Study of Tumor Necrosis Factor Receptor Fusion Protein Etanercept (Enbrel) in Psoriasis of the Hands and/or Feet: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Tumor Necrosis Factor Receptor Fusion Protein Etanercept (Enbrel) in Psoriasis of the Hands and/or Feet (NCT00585650), a randomized phase 1, phase 2 study. The primary outcome is The Number of Subjects Who Achieve a 50% Reduction in the Palmoplantar Psoriasis Severity Index at 12 Weeks..

2. Clinical Question

The central question is about a defined change in a measure of psoriasis severity, not a general assessment of every aspect of the condition. The palmoplantar psoriasis severity index (PPPASI) adapts the psoriasis area and severity index (PASI) to lesions on the hands and feet. The outcome is whether a participant reaches the specified reduction by Week 12.

This distinction matters: the registry record reports group counts for the outcome, but counts alone do not establish how reliably the groups differ. No effect estimate, confidence interval, or statistical test for the two-group comparison is reported. The record also does not give individual participant measurements or a more detailed account of baseline severity and change over time. The posted information therefore describes the trial question and the recorded endpoint counts, while leaving the comparative uncertainty unresolved.

3. Trial Design

This was a randomized, double-blind, parallel-group, placebo-controlled study. The registry lists the study as Phase 1 and Phase 2 and as completed. It was sponsored by the University of California, Irvine. The recorded start was 2007-05, and the primary completion was 2008-05.

The intervention group received etanercept (Enbrel) 50 mg twice weekly for 12 weeks. The placebo group received placebo injections twice weekly for 12 weeks. The study description identifies the intended population as people with moderate to severe plaque psoriasis of the hands and/or feet. The registry record lists 20 enrolled participants, with 8 in the etanercept group and 12 in the placebo group for the primary outcome.

Randomization is intended to assign participants to groups by chance, helping make baseline characteristics comparable on average. Double masking means that the study was designed to keep treatment assignment concealed from participants and relevant study personnel; the record does not specify who was masked or how masking was maintained. A parallel-group design assigns participants to one group rather than having each participant receive both interventions.

The primary outcome was assessed at Week 12 and counted participants who achieved a 50% reduction in PPPASI. The primary outcome population is described as intention to treat. The registry record does not report the randomization procedure, allocation concealment details, protocol deviations, or an account of follow-up. A rationale for the group-size imbalance is not reported in the registry record. The study's own sample-size justification and detailed statistical analysis plan are also not reported in the registry record, so they cannot be inferred from the enrollment count or design description.

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

Analysis population for the primary outcome, as defined in the registry: Intention to treat

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 The Number of Subjects Who Achieve a 50% Reduction in the Palmoplantar Psoriasis Severity Index at 12 Weeks., measured over Week 12.

The primary endpoint is the number of participants who achieved a 50% reduction in the palmoplantar psoriasis severity index at Week 12. It is a binary responder outcome: a participant either meets the reduction threshold or does not. The registry record gives the endpoint's unit as participants and identifies the population as intention to treat.

PPPASI is a version of PASI modified to assess psoriasis lesions on the hands and feet. The registry describes severity assessment through erythema, induration, and desquamation. Each of these clinical signs is measured on a scale from 0 to 4, with 4 representing the most severe level. PASI is described in the record as a widely used tool for measuring psoriasis severity; the palmoplantar adaptation focuses assessment on the affected hand and foot areas rather than the entire body.

A responder threshold can make a clinical outcome easier to interpret as a count of participants meeting a specified level of improvement. However, the count does not show the full distribution of severity scores or how close participants came to the threshold. Nor does it indicate the magnitude of change among responders or nonresponders. Those details are not reported in the registry record. The endpoint counts are recorded as 8 in the etanercept group and 12 in the placebo group, but there is no estimable two-arm comparison posted. Consequently, the counts alone do not quantify a treatment-group difference or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a binary outcome because it classifies each participant according to whether they reached the stated PPPASI reduction threshold by Week 12. For a two-group comparison, statistical analysis would ordinarily relate the number meeting the criterion to the number assessed in each group. The registry record contains the group counts but marks the binary two-arm comparison as not estimable. No inferential estimate or test is posted, and none should be reconstructed from the counts alone.

