Wearable LITUS Device for Osteoarthritis of the Knee: a Randomized Double-Blind Placebo-Controlled Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Wearable LITUS Device for Osteoarthritis of the Knee: a Randomized Double-Blind Placebo-Controlled Trial (NCT02083861), a randomized na study. The primary outcome is Pain on the Numeric Rating Scale (NRS) Change From Baseline to Study Conclusion.

2. Clinical Question

The study was designed to evaluate a wearable therapeutic ultrasound device in patients with knee osteoarthritis. Its stated aims also included mobility, range of motion, muscle strength in the affected leg, and quality of life. The posted primary results concern pain change; the registry record lists quality of life, range of motion, and muscle strength as secondary outcomes, but outcome results for those measures are not included in the record summarized by these results.

The clinical comparison of interest is not simply whether pain changed within each arm. It is whether the change differed between participants assigned to active ultrasound and participants assigned to a placebo device. A within-arm mean describes the average change among analyzed participants in that arm. A between-arm contrast would quantify the difference in average change attributable to assignment under the trial comparison. The posted figures give the two arm means and their intervals, but do not report that direct contrast, a test of the contrast, or its confidence interval.

The outcome population also matters when interpreting the question. The registry says that patients who completed the entire study were included in the primary analysis. It does not state in this record whether that population was defined before the study, how participants who did not complete were handled, or whether another analysis population was used.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group study with a placebo device comparator. The registry record describes the study as completed and reports enrollment of 93. Its listed condition is knee osteoarthritis. The study is titled as a randomized, double-blind, placebo-controlled trial, while its masking field specifies quadruple masking; the record does not identify the roles covered by masking.

The active group received the Sam Ultrasonic Diathermy Device for 4 hours every day for 6 weeks. The device emitted continuous ultrasound at 3 megahertz (MHz) and 0.132 watts/cm2 intensity. The placebo group wore the same named device for the same described daily duration and study period, but the device did not emit ultrasound. The description says that the placebo device appeared and operated identically to the active device. This design aims to make the experience of wearing the device similar across groups while varying ultrasound emission.

The registry lists 51 participants in the active arm and 33 in the placebo arm for the primary outcome results. The outcome description says the analysis included patients who completed the entire study. These arm counts should be read as the reported analysis counts, not as the total enrollment or as evidence about all participants randomized. The registry gives separate safety denominators of 55 for the active group and 35 for placebo, so the outcome-analysis and safety populations are not identical in the posted record.

The study start is listed as 2014-03 and primary completion as 2014-10. No phase designation beyond NA is listed. The registry record does not report the randomization procedure, allocation concealment method, the detailed masking procedures, or the rationale for the enrollment target. It also does not report a formal protocol description for the analysis beyond the outcome information presented.

A parallel design assigns participants to a group and assesses outcomes in that group over the trial period, rather than having each participant receive both conditions in sequence. Randomization is intended to make treatment groups comparable on average, including with respect to factors that may affect the outcome. However, the registry results do not include enough information to assess how randomization was implemented or whether the groups were balanced on baseline characteristics. Those details are 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

Analysis population for the primary outcome, as defined in the registry: Patients that completed the entire study were included in analysis.

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 Pain on the Numeric Rating Scale (NRS) Change From Baseline to Study Conclusion, measured over Baseline, Week 6.

The primary endpoint is change in pain from baseline to study conclusion, assessed with the Numeric Rating Scale (NRS). The registry describes the NRS as ranging from 0-10, with 0 meaning no pain and 10 the worst pain possible. The stated timeframe is baseline and Week 6. The reported arm-level measure is the mean change, with a 95% confidence interval.

A change score expresses how a participant’s measured outcome at follow-up differs from the baseline measurement. A negative mean change on this scale is a decrease in the measured pain score compared with baseline. The active arm’s reported mean change is -1.96 units on a scale, and the placebo arm’s is -0.85 units on a scale. These are arm-level averages among the participants included in the analysis, not descriptions of every individual participant’s response.

Pain is a central outcome for a study whose stated purpose includes evaluating whether the device can reduce pain. A numeric scale turns a participant’s reported pain into a measure that can be summarized and compared statistically. The scale does not, by itself, show whether a change is important to each participant, how consistently individuals changed, or how the groups differed after accounting for the trial design.

