Study to Observe the Safety and Efficacy of Etanercept (Enbrel®) in Patients With Moderately Active Rheumatoid Arthritis in Every Day Clinical Practice in Austria: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Observe the Safety and Efficacy of Etanercept (Enbrel®) in Patients With Moderately Active Rheumatoid Arthritis in Every Day Clinical Practice in Austria (NCT01877239), a registered phase not stated study. The primary outcome is Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 24.

2. Clinical Question

The study focuses on outcomes during routine clinical practice rather than a randomized comparison between treatments. The question is therefore descriptive: it concerns the proportion meeting the stated remission threshold at the specified assessment time. It does not, on its own, estimate how that proportion compares with what would have happened without etanercept or with a different treatment.

The registry describes observation over 52 weeks. Secondary outcomes concern CDAI disease-activity status at Week 12 and Week 52, and change in CDAI scores from baseline at Week 12, Week 24 and Week 52. Those measures provide context about disease activity at other assessment times, but their numerical findings are not reported in the registry record.

3. Trial Design

This was a prospective, multicenter, non-interventional observational study of etanercept in people with moderately active rheumatoid arthritis in everyday clinical practice in Austria. The registry record lists Pfizer as the sponsor, enrollment of 111, and status as completed. The recorded start date is 2012-12-10, and the primary completion date is 2016-01-07.

Participants were to be observed over 52 weeks. The intervention entry is classified as non-intervention, and the record does not describe random assignment or a treatment allocation procedure. Allocation is not stated. This design is different from a randomized controlled trial: treatment use and clinical care are observed in practice, not assigned by a randomized study protocol described in the registry record. No like-for-like control comparison is specified.

The primary outcome is the percentage of participants with CDAI remission at Week 24. Its analysis population is called the Eligible Set and is defined by consent, receipt of at least one dose of etanercept, and evaluable CDAI assessments at baseline and Week 24. The arm description also defines a Full Analysis Set as participants who gave written informed consent. The registry record does not explain the relationship between that set and the Eligible Set beyond these definitions.

Secondary outcomes include CDAI disease-activity status at Week 12 and Week 52, plus change from baseline in CDAI scores at Week 12, Week 24 and Week 52. The record lists three outcome measures and no statistical analyses. Numerical results for the primary and secondary outcomes are not reported in the registry record. The entry does not report a statistical analysis plan, a sample-size justification, or details of how missing assessments were handled.

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.

Before assignment: A total of 111 participants were enrolled in the study but due to the loss of all study data and material at one site with 35 participants, the number of participants that could be included in the analysis was 76.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eligible Set included all participants who had given written informed consent and had received at least one dose of etanercept with evaluable CDAI assessments at baseline and Week 24.

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.

Population: Full Analysis Set (FAS) included any participants who had given written informed consent.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 24, measured over Week 24.

The primary endpoint is the percentage of participants with CDAI remission at Week 24. CDAI, the Clinical Disease Activity Index, combines four measures: swollen joint counts and tender or painful joint counts based on a 28-joint assessment, along with the participant’s and physician’s global assessments of disease activity. The global assessments use a 0–10 cm visual analog scale, with higher scores indicating greater affection due to disease activity. The total CDAI score ranges from 0–76.

The registry defines remission as a CDAI score <= 2.8. It also describes low disease activity as a score > 2.8 to 10, moderate disease activity as > 10 to 22, and high disease activity as >22. These categories turn the underlying score into clinically interpretable levels of disease activity. The primary endpoint focuses on the proportion that falls within the remission category at a prespecified assessment time.

In general, a percentage is useful for expressing how common a defined outcome is within a specified population. Interpretation depends on both the outcome definition and who is included in the denominator. Here, the endpoint population requires consent, at least one etanercept dose, and evaluable CDAI assessments at baseline and Week 24. The registry specifies a 95% confidence interval, but does not report the percentage or its interval. The endpoint therefore cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is limited. It specifies a percentage endpoint and a 95% confidence interval for the primary outcome, but does not report the numerical estimate, interval, or a detailed analysis plan. The concepts below explain how these measures are generally interpreted; they do not identify methods that the study used unless the registry record explicitly says so.

