Apremilast for Atopic Dermatitis - A Pilot Study in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Apremilast for Atopic Dermatitis - A Pilot Study in Adults (NCT01393158), a non-randomized phase 2 study. The primary outcome is Change in EASI Scores.

2. Clinical Question

The study’s stated purpose was to obtain preliminary data about apremilast safety and tolerability in atopic dermatitis to support the design of larger controlled studies. That purpose is important when interpreting the registry entry: this pilot was not described as a randomized comparison capable of isolating the effect of apremilast from other explanations for a change over time.

The primary question concerns changes in a clinician-assessed composite score, not a direct comparison of the two dose schedules. Because the arms had different scheduled durations and allocation was non-randomized, the Month 3 and Month 6 outcomes arise under different follow-up periods. A difference between arm-level changes, if reported, would therefore not by itself identify a dose effect. The numerical outcome data and detailed analysis are not reported in the registry record.

3. Trial Design

This completed Phase 2 study evaluated oral apremilast in adults with atopic dermatitis. The registry record gives enrollment as 16 and lists Oregon Health and Science University as the sponsor. The recorded start was 2009-05, and primary completion was 2011-07. The study status is completed.

The allocation is recorded as non-randomized, masking as none, and the model as sequential. These features matter for interpretation. Without random allocation, differences among participants assigned to different regimens may reflect how participants entered or proceeded through the study, rather than the dose itself. With no masking, expectations or knowledge of treatment could potentially influence assessments or reporting. The registry record does not describe procedures intended to address these risks.

The arm descriptions specify 20 mg BID orally for 3 months and 30 mg BID orally for 6 months. Thus the scheduled assessment windows differ. The primary endpoint timeframe follows those schedules: baseline to Month 3 for the 20 mg arm and baseline to Month 6 for the 30 mg arm. The registry record does not describe a concurrent control group, and its listed dose arms should not be treated as randomized controls for one another.

The stated purpose was to obtain preliminary safety and tolerability data that could support the design of larger controlled studies. That is a developmental objective, distinct from confirming a treatment effect in a controlled efficacy trial. The record does not report a sample-size justification, the planned statistical analysis, or whether interim analyses were planned. These details should not be inferred from the pilot designation or from the enrollment count.

The registry lists four outcome measures and zero analyses. It names secondary outcomes concerning IGA categories, pruritus on a Visual Analog Scale, and DLQI scores, in addition to the primary endpoint. Numerical findings for the primary endpoint are not reported in the registry record. Consequently, the design features can be described, but the magnitude and precision of the measured outcome changes cannot be evaluated from this record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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 Change in EASI Scores, measured over Mean change in EASI score measured at Baseline and Month 3, (if on 20mg arm) or Baseline and Month 6 (if on 30mg arm).

The primary endpoint is change in EASI score. EASI is a composite measure of physical signs and affected body surface area in atopic dermatitis. The registry description identifies erythema, population, excoriation, and lichenification as the signs contributing to severity, with assessments across the head/neck, trunk, arms, and legs. The score combines severity with the area affected, weighting body regions according to their size. Its stated scale ranges from 0-72.

The endpoint compares the baseline score with a follow-up score. The scheduled follow-up is Month 3 for the 20 mg arm and Month 6 for the 30 mg arm. The registry describes the endpoint as mean change and specifies standard deviation as the dispersion measure. It also says baseline EASI was subtracted from the later score in describing the final outcome. The record does not provide the resulting means or standard deviations, so the direction and size of the observed changes cannot be determined from the numerical results.

In general, a composite clinical score can summarize several related features in a single measure, making it useful for tracking overall changes in disease signs and extent. A change score expresses how a participant’s measured value differs from baseline over the stated follow-up period. It does not, by itself, establish that an intervention caused the change. In this study, the non-randomized allocation and different follow-up durations are especially relevant to that distinction.