The registry record does not report the actual between-arm difference in mean change or its confidence interval. The arm-specific means therefore describe observed changes, but they do not fully answer the comparative question. The record also does not provide the distribution of individual scores, a standard deviation, or another measure of participant-to-participant variability for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is continuous: it is a numeric pain score summarized as a mean change. For each arm, the reported value is the average change among participants included in that arm’s analysis. The registry provides a 95% confidence interval for each mean. It does not provide the standard deviation, standard error, or individual-level data for the outcome, so those quantities cannot be read directly from the arm summaries.

What the confidence intervals describe

A confidence interval communicates the uncertainty associated with an estimate under a statistical procedure and its assumptions. A narrower interval generally indicates greater precision than a wider interval for the same type of estimate. The active-arm interval runs from -2.92 to -1.0, and the placebo-arm interval runs from -1.96 to 0.26. These ranges characterize uncertainty around their respective arm means; they do not describe the range of changes among participants.

The interval for an arm mean answers a different question from an interval for the difference between arms. The treatment comparison requires a contrast between the arm means, together with an uncertainty estimate for that contrast. The registry record does not report that comparative estimate or interval. It is therefore not appropriate to infer a formal between-arm result from the fact that one arm’s interval is entirely below 0 and the other arm’s interval includes 0. Separate intervals do not provide the same information as a direct comparison.

Why the analysis population matters

The registry specifies that patients who completed the entire study were included in the primary analysis. An analysis restricted to completers describes people with observed completion data, but it can differ from an analysis that retains all randomized participants. If completion is related to pain, treatment assignment, or other participant characteristics, excluding participants without a complete outcome may affect the estimate. This is a general concern about missing outcome data; the record does not show whether that concern affected this trial or in what direction.

The registry record does not report whether the primary analysis followed an intention-to-treat principle, whether any imputation was used, or how missing measurements were handled. It also does not report reasons for loss to follow-up or the number of participants with missing endpoint measurements by arm. The arm counts for the primary outcome therefore should be interpreted according to the stated completer population, rather than assumed to represent every randomized participant.

What randomization and masking contribute

Random allocation is intended to reduce systematic differences between groups at the point of assignment. Masking can reduce the influence of expectations or knowledge of assignment on participant reports, care, or outcome assessment. The record labels the design randomized and quadruple-masked and describes the placebo device as appearing and operating identically, except that it does not emit ultrasound. These design features are relevant to the credibility of a comparison, but the registry does not describe the randomization method, allocation concealment, or which people were masked.

Even with randomization and masking, analysis choices and incomplete follow-up can affect interpretation. The outcome population is described as patients completing the entire study, while safety denominators are reported separately. The registry record does not explain how those populations were determined or whether outcome analyses adjusted for baseline measures or other variables.

Planning illustrations and observed results

Sample-size calculations are planning exercises: they describe the number of participants that would be needed under specified assumptions to detect a target effect with a chosen design and power. The planning assumptions described for this trial use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. These assumptions describe an illustration based on the observed effect, not the trial’s original design justification.

Such calculations do not measure the power actually achieved in the completed trial. A post hoc calculation based on an observed estimate is especially dependent on that estimate and does not replace the confidence interval or direct comparative result. The registry record does not report the trial’s own sample-size justification. Planning figures, where used, should therefore be read as hypothetical planning illustrations, not as observed power or proof that the trial could reliably detect a particular effect.

For continuous outcomes, variability affects precision: greater variation among participants generally makes the estimated mean or contrast less precise for a given amount of data. The record gives confidence intervals but does not report a dispersion measure for the endpoint. No additional measure of variability should be inferred from the arm means alone.

Multiplicity and the scope of inference

The registry lists three secondary outcomes: quality of life measured with WOMAC, range of motion in the treated knee, and muscle strength in the treated knee. It reports four outcome measures overall, but only the primary pain results are included in the posted results. The registry record does not report a multiplicity adjustment, a hierarchy of outcome testing, or a statistical analysis plan specifying how multiple outcomes were handled.

When several outcomes or comparisons are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiple testing. That is a general statistical issue, not evidence that a particular adjustment was or was not appropriate in this trial. With the analysis details and secondary results not reported in the registry record, the scope and confirmatory status of any secondary conclusions cannot be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, pain change on the NRS, and three secondary outcomes: quality of life measured with WOMAC, range of motion in the treated knee, and muscle strength in the treated knee. It reports four outcome measures overall. The posted results described for the primary endpoint include arm means and confidence intervals, but results for the secondary outcomes are not reported in the registry record.

