Sustained Acoustic Medicine (SAM) Combined With a Diclofenac Ultrasound Coupling Patch for Knee Osteoarthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sustained Acoustic Medicine (SAM) Combined With a Diclofenac Ultrasound Coupling Patch for Knee Osteoarthritis (NCT04391842), a na phase 1 study. The primary outcome is Change in Pain Units on a Scale (0-10) 0 Being Least, 10 Being Worst Pain From Baseline.

2. Clinical Question

In practical terms, this design can describe what happened to pain ratings among participants receiving the combined intervention, if those outcome data are reported. A single-group change does not by itself show what would have happened over the same period without the intervention. Natural symptom variation, expectations, concurrent care, and other influences cannot be separated from the treatment combination using this design alone.

3. Trial Design

The registry record identifies this as a Phase 1 study with a single-group model and no masking. Allocation is recorded as not applicable. The study status is completed, and enrollment is recorded as 34. The record gives a start date of 2019-09-01 and a primary completion date of 2019-12-31.

Participants in the experimental group received a combination product described as a SAM ultrasound device with a 1% diclofenac patch. The arm description specifies treatment for 4 hours every day for 7 days. The device emitted continuous ultrasound at 3 megahertz and an intensity of 0.132 watts/cm2. The intervention therefore combined a device procedure and a topical drug delivery approach; the design does not isolate their individual contributions.

There is no randomized control group described, and no masking is recorded. Participants and investigators could therefore have been aware of treatment, although details of who assessed outcomes and how assessments were conducted are not reported in the registry record. Without a concurrent comparison group, differences between baseline and follow-up are descriptive changes within the treated group, not randomized estimates of a treatment contrast.

The primary outcome was change in pain units on a 0-10 scale from baseline, with a 7-day timeframe. The registry also lists change in WOMAC scores as a secondary outcome, with a stated range from 0, no difficulty, to 2400, extreme difficulty. The record lists two outcome measures and two analyses, but does not describe the analysis methods or provide numerical endpoint results. It also does not report the recruitment setting, eligibility criteria in detail, adherence, participant flow, or reasons for any missing observations.

Although the study is marked completed, completion status is not itself evidence that every planned measure was collected or analyzed. The protocol, sample-size justification, and any planned interim analyses are not reported in the registry record. In the absence of a comparator, the study can offer early descriptive information about the combined regimen, but cannot establish a comparative effect.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change in Pain Units on a Scale (0-10) 0 Being Least, 10 Being Worst Pain From Baseline, measured over 7 days.

The primary endpoint is change from baseline in self-described pain on a scale from 0 to 10, where 0 is least pain and 10 is worst pain. The registry gives a timeframe of 7 days and describes pain ratings before and after treatment. In an endpoint framed as change, the key quantity is how the follow-up rating differs from the baseline rating for the participants included in the analysis.

Pain is a patient-reported symptom, so a rating scale allows participants to express their experience in a format that can be analyzed as a continuous measure. A mean change can describe the average direction and size of change in the analyzed group; a measure of dispersion can show how much individual changes vary around that average. Neither summary alone describes every participant's experience.

Because lower values on this scale indicate less pain, a decrease in a participant's rating would represent lower reported pain than at baseline. That is an interpretation of the scale's direction, not a claim about the observed results. Numerical primary-endpoint results, including the mean change and its variability, are not reported in the registry record. Consequently, the magnitude, consistency, and precision of the reported endpoint cannot be evaluated from the registry information.

A within-group change is also not equivalent to a controlled treatment effect. Without a comparison group measured over the same period, the endpoint cannot distinguish an intervention-related change from other reasons pain ratings may change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: pain is recorded on a numeric scale and the endpoint is described as change from baseline. For a continuous endpoint, analysts commonly summarize the group with a mean and a measure of dispersion. The mean describes the arithmetic average, while a standard deviation describes how spread out observations are around that average. These quantities answer different questions: a group average does not imply that each participant changed by that amount, and dispersion is not the same thing as uncertainty in the mean.

What does a change score represent?

A change score compares a participant’s follow-up measurement with that participant’s baseline measurement. In this study, the stated comparison is between baseline and post-treatment pain ratings over 7 days. The sign and magnitude of a change depend on the analysis convention, which is not described in detail in the registry record. The scale itself gives the direction of symptom severity: zero is least pain and 10 is worst pain. No numerical change estimate is reported, so no direction or size of observed change can be stated.

Change scores can be useful because they describe how measurements move over time within the same participants. They do not, on their own, account for what would have occurred over that time without treatment. In a randomized controlled design, the difference between groups can help estimate the effect of assignment under the study conditions. In this single-group study, there is no concurrent randomized group to provide that comparison.

How should uncertainty be read?

A confidence interval is a statistical summary of uncertainty around an estimated effect. A narrow interval indicates greater precision than a wide interval, under the assumptions of the analysis. Whether an interval includes a particular reference value can be relevant to statistical interpretation, but a confidence interval does not resolve design limitations such as the absence of a control group. The registry record does not report a confidence interval for the primary outcome.

