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 Trial to Evaluate UltraSound in the Treatment of Tibial Fractures (NCT00667849), a randomized na study. The primary outcome is Change From Baseline in the SF-36 Physical Component Summary (PCS) Score of the Short Form-36 (SF-36).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00667849 |
| Phase | NA |
| Condition | Tibial Fractures |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 501 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Bioventus LLC |
| Results posted | Yes |
2. Clinical Question
Population
People with tibial fractures treated with intramedullary nailing were the population of interest. The primary outcome population was the Full Analysis Set: randomized subjects with at least one post-treatment set of adjudicated x-rays. The registry does not provide further eligibility details in this record.
Intervention
Participants assigned to the Exogen 4000+ device received low-intensity, pulsed ultrasound. The study description identifies the intended use as treatment of tibial fractures after intramedullary nailing.
Comparator
The comparator was a sham device described as identical except that it did not administer ultrasound. This comparison was intended to distinguish outcomes in the device group from those in the sham group.
Primary question
The primary question was whether the groups differed in change from baseline in the SF-36 Physical Component Summary score over 365 days. The record reports least-squares mean changes for each group, with 95% confidence intervals. It does not report a treatment contrast or a statistical test for the between-group difference.
The trial was randomized, parallel-group, and quadruple-masked according to the registry. The record does not identify which roles were masked, so the masking label should not be expanded into assumptions about participants, clinicians, assessors, or analysts. The intended comparison is the device against sham, not ultrasound against no treatment in a broader clinical setting.
3. Trial Design
The registry describes a randomized, parallel trial with two device groups: Exogen 4000+ and sham. The sham is described as an identical device with the exception that ultrasound was not administered. The listed masking designation is quadruple; the registry record does not specify which study roles that designation covers. The trial phase is listed as NA.
Enrollment is recorded as 501. The primary outcome population is defined as the Full Analysis Set, consisting of randomized subjects with at least one post-treatment set of adjudicated x-rays. The reported outcome group sizes are 241 for Exogen 4000+ and 242 for sham. These outcome counts are not the same as the enrollment figure, and the record does not give a participant flow explanation for the difference. Safety counts use groups of 250 and 251 at risk, respectively.
The study’s stated purpose was to determine the effect of low-intensity, pulsed ultrasound on tibial fractures treated with intramedullary nailing. The primary outcome was change from baseline in the SF-36 Physical Component Summary score, assessed over 365 days. The description refers to assessments at baseline and 6 post baseline time points and identifies a mixed effects repeated measure single point estimate.
The registry lists the study status as terminated. The reason for termination and whether termination affected the planned follow-up or analyses are not reported in the registry record. The start is recorded as 2008-09 and primary completion as 2012-12. Further protocol details, including the allocation procedure and the timing or conduct of any interim analyses, 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
| Stage | Exogen 4000+ | Sham |
|---|---|---|
| STARTED | 250 | 251 |
| COMPLETED | 142 | 130 |
| NOT COMPLETED | 108 | 121 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) is all subjects randomized with at least one post treatment set of adjudicated x-rays.
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 | Exogen 4000+ | Sham | Total |
|---|---|---|---|---|
| Participants analysed | 250 | 251 | 501 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 244 | 239 | 483 |
| Age, Categorical: >=65 years | Participants | 6 | 12 | 18 |
| Age, Continuous | years | 37.1 (SD 13.2) | 39.1 (SD 14.6) | 38.3 (SD 13.9) |
| Sex: Female, Male: Female | Participants | 81 | 75 | 156 |
| Sex: Female, Male: Male | Participants | 169 | 176 | 345 |
| Region of Enrollment: Canada | participants | 82 | 85 | 167 |
| Region of Enrollment: United States | participants | 168 | 166 | 334 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in the SF-36 Physical Component Summary (PCS) Score of the Short Form-36 (SF-36), measured over Over 365 days.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline in the SF-36 Physical Component Summary (PCS) score, a component score from the Short Form-36. The registry reports this outcome in units on a scale and specifies least-squares means with 95% confidence intervals. Its timeframe is over 365 days.
