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 HIFU Treatment of Cutaneous Neurofibromas in Neurofibromatosis Type 1: Safety and Efficacy (NCT05119582), a na na study. The primary outcome is Short Term Safety Profile - Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05119582 |
| Phase | NA |
| Condition | Cutaneous Neurofibroma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Joergen Serup |
| Results posted | Yes |
2. Clinical Question
Population
Adults over 18 years of both sexes with neurofibromatosis type 1 and cutaneous neurofibromas close to the skin surface. The study summary describes 20 participants across two centers, with each participant having a minimum of 8 neurofibromas eligible for treatment.
Intervention
High-intensity focused ultrasound treatment using the TOOsonix System ONE-M. The device is described as focusing ultrasound below the skin surface to heat targeted tissue.
Comparator
There is no concurrent control group. The registry lists a single treatment group, and allocation is recorded as NA. The study therefore does not provide a randomized comparison with another treatment or with no treatment.
Primary question
What short-term safety events occur after treatment, particularly whether participants have an Overall AE Score larger than Grade 2 at the 3-month follow-up? The registry defines treatment as tolerable under its endpoint criterion if less than 30% of treated participants meet that score threshold. The result for that criterion is not reported in the registry record.
The clinical question concerns safety after treatment rather than a comparison of treatment effects between groups. The listed primary outcome is a participant-level count of those experiencing adverse events, with the assessment focused on events requiring medical intervention within three months. A secondary outcome concerns long-term safety and adverse events, but its results are not reported in the registry record.
The study summary describes treatment of cutaneous neurofibromas in people with neurofibromatosis type 1. Although participants may have multiple eligible lesions, the primary outcome is defined in terms of participants and their adverse-event grades, not a count of lesions that change after treatment. The registry record does not report a primary efficacy outcome assessing lesion removal or change.
3. Trial Design
This is a completed, single-group device study of the TOOsonix System ONE-M for cutaneous neurofibromas. The registry lists the study phase as NA, allocation as NA, masking as none, and the model as single group. No concurrent comparator is listed. These design features mean the posted results describe participants treated with the device rather than a randomized treatment contrast.
The enrollment is 20. The study summary describes 20 adults of both sexes distributed between two centers; each participant was to have a minimum of 8 cutaneous neurofibromas eligible for treatment. The summary describes treatment of neurofibromas close to the skin surface in people with neurofibromatosis type 1. The study started on 2022-04-13, reached primary completion on 2024-01-17, and has a completed status in the registry.
The primary outcome is short-term safety measured as adverse events in participants, with a timeframe of 3 months. The endpoint description emphasizes the grade of events requiring medical intervention and specifies an Overall AE Score threshold at the 3-month follow-up. A secondary outcome is long-term safety, also described in terms of adverse events. Results for the primary endpoint criterion and the secondary outcome are not reported in the registry record.
The registry lists three outcome measures and zero analyses. It does not report a statistical analysis plan, a sample-size justification, or details of how the two centers contributed to analysis. The presence of sample-size planning illustrations does not establish the study’s original design justification: the stated illustration assumptions use two arms with equal allocation, whereas the trial is registered as a single-group study. The record does not identify a control arm or a planned between-group 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.
Overall Study
| Stage | TOOsonix System ONE-M |
|---|---|
| STARTED | 20 |
| COMPLETED | 20 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The grade of any adverse events (AE) requiring medical intervention within three months of treatment was measured.
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 | TOOsonix System ONE-M |
|---|---|---|
| Participants analysed | 20 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 20 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 4 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: Sweden | participants | 10 |
| Region of Enrollment: Denmark | participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Short Term Safety Profile - Adverse Events, measured over 3 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is short-term safety, expressed as a count of participants with adverse events. Its timeframe is 3 months. The endpoint description focuses on the grade of adverse events requiring medical intervention and uses a participant-level Overall AE Score at the 3-month follow-up. Under the registry’s stated criterion, treatment is considered tolerable if less than 30% of treated participants have an Overall AE Score larger than Grade 2. The grading scale is based on Common Terminology Criteria for Adverse Events, CTCAE Ver 5.0, Nov 27, 2017.
A participant-level safety endpoint is useful because it records whether people experience events of concern during the specified follow-up period. It also makes clear that the measure is not a lesion-level count: a participant may have multiple treated neurofibromas, but the primary outcome is framed around the participant’s adverse-event experience. The grading criterion distinguishes more severe event scores from lower scores according to the specified scale.