The registry also gives EASI severity descriptions, but the primary result is defined as a mean change, not as the number of participants moving between severity categories. The record does not report the primary numerical outcome, its uncertainty, or participant-level data.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with identifying what was measured, when it was measured, and what groups were compared. Here, the primary measure is change in EASI score from baseline to a scheduled follow-up. The follow-up differs by arm: Month 3 for the 20 mg regimen and Month 6 for the 30 mg regimen. The registry calls the outcome a mean and identifies standard deviation as its dispersion measure. It does not report the numerical mean changes or standard deviations, nor does it describe the analysis used to estimate them.

What does a mean change represent?

In general, a mean change is an average of participant-level differences between a starting measurement and a later measurement. It provides a summary of the direction and typical magnitude of change in the analyzed group. The meaning depends on how the difference is defined. The registry description says baseline EASI was subtracted from the later score when describing the final outcome. The record does not provide values that would allow the direction of the observed mean change to be checked or interpreted.

In general, the standard deviation describes how spread out individual measurements or changes are around their mean. It is a description of variability, not a measure of certainty in the mean estimate. A standard error or confidence interval is often used to convey precision, but neither is reported for the primary endpoint in the registry record. It would not be valid to derive either from enrollment alone.

Why does allocation matter?

In general, random allocation is used to make treatment groups comparable, on average, with respect to measured and unmeasured participant characteristics. This study is listed as non-randomized and sequential. The registry record does not specify the sequence rules or how participants entered each arm. Without those details and without random allocation, the groups may differ for reasons unrelated to dose. A comparison of their results would therefore be vulnerable to confounding.

The design also has no masking. In general, masking can reduce the influence of treatment knowledge on assessments, participant reports, and other decisions. The registry record lists none, but does not describe whether any outcome assessment procedures were standardized or whether other safeguards were used. Those details are not reported in the registry record.

The different scheduled durations also affect interpretation. A change from baseline to Month 3 and a change from baseline to Month 6 are not measurements over the same period. In general, longer follow-up allows more time for outcomes to change and may also involve different patterns of attendance or missingness. A difference between those arm-level changes would not isolate a dose contrast, even if the numerical results were available.

What can uncertainty tell a reader?

In general, a confidence interval expresses uncertainty around an estimated effect under a specified statistical model. A narrow interval indicates greater precision than a wide interval, although interpretation also depends on the analysis and the study design. A p-value addresses compatibility of the data with a specified null hypothesis under model assumptions; it does not measure the probability that a treatment works. The registry record does not report a confidence interval, p-value, or other inferential result for the primary endpoint.

In general, variability can be greater than expected under a simple model when observations are more dispersed than the model assumes. Over-dispersion matters because standard errors and inferential tests can be misleading if the analysis treats the data as less variable than they are. That concept is not a claim about this study’s EASI results: the registry record does not report an analysis diagnosing over-dispersion, and the named primary endpoint is summarized as a continuous mean outcome.

How should planning calculations be understood?

The registry’s planning assumptions describe an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the intended effect to detect is expressed as a fraction of the observed effect. Such calculations are prospective illustrations, not evidence that the study had a particular probability of detecting an effect. They are not observed power. The record does not state that these assumptions were the trial’s own design justification, and the sample-size justification is not reported in the registry record.

In general, planning calculations depend on assumptions about the target effect, variability, significance level, and allocation. If the observed effect is unstable or imprecisely estimated, calculations based on it may also be unstable. No planning values or observed primary effect are reported in the registry record, so no numerical sample-size interpretation can be made from the posted information.

What analysis details are missing?

The registry lists zero analyses. It does not describe the model used for the primary endpoint, whether the analysis adjusted for baseline EASI, whether observations were analyzed according to the assigned arm, or how incomplete follow-up was treated. These items are not reported in the registry record. They matter because different reasonable choices can lead to different estimates and uncertainty, particularly in a small pilot with unequal follow-up schedules.

General statistical principles can clarify what the methods would mean, but they cannot supply the missing study-specific analysis. The posted record supports description of the endpoint, design, and event counts; it does not support reconstructing an unreported analysis or estimating an outcome from the enrollment figure.