The SF-36 PCS is a patient-reported measure of physical health status. Such measures can capture participants’ perceptions of physical functioning and health rather than relying only on a clinical event or imaging finding. That makes a change score relevant to a study asking whether participants’ physical health status changes during follow-up. This is a general explanation of the type of measure, not a claim about how the score behaved in this trial.
The record describes the score range as -100 worst, 0 best. Because the endpoint is a change from baseline, its sign should be read in the context of the score definition and the specified change convention. The registry does not provide a separate explanation of the sign convention. The reported estimates are negative in both groups; those values alone do not establish whether the groups differ.
Repeated assessments can describe how outcomes evolve over time rather than focusing on a single follow-up visit. The registry says that assessments occurred at baseline and 6 post baseline time points, with a mixed effects repeated measure single point estimate. The specific visit-level estimates and model details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports a least-squares mean change of -6.9 units for Exogen 4000+, with a 95% confidence interval from -8.0 to -5.9. For sham, it reports -7.5 units, with a 95% confidence interval from -8.6 to -6.5. The reported group sizes are 241 and 242, respectively. These are estimates for each group, not an estimate of the difference between groups.
A confidence interval communicates uncertainty around an estimate under the statistical model used. Here, each interval describes uncertainty around its group’s estimated mean change. The intervals do not directly answer the primary comparative question. A formal comparison would ordinarily be expressed through a treatment contrast with its uncertainty, or through an appropriate test. Neither a between-group estimate nor its confidence interval or p-value is reported in the registry record. The registry lists zero analyses.
The estimates are relatively close in the sense that both are negative and their confidence intervals overlap. That observation is descriptive and is not a substitute for a test or confidence interval for the difference. Overlap between separate group intervals does not itself quantify the uncertainty in the between-group contrast. No difference should be calculated from the displayed arm summaries.
The endpoint description specifies a mixed effects repeated measure approach and calls the reported quantity a single point estimate. Least-squares means are model-based estimates; they are not necessarily identical to simple averages of observed scores. The registry does not report the model specification, covariates, covariance structure, or any adjusted group contrast. As a result, the reported estimates can be described, but the modeling choices cannot be independently assessed from this record.
The outcome population is the Full Analysis Set defined by randomization and at least one post-treatment set of adjudicated x-rays. This is the population definition recorded for the primary endpoint; it should not be assumed to mean that every randomized participant contributed a complete set of SF-36 measurements. The record does not report how many participants had missing endpoint data, how missing values were handled, or whether all participants in the defined set were included in the model.
The trial is listed as terminated, but the reason and implications are not reported. The status alone does not establish why the trial ended or whether the endpoint analysis was affected. The available evidence supports a description of the arm-level estimates and their uncertainty, not a conclusion about the size or statistical certainty of a treatment effect.
9. Statistical Methods Explained
The registry identifies this as a randomized, parallel-group comparison of Exogen 4000+ with sham. Random allocation is intended, in general, to reduce systematic differences between groups at the start of a trial. It does not guarantee that every baseline characteristic will be identical, and details of the allocation process are not reported in the registry record. The parallel design means the groups receive their assigned device condition during the same trial rather than crossing over between conditions; further design details are not reported.
What do the reported estimates represent?
The primary outcome is a continuous measure: change in SF-36 PCS score from baseline. For a continuous endpoint, a group mean summarizes the center of the observed or modeled score changes. The registry labels the estimates as least-squares means. In general, a least-squares mean is derived from a statistical model and can account for terms included in that model. The model terms and the exact estimation procedure beyond the mixed effects repeated measure description are not reported in the registry record.
The reported estimates are -6.9 for Exogen 4000+ and -7.5 for sham. Each is accompanied by a 95% confidence interval. In general, a confidence interval expresses the precision of an estimate under the assumptions of the analysis. It is not a range guaranteed to contain the true value, and it does not by itself provide the probability that a particular hypothesis is true. The intervals concern the individual group estimates, not the difference between groups.
Why is a direct contrast important?
