REPArE: Rating Evaluations in Psoriatic Arthritis (PsA) With Etanercept (Enbrel®): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for REPArE: Rating Evaluations in Psoriatic Arthritis (PsA) With Etanercept (Enbrel®) (NCT00127842), a na phase 4 study. The primary outcome is Percentage of Participants With Improvement of ≥ 0.50 Units From Baseline to Month 24 in the HAQ DI.

2. Clinical Question

3. Trial Design

REPArE was a Phase 4, completed, single-group study sponsored by Amgen. Its stated objective was to describe the long-term effectiveness and safety of etanercept among patients with psoriatic arthritis in a Canadian clinical practice setting. The registry lists an enrollment of 110. The study start and primary completion are both recorded as 2005-08; the registry does not provide more detailed dates in this record.

Participants received open-label etanercept by subcutaneous injection at 50 mg/week for 24 months. Open-label means that treatment was not masked. With a single group and no comparator, the design can describe outcomes observed among participants receiving the intervention, but it cannot make a randomized, concurrent comparison between etanercept and another treatment or a control condition. Changes over time could not be separated from other influences using a control group in this design.

The primary endpoint assessed improvement in HAQ-DI from baseline to month 24. The registry also lists secondary outcomes relating to work and productivity, physician global assessment, and patient global assessment. These include changes from baseline to month 24, with percentage change specified for the global assessments. The record lists 11 outcome measures, but does not report detailed analysis results for them.

The record does not report the rationale for the enrollment target, recruitment procedures, eligibility criteria, or details of how participants were followed in practice. Although the study is marked completed, completion status alone does not establish that every participant completed the planned treatment or had a month-24 assessment. Those details are not reported in the registry 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:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set, composed of all participants who received at least one dose of study medication and had at least one baseline and at least one post-baseline measurement for the endpoint of interest. Imputation by last observation carried forward (LOCF) was applied.

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 Percentage of Participants With Improvement of ≥ 0.50 Units From Baseline to Month 24 in the HAQ DI, measured over Baseline and 24 months.

The primary endpoint was the percentage of participants whose HAQ-DI improved by at least 0.50 units from baseline to month 24. The HAQ-DI is a self-reported measure of functional status for people with psoriatic arthritis. It asks about activities including dressing and grooming, rising, eating, walking, hygiene, reach, grip, and other activities. For each task, response categories range from no difficulty to being unable to do the task. The task scores are summed and averaged to produce an overall score from 0 to 3; zero represents no disability and three represents very severe, high-dependency disability.

Using a threshold turns a change in a continuous score into a responder outcome: each participant either meets the stated improvement criterion or does not. Reporting a percentage can make the outcome easier to understand as the proportion meeting that criterion. It also means that the result depends on the chosen threshold; it does not describe the full distribution of score changes or the size of change among participants who meet it.

The registry identifies the assessment time points as baseline and 24 months and specifies a 95% confidence interval as the measure of dispersion. It does not report the endpoint estimate, the interval limits, or the count of participants meeting the criterion. The HAQ-DI description explains what the instrument measures, but the registry does not report additional information about its measurement properties or the reason for selecting this particular threshold.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design show?

This study is listed as single-group and open-label, with no comparator. In general, a single-group study can describe what was recorded among participants receiving an intervention, including measurements at different time points. It does not create a concurrent counterfactual comparison: there is no control group showing what might have happened over the same period under another condition. As a result, a change from baseline is descriptive and cannot, by itself, isolate the effect of treatment from other influences.

Open-label means that treatment was not masked. In general, awareness of treatment can influence reporting, expectations, clinical assessments, or care decisions. This is relevant to patient-reported measures such as the HAQ-DI and to global assessments. The registry does not report additional procedures used to limit these influences.

How should the responder endpoint be understood?

The primary measure is a proportion: participants are classified according to whether they meet the stated improvement threshold on the HAQ-DI between baseline and month 24. The resulting percentage summarizes the share meeting that criterion, rather than the average score change across the group. This distinction matters because participants just meeting the threshold and participants with larger changes are counted in the same responder category. Participants who do not meet the threshold may also have had changes in either direction.

General statistical explanation: converting a continuous score into a responder outcome can make a result more readily interpretable, but it discards detail about the amount and distribution of change. The threshold is part of the endpoint definition, not a complete account of every participant's functional status. The record does not report the primary estimate or the underlying score changes, so neither the responder result nor the broader distribution can be assessed.

What does the confidence interval contribute?

The endpoint specifies a 95% confidence interval. In general, a confidence interval conveys uncertainty around an estimate under the statistical method's assumptions. It is not a guarantee that the true value lies in a particular interval, and it does not establish whether an estimate is important in clinical terms. Interpretation requires the estimate, both interval limits, and knowledge of the analysis population and method.

