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 Laryngeal Vibration for Spasmodic Dysphonia (NCT03746509), a randomized na study. The primary outcome is Voice Assessment During First Visit.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03746509 |
| Phase | NA |
| Condition | Spasmodic Dysphonia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 42 |
| Arms in the primary outcome | 4 |
| Lead sponsor | University of Minnesota |
| Results posted | Yes |
2. Clinical Question
Population
People with spasmodic dysphonia were eligible for the study. The registry describes the condition and reports an enrollment of 42, but does not give further participant characteristics in the primary outcome description. The posted outcome groups have their own reported numbers of participants; those numbers describe the endpoint summaries and should not be treated as a description of every analysis population.
Intervention
The intervention was laryngeal vibration using the device designated as treatment, at 100Hz. The registry describes low-high and high-low schedules: one begins with lower-frequency-of-session intensity and then switches to higher intensity, while the other reverses that order. The described low-intensity schedule is once a week for 4 weeks, and the high-intensity schedule is every second day of the week. The registry's descriptions of the later schedule periods are truncated, so their full duration is not reported in the registry record.
Comparator
The comparator was laryngeal vibration designated as comparator, at 5Hz, also delivered in low-high and high-low schedules. These groups likewise differ in the order of the lower- and higher-intensity schedules. The registry describes the same session frequencies and an initial duration of 4 weeks for each schedule, but its arm descriptions are incomplete. It does not report enough detail to reconstruct the complete treatment sequence.
Primary question
The primary endpoint was relative change in Smoothed Cepstral Peak Prominence (CPPS), measured in decibels from voice signals before and after vibration during the laboratory testing at Week 1. The registry says an increase in CPPS indicates improved voice symptoms. The statistical question of interest is whether the treatment schedules and comparator schedules differ in this voice-quality measure. The record reports medians by group, but does not post an analysis estimating a between-group difference or testing that question.
3. Trial Design
The registry identifies this as a randomized, single-masked, parallel trial of laryngeal vibration for spasmodic dysphonia. It lists the study as completed, with an enrollment of 42. The recorded start date is 2019-04-02 and the primary completion date is 2022-07-20. The phase is listed as not applicable. The sponsor is the University of Minnesota.
Four groups are described. Two receive the treatment device, identified as 100Hz vibration, and two receive the comparator device, identified as 5Hz vibration. Within each device type, one schedule starts at low intensity and switches to high intensity, while the other starts high and switches to low. The registry describes once-a-week sessions as low intensity and sessions every second day of the week as high intensity. Its descriptions are cut off before the full schedules are specified, so the complete intervention duration and sequence are not reported in the registry record.
Randomization is reported, but the method used to generate the allocation sequence, conceal assignments, or stratify participants is not reported in the registry record. Single masking is reported, but the identity of the masked party is not reported in the registry record. The record describes the overall structure as parallel, while also describing schedule changes within the groups; further design details about those changes are not reported.
The primary outcome was voice assessment during the first visit, with testing in the laboratory at Week 1. The endpoint description concerns relative CPPS before and after vibration applied to the laryngeal muscles. EEG cortical activity at baseline and change from baseline are listed as secondary outcomes. The record lists four outcome measures in total, but does not provide a full description of every measure in the available outcome information.
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 | Low-High Treatment | High-Low Treatment | Low-High Comparator | High-Low Comparator |
|---|---|---|---|---|
| STARTED | 11 | 10 | 11 | 10 |
| COMPLETED | 7 | 8 | 9 | 9 |
| NOT COMPLETED | 4 | 2 | 2 | 1 |
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 | Low-High Treatment | High-Low Treatment | Low-High Comparator | High-Low Comparator | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 11 | 10 | 11 | 10 | 42 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 | 4 | 4 | 8 | 20 |
| Age, Categorical: >=65 years | Participants | 7 | 6 | 7 | 2 | 22 |
| Sex: Female, Male: Female | Participants | 7 | 5 | 7 | 4 | 23 |
| Sex: Female, Male: Male | Participants | 4 | 5 | 4 | 6 | 19 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 1 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 2 | 2 |
| Race (NIH/OMB): White | Participants | 11 | 10 | 10 | 8 | 39 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Voice Assessment During First Visit, measured over Testing performed in lab at Week 1.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | decibel |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is relative Smoothed Cepstral Peak Prominence (CPPS), a measure derived from participants' voice signals. It is expressed in decibels. The registry describes CPPS as an indicator of voice quality and states that an increase in its value indicates an improvement in voice symptoms. The measurement was taken before and after vibration was applied to the laryngeal muscles during each study visit; the primary outcome is specified as testing performed in the laboratory at Week 1.
