Pilot Study Evaluating the Efficacy of a Topical PDE4 Inhibitor for Morphea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study Evaluating the Efficacy of a Topical PDE4 Inhibitor for Morphea (NCT03351114), a na phase 2 study. The primary outcome is Number of Participants Who Had a Reduction in Dermal Thickness of Sentinel Plaque.

2. Clinical Question

In practical terms, the study asks whether participants receiving the ointment showed a change in a selected affected plaque over the study period, alongside other measures of disease and patient-reported impact. Because the design has one group, any observed change would describe change over time among participants receiving the intervention; it would not, by itself, distinguish an intervention effect from change that might have occurred for other reasons. The registry record does not report the primary outcome result, so the stated question cannot be answered from the posted registry information.

3. Trial Design

This completed Phase 2 study is described as a pilot evaluation of crisaborole 2% ointment for morphea. Duke University is listed as the sponsor. The study began on 2018-09-01, and primary completion is recorded as 2020-03-10. Enrollment is listed as 8.

The design is single group, with allocation recorded as NA and masking recorded as none. Participants received crisaborole 2% ointment applied to affected skin twice per day. There is no listed randomized or concurrent control arm. The record therefore describes a treatment group followed over time, not a between-group experiment in which outcomes can be compared across assigned treatments.

The primary outcome concerns participants whose sentinel plaque had a reduction in dermal thickness, with assessment at baseline and 12 weeks. Its description refers to a 4 mm skin punch biopsy at each time point on the same affected plaque. Four secondary outcomes are listed: percentage reduction in DIET Score of the sentinel plaque, percentage reduction in LoSCAT Score, percentage reduction in Skindex-29 Score, and change in dermal thickness of the sentinel plaque by ultrasonography. The record lists 5 outcome measures overall.

Although the study status is completed, completion does not establish that results were posted. The registry record lists 0 analyses and does not report primary or secondary outcome estimates. It also does not report participant flow, how many completed each assessment, or the analysis population. These omissions limit what can be concluded about the experience of participants after enrollment and about the outcomes the pilot set out to evaluate.

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

Reasons for not completing this period:

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 Number of Participants Who Had a Reduction in Dermal Thickness of Sentinel Plaque, measured over Baseline, 12 weeks.

The primary endpoint is titled as the number of participants who had a reduction in dermal thickness of a sentinel plaque. A sentinel plaque is selected at baseline, and the description specifies assessment at baseline and 12 weeks using a 4 mm skin punch biopsy on the same affected plaque. The endpoint is therefore framed as a participant count reflecting change in a selected lesion over time, rather than as a comparison between treatment groups.

Dermal thickness is a measure of the affected skin feature targeted by this outcome. Using the same plaque at both assessments is intended to make the before-and-after measurement refer to the same site. However, the registry record does not explain how biopsy findings were converted into a determination of reduction, what size of change counted, or how the participant-level count was derived. The title and description also use different levels of detail: the title specifies a count of participants with reduction, while the description refers to change in dermal thickness on biopsy.

The registry record does not report the number of participants meeting the endpoint, the magnitude or distribution of the measured changes, or uncertainty around the result. Thus, the endpoint's planned measurement is described, but its observed outcome and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpretation depends on separating the study design, the outcome definition, the analysis, and the evidence actually reported. The registry record gives design and endpoint descriptions, but does not report estimates or analyses. General statistical concepts can clarify what those missing results would ordinarily contribute, without implying that the trial used a particular method.

What does a single-group design estimate?

In a single-group study, participants receive the intervention and outcomes can be assessed over time. If measurements at baseline and follow-up were reported, their difference would describe within-participant or within-group change, depending on the analysis. Such a change is not automatically the causal effect of treatment. A concurrent comparison group can help account for changes that would occur over time regardless of treatment; this study has no listed comparison group. Consequently, any change in the treated group alone would not isolate the treatment effect from natural history, measurement variation, or other influences.

What is a participant-count endpoint?

The primary outcome is framed as the number of participants with a reduction in dermal thickness of a sentinel plaque. This is a binary outcome at the participant level: a participant either meets the endpoint definition or does not. A count can communicate how many participants experienced the defined event, but its meaning depends on a clear rule for classifying a reduction. The registry description identifies baseline and 12-week biopsy assessments but does not report a threshold or classification rule. It also does not report the observed count, so the endpoint cannot be interpreted quantitatively from the registry record.

For binary outcomes, a proportion is often used to describe the event frequency, and an interval estimate can express uncertainty. Those quantities require reported outcome data and a defined denominator. The record does not report the outcome count or the number assessed at the endpoint, so an event frequency and its uncertainty are not available. No such quantity should be inferred from enrollment alone.

Why does a confidence interval matter?

