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 Microvascular Flow Assessment Repeatability Study: The MARS Study (NCT01242020), a non-randomized na study. The primary outcome is Variability of Repeated Measures for Each Subject.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01242020 |
| Phase | NA |
| Condition | Obesity |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pennsylvania |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes healthy participants in two groups: “Lean Healthy Subjects,” defined as BMI ≥18 and ≤25, and “Obese Healthy Subjects,” described as obesity grade I–II with BMI >30 and ≤35. The record lists obesity as a condition and reports enrollment of 6. The adverse-event record lists 6 lean participants at risk and 0 obese participants at risk.
Intervention
The intervention is perflutren lipid microsphere injectable suspension. The study summary identifies DEFINITY® as the contrast agent used with ultrasound to image blood vessels in the abdomen, neck, thigh and calf. The summary says images were to be obtained on two different days.
Comparator
This was not a randomized comparison. The lean and obese groups are not like-for-like control arms, and the primary question concerns repeat measurements within each subject rather than a treatment contrast between groups.
Primary question
How variable are repeated measurements of periadventitial, subcutaneous and skeletal-muscle microvascular flow for each subject? The primary outcome describes this variability using the coefficient of variation, with a timeframe of up to 30 days. Reliable data for those flow measurements were not collected for the outcome measure, so the registry record does not report an answer to the repeatability question.
3. Trial Design
The MARS Study, registered as NCT01242020, was a non-randomized, unmasked, parallel-design study sponsored by the University of Pennsylvania. Its official title describes a repeatability study of periadventitial adipose tissue, subcutaneous adipose tissue and skeletal muscle using contrast-enhanced ultrasound (CEU). The registry lists the phase as not applicable. Enrollment was 6.
The study summary describes ultrasound imaging of the abdomen, neck, thigh and calf with a contrast agent. It says two sets of pictures would be taken on two different days to assess whether results were similar across occasions. The listed intervention is perflutren lipid microsphere injectable suspension. The summary identifies DEFINITY® and explains that its use to image blood vessels in these body areas was to be conducted under an FDA Investigational New Drug application because that use differed from its stated approved use for cardiac ultrasound contrast.
The registry lists lean healthy and obese healthy groups, but the non-randomized allocation means they should not be read as randomized treatment and control arms. The listed arm descriptions define the groups by BMI. The adverse-event record lists 6 participants at risk in the lean group and none in the obese group; the registry does not report an arm-specific enrollment breakdown elsewhere in the registry record for this account.
The study started in 2011-01, had a primary completion date of 2011-05, and is listed as terminated. The reason for termination is not reported in the registry record. The record lists two outcome measures, including the primary variability outcome and a secondary measure of microvascular flow in the named tissues. It reports no analyses. It does not report a randomized efficacy comparison, and the study’s stated purpose was measurement repeatability.
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 | Lean Healthy Subjects | Obese Healthy Subjects |
|---|---|---|
| STARTED | 6 | 0 |
| COMPLETED | 3 | 0 |
| NOT COMPLETED | 3 | 0 |
Reasons for not completing this period:
| Reason | Lean Healthy Subjects | Obese Healthy Subjects |
|---|---|---|
| Withdrawal by Subject | 2 | 0 |
| Failed screening | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Reliable data for periadventitial microvascular flow, subcutaneous microvascular flow, and skeletal microvascular flow were not collected for the Outcome Measure.
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 | Lean Healthy Subjects | Obese Healthy Subjects | Total |
|---|---|---|---|---|
| Participants analysed | 6 | 0 | 6 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 | 0 | 6 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 2 | 0 | 2 |
| Sex: Female, Male: Male | Participants | 4 | 0 | 4 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 0 | 3 |
| Race (NIH/OMB): White | Participants | 3 | 0 | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Variability of Repeated Measures for Each Subject, measured over up to 30 days.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the variability of repeated measurements for each subject, expressed as a coefficient of variation (CV), for periadventitial microvascular flow, subcutaneous microvascular flow and skeletal-muscle flow. The registered timeframe is up to 30 days. This endpoint addresses whether repeated imaging measurements of the same subject produce similar values across measurement occasions, rather than whether one intervention changes a clinical outcome.
In general, a coefficient of variation expresses the size of variability relative to the scale of the measurements. It can help compare measurement consistency when the underlying quantities differ in magnitude. A smaller coefficient would generally indicate less variation relative to the measurement level, but the registry record does not provide a CV value or a threshold for judging acceptable repeatability.