Using a voice-signal measure gives the study a quantitative outcome for assessing voice quality, rather than relying only on a general description of symptoms. As a general statistical point, a quantitative endpoint can represent variation across participants and can be summarized by a measure of central tendency. The registry specifies the median as the summary measure and the inter-quartile range as the dispersion measure. However, the posted arm results do not include a value for the dispersion measure, so the spread of individual participant measurements cannot be read from those summaries.
The endpoint is described as a relative CPPS value, but the registry does not explain the exact calculation used to derive that relative value. It also does not describe a clinically important threshold for interpreting a change. The reported group summaries therefore indicate the central values recorded for this endpoint, but do not alone establish how large a change would matter to participants or whether any group difference is statistically reliable.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports the primary outcome as a median relative CPPS value for each of the four groups. For Low-High Treatment, the value is 0.045, with reported lower and upper values of -0.79 and 1.28. For High-Low Treatment, the value is 0.17, with reported lower and upper values of -0.91 and 1.05. For Low-High Comparator, the value is 0.13, with reported lower and upper values of 0.01 and 1.14. For High-Low Comparator, the value is -0.47, with reported lower and upper values of -0.64 and 0.56. The endpoint unit is decibel, and the registry specifies medians.
The registry does not identify the statistical meaning of the lower and upper values accompanying these medians. They should therefore not be interpreted as confidence intervals, ranges, or another particular uncertainty measure without further documentation. The dispersion measure named for the outcome is the inter-quartile range, but no such values are posted with these group summaries. As a result, the variability of the participant-level measurements is not fully conveyed.
The median values differ across groups, and the reported bounds also vary. Those descriptive summaries do not constitute a formal comparison between treatment and comparator, or between the two schedule orders. A treatment effect would ordinarily be expressed using an explicit contrast, such as a difference between group outcomes, with an estimate of its uncertainty and a clearly described analysis. The registry results do not post such a contrast, a test statistic, or a p-value. The analysis count is listed as 0, and the registry notes that values are missing or not estimable for a two-arm comparison for this other endpoint.
Consequently, the available record supports describing the individual group summaries, but not a conclusion about whether treatment differs from comparator. A positive median is not by itself evidence of a reliable effect, and a negative median is not by itself evidence of a reliable effect in the opposite direction. General statistical reasoning requires attention to the size and uncertainty of a contrast, not just the direction of separate group summaries.
There are also differences between the numbers reported for endpoint groups and the numbers listed at risk in the safety record. These are different record entries, and the registry does not explain their relationship. They should not be combined or used to infer participant flow. The status is completed, but completion status does not substitute for a posted comparative analysis or explain why such an analysis is absent.
9. Statistical Methods Explained
The registry reports randomized allocation and a parallel model. Randomization is a design approach intended, in general, to reduce systematic differences between groups at the point of assignment. It does not guarantee that groups will be alike in every characteristic, especially in a small study, and it does not itself provide an estimate of the treatment effect. To interpret a randomized study, readers still need a clear account of the outcome analysis, the group contrast, and its uncertainty. Those analysis details are not reported in the registry record for the primary endpoint.
What does the median describe?
The median is the middle of an ordered set of observations. As a general statistical concept, it describes a typical central value and is less influenced by unusually high or low observations than the arithmetic mean. The registry specifies the median for relative CPPS. It also names the inter-quartile range as the dispersion measure, which would describe the spread of the central part of the observed values. The posted arm results give no inter-quartile range values. Without them, readers cannot assess the within-group spread from the listed summaries alone.
The endpoint entries include a median and a lower and upper value for each group. The registry does not label those lower and upper values with a statistical interpretation. They therefore cannot safely be treated as confidence limits or as a description of the full data range. General statistical interpretation depends on knowing how such bounds were calculated and what population or uncertainty they represent. That information is not reported in the registry record.
Why is a group contrast needed?
A comparison of group medians is not equivalent to an estimated treatment effect. General statistical analysis would define a contrast that matches the research question, for example comparing outcomes between a treatment group and an appropriate comparator under a specified schedule and time point. That contrast would need an estimate and a measure of uncertainty. A test of a null hypothesis, if used, would also need its assumptions and analysis population stated. The registry lists no analysis entries, and it does not post a two-arm comparison for this endpoint. There is therefore no registry-based inferential result to interpret.
The study has two schedule orders for each device type. A complete analysis would need to clarify whether the main comparison concerned device frequency, schedule order, change over time, or another prespecified contrast. It would also need to explain whether schedule and period effects were addressed. Although the registry describes low-high and high-low sequences, the analysis plan and the relationship between those sequences and the primary comparison are not reported in the registry record. No model specification, adjustment variables, or approach to repeated measurements is reported.
How should uncertainty be considered?