In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method used. A narrow interval indicates greater precision than a wide interval, while either interval must be interpreted in light of the study design and its assumptions. For a single-group pilot, an interval around a change estimate would describe precision about that group’s observed change; it would not resolve the absence of a control group. The registry record does not report an estimate or interval for the primary endpoint.

A p-value is also not a measure of effect size or clinical importance. It relates the observed data to a specified null hypothesis under a statistical model. It does not establish causality, and it does not describe the range of plausible effect sizes as directly as an interval estimate. No p-value or inferential analysis is reported in the registry record.

What does the analysis plan tell the reader?

A statistical analysis plan ordinarily specifies how outcomes will be summarized and compared, how the analysis population will be defined, and how missing observations and multiple outcomes will be handled. The registry record does not report those details. The listed value of 0 analyses means that the record does not include outcome analyses; it should not be interpreted as evidence that the study had no protocol or that no analysis occurred outside the registry. A specific model, hypothesis test, covariate adjustment, or handling rule cannot be attributed to the study from the information recorded.

The registry also includes planning illustrations based on an observed effect and a hypothetical two-arm framework. Those are planning calculations, not a description of this trial’s single-group design, and they are not observed power. No outcome estimate is reported in the registry record from which the observed effect could be evaluated. Accordingly, planning figures should not be treated as a trial result or as evidence that the design had a particular probability of detecting an effect.

How should dispersion and model assumptions be considered?

General statistical methods rely on assumptions about the data and their variability. For count data, over-dispersion means that observed variability is greater than expected under a simpler model, which can make standard errors too small if the model fails to account for it. The primary outcome is described as a participant count with an event, but the record does not report an analysis model or a dispersion estimate. There is no basis to say that over-dispersion was present or that a particular adjustment was used.

Because the endpoint is binary at the participant level, a method for a continuous measurement should not be assumed merely because the underlying feature is dermal thickness. The registry description does not specify whether the analysis used the raw biopsy measurement, a thresholded participant-level outcome, or both. It does not report the statistical treatment of repeated assessments or the source of the final classification. These are meaningful distinctions for interpreting the estimand and uncertainty.

In short, general methods explain what would be needed to evaluate an estimate: an operational endpoint definition, the number assessed, a suitable analysis, and a measure of uncertainty. The registry record does not report those outcome-analysis details, so no inferential result can be reconstructed from the design description alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Crisaborole 2% Ointment")
n      <- c(7)
events <- c(5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Crisaborole 2% Ointment  7  5  71.4  29.0  96.3  35.9  91.8  34.9  91.5

11. Multiplicity, Missing Data and Analysis Populations

The study lists a primary outcome and 4 secondary outcomes. The secondary outcomes concern DIET Score, LoSCAT Score, Skindex-29 Score, and dermal thickness measured by ultrasonography. When a study assesses multiple outcomes, the chance of at least one apparently unusual result can increase if each outcome is tested separately without an appropriate strategy. General approaches include identifying a primary endpoint in advance, adjusting inference across selected comparisons, or treating secondary findings as exploratory. The registry record does not report a multiplicity strategy, so it is not possible to determine how the family of outcomes was handled.

The record gives a primary outcome timeframe of baseline and 12 weeks, but does not report outcome results or analyses for that endpoint or the secondary outcomes. It also does not describe how missing outcome measurements were addressed, whether any participants discontinued, or how many participants contributed data to each assessment. Those details are important because missingness can affect both the interpretation and the precision of an estimate, particularly if the participants with observed data differ from those without it.

The analysis population is not described in the registry record. It does not state whether analyses were planned for all enrolled participants, only those who completed treatment, or another defined group. Nor does it report whether analyses were adjusted or whether any sensitivity analyses were conducted. These matters are not interchangeable: the target population, missing-data assumptions, and multiplicity approach each shape what an estimate and its uncertainty mean. The listed 0 analyses indicates that outcome analyses are not included in the registry record; it does not resolve what analysis may have been conducted elsewhere.

12. 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.

For the Crisaborole 2% Ointment group, the registry lists 0 serious adverse events, 0 other adverse events, and 0 deaths. It lists 8 participants at risk for each of the serious-event and other-event summaries. These entries describe the event counts posted in the registry record; they do not provide event-specific follow-up time, severity detail beyond the serious-event category, or a narrative assessment of causality.

A count of 0 means that no events are recorded in that category for this group in the posted data. It does not prove that the intervention has no risk, nor does it rule out events that were not captured, not reported, or too uncommon to appear in a small pilot. The record does not report a broader safety analysis or information about monitoring and ascertainment. The event counts should therefore be read as a limited descriptive record, not as a comprehensive estimate of safety.

The registry record does not report efficacy outcomes, and the safety counts cannot fill that gap. They also should not be compared with another group, because no control group is listed. Interpreting safety comparatively would require an appropriate comparison and sufficiently detailed reporting.