What does an effect estimate describe?

In general, an effect estimate summarizes the contrast between groups using a defined scale. For binary outcomes, possible scales include a difference in response probabilities or a relative measure comparing them. Each scale answers the comparison in a different way. The choice of scale and the precise estimator should be specified by an analysis plan. The registry record does not report a comparative estimate or identify a planned effect scale for this endpoint. No new estimate can be established from the posted information without making analytic choices that are not documented.

What does a confidence interval add?

In general, a confidence interval conveys uncertainty around an estimated effect. Its width depends on the information in the data and the assumptions of the method. In a small trial, each observed participant can have substantial influence on a binary outcome estimate, so uncertainty may be important. This is a general statistical consideration, not a claim about a particular interval in this study: no interval is reported in the registry record. Without an effect estimate and interval, readers cannot judge the precision of the comparative result from the posted endpoint data.

How should hypothesis tests be read?

In general, a hypothesis test evaluates the data against a specified null hypothesis under the test's assumptions. Its p-value is not the probability that a treatment works or that the null hypothesis is true. A small p-value does not itself establish clinical importance, and a larger p-value does not establish equivalence. A test result should be considered alongside the effect estimate, interval, design, and data quality. No two-group test or p-value is reported for the primary endpoint, so there is no reported test result to interpret.

Why can a binary comparison be not estimable?

In general, an analysis can fail to produce a valid comparative estimate when required outcome information or a suitable analysis input is unavailable. For example, a registry entry might not contain the counts or definitions needed for the intended model. The record specifically indicates that values are missing or not estimable for a two-arm comparison of the binary endpoint. The reason beyond that description is not reported in the registry record. It would be inappropriate to presume a particular cause or to select an alternative model without the underlying data and analysis details.

What role do modeling assumptions play?

In general, statistical models translate observed data into estimates while relying on assumptions about the outcome and design. For count data, over-dispersion means that variability is greater than a model's assumptions would predict; accounting for it can affect uncertainty estimates. That concept is general, and it does not establish that over-dispersion is relevant to this trial's binary endpoint. The record does not report a model, an over-dispersion assessment, covariate adjustment, or a detailed statistical plan. The endpoint's binary nature should not be confused with a continuous or count outcome analysis.

What can planning calculations tell readers?

In general, a sample-size calculation uses assumptions about the effect to detect, the analysis method, the allocation, and the significance level to estimate a planning requirement. Such a calculation is not evidence of what the trial actually observed, and it is not a retrospective measure of power. The registry record does not report the study's original sample-size justification. Any planning illustration based on a stated fraction of an observed effect is a separate hypothetical exercise, not the trial's design rationale and not observed power. No planning values are reported in the registry record.

For this study, the stated planning assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation. Those are assumptions for a planning illustration, not a description of the trial's actual group allocation: the recorded outcome group sizes are 8 and 12. The effect for such an illustration is framed as a fraction of the observed effect. Because no comparative effect is estimable in the registry record, the posted information cannot support interpreting a planning calculation as a trial finding. It also cannot establish whether the original study was adequately sized.

Finally, statistical interpretation depends on a transparent definition of the analysis population and outcome handling. The primary endpoint identifies an intention-to-treat population, but details of participant inclusion, missing outcomes, and deviations are not reported in the registry record. These omissions limit replication and appraisal. The reported outcome counts and the absence of an estimable comparison should therefore be presented together, without substituting an unplanned calculation for the missing sponsor analysis.

