Immediate Effect of Ultrasound Therapy on Bilateral Masseter Myalgia: Randomized Single Blinded Investigational Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immediate Effect of Ultrasound Therapy on Bilateral Masseter Myalgia: Randomized Single Blinded Investigational Trial (NCT02295644), a randomized na study. The primary outcome is Self Report of Pain.

2. Clinical Question

3. Trial Design

This was a randomized, single-blind, parallel-group investigational trial. The registry lists the trial as completed and records enrollment of 28. Its start is listed as 2014-11 and its primary completion as 2015-05. The registry does not state who was blinded, how the random sequence was generated, or how treatment assignment was concealed.

Participants were allocated to one of four ultrasound-setting groups. All settings used a frequency of 1 MHz and treatment of the masseter muscle. The groups differed in intensity, duty cycle, or both: 0.4 Watts per square centimeter with a 50% duty cycle; 0.4 Watts per square centimeter with a 100% duty cycle; 0.8 Watts per square centimeter with a 50% duty cycle; and 0.8 Watts per square centimeter with a 100% duty cycle. The description states that ultrasound was applied to both masseters for five minutes on each side.

The registry describes a study of immediate effects, with pain measured immediately before and after the intervention. The posted group summaries give the number of participants, mean change, and standard deviation for each setting. The group counts are 7, 7, 6, and 5. The registry does not explain how these counts relate to the enrollment total of 28 or identify the participants included in each analysis.

The study’s broader aims included exploring peripheral and central physiological changes, examining response across intensity and duty-cycle settings, and assessing whether masseter treatment elicited an effect in the temporalis muscle. Detailed methods and results for those aims are not reported in the registry record. The sample-size justification, eligibility and exclusion details beyond the stated population, and procedures for handling departures from the planned treatment are also not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

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: One in group C and two in group D did not meet inclusion criterion of reporting current pain intensity of ≥4 on the Diagnostic Criteria for TMD.

6. Primary Endpoint

The registry lists the primary outcome as Self Report of Pain, measured over Immediately before and after the intervention, difference used..

The primary endpoint was self-reported pain intensity, measured on a scale from 0 to 10. The registry defines 0 as no pain and 10 as the worst pain ever. The analysis measure was the difference between scores immediately before and immediately after the ultrasound intervention. A change score is intended to capture how a participant’s reported pain level differs across those two assessments, rather than describing only the score at one time.

Pain intensity is relevant to the trial’s stated focus on immediate management of painful masticatory muscle and tissues. The registry also describes temporomandibular disorders as involving pain and decreased functional capacity, but functional capacity is not the primary endpoint reported in the results summarized for this measure. The registry gives the outcome unit as scores on the pain intensity scale and summarizes each group using a mean and standard deviation.

The posted group means are negative: -0.86, -2.0, -1.4, and -1.3 for the four settings, respectively. The registry does not specify the subtraction order used to calculate the difference. Therefore, the direction of these negative values should not be assigned a clinical meaning based on the sign alone. The registry also does not report confidence intervals for the group means or a confidence interval for a between-group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: it is a numerical pain score and is summarized by a mean and standard deviation. A mean describes the average observed score change in a group. A standard deviation describes the spread of individual observations around that group mean. It does not, by itself, indicate how precisely the mean has been estimated; precision also depends on the number of observations and is commonly conveyed with a confidence interval.

The registry reports ANOVA for analyses involving the four groups. In general, analysis of variance tests whether the observed group means are compatible with a model in which all groups share the same mean. An overall ANOVA is an omnibus test: it assesses the set of group means together rather than estimating each pairwise difference. If an omnibus result indicates evidence of differences, additional comparisons can help identify which groups differ and by how much. Those follow-up comparisons and their estimates are not reported in the registry record.

ANOVA relies on assumptions about the data and model, including appropriate independence of observations and a suitable description of variability within groups. In many standard applications, the model also assumes that residual variation is similar across groups and that residuals are reasonably compatible with a normal distribution. These are general statistical considerations; whether and how the trial investigators assessed them is not reported in the registry record. With small group counts, estimates and tests can be sensitive to individual observations and to departures from model assumptions.