In general, a confidence interval quantifies the uncertainty around an estimate under a statistical model and procedure. A narrow interval suggests greater precision than a wide interval, while an interval that includes values on either side of a null contrast may be compatible with different conclusions. These general concepts apply only when the interval type and the estimate are identified. The registry does not state what the lower and upper values beside the medians represent, and it does not post a between-group estimate or confidence interval. They should not be used as substitutes for uncertainty around a treatment contrast.
Likewise, a p-value would not measure the size or clinical importance of an effect. It is a measure tied to a specified statistical test and its assumptions. No p-value or test for the primary outcome is posted. It would be inappropriate to infer significance or lack of significance from the medians or the unlabeled bounds.
What does over-dispersion mean in general?
Over-dispersion is a general issue that arises when observed variability is greater than a statistical model assumes. If a model underestimates variability, its uncertainty estimates can be too small and its tests can appear more conclusive than warranted. Appropriate methods depend on the outcome type and model. The primary endpoint is described as a continuous voice measure summarized by medians, and no model is reported. There is no basis for claiming that over-dispersion was present or that any particular correction was used. This general concept is relevant only as a reminder that model assumptions matter when an inferential analysis is performed.
What can planning illustrations tell readers?
General sample-size planning uses assumptions about the effect to detect, variability, allocation, and a chosen significance level and power. The registry's planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. These are planning assumptions, not observed trial results. The registry record does not describe these illustrations as the trial's original design justification, and no specific planning counts are included in the outcome information. They cannot be interpreted as observed power. The trial's own sample-size justification is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures and two secondary outcomes concerning cortical activity measured using electroencephalography at baseline and change from baseline. The primary outcome is relative CPPS at the first visit. The record does not provide a complete account of all outcome definitions, the hierarchy among outcomes, or which outcomes were designated as confirmatory. A multiplicity strategy for handling the possibility of several outcome tests is not reported in the registry record.
Multiplicity matters in general when several hypotheses are tested: considering more tests can increase the chance of at least one apparently unusual result by chance. Procedures for addressing that issue depend on the analysis plan and the intended interpretation of each endpoint. No analysis entries are listed for the posted results, and no inferential results for the primary endpoint are available. The record therefore does not establish whether multiplicity adjustments were planned or used.
The registry does not describe missing outcome data, participant exclusions, or reasons that endpoint data might be unavailable. It does not report an imputation method, a sensitivity analysis, or a missing-data assumption. The analysis population—such as whether all randomized participants or only those with observed measurements were included—is not reported in the registry record. Group counts attached to the endpoint summaries do not, by themselves, explain exclusions or missing observations.
For the same reason, the differing counts in the safety entries should not be used to reconstruct outcome follow-up or participant flow. The registry does not give a flow account linking enrollment, assignment, outcome measurement, and safety monitoring. Without those details, readers cannot determine how missingness or analysis-population choices may have affected the posted summaries.
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 |
|---|---|---|---|
| Low-High Treatment | 0 | 11 | 0.0% |
| High-Low Treatment | 0 | 10 | 0.0% |
| Low-High Comparator | 0 | 11 | 0.0% |
| High-Low Comparator | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Low-High Treatment | 0 of 11 |
| High-Low Treatment | 0 of 10 |
| Low-High Comparator | 0 of 11 |
| High-Low Comparator | 0 of 10 |
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 |
|---|---|
| Low-High Treatment | 0 of 11 |
| High-Low Treatment | 0 of 10 |
| Low-High Comparator | 0 of 11 |
| High-Low Comparator | 0 of 10 |
The safety record lists serious adverse events, other adverse events, and deaths by group. For Low-High Treatment, 11 participants are listed at risk for serious and other adverse events, with 0 affected in each category and 0 deaths. For High-Low Treatment, the corresponding number at risk is 10, with 0 serious events, 0 other events, and 0 deaths. For Low-High Comparator, 11 are listed at risk, with 0 serious events, 0 other events, and 0 deaths. For High-Low Comparator, 10 are listed at risk, with 0 serious events, 0 other events, and 0 deaths.
These entries describe what was recorded in the registry for the stated groups. Zero recorded events does not establish that an event was impossible, nor does it establish that the groups have identical safety profiles. General statistical interpretation of uncommon events depends on the amount and duration of observation, the event definitions, and complete reporting. The registry does not provide detailed follow-up duration for safety, event definitions, or a narrative of how events were collected. No serious-event terms are listed.
The counts at risk in the safety record are not the same as the endpoint group counts reported for the primary outcome. The record does not explain that difference, so the figures should be read as separate entries rather than reconciled into a participant-flow account.