The record does not report a statistical plan describing a hierarchy among outcomes, an adjustment for testing multiple outcomes, or how multiplicity was considered. When several hypotheses are examined, there is a general risk that at least one result may appear notable by chance; adjustment or a prespecified testing hierarchy can address that concern. Without the analysis plan and results for the other outcomes, it is not possible to determine how the trial handled this issue or how much emphasis to place on any unreported secondary findings.

For the primary endpoint, the registry states that patients who completed the entire study were included in the analysis. It does not report whether this was the only analysis population, whether the analysis followed an intention-to-treat approach, how participants who did not complete were handled, or whether missing scores were imputed. Reasons for missing data and their distribution by arm are not reported in the registry record.

The outcome-analysis counts are 51 for active ultrasound and 33 for placebo. Safety is reported with denominators of 55 and 35, respectively. These distinct counts indicate that the record presents different populations for outcome and safety summaries; it does not explain the discrepancy between those sets of denominators. The enrollment of 93 is a separate trial-level figure and should not be treated as the analysis count for every outcome.

Because missing-data handling and analysis-population details are not reported, the possible influence of incomplete follow-up on the estimated mean changes cannot be assessed from these results alone. This uncertainty is separate from the confidence intervals, which describe statistical uncertainty in the reported estimates under the method used; they do not account automatically for bias caused by missing outcome data.

11. 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.

The registry reports zero serious adverse events in each safety group: 0 among 55 participants at risk in the active ultrasound group and 0 among 35 participants at risk in the placebo group. It also reports zero other adverse events in each group, with the same respective denominators. Deaths are reported as 0 in both groups. No serious adverse event terms are listed.

These figures mean that the posted record reports no events of the listed types among the participants included in the safety denominators. They do not establish that no such events occurred outside those recorded populations, nor do they show that the two groups have identical safety profiles. When no event is observed, the data still allow uncertainty about the event frequency that might occur in a broader population. A zero count is not proof that the underlying risk is zero.

The safety denominators differ from the primary outcome analysis counts: the adverse-event groups include 55 active and 35 placebo participants, while the primary outcome results include 51 and 33. The registry record does not explain the population definitions or denominator differences. It also does not provide detailed timing, duration, severity grading, or causal assessments for adverse events in the information.

These results are a descriptive account of reported events, not a comparative statistical analysis. The registry record does not provide a formal comparison of adverse-event frequencies or an assessment of precision for those frequencies. Therefore, the counts should be read as the recorded observations within the stated denominators, not as a conclusion about relative safety.

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

The results describe average pain-score changes among participants who completed the study and were included in the primary analysis. The active ultrasound group’s mean change was -1.96 units on a scale, with a 95% confidence interval from -2.92 to -1.0. The placebo group’s mean change was -0.85 units on a scale, with a 95% confidence interval from -1.96 to 0.26. On the NRS, lower scores indicate less pain, so negative changes correspond to lower average scores at follow-up than at baseline.

Those arm-specific estimates do not by themselves answer whether active ultrasound produced a different change from the placebo device. A direct between-arm estimate and its uncertainty are not reported in the registry record. Nor are a comparative p-value or an adjusted analysis result reported. The posted numbers therefore support description of the two analyzed groups, but do not permit a complete statistical assessment of the treatment contrast.

The registry record’s completer-only analysis description limits the population to which the observed means directly pertain. It does not report how people who did not complete the study were handled or why they were not included. The reported safety counts use different denominators from the primary outcome analysis, and the record does not explain that difference.

The study’s stated purpose also includes mobility, range of motion, muscle strength, and quality of life. Although the registry lists secondary outcomes for WOMAC quality of life, treated-knee range of motion, and treated-knee muscle strength, their results are not reported with the primary results. Thus the pain estimates cannot answer what happened to those other outcomes.

In general, a trial’s results should be interpreted in light of the estimates, their precision, the analysis population, and the completeness of the outcome data. Here, the confidence intervals quantify uncertainty around arm means, while important information about the direct comparison, missing-data handling, and analysis plan is not reported in the registry record. The available numbers are not sufficient to support a broad conclusion about the device’s effects or safety beyond the observations recorded for these participants.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it illustrates the distinction between describing change within each group and estimating a difference between groups. The active and placebo arms each have a reported mean change from baseline, but the scientific comparison is the contrast between those means. A direct contrast with its confidence interval would show both the estimated comparative effect and its precision. That result is not reported in the registry record.