The registry record does not report the confidence interval limits or the endpoint estimate. It also does not describe the method used to calculate the interval. Therefore, the precision of the primary endpoint estimate cannot be evaluated from the record. A confidence interval should not be reconstructed without the relevant counts and analysis details.

What does the analysis population mean?

The defined Full Analysis Set includes participants who received at least one dose and had at least one baseline and one post-baseline measurement for the endpoint of interest. This definition ties inclusion to treatment exposure and endpoint measurements. It is not the same as assuming that every enrolled participant contributed data to the primary endpoint. The size of this endpoint-specific analysis set is not reported.

The registry states that last observation carried forward was applied. In general, this imputation method uses a participant's last observed value in place of a later missing value. It can preserve an analysis record when a later measurement is absent, but its implications depend on why data are missing and whether the last observed value is a reasonable stand-in for the unobserved value. The registry does not report the amount or pattern of missing data, the timing of last observations, or sensitivity analyses using other approaches.

What can the planning assumptions establish?

The registry describes sample-size illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated target effect is expressed as a fraction of the observed effect. These are planning illustrations, not observed trial findings and not observed power. The study itself is single-group, so a hypothetical equal-allocation comparison does not change the actual design or supply a control group.

General statistical explanation: power is a design-stage probability of detecting a specified effect under stated assumptions. A planning calculation depends on the effect chosen, variability, significance criterion, allocation, and analysis method. An illustration based on an observed effect is especially dependent on that effect estimate and should not be read as proof that a completed study had a particular probability of success. The registry record does not report the values of the illustrations in the registry record for this analysis, nor does it report the trial's own sample-size justification.

More broadly, the record does not report a detailed statistical analysis plan, the estimator used for the primary percentage, handling of any other missing endpoint data, or interim analyses. These omissions prevent a fuller assessment of how the statistical methods were prespecified and implemented. No unadjusted recalculation is appropriate without the endpoint counts and associated analysis information.

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("Enbrel")
n      <- c(109)
events <- c(61)
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  Enbrel  109  61  56.0  46.1  65.5  46.6  64.9  46.6  64.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures. The primary outcome is the month-24 HAQ-DI improvement threshold; secondary outcomes include work absence, reduced productivity at paid work, unpaid labour production, impediments to paid and unpaid labour, and physician and patient global assessments. The registry record does not report a multiplicity adjustment, a hierarchy for testing secondary outcomes, or a statistical analysis plan. It therefore does not establish how the family of outcomes was handled in inferential testing. In general, examining multiple outcomes can increase the chance of at least one apparently notable result arising by chance, so the planned testing strategy matters when interpreting a collection of findings.

The record lists zero analyses in its structured analysis information. That does not establish that no analyses were conducted; it means the registry information does not contain analysis records. The endpoint estimate, confidence interval limits, and outcome-specific analysis counts are not reported.

For the primary endpoint, the analysis population is defined as participants who received at least one dose and had at least one baseline and one post-baseline endpoint measurement. The registry says last observation carried forward was applied. It does not report the number of missing month-24 measurements, reasons for missingness, participant flow, or sensitivity analyses. General statistical explanation: missing-data methods rely on assumptions about why values are missing and how missing values relate to observed measurements. Without detail on missingness and alternative analyses, robustness to those assumptions cannot be assessed.

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: angina pectoris (0.9%), cardiac arrest (0.9%), myocardial infarction (0.9%), appendicitis perforated (0.9%), umbilical hernia (0.9%).

For the Enbrel group, the registry lists 110 participants at risk for serious adverse events and 14 participants affected. It lists 110 at risk for other adverse events and 67 affected. These are separate registry categories; the figures do not indicate whether the same participant experienced events in both categories. The record does not provide a comparison group, so these counts describe reports in the treated group rather than comparative risks.

The listed serious adverse event terms are angina pectoris, cardiac arrest, myocardial infarction, perforated appendicitis, umbilical hernia, and abdominal abscess. Each is listed as 0.9%. The registry record does not provide the event counts corresponding to those listed percentages in the available information, and it does not state whether these terms exhaust all serious adverse events. Deaths are not reported in the registry record.

Adverse-event counts describe what was recorded; they do not establish that treatment caused an event. The registry does not report event timing, severity beyond the serious-event classification, duration, outcome, or investigator assessment of relatedness. Without a control group, these figures cannot be used to estimate a comparative difference in safety outcomes.

