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 A Study of Tocilizumab (RoActemra) in Tocilizumab-Naive Participants With Rheumatoid Arthritis and Inadequate Response to Non-Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) and/or Biologic Therapy (NCT02001987), a na phase 3 study. The primary outcome is Change From Baseline in Disease Activity Score Based on 28-joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02001987 |
| Phase | Phase 3 |
| Condition | Rheumatoid Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 139 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants had moderate to severe active rheumatoid arthritis and were tocilizumab-naive. The study description focuses on people with an inadequate response or intolerance to non-biologic conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biologic therapy. The registry lists 139 participants enrolled.
Intervention
Participants received subcutaneous tocilizumab at a dose of 162 mg once a week for the 24-week core study period. It was used either alone or with methotrexate or other csDMARDs, at the investigator’s discretion.
Comparator
There was no separate control group. The study was open-label, single-group, and not randomized. The monotherapy and combination-therapy groups were not described as randomized, like-for-like treatment arms, so their outcomes should not be read as a controlled comparison.
Primary question
The primary outcome was the mean change from baseline to Week 24 in the Disease Activity Score based on 28 joints and erythrocyte sedimentation rate (DAS28-ESR). The registry record does not report the observed change, its standard deviation, or an inferential estimate, so the magnitude and precision of the primary result are not reported in the registry record.
3. Trial Design
This was a Phase 3, multicenter, open-label, single-group study sponsored by Hoffmann-La Roche. The registry lists an enrollment of 139 and a completed status. The recorded start was 2014-01 and the primary completion was 2015-12. The study description says it had two parts and assessed tocilizumab as monotherapy or in combination with methotrexate or other csDMARDs. The available treatment description specifies weekly subcutaneous tocilizumab for a 24-week core period; further details of the second part are not reported in the registry record.
Open-label means participants and investigators were not masked to treatment assignment. In this study there was no randomized assignment and no separate control group. As a result, change over time can be described, but the design does not isolate the treatment effect from other influences such as the natural course of disease, expectations, changes in accompanying care, or selection of participants. These are general considerations for an uncontrolled, open-label design, not findings about what occurred in this study.
The treatment approach allowed monotherapy or combination therapy at investigator discretion. The registry reports 43 participants in the tocilizumab monotherapy group and 96 in the combination group, alongside the overall group of 139. Because treatment composition was not randomized, differences between these groups could reflect differences in the participants or clinical decisions as well as any difference in treatment context. The registry record does not report a protocol-defined comparative analysis between those groups.
The record gives the study’s status, enrollment, treatment description, and outcome definitions, but does not report a sample-size justification, detailed allocation procedures, or a statistical analysis plan. Those design details should not be inferred from the phase designation or from the number enrolled.
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: Analyses of primary/ secondary outcome measures were planned and performed in different analysis populations described in respective analysis population descriptions. Analyses of few secondary outcome measures and adverse events were planned and performed according to predefined subgroup populations and have been presented accordingly.
Core Study Period (24 Weeks)
| Stage | TCZ - All Participants |
|---|---|
| STARTED | 139 |
| COMPLETED | 116 |
| NOT COMPLETED | 23 |
Reasons for not completing this period:
| Reason | TCZ - All Participants |
|---|---|
| Adverse Event | 9 |
| Death | 1 |
| Non-Serious Hypersensitivity Reaction | 2 |
| Physician Decision | 1 |
| Withdrawal by Subject | 4 |
| Protocol Violation | 3 |
| Lack of Efficacy | 3 |
LTE Period (52 Weeks)
| Stage | TCZ - All Participants |
|---|---|
| STARTED | 116 |
| COMPLETED | 107 |
| NOT COMPLETED | 9 |
Reasons for not completing this period:
| Reason | TCZ - All Participants |
|---|---|
| Lost to Follow-up | 2 |
| Physician Decision | 2 |
| Withdrawal by Subject | 1 |
| Lack of Efficacy | 1 |
| Other | 3 |
Analysis population for the primary outcome, as defined in the registry: FAS; Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure. In case of missing value, Last Observation Carried Forward (LOCF) method 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.