A p-value describes how unusual the observed data, or data more extreme, would be under the null model and its assumptions. It does not tell readers the probability that the null model is correct, nor does it convey the size of a difference. The three p-values reported for the four-group analyses are 0.17, 0.14, and 1.0, but their correspondence to named endpoints is not stated. The significance criterion and any planned decision rules are not reported in the registry record. No confidence intervals for the ANOVA results or treatment contrasts are reported, so the precision of between-group effects cannot be judged from those tests alone.

The posted summaries include mean changes and standard deviations by group. These are not the same as adjusted treatment effects. No adjusted model estimates or covariate adjustments are reported in the registry record. The record also does not provide the individual observations, so independent recalculation of the full analysis is not possible from the posted group summaries alone.

For a two-arm comparison, a recalculated estimate would be an unadjusted calculation from the posted summary statistics. It would not replace the trial’s own analysis. In this record, the two-arm comparison values are missing or not estimable for the continuous endpoint, so no such recalculated contrasts are available to compare with the registry-reported ANOVA results. The record does not flag a discrepancy between a recalculation and the reported analysis.

Sample-size illustrations are planning exercises, not measures of the power achieved by the completed trial. The stated assumptions for such illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. These assumptions describe a hypothetical planning calculation, not the trial’s documented design justification. The sample-size justification used by the investigators is not reported in the registry record. Any sample size derived from an observed effect should be interpreted cautiously as an illustration, not as observed power or proof that the study was adequately sized.

Multiplicity arises when several outcomes, contrasts, or analyses are considered. The registry lists three outcome measures and reports three ANOVA p-values, but it does not connect each p-value to a named outcome or describe a strategy for accounting for multiple testing. Without that information, the overall chance of false-positive findings across all analyses cannot be assessed from the record. The statistical analysis plan, including prespecified contrasts, any interim analyses, and the handling of multiple comparisons, is not reported in the registry record.

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.

R code and output

arm <- c("A (0.4W/Square Centimeter, 50%)", "B (0.4W/Square Centimeter, 100%)", "C (0.8W/Square Centimeter, 50%)", "D (0.8W/Square Centimeter, 100%)")
n   <- c(7, 7, 6, 5)
m   <- c(-0.86, -2, -1.4, -1.3)
sp  <- c(1.4, 0.87, 1.1, 1.4)
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  A (0.4W/Square Centimeter, 50%)  7  -0.860  1.400  -2.155  0.435
CARM  B (0.4W/Square Centimeter, 100%)  7  -2.000  0.870  -2.805  -1.195
CARM  C (0.8W/Square Centimeter, 50%)  6  -1.400  1.100  -2.554  -0.246
CARM  D (0.8W/Square Centimeter, 100%)  5  -1.300  1.400  -3.038  0.438

11. Analyses Reported by the Sponsor

The registry reports three ANOVA p-values for analyses of all four groups: 0.17, 0.14, and 1.0. It does not specify which value belongs to the primary pain endpoint, so none can be assigned to that endpoint with confidence from the record alone. The posted arm summaries give the group means and standard deviations, but no two-arm recalculated estimates are available for this continuous outcome because the comparison values are missing or not estimable.

As a result, the registry-reported analyses cannot be directly checked against recalculated pairwise differences using the available summaries. This is not a case in which a recalculated result conflicts with the sponsor’s reported result; the required two-arm comparison estimates are unavailable. The record does not flag a discrepancy. Where a genuine discrepancy exists, the sponsor’s own analysis takes precedence, but no such discrepancy is identified for this trial.

The lack of a recalculated contrast does not establish that the reported ANOVA is incorrect. It means that the available information does not permit an independent comparison of pairwise treatment effects. The p-values also do not supply estimates of the size or precision of those effects.