The research question compares the assigned device with sham, so the central statistical quantity is the difference between the groups, estimated with suitable uncertainty. Separate group estimates give context about change in each arm, but they do not replace a treatment contrast. A direct contrast and its confidence interval would show the estimated size and precision of the comparative result. A p-value could address compatibility with a specified null hypothesis under the test’s assumptions, but it would not convey the magnitude or precision as fully as an interval. The registry record does not report a comparative estimate, confidence interval, or p-value.
It is also important not to treat confidence-interval overlap as a formal test. The group intervals are not the same as a confidence interval for their difference. The uncertainty of a contrast depends on the variability and relationship of the estimates under the analysis model. Those details are not reported. No contrast should be reconstructed from the arm estimates.
What does the repeated-measures description imply?
Repeated-measures methods are generally used when an outcome is collected from the same participants on multiple occasions. A mixed effects model can represent the relationship among measurements from a participant and can estimate an overall or specified model-based outcome. The registry describes assessments at baseline and 6 post baseline time points and refers to a mixed effects repeated measure single point estimate. It does not report whether the estimate is averaged over visits, tied to a particular visit, or formed using other model terms. The model specification and covariance assumptions are not reported in the registry record.
Repeated measures often create challenges when observations are missing. A model may use available measurements under specified assumptions, but the presence of a mixed effects description does not establish how missing data were handled or whether the assumptions were appropriate. Imputation methods, sensitivity analyses, and the amount or pattern of missingness are not reported in the registry record.
How should the group counts be understood?
The primary outcome groups have 241 and 242 participants reported, while the safety groups have 250 and 251 at risk. The endpoint population has a specific definition based on randomization and at least one post-treatment set of adjudicated x-rays. The registry does not provide a participant flow account explaining how the outcome and safety populations relate to enrollment or to one another. Counts for an outcome should not be taken to mean that all participants had complete observations at every assessment.
The registry reports 501 enrolled participants overall. Group counts used for the endpoint and safety summaries are distinct analysis denominators, and their differences should not be interpreted without additional flow and missing-data information. The record does not report a protocol-defined analysis population beyond the stated Full Analysis Set definition, nor does it describe any per-protocol or other sensitivity analysis.
What can planning calculations tell readers?
General sample-size planning illustrations depend on assumptions about the target effect, variability, significance level, allocation, and statistical method. The planning assumptions recorded for this trial’s illustrations specify a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect framed as a fraction of the observed effect. These are planning illustrations based on the observed effect, not the trial’s own design justification. Their results are not reported in the registry record. They are not observed power and cannot establish the probability that the trial detected an effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures and no posted secondary results. It also lists zero analyses. The record does not identify which outcomes were designated secondary, provide a complete set of outcome-specific analyses, or report a multiplicity adjustment. Therefore, it is not possible to determine from this record whether multiple outcomes or repeated comparisons were accounted for in the inferential plan. Any multiplicity strategy is not reported in the registry record.
The primary outcome description identifies a Full Analysis Set as all subjects randomized with at least one post-treatment set of adjudicated x-rays. That definition is relevant to interpreting the reported endpoint counts, but it does not explain how missing SF-36 observations were treated. The number and timing of missing measurements, reasons for missingness, imputation procedures, and sensitivity analyses are not reported in the registry record.
The record describes a mixed effects repeated measure single point estimate. This does not, by itself, specify the handling of incomplete outcome data. In general, conclusions from models using repeated measurements depend on model assumptions, including assumptions about the relationship among measurements and the process leading to missing observations. The relevant assumptions and diagnostics are not reported.
There is no reported account of all randomized participants’ progress through follow-up or of exclusions from the primary outcome analysis. The distinction between enrollment, the primary outcome group counts, and safety counts is visible in the record, but the participant flow explaining those denominators is not reported in the registry record.