Population: Full Analysis Set (FAS) included all participants who received at least one dose of SC TCZ.
| Characteristic | Unit | TCZ - All Participants |
|---|---|---|
| Participants analysed | 139 | |
| Age, Continuous | years | 57.3 (SD 13.8) |
| Sex: Female, Male: Female | Participants | 103 |
| Sex: Female, Male: Male | Participants | 36 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Disease Activity Score Based on 28-joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24, measured over Baseline, Week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline to Week 24 in DAS28-ESR, reported as a mean on a scale with units. DAS28-ESR combines erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), and the patient global assessment of disease activity (PGA). Joint counts cover 28 joints, while PGA is assessed on a 100-millimeter visual analog scale. Higher DAS28-ESR scores indicate higher disease activity; a negative change from baseline indicates improvement in the score.
Using a composite measure can describe several aspects of disease activity in one outcome. In general, repeated measurements of a continuous score can show how the group’s average value changes over time. The registry also lists secondary outcomes based on DAS28-ESR, ACR response criteria, and EULAR response, which address related but distinct summaries of participants’ disease activity or response.
The primary endpoint is defined, but its observed mean change and standard deviation are not reported in the registry record. The record states that the analyzed population was the full analysis set and that last observation carried forward was applied when values were missing. Without the posted primary outcome estimate and its variability, the direction and size of the group’s average change, and the precision of that estimate, cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically relevant measurement question: how the average DAS28-ESR score changed from baseline to Week 24 among participants treated with tocilizumab. However, it does not report the numerical primary outcome result. In particular, the mean change and standard deviation are not reported in the registry record. Therefore, the direction, magnitude, and variability of the observed primary outcome cannot be described from this record, and no conclusion about statistical precision can be drawn.
The study’s single-group design is important when interpreting any change over time. A before-and-after comparison can describe how outcomes changed among enrolled participants, but without a randomized control group it cannot determine how much of that change was caused by the treatment. General influences on a before-and-after result can include the underlying course of the condition, concurrent treatments, changes in care, participant expectations, and regression to the mean. The registry record does not establish the contribution of any of these influences.
The two treatment contexts—tocilizumab alone and tocilizumab with methotrexate or other csDMARDs—also do not constitute a randomized comparison. Their group sizes are reported as 43 and 96, respectively, but the record does not describe randomized assignment between them. Any difference between their outcomes, if reported elsewhere, could not automatically be attributed to the accompanying medication because treatment choice was at investigator discretion and group comparability is not established.
Several secondary outcomes are listed, including DAS28-ESR changes and response categories at Week 24 and other assessments. Listing outcome definitions does not itself provide their results. The registry record reports 53 outcome measures and 0 analyses in the information available for this analysis; numerical secondary outcome results and inferential estimates are not reported in the registry record.
The adverse-event counts describe events recorded among participants at risk, but they are not substitutes for the primary efficacy result. Nor do they establish comparative safety, because there was no control group. A careful reading therefore distinguishes what is described—the trial design, endpoint definition, participant counts, and adverse-event counts—from what cannot be evaluated from the record: the estimated primary outcome change, its uncertainty, and a controlled treatment effect.
9. Statistical Methods Explained
What does a mean change describe?
For a continuous outcome such as DAS28-ESR, a mean change summarizes the average difference between participants’ baseline and follow-up measurements. A negative value for this outcome would indicate an average decrease in disease-activity score, which the registry defines as improvement in disease activity. This is a general explanation of the measure’s direction, not a statement of the study’s result. The observed mean change is not reported in the registry record.
A mean provides a compact group summary, but it does not show how individual participants’ changes were distributed. The standard deviation describes spread around the mean. A larger spread means participant changes varied more widely around the group average; it is not the same quantity as the uncertainty in the estimated mean. The registry defines the primary outcome as a mean with standard deviation, but neither the numerical mean change nor its standard deviation is reported in the registry record.
How would uncertainty be described?
In general, a confidence interval gives a range of values compatible with the observed data under the statistical method used. Its width reflects precision: a narrower interval indicates a more precise estimate, while a wider interval indicates greater uncertainty. A confidence interval for a mean change would help readers assess not only the estimated average but also the uncertainty around it. No confidence interval for the primary outcome is reported in the registry record.