A p-value, when used, describes how compatible the observed data are with a specified statistical model and null hypothesis. It does not measure the probability that a treatment works, nor does it establish clinical importance. The registry record does not report a primary-endpoint p-value or the statistical procedure used to obtain one. It is therefore not possible to assess statistical significance from the registry information.

Why do assumptions matter?

Analyses of continuous outcomes often rely on assumptions about the distribution of measurements or errors. For example, a normal approximation may be used for some estimates, while other methods may be appropriate when observations are skewed or when model assumptions are not met. The registry record does not specify the analytic model, diagnostic checks, or any adjustment for baseline characteristics. General statistical explanations do not establish which methods were used in this study.

Over-dispersion is a general concern when observed variability is greater than a model expects. If a model understates variability, its uncertainty estimates can be too small and its intervals or tests can be misleading. Whether over-dispersion is relevant depends on the outcome and model. No such model details or diagnostics are reported for this endpoint, so it is not possible to say whether this issue arose in the analysis.

What do the planning illustrations mean?

Any sample-size illustrations associated with the posted results are planning calculations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is based on the observed effect and asks what planning would look like for a stated fraction of that effect. Such calculations do not change the single-group design of the actual study, and they do not show that the study had a particular probability of detecting an effect. The registry record does not report a design justification or establish that those assumptions were used to plan this trial.

Power is a property of a design under specified assumptions about an effect, variability, sample size, and analysis. It is not a retrospective measure of whether a result is trustworthy. In particular, calculating a hypothetical sample size from an observed estimate can be unstable when that estimate is imprecise. The planning illustrations should therefore be interpreted as conditional planning scenarios, not as evidence of the strength of the trial’s findings.

What can be inferred from a single group?

A single-group estimate can describe the observed experience of participants who received the intervention, provided the outcome data and analysis are reported. It cannot control for time trends or other factors in the way a randomized comparison can. Masking is recorded as none, and the registry does not describe blinded outcome assessment. For a participant-reported outcome, awareness of treatment may influence expectations or reporting; this is a general potential source of bias, not evidence that it occurred in this study.

The registry lists two outcome measures and two analyses, but does not report the statistical plan, missing-data methods, analysis populations, or any multiplicity adjustment. Those details matter for understanding how outcomes were selected and how uncertainty was calculated. In their absence, the results cannot be independently interpreted as if a complete prespecified analysis were documented.

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("Experimental: SAM Ultrasound and Diclofenac Patch")
n   <- c(32)
m   <- c(2)
sp  <- c(2.41)
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  Experimental: SAM Ultrasound and Diclofenac Patch  32  2.000  2.410  1.131  2.869

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses. It identifies pain change as the primary outcome and WOMAC score change as a secondary outcome. The WOMAC scale is described as ranging from 0, no difficulty, to 2400, extreme difficulty. The registry record does not report how the two analyses were conducted, whether additional outcomes or subgroups were examined, or whether any multiplicity adjustment was planned or applied.

Multiplicity is a general statistical issue that arises when several hypotheses are tested. The more tests that are considered, the greater the chance that at least one result may appear unusual by chance if each test is interpreted in isolation. Adjustment procedures can address this issue, but they may also affect precision or the interpretation of individual tests. Without the analysis plan and reported results, it is not possible to determine how multiplicity was handled in this study.

Missing-data handling is also not reported in the registry record. The enrollment figure alone does not establish how many participants contributed data to each endpoint, whether measurements were incomplete, or how any missing observations were treated. The registry does not describe imputation, complete-case analysis, sensitivity analyses, or reasons for missingness. These details can influence both the estimate and its uncertainty, especially when missingness is related to participant experience or outcome values.

The analysis population is not reported. The record does not state whether analyses included all enrolled participants, only those who completed treatment, or another defined group. It also does not report participant flow or adherence. Accordingly, the observed-data basis for any endpoint estimate cannot be assessed from the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

For the experimental group, the registry records zero serious adverse events among 34 participants at risk, zero other adverse events among 34 at risk, and zero deaths. These are the event counts recorded in the registry, not a guarantee that risk was absent. A zero count can occur even when an event is possible, particularly when follow-up and observation are limited.

The record does not report serious adverse event terms, so there are no listed serious-event types to characterize. It also does not describe event definitions, the method or frequency of safety monitoring, how events were attributed, or the completeness of event collection. The intervention period is described as 7 days, but the safety follow-up duration is not reported in the registry record.

These figures should be read as descriptive counts within the study, not as a comparative safety estimate. There is no control group against which to compare event frequency, and the study’s size and design do not establish the absence of uncommon or delayed harms. The recorded zero counts do not establish that the intervention is safe or unsafe.