The endpoint description states the assessment and threshold, but the result for the threshold is not reported in the registry record. The posted safety counts list serious and other adverse events, but those counts do not by themselves give the Overall AE Score distribution or establish how many participants crossed the endpoint’s Grade 2 threshold. The primary endpoint criterion therefore cannot be evaluated from the reported outcome result in this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry lists 20 participants at risk for the safety summaries. The posted counts are 0 serious adverse events, 0 other adverse events, and 0 deaths. These are descriptive safety counts for the treated group. They do not constitute a comparison with an untreated group or another treatment, because the registered model is single group and no comparator is listed.
These counts should be distinguished from the primary endpoint criterion. That criterion concerns the proportion of treated participants with an Overall AE Score larger than Grade 2 at the 3-month follow-up, with the stated tolerability threshold of less than 30%. The registry record does not report the number of participants meeting that score criterion or a result against the threshold. Consequently, the posted event counts cannot be substituted for the primary endpoint result. In particular, the record does not provide the score distribution, the number of events requiring medical intervention by grade, or a separate result for the primary criterion.
A zero count in the posted safety summary means that no events of the listed type are recorded in those counts for the participants at risk. It does not demonstrate that an event is impossible, and it does not quantify how uncertain the underlying event frequency may be. A confidence interval would express uncertainty around an estimated event frequency; no such interval is reported in the registry record. Without that interval or another uncertainty measure, the precision of the observed safety counts cannot be assessed from the posted results alone.
The record lists zero analyses and does not report inferential estimates, hypothesis tests, or a statistical analysis plan. There is therefore no reported p-value or adjusted estimate to interpret. The listed adverse-event counts should be read as descriptive, not as evidence from a statistical test that compares treatment with an alternative. No efficacy conclusion follows from these safety counts, and no comparative effect can be estimated from a single treatment group.
The registry’s planning illustration assumptions refer to a two-arm design, equal allocation, a two-sided significance level of 0.05, a normal approximation, and effects defined as fractions of the observed effect. Those assumptions describe planning calculations, not the single-group design registered for this study. They are not observed power and do not supply a missing primary endpoint result. A sample-size illustration cannot resolve the absence of an outcome estimate, a comparison group, or an uncertainty interval.
Overall, the posted safety summary contains zero recorded serious adverse events, zero other adverse events, and zero deaths among the 20 participants at risk. The record does not report the primary score-based safety result or long-term outcome results. Interpretation should remain limited to those recorded counts and the information explicitly described in the registry.
9. Statistical Methods Explained
The primary outcome is a binary participant-level event measure: each participant either meets the specified adverse-event criterion or does not. For a binary outcome, a basic descriptive summary is the number of participants with the event and the number assessed. A proportion can also describe the frequency, but no primary-outcome event count or proportion is reported in the registry record. The posted safety figures give counts for serious and other adverse events, which are not interchangeable with the primary Overall AE Score criterion.
In a single-group study, the observed event frequency describes the treated group during the stated follow-up. It does not estimate the difference between treatment and a comparator because no comparator group is registered. A treatment-versus-control effect would require results from both groups and a defined comparison. The registry record does not report such a comparison, a relative effect, or an adjusted estimate. Descriptive statistics can still document what was recorded among participants, but they cannot isolate a treatment effect from other explanations for an observed outcome.
Confidence intervals are a general statistical tool for expressing the uncertainty around an estimate. For a binary endpoint, an interval around an event proportion indicates which values are reasonably compatible with the observed data under the method’s assumptions. A narrow interval indicates greater precision than a wide interval; neither is a guarantee about future participants. No confidence interval for the primary endpoint or the posted safety counts is reported in the registry record. The interval method is also not reported, so it cannot be assessed whether a particular method would be appropriate for a small or zero-event sample.
When the observed count is zero, that count remains a valid description of what was recorded, but it does not imply that the underlying event probability is exactly zero. Estimates based on few participants can be imprecise. A confidence interval can communicate that uncertainty, while a count alone cannot. No interval is available in the registry record, and none should be inferred from the zero counts.
The primary endpoint uses a severity score based on CTCAE grading. A thresholded score turns a graded clinical assessment into a binary endpoint: participants are classified according to whether their Overall AE Score is above the stated Grade 2 boundary. This can make a safety criterion easier to interpret, but the classification depends on the actual score and its assessment. The registry describes the rule but does not report the count above the threshold, the distribution of scores, or the primary endpoint analysis. It is therefore not possible to evaluate the endpoint criterion from the reported safety counts alone.