A p-value, when reported, summarizes how unusual the data would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an effect. The registry information available for this analysis contains no inferential analyses; a p-value for the primary outcome is not reported in the registry record. It would be inappropriate to infer one from the study design or outcome definition.
Why does the design affect the analysis?
In a randomized controlled trial, random assignment can support comparisons between groups by balancing measured and unmeasured characteristics on average. This study was not randomized and had a single group. A within-group change can therefore describe the participants’ observed course over time, but it does not provide the same controlled contrast. General statistical adjustment cannot, by itself, guarantee removal of bias from factors that were not measured or adequately modeled. The registry record does not report an adjusted causal analysis.
The monotherapy and combination groups also need cautious interpretation. Treatment context was at investigator discretion, rather than assigned in a like-for-like randomized comparison. General concerns include confounding by indication: clinical features that influence a treatment choice may also relate to outcome. The record does not report enough information to assess whether the groups were comparable or whether an analysis accounted for such differences.
Why can over-dispersion matter?
Over-dispersion is a general issue for count or binary-outcome models when observed variability is greater than the model assumes. If unaccounted for, standard errors can be too small and confidence intervals too narrow, creating an overly precise impression. This concept is relevant to some analyses of event counts or response proportions, but the registry information does not report a fitted model, model diagnostics, or an analysis requiring an over-dispersion assessment. No claim can be made about whether it arose in this study.
What can the posted outcome definitions establish?
The registry lists 53 outcome measures, including the primary continuous outcome and secondary measures based on DAS28-ESR, ACR response, and EULAR response. The outcome definitions identify what was intended to be measured and at what assessments; they do not establish that a result was statistically significant or clinically important. The registry information available for this analysis lists 0 analyses, and numerical estimates for the primary outcome are not reported in the registry record.
General statistical interpretation requires attention to the estimate, its uncertainty, the analysis population, missing data, and the design that generated the data. In this case, the record identifies a full analysis set and a missing-value method for the primary outcome, but does not report the primary estimate or uncertainty. Accordingly, no recalculated estimate, comparison, or power conclusion can be drawn from the registry information. Any sample-size planning illustration is conceptually separate from observed study results and does not constitute observed power.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 53 outcome measures, including the primary DAS28-ESR change and multiple secondary outcomes based on disease-activity scores and response criteria. When many outcomes or repeated assessments are considered, the chance of obtaining at least one apparently notable result can increase. General statistical approaches to multiplicity may include defining a hierarchy of outcomes or adjusting inference across tests. The registry record does not report a multiplicity strategy, a testing hierarchy, or an analysis plan. The presence of numerous listed outcomes does not establish that all were analyzed or that any particular adjustment was used.
The primary outcome population is described as the full analysis set. The registry states that last observation carried forward was applied in case of a missing value. This method uses an earlier observed value in place of a missing later value. As a general matter, that approach assumes the carried-forward value is a suitable representation of the missing measurement; if participants’ outcomes would have changed after their last observation, the method may not reflect that change. The record does not report how many primary outcome values were missing, the reasons for missingness, or sensitivity analyses assessing alternative assumptions.
The registry record also does not report details about exclusions from the full analysis set or how missing data were handled for each secondary outcome. These omissions limit assessment of how robust the results would be to different analysis-population or missing-data choices. Numerical primary and secondary outcome results are not reported in the registry record, so the influence of multiplicity and missing-data decisions on the findings cannot be evaluated from the information available.