12. What the Result Does, and Does Not, Mean
The primary endpoint summaries describe median relative CPPS values for the four randomized groups during laboratory testing at Week 1. The registry identifies CPPS as a voice-quality indicator and states that an increase indicates improvement in voice symptoms. The entries are useful as descriptive summaries of the posted group results, but the dispersion values are absent and the statistical meaning of the accompanying lower and upper values is not identified.
The results do not establish whether 100Hz treatment differs from the 5Hz comparator. No formal between-group estimate, test, p-value, or analysis entry is posted for this endpoint. Separate medians cannot answer a comparative question on their own, particularly when the record does not describe how the primary contrast was defined or how repeated measures and schedule order were handled. The listed bounds cannot resolve this issue because their meaning is not specified.
The registry's description gives a rationale for studying laryngeal vibration, including potential voice-quality and neurophysiological outcomes, but those aims are not the same as evidence that the posted results demonstrate an effect. The two secondary outcomes concern EEG cortical activity, but detailed results for them are not included in the registry record for interpretation. The record lists four outcome measures, while the details of all measures and analyses are not reported.
Completion status indicates that the study is recorded as completed; it does not mean that every outcome or analysis has been posted. The summaries should therefore be read as limited registry reporting, not as a complete account of all study findings. The findings cannot establish the size, precision, or clinical importance of a treatment effect from the information recorded. No medical conclusion follows from these descriptive entries alone.
13. Why This Trial Matters Statistically
This trial raises several statistical questions that are important in clinical research. The study compares two vibration frequencies and includes low-high and high-low schedule orders. Those features mean that a useful analysis needs to make clear which contrast answers the primary research question and how differences in schedule order are handled. The registry describes the groups but does not report the analysis plan or a comparative estimate.
The primary endpoint is a quantitative voice measure, summarized by medians. That choice makes the interpretation dependent on both the central values and the distribution of participant measurements. The inter-quartile range is named as the dispersion measure, but values are not posted. The lower and upper values accompanying the medians are not identified, so readers cannot use them to judge precision. This illustrates why a result needs clear definitions of its estimate and uncertainty, not only a point summary.
The registry also lists EEG outcomes alongside the voice endpoint. When a study examines multiple outcomes, prespecification and multiplicity handling help readers distinguish primary evidence from exploratory findings. The available record does not describe those procedures. It likewise does not describe missing-data handling or the analysis population, both of which can affect how endpoint summaries should be understood.
Finally, the study's planning assumptions are not a substitute for its original design justification or a completed analysis. Planning illustrations based on observed effects are forward-looking calculations under assumptions; they are not observed power and do not establish the reliability of an estimated effect. The absence of a posted comparative analysis limits what can be inferred from the medians, regardless of the trial's completed status.
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 for interpreting this trial from the registry record is the lack of a posted comparative analysis for the primary endpoint. The record gives group medians but no estimate of a treatment-versus-comparator contrast, no test result, and no p-value. It also does not explain the statistical meaning of the lower and upper values reported with each median. Although the outcome definition names the inter-quartile range, no dispersion values are posted.
The descriptions of the intervention arms are incomplete. They identify the device frequencies and the order and schedule frequency of low- and high-intensity periods, but are truncated before all durations and sequence details are stated. This prevents a full reconstruction of the exposure being compared. Masking is described as single, but the identity of the masked party is not reported in the registry record.
Other limitations concern reporting rather than the intervention itself. The registry does not describe the allocation method, analysis model, primary contrast, analysis population, missing-data approach, or sensitivity analyses. It lists four outcome measures, but full details for all measures and the multiplicity strategy are not reported. EEG outcomes are named, but their results are not included in the registry entries.
The endpoint counts and safety counts differ, and the record does not explain the relationship between them. It does not provide a participant-flow account or detailed safety follow-up information. The sample-size rationale for the trial is not reported in the registry record. Together, these gaps mean that the posted summaries cannot be used to assess precision, missingness, or the robustness of the intended treatment comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Laryngeal Vibration for Spasmodic Dysphonia — NCT03746509.
- Registry record last updated 2025-05-04; status last verified 2025-04.
- Results first posted 2024-03-15.
- 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
The registry record describes a completed randomized, single-masked, parallel study of laryngeal vibration for spasmodic dysphonia, sponsored by the University of Minnesota. Enrollment is listed as 42. The study compares treatment vibration at 100Hz with a 5Hz comparator, using low-high and high-low schedules.
The primary outcome is median relative CPPS in decibels during laboratory testing at Week 1. Four group medians and accompanying lower and upper values are posted, but the meaning of those bounds is not identified. No two-arm comparison or analysis entry is posted for the primary endpoint. The registry also names EEG cortical activity as a secondary outcome. It records zero serious adverse events, zero other adverse events, and zero deaths in each group. Important details about the analysis plan, missing data, participant flow, and complete intervention schedules are not reported in the registry record.