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

The registry record establishes that a completed Phase 2 pilot study evaluated crisaborole 2% ointment applied to affected skin twice per day in participants with morphea. It describes a single-group design and identifies dermal thickness of a sentinel plaque as the primary outcome, assessed at baseline and 12 weeks. It also lists four secondary outcomes and posts adverse-event counts for the treatment group.

What the record does not establish is the observed primary outcome result. It does not report how many participants had a reduction, the size of any change, or uncertainty around the result. It likewise does not report the secondary outcome findings. As a result, the registry information cannot quantify clinical change or show how consistent the observed responses were. A completed status does not substitute for posted outcome data.

Even if before-and-after results were available, this design would describe change in a treated group rather than a treatment-versus-control effect. In general, within-group change can reflect several influences, including the intervention, natural variation over time, and measurement variability. Without a control group, those contributions cannot be separated by a randomized comparison. This is a limitation of the design for causal interpretation, not a statement that the intervention did or did not cause change.

The listed serious adverse event counts are descriptive and should not be read as proof of absence of risk. The record does not provide the outcome and safety detail needed for broad conclusions about efficacy or safety. The most defensible reading is that the registry documents the pilot’s intended questions and basic design, while leaving its clinical outcome results unreported.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a study being completed and its results being available in a registry record. The design, intended endpoints, and event counts are documented, but the primary and secondary outcome estimates are not. Without those estimates, there is no basis for evaluating the observed amount of change or its precision.

The single-group format also makes the estimand important. A change from baseline within treated participants is a different quantity from a difference between treatment groups. The former describes what happened over time in the group; the latter can support a comparative treatment-effect interpretation when the design and analysis are appropriate. Because no comparator is listed, those questions should not be conflated.

The endpoint description highlights another statistical principle: outcomes need operational definitions. A title that refers to participants with a reduction indicates a participant-level classification, while the description identifies biopsy assessments of dermal thickness. The record does not define the threshold or the derivation of that classification. Clear definitions matter because the event count, its denominator, and any uncertainty estimate depend on how the endpoint is constructed.

Finally, the study illustrates why outcome reporting, analysis populations, missing-data handling, and multiplicity plans matter. These details help readers understand which data support an estimate and how robust its interpretation may be. Their absence from the registry record does not establish what occurred in the study conduct, but it limits what can be assessed from the posted information. The statistical value of the record is therefore primarily in its description of the planned clinical question and in making the limits of available evidence explicit.

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 principal limitation for interpretation is that the registry record does not report primary or secondary outcome results, despite listing the study as completed. The primary endpoint description also leaves the operational rule for classifying a participant as having a reduction unspecified. Without that rule and the observed counts or measurements, the outcome cannot be independently interpreted or its precision assessed.

The single-group, unmasked design has no listed control arm and does not provide a randomized comparison. Any change over time, if reported elsewhere, could not be attributed to the ointment by comparison with a concurrent untreated or differently treated group. Lack of masking can also matter for assessments that involve judgment, although the registry record does not describe assessor procedures or say whether outcome assessment was masked.

The listed enrollment is 8, but the record does not report how many participants completed follow-up or contributed data to each outcome. It does not describe missing observations, participant discontinuations, the analysis population, or any method for addressing missing data. It also does not report a sample-size justification, analysis plan, multiplicity approach, or outcome uncertainty estimates. These omissions limit assessment of precision, potential bias, and the reliability of any unreported analysis.

The registry lists adverse-event counts but does not provide a detailed safety account or a comparator. Those counts cannot support a comparative safety assessment, and they do not establish absence of risk. Together, these trial-specific limitations mean the record is useful for understanding the study’s design and intended measurement, but insufficient for a quantitative assessment of its clinical outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study Evaluating the Efficacy of a Topical PDE4 Inhibitor for Morphea — NCT03351114.
• Registry record last updated 2021-04-01; status last verified 2021-03.
• Results first posted 2021-04-01.
• 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 Phase 2, single-group pilot study sponsored by Duke University, evaluating crisaborole 2% ointment for morphea. The ointment was applied to affected skin twice per day, and enrollment is listed as 8. Masking is recorded as none, and no comparator group is listed.

The primary outcome is the number of participants with a reduction in dermal thickness of a sentinel plaque, assessed from baseline to 12 weeks. Four secondary outcomes are listed, covering DIET Score, LoSCAT Score, Skindex-29 Score, and ultrasonographic dermal thickness. The record lists 5 outcome measures and 0 analyses.

For the treatment group, the registry lists 0 serious adverse events, 0 other adverse events, and 0 deaths. Primary and secondary outcome results, analysis details, and outcome uncertainty are not reported in the registry record. The study’s design and intended assessments are documented, but its clinical results cannot be evaluated from the posted registry information.