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 |
|---|---|---|---|
| TCZ MONO - All Participants | 5 | 43 | 11.6% |
| TCZ COMBO - All Participants | 11 | 96 | 11.5% |
| TCZ - All Participants | 16 | 139 | 11.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| TCZ MONO - All Participants | 28 of 43 |
| TCZ COMBO - All Participants | 65 of 96 |
| TCZ - All Participants | 93 of 139 |
Most frequent serious adverse event terms
| Event term | Organ system | TCZ MONO - All Participants | TCZ COMBO - All Participants | TCZ - All Participants |
|---|---|---|---|---|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 2 of 43 | 1 of 96 | 3 of 139 |
| Abdominal pain | Gastrointestinal disorders | 1 of 43 | 0 of 96 | 1 of 139 |
| Diarrhoea | Gastrointestinal disorders | 1 of 43 | 0 of 96 | 1 of 139 |
| Dyspepsia | Gastrointestinal disorders | 1 of 43 | 0 of 96 | 1 of 139 |
| Gastric ulcer | Gastrointestinal disorders | 0 of 43 | 1 of 96 | 1 of 139 |
| Gastric volvulus | Gastrointestinal disorders | 0 of 43 | 1 of 96 | 1 of 139 |
| Intestinal ischaemia | Gastrointestinal disorders | 0 of 43 | 1 of 96 | 1 of 139 |
| Vomiting | Gastrointestinal disorders | 1 of 43 | 0 of 96 | 1 of 139 |
| Disseminated tuberculosis | Infections and infestations | 0 of 43 | 1 of 96 | 1 of 139 |
| Meningitis tuberculous | Infections and infestations | 0 of 43 | 1 of 96 | 1 of 139 |
Most frequent non-serious adverse event terms
| Event term | Organ system | TCZ MONO - All Participants | TCZ COMBO - All Participants | TCZ - All Participants |
|---|---|---|---|---|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 8 of 43 | 11 of 96 | 19 of 139 |
| Bronchitis | Infections and infestations | 7 of 43 | 9 of 96 | 16 of 139 |
| Rhinitis | Infections and infestations | 2 of 43 | 11 of 96 | 13 of 139 |
| Nasopharyngitis | Infections and infestations | 4 of 43 | 8 of 96 | 12 of 139 |
| Asthenia | General disorders | 1 of 43 | 9 of 96 | 10 of 139 |
| Alanine aminotransferase increased | Investigations | 2 of 43 | 8 of 96 | 10 of 139 |
| Headache | Nervous system disorders | 2 of 43 | 8 of 96 | 10 of 139 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1 of 43 | 8 of 96 | 9 of 139 |
| Back pain | Musculoskeletal and connective tissue disorders | 4 of 43 | 5 of 96 | 9 of 139 |
| Diarrhoea | Gastrointestinal disorders | 3 of 43 | 6 of 96 | 9 of 139 |
Serious events with the highest arm-level rate: rheumatoid arthritis (4.7%), abdominal pain (2.3%), diarrhoea (2.3%), dyspepsia (2.3%), vomiting (2.3%).
The registry reports serious adverse events for the monotherapy group, the combination group, and the overall tocilizumab group. Serious adverse events were recorded for 5 of 43 participants in the monotherapy group, 11 of 96 in the combination group, and 16 of 139 overall. Other adverse events were recorded for 28 of 43, 65 of 96, and 93 of 139, respectively. These are participant counts in the registry’s safety summaries, not estimates from a controlled comparison.
The record lists serious-event terms and percentages: rheumatoid arthritis, 4.7%; abdominal pain, diarrhoea, dyspepsia, vomiting, and lung disorder, each 2.3%. These entries describe reported terms and percentages; they do not establish that every event was caused by treatment. The record does not provide a control group for comparison, and the serious-event categories should not be interpreted as comparative risks against an untreated or alternative-treatment group.
Deaths are recorded as null in the safety information. That means a death count is not reported in the registry record; it should not be read as a count of zero. The safety summaries also do not, on their own, describe event timing, duration, recurrence, or clinical attribution. The listed counts are therefore descriptive and should be read with the study’s open-label, single-group design in mind.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase 3, open-label, single-group study enrolled 139 tocilizumab-naive participants with active rheumatoid arthritis and assessed a 24-week treatment period. It defines a primary outcome based on change in DAS28-ESR from baseline to Week 24 and describes use of the full analysis set with last observation carried forward for missing values. It also reports adverse-event counts and lists secondary outcomes.
Those design and outcome details do not establish the size or precision of the primary outcome change. The numerical primary result, its standard deviation, and any confidence interval or p-value are not reported in the registry record. Consequently, the record does not support a statement about how large the average change was or how certain that estimate would be. The absence of an inferential result is not evidence that there was no change; it means the result is not reported in the registry record.