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 |
|---|---|---|---|
| Exogen 4000+ | 3 | 250 | 1.2% |
| Sham | 5 | 251 | 2.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Exogen 4000+ | 98 of 250 |
| Sham | 97 of 251 |
Most frequent serious adverse event terms
| Event term | Organ system | Exogen 4000+ | Sham |
|---|---|---|---|
| Broken screw | Surgical and medical procedures | 1 of 250 | 1 of 251 |
| acute chest pain | Cardiac disorders | 0 of 250 | 1 of 251 |
| Allergic reaction | Immune system disorders | 1 of 250 | 0 of 251 |
| Infection, tissue | Infections and infestations | 1 of 250 | 0 of 251 |
| Renal dysfunction (creatinine 2x BL level | Renal and urinary disorders | 0 of 250 | 1 of 251 |
| Tendonitis | Musculoskeletal and connective tissue disorders | 1 of 250 | 0 of 251 |
| sternal wire closure disruption | Cardiac disorders | 0 of 250 | 1 of 251 |
| cough, vomiting, leukocytosis, increased troponin | Gastrointestinal disorders | 0 of 250 | 1 of 251 |
| infection tissue | Infections and infestations | 0 of 250 | 1 of 251 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Exogen 4000+ | Sham |
|---|---|---|---|
| Pain | Nervous system disorders | 48 of 250 | 49 of 251 |
| Other local event | Musculoskeletal and connective tissue disorders | 19 of 250 | 20 of 251 |
| Edema | Blood and lymphatic system disorders | 18 of 250 | 15 of 251 |
| Other, not listed on AE form | General disorders | 7 of 250 | 21 of 251 |
| accident/fall | Injury, poisoning and procedural complications | 14 of 250 | 7 of 251 |
| Pain | General disorders | 8 of 250 | 8 of 251 |
| Infection, tissue | Infections and infestations | 6 of 250 | 9 of 251 |
| Rash/redness at treated area | Skin and subcutaneous tissue disorders | 10 of 250 | 3 of 251 |
| Wound complication | Infections and infestations | 7 of 250 | 5 of 251 |
| Non-union | Musculoskeletal and connective tissue disorders | 8 of 250 | 4 of 251 |
Serious events with the highest arm-level rate: allergic reaction (0.4%), infection, tissue (0.4%), broken screw (0.4%), tendonitis (0.4%), acute chest pain (0.4%).
The serious adverse event summaries list 3 affected participants among 250 at risk in the Exogen 4000+ group and 5 among 251 at risk in the sham group. These are counts for the groups recorded as at risk. They should be read as reported counts, not as a complete account of the timing, duration, severity, relatedness, or clinical course of events. Those details are not reported in the registry record.
The listed serious adverse event terms each carry a reported value of 0.4%: Allergic reaction, Infection, tissue, Broken screw, Tendonitis, acute chest pain, and Renal dysfunction (creatinine 2x BL level. The last term appears without a closing parenthesis in the record and is retained as recorded. The registry does not give enough detail in this summary to establish whether each term occurred in one participant, whether terms overlap within participants, or how the terms were coded.
Other adverse events are reported as 98 affected among 250 at risk for Exogen 4000+, and 97 among 251 at risk for sham. Death counts are not reported in the registry record. These safety summaries are descriptive; they do not by themselves establish that an event was caused by a device or that the groups differ. No inference should be made from the counts alone about event severity or comparative safety.
12. What the Result Does, and Does Not, Mean
The posted primary outcome estimates describe change in SF-36 PCS score for each group over the specified follow-up period. The estimate for Exogen 4000+ is -6.9, with a 95% confidence interval from -8.0 to -5.9. The estimate for sham is -7.5, with a 95% confidence interval from -8.6 to -6.5. These are group-specific least-squares means, not a reported estimate of the contrast between treatments.
Accordingly, the posted results do not establish the size or precision of a difference between Exogen 4000+ and sham on the primary outcome. The comparative estimate, its confidence interval, and a p-value are not reported in the registry record. The two group estimates and their intervals can be described, but they should not be converted into an unadjusted treatment difference. A direct group contrast would be needed to assess the comparative question using the intended analysis.
The measure is a patient-reported physical health summary score, and its recorded scale runs from -100 worst to 0 best. The estimates are changes from baseline, so interpretation should account for the scale and change convention. The registry does not explain the sign convention further. The values alone do not justify a statement that one assignment improved or worsened physical health relative to the other.
