A Study to Evaluate the Efficacy of an Oral Medication in the Treatment and Prevention of Digital Ulcers in Patients With Systemic Sclerosis (Scleroderma).: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy of an Oral Medication in the Treatment and Prevention of Digital Ulcers in Patients With Systemic Sclerosis (Scleroderma). (NCT00725361), a na na study. The primary outcome is New Digital Ulcers (DU) 4 Weeks Prior to Week 24.

2. Clinical Question

3. Trial Design

This completed pilot study evaluated ambrisentan in patients with systemic sclerosis and digital ulcers. The registry record lists Stanford University as the sponsor, an enrollment of 20, a study start of 2008-06, and primary completion in 2010-12. The phase is listed as NA. The record identifies ambrisentan as the drug intervention and describes a single active group.

The model is single-group, allocation is listed as NA, and masking is listed as NONE. No control group is recorded. These features matter when interpreting outcomes: observations in the active group can describe what was recorded during the study, but do not by themselves estimate how the same participants would have fared under a different treatment or without ambrisentan. The study is not a randomized comparison, and its arms should not be treated as like-for-like controls.

The primary outcome is the number of new digital ulcers during the 4 weeks before week 24, assessed at week 24 from baseline. The registry also names outcomes concerning new ulcers in the 4 weeks before week 12, healing of baseline ulcers at week 12, and change in the Scleroderma Health Assessment Questionnaire at week 24 compared with baseline. Those outcomes provide additional questions about ulcer occurrence, healing, and reported health status, but their results are not reported in the registry record.

The record does not report the dosing regimen, treatment adherence, participant flow, or detailed eligibility criteria. It also does not describe a protocol rationale for the enrollment or an analysis plan. Completion status indicates the study is recorded as completed; it does not supply the missing endpoint 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 New Digital Ulcers (DU) 4 Weeks Prior to Week 24, measured over 4 weeks prior to week 24.

The primary endpoint measures the number of new digital ulcers that developed during the 4 weeks before week 24, with assessment at week 24 from baseline. It focuses on recent ulcer occurrence at a specified point in follow-up rather than on all ulcers over the full study period. Digital ulcer occurrence is relevant to the stated study aim of evaluating treatment and prevention, while the fixed assessment window defines which events the endpoint counts.

The registry classifies the outcome as continuous and specifies a mean with standard deviation. In general, a mean describes the average outcome in a group, and the standard deviation describes how much individual observations vary around that average. Because the outcome is a number of ulcers, the underlying observations are counts, even though the registry labels the measure continuous. The summary choice should be kept in mind when interpreting any reported estimate, particularly if observations are unevenly distributed or include many low values.

The endpoint description does not state how ulcers were identified or adjudicated, or how missing assessments were handled. Most importantly, the registry record does not report the observed mean, standard deviation, or another numerical primary result. The endpoint definition therefore explains what the study intended to measure, but it does not show what was observed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean with standard deviation describe?

For the primary outcome, the registry specifies a mean and standard deviation. In general, the mean is the arithmetic average of participants’ outcome values. The standard deviation describes the spread of those individual values around the mean. It is not the same as a standard error, which describes the sampling uncertainty of an estimate, and neither quantity is itself a confidence interval. A mean gives a compact description of the group, while the standard deviation helps show whether outcomes are clustered or dispersed.

The outcome is a count of new digital ulcers, although the registry categorizes it as continuous. Count outcomes are nonnegative and take discrete values. A mean can still summarize a count outcome, but its interpretation depends on the distribution of observations. If many participants have low counts and a small number have much higher counts, the mean and standard deviation may not convey the full pattern. A distribution-sensitive analysis can sometimes be useful in such settings, but the registry record does not report a specific statistical model or diagnostic assessment.

Why does the single-group design matter?

With a single group, the primary outcome can describe ulcer occurrence among participants receiving ambrisentan, if the result is reported. It cannot by itself estimate a treatment contrast against an untreated or differently treated group. General statistical methods for causal comparison rely on a comparison that helps account for what would have happened without the intervention. Random allocation is one way to support such a comparison; this record lists allocation as NA and provides no control group. Comparisons with a group’s earlier status, if available, would still need to account for time and other changes, and the registry does not report such an analysis for the primary outcome.

There is no reported inferential analysis for the primary outcome. In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A p-value, when used, measures how surprising data would be under a specified null model; it does not measure the probability that a treatment works or the size of a clinical effect. Neither an interval nor a p-value can be interpreted for this endpoint from the registry record because no primary numerical result or corresponding analysis is reported.

What do planning assumptions mean?

Any sample-size calculations associated with this study are planning illustrations, not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. These are assumptions for a hypothetical planning calculation. They do not describe the actual single-group design, and they do not establish that the study was designed with those assumptions.

