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 An Open-Label Study of RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Active Rheumatoid Arthritis (NCT01951170), a na phase 3 study. The primary outcome is Change From Baseline in Genant-modified Total Sharp Score (mTSS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01951170 |
| Phase | Phase 3 |
| Condition | Rheumatoid Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 52 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
People with moderate to severe active rheumatoid arthritis. The Full Analysis Set included enrolled participants who received at least one dose of subcutaneous tocilizumab; for the primary endpoint, the analyzed number refers to participants who had a Week 24 X-ray.
Intervention
Subcutaneous tocilizumab, described as 162 mg once weekly, with study treatment lasting 24 weeks.
Comparator
None. This was a single-group study, not a randomized comparison. The registry lists no control group.
Primary question
What was the change from baseline to Week 24 in the Genant-modified Total Sharp Score, a measure combining bone erosion and joint-space narrowing?
The central question concerns structural joint damage over the study period, rather than a comparison of treatment groups. The mTSS change is defined as the Week 24 score minus the baseline score. Under the registry’s definitions, an increase represents progression or worsening, no change represents halting of progression, and a decrease represents improvement.
The record identifies this as a Phase 3, open-label study with an enrollment of 52. Because there is no concurrent comparator, the study’s primary endpoint can describe observed within-participant change among those with the required imaging, but it cannot by itself distinguish a treatment-associated change from other explanations, such as the course of disease over time or measurement variation.
The registry record does not report the primary endpoint’s median, full range, or number analyzed. It therefore does not establish from the posted result whether the observed changes tended toward progression, no change, or improvement. The study’s title refers to non-progression, but a title is not a reported outcome result.
3. Trial Design
This was a Phase 3, open-label, single-group study of tocilizumab in people with moderate to severe active rheumatoid arthritis. The registry lists enrollment of 52 and identifies Hoffmann-La Roche as the sponsor. The study began in 2013-11, had primary completion in 2015-08, and is marked completed.
Participants received subcutaneous tocilizumab. The study description specifies 162 mg once weekly, and the treatment period is described as 24 weeks. The record lists no allocation to different groups and no masking. With a single group and no comparator, the design is not a randomized controlled comparison. Open-label means treatment assignment was not concealed from participants and study personnel as masking; the registry does not describe additional blinding arrangements.
The primary outcome was change from baseline to Week 24 in the Genant-modified Total Sharp Score. The outcome description explains that the score combines bone erosion and joint-space narrowing assessed on hand, wrist, and foot images. Secondary outcomes include measures of disease activity and response, patient and physician assessments, disability, and fatigue. The record lists 20 outcome measures and 1 analysis, but does not describe how those outcomes were selected for reporting or analyzed.
The primary endpoint’s population is defined as the Full Analysis Set: enrolled participants who received at least one dose of subcutaneous tocilizumab. For this endpoint, however, the analyzed number represents participants for whom the Week 24 X-ray was performed. The actual number analyzed is not reported in the registry record. Neither a protocol-level sample-size justification nor a detailed statistical analysis plan is reported in the registry record.
The absence of a control group is central to interpreting this design. It allows description of change over time in the studied group, subject to the endpoint’s available observations, but does not provide a like-for-like estimate of what would have happened under another treatment or without study treatment.
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
| Stage | Tocilizumab |
|---|---|
| STARTED | 52 |
| COMPLETED | 51 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Tocilizumab |
|---|---|
| Investigator decision | 1 |
Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) included all enrolled participants who received at least one dose of subcutaneous tocilizumab. Here, the number analyzed represents the number of participants for whom the Week 24 X-ray was performed.
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 enrolled participants who received at least one dose of subcutaneous tocilizumab.
| Characteristic | Unit | Tocilizumab |
|---|---|---|
| Participants analysed | 52 | |
| Age, Continuous | years | 56.87 (SD 11.525) |
| Sex: Female, Male: Female | Participants | 41 |
| Sex: Female, Male: Male | Participants | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Genant-modified Total Sharp Score (mTSS), measured over From baseline to Week 24.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | units on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change from baseline to Week 24 in the Genant-modified Total Sharp Score, or mTSS. The measure combines scores for bone erosion and joint-space narrowing. Erosion is assessed across specified locations in the hands, wrists, and feet using an 8-point scale, from 0 for normal to 3.5 for very severe erosion. Joint-space narrowing is assessed at specified locations using a 9-point scale, from 0 for normal to 4.0 for definite ankylosis. The total mTSS ranges from 0, normal, to 292, the worst possible total score.