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

The registry record establishes the study question, treatment regimen, primary endpoint definition, analysis-population criteria, and some adverse-event counts. It does not report the observed primary endpoint percentage or its confidence interval. Therefore, it is not possible to describe from this record how many participants met the HAQ-DI improvement threshold or how precisely that percentage was estimated.

The study's stated aim was to describe long-term effectiveness and safety in a Canadian clinical practice setting. Its single-group, open-label design can contribute descriptive information about participants receiving etanercept, but it cannot provide a randomized comparison with a control condition. Any observed change from baseline would not, by itself, establish that treatment caused the change. The result information needed even for a descriptive assessment of the primary endpoint is not reported in the record analyzed.

The endpoint focuses on a threshold for improvement in functional status, not every aspect of psoriatic arthritis or every change in daily life. The registry also identifies work and global-assessment outcomes, but their results are not reported in the available record. The safety figures identify participants affected by adverse events in the treated group; without a comparison group or information on relatedness, they cannot determine whether treatment caused those events.

These limitations do not show that the treatment had no effect, nor do they establish that it had an effect. They indicate that the registry information available for this account is insufficient to characterize the primary result, its precision, or comparative benefit and harm. The findings should be understood as incomplete registry reporting rather than as a positive or negative conclusion about treatment.

14. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a long-term descriptive objective and a design without a comparator. A single-group study can document participant outcomes in a clinical practice setting, but the absence of a concurrent control limits causal interpretation. That distinction is central when a question concerns change over time: a before-and-after result, even if reported, would not separate treatment-related change from other explanations.

The primary endpoint also illustrates how a continuous patient-reported measure can be turned into a responder outcome. A threshold-based percentage is straightforward to describe, but it omits information about the size and spread of score changes. Interpreting it requires both the observed percentage and its uncertainty, neither of which is reported in the registry record available for this analysis.

The stated use of last observation carried forward makes missing-data handling relevant to interpretation. The method is identified, but missingness patterns and sensitivity analyses are not reported. Without those details, readers cannot assess whether the endpoint result would be sensitive to assumptions about unobserved month-24 measurements.

The registry also lists multiple secondary outcomes, while the statistical testing strategy is not reported. This highlights why prespecified outcome hierarchies and multiplicity methods matter for interpreting collections of findings. Here, the absence of reported endpoint estimates and analysis details means that the record supports explanation of the design and methods, but not a statistical judgment about the study's observed effectiveness.

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 main trial-specific limitation is the single-group, open-label design. There is no comparator, and allocation is recorded as NA. As a result, the study cannot make a randomized comparison or control for changes over time that may occur independently of the intervention. The lack of masking may also be relevant to participant-reported and clinician-assessed outcomes.

The registry record does not report the primary endpoint estimate, its confidence interval, the count meeting the improvement threshold, or the size of the endpoint-specific analysis population. Although the record marks the study completed, it does not report participant flow, completion of the planned 24-month regimen, adherence, dose changes, or loss to follow-up. The enrollment figure should not be read as the number analyzed for the primary endpoint.

Last observation carried forward is identified for the Full Analysis Set, but the extent and pattern of missing data and the results of sensitivity analyses are not reported. The registry also does not report the statistical analysis plan, the method used for the confidence interval, adjustment for multiple outcomes, or interim analyses. The record lists secondary outcomes, but their estimates and analysis details are not reported.

For safety, participant counts are reported without a comparator, detailed event timing, relatedness assessments, or outcome information. Deaths are not reported in the registry record. The serious-event terms are listed with percentages, but the available information does not include the corresponding counts. These reporting gaps limit interpretation of both effectiveness and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: REPArE: Rating Evaluations in Psoriatic Arthritis (PsA) With Etanercept (Enbrel®) — NCT00127842.
• Registry record last updated 2014-04-24; status last verified 2014-03.
• Results first posted 2014-04-24.
• 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

REPArE (NCT00127842) is a completed Phase 4, single-group, open-label study sponsored by Amgen. It concerned psoriatic arthritis in a Canadian clinical practice setting and listed an enrollment of 110. Participants received etanercept by subcutaneous injection at 50 mg/week for 24 months.

The primary endpoint was the percentage of participants with improvement of at least 0.50 units on the HAQ-DI from baseline to month 24. The endpoint population required treatment exposure and baseline and post-baseline measurements; last observation carried forward was applied. The registry lists secondary work and global-assessment outcomes.

The record reports adverse-event participant counts for the Enbrel group but has no comparator. It does not report the primary endpoint estimate or confidence interval, detailed analysis results, the statistical analysis plan, or deaths. Thus, the record describes the design and measures but does not allow the primary outcome's magnitude or precision to be assessed.