Multiplicity is a general concern when a study measures several outcomes or makes several statistical comparisons. More opportunities to test hypotheses can increase the chance of at least one false-positive finding if testing is not planned and controlled. The registry lists three outcome measures and zero analyses. It does not report a multiplicity strategy, a hierarchy among outcomes, or which analyses were designated for confirmatory interpretation. No multiplicity-adjusted result is reported. The absence of a reported plan does not establish that a particular procedure was or was not used outside the registry record.
Missing-data handling is another general part of an analysis plan. An outcome may be unavailable when a participant does not complete follow-up or an assessment is not recorded. Analysis methods can specify how such observations are handled and whether the denominator includes all enrolled participants or only those with available measurements. The registry record does not report missing-data counts, follow-up completeness for the primary endpoint, imputation methods, or a defined analysis population. The safety summary gives 20 participants at risk, but that figure alone does not document completeness for every endpoint or visit.
Sample-size calculations are planning tools, not outcome analyses. The registry’s described illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a stated fraction of the observed effect. Those are planning assumptions, and the record does not present a sample-size justification for the registered single-group design. The two-arm assumptions do not match the listed single-group structure. Any resulting sample-size illustration is not observed power and cannot be read as evidence that the study was adequately powered for its primary endpoint.
Over-dispersion is a general issue for count data when variability exceeds what a chosen count model expects. The registered primary endpoint, however, is defined as a count of participants with an event, a binary participant-level outcome rather than a repeated-event count model. The record does not report a model for recurrent events or a distributional assumption requiring an over-dispersion assessment. Similarly, it does not report an adjustment for center, participant characteristics, or the number of lesions treated. Such methods cannot be presumed from the study description.
In short, the registry provides the outcome definition and descriptive safety counts but does not report the primary endpoint analysis, confidence intervals, hypothesis tests, missing-data methods, or an analysis plan. Statistical interpretation is consequently limited to the reported counts and the stated design.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures: a primary short-term safety measure and a secondary long-term safety measure are described in the record, while the details of the remaining listed measure are not included in the outcome information. It lists zero analyses. No multiplicity procedure, testing hierarchy, or plan for prioritizing outcomes is reported in the registry record. Since no inferential results are listed, there are no reported p-values or adjusted tests to interpret.
Missing-data methods are also not reported in the registry record. The record does not state how incomplete visits, missing event grades, or participants without a recorded endpoint assessment were handled. Although 20 participants are listed as at risk in the safety summary, that number does not establish that all participants completed each assessment or had complete data for every outcome. A separate analysis-population definition is not reported.
These omissions limit assessment of how outcome availability, outcome selection, and analysis choices may affect interpretation. They do not establish that data were missing or that a particular analysis was performed; they mean the registry record does not describe those details. The primary score-based endpoint result and long-term safety result are not reported, so neither can be compared across outcomes or assessed for consistency.
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 |
|---|---|---|---|
| TOOsonix System ONE-M | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| TOOsonix System ONE-M | 0 of 20 |
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 |
|---|---|
| TOOsonix System ONE-M | 0 of 20 |
The registry’s safety figures list 20 participants at risk, 0 serious adverse events, 0 other adverse events, and 0 deaths. These are counts for the treated group, not a comparison with a control group. The study is registered as single group, so the counts describe what is recorded among participants receiving the device treatment.
Zero recorded events should not be read as proof that such events cannot occur. Counts alone do not show the precision of an event-frequency estimate, and no confidence interval is reported in the registry record. The figures also should not be interpreted as the primary endpoint result: that endpoint is based on the Overall AE Score threshold at 3 months, and the number of participants exceeding Grade 2 is not reported.
The event counts are bounded to the outcomes and follow-up information posted in the record. The registry describes a long-term safety outcome, but its results are not reported. Therefore, the short-term safety counts do not establish the long-term event experience, nor do they address outcomes that are not included in the posted safety summary.
12. What the Result Does, and Does Not, Mean
The record documents a completed single-group study of a focused-ultrasound device for cutaneous neurofibromas in adults with neurofibromatosis type 1. It reports that the safety summary includes 20 participants at risk and records 0 serious adverse events, 0 other adverse events, and 0 deaths. These counts describe the posted safety data for the treated group.