The change is calculated as the Week 24 score minus the baseline score. The registry defines an increase as disease progression or joint worsening, no change as halting of progression, and a decrease as improvement. This direction makes the endpoint interpretable as a measure of structural change during the study period. Structural imaging outcomes can complement symptom or disease-activity measures because they assess joint damage rather than only reported symptoms or clinical activity.
In general, a change score summarizes the difference between measurements taken at two times in the same participant. Its interpretation depends on the measurement’s reliability, the timing and availability of both assessments, and the distribution of changes across participants. The registry specifies that the primary result is to be expressed as a median with a full range. However, the median, range, and number analyzed are not reported in the registry record, so the magnitude and spread of the observed change cannot be described from the posted primary result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes the primary endpoint and its interpretation but does not report the result itself. In particular, it gives no median change in mTSS, no full range, and no number analyzed for the Week 24 X-ray outcome. Consequently, the posted record does not show whether the group’s typical observed change was an increase, no change, or a decrease. It also does not show how widely individual changes varied.
The endpoint is defined as Week 24 mTSS minus baseline mTSS. By that definition, positive change indicates worsening or progression, zero indicates no change, and negative change indicates improvement. These directions are part of the endpoint definition, not findings from this study. The study title’s reference to non-progression cannot substitute for the missing numerical outcome result.
The registry identifies a median and full range as the summary format. In general, the median describes the middle value when observations are ordered, while the full range gives the lowest and highest observed values. These summaries can help describe a distribution that is not well represented by a mean alone, but the range is sensitive to extreme observations and does not indicate how many participants had values near either end. Because neither statistic is posted for the primary endpoint, those features cannot be assessed.
The primary endpoint population is described as participants who received at least one dose, with the endpoint’s analyzed number restricted to those for whom a Week 24 X-ray was performed. The actual analyzed count is absent. This matters because the number with endpoint data determines how much direct information supports the reported summary, and because those with missing imaging might differ from those with imaging. The record does not provide enough information to assess that possibility.
The study was single-group and open-label, with no randomized comparator. Accordingly, even a reported within-group change would describe what was observed over time in this cohort; it would not isolate a causal effect by comparison with another group. General statistical interpretation of a before-and-after result must account for natural history, concurrent care, measurement variability, and selection into the observed-data set. The registry record does not report analyses addressing these considerations.
The record also does not report a confidence interval, hypothesis test, or other measure of uncertainty for the primary endpoint. Without such information, the precision of any estimated change cannot be assessed from the registry result. No conclusion about the treatment’s efficacy or lack of efficacy follows from the absence of a posted endpoint estimate; the appropriate conclusion is that the primary numerical result is not reported in the registry record.
9. Statistical Methods Explained
What does the primary statistic summarize?
The primary outcome is a change score for mTSS from baseline to Week 24, summarized by a median and full range. Each participant’s change is defined by subtracting the baseline score from the Week 24 score. The registry describes mTSS as a combination of bone erosion and joint-space narrowing scores based on hand, wrist, and foot imaging.
In general, a median is the central observation after values are ordered. It is less affected by extreme values than a mean, which can be useful when changes are unevenly distributed. A full range reports the minimum and maximum observed values. It conveys the extremes but does not show the density of observations between them. Neither statistic is reported for this primary endpoint in the registry record, so the planned summary format can be explained but not interpreted as a study finding.
Why does the endpoint’s analyzed population matter?
The Full Analysis Set is defined as enrolled participants who received at least one dose of subcutaneous tocilizumab. For the primary endpoint, the registry says the number analyzed represents participants for whom the Week 24 X-ray was performed. The record does not give that number. Thus, enrollment of 52 should not be mistaken for the endpoint’s analyzed count.
In general, an analysis based on participants with observed follow-up measurements can be affected if missing observations are related to outcomes. For example, if people without a Week 24 image differ systematically from those with one, a summary among imaged participants may not represent the entire enrolled group. This is a general consideration, not evidence that such a pattern occurred in this study. Reasons for missing imaging and any methods used to address it are not reported in the registry record.
What can a single-group change establish?
The study has a single-group model and no comparator. The endpoint therefore describes change over time in participants who received tocilizumab and had the required imaging. In general, a before-and-after comparison does not by itself separate a treatment effect from other changes over time. Randomized comparison groups can help address some alternative explanations by providing a concurrent reference, but this study did not include one.