What does a percentage describe?

In general, a percentage expresses the share of people in a defined group who meet a specified condition. For this endpoint, the condition is CDAI remission at Week 24, and the registry defines the relevant group as the Eligible Set. Both parts are essential: the threshold states what counts as remission, while the population definition states who is included in the estimate. The registry record does not give the numerical percentage or the number of people in the Eligible Set.

A percentage is a descriptive measure, not a direct measure of treatment effect. In a randomized comparison, a contrast between groups can support an estimate of a treatment difference under the assumptions of the analysis. Here, no randomized comparator is specified. Thus, even a reported remission percentage would describe the observed group, rather than quantify an effect relative to a control group.

What does a confidence interval communicate?

The registry specifies a 95% confidence interval. In general, a confidence interval communicates the statistical precision of an estimate, taking account of sampling variability under the method used. A narrower interval indicates greater precision than a wider interval. The interval does not show all sources of uncertainty: it does not automatically account for bias from selection, missing observations, outcome measurement, or differences between participants receiving care in practice.

The registry does not report the interval endpoints or the method used to calculate the interval. It is therefore not possible to evaluate its width, check the calculation, or determine whether any particular interval method was applied. The stated confidence level should not be mistaken for a probability that the true value lies within a particular calculated interval after the data have been observed.

How is CDAI used?

CDAI combines swollen and tender or painful joint counts based on a 28-joint assessment with participant and physician global assessments. The global assessments use a 0–10 cm visual analog scale, and higher scores indicate greater affection due to disease activity. The four components are added to form a total score from 0–76. The registry defines remission as <= 2.8, low disease activity as > 2.8 to 10, moderate disease activity as > 10 to 22, and high disease activity as >22.

In general, a threshold-based outcome simplifies a continuous or graded measure into a category that can be summarized as a proportion. That can make a result easier to interpret, but it also means participants with scores on opposite sides of a threshold are classified differently even when their scores are close. The registry provides the threshold definitions; it does not report the distribution of CDAI scores at Week 24.

What does the analysis population imply?

The primary endpoint population is defined by having consented, received at least one dose of etanercept, and had evaluable CDAI assessments at both baseline and Week 24. Requiring measurements at both times makes the endpoint depend on assessment availability, in addition to consent and treatment exposure. In general, analysis populations that require observed outcomes can differ from the enrolled population if some participants do not contribute the required measurements.

The registry also defines a Full Analysis Set as people who gave written informed consent. It does not state how that set was used for the primary outcome or reconcile it with the Eligible Set. The number in either population is not reported in the registry record. Nor does the record describe imputation, sensitivity analyses, or another approach to missing CDAI assessments. The consequences of missing assessments therefore cannot be evaluated.

What can planning calculations establish?

The study’s sample-size illustrations are planning calculations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record notes that time-to-event illustrations use total events, while other illustrations use participants per arm. These are general design assumptions and do not establish that the observational study was designed with those features.

The registry characterizes those calculations as planning illustrations based on the observed effect, not as the study’s own design. No numerical illustration results or observed primary effect are reported in the registry record. Such planning calculations, in general, describe sample sizes under chosen assumptions. They cannot replace reporting the study’s actual outcome estimate and uncertainty, and they should not be described as observed power.

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("Etanercept")
n      <- c(61)
events <- c(27)
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  Etanercept  61  27  44.3  31.5  57.6  32.5  56.7  32.5  56.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes, but does not report a statistical analysis plan or any statistical analyses. It therefore does not state whether or how multiplicity across outcomes or assessment weeks was addressed. Multiplicity arises in general when several statistical questions are considered: the more questions tested, the greater the opportunity for at least one apparently unusual result to occur by chance. Whether that issue affected this study’s conclusions cannot be assessed without the planned analysis and numerical results.