The single-group design also limits causal interpretation. Any observed change from baseline would describe what happened among participants during the study, not what would have happened to comparable participants under a different treatment. Without a randomized control group, the study cannot separate a treatment-associated change from other time-related or care-related influences. The monotherapy and combination groups are not a randomized comparison, so their counts do not establish which treatment context produced a better outcome.
The adverse-event counts are descriptive. They do not demonstrate comparative safety, and the reported event terms do not by themselves establish treatment causation. A null entry for deaths is not a reported zero. Overall, the record is useful for understanding the study’s design, endpoint definition, analysis-population description, and reported safety counts, while leaving the central numerical efficacy result and its uncertainty unavailable in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between defining an outcome and reporting its result. The registry specifies a continuous primary measure, the assessment time, the direction of improvement, and the use of a mean and standard deviation. Those details are necessary to understand an endpoint, but they are not enough to evaluate its observed magnitude or precision. The primary numerical result is not reported in the registry record.
The design also illustrates why the comparison structure matters. A single-group study can describe change over time, but it lacks a concurrent randomized control group for estimating a treatment contrast. The study’s monotherapy and combination contexts may be clinically distinct, yet investigator discretion rather than random assignment means they cannot be treated as equivalent groups for causal comparison without further evidence and methods. That distinction is fundamental when interpreting trial results.
The registry further identifies numerous secondary outcomes and a missing-data approach for the primary endpoint. These details raise important statistical questions about multiplicity, analysis populations, and assumptions behind handling missing observations. Because the record does not report an analysis plan or outcome estimates, those questions remain unresolved rather than answered by the outcome listings.
Finally, the safety counts show how descriptive event summaries can be presented without implying comparative risk. Counts from an uncontrolled study can describe events among participants, but they do not supply a counterfactual comparison. Taken together, the record highlights that statistical interpretation depends not only on outcome definitions and participant counts, but also on complete estimates, uncertainty measures, analysis choices, and a design capable of answering the intended comparison.
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.
The most direct limitation of the registry information is that the primary outcome’s numerical result is not reported in the registry record. The mean change and standard deviation are absent, as are a confidence interval and p-value. This prevents assessment of the observed size, variability, and precision of the primary outcome. Numerical results for the listed secondary outcomes are also not reported in the registry record.
The study’s open-label, single-group design means there is no randomized control group to provide a concurrent comparison. The record therefore cannot distinguish a change occurring during follow-up from a change attributable to treatment. In addition, the choice between monotherapy and combination therapy was at investigator discretion. The reported groups are not a like-for-like randomized comparison, and the registry does not report a comparative analysis that would address differences between them.
For the primary outcome, the registry identifies the full analysis set and says last observation carried forward was used when values were missing. It does not report the number or pattern of missing values, reasons for missingness, or sensitivity analyses. Those omissions prevent assessment of how dependent the result might be on the missing-data method. The record also does not report a multiplicity plan despite listing 53 outcome measures.
Sample-size justification, detailed statistical planning, and a reported analysis are not available in the registry record. The registry’s null entry for deaths does not provide a death count. These limitations do not establish that the trial’s analyses were inadequate; they define what cannot be evaluated from the information reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Tocilizumab (RoActemra) in Tocilizumab-Naive Participants With Rheumatoid Arthritis and Inadequate Response to Non-Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) and/or Biologic Therapy — NCT02001987.
- Registry record last updated 2018-11-02; status last verified 2018-03.
- Results first posted 2018-11-02.
- 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
NCT02001987 is a completed Phase 3, multicenter, open-label, single-group study sponsored by Hoffmann-La Roche. The registry lists 139 participants and describes tocilizumab-naive participants with active rheumatoid arthritis and an inadequate response or intolerance to prior therapy. Treatment was subcutaneous tocilizumab at 162 mg once a week, alone or with methotrexate or other csDMARDs, for the 24-week core period.
The primary endpoint was mean change in DAS28-ESR from baseline to Week 24. The full analysis set was used, with last observation carried forward for missing values. The registry record does not report the numerical primary outcome result or its uncertainty. It lists 53 outcome measures and 0 analyses in the available information. Safety summaries include serious and other adverse-event counts; a death count is not reported in the registry record. The uncontrolled, open-label design does not provide a randomized treatment comparison.