The outcome description says reliable data for the specified flow measures were not collected for the outcome measure. Consequently, there is no reported estimate of the CV, no reported uncertainty interval, and no registry result indicating how repeatable any tissue-specific measurement was. The record’s secondary outcome names microvascular flow in the periadventitial, subcutaneous and skeletal-muscle tissues, but does not report a result for that measure either.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical limitation is that the registry record reports no reliable primary-outcome data. Although the study was designed to examine repeatability, its stated outcome does not include usable measurements from which repeatability can be quantified. No coefficient of variation, standard error, confidence interval or other endpoint estimate is reported. The record therefore does not support a numerical conclusion about the consistency of the CEU measurements across occasions or tissues.
The design description and the results record answer different questions. The summary describes a plan to obtain images on two different days, while the outcome population statement says reliable flow data were not collected. A planned repeated-measurement procedure is not itself evidence that the resulting measurements were repeatable. Nor does the absence of a reported estimate mean that the method had high or low variability; the amount of variability is unknown from the registry record.
The record lists enrollment of 6, but this count alone does not tell readers how many usable repeated observations were obtained for each tissue, or whether any participant contributed complete measurements. The adverse-event denominators identify 6 lean participants and 0 obese participants at risk. Those safety denominators do not establish the number with evaluable primary outcomes. The number with reliable endpoint data is not reported in the registry record.
The study was non-randomized and unmasked, and the registry itself cautions that the arms are not a like-for-like control comparison. Thus, the lean and obese groups should not be interpreted as a randomized comparison, and the record cannot establish a causal difference between them. In addition, no analysis results are listed. The reason for termination, any prespecified analysis plan, and any explanation for the lack of reliable outcome data are not reported in the registry record.
In general, a confidence interval describes the range of values compatible with an estimate under a statistical model, reflecting sampling uncertainty. There is no endpoint estimate or interval to interpret in this record. Even if repeated measurements had been available, the precision of a repeatability estimate would depend on the amount and structure of evaluable data, neither of which is detailed in the outcome record.
Any sample-size illustration based on an observed effect is a planning exercise, not an analysis of this study’s observed power. Here the primary outcome lacks reliable reported data, and the registry does not present an observed effect estimate that readers can use to assess repeatability. The posted record supports describing the research objective and design, but not judging measurement performance or comparing tissue-specific flow values.
9. Statistical Methods Explained
The registry record identifies a measurement-repeatability objective, not a randomized treatment-effect question. That distinction matters when interpreting statistical methods. A repeatability analysis asks how much repeated readings vary under the study’s measurement conditions. A randomized comparison instead estimates differences between assigned groups. The record describes non-randomized allocation and explicitly cautions that its arms are not a like-for-like control comparison.
What does a coefficient of variation describe?
In general, the coefficient of variation (CV) expresses the standard deviation of measurements relative to their mean. It is a scale-relative description of dispersion: the same absolute spread can represent different relative variability when measurement levels differ. For this study, the registered endpoint says repeated-measure variability would be expressed as a CV for periadventitial, subcutaneous and skeletal-muscle microvascular flow, assessed for each subject.
A CV is not a direct measure of agreement by itself. In general, interpretation also depends on how measurements were collected, the number and timing of repeated readings, and whether the analysis separates within-subject variability from differences between subjects. The registry summary mentions two imaging occasions on different days, but details such as a precise measurement schedule, the model used to estimate variability, and criteria for acceptable repeatability are not reported in the registry record. Most importantly, no reliable endpoint data or CV estimates are reported.
Why do repeated measurements need an analysis plan?
In general, repeated readings from the same person are related rather than independent. Treating them as unrelated observations can misrepresent the amount of information in the data. A repeatability analysis may distinguish variation within a participant across occasions from variation between participants. Which method is appropriate depends on the data structure and the estimand. The registry record does not report the planned statistical method, the handling of multiple tissues, or any model used for the primary endpoint.
The primary outcome names three tissue types. In general, reporting separate estimates for each tissue can make the findings easier to interpret, while combining measures requires a clear definition of the combined target. The record does not state whether a single summary across tissues was intended, how tissue-specific estimates would be compared, or whether one tissue was designated as more important. The result description says reliable data for the named flow measures were not collected, so none of these analytic choices can be evaluated from reported results.
How should group labels be interpreted?
The registry describes lean healthy and obese healthy groups using BMI ranges. Since allocation was non-randomized, any difference between these groups could reflect group composition or other differences, not necessarily an effect attributable to the contrast agent or imaging procedure. In this study, the stated primary question is within-subject repeatability, not a causal comparison between BMI groups. No group comparison estimate is reported.
Masking is listed as none. In general, lack of masking can matter when an outcome depends on judgment or decisions during measurement. The record does not report whether image acquisition, image processing or measurement extraction were performed with safeguards against observer influence. It would be inappropriate to infer that such procedures were used or omitted beyond the registry’s masking entry.
What can planning calculations tell readers?
In general, a sample-size calculation depends on an assumed effect, a variability model, a significance level, a desired power and the planned allocation. The registry’s planning description says its illustration uses a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of an observed effect. Such an illustration is not the study’s own design justification and is not observed power. Participants-per-arm figures are planning quantities, not counts observed in a trial.
For a repeatability study, a planning illustration based on an observed effect is not a substitute for a reported repeatability estimate and its uncertainty. The registry does not report its own sample-size justification or statistical plan. Given that reliable primary-outcome data were not collected, a planning calculation cannot establish the precision achieved in this study.
What does over-dispersion mean in general?
For outcomes analyzed with a count model, over-dispersion means that observed variability exceeds what a simpler model assumes. In general, ignoring it can make uncertainty appear smaller than it should. The registered primary endpoint is a CV for continuous flow measurements, and no count-model analysis is reported, so over-dispersion is not a reported issue in this record. It is a general statistical concept, not an explanation of the study’s missing endpoint data.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures: the primary repeated-measure variability outcome and a secondary outcome of microvascular flow in periadventitial, subcutaneous and skeletal-muscle tissues. The primary outcome itself covers three tissue types. When multiple outcomes or tissue-specific tests are analyzed, the chance of at least one apparently unusual result can increase. In general, a statistical plan can address multiplicity by identifying a primary comparison, adjusting inference, or treating secondary analyses as exploratory.
The registry record does not report whether a multiplicity adjustment was planned, whether tissue-specific analyses were prespecified, or how the primary and secondary outcomes would be related in the analysis. It also lists no analyses. Because reliable primary-outcome data were not collected, the record does not present multiple endpoint estimates or tests whose multiplicity can be assessed.
Missing-data details are limited. The primary outcome statement says reliable data for periadventitial microvascular flow, subcutaneous microvascular flow and skeletal-muscle flow were not collected for the outcome measure. The reason, extent and pattern of unavailable or unreliable measurements are not reported in the registry record. It does not say whether measurements were absent, technically unusable, or excluded for another reason; those possibilities should not be assumed.
The record does not specify an analysis population, such as all enrolled participants or participants with evaluable repeated measurements. It also does not state how incomplete repeated measurements would have been handled. The enrollment count is not a substitute for an endpoint-specific denominator. As a result, readers cannot determine the number of participants or measurements contributing to any primary analysis.
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 |
|---|---|---|---|
| Lean Healthy Subjects | 0 | 6 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Lean Healthy Subjects | 0 of 6 |
| Obese Healthy Subjects | 0 of 0 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lean Healthy Subjects | 0 of 6 |
| Obese Healthy Subjects | 0 of 0 |
The adverse-event record lists 6 lean healthy subjects at risk and 0 with a serious adverse event; it lists 6 lean subjects at risk and 0 with other adverse events. For the obese healthy group, the record lists 0 at risk and 0 affected for both serious and other adverse events. Deaths are listed as 0 in both groups. No top serious adverse-event terms are listed.
These figures describe what the registry reports, not a comparative safety estimate. In particular, the obese group has no participants listed at risk, so its zero affected count is not evidence about event frequency in an exposed obese group. The record does not report whether events were judged related to the intervention, the duration of safety follow-up, or additional detail about event ascertainment. The listed counts do not establish that no unrecorded events occurred.
In general, zero events among a limited number of participants does not prove that an event cannot occur; it only indicates that none are recorded among the listed participants at risk. These safety entries should also be kept separate from the repeatability endpoint: they do not supply information about measurement reliability.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the MARS Study was intended to assess repeatability of CEU measurements of microvascular flow in several tissue types. It describes imaging on two different days and names a CV-based primary endpoint with a timeframe of up to 30 days. It also identifies a perflutren lipid microsphere injectable suspension as the intervention and describes lean and obese healthy participant groups.
It does not establish how reproducible the measurements were. The primary outcome statement says reliable data were not collected, and no CV estimate, uncertainty interval or analysis result is reported. The appropriate interpretation is not that repeatability was good or poor, but that the registry record does not provide the data needed to assess it.
The record also does not support a treatment-effect conclusion. The design was non-randomized, unmasked and not a like-for-like control comparison. Its stated purpose is methodological repeatability, rather than a randomized comparison of clinical benefit. The record does not report an outcome demonstrating a clinical effect, and no medical conclusion should be drawn from the absence of usable measurement results.