The available safety figures report serious and other adverse event counts by group. They are descriptive summaries, and event attribution, timing, and fuller clinical details are not reported. The record also lists the study as terminated without reporting the reason. Neither that status nor the arm-level summaries, by themselves, establish a treatment benefit, lack of benefit, or cause for termination.
In general, a trial result is most informative when the estimated between-group effect is reported with its uncertainty, alongside a clear account of the analysis population and missing data. Those elements are not fully available in this registry record. The appropriate reading is therefore limited to the reported group estimates, confidence intervals, counts, and explicit gaps in the comparative analysis.
13. Why This Trial Matters Statistically
This trial illustrates why arm-level results and comparative results are not interchangeable. The primary question concerns Exogen 4000+ versus sham, but the registry reports a least-squares mean and confidence interval for each group without a treatment contrast. A reader can describe the individual estimates, yet cannot use them as a substitute for the estimated between-group effect and its uncertainty.
The example also highlights the role of outcome definition and analysis population. The primary endpoint is a change in a patient-reported physical health score, and the stated Full Analysis Set depends on randomization and the availability of at least one post-treatment set of adjudicated x-rays. That definition does not explain the completeness of SF-36 follow-up, making clear participant flow and missing-data reporting important for interpretation.
The repeated assessment description brings another general statistical issue into view: measurements from the same participant are related, so analysis needs to account for that structure. The registry identifies a mixed effects repeated measure approach, but does not report enough model detail to assess its specification. Naming a method is useful, but reproducibility and appraisal also depend on reporting the model and its assumptions.
Finally, the safety counts show why denominators and event definitions matter. Serious and other adverse event counts are reported for different at-risk group sizes, while deaths are not reported. Those summaries are useful descriptive information, but they do not provide a complete account of events or establish causation. The record’s terminated status is also relevant context, while the reason and analytical consequences remain unreported.
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 principal limitation of the available statistical record is the absence of a reported between-group result for the primary endpoint. Although arm-specific least-squares means and 95% confidence intervals are given, a comparative estimate, its uncertainty, and a test result are not reported in the registry record. This prevents direct assessment of the main comparative question from the posted outcome summary.
The repeated-measures analysis is named but not described in sufficient detail for independent evaluation. The model terms, covariance structure, any baseline adjustment, and the exact interpretation of the single point estimate are not reported in the registry record. The record also does not describe the amount or pattern of missing SF-36 data, methods for handling missing observations, or sensitivity analyses.
The reported endpoint population is defined using post-treatment adjudicated x-rays, while the endpoint and safety counts differ. A participant flow account explaining these denominators is not reported in the registry record. The record does not provide enough information to assess the completeness of follow-up or whether exclusions from analysis could affect interpretation.
The registry lists the trial as terminated, but does not report the reason or whether termination changed the follow-up, analysis, or reporting plan. It also does not report a multiplicity strategy for the listed outcome measures. The serious adverse event terms and counts lack further detail about timing, coding, relatedness, and participant-level overlap. These limitations constrain interpretation of both the efficacy summaries and the safety information without establishing what the unreported details would show.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Trial to Evaluate UltraSound in the Treatment of Tibial Fractures — NCT00667849.
- Registry record last updated 2015-12-08; status last verified 2015-11.
- Results first posted 2015-12-08.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT00667849 is a randomized, parallel-group trial listed as quadruple-masked, comparing Exogen 4000+ with a sham device for tibial fractures treated with intramedullary nailing. Enrollment is recorded as 501, and the study status is terminated. The primary outcome is change from baseline in SF-36 Physical Component Summary score over 365 days, reported as least-squares means with 95% confidence intervals.
The registry reports arm-level endpoint estimates of -6.9 for Exogen 4000+ and -7.5 for sham. It does not report a comparative estimate, confidence interval for the difference, or p-value. Serious adverse event counts are 3 of 250 and 5 of 251, respectively; other adverse event counts are 98 of 250 and 97 of 251. Death counts are not reported in the registry record. Further details on the analysis model, missing data, participant flow, multiplicity, and reason for termination are not reported in the registry record.