The primary outcome is assessed at Week 24. Secondary measures include CDAI disease-activity status at Week 12 and Week 52, plus change from baseline at Week 12, Week 24 and Week 52. The registry does not identify a hierarchy among the secondary measures, specify which were intended as confirmatory, or report adjustments for multiple comparisons. No result-level interpretation is available for those outcomes in the registry record.

Missing data are also insufficiently described. The Eligible Set requires evaluable CDAI assessments at baseline and Week 24, but the number meeting this definition and the reasons other assessments may be unavailable are not reported in the registry record. The record does not say whether missing outcome values were imputed, excluded, or handled in another way. In general, missing outcome data can affect a percentage estimate if the participants with observed assessments differ from those without them.

The Full Analysis Set is defined as participants who gave written informed consent, while the Eligible Set adds treatment exposure and evaluable-assessment requirements. The registry record does not describe how these populations relate analytically. Without a population-specific result, denominator, missing-data method, and analysis plan, the robustness of the primary estimate cannot be evaluated.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (2.6%), disease recurrence (1.3%), borrelia infection (1.3%), fall (1.3%), ligament injury (1.3%).

The registry reports serious adverse event figures for the Etanercept group: 76 participants at risk and 8 affected. For other adverse events, it reports 76 at risk and 16 affected. These are separate descriptive figures in the registry record; they should not be combined or treated as a comparison between study arms. The record does not report deaths.

Among the listed serious-event terms, atrial fibrillation is reported as 2.6%, and disease recurrence, Borrelia infection, fall, ligament injury and bursitis are each reported as 1.3%. These term-level percentages describe what the registry lists, but the record does not explain whether the terms refer to participants, events, or another counting convention. They should not be added together: an individual may contribute to more than one event term, and the registry does not provide information that would establish non-overlap.

In general, an at-risk count describes the group used for the safety summary, while an affected count describes participants recorded as having an event under that summary. A serious adverse event is not necessarily caused by the treatment being observed. In this non-interventional study, the figures are descriptive and there is no randomized control comparison specified. They cannot, by themselves, quantify an excess risk attributable to etanercept. Further details on event definitions, timing, relatedness, and handling of repeat events are not reported in the registry record.

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

The registry record establishes that this was a prospective, non-interventional observational study of etanercept in moderately active rheumatoid arthritis in everyday clinical practice in Austria. It defines a primary endpoint based on CDAI remission at Week 24 and specifies a 95% confidence interval. It also describes secondary CDAI outcomes at other assessment weeks and provides limited safety counts.

What the record does not establish is the numerical primary result. The percentage of participants meeting the remission definition and the confidence interval are not reported in the registry record. The numerical secondary outcomes are also not reported. Consequently, the posted registry information cannot show the observed remission proportion, its precision, or how CDAI changed over the assessment period. A description of the planned outcome is not a substitute for its observed value.

Even if the primary percentage were reported, the study’s observational design would remain important to interpretation. No randomized comparator is specified, and allocation is not stated. An outcome proportion in an observed treatment group does not, by itself, distinguish the treatment’s contribution from other influences on outcomes in routine practice. It cannot support a randomized treatment contrast where none is described.

The safety figures likewise describe recorded events rather than causal effects. The record reports the at-risk counts and affected counts, and lists several serious-event terms with percentages. It does not provide a randomized comparison or sufficient details to establish that an event was caused by treatment. These figures should be read as a registry safety summary, not as proof of either causation or absence of risk.

Overall, the study record is informative about its setting, outcome definitions, analysis-population criteria, and some safety summaries. It is not informative enough to judge the primary clinical outcome numerically or to estimate a comparative treatment effect. The distinction between what was measured and what was reported is central: the endpoint is defined, but its result is not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable for asking a clinically framed question in routine practice while using a defined disease-activity threshold. CDAI combines joint counts and global assessments, and the remission cutoff of <= 2.8 translates a score into a proportion-based endpoint at Week 24. Such a measure can be straightforward to communicate, provided the population and denominator are also clear.