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("Subjects Receiving Etanercept 50 mg Twice Week for", "Subjects Receiving Placebo for the First 12 Weeks")
n      <- c(8, 12)
events <- c(8, 12)
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  Subjects Receiving Etanercept 50 mg Twice Week for  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  Subjects Receiving Placebo for the First 12 Weeks  12  12  100.0  73.5  100.0  75.8  100.0  75.3  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no posted secondary outcomes. This limits what can be said about multiplicity, the issue of interpreting results when multiple outcomes or analyses are considered. The record does not report whether the study planned multiple comparisons, subgroup analyses, repeated looks at the data, or any adjustment for multiplicity. An interim-analysis plan is not reported in the registry record. Their absence from the posted information should not be read as proof that such procedures were or were not used.

The primary endpoint population is described as intention to treat. In general, intention-to-treat analysis seeks to analyze participants according to their randomized group, regardless of treatment received, but the exact implementation depends on the protocol and handling of missing outcomes. The registry record does not report how missing Week 12 assessments were handled, how many outcomes were missing, or whether any participants were excluded from the outcome analysis. It also does not provide a detailed participant flow or explain deviations from assigned treatment.

These details matter for a responder endpoint because the classification depends on having sufficient outcome information to determine whether the threshold was reached. The group sizes and recorded outcome counts are listed, but the method used to derive them is not explained. The record does not report imputation, sensitivity analyses, or alternative assumptions for missing data. Thus, the posted counts can be described, while the robustness of the response classification and the treatment of missing outcomes remain unclear.

No multiplicity correction or missing-data strategy should be inferred. The registry record does not report a detailed statistical analysis plan that would resolve these questions. With no secondary outcomes posted and no estimable primary comparison, the available information does not support broader claims based on unreported analyses.

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 non-serious adverse event terms

The registry record reports zero serious adverse events among the 8 participants at risk in the etanercept group and zero among the 12 participants at risk in the placebo group. It lists 3 other adverse events in the etanercept group and 4 in the placebo group. These are the posted counts, not comparative estimates. No deaths are reported in the safety entries; whether deaths were absent or simply not recorded is not explained in the registry record.

Serious adverse events and other adverse events are distinct categories in the record. The record does not provide definitions, event descriptions, severity grades, or a detailed accounting of whether counts represent participants or event occurrences. No serious-event terms are listed. Without those details, the counts cannot convey the nature, timing, duration, or clinical consequences of events.

Zero recorded serious adverse events in these groups does not establish that serious events are impossible or that the groups have equivalent safety. The trial enrolled a small number of participants, and the registry record does not provide a statistical safety comparison or detailed follow-up information. The counts should be read as the safety information recorded for this trial, with the limits of reporting and sample size in mind.

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

The registry record documents a randomized, double-blind, placebo-controlled study of etanercept for plaque psoriasis of the hands and/or feet, with a Week 12 responder endpoint. It records 8 participants in the etanercept group and 12 in the placebo group for the outcome. It does not provide an estimable two-group comparison. These registry entries describe what is posted; they do not establish a comparative treatment effect.

The endpoint asks whether participants achieved a 50% reduction in PPPASI, a severity index adapted to lesions on the hands and feet. This threshold-based outcome is one specific way of summarizing change. It does not capture every possible aspect of psoriasis, the degree of change beyond the threshold, or outcomes at other times. The registry record does not post secondary outcomes.

The lack of an estimable comparison means readers cannot determine from the posted results how large a difference between groups might be, how precise an estimate would be, or whether the data are compatible with a range of possible effects. The counts should not be converted into a claim of benefit, lack of benefit, or equivalence. No confidence interval or test result is reported to support such a conclusion.

The record also leaves important methods details unresolved, including the handling of missing outcomes and the statistical analysis plan. The stated intention-to-treat population is useful context but does not, by itself, explain how the outcome counts were assembled. Safety counts are likewise limited: they describe recorded events but do not constitute a detailed or comparative safety analysis.