The study was open-label. In general, knowledge of treatment can influence subjective reporting and some clinical assessments. The primary endpoint is based on imaging scores, but the registry does not report masking of image readers or other safeguards against assessment bias. No assumptions about such procedures can be made from the record.
How should uncertainty be considered?
In general, a confidence interval expresses a range of values compatible with the data under a specified statistical method, and its width conveys precision. A hypothesis test or p-value addresses compatibility with a defined null hypothesis under its assumptions; it does not measure the size or clinical importance of an effect. The registry record does not report a confidence interval, p-value, or other uncertainty estimate for the primary endpoint. Precision and statistical evidence for the primary result therefore cannot be assessed from the posted record.
The sample-size assumptions described for planning illustrations use 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 stated fraction of the observed effect. These are planning assumptions, not a description of this single-group trial’s actual design. Any planning counts are illustrations rather than observed power. The trial’s own sample-size justification is not reported in the registry record. The illustration’s assumptions do not establish that the study was designed around them.
What does over-dispersion mean in general?
In general, over-dispersion occurs when observed variability is greater than a statistical model expects. If a model understates variability, standard errors may be too small and uncertainty may appear narrower than warranted. This concept is relevant to some count and response models, but the registry record does not identify a model for the primary endpoint or report an over-dispersion assessment. No claim that over-dispersion occurred in this study is supported.
How should the other outcomes be viewed?
The registry lists secondary outcomes covering DAS28-ESR remission, ACR20/50/70 responses, EULAR response, patient and physician global assessments, pain, disability, and fatigue. It lists 20 outcome measures and 1 analysis. These record-level counts do not explain how many hypotheses were tested, which outcomes were considered confirmatory, or whether any multiplicity adjustment was used. The statistical analysis plan is not reported in the registry record, so the analysis strategy and the status of individual outcomes cannot be reconstructed from these counts alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures and 1 analysis. It does not describe the hierarchy or prioritization of outcomes, whether each secondary outcome was formally tested, or whether any adjustment was made for multiple comparisons. The multiplicity plan is not reported in the registry record. In general, when many hypotheses are tested, the chance of at least one apparently unusual result can increase; adjustment procedures or a prespecified testing hierarchy can address that issue. This is a general statistical consideration, not a statement about what happened in this study.
The primary endpoint’s analysis population is described as the Full Analysis Set, consisting of enrolled participants who received at least one dose. The endpoint-specific analyzed number refers to participants with a Week 24 X-ray. The record gives enrollment of 52 but does not report how many participants had the required Week 24 image or the primary outcome value. Enrollment therefore cannot be treated as the number contributing to the primary endpoint.
The registry does not report reasons for unavailable Week 24 imaging, the amount or pattern of missing data, or any method for handling missing observations. It also does not report imputation procedures or sensitivity analyses. In general, missing-data assumptions matter because conclusions based on observed cases may depend on whether missingness is related to participant characteristics or outcomes. Without the missingness details and analysis methods, the effect of unavailable imaging cannot be evaluated from the registry record.
The record does not provide a detailed analysis plan, so it is not possible to determine whether the posted outcomes reflect prespecified analyses or whether any additional analyses were conducted. No unreported methods or safeguards should be inferred.
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 |
|---|---|---|---|
| Tocilizumab | 3 | 52 | 5.8% |
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 |
|---|---|
| Tocilizumab | 35 of 52 |
Most frequent serious adverse event terms
| Event term | Organ system | Tocilizumab |
|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 1 of 52 |
| Ankle fracture | Injury, poisoning and procedural complications | 1 of 52 |
| Asthma | Respiratory, thoracic and mediastinal disorders | 1 of 52 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tocilizumab |
|---|---|---|
| Upper respiratory tract infection | Infections and infestations | 15 of 52 |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 11 of 52 |
| Neutropenia | Blood and lymphatic system disorders | 6 of 52 |
| Diarrhoea | Gastrointestinal disorders | 5 of 52 |
| Mouth ulceration | Gastrointestinal disorders | 4 of 52 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 4 of 52 |
| Paraesthesia | Nervous system disorders | 4 of 52 |
| Nausea | Gastrointestinal disorders | 3 of 52 |
| Contusion | Injury, poisoning and procedural complications | 3 of 52 |
| Laceration | Injury, poisoning and procedural complications | 3 of 52 |
Serious events with the highest arm-level rate: anaemia (1.9%), ankle fracture (1.9%), asthma (1.9%).