The arm-level confidence intervals also demonstrate why separate within-group intervals should not be treated as a test of the treatment comparison. An interval around an arm mean addresses uncertainty about that mean. A between-arm analysis addresses uncertainty about a difference. These are related but distinct statistical quantities, and the latter cannot be substituted by visually comparing the former.

The stated completer analysis and distinct safety denominators make analysis populations important to interpretation. The primary pain results include 51 active and 33 placebo participants, while the safety summaries use denominators of 55 and 35. Enrollment is reported as 93. Without an account of participant flow and missing outcomes, it is not possible to establish from the registry record why these populations differ or how incomplete data may have affected the results.

The trial also lists several outcomes, while the posted primary results concern pain. Multiple outcomes raise general questions about prespecification, testing hierarchy, and multiplicity. The registry record does not report those analysis details or results for the listed secondary outcomes. That absence limits the scope of statistical interpretation, rather than demonstrating that a particular analysis was inappropriate.

Finally, planning calculations based on an observed effect are not the same as a prospective design justification or observed power. A planning illustration can show how assumptions affect a hypothetical sample size, but it cannot repair an unreported comparative estimate or establish the precision achieved in the trial. Clear reporting of the treatment contrast, missing-data approach, and planned analyses is necessary to judge what the trial estimates and how reliably.

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 primary outcome analysis is described as including patients who completed the entire study. The registry record does not report the number or reasons for non-completion by group, how missing measurements were handled, or whether participants with incomplete data contributed to another analysis. This restricts interpretation to the stated completer population and leaves the potential influence of missing outcome data uncertain.

The reported primary endpoint results are arm-specific means with 95% confidence intervals. A direct difference between the active and placebo arms, its confidence interval, and a p-value are not reported in the registry record. Without the comparative estimate, the size and precision of the contrast cannot be assessed directly from the posted results. The record also does not report a dispersion measure or individual outcome data.

The safety denominators differ from the outcome-analysis counts, and the registry does not explain why. It reports zero serious adverse events, zero other adverse events, and zero deaths in each safety group, but no event details beyond those counts are included. These summaries cannot by themselves characterize the full range of safety outcomes or the uncertainty around event frequencies.

The registry lists three secondary outcomes, but their results are not reported in the results. A statistical analysis plan, adjustment for multiple outcomes, and the status of any prespecified secondary analyses are also not reported in the registry record. Consequently, interpretation is limited to the posted primary endpoint information and cannot extend to the stated secondary aims.

Other trial details that could aid assessment—including baseline group characteristics, randomization implementation, allocation concealment, reasons for withdrawals, and the roles covered by quadruple masking—are not reported in the registry record. The results should therefore be read as a limited account of the reported endpoint and safety counts, not as a complete account of trial conduct or analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Wearable LITUS Device for Osteoarthritis of the Knee: a Randomized Double-Blind Placebo-Controlled Trial — NCT02083861.
• Registry record last updated 2018-05-07; status last verified 2018-04.
• Results first posted 2018-05-07.
• 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.

18. Record Summary

The registry record describes a completed randomized, quadruple-masked, parallel-group, placebo-controlled study of a wearable ultrasound device for knee osteoarthritis. Enrollment was 93. The active group used the Sam Ultrasonic Diathermy Device for 4 hours every day for 6 weeks; the placebo device appeared and operated identically but did not emit ultrasound.

The primary outcome was mean change in pain on the NRS from baseline to Week 6. Among patients who completed the entire study, the active group mean change was -1.96 units on a scale, with a 95% confidence interval from -2.92 to -1.0; the placebo mean change was -0.85 units on a scale, with a 95% confidence interval from -1.96 to 0.26. The registry record does not report a direct between-arm estimate or its uncertainty.

Safety summaries report zero serious adverse events, zero other adverse events, and zero deaths in both groups, using denominators of 55 for active ultrasound and 35 for placebo. The primary outcome analysis counts were 51 and 33, respectively. Missing-data methods, a formal statistical analysis plan, and results for the listed secondary outcomes are not reported in the registry record.