Scleroderma ARFI Imaging of the Skin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Scleroderma ARFI Imaging of the Skin (NCT02006420), a registered phase not stated study. The primary outcome is Mean Skin Stiffness.

2. Clinical Question

3. Trial Design

This is a completed, cross-sectional study with a single visit lasting less than one hour, according to the primary-outcome timeframe. The registry lists enrollment of 45 and a study start of 2013-12, with primary completion in 2015-12. The sponsor is the University of Michigan. The listed intervention is ARFI-SVI ultrasound, a device-based imaging procedure.

The procedure description specifies ultrasound imaging of the forearm and thigh. Both the Scleroderma and healthy-volunteer control arm descriptions refer to this imaging, lasting approximately 5-10 minutes. The record therefore describes measurement in two groups rather than a treatment assignment intended to compare clinical care. It explicitly states that the study was not randomized, that allocation was not stated, and that the arms are not a like-for-like control comparison. Further details about how participants entered the groups are not reported in the registry record.

The primary outcome is mean skin stiffness, expressed as shear wave velocity in meters per second. The listed secondary outcomes concern durometer scoring, landmark scores, and MRSS scores for scleroderma participants, along with linear relationships between ultrasound stiffness and these measures. The record lists 7 outcome measures and 10 analyses. It does not report the detailed analysis plan, including how each measure was summarized or how each analysis was selected.

The registry status is COMPLETED, but completion status alone does not provide evidence about the direction or size of an outcome. Numerical primary and secondary results are not reported in the registry record. The study design and aims can therefore be described, but its outcome findings cannot be assessed from the record’s reported results.

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

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 Mean Skin Stiffness, measured over Cross-sectional study, 1 visit, <1 hr.

The primary endpoint is mean skin stiffness measured using ultrasound shear wave velocity imaging. The outcome description says measurements were taken from the forearm and thigh of patients with scleroderma. Shear wave velocity is expressed in meters per second. The registry identifies the summary measure as a mean and the associated measure of dispersion as a standard deviation.

In general, shear wave velocity imaging estimates a property related to tissue stiffness by measuring how a mechanically induced wave travels through tissue. The study summary presents this approach as a way to assess skin hardness without relying only on physical examination or a skin biopsy. That is the rationale stated for investigating the technique; the registry record does not establish that it replaces either assessment.

A mean describes the average measured value for the observations included in an analysis. A standard deviation describes how dispersed individual measurements are around that average. Reporting both can help readers understand the typical measured value and the variability in the group. Neither measure, on its own, establishes whether ultrasound can distinguish groups reliably or whether it can quantify fibrosis accurately.

The registry record does not report the numerical mean or standard deviation for the primary outcome, a between-group estimate, or a confidence interval. Consequently, the endpoint’s measurement scale and intended use are clear, but the size and precision of the observed findings are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure, summarized as a mean with a standard deviation. In general, a continuous outcome can take values across a measurement scale rather than being limited to categories such as event or no event. Here, the measurement scale is shear wave velocity in meters per second. The mean conveys the average measurement in an analyzed group; the standard deviation conveys how much the measurements vary around that average.

What does a confidence interval describe?

In general, a confidence interval expresses uncertainty around an estimate. A narrow interval indicates greater precision than a wide interval, though precision is not the same as freedom from bias. For this study, the registry record does not report a confidence interval for mean skin stiffness or for a comparison between groups. Without an estimate and its interval, readers cannot evaluate the precision of the primary result from the registry record.

What would a group comparison mean?

In general, comparing group means can describe how an average measurement differs across groups. Such a contrast does not by itself show that group membership caused the difference. This distinction matters particularly when groups are not randomized or not otherwise shown to be comparable. The record explicitly says the study was not randomized, allocation was not stated, and the arms are not a like-for-like control comparison. It does not report a covariate-adjustment plan or details that would establish comparability.

The primary outcome is cross-sectional, with measurement at a single visit. In general, cross-sectional measurements describe observations at a particular assessment rather than change over time. They cannot, without additional design and data, establish how a measurement changes over time or whether a change follows from an intervention. This registry record describes imaging as an assessment, not a randomized treatment comparison.

How should associations with other assessments be read?

The listed secondary outcomes include linear relationships between ultrasound skin stiffness and durometer scoring, landmark scores, and MRSS scores. In general, a linear relationship describes whether values tend to vary together in a pattern that can be represented by a straight-line association. An association does not show that one measure causes another, nor does it automatically demonstrate that two measures can be used interchangeably. The registry record does not report coefficients, uncertainty intervals, plots of these relationships, or numerical secondary results.