For the tocilizumab group, the registry lists 52 participants at risk for serious adverse events and 3 participants affected. It lists 52 at risk for other adverse events and 35 affected. These are participant counts in the posted safety record; they are not event rates adjusted for time at risk, and the record does not describe exposure-adjusted analyses.
The registry lists Anaemia, Ankle fracture, and Asthma among the top serious adverse event terms, each at 1.9%. These entries identify terms and percentages as recorded; they do not provide a complete account of all event details, timing, duration, severity, or relatedness to treatment. The registry record does not report a death count.
In general, a count of participants affected is different from a count of total events, because one participant may experience more than one event. The posted summary does not give enough detail to determine event recurrence or the circumstances around each event. These safety figures describe what the registry reports for this group and should not be read as a comparison with another treatment or with an untreated group. No control group is listed, so comparative safety conclusions cannot be drawn from these counts alone.
12. What the Result Does, and Does Not, Mean
The study record establishes that a completed, open-label, single-group study enrolled 52 participants with moderate to severe active rheumatoid arthritis and assessed change in mTSS from baseline to Week 24. It also defines how the endpoint is scored and the direction assigned to an increase, no change, or decrease. The registry lists several secondary outcome domains and safety counts.
However, the primary endpoint’s numerical result is not reported in the registry record. The median change, full range, and number analyzed are absent. As a result, the posted record does not establish the direction, size, or variability of the primary endpoint change. The study title’s emphasis on non-progression is not itself evidence that non-progression was observed.
Even if the within-group endpoint result were available, the single-group design would limit what it could establish. In general, observing change over time does not identify how much of that change is attributable to an intervention, because there is no concurrent randomized comparator to help distinguish treatment-associated change from other influences. The open-label design is also relevant when interpreting outcomes that may be affected by awareness of treatment, although the primary outcome is an imaging score and the registry does not describe image-reader masking.
The safety record reports that 3 of 52 participants were affected by serious adverse events and 35 of 52 by other adverse events. These are descriptive counts, not comparative estimates. The record does not report a death count or detailed event narratives. It therefore does not support a comparison of risk against another group or a comprehensive assessment of the nature and timing of events.
In general, a study result should be interpreted alongside its uncertainty, analysis population, missing-data handling, and design. The registry record does not report uncertainty estimates for the primary result, its actual analyzed count, a detailed missing-data approach, or a full statistical analysis plan. Those absences constrain interpretation; they do not establish that an effect was absent or that the intervention had no effect.
13. Why This Trial Matters Statistically
This trial is statistically notable for the contrast between its title’s focus on non-progression of structural joint damage and the information available in the posted primary outcome record. The registry explains a clinically interpretable imaging measure, defines its direction, and specifies a median and full-range summary. But it does not provide the numerical primary result or the number of participants contributing to it. This illustrates why an endpoint description and an outcome finding are not interchangeable.
The design also makes the inferential scope clear. A single-group, open-label study can describe observed changes among participants who received treatment, but it does not offer a randomized comparator for estimating a between-group treatment effect. The endpoint’s population further depends on Week 24 imaging, while the actual number with that imaging is not stated. Readers therefore need both the design details and the endpoint-specific reporting to assess what the data can support.
The record includes a range of secondary measures spanning disease activity, response criteria, patient and physician assessments, disability, and fatigue. Such breadth can provide different perspectives on disease status, but interpretation depends on knowing which analyses were planned, how multiplicity was handled, and how missing data were addressed. Those methods are not described in the registry record.
More broadly, this study illustrates a general principle of clinical-trial reporting: a protocol-defined measure, an enrolled sample, and safety counts do not replace a reported estimate with its analysis population and uncertainty. Transparent reporting of those elements is essential for distinguishing what was measured from what the observed data show and how precisely they show it.
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.
Several limitations specific to this record restrict interpretation. First, the registry does not report the primary endpoint’s median change, full range, or endpoint-specific analyzed count. The principal result therefore cannot be characterized in magnitude, direction, or spread.
Second, the primary endpoint depends on a Week 24 X-ray, but the record does not state how many participants had that image. Although enrollment is listed as 52, that number is not identified as the primary endpoint’s analyzed sample. Reasons for absent imaging, missing-data methