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 Treatment of Negative Symptoms of Schizophrenia With Transcranial Magnetic Stimulation (TMS) (NCT00517075), a randomized phase 2 study. The primary outcome is Clinical Improvement of Negative Symptoms (Positive and Negative Syndrome Scale [PANSS] Negative Symptoms Subscale) Relative to Pre-treatment Baseline..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00517075 |
| Phase | Phase 2 |
| Condition | Schizophrenia, Schizoaffective Disorder |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 14 |
| Arms in the primary outcome | n/a |
| Lead sponsor | New York State Psychiatric Institute |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with schizophrenia or schizoaffective disorder. The registry lists an enrollment of 14. The record does not provide further eligibility details, participant characteristics, or information about who was included in the primary outcome population. Its stated rationale focuses on negative symptoms and social dysfunction in schizophrenia, while the condition list also includes schizoaffective disorder.
Intervention
The planned intervention was high-frequency repetitive transcranial magnetic stimulation (rTMS), directed to either the left dorsolateral prefrontal cortex (DLPFC) or the left inferior parietal lobe (IPL). The registry rationale links hypoactivity in the DLPFC and abnormalities in the IPL with negative symptoms. The intervention descriptions also include an open crossover option: participants who did not respond could possibly receive active treatment at a target not treated during the randomized phase.
Comparator
The planned comparison included sham, described as placebo, high-frequency rTMS. The record describes active and sham conditions randomized in a 2:1 ratio for the IPL arm, and a sham condition targeting the DLPFC or IPL. It also lists active high-frequency treatment to the left DLPFC. How the randomized comparisons were ultimately implemented is not reported in the registry record.
Primary question
The primary question was whether rTMS would improve negative symptoms relative to pretreatment baseline, as measured by the PANSS Negative Symptoms Subscale. The study hypothesis was that active stimulation at the left DLPFC or left IPL would reduce negative symptom severity more than sham stimulation. The record also describes a hypothesis about social dysfunction, assessed with the Social Adjustment Scale, the Social Adaptation Self-Evaluation Scale, and the Social Functioning Scale. The primary outcome data were not analyzed or presented.
3. Trial Design
The registry describes a randomized, triple-masked, crossover Phase 2 study, with enrollment listed as 14. The study is titled as an investigation of TMS for negative symptoms of schizophrenia; its official title also names social dysfunction. The listed conditions are schizophrenia and schizoaffective disorder. The sponsor is the New York State Psychiatric Institute. The recorded start was 2004-09, and primary completion was 2011-06. The current status is terminated.
The intervention descriptions identify high-frequency rTMS directed to the left IPL or left DLPFC, as well as sham treatment. One arm description says active and sham conditions were randomized in a 2:1 ratio for left IPL treatment and describes double-blinding. Another describes sham treatment to the DLPFC or IPL, also with active and sham conditions randomized in a 2:1 ratio. A separate arm description identifies active high-frequency DLPFC treatment. The registry’s overall masking field says triple; which roles were masked, and how masking was maintained, are not reported in the registry record.
The design is labeled crossover. The arm descriptions say that, after the randomized phase with three arms, participants who did not respond could have the possibility of receiving open active treatment at a target not treated in the randomized phase. This describes an option, not evidence that the open phase occurred or that participants received it. The record does not report the crossover sequence, treatment-period details, washout procedures, or numbers entering each phase. It also does not provide a statistical analysis plan or explain how the randomized and open phases were intended to contribute to the primary analysis.
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
| Stage | High Frequency rTMS | Active High Frequency rTMS | Sham/Placebo | Open Cross Over High Frequency rTMS |
|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.
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: P.I. has left the institution and NYSPI has no access to the data. Results will not be analyzed or presented.
| Characteristic | Unit | High Frequency rTMS | Active High Frequency rTMS | Sham/Placebo | Open Cross Over High Frequency rTMS | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 0 | 0 | 0 | 0 | 0 | |
| Gender: Female | — | — | — | — | — | |
| Gender: Male | — | — | — | — | — | |
| Region of Enrollment: United States | participants | — | — | — | — | — |
6. Primary Endpoint
The registry lists the primary outcome as Clinical Improvement of Negative Symptoms (Positive and Negative Syndrome Scale [PANSS] Negative Symptoms Subscale) Relative to Pre-treatment Baseline., measured over At baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is described as clinical improvement in negative symptoms relative to pretreatment baseline, measured with the Positive and Negative Syndrome Scale (PANSS) Negative Symptoms Subscale. The registry lists assessments at baseline, every 2 weeks during rTMS sessions, and at monthly follow-up visits. The primary outcome description does not give a numerical result, a summary measure, or a definition of improvement beyond the stated comparison with baseline.