Mean and standard deviation are useful summaries, but they do not reveal every feature of a measurement distribution. In general, skewness, outliers, or clustering can affect how well a mean represents typical observations. The registry record does not report distributional checks, transformations, robust methods, or another summary approach. There is consequently no basis in the record for evaluating how the outcome distribution was handled.

What do the sample-size assumptions represent?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. In general, such illustrations show the sample size that would be needed under stated assumptions to detect a target effect. They are planning calculations, not observed power and not evidence that the study was designed with those assumptions. The registry record does not report a sample-size justification from the trial’s own design or the numerical observed effect needed to assess the illustrations. They should not be read as a post hoc demonstration that the study could or could not detect a meaningful effect.

More generally, a statistical significance level sets a rule for how unusual data must be under a specified null model before a result is called statistically significant. It does not measure the size or clinical importance of an effect. A two-sided approach considers departures in either direction. These are general explanations of the planning assumptions, not a description of a fully reported trial analysis plan. The registry record does not report the inferential methods used for the primary outcome.

Why do dispersion and measurement error matter?

In general, variability between people and measurement error can both contribute to spread in observed values. A standard deviation summarizes total observed spread, but does not separate those sources. Repeated measurements, reliability analyses, or other measurement studies may help characterize repeatability, but the registry record does not report such results. The ultrasound procedure is described as imaging the forearm and thigh, but the record does not state how measurements from these sites were combined for the primary mean.

In general, over-dispersion means observed variability is greater than a statistical model assumes. It can make standard errors and confidence intervals too small if the model does not account for it. This concept is relevant when assessing statistical models, but the registry record does not report a model or a variance assessment for the primary endpoint. It would be inappropriate to infer that over-dispersion occurred or that a particular correction was used.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and 10 analyses. The outcomes include mean skin stiffness and secondary measures involving durometer scoring, landmark scores, and MRSS scores for scleroderma participants, as well as linear relationships between ultrasound stiffness and these assessments. The presence of multiple outcomes and analyses raises a general multiplicity question: when many statistical questions are examined, the chance of at least one apparently notable result can increase if no adjustment or interpretation plan is specified.

The registry record does not report a multiplicity strategy, such as a prespecified hierarchy, adjustment procedure, or distinction between confirmatory and exploratory analyses. It also does not report the statistical analysis plan. The listed number of analyses alone does not show whether all were tested, how results were interpreted, or whether any adjustment was used. No conclusion about multiplicity control can be drawn from the record.

Missing-data handling is also not reported in the registry record. The record does not state whether any primary or secondary measurements were missing, how missing observations were handled, or which analysis population was used for each outcome. The enrollment figure does not establish the number of observations included in an outcome analysis. The adverse-event risk counts are presented separately and should not be treated as the analysis population for skin stiffness.

In general, missing observations can affect both the estimate and its precision, particularly when the reasons for missingness are related to participants’ measurements or characteristics. Readers would need information about missingness and analysis populations to judge whether the reported estimates represent the intended groups. Such information is not reported in the registry record, and there are no numerical endpoint results in the record to assess in that context.

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 adverse-event record lists a Scleroderma group with 24 at risk and a Control group with 21 at risk. For each listed group, the counts for serious adverse events, other adverse events, and deaths are 0. No top serious adverse-event terms are listed. These figures describe the registry’s reported safety counts for the groups; they do not provide outcome information about skin stiffness.

A zero count means that no event was recorded in that category for the listed group in the registry record. It does not establish that an event is impossible, or that the procedure has no risk. The record does not report the details needed to assess the period or method of adverse-event surveillance, definitions used, or completeness of event capture. It also does not explain how the at-risk counts relate to the enrollment figure or to the primary-outcome analysis population.

In general, safety counts should be interpreted alongside the period of observation, event definitions, and completeness of follow-up. Those details are not reported in the registry record. The recorded zeros are therefore best read narrowly as the adverse-event counts entered for the listed groups, rather than as a comprehensive estimate of safety.

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

The study addresses a measurement question: whether ultrasound shear wave velocity imaging can characterize skin stiffness in scleroderma and how that measurement relates to other skin assessments. Its primary outcome is mean skin stiffness in meters per second, measured from the forearm and thigh. The registry summary describes a possible role in distinguishing normal skin from skin affected by scleroderma and in quantifying fibrosis, but these statements describe the investigators’ aims and hypothesis.

The registry record does not report numerical primary-outcome results. It therefore does not show the observed mean stiffness in either group, the size or direction of a group contrast, or the precision of an estimate. The listed secondary outcomes also lack reported numerical findings. No conclusion about the strength of relationships with durometer, landmark, or MRSS scores can be drawn from the record.

