This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study Evaluating Efficacy / Safety of Etanercept + Methotrexate Compared to Usual Treatment in Moderate RA Subjects (NCT00706797), a randomized phase 4 study. The primary outcome is Change From Baseline in Modified Total Sharp Score (TSS) at Week 52.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00706797 |
| Phase | Phase 4 |
| Condition | Rheumatoid Arthritis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 141 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Wyeth is now a wholly owned subsidiary of Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Participants had moderate rheumatoid arthritis disease activity despite methotrexate monotherapy. The primary endpoint’s stated analysis population was a modified intent-to-treat population: participants needed an erosion at randomization confirmed by a blinded expert assessor, at least 1 dose of study treatment, and data for randomization and 1 post-randomization X-ray. The registry record does not provide analyzed efficacy results for this population.
Intervention
The intervention was etanercept (ETN) 50 milligrams by subcutaneous injection once weekly, together with continuation of the participant’s current methotrexate (MTX) dose. The record says MTX could be oral, subcutaneous, or intramuscular.
Comparator
The comparator was usual care using disease-modifying antirheumatic drugs (DMARDs) drawn from a list of the six most commonly prescribed in participating countries: methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A, and gold. The record does not specify which treatment each participant in this group received.
Primary question
The primary question concerned the change from baseline in modified Total Sharp Score (TSS) at Week 52. TSS is a radiographic measure of joint damage. Although this endpoint was specified, the registry record says efficacy data were not analyzed because of early termination, so it does not establish the comparative radiographic effect.
3. Trial Design
This was a Phase 4, randomized, parallel-group study with no masking. Its official title describes it as open-label. The registry lists rheumatoid arthritis as the condition and enrollment as 141. It records a start date of 2008-09, primary completion in 2009-12, and a status of terminated. The reason for termination is not reported in the registry record.
The comparison was between etanercept added to ongoing methotrexate and usual DMARD treatment. In the etanercept-plus-methotrexate group, participants received ETN 50 milligrams by subcutaneous injection once weekly and continued their current MTX dose, which could be taken orally or administered subcutaneously or intramuscularly. Usual care could include DMARDs from the listed set of commonly prescribed drugs. The registry does not specify the treatment choices made within that group or whether the usual-care regimen changed during follow-up.
Random allocation supports a planned comparison between groups, but does not by itself resolve the limitations created by early termination or absent efficacy analyses. The open-label design means masking was not used, as stated in the record. The record does not describe allocation concealment, the randomization procedure, or any steps taken to limit bias in outcome assessment beyond the stated use of a blinded expert assessor to confirm erosions for the primary population definition.
The primary endpoint was change in modified TSS at Week 52. The registry also lists secondary radiographic and disease-activity outcomes, including erosion and joint-space-narrowing changes, radiographic progression, DAS28 thresholds, and EULAR response. The record lists 18 outcome measures and 0 analyses. It therefore identifies intended measures but does not supply analyzed comparative efficacy results for them.
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: 141 participants were randomized, 1 participant performed all the planned visits, and 140 participants were discontinued before completion of the study; 115 participants prematurely withdrew due to discontinuation of the study by the sponsor.
Overall Study
| Stage | Usual Care | ETN + MTX |
|---|---|---|
| STARTED | 70 | 71 |
| Safety Population | 63 | 71 |
| COMPLETED | 1 | 0 |
| NOT COMPLETED | 69 | 71 |
Reasons for not completing this period:
| Reason | Usual Care | ETN + MTX |
|---|---|---|
| Lack of Efficacy | 3 | 0 |
| Adverse Event | 0 | 3 |
| Withdrawal by Subject | 8 | 1 |
| Death | 1 | 0 |
| Discontinuation of study by sponsor | 52 | 63 |
| Protocol Violation | 3 | 2 |
| Lost to Follow-up | 1 | 2 |
| Other | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Modified intent-to-treat (mITT) population including all participants with an erosion at randomization confirmed by the blinded expert assessor, received at least 1 dose of subject treatment, and had data for randomization and 1 post randomization X-ray. Efficacy data not analyzed due to early termination of the study.
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.
| Characteristic | Unit | Usual Care | ETN + MTX | Total |
|---|---|---|---|---|
| Participants analysed | 63 | 71 | 134 | |
| Age Continuous | years | 57.3 (SD 12.1) | 53.8 (SD 13.1) | 55.5 (SD 12.7) |
| Sex: Female, Male: Female | Participants | 50 | 56 | 106 |
| Sex: Female, Male: Male | Participants | 13 | 15 | 28 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Modified Total Sharp Score (TSS) at Week 52, measured over Baseline, Week 52.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | scores on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in modified Total Sharp Score (TSS) at Week 52. TSS combines scores for joint-space narrowing and bone erosions, and the modified scale ranges from 0, indicating no damage, to 448, indicating bad joint status. The component ranges are 0 to 168 for joint-space narrowing and 0 to 280 for erosions. An increase from baseline represents disease progression and/or joint worsening; no change represents halting of progression; a decrease represents improvement, according to the registry description.
Radiographic scoring is used to assess structural joint changes, rather than relying only on symptoms or clinical disease-activity measures. It can therefore address a distinct aspect of rheumatoid arthritis. The endpoint’s interpretation depends on the scale and direction: higher change indicates worsening, while a lower or negative change indicates less damage or improvement relative to baseline. These are definitions of the measure, not findings from this trial.
The record specifies the measure and the Week 52 time point, but says efficacy data were not analyzed because of early termination. It does not report a group estimate, a between-group contrast, variability for the endpoint, or uncertainty around an effect. Thus the endpoint’s intended role can be described, but the record does not permit a conclusion about the observed comparative radiographic outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The key interpretive fact is that the planned primary radiographic outcome has no analyzed efficacy result in the registry record. The trial was terminated, and the record states that efficacy data were not analyzed due to early termination. There is therefore no reported between-group estimate for change in modified TSS at Week 52, and no accompanying confidence interval or test result to describe. The stated endpoint and its scale should not be mistaken for evidence of an effect.
The record lists enrollment as 141, but that figure does not establish how many participants contributed usable primary-endpoint data. The primary analysis population was restricted to participants who met the specified radiographic, treatment-exposure, and imaging-data criteria. The record does not give the number meeting those criteria, the number with Week 52 measurements, or a disposition of participants by group. It also does not report why the trial ended early.
Randomization is a design feature intended to make groups comparable at the start of a trial. It cannot make an unreported analysis available or resolve uncertainty about outcomes after early termination. Similarly, a lack of reported efficacy analysis is not evidence that groups had the same outcome, nor is it evidence that either group had a better outcome. The registry record supports neither conclusion.
The listed secondary outcomes cover radiographic changes and several measures of disease activity and response. Their presence indicates what the study planned to assess, not what the results were. The record lists 18 outcome measures and 0 analyses. Without reported estimates and their uncertainty, it is not possible to assess the direction, magnitude, or precision of any secondary comparison either.
The safety entries are descriptive counts. The record lists participants at risk and affected for serious adverse events and other adverse events in each group, as well as selected serious-event terms with percentages. These entries should not be treated as a complete comparative safety analysis: the record does not report a statistical comparison, exposure-adjusted rates, or attribution to study treatment. Deaths are not reported in the registry record. A count of events or affected participants alone does not establish whether a treatment caused an event.
Overall, the registry describes a randomized, open-label comparison and specifies a clinically relevant radiographic endpoint, but the early termination and absence of efficacy analyses prevent interpretation of comparative efficacy. Any broader conclusion would go beyond the results documented in the record.
9. Statistical Methods Explained
What does the endpoint estimate?
The primary outcome is a continuous measure: change in modified TSS from baseline to Week 52. A continuous measure can take values across a scale rather than being limited to categories such as response or nonresponse. The registry identifies the planned summary as a mean and the dispersion as a standard deviation. A mean describes the average score change in a group; a standard deviation describes how spread out individual measurements are around that group average. These summaries answer different questions and should not be confused.
For a randomized comparison, an informative treatment-effect summary would normally compare the groups’ changes, rather than interpret a change in one group alone. Within-group change can reflect many influences, including the course of disease and other care. A between-group contrast is the relevant comparative quantity, but no such efficacy estimate is reported in this record. This is general statistical interpretation, not a statement about an analysis that was performed.
What does uncertainty mean?
A confidence interval is a way to express the statistical uncertainty around an estimated effect. A narrower interval indicates greater precision under the assumptions of the analysis; a wider interval indicates less precision. It does not guarantee that the estimate is correct, and it does not replace consideration of design, missing data, or measurement quality. No confidence interval for the primary endpoint is reported in the registry record.
A hypothesis test and a confidence interval are related but serve different communicative purposes. A test assesses compatibility with a specified null hypothesis under a model; an interval displays a range of effect values compatible with the data and model at a stated confidence level. Neither can be interpreted when the relevant estimate and analysis are absent. No primary efficacy test result or p-value is reported.
Why does the study design matter?
Randomization is intended to reduce systematic differences between groups at assignment. In an open-label trial, participants and study personnel are not masked to assigned treatment, according to the registry description. Knowledge of treatment can influence behavior, co-interventions, reporting, or assessment. The record does state that a blinded expert assessor confirmed the erosion criterion used in defining the primary analysis population. It does not describe whether the radiographic readings themselves were masked or how readings were standardized, so those details are not reported in the registry record.
The parallel-group design compares groups followed under their assigned strategies, rather than using a crossover in which participants receive treatments in sequence. The registry identifies the model as parallel and the allocation as randomized. It does not report the specific randomization method or allocation-concealment procedures. Those omissions limit detailed assessment of how assignment was carried out, but they do not alter the central fact that no primary efficacy analysis is available.
How should the analysis population be read?
The modified intent-to-treat population is defined in the record by eligibility for this endpoint: a confirmed erosion at randomization, receipt of at least 1 dose of study treatment, and data for randomization and 1 post-randomization X-ray. This definition is narrower than simply referring to everyone enrolled. The record does not give the number included, explain how participants outside the definition were handled, or report an analyzed population for the primary endpoint. It says efficacy data were not analyzed due to early termination.
In general, analysis-population definitions matter because results can differ depending on who is included and how missing measurements are handled. Requiring post-randomization imaging may mean that participants without such imaging are not represented in this population. That observation describes the stated eligibility rule; it does not establish how many participants lacked imaging or whether exclusions biased an estimate. Those details are not reported in the registry record.
What do planning calculations mean?
Sample-size calculations are planning tools, not observed trial results. The planning assumptions described for the posted illustration use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. Such calculations can illustrate the amount of information a future design might seek under specified assumptions. They do not establish that a study had a particular probability of detecting an effect after it was conducted.
In particular, a planning calculation based on an observed effect is not observed power. A sample-size illustration cannot recover an efficacy result that was not analyzed, and it does not show that the trial’s original design used those assumptions. The registry record does not report the trial’s own sample-size justification or statistical plan. Since the primary efficacy analysis was not conducted as reported, planning illustrations should not be read as inferential evidence about the treatment comparison.
What can be learned from the registry entries?
The registry distinguishes specified outcomes from analyzed outcomes: it lists 18 outcome measures and 0 analyses. This distinction is important. An outcome name, scale, time point, or threshold documents what was to be measured, but does not provide an effect estimate. Statistical interpretation requires the analyzed data, a defined contrast, and information about uncertainty. Those elements are absent for the primary efficacy outcome in this record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary radiographic endpoint and secondary outcomes spanning radiographic change and clinical disease activity. These include change in erosions and joint-space narrowing at Week 52; the percentage with no radiographic progression; DAS28 improvement, remission, and low disease activity thresholds; a DAS28 response; and EULAR response. The record lists 18 outcome measures and 0 analyses.
When a study evaluates multiple outcomes or comparisons, multiplicity can increase the chance of at least one apparently notable result arising by chance if each is tested separately. Statistical plans may address this through a prespecified hierarchy, adjustment, or a clearly defined distinction between confirmatory and exploratory outcomes. The registry record does not report a multiplicity strategy or a statistical analysis plan, so it is not possible to determine how the listed secondary outcomes would have been interpreted together.
The primary analysis population is described as participants with a confirmed erosion at randomization, at least 1 dose of treatment, and data for randomization and 1 post-randomization X-ray. The record does not report the size of this population or how missing endpoint measurements were handled. It also does not describe imputation, sensitivity analyses, or other methods for assessing the impact of missing data. Because the record says efficacy data were not analyzed due to early termination, it provides no basis for assessing attrition-related bias in an efficacy estimate.
The record’s enrollment figure is not a substitute for the analyzed population size. Reasons for missing data, participant disposition by group, and the relation between missingness and outcomes are not reported in the registry record. These gaps make it impossible to evaluate the robustness of a primary or secondary efficacy result, quite apart from the fact that no efficacy analysis is reported.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Usual Care | 4 | 63 | 6.3% |
| ETN + MTX | 5 | 71 | 7.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Usual Care | 27 of 63 |
| ETN + MTX | 37 of 71 |
Most frequent serious adverse event terms
| Event term | Organ system | Usual Care | ETN + MTX |
|---|---|---|---|
| Pneumonia | Infections and infestations | 0 of 63 | 2 of 71 |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 63 | 2 of 71 |
| Cardiac failure | Cardiac disorders | 1 of 63 | 0 of 71 |
| Bursitis | Musculoskeletal and connective tissue disorders | 1 of 63 | 0 of 71 |
| Gastritis | Gastrointestinal disorders | 1 of 63 | 0 of 71 |
| Bronchopneumonia | Infections and infestations | 1 of 63 | 0 of 71 |
| Pyothorax | Infections and infestations | 0 of 63 | 1 of 71 |
| Hiatus hernia | Gastrointestinal disorders | 0 of 63 | 1 of 71 |
| Transient ischaemic attack | Nervous system disorders | 0 of 63 | 1 of 71 |
| Atrial fibrillation | Cardiac disorders | 0 of 63 | 1 of 71 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Usual Care | ETN + MTX |
|---|---|---|---|
| Hypertension | Vascular disorders | 4 of 63 | 2 of 71 |
| Injection site rash | General disorders | 0 of 63 | 4 of 71 |
| Upper respiratory tract infection | Infections and infestations | 1 of 63 | 3 of 71 |
| Urinary tract infection | Infections and infestations | 2 of 63 | 2 of 71 |
| Nausea | Gastrointestinal disorders | 3 of 63 | 0 of 71 |
| Asthenia | General disorders | 1 of 63 | 2 of 71 |
| Injection site reaction | General disorders | 0 of 63 | 3 of 71 |
| Nasopharyngitis | Infections and infestations | 0 of 63 | 3 of 71 |
| Transaminases increased | Investigations | 1 of 63 | 2 of 71 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 63 | 2 of 71 |
Serious events with the highest arm-level rate: pneumonia (2.8%), basal cell carcinoma (2.8%), cardiac failure (1.6%), bursitis (1.6%), gastritis (1.6%).
The safety entries list serious adverse events and other adverse events separately for Usual Care and ETN + MTX. For serious adverse events, the registry lists 63 participants at risk and 4 affected in Usual Care, and 71 at risk and 5 affected in ETN + MTX. For other adverse events, it lists 63 at risk and 27 affected in Usual Care, and 71 at risk and 37 affected in ETN + MTX. These are the posted counts; they should not be converted into an unreported causal conclusion.
The record also lists pneumonia and basal cell carcinoma at 2.8% each, and cardiac failure, bursitis, gastritis, and bronchopneumonia at 1.6% each among the serious-event terms. The registry does not provide context sufficient to interpret these percentages as treatment-specific risk estimates, such as an explicit denominator for each term or a comparative analysis. The percentages should therefore be read as descriptive entries, not as evidence that treatment caused an event or changed its risk.
Deaths are not reported in the registry record. It also does not report event timing, duration of exposure, event-level details, or a statistical comparison between groups. Counts can describe what was recorded, but differences in counts alone do not account for exposure, chance variation, or other factors relevant to causal interpretation.
12. What the Result Does, and Does Not, Mean
The record documents a randomized comparison of etanercept added to methotrexate versus usual DMARD treatment in participants with moderate rheumatoid arthritis disease activity who continued to have moderate activity on methotrexate monotherapy. It specifies a radiographic primary endpoint at Week 52 and describes the treatment strategies and target population. These design details establish the question the trial set out to examine.
They do not establish the answer. The registry says the trial was terminated and efficacy data were not analyzed due to early termination. It reports no primary endpoint estimate, no between-group comparison, and no precision measure. The record therefore cannot show whether the groups differed in radiographic change, the size or direction of any difference, or how uncertain an estimate would have been.