The record does not report the result for its primary score-based endpoint. Although it defines a 3-month criterion based on whether a participant’s Overall AE Score is larger than Grade 2, it does not state how many participants met that criterion. The posted counts therefore cannot determine whether the specified threshold was met. The registry also does not report results for the secondary long-term safety outcome.
The design does not include a concurrent comparator. As a result, the record cannot estimate a difference between this device treatment and another treatment or no treatment. The safety counts alone also do not establish efficacy, lesion response, or a causal effect. No efficacy outcome result is reported in the registry record.
More broadly, the available record does not include confidence intervals, a statistical analysis plan, missing-data methods, or analysis-population definitions. These omissions mean that uncertainty and the handling of incomplete outcome data cannot be evaluated from the registry information. The zero event counts are descriptive observations, not proof of zero risk. They should be interpreted alongside the absent primary endpoint result and the single-group design, rather than as a complete assessment of safety or treatment effect.
13. Why This Trial Matters Statistically
This study raises statistical questions common to device evaluations with a single treatment group. A safety count can be informative as a record of events observed among treated participants, but it does not provide a treatment contrast. Without a comparator, differences from an alternative approach cannot be estimated, and observed outcomes cannot be attributed to the device by comparison with another group.
The distinction between an event count and a prespecified graded endpoint is also important. The registry defines a primary criterion using an Overall AE Score threshold at 3 months, while the posted safety figures report serious events, other events, and deaths. Those summaries answer different questions. Reporting the endpoint’s actual count and uncertainty would be needed to evaluate the criterion as defined; that result is not reported in the registry record.
There is an additional design-versus-planning issue. The registry describes sample-size illustrations using assumptions for two equally allocated arms, but the registered study has a single group. Planning calculations do not replace a design-specific justification, and they are not evidence of observed power. This distinction matters when readers encounter planning estimates alongside a study that lacks a concurrent comparison.
Finally, complete interpretation depends on transparent reporting of analysis populations, missing data, outcome definitions, and uncertainty. The registry gives some core design and safety information, but does not report those statistical details or the primary endpoint result. These limitations illustrate why clear outcome reporting is essential for judging what a small single-group safety study can and cannot establish.
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 main limitation is that the registry record does not report the primary endpoint result, despite specifying a threshold-based safety criterion at 3 months. The score distribution and number of participants above the Grade 2 boundary are not reported. The event counts available in the record cannot replace that missing endpoint result.
The study has a single-group design and no concurrent comparator. Accordingly, its posted counts cannot estimate comparative safety or a treatment effect relative to another approach. The enrollment is 20, and no confidence intervals or other measures of uncertainty are reported, limiting assessment of the precision of the descriptive counts.
The study summary describes participants at two centers and a minimum of 8 eligible neurofibromas per participant, but center-specific results and lesion-level outcome results are not reported. The record does not explain whether analyses account for participants having multiple lesions. This matters for interpreting any lesion-based claims, although the primary endpoint is defined at the participant level.
The registry does not report missing-data handling, follow-up completeness, analysis-population definitions, or a statistical analysis plan. The secondary long-term safety outcome is listed, but its result is not reported. The record also does not report a sample-size justification tailored to the single-group design; the stated planning illustration assumptions refer to two arms. These omissions constrain interpretation to the study description and the descriptive safety counts that are posted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: HIFU Treatment of Cutaneous Neurofibromas in Neurofibromatosis Type 1: Safety and Efficacy — NCT05119582.
- Registry record last updated 2024-10-16; status last verified 2024-07.
- Results first posted 2024-10-16.
- 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.
18. Record Summary
The registry record describes a completed, single-group study of the TOOsonix System ONE-M for cutaneous neurofibromas in adults with neurofibromatosis type 1. Enrollment is 20, with the study summary describing participants across two centers. Allocation is listed as NA, masking as none, and phase as NA. The primary outcome is short-term safety over 3 months, based on adverse-event grading and a specified Overall AE Score threshold.
The posted safety summary lists 0 serious adverse events, 0 other adverse events, and 0 deaths among 20 participants at risk. The primary score-based endpoint result and the secondary long-term safety result are not reported in the registry record. The record lists three outcome measures and zero analyses, and does not report confidence intervals, missing-data methods, or a statistical analysis plan. With no concurrent comparator, the safety counts are descriptive and do not establish comparative effects.