The choice of this outcome follows the study’s central hypothesis: active high-frequency stimulation at the left DLPFC or left IPL might reduce negative symptom severity more than sham stimulation. A symptom scale can translate a clinical construct into a recorded measure that can be compared across assessment times and treatment conditions. In general, repeated measurements can describe how an outcome changes over time, but their interpretation depends on the planned analysis, the completeness of follow-up, and how treatment periods are handled. Those details are not reported in the registry record.
The record also names social-function measures as part of the study rationale, but these are not the registered primary outcome. The primary outcome field states that the principal investigator left the institution, the institute had no access to the data, and the results would not be analyzed or presented. Consequently, the record does not support an estimate of change in PANSS negative symptoms or a comparison between active and sham treatment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinical question and a planned primary measure, but it does not report an analyzed primary outcome. It explicitly says that the data were inaccessible after the principal investigator left the institution and that results would not be analyzed or presented. Accordingly, there is no reported treatment contrast, estimate of symptom change, confidence interval, or primary-outcome significance test to interpret. The record does not establish whether active stimulation differed from sham on negative symptoms.
The absence of an estimate is different from an estimate showing no difference. Without analyzed outcome data, the direction and size of any treatment contrast are unknown, and its precision cannot be assessed. No conclusion about the stated hypothesis follows from the lack of a reported result. This applies both to the comparison with sham and to changes relative to pretreatment baseline.
The registry lists secondary outcomes involving global clinical improvement, social functioning, depression, theory of mind, smoking behaviors, cognitive function, and cortical excitability. It does not provide results for these outcomes. Nor does it report how many participants contributed data to any outcome, whether all planned assessments took place, or whether an analysis was conducted for any secondary measure. The primary outcome statement specifically explains why its results were not analyzed or presented; the broader outcome fields do not supply results that would fill that gap.
The adverse-event fields require similar restraint. For each listed group, the record displays zero in the serious and other event fields for participants at risk and affected, while deaths are recorded as null. These entries do not provide interpretable group-specific event rates or a clear account of event ascertainment. In particular, zero values in fields for participants at risk are not a basis for concluding that no adverse events occurred. The registry does not report further adverse-event details.
Overall, this record documents a terminated study with an enrollment listing and a planned randomized crossover design, but without a reported primary efficacy analysis. Its hypotheses and design description should not be mistaken for findings. The statistical evidence needed to quantify treatment effects, assess uncertainty, or compare the intended intervention conditions is not reported in the registry record.
9. Statistical Methods Explained
What does a randomized comparison contribute?
In general, random allocation aims to make treatment groups comparable with respect to factors that could influence an outcome, including factors that were not measured. This supports a causal interpretation when the allocation is implemented as planned and the analysis respects the design. Randomization does not itself guarantee that groups are balanced in a small study, nor does it replace reporting the actual treatment assignments, outcome data, and analysis. The registry labels this study randomized, but it does not report the allocation procedure or an analyzed comparison.
What does crossover mean statistically?
In general, a crossover design exposes participants to treatment conditions in sequence, allowing within-participant comparisons when the design and analysis support them. Repeated observations from the same participant are related, rather than independent. An analysis therefore needs to account for that dependence. The interpretation may also depend on treatment order, period effects, and whether an earlier treatment can influence a later observation. The registry labels the design crossover but does not report sequence details, a washout procedure, period-specific data, or the planned model. It is not possible to determine from the record how those design features were handled.
The registry describes an open active-treatment option for participants who did not respond during the randomized phase, at a target not treated in that phase. Open treatment is not the same comparison as a randomized active-versus-sham contrast: treatment assignment and masking differ. In general, combining data from randomized and open phases requires a clearly defined estimand and analysis strategy. The record does not say whether the open phase occurred, how response was defined, or whether those observations were included in any analysis.
Why do estimates and confidence intervals matter?