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("Apremilast 20 BID", "Apremilast 30mg BID")
n   <- c(6, 10)
m   <- c(-8.8, -8.2)
sp  <- c(11.6, 9.1)
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  Apremilast 20 BID  6  -8.800  11.600  -20.973  3.373
CARM  Apremilast 30mg BID  10  -8.200  9.100  -14.710  -1.690

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary endpoint, Change in EASI Scores, and secondary outcomes concerning IGA categories, pruritus on a Visual Analog Scale, and DLQI scores. It also lists four outcome measures and zero analyses. The record does not report how these outcomes were analyzed or whether any adjustment for multiple comparisons was planned. Multiplicity procedures are not reported in the registry record.

In general, examining multiple outcomes or multiple comparisons can increase the chance of observing apparently notable results by chance. Prespecified priorities and an analysis plan help readers distinguish primary questions from exploratory ones. The registry identifies a primary endpoint, but that designation alone does not reveal whether secondary outcomes were tested, how results were selected for reporting, or what inferential threshold was used. Those details are not reported in the registry record.

The record also does not describe missing-data methods. It does not say how many participants had endpoint measurements available at each scheduled assessment, whether participants discontinued, or how any missing EASI scores were handled. These details are not reported in the registry record. In general, missingness can affect an estimated mean change if participants with observed follow-up differ systematically from those without it. The enrollment count cannot establish the number included in an endpoint analysis.

The analysis population is not reported in the registry record. It is therefore unclear which participants were included in each outcome calculation and whether all enrolled participants were analyzed. The statistical plan, any interim analyses, and any rules for stopping or changing treatment are also not reported in the registry record. They should not be inferred from the completed status or the pilot designation.

These gaps constrain interpretation rather than proving that particular procedures were or were not used. The registry record does not give enough information to assess multiplicity control, robustness to missing observations, or alignment between planned and reported analyses.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse-event counts by arm. For Apremalist 20mg BID, 0 serious events are reported among 6 participants at risk; for Apremalist 30mg BID, 0 are reported among 10 participants at risk. Deaths are recorded as 0 in each group. The record also lists other adverse events affecting 2 of 6 participants in the 20 mg group and 9 of 10 participants in the 30 mg group.

These are descriptive counts from a non-randomized, unmasked study. They do not establish that one regimen is safer than another. The groups had different doses and scheduled durations, and the registry does not provide event descriptions, severity details for the other events, exposure-adjusted rates, or a statistical comparison. The duration difference also means that time at risk may not be comparable from these counts alone.

In general, zero recorded serious events does not show that the underlying risk is zero. A small study may not be able to characterize uncommon events precisely. The registry’s safety counts should therefore be read as what was recorded in this pilot, not as a definitive estimate of safety. The record’s stated purpose included preliminary safety and tolerability data; broader safety conclusions are not supported by these counts alone.

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

The registry record documents a completed Phase 2 pilot of apremilast in adults with atopic dermatitis. It identifies the primary endpoint as mean change in EASI score and describes the scheduled assessments for the 20 mg and 30 mg arms. It also records serious and other adverse-event counts. These registry entries allow readers to understand the study’s broad question and design.

The record does not report numerical results for the primary EASI endpoint. It therefore does not show the observed mean change, its variability, or its precision. No claim about the direction or magnitude of change can be made from the endpoint description alone. The absence of a reported numerical result should not be interpreted as evidence of no change; it means that the result is not reported in the registry record.

The study also does not establish a causal difference between doses. Allocation was non-randomized, masking was absent, the model was sequential, and the arms had different durations. These design features leave open alternative explanations for any difference that might be observed. There is no listed randomized comparator, and the record does not provide an adjusted analysis that could address these limitations.

In general, a pilot study can help characterize procedures, collect preliminary observations, and inform the design of later research. The stated purpose was to obtain preliminary safety and tolerability data to support larger controlled studies. That purpose is distinct from providing a definitive estimate of treatment effect. The registry record does not report a sample-size justification or detailed statistical plan, so the intended precision and analysis strategy cannot be assessed.

The adverse-event counts are also descriptive rather than comparative evidence. Zero recorded serious events in the listed groups does not rule out uncommon harms, and the other-event counts do not establish a difference in risk between regimens. Overall, this registry entry supports a description of the pilot’s structure and recorded safety counts, but not a conclusion that apremilast does or does not improve atopic dermatitis or that one dose is preferable.

