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 Transcranial Magnetic Stimulation for the Treatment of Auditory Hallucinations in Schizophrenia (NCT01595503), a randomized na study. The primary outcome is Change in Severity of Auditory Hallucinations.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01595503 |
| Phase | NA |
| Condition | Schizophrenia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan |
| Results posted | Yes |
2. Clinical Question
Population
People with schizophrenia and auditory hallucinations were the intended population. The study description focuses on refractory auditory hallucinations. The registry record reports enrollment of 5, but does not provide a detailed description of participant characteristics or eligibility criteria in the information recorded for this trial.
Intervention
One study approach used repetitive transcranial magnetic stimulation (rTMS) with functional magnetic resonance imaging (fMRI)-based targeting. The language task and fMRI were used to identify a language-processing region as the stimulation target.
Comparator
The other approach used rTMS with landmark-based targeting. The brief summary describes this method as locating the stimulation site with scalp landmarks. The registry record does not report further procedural details for either approach.
Primary question
The intended comparison concerned change in auditory-hallucination severity after two weeks, contrasting the two targeting approaches. The record says the original groups were planned for separate analysis, but the data available when results were reported could no longer be separated. Treated participants were therefore included in a single arm, so the posted results cannot provide a comparison of the targeting methods.
3. Trial Design
The registry describes a randomized, double-masked, parallel trial sponsored by the University of Michigan. It lists two procedures: rTMS with fMRI-based targeting and rTMS with landmark-based targeting. The brief summary says the study was designed to examine rTMS for auditory hallucinations in schizophrenia while comparing these two ways of selecting a stimulation site. The record does not report the allocation procedure or how masking was implemented.
Enrollment is listed as 5. The study status is terminated. The recorded start is 2011-05 and the primary completion is 2012-08. The registry record does not report why the trial was terminated, whether the planned enrollment was reached, or whether termination followed a prespecified rule. It also does not report a protocol-level explanation for the enrollment target.
The intended design would have allowed a comparison between groups receiving the same general intervention with different targeting methods. However, the registry states that the original groups were planned for separate analysis and that the data available at results reporting were no longer separable. All treated participants were consequently included in one arm. This change in the presentation of the results prevents an estimate of the difference between the targeting approaches from being read from the posted results.
The record lists one outcome measure and no analyses. It does not report numerical results for the primary outcome, participant flow by original group, or the number of participants with outcome data at the two-week timeframe. A statistical analysis plan, details of randomization, and details of blinding are not reported in the registry record. These omissions limit what can be concluded about how closely the reported data correspond to the intended randomized comparison.
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: The study was terminated because of the small enrollment (2 or 3 subjects per treatment arm), the data that was examined was pooled for all the subjects. At the time of results reporting it is impossible to disambiguate the two arms. Randomization tables are not available; hence, we cannot report the results by treatment arm.
Overall Study
| Stage | rTMS With Either fMRI-based Targeting or Landmark Based Targeting. |
|---|---|
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The two original groups: with fMRI targeted and landmark based were planned to be analyzed separately, the data available at the time of results reporting, is no longer separable. Thus all treated participants are included in a single arm. While this does not allow comparison between the two approaches to rTMS usage, it still allows one to see the impact of using rTMS with one method or the other, albeit still in a tiny sample size.
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 | rTMS With fMRI-based Targeting or Landmark Based Targeting |
|---|---|---|
| Participants analysed | 5 | |
| Age, Continuous | years | 39.8 (SD 12.5) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Severity of Auditory Hallucinations, measured over Two weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary outcome is titled “Change in Severity of Auditory Hallucinations.” It uses the Hallucination Change Scale, reported as a score on a scale, with the timeframe listed as two weeks. The description defines the baseline score as 10. Scores range from 0, described as no hallucinations, to 20, described as hallucinations twice as bad as baseline. Under that interpretation, a score < 10 indicates reduced hallucinations, while a score > 10 indicates increased hallucinations.
The measure is intended to represent the direction and degree of change in hallucination severity relative to the defined baseline. This makes it relevant to the study question, which concerns whether different targeting approaches are associated with different changes over the stated timeframe. The primary outcome is specified as a mean with standard deviation, a way to describe the average score and its variability in a group.