12. Multiplicity, Missing Data and Analysis Populations

The record reports three ANOVA p-values, 0.17, 0.14, and 1.0, for analyses involving the four groups. It also lists three outcome measures, but does not map each p-value to a specific outcome. Without that mapping, it is not possible to determine which reported test pertains to the primary pain measure or to reconstruct the full set of analyses.

When several outcomes or group comparisons are tested, the chance of at least one apparently unusual result can increase. Statistical approaches to multiplicity can adjust interpretation or testing, but the appropriate approach depends on the planned questions and analysis strategy. Whether the investigators prespecified a hierarchy of outcomes, adjusted for multiple comparisons, or treated the tests as exploratory is not reported in the registry record. The registry also does not state whether interim analyses were conducted.

Missing-data procedures are not reported in the registry record. It is not stated how participants with a missing pre-intervention or post-intervention score would be handled, whether any scores were imputed, or whether the analysis used all randomized participants. The record does not describe an intention-to-treat population, a per-protocol population, or another defined analysis population.

The registry lists enrollment of 28 and arm counts of 7, 7, 6, and 5. It does not explain how those counts were determined, whether they represent all randomized participants or only those with usable outcome data, or why they do not match the enrollment figure. No conclusions about attrition or exclusions can be drawn without that accounting.

The planned sample-size justification and the statistical analysis plan are not reported in the registry record. The record therefore does not establish whether the trial was designed around the primary endpoint, a particular contrast, or a specified degree of precision. These omissions make it difficult to assess the role of multiplicity, missing observations, and analysis-population decisions in the reported results.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event record lists no serious adverse events and no other adverse events in the reported groups. The at-risk counts are 7, 7, 6, and 5 for the four settings, respectively, and the corresponding affected counts are 0 in each category. These are counts recorded in the registry, not evidence about events beyond the recorded categories or reporting period.

The registry does not report deaths as numerical counts; those entries are unspecified. The period during which adverse events were collected, the definitions used, and the approach to soliciting or recording events are not reported in the registry record. It is therefore not possible to establish from these figures alone how completely adverse events were monitored or whether the counts cover the full study period.

Zero recorded events in the listed groups should be interpreted narrowly: no events are listed among the stated numbers at risk for the reported categories. These figures do not establish that an event could not occur, and the small group counts limit what can be learned about uncommon events. The adverse-event data also do not provide a comparative estimate of risk across settings.

14. What the Result Does, and Does Not, Mean

The trial record describes a randomized comparison of four ultrasound settings and reports immediate pre-intervention to post-intervention pain-score changes. The group means were -0.86, -2.0, -1.4, and -1.3, with standard deviations of 1.4, 0.87, 1.1, and 1.4. These figures describe the observed summaries for the listed arm counts. Because the subtraction order for the change score is not stated, the sign alone does not establish whether a negative value represents a decrease or increase in pain score.

The registry also reports three ANOVA p-values, but does not identify which is associated with the primary endpoint. There are no reported confidence intervals for the group means or contrasts, and no pairwise estimates are available for independent recalculation. Consequently, the record does not show the magnitude and precision of each difference between ultrasound settings in a way that supports a detailed comparison.

The study’s stated aims included exploring dose response and possible segmental effects in the temporalis muscle. Results for those aims are not reported in the registry record. The posted pain summaries and ANOVA p-values therefore do not establish whether changing intensity or duty cycle produced a systematic response, nor whether treatment of the masseter affected the temporalis muscle.

These findings should not be interpreted as evidence that ultrasound does or does not work. The study compared four active settings and does not list a no-treatment or sham group. Its immediate outcome also does not describe longer-term pain or function. The registry does not provide the analysis plan, sample-size justification, or the details needed to assess missing observations and participant flow.

The appropriate reading is descriptive and limited to the posted record: it reports group summaries, several four-group ANOVA p-values, and no recorded adverse events in the listed categories. The mapping of analyses, uncertainty around treatment contrasts, and results for the broader aims remain unclear or unreported.