In general, sample-size planning asks how many participants per arm would be needed to detect a prespecified effect under chosen assumptions. Such a calculation depends on the effect size, variability, test, allocation, and target power. If the assumed effect is derived from an observed estimate, it can be uncertain, especially when that estimate comes from a small or uncontrolled study. Planning figures do not show the probability that the completed study detected an effect, and they should not be read as observed power. The registry record does not report a protocol-based sample-size justification or the actual statistical plan.

The stated planning assumptions describe equal allocation between two arms, whereas this trial is recorded as single-group. That difference makes the distinction between hypothetical planning and the conducted design particularly important. The registry does not report a control arm, a randomized allocation, or an observed primary effect that could ground an interpretation of the planning illustration.

What can be inferred from the posted record?

The study’s status is completed, and the primary outcome is defined, but the primary numerical result is not reported in the registry record. In general, a complete statistical interpretation would consider the estimate, its uncertainty, the number of participants contributing data, the analysis population, and how missing observations were handled. These details help determine the scope and reliability of an estimate. Their absence does not show that no analyses were conducted; it means those details are not reported in the registry record.

For outcomes based on counts, general concerns include variation between participants and possible over-dispersion. Over-dispersion occurs when observed variability exceeds what a chosen statistical model assumes. If present, it can make standard errors too small under an unsuitable model, leading to overly narrow confidence intervals or misleading tests. The registry record does not identify a model or report whether over-dispersion was assessed, so it is not possible to say whether this concern applied in the study.

These general concepts explain how to read a reported result if one is available, but they do not fill in missing study findings. Here, the endpoint’s definition, summary type, and design are recorded, while the primary estimate and analysis details are not. Statistical interpretation must therefore remain limited to the design and reporting information.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Active")
n   <- c(16)
m   <- c(0.06)
sp  <- c(0.68)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Active  16  0.060  0.680  -0.302  0.422

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures. The primary outcome concerns new digital ulcers during the 4 weeks before week 24. Named secondary outcomes concern new ulcers in the 4 weeks before week 12, complete healing of all baseline digital ulcers at week 12, complete healing of > 50% of baseline digital ulcers at week 12, and change in SHAQ at week 24 compared with baseline. Considering multiple outcomes can raise a multiplicity issue: in general, testing many hypotheses can increase the chance of finding an apparently notable result by chance. The registry record does not report whether multiplicity was addressed, which outcomes were formally tested, or whether any analysis hierarchy was prespecified.

The registry reports 0 analyses. This means the record does not contain reported analysis entries; it should not be taken as proof that no analyses were performed outside the registry. No analysis population is described. The record does not state whether analyses included all enrolled participants, only participants who completed follow-up, or another defined group.

Missing-data handling is also not reported in the registry record. It does not say how many participants contributed data to each outcome, whether any week 24 assessments were unavailable, or whether missing observations were imputed or otherwise handled. These details matter because the analysis can be affected when outcome availability is related to participants’ health or response. Without the relevant reporting, neither the extent nor the potential direction of missing-data bias can be assessed.

The registry also does not report a statistical analysis plan or a sample-size justification specific to the trial. As a result, it is unclear from the record which analyses were intended in advance and how the primary and secondary outcomes were to be handled. These reporting gaps limit reproducibility and make it difficult to distinguish planned analyses from later exploratory work.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (5.0%), shortness of breath (5.0%), raynaud attack (5.0%).

For the active group, the registry reports 20 participants at risk for serious adverse events and 3 affected. It also reports 20 at risk for other adverse events and 15 affected. These figures describe recorded events in the group; they do not, on their own, establish that ambrisentan caused an event. The record does not provide a control group for comparison, and the meaning of the other-event category is not further explained in the available information.

The listed serious adverse event terms are acute myocardial infarction, shortness of breath, and Raynaud attack, each reported as 5.0%. These percentages should be read as the registry’s reported values, not converted into counts or interpreted as estimates of treatment-related risk. The record does not report details such as timing, severity beyond the serious classification, recurrence, or attribution to the study drug.

Deaths are not reported in the registry record. The serious-event and other-event figures are separate safety summaries and should not be added together or treated as a measure of efficacy. They also do not provide a complete account of safety without details on event definitions, follow-up, and how events were collected. A small single-group record cannot establish whether an event rate differs from what would occur under another treatment or without the intervention.

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

The registry record establishes that a completed pilot study evaluated ambrisentan in patients with systemic sclerosis and digital ulcers. It identifies a primary outcome focused on new digital ulcers in the 4 weeks before week 24, and it describes additional outcomes related to ulcer occurrence, healing, and SHAQ. The record also gives the study model, masking status, enrollment, sponsor, and selected adverse event information. These details help readers understand what was studied and what questions the investigators intended to examine.