The registry does identify an Eligible Set rather than simply treating enrollment as the endpoint denominator. Eligibility for that primary analysis requires consent, at least one dose of etanercept, and evaluable CDAI measurements at baseline and Week 24. This distinction matters because enrollment and the population contributing to a particular estimate need not be identical. The number in the Eligible Set is not reported in the registry record, so the denominator and resulting precision cannot be checked.

The observational setting also highlights a basic distinction in statistical interpretation. Describing outcomes among people treated in everyday practice can address what was observed in that setting. It does not provide the same causal comparison as randomized assignment to alternative groups. The registry does not specify a comparator, and allocation is not stated. Readers therefore need to distinguish a descriptive percentage from an estimate of treatment effect.

Finally, the record illustrates why outcome reporting is as important as outcome specification. It defines the primary endpoint and confidence-interval level, but does not report the primary estimate or interval. Without those numerical results, readers cannot assess either the observed outcome or its precision. The study can be characterized by its question and design, but the registry record cannot support a numerical conclusion about its primary endpoint.

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 limitation for interpreting this study from its registry record is the absence of numerical outcome results. The primary endpoint is defined, but the remission percentage and its 95% confidence interval are not reported in the registry record. The listed secondary outcomes also lack numerical results. This prevents assessment of the size and precision of the observed outcomes.

The primary analysis population is narrower than the enrollment description: the Eligible Set requires consent, at least one etanercept dose, and evaluable CDAI assessments at baseline and Week 24. The number meeting those criteria is not reported. The Full Analysis Set is separately defined by consent, but the registry does not explain how the two sets relate or which set contributes to each reported outcome. These omissions limit evaluation of the denominator and analysis population.

The study is observational and non-interventional. No randomized comparator is specified, and allocation is not stated. Therefore, the record does not provide a like-for-like control comparison for estimating a treatment contrast. Routine-practice observations may reflect factors beyond treatment, and the registry record does not provide information sufficient to separate those influences.

The statistical analysis plan is not reported. The record does not describe how missing CDAI assessments were handled, whether any sensitivity analyses were conducted, or how multiple outcomes and assessment times were considered. It also does not report a sample-size justification as part of the study design. Planning illustrations are described as calculations based on the observed effect rather than the trial’s own design; no numerical illustration results are reported in the registry record.

Safety interpretation is limited as well. The record gives at-risk and affected counts and several serious-event terms, but does not report deaths or explain event relatedness, timing, or the term-level counting convention. The figures are descriptive and cannot establish causation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Observe the Safety and Efficacy of Etanercept (Enbrel®) in Patients With Moderately Active Rheumatoid Arthritis in Every Day Clinical Practice in Austria — NCT01877239.
• Registry record last updated 2018-12-03; status last verified 2018-04.
• Results first posted 2018-12-03.
• 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

NCT01877239 is a completed prospective, multicenter, non-interventional observational study of etanercept in moderately active rheumatoid arthritis in everyday clinical practice in Austria. Pfizer is listed as the sponsor. The registry reports enrollment of 111, a start date of 2012-12-10, and a primary completion date of 2016-01-07.

The primary outcome is the percentage of participants with CDAI remission at Week 24, defined as a score <= 2.8, with a specified 95% confidence interval. The Eligible Set requires consent, at least one dose of etanercept, and evaluable CDAI assessments at baseline and Week 24. Secondary outcomes concern CDAI status and change from baseline at specified assessment weeks.

The numerical primary and secondary outcome results are not reported in the registry record, and the record lists no statistical analyses. Safety figures include 8 affected among 76 at risk for serious adverse events and 16 affected among 76 at risk for other adverse events. These observational figures do not establish causation or a comparative treatment effect.