Enrollment of 6 is a study-level count, not an endpoint-specific sample size. The adverse-event record identifies 6 lean participants at risk and none in the obese group, but those safety denominators do not show how many participants had usable repeated flow measurements. The reason the study was terminated and the reason for missing reliable endpoint data are not reported in the registry record.
In general, measurement studies can inform whether an imaging measure is sufficiently consistent for later research, but this record does not provide the estimates needed to make that judgment. It documents the study’s question and selected design details, while leaving its central quantitative result unresolved.
13. Why This Trial Matters Statistically
Repeatability is an important statistical property because a measurement that varies substantially across repeated assessments can make it harder to distinguish genuine differences from measurement noise. In general, evaluating repeatability can help researchers understand whether an imaging measure is suitable for use in subsequent research. The MARS Study’s registered objective directly addresses this measurement question for CEU estimates of microvascular flow in periadventitial, subcutaneous and skeletal-muscle tissues.
The record is also a useful example of why a study objective and a study result must be distinguished. A registry can describe a planned repeated-measure procedure and a primary endpoint, while the results record may not contain usable data for that endpoint. Here, the endpoint statement says reliable data were not collected. Without reported estimates, readers cannot judge the size or precision of the measurement variability.
Its design details matter to interpretation. The study was non-randomized and unmasked, and its groups are explicitly not a like-for-like control comparison. That means the group labels should not be mistaken for randomized arms or for a basis to infer causal effects. The main statistical question is repeatability within subjects, not a randomized difference between lean and obese groups.
The record also illustrates why denominators need context. Enrollment was 6, while the safety record lists 6 lean participants and 0 obese participants at risk. Neither the total enrollment nor the safety counts establish how many participants contributed reliable repeated measurements. Reporting endpoint-specific participation and reasons for unusable data would be necessary to understand the evidence base for a repeatability estimate.
Statistically, the record is informative about the intended measurement target but not its performance. That distinction prevents a study’s rationale from being mistaken for a demonstrated result.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpretation is that reliable data for the primary flow outcomes were not collected, according to the registered outcome population statement. The record consequently contains no reported CV estimates or uncertainty measures for the repeated measurements. The central repeatability question remains unanswered in the posted results.
The registry record does not explain why reliable data were unavailable, how many measurements were attempted, how many were unusable, or whether the limitation affected all named tissue types. It does not report endpoint-specific participant counts, the number of completed measurement occasions, or how incomplete records would have been handled. The reasons for termination are also not reported in the registry record.
Methodological detail is sparse. The record does not report the statistical analysis plan, the method for estimating CVs, a threshold for acceptable repeatability, a sample-size justification, or an approach to multiplicity across tissue types and outcomes. Masking is listed as none, but additional procedures for image acquisition or measurement assessment are not described. These omissions prevent evaluation of how the planned endpoint would have been estimated and interpreted.
The study was non-randomized, so the lean and obese groups are not comparable randomized arms. The record itself warns against treating them as a like-for-like control comparison. The adverse-event record lists no obese participants at risk, which further limits any interpretation of safety counts for that group. Enrollment of 6 is small in absolute terms, but the registry entries do not permit a calculation of precision or power for the intended endpoint; neither should be inferred from enrollment alone.
The record is listed as terminated, but provides no reason. Without reliable outcome data, analysis details or an explanation of termination, readers cannot distinguish among possible causes of the missing endpoint results. No such cause should be inferred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Microvascular Flow Assessment Repeatability Study: The MARS Study — NCT01242020.
- Registry record last updated 2017-08-11; status last verified 2017-08.
- Results first posted 2017-08-10.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT01242020, the MARS Study, was a non-randomized, unmasked repeatability study sponsored by the University of Pennsylvania, with enrollment of 6. It evaluated contrast-enhanced ultrasound as a method for imaging microvascular flow in periadventitial, subcutaneous and skeletal-muscle tissues. The listed intervention was perflutren lipid microsphere injectable suspension.
The primary endpoint was within-subject variability of repeated flow measurements, expressed as a coefficient of variation, over a timeframe of up to 30 days. The study summary describes imaging on two different days. Reliable data for the primary outcome were not collected, and no analyses are listed. The study is recorded as terminated; the reason is not reported in the registry record.
The adverse-event record lists 6 lean participants at risk and 0 obese participants at risk, with no serious events, other events or deaths recorded in either group. The record does not establish measurement repeatability or a causal difference between groups.