The record does not report the primary outcome result or the results of the named secondary outcomes. Therefore, it cannot show how many new ulcers were observed on average, how variable participant outcomes were, or whether ulcer occurrence changed over time. It cannot support a claim that ambrisentan did or did not affect ulcer outcomes. No effect estimate or measure of precision is reported for the primary endpoint.

The design also sets boundaries on interpretation. A single-group study without a control group can describe outcomes among participants receiving the intervention, but cannot provide a randomized comparison. Even if outcomes had been reported, a change from baseline would not by itself show that the intervention caused the change. Other explanations could not be separated from a treatment effect using a controlled comparison that the registry does not record.

The safety figures indicate that serious and other adverse events were recorded, but they do not determine causality or comparative risk. The registry does not report the details needed to assess attribution or compare event rates with a control group. Overall, the record documents the study’s purpose and selected design and safety details, but the missing efficacy results and analysis details prevent an assessment of treatment effect, its precision, or its clinical importance.

14. Why This Trial Matters Statistically

This study matters statistically because it illustrates the difference between a clearly defined research question and a reported result. The primary endpoint is specific about the outcome, assessment time, and reference period: new digital ulcers in the 4 weeks before week 24, assessed at week 24 from baseline. That definition lets readers identify the intended measure. But without the observed value and its variability, the endpoint cannot answer the clinical question on its own.

The single-group design also makes the distinction between description and comparison central. A mean for participants receiving ambrisentan, if reported, would describe that group. It would not provide a controlled estimate of what the outcome would have been under an alternative. Statistical significance cannot repair the absence of a comparator or remove the limitations of an uncontrolled design. Appropriate interpretation depends on both the analysis and the design that generated the data.

The primary outcome is a count summarized as a mean and standard deviation. This combination provides a familiar summary, while also raising general questions about the distribution and variability of counts. A reader would need the actual observations or further statistical detail to judge whether the summary adequately represents the data. The registry record does not report those details or a specific model.

The record also demonstrates why outcome multiplicity, missing data, analysis populations, and prespecified methods matter. Multiple named outcomes may raise questions about which findings were primary and how uncertainty was handled. Missing information about who contributed data and how unavailable observations were treated makes the reported evidence harder to evaluate. Here, those analysis details and the outcome results are not reported in the registry record, so the study’s statistical contribution is chiefly its documented design and endpoint definitions rather than an interpretable efficacy estimate.

15. Limitations

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

The most direct limitation for interpreting efficacy is that the registry record does not report the primary outcome result. It also does not report results for the named secondary outcomes. Without endpoint estimates, measures of variability, or uncertainty intervals, readers cannot assess the size or precision of any observed outcome. The study’s completed status does not substitute for results reporting.

The design is single-group, with allocation listed as NA and masking listed as NONE. No control group is recorded, and the registry cautions that the study is not a randomized comparison. Accordingly, the record cannot support a like-for-like treatment comparison. The active group’s outcomes, even if numerical values were available, could not by themselves separate an intervention effect from other explanations for change over time.

The registry provides limited information about conduct and analysis. Eligibility details, dosing regimen, participant flow, outcome-assessment procedures, analysis populations, and missing-data methods are not reported in the registry record. It also does not report a protocol-based sample-size justification, a statistical analysis plan, or whether multiplicity was addressed. These omissions make it difficult to assess how outcomes were defined and analyzed in practice.

The listed adverse event information is also limited. Event attribution, timing, and further clinical detail are not reported, and the single-group design offers no concurrent comparison for safety. The death information is not reported in the registry record. These limitations are specific to the information available for this study and should be kept distinct from conclusions about the underlying clinical question.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy of an Oral Medication in the Treatment and Prevention of Digital Ulcers in Patients With Systemic Sclerosis (Scleroderma). — NCT00725361.
• Registry record last updated 2017-03-31; status last verified 2017-03.
• Results first posted 2017-02-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed pilot study of ambrisentan for treatment and prevention of digital ulcers in patients with systemic sclerosis. Stanford University is listed as sponsor, enrollment is 20, the model is single-group, allocation is NA, and masking is NONE. The primary outcome is the number of new digital ulcers in the 4 weeks before week 24, assessed at week 24 from baseline.

The record names secondary outcomes concerning new ulcers before week 12, healing of baseline ulcers at week 12, and change in SHAQ at week 24 compared with baseline. It reports selected serious and other adverse event figures for the active group. The primary and secondary outcome results, analysis population, missing-data methods, and statistical analysis plan are not reported in the registry record. The design and endpoint definitions can be described, but the record does not provide an efficacy estimate or a controlled comparison.