confidence interval, and inferential test for the active-versus-placebo contrast are not available from these entries.
In general, a confidence interval describes the range of effect values compatible with the data under the chosen statistical model and its assumptions. It communicates precision as well as the direction and scale of an estimate. No interval for a treatment contrast is reported, and the posted arm data do not support calculating one. The absence of an interval is not a finding of equivalence or proof that the arms are alike; it reflects that a comparative estimate cannot be formed.
How should the design masking be understood?
The record labels the study quadruple-masked. Masking is intended to limit the influence of knowledge about assigned treatment on aspects of trial conduct or outcome assessment. The record does not identify which roles were masked or describe how masking was maintained. Regardless of the masking designation, it cannot resolve the central data limitation: no active-arm participant appears in the primary endpoint results.
What do the planning assumptions mean?
The record describes sample-size planning assumptions using a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Planning calculations based on an observed effect are illustrations of the sample size that might be needed under those assumptions; they are not observed power and do not show that the trial had a particular chance of detecting an effect. The record also indicates that values were missing or not estimable for a two-arm comparison for this count outcome. With no estimable observed two-arm effect, the planning illustration cannot supply evidence about treatment efficacy or safety.
More generally, a significance threshold is a rule used in a planned inferential procedure, not a measure of clinical importance. A normal approximation is a simplifying model assumption. Equal allocation describes a planned balance between arms, not what occurred in the posted outcome data. The record's planning assumptions do not establish that these methods were used for a completed analysis. The statistical analysis plan and any interim analysis procedures are not reported in the registry record.
What analysis can be supported?
The primary outcome entries support a narrow descriptive account: one placebo participant is represented, and the active arm has no participants or posted value. They do not support a comparative count model or a treatment-effect conclusion. The registry lists no analyses. It also does not report a confidence interval, p-value, adjustment procedure, or model specification for this primary endpoint. Those details should not be inferred from the randomized and masked design labels or from the sample-size assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the Penn Alcohol Craving Scale as a secondary outcome and reports three outcome measures, but it does not report outcome analyses. The primary endpoint is adverse-event frequency. The record does not describe a hierarchy of outcomes, a strategy for controlling multiplicity, or whether any outcome was designated for confirmatory inference beyond the endpoint listing. Those details are not reported in the registry record.
Multiplicity arises when several outcomes, time points, or comparisons are tested. In general, considering many statistical tests can increase the chance of at least one apparently notable result even when no underlying effect exists. Prespecified outcome priorities and suitable adjustment methods can help readers interpret a group of tests. No such inferential results or adjustment approach are reported, so there is no basis to evaluate multiplicity-adjusted findings.
The primary outcome description specifies collection after the last, or 10th, session, within a timeframe of up to 2 weeks. The brief summary describes phone follow-up for craving and other symptoms. The record does not state how missing endpoint observations, incomplete treatment, or missing follow-up assessments were handled. It does not report imputation, sensitivity analyses, or a missing-data model. These methods are not reported in the registry record.
The analysis population is also not defined beyond the primary outcome note that only one participant was randomized, to placebo. The record does not state whether an intention-to-treat, per-protocol, or safety population was used for a formal analysis. Because the registry reports no analyses and no active-arm participant for the primary outcome, population definitions cannot create a valid two-arm comparison. The posted entries should be interpreted as limited descriptive data, with the handling of missing observations and any analysis population remaining unspecified.
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 |
|---|---|---|---|
| Placebo | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Active | 0 of 0 |
| Placebo | 0 of 1 |
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 |
|---|---|
| Active | 0 of 0 |
| Placebo | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Active | Placebo |
|---|---|---|---|
| eye blinking and transient blurriness and seeing black dots, likely due to dry eyes | Eye disorders | 0 of 0 | 1 of 1 |
The serious-adverse-event entries report one participant at risk in the placebo group and zero serious adverse events affecting participants in that group. The same group has zero deaths. The active group has zero participants at risk, zero serious adverse events, and zero deaths. The empty list of top serious-event terms indicates that no such terms are listed in the record.
The active-group zeros should not be read as evidence that active rTMS had no serious adverse events: there were no active participants at risk in the posted safety data. For placebo, the absence of a recorded serious event is a descriptive finding among the participant represented, not a precise estimate of the risk in a broader population. Very limited exposure cannot rule out uncommon events or establish comparative safety.
The record also reports one other adverse event affecting one participant at risk in the placebo group. That entry is not a serious adverse event. The safety counts are distinct from the primary endpoint's count of total adverse-event frequency; an affected-participant count and a total event count can describe different quantities. The registry does not give further event details for the listed non-serious event. These data describe what was recorded in this small, terminated study and do not establish a safety difference between the arms.