Even a reported difference between groups would need careful interpretation. The study was not randomized, allocation was not stated, and the registry says the arms are not a like-for-like control comparison. In general, that design can describe observed measurements, but it does not by itself establish that scleroderma caused a difference or that the measurement will perform similarly in other settings.

The record does not report diagnostic accuracy, a cutoff value, sensitivity, specificity, or evidence that the ultrasound measurement can replace a physical examination or skin biopsy. It also does not report evidence that the technique improves clinical decisions or outcomes. The stated possibility of confirming a diagnosis is an aim in the summary, not a result established by the posted data.

The defensible conclusion is about scope: the registry documents a completed cross-sectional assessment of an ultrasound-based skin-stiffness measure and related outcomes. The numerical findings needed to judge its measurement performance are not reported in the registry record. Absence of reported results should not be interpreted as evidence of no difference or no association.

13. Why This Trial Matters Statistically

This study is statistically relevant because it treats skin stiffness as a measurable continuous outcome and examines whether an imaging-derived measure corresponds to other assessments. Establishing how a new measurement behaves is an important statistical task: the average value, variability, precision, and association with relevant measures all bear on whether the measure is informative. The registry identifies these intended questions through its primary and secondary outcomes.

The study also illustrates the distinction between a measurement hypothesis and a demonstrated result. The stated hypothesis is that ARFI/SVI might distinguish normal skin from skin affected by scleroderma. Testing that idea requires reported group measurements and estimates of uncertainty. The registry record gives the outcome definition but not the numerical results needed to evaluate the hypothesis. A clear endpoint and an appealing rationale cannot stand in for the results.

Design affects interpretation as much as analysis. The record says the study was not randomized and that the groups are not a like-for-like control comparison. In general, group differences in such settings may be associated with factors besides the condition under study. Recognizing this constraint helps distinguish descriptive evidence about measured values from causal evidence.

The record’s multiple outcomes also raise questions about how analyses were prioritized and interpreted. With outcomes spanning different assessments and relationships, a statistical plan can help clarify which questions are primary and how exploratory findings should be treated. That plan is not reported in the registry record. The study is thus a useful example of why design, measurement, analysis transparency, and numerical results all matter when evaluating a proposed biomarker.

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.

A central limitation of the registry record is that it does not report numerical results for the primary endpoint or the listed secondary outcomes. There are no reported group means or standard deviations for skin stiffness, no estimate of a group contrast, and no uncertainty interval or p-value. The endpoint is defined, but the size and precision of the findings cannot be evaluated from the record.

The design is cross-sectional and nonrandomized. The registry says allocation was not stated and the arms are not a like-for-like control comparison. It does not report detailed eligibility criteria, participant characteristics, group comparability, or adjusted analyses. These omissions limit assessment of whether any observed difference could be attributed to disease status rather than other group differences. The numerical data required to assess such differences are also not reported.

Further measurement details are not reported in the registry record. The outcome description identifies forearm and thigh measurements but does not say how site-specific observations were combined into the primary mean. It does not report repeatability, measurement error, operator procedures, or distributional diagnostics. The record also does not report the analysis plan, handling of missing data, analysis populations, or multiplicity strategy.

The study summary raises possible diagnostic and fibrosis-assessment uses, but diagnostic accuracy measures, a decision threshold, and validation results are not reported in the registry record. The completed status does not resolve these gaps. Finally, the safety record’s zero event counts lack reported surveillance details, so they cannot be treated as a complete characterization of procedural risk.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Scleroderma ARFI Imaging of the Skin — NCT02006420.
• Registry record last updated 2019-07-05; status last verified 2019-04.
• Results first posted 2019-07-05.
• 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

NCT02006420, titled “Scleroderma ARFI Imaging of the Skin,” is a completed study sponsored by the University of Michigan. The registry lists enrollment of 45, a start date of 2013-12, and primary completion in 2015-12. It describes a cross-sectional, single-visit assessment of skin stiffness using ARFI-SVI ultrasound imaging of the forearm and thigh.

The primary outcome is mean skin stiffness measured as shear wave velocity in meters per second, with standard deviation specified as the dispersion measure. Listed secondary outcomes include durometer, landmark, and MRSS assessments and their relationships with ultrasound stiffness. The study was not randomized, allocation was not stated, and the arms are not a like-for-like control comparison.

Numerical primary and secondary outcome results, the statistical analysis plan, and details on missing data are not reported in the registry record. The adverse-event record lists zero serious events, other events, and deaths in both groups.