15. Why This Trial Matters Statistically

This trial illustrates how a registry can describe a randomized multi-arm study while leaving important interpretive details unresolved. Four settings allow comparisons across two intensity levels and two duty-cycle levels, but an overall ANOVA does not by itself explain which settings differ or quantify the size of any pairwise difference. Group means and standard deviations add useful descriptive information, yet they do not replace contrast estimates and confidence intervals.

The trial also highlights the value of clearly linking each reported test to its endpoint. Three p-values are listed, alongside three outcome measures, but the registry does not identify which result corresponds to the primary pain measure. Without that link, even a technically familiar test can be hard to interpret. Clear reporting of the analysis population, missing-data methods, planned contrasts, and multiplicity strategy would help readers understand how the results relate to the study questions.

The posted record distinguishes an immediate outcome from broader aims concerning physiological changes, dose response, and effects in the temporalis muscle. Those aims require results and methods specific to each question; a summary of immediate pain scores alone cannot answer them. The lack of a no-treatment or sham group also means that the four-group comparison is about differences among ultrasound settings, rather than a comparison of ultrasound with no intervention.

Finally, the enrollment figure and the arm counts are not reconciled in the registry. Reporting participant flow and analysis populations would clarify how many participants contributed to the primary outcome and why. These are practical lessons in interpreting small randomized trials: transparent denominators, mapped analyses, and uncertainty estimates are central to understanding what the data can support.

16. 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.

Several limitations are specific to the information available for this trial. The reported group counts are 7, 7, 6, and 5, while the registry records enrollment of 28. The record does not reconcile those figures or explain whether the arm counts refer to randomized participants, participants treated, or participants with evaluable outcomes. Participant flow and exclusions are not reported in the registry record.

The primary endpoint is an immediate change score, but the registry does not state the subtraction order. That makes the sign of each mean change difficult to interpret. The record also does not provide baseline and post-intervention group means separately, so the change summaries cannot be checked against the component measurements.

Three ANOVA p-values are reported without a mapping to the named outcome measures. No confidence intervals or between-group effect estimates are reported, and the available summary data do not support recalculated two-arm comparisons. The analysis population, missing-data approach, model assumptions, prespecified contrasts, and multiplicity strategy are not reported in the registry record.

The registry describes single blinding but does not identify who was blinded or how blinding was maintained. Details of sequence generation, allocation concealment, adherence, and treatment fidelity are also not reported in the registry record. The sample-size justification is not reported, so the rationale for the enrollment target cannot be assessed.

The primary outcome concerns an immediate assessment. The record does not provide longer-term outcomes, and results for the stated physiological, dose-response, and temporalis-muscle aims are not reported in the registry record. The adverse-event entries list zero affected participants in the stated categories, but event-collection duration and methods are not described.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Immediate Effect of Ultrasound Therapy on Bilateral Masseter Myalgia: Randomized Single Blinded Investigational Trial — NCT02295644.
• Registry record last updated 2018-06-07; status last verified 2018-05.
• Results first posted 2016-10-07.
• 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.

20. Record Summary

The registry record describes a completed, randomized, single-blind, parallel-group trial of four therapeutic ultrasound settings in adult females with bilateral masseter myalgia. Enrollment is listed as 28. The settings combined intensities of 0.4 or 0.8 Watts per square centimeter with duty cycles of 50% or 100%, using 1 MHz ultrasound on the masseter muscles for five minutes on each side.

The primary endpoint was self-reported pain intensity on a 0-to-10 scale, measured immediately before and after treatment, with the difference used. Arm counts were 7, 7, 6, and 5; mean changes were -0.86, -2.0, -1.4, and -1.3. The registry reports three ANOVA p-values, 0.17, 0.14, and 1.0, without identifying their outcome mapping. No two-arm recalculated estimates are available, and no confidence intervals for treatment contrasts are reported.

The record lists zero serious and other adverse events among the stated at-risk counts. It does not explain the enrollment-to-arm-count accounting, the change-score direction, missing-data handling, analysis populations, or multiplicity procedures. Results for the broader stated aims are not reported in the registry record.