12. What the Result Does, and Does Not, Mean
The result establishes that the registry contains a primary-outcome value of 1.0 for the placebo arm and no active-arm participants or outcome value. The primary outcome description identifies the sole randomized participant as assigned to placebo. This is a description of the posted record, not a comparative estimate of the effect of rTMS.
It does not show whether active rTMS changes adverse-event frequency, because there are no active-arm observations for this endpoint. It also does not answer whether craving changed: the Penn Alcohol Craving Scale is listed as a secondary outcome, but no result for that scale is reported. The study summary's stated goal of reducing alcohol craving should not be confused with an observed finding. No treatment benefit, lack of benefit, or equivalence can be inferred from the available outcome entries.
The safety entries likewise do not support a robust comparison. The placebo arm has one participant represented and no reported serious adverse events or deaths; the active arm has no participants at risk. Those details do not characterize the safety profile of active rTMS or establish that either arm is safer. The absence of reported serious events in the placebo participant is limited information, not proof that serious events cannot occur.
The brief summary's intended enrollment of 20 differs from the registry's recorded enrollment of 2, while the primary endpoint note says only 1 participant was randomized. The registry status is terminated. The reason for termination and the extent to which planned sessions and follow-up were completed are not reported. Thus the record documents a study design and a small amount of observed outcome information, but not the planned comparative evidence.
For clinical and statistical interpretation, the key distinction is between an outcome being registered and a treatment effect being estimated. Outcomes and procedures are described, but no analysis is reported and the primary endpoint lacks active-arm data. Accordingly, conclusions about the intervention's effects remain unresolved by this record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the gap between a randomized design and an estimable comparison. The registry describes random allocation, masking, and a placebo arm, features intended to support a controlled evaluation. Yet the primary outcome record includes no active-arm participants. Without observations in both arms, the central comparative quantity cannot be estimated, regardless of the design label.
The distinction between planned and recorded enrollment also matters. The brief summary describes an intended enrollment of 20, while the registry lists enrollment of 2 and the endpoint description states that only 1 participant was randomized. A planned enrollment describes the study's objective, not the data available for analysis. Interpreting the posted results against the intended study requires keeping those different quantities separate.
The endpoint choice highlights another statistical distinction: an adverse-event count and a craving score measure different aspects of a trial. The primary outcome is event frequency, whereas the stated treatment goal concerns alcohol craving and the Penn Alcohol Craving Scale is listed as secondary. Without reported craving results, the safety endpoint cannot stand in for evidence about craving.
Finally, a single-arm observation and safety counts from minimal exposure carry substantial uncertainty, even when their recorded values are clear. Descriptive reporting is still useful because it makes the available experience visible, but it cannot substitute for a treatment-effect estimate. The record therefore matters for understanding what was registered, what was recorded, and why those are not equivalent to a completed comparative analysis.
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 most direct limitation is that the primary outcome has no active-arm participants and only one placebo participant. A treatment contrast cannot be estimated from these data. The recorded enrollment of 2 is lower than the brief summary's intended enrollment of 20, and the outcome description specifies that only one participant was randomized. The record does not explain the difference or the reason the study was terminated.
The primary endpoint is a count of adverse events after the planned treatment course. The registry does not report whether the participant completed all 10 sessions, whether every planned session-level log was available, or how incomplete observation would be handled. The timeframe is described as immediately after the last, or 10th, session and up to 2 weeks, but completed endpoint timing is not reported.
Although alcohol craving is the stated study goal and the Penn Alcohol Craving Scale is listed as a secondary outcome, no result for that scale appears in the record. The registry reports three outcome measures but lists only one secondary outcome name. Outcome definitions beyond the primary endpoint, outcome-analysis details, multiplicity procedures, and missing-data methods are not reported in the registry record.
The safety information is limited by the lack of active-arm exposure and the minimal number of participants represented in the placebo group. The record does not provide further details about the non-serious event. The reason for termination, the status of follow-up calls, and the analysis population are also not reported. These limitations make the record unsuitable for drawing comparative conclusions about efficacy or safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pilot rTMS for AUD+mTBI — NCT03995173.
- Registry record last updated 2026-10-30; status last verified 2026-10.
- Results first posted 2026-10-30.
- 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
NCT03995173 is a Phase 2 randomized, quadruple-masked, parallel-group study sponsored by the VA Office of Research and Development. It concerns active versus placebo rTMS for veterans with alcohol use disorder and co-occurring mild traumatic brain injury and/or post-traumatic stress disorder. The record lists enrollment of 2, a start date of 2019-03-21, a primary completion date of 2020-03-31, and terminated status.
The primary endpoint is total adverse-event frequency after the planned treatment course. The outcome note says only 1 participant was randomized, to placebo. The posted primary outcome is 1.0 in placebo and has no active-arm value because the active arm has no participants. No outcome analyses are reported. The Penn Alcohol Craving Scale is listed as a secondary outcome, but its result is not reported in the registry record. The available data are descriptive and do not support a treatment comparison.