Accordingly, the result's meaning is chiefly descriptive. The study posed a focused question and posted group counts for its primary endpoint, but the registry information does not support a precise comparative conclusion. A complete report with the sponsor's analysis, uncertainty estimates, and fuller methods would be needed to interpret the outcome more fully.

14. Why This Trial Matters Statistically

This trial illustrates a basic distinction in clinical statistics: a study can have a defined randomized design and a clinically focused endpoint while still lacking a usable comparative estimate in its registry results. The outcome is specific, the treatment period is stated, and group counts are recorded. Yet the binary two-arm comparison is marked not estimable. Without a contrast and its uncertainty, the central comparative question remains unanswered by the posted statistics.

The example also shows why endpoint counts should not be mistaken for a complete analysis. A count needs clear denominators, definitions, and transparent handling of unavailable outcomes to support comparison. The record identifies the intention-to-treat population and group sizes, but does not explain missing data or provide the sponsor's inferential result. Statistical reporting needs both an interpretable outcome and a defensible account of how that outcome was analyzed.

Small trials can be valuable for focused research questions, but estimates from small groups are often especially sensitive to individual observations. General statistical practice therefore emphasizes reporting uncertainty, not just point estimates or counts. Here, no comparative estimate or confidence interval is posted, so readers cannot assess precision. That limitation is not repaired by a sample-size planning illustration: planning scenarios are not evidence about observed treatment effects, and they do not substitute for an analysis.

Finally, the record underscores the importance of distinguishing no reported result from a demonstrated absence of an effect. When a comparison is not estimable, neither a positive conclusion nor a null conclusion follows. Accurate interpretation requires stating what the registry record contains, identifying what is not reported, and avoiding claims that exceed the evidence available.

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 is that the registry record does not report an estimable statistical comparison for the primary binary endpoint. Although it lists counts in both groups, it gives no effect estimate, confidence interval, or test result. The reason the comparison is not estimable is not reported in the registry record beyond the note that the necessary values are missing or not estimable.

The enrolled sample is small, with 20 participants listed and outcome group sizes of 8 and 12. This limits the amount of information available for estimating response patterns and safety events. No study-specific sample-size justification is reported, so the adequacy of enrollment relative to the intended question cannot be assessed from the registry entry.

The primary endpoint is a threshold-based response at Week 12. The registry record does not provide the underlying PPPASI values, baseline scores, participant-level change, or response data at other times. The endpoint therefore cannot describe the full distribution or magnitude of severity changes. No secondary outcomes are posted, and longer-term outcomes are not reported in the registry record.

Further limitations concern methods transparency. The record does not report the randomization procedure, allocation concealment, who was masked, a detailed analysis plan, handling of missing outcomes, protocol deviations, or participant flow. The primary population is labeled intention to treat, but the implementation of that population is not described. The safety information lists event counts without definitions, event terms for serious events, or detailed follow-up. These gaps restrict appraisal of bias, robustness, and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Tumor Necrosis Factor Receptor Fusion Protein Etanercept (Enbrel) in Psoriasis of the Hands and/or Feet — NCT00585650.
• Registry record last updated 2023-08-18; status last verified 2023-08.
• Results first posted 2011-11-08.
• 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 study is listed as completed and randomized, double-blind, parallel-group, and placebo-controlled. It is recorded as Phase 1 and Phase 2, with 20 participants enrolled. The intervention was etanercept 50 mg twice weekly for 12 weeks; the comparator was placebo injections on the same schedule. The primary endpoint was the number of participants achieving a 50% reduction in PPPASI at Week 12, in an intention-to-treat population.

The registry record lists 8 participants in the etanercept group and 12 in the placebo group for the endpoint. It does not report an estimable two-group comparison, effect estimate, confidence interval, or p-value. No secondary outcomes are posted. Serious adverse event counts are zero in both groups; other adverse event counts are 3 and 4. A comparative efficacy conclusion, detailed missing-data assessment, and full statistical interpretation cannot be established from the posted information.