In general, an effect estimate describes the observed contrast on the chosen outcome, while a confidence interval conveys the uncertainty around that estimate under the analysis assumptions. The estimate and its interval help readers judge both the magnitude compatible with the data and the precision of the result. A significance test alone would not describe the size or precision of an effect. Here, the registry does not report a primary outcome estimate, confidence interval, or test, so those features cannot be assessed.
What would repeated measurements require?
The primary outcome schedule includes baseline assessments, repeated assessments during rTMS sessions, and monthly follow-up visits. In general, repeated measurements can reveal the timing and pattern of change, but observations from the same person are correlated. Analysis choices may include a prespecified time point, a summary across times, or a model of the trajectory. Those choices can lead to different interpretations and should be specified in advance. The registry does not state which approach was intended, how baseline would enter the analysis, or how follow-up measurements would be used.
Missing observations can also affect repeated-measures analyses. In general, the consequences depend on why observations are missing and on the assumptions used by the analysis. The registry does not report attendance, missingness, reasons for missing data, or a missing-data strategy. Without those details, the completeness of follow-up and the robustness of any hypothetical estimate cannot be evaluated.
What can the planning illustration establish?
The record describes a sample-size illustration based on a fraction of an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; it distinguishes participant-per-arm calculations from total-event calculations for time-to-event outcomes. These are stated assumptions for a planning illustration, not the trial’s own design justification. The registry does not report a planning effect estimate or sample-size justification for this study, and no primary outcome effect was analyzed or presented. Thus the illustration cannot establish observed power or provide evidence that the study could detect a particular clinical effect. Any numerical planning values require a reported effect and calculation assumptions; they should not be treated as trial results.
Finally, the registry records no analyses in its analysis count and says the primary outcome would not be analyzed or presented. No analysis method, adjustment strategy, or model specification is reported. Statistical interpretation is therefore limited to describing the intended design and outcome, not evaluating an estimated treatment effect.
10. Multiplicity, Missing Data and Analysis Populations
The study description includes a primary negative-symptom outcome and several secondary outcomes, while the brief summary also states hypotheses about social dysfunction. Testing multiple outcomes, time points, or treatment contrasts can increase the chance of finding a nominally unusual result even when there is no underlying effect. In general, a statistical plan can address this by defining a primary contrast, specifying which analyses are confirmatory, and stating whether and how multiplicity will be controlled. Such a plan is not reported in the registry record. The primary outcome itself has multiple planned assessment times, but the record does not identify which time point or summary would anchor a treatment comparison.
The record does not report an analysis population, participant flow, numbers contributing outcome data, or the handling of missing measurements. It also does not say whether analyses would follow randomized assignment or use another population definition. These omissions matter in general because decisions about eligibility for analysis and incomplete observations can affect both the estimated contrast and its interpretation. No missing-data assumptions or sensitivity analyses are reported.
The registry describes a crossover design and a possible open-treatment phase for nonresponders, but it does not report how these phases would be analyzed together or separately. The roles of treatment sequence, period, and within-participant correlation are not specified. It also does not describe an interim analysis or a statistical monitoring procedure; these matters are not reported in the registry record. Given the explicit statement that the primary outcome data would not be analyzed or presented, multiplicity and missing-data methods cannot be assessed from observed analyses. The record supports identifying these unanswered questions, not inferring how the investigators would have resolved them.
11. What the Result Does, and Does Not, Mean
The record establishes that a randomized, triple-masked crossover study was planned to investigate high-frequency rTMS for negative symptoms and social dysfunction, with sham treatment included in the described design. It identifies a primary measure, the PANSS Negative Symptoms Subscale, and a schedule of baseline, treatment-period, and follow-up assessments. These registry entries describe the research question and intended measurement strategy; they are not evidence of an effect.
The record does not provide analyzed primary outcome data. It states that results would not be analyzed or presented because the principal investigator left the institution and the institute had no access to the data. Therefore, the record cannot show whether negative symptoms changed, whether changes differed between active and sham conditions, or how uncertain any contrast would be. The same limitation applies to the listed secondary outcomes, for which results are not reported.
This absence should not be interpreted as proof that rTMS had no effect, nor as proof that it had an effect. It is an absence of a reported analysis, not a treatment estimate compatible with a particular conclusion. The intervention hypotheses, arm descriptions, and outcome schedule cannot substitute for results.