Absence of an analyzed result is not evidence of no effect, and it is not evidence of benefit or harm. It should not be interpreted as equivalence between treatments. Equivalence or non-inferiority conclusions require an appropriate design, a prespecified margin, and an analysis with adequate precision; those details and results are not reported in the registry record.
The listed secondary endpoints and safety counts provide descriptive information about what was measured or recorded, but they do not fill the primary efficacy gap. The registry does not report analyzed results for the secondary outcomes, nor does it provide a comparative safety analysis or establish causation for adverse events. The serious-event figures can be read as posted counts, with the stated limitations.
Accordingly, the most defensible interpretation is narrow: this was an early-terminated, open-label randomized study whose registry record describes its planned comparison and outcomes but does not report an analyzed efficacy result. Any conclusion about comparative effectiveness or a treatment’s clinical value would require evidence beyond the results documented.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a study question and an answer supported by analyzed data. Randomization, a defined comparison, and a specified radiographic endpoint are important design features, but they cannot substitute for an estimate and its uncertainty. The registry record states that efficacy data were not analyzed after early termination, leaving the central comparative question unresolved in the posted results.
It also illustrates why analysis populations must be described. The primary endpoint was intended for a modified intent-to-treat population with a confirmed erosion, treatment exposure, and post-randomization imaging. That definition is more specific than enrollment alone. Without the population size, participant disposition, and endpoint-data availability, readers cannot judge how much of the enrolled group could contribute to the planned radiographic assessment.
The record’s safety counts provide another useful distinction: descriptive event counts are not the same as comparative risk estimates. Causal safety interpretation depends on more than tallying events, and this record does not report a comparative safety analysis or exposure-adjusted estimates.
Finally, the trial highlights the limits of registry outcome listings. A measure, time point, or threshold can be clearly specified even when no analyzed result is posted. Keeping planned outcomes separate from analyzed findings prevents the study’s intended objectives from being mistaken for evidence. Here, the registry’s stated endpoint and design explain what was asked, while the absence of efficacy analyses limits what can be concluded.
14. 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.
Early termination is a central limitation because the registry explicitly says efficacy data were not analyzed. The record does not state why the trial was terminated, when the decision was made, or whether any interim analyses informed it. Those details are not reported in the registry record and should not be inferred.
The primary endpoint requires radiographic measurements at baseline and after randomization, and the stated modified intent-to-treat population also requires a confirmed erosion and at least 1 dose of treatment. The record does not report how many participants met these criteria, how many had Week 52 imaging, or what happened to participants without endpoint data. It therefore does not permit assessment of missingness, follow-up completeness, or the representativeness of the intended analysis population.
The study was open-label, with masking listed as none. The registry mentions a blinded expert assessor for confirming erosions at randomization, but does not report masking procedures for radiographic outcome readings or describe assessment reliability. The allocation method and concealment procedures are also not reported in the registry record.
The usual-care group could use DMARDs from a specified list, but the record does not identify the treatments actually used by participants or provide details about changes in usual care. That limits interpretation of the comparator as a single uniform regimen. The registry also does not provide the statistical analysis plan, a multiplicity approach, the original sample-size justification, or methods for handling missing data. These omissions, together with the lack of efficacy analyses, mean that neither the planned comparative estimate nor its robustness can be evaluated.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Evaluating Efficacy / Safety of Etanercept + Methotrexate Compared to Usual Treatment in Moderate RA Subjects — NCT00706797.
- Registry record last updated 2011-06-21; status last verified 2011-06.
- Results first posted 2011-01-10.
- 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.
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18. Record Summary
The registry describes a Phase 4, randomized, open-label, parallel-group trial in moderate rheumatoid arthritis. It compared etanercept 50 milligrams by weekly subcutaneous injection added to ongoing methotrexate with usual DMARD treatment. Enrollment is listed as 141; the study started in 2008-09, had primary completion in 2009-12, and is recorded as terminated.
The primary endpoint was change from baseline in modified TSS at Week 52. The registry states that efficacy data were not analyzed due to early termination. It lists 18 outcome measures and 0 analyses, so the record does not provide a comparative primary efficacy result. Adverse-event counts and selected serious-event terms are listed descriptively; deaths are not reported in the registry record. The reason for termination and the statistical analysis plan are also not reported.