14. Why This Trial Matters Statistically

This trial matters statistically because its design illustrates why an endpoint definition and a numerical result are not the same thing. The registry specifies EASI change as the primary measure and identifies the assessment periods, but it does not report the resulting mean changes or their dispersion. Readers can understand what the investigators intended to measure without being able to evaluate what was observed.

The design also highlights the limits of comparing non-randomized groups. Randomization is a tool for reducing systematic differences between groups; its absence means that participant characteristics and treatment assignment may be entangled. Here, the sequential model and lack of masking add further context, while the arms differ in dose and follow-up duration. Any apparent contrast between arms would need cautious interpretation even if numerical outcomes were available.

The stated pilot objective gives the study a different statistical role from a large controlled trial. Preliminary safety and tolerability observations can inform later research, but they do not automatically answer a confirmatory efficacy question. The registry does not report a sample-size justification, primary outcome estimates, or the detailed statistical methods needed to assess precision and robustness.

For clinical researchers, the entry is a reminder to distinguish design information, outcome definitions, observed results, and inferential conclusions. Each serves a different purpose. Reporting a measure without its numerical result leaves the central outcome question unresolved, and reporting event counts without a comparable control design does not establish a relative safety effect. Clear reporting of analysis populations, missing data, and uncertainty would be needed to support stronger interpretation.

The useful statistical lesson is not a conclusion about treatment efficacy. It is that study design and transparent results jointly determine what can be learned. In this record, design features are identifiable, but the primary numerical outcome and analysis details are not reported in the registry record.

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.

Several limitations specific to this registry entry restrict interpretation. The study is non-randomized, unmasked, and sequential, so treatment groups cannot be assumed to be comparable. The registry record does not describe the sequence rules, participant assignment process, or any methods used to address baseline differences. It also lists no separate control group.

The dose arms have different scheduled follow-up periods: 20 mg BID for 3 months and 30 mg BID for 6 months. This prevents a straightforward comparison of change over the same duration. It also means that the event counts may reflect different periods of observation; exposure-adjusted safety summaries are not reported in the registry record.

The primary endpoint is named and described, but its numerical findings are not reported in the registry record. The record does not provide arm-level means, standard deviations, confidence intervals, or a statistical test. Without those results, the primary outcome’s magnitude, direction, and precision cannot be assessed. The registry also lists zero analyses, and the analysis model, analysis population, and handling of incomplete observations are not reported in the registry record.

The record does not describe participant characteristics beyond the adult atopic dermatitis population, detailed eligibility criteria, adherence, discontinuations, or the amount of follow-up available for each outcome. These details are not reported in the registry record and should not be inferred from enrollment. The sample-size justification, multiplicity procedures, interim analyses, and statistical plan are also not reported.

Finally, a pilot with the stated preliminary purpose is not a basis for definitive comparative conclusions. The safety counts are descriptive, and the lack of a randomized comparator limits causal interpretation. These limitations reflect what the registry record reports and omits; they do not establish what may have been described in other materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Apremilast for Atopic Dermatitis - A Pilot Study in Adults — NCT01393158.
• Registry record last updated 2020-01-14; status last verified 2019-12.
• Results first posted 2020-01-14.
• 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

This completed Phase 2 pilot study evaluated oral apremilast in adults with atopic dermatitis. It was non-randomized, unmasked, and sequential, with enrollment of 16 participants. The arm descriptions specify 20 mg BID for 3 months and 30 mg BID for 6 months.

The primary endpoint was mean change in EASI score from baseline to Month 3 or Month 6, according to arm. Secondary outcomes included IGA categories, pruritus Visual Analog Scale score, and DLQI score. Numerical primary endpoint results and detailed analysis methods are not reported in the registry record.

The registry records no serious adverse events or deaths in either group and reports other adverse events in each. These descriptive counts do not establish a comparative safety effect. The study’s stated aim was to obtain preliminary safety and tolerability data to support the design of larger controlled studies.