The registry’s adverse-event entries also do not support a safety conclusion. Although the listed fields display zero values for at-risk and affected participants, deaths are null and no further event information is given. The record does not explain these fields or provide event rates and ascertainment details. The appropriate statistical interpretation is consequently narrow: the registry documents the study’s stated design and the reason its primary results were unavailable, while leaving treatment effects and their precision undetermined.
12. Why This Trial Matters Statistically
This record is statistically important because it makes visible the distinction between a registered hypothesis and an analyzed result. The trial description specifies a randomized, triple-masked crossover design and a primary outcome, but the registry also states that the data were inaccessible and that the primary results would not be analyzed or presented. A detailed planned design does not yield an effect estimate when the outcome data are unavailable for analysis.
The study also illustrates why outcome timing and design structure matter. The primary measure was scheduled repeatedly during treatment and follow-up, and the design was labeled crossover with a possible open-treatment phase. In general, those features require clear definitions of the target contrast, analysis population, assessment time, and handling of repeated observations and treatment sequence. Without a reported analysis plan or results, readers cannot determine how those issues would have been addressed.
Another statistical lesson is that missing results are not equivalent to a null finding. Without an estimate and its uncertainty, neither the magnitude nor the direction of a treatment contrast is known. The record therefore cannot answer its stated comparative question. This distinction is essential when interpreting terminated studies and when separating the intent of a trial from the evidence it ultimately reports.
Finally, registration details can clarify what was proposed and what remains unavailable. Here, the record gives the primary measure, intended assessment schedule, intervention targets, and a reason for non-analysis. It does not provide the results needed to assess efficacy, precision, or the secondary hypotheses. Transparent recognition of those boundaries is more informative than treating absent analyses as evidence for or against the intervention.
13. 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 main limitation is explicit: the principal investigator left the institution, the New York State Psychiatric Institute had no access to the data, and the primary outcome results would not be analyzed or presented. No primary outcome estimate, uncertainty interval, or treatment comparison is reported. The record also lists no analyses. This prevents statistical assessment of the central hypothesis and makes it impossible to evaluate precision or the direction of any observed contrast.
Other design and reporting details are incomplete. The record labels the study randomized, triple-masked, and crossover, while arm descriptions refer to double-blinding in some conditions. It does not explain which participants or study personnel were masked, how randomization was implemented, or how treatment sequence and period effects would be addressed. The proposed open crossover option is described, but whether it occurred is not reported. Neither the number entering each phase nor the analysis population is given.
The registry lists an enrollment of 14, but does not report participant characteristics, outcome completion, missingness, or reasons for any unavailable observations beyond the stated loss of data access. It does not report an analysis plan, multiplicity strategy, missing-data method, or sample-size justification specific to the trial. The stated sample-size assumptions describe a planning illustration, not a documented trial-specific rationale or observed power.
Adverse-event entries are difficult to interpret because the record gives zero values in the at-risk and affected fields and null for deaths, without additional descriptions of collection or ascertainment. Taken together, these gaps mean that the registry can describe the trial’s intended question and recorded status but cannot support estimates of treatment effect or a detailed assessment of its execution.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Treatment of Negative Symptoms of Schizophrenia With Transcranial Magnetic Stimulation (TMS) — NCT00517075.
- Registry record last updated 2017-01-13; status last verified 2017-01.
- Results first posted 2017-01-13.
- 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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17. Record Summary
NCT00517075 is a terminated Phase 2 study sponsored by the New York State Psychiatric Institute. The registry lists an enrollment of 14, a recorded start of 2004-09, and primary completion in 2011-06. It describes a randomized, triple-masked crossover study of high-frequency rTMS directed to the left DLPFC or left IPL, with sham treatment included in the randomized-phase descriptions and a possible open active-treatment option for nonresponders.
The primary outcome was clinical improvement in negative symptoms relative to pretreatment baseline on the PANSS Negative Symptoms Subscale, with assessments planned at baseline, every 2 weeks during rTMS sessions, and monthly follow-up visits. The primary outcome record states that the data were inaccessible after the principal investigator left the institution and that results would not be analyzed or presented. No primary treatment effect or analysis is reported, so the registry describes the study question but does not provide an answer to it.