The registry record does not report the observed mean, standard deviation, or other numerical outcome result. It also does not clarify in the available description how scores were collected, who rated them, or how any missing two-week assessments were handled. Consequently, the scale’s scoring rules can be described, but the observed severity or change in severity cannot be determined from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive issue is that the trial’s intended comparison is not available in the reported results. The record describes randomization to two targeting methods, but also states that the data available when results were reported could no longer be separated into the original groups. Treated participants were included in a single arm. A combined group cannot show whether outcomes differed between fMRI-based and landmark-based targeting, because the group identity needed to make that contrast is not retained in the reported results.
The registry lists a primary outcome and a two-week timeframe, but reports no numerical primary outcome values and no analyses. Therefore, the direction and size of the observed outcome, its variability, and the precision of any estimate cannot be assessed from this record. There is no reported between-group estimate, confidence interval, or p-value to interpret. The absence of those results is not evidence that the methods had the same outcome; it means that the registry record does not provide a usable statistical comparison.
Enrollment was 5, and the study is marked terminated. With such a small recorded enrollment, even a complete set of individual observations would generally be expected to provide limited precision for estimating an average or comparing groups. That is a general statistical point, not a calculation of precision for this trial. The record does not supply outcome values from which a confidence interval or other measure of uncertainty could be assessed.
For a continuous outcome, a group mean describes the central level of the recorded scores, while a standard deviation describes how spread out those scores are around the mean. Neither statistic alone answers the randomized comparison question: the relevant contrast would be the difference between groups, accompanied by information about uncertainty. Since the original group data are not separable in the reported results, that contrast cannot be recovered from the combined-arm description.
The registry reports zero serious adverse events and zero other adverse events among 5 at risk in the rTMS group. These are descriptive safety counts in a small group, not a precise estimate of how often such events might occur in a broader population. A zero count does not establish that an event is impossible or that there is no risk. The record also lists zero deaths. No further numerical safety analyses are reported.
Overall, the record documents the trial’s question and the endpoint definition, but it does not provide outcome evidence that can distinguish between the targeting methods. No conclusion about comparative efficacy or equivalence follows from the unavailable comparison. The trial status and the inability to separate groups are essential context when reading any single-arm information in the registry.
9. Statistical Methods Explained
What does a randomized comparison aim to estimate?
General: In a randomized trial, assignment is intended to make the groups comparable, on average, with respect to factors that could influence the outcome. The analysis can then estimate the difference in outcomes associated with assignment to the competing approaches, subject to the trial’s conduct, outcome measurement, and missing-data handling. Randomization is a design feature; it does not by itself guarantee that a useful comparison can be made if the group identities or outcome data are unavailable.
For this trial, the intended contrast was between rTMS using fMRI-based targeting and rTMS using landmark-based targeting. The registry record says the original groups were planned to be analyzed separately, but the data at results reporting were no longer separable. Once the results are represented as one arm, the planned randomized contrast is not reported. The record gives no group-specific outcome estimates that would allow that contrast to be reconstructed.
What do the mean and standard deviation describe?
General: A mean is an average that summarizes the location of continuous observations. A standard deviation describes their dispersion around the mean. The pair can help readers understand both the typical score and how much individual observations vary, but it does not by itself quantify the uncertainty in a group estimate or a between-group difference. That uncertainty is commonly described with a confidence interval, which gives a range of values compatible with the data and the method used to construct it.
The registry identifies the primary outcome as a mean with standard deviation, but does not report either statistic numerically. It also does not report a confidence interval for a group result or for a comparison. No uncertainty estimate for the primary outcome can therefore be assessed from the registry record.
Why does a comparison need more than an outcome scale?
General: A scale defines what is measured and how its values should be interpreted. An analysis must additionally identify the observations to include, the groups being contrasted, and the statistical summary used to estimate the contrast. If group labels are unavailable, a combined average does not reveal how scores were distributed between the randomized approaches. A result can describe the combined participants but cannot answer which approach had the more favorable average or whether the approaches differed.
The Hallucination Change Scale description anchors a baseline score at 10 and gives the direction of scores relative to that point. This scoring information explains how a score would be interpreted. It does not substitute for reported outcome values, nor does it identify the outcome in each original targeting group. The record’s statement that all treated participants were included in a single arm is therefore a substantive constraint, not merely a presentation detail.
What can a p-value or confidence interval tell a reader?