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

The registry record establishes that a completed Phase 1, single-group study evaluated a combined SAM ultrasound and diclofenac patch regimen in patients with stage II and stage III knee osteoarthritis. The stated schedule was 4 hours of device treatment every day for 7 days, with continuous ultrasound at 3 megahertz and 0.132 watts/cm2 intensity. Enrollment is recorded as 34.

The primary question concerned change from baseline in self-described pain on a 0-10 scale over 7 days. The registry record does not report numerical results for this endpoint. It therefore does not establish the average change, participant-to-participant variation, or precision of the estimate. It cannot support a claim that pain improved, worsened, or remained unchanged.

Even if a within-group change were available, the single-group design would not establish that the intervention caused it. There is no randomized comparator, and masking is recorded as none. Changes could reflect the intervention, but could also arise from other influences over time. In addition, because the device and diclofenac patch were used together, the design cannot separate their effects.

The record also lists WOMAC change as a secondary outcome, but numerical results are not reported in the registry information. Safety counts are recorded as zero serious adverse events, zero other adverse events, and zero deaths in the experimental group. Those counts are descriptive and do not demonstrate that no harm is possible.

Thus, the registry information describes the study question and design but does not provide enough outcome data to judge the magnitude or precision of the primary result. It also does not offer a controlled estimate of treatment effect. Interpretation should remain limited to what the record reports, rather than treating completion, enrollment, or event counts as evidence of efficacy or comparative safety.

14. Why This Trial Matters Statistically

This study raises several statistical issues that matter when interpreting early clinical research. First, it uses a within-group change in a patient-reported pain measure. Such a measure can describe symptom trajectories, but causal interpretation depends on the design. Without a concurrent comparison group, the study cannot distinguish intervention-related change from natural fluctuation, expectations, concurrent care, or other changes over time.

Second, the intervention combines a device and diclofenac patch. Even if outcome changes were reported, a single combined-treatment group could not establish which component contributed to those changes. This is an attribution limitation as well as a design limitation.

Third, the primary outcome is a continuous measure. Its interpretation depends not only on an average change but also on variability and uncertainty. The registry record does not report numerical endpoint estimates or confidence intervals, so neither the magnitude nor precision can be assessed. This illustrates why a completed study record and an enrollment figure are not substitutes for transparent outcome reporting.

Finally, the record lists multiple outcomes and analyses but does not report the statistical plan, multiplicity handling, missing-data procedures, or analysis population. Those decisions shape how results should be understood. Their absence limits appraisal of the reported record, independently of the study’s small-scale, early-phase setting. A clear report of estimates, uncertainty, participant flow, and analysis methods would be needed to support a fuller statistical interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation is the absence of numerical primary and secondary outcome results in the registry record. Without those estimates, readers cannot assess the direction, magnitude, variability, or precision of changes in pain or WOMAC scores. The completed status does not fill this reporting gap.

The single-group design has no randomized control condition, and masking is recorded as none. Changes over time therefore cannot be attributed to treatment with the confidence that a controlled comparison may offer. The combined intervention further prevents separation of the device’s contribution from the diclofenac patch’s contribution.

The registry record does not report detailed eligibility criteria, participant characteristics, adherence, participant flow, or the analysis population. It does not describe missing-data methods, the statistical model, confidence intervals, or the planned approach to multiplicity. The protocol, sample-size justification, and interim analyses are not reported in the registry record. These omissions limit assessment of whether the reported analyses, if any, followed a prespecified plan.

The primary timeframe is 7 days, and the safety follow-up duration is not reported in the registry record. The short stated treatment and assessment period does not establish longer-term outcomes. Safety counts are recorded, but the event-collection procedures and definitions are not described. These limitations are specific to the design and reporting available for this trial and should constrain conclusions drawn from it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sustained Acoustic Medicine (SAM) Combined With a Diclofenac Ultrasound Coupling Patch for Knee Osteoarthritis — NCT04391842.
• Registry record last updated 2023-06-27; status last verified 2023-06.
• Results first posted 2021-09-23.
• 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.

19. Record Summary

The registry record describes NCT04391842, a completed Phase 1, single-group study of Sustained Acoustic Medicine combined with a 1% diclofenac ultrasound coupling patch for knee osteoarthritis. Enrollment is recorded as 34. The device regimen was described as 4 hours daily for 7 days, with continuous ultrasound at 3 megahertz and 0.132 watts/cm2.

The primary endpoint was change from baseline in self-described pain on a 0-10 scale over 7 days. WOMAC score change was listed as a secondary outcome, with a range from 0 to 2400. Numerical results for these outcomes are not reported in the registry record. The design has no randomized comparison group and no masking is recorded, so within-group change would not by itself establish a causal treatment effect.

The experimental group’s recorded safety counts were zero serious adverse events, zero other adverse events, and zero deaths. These are descriptive counts, not proof of no risk. The record does not report the statistical plan, missing-data approach, or analysis population.