General: A p-value is a measure, under a specified statistical model and null hypothesis, of how incompatible the observed data are with that hypothesis. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. A confidence interval communicates uncertainty around an estimate and can show which effect sizes remain compatible with the data and analysis assumptions. Both depend on an analysis of the relevant data; neither can be inferred from randomization alone.
The registry lists no analyses and no p-values or confidence intervals for the primary outcome. There is consequently no inferential result to interpret. In particular, the absence of a reported significant test cannot be read as evidence of no difference, because the record does not report a test of the targeting approaches.
How should the planning illustration be understood?
General: A sample-size calculation is a planning exercise that asks how many participants might be needed for a future study under chosen assumptions about the target effect, variability, significance level, allocation, and statistical model. Its output is not an observed result, and it does not measure the power achieved by a completed study. Any planning estimate depends on its assumptions, so it should not be mistaken for evidence that the planned effect occurred.
The registry’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect and describes the calculation as a planning illustration rather than the trial’s own design. No numeric planning outputs are stated in the registry record. These assumptions do not supply missing outcome estimates or restore the unavailable comparison between the original groups.
General: Small samples can make estimates highly sensitive to individual observations and can produce wide uncertainty. Whether that occurred for this endpoint cannot be quantified without the observations and analysis. With enrollment listed as 5 and no numerical outcome results, it would not be appropriate to claim a particular precision, statistical significance, or power for the trial. The posted information supports a description of the design and its reporting limitations, not a reconstructed efficacy analysis.
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.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| rTMS | 5 | 5.900 | 1.700 | 3.789 to 8.011 |
R code and output
arm <- c("rTMS")
n <- c(5)
m <- c(5.9)
sp <- c(1.7)
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 rTMS 5 5.900 1.700 3.789 8.01111. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure, titled “Change in Severity of Auditory Hallucinations,” and identifies it as the primary outcome. It does not report a multiplicity procedure or explain how testing across outcomes, timepoints, subgroups, or other analyses was handled. Listing one outcome measure is not enough to establish that there was only one analysis or that no multiplicity issue arose. The record lists no analyses, so there are no reported tests from which to assess adjustment or selective reporting.
Missing-data handling is not reported in the registry record. The outcome timeframe is two weeks, but the record does not state how many participants had a score at that time, whether any observations were missing, why data might be missing, or how missing observations were treated. General: Missingness can affect interpretation if participants with observed outcomes differ systematically from those without them. Methods such as complete-case analysis or imputation make different assumptions; the appropriate interpretation depends on the data and plan. No particular method can be attributed to this trial from the available record.
The analysis population is also not described in detail. The registry states that all treated participants were included in a single arm because the original groups were no longer separable in the data available at results reporting. It does not report whether analysis was based on assignment, treatment received, or another population definition, nor does it provide participant flow by original group. The inability to preserve the separate groups limits interpretation of the randomized design and prevents a reported comparison of targeting methods.
12. 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 |
|---|---|---|---|
| rTMS | 0 | 5 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| rTMS | 0 of 5 |
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 |
|---|---|
| rTMS | 0 of 5 |
The registry reports a single rTMS safety group. Among 5 at risk, it lists 0 participants affected by serious adverse events and 0 affected by other adverse events; deaths are listed as 0. These are the recorded counts for this group. The registry does not list serious adverse event terms.
General: A count of zero means no events of that category were recorded among the participants included in the stated risk group. It does not demonstrate that the event cannot occur, and a small group can provide little information about uncommon harms. A more precise assessment would require additional data and an appropriate uncertainty analysis. No such analysis is reported in the registry record.
These safety figures do not compare the two targeting approaches. The record presents a single rTMS group, and the original groups were not separable in the reported data. The figures should therefore be read as descriptive counts for the recorded group, not as evidence that one targeting method has a different safety profile from the other.
13. What the Result Does, and Does Not, Mean
The record establishes that a randomized, double-masked, parallel study was intended to compare fMRI-based and landmark-based targeting for rTMS in schizophrenia-related auditory hallucinations. It defines a primary severity outcome and gives a two-week timeframe and scoring interpretation. It also records enrollment of 5 and a terminated status. These details describe the question and the trial’s context, but they do not provide a numerical result for the primary outcome.
The key limitation is that the original targeting groups could not be separated in the data available when results were reported. The treated participants were included in a single arm. As a result, the posted results do not estimate the difference between the targeting methods. They cannot establish that one method produced a greater reduction, that the methods were equivalent, or that there was no difference. Those conclusions would require a reported comparison with relevant outcome data and an analysis.
The scale description indicates how scores relate to the defined baseline: scores below 10 represent reduced hallucinations, and scores above 10 represent increased hallucinations. But without observed scores, means, or variability, the record does not show whether participants’ hallucinations changed in either direction or how consistently they changed.
The safety counts report no serious or other adverse events and no deaths in the recorded rTMS group. Given enrollment of 5, these counts are descriptive and do not establish the absence of risk. The record does not report a comparative safety analysis by targeting method.
In short, the registry record documents a clinically focused randomized study but does not offer a separable randomized outcome comparison. Its primary statistical meaning is therefore limited: the design intended to compare two approaches, while the posted results do not support judging their relative outcomes.
14. Why This Trial Matters Statistically
This trial illustrates why preservation and reporting of randomized group information are central to statistical interpretation. Randomization creates the basis for comparing approaches, but a comparison requires results that retain the distinction between the assigned groups. In this record, the original groups were planned for separate analysis, yet the available data at results reporting were no longer separable. The resulting single-arm presentation cannot answer the original comparative question.
The case also distinguishes an outcome definition from an outcome result. The registry gives a scale, a baseline reference, a direction of interpretation, and a timeframe. Those details make the intended measurement understandable. They do not tell readers what scores were observed, how variable they were, or whether the targeting strategies differed. Statistical transparency requires both a clear measure and interpretable numerical results.
Enrollment of 5 underscores why estimates from small trials need careful attention to uncertainty, although the specific precision cannot be assessed without results. General: Small studies can be useful for feasibility or early investigation, but their estimates may be unstable and their ability to identify differences limited. The registry does not report whether feasibility was an objective or provide a sample-size justification, so those purposes should not be assumed for this trial.
Finally, the record shows how trial status, outcome availability, group separability, and analysis reporting all shape the conclusions a reader can draw. A randomized label alone does not make an unavailable comparison interpretable. Here, the central statistical lesson is to distinguish the question a study was designed to ask from the evidence its registry results actually report.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most consequential trial-specific limitation is that the original fMRI-based and landmark-based groups were no longer separable in the data available at results reporting. The registry states that all treated participants were included in one arm. This prevents assessment of the intended comparison, regardless of the randomized design.
The registry reports enrollment of 5 and a terminated status, but does not report the reason for termination, the target enrollment, or whether the planned enrollment was reached. The record does not provide a numerical result for the primary outcome, group-specific results, or analyses. Thus, neither the direction nor the precision of an outcome estimate can be evaluated.
The available record also does not report participant characteristics, group-specific participant flow, the number with two-week outcome data, missing-data procedures, the analysis population definition, or a statistical analysis plan. Details of allocation and masking are not provided beyond the randomized and double-masked design labels. The scale’s description identifies its range and reference point, but the record does not explain who collected or rated the outcome.
Safety reporting is limited to counts for a single rTMS group and does not distinguish the targeting approaches. The absence of recorded events in that group should not be interpreted as a precise estimate of safety. Taken together, these gaps mean that the registry record supports a description of the intended study question and reported safety counts, but not a comparative analysis of efficacy or safety.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Transcranial Magnetic Stimulation for the Treatment of Auditory Hallucinations in Schizophrenia — NCT01595503.
- Registry record last updated 2021-12-08; status last verified 2021-11.
- Results first posted 2021-12-08.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
NCT01595503 is a University of Michigan trial titled “Transcranial Magnetic Stimulation for the Treatment of Auditory Hallucinations in Schizophrenia.” Its official title describes functional targeting of rTMS for refractory auditory hallucinations. The registry lists a randomized, double-masked, parallel design, enrollment of 5, a start of 2011-05, primary completion of 2012-08, and terminated status.
The intended comparison was rTMS with fMRI-based targeting versus rTMS with landmark-based targeting. The primary outcome was change in auditory-hallucination severity at two weeks, measured with the Hallucination Change Scale. The original groups could no longer be separated in the data reported, so treated participants were included in a single arm. The registry lists no analyses and does not report numerical primary outcome results. It records 0 serious adverse events, 0 other adverse events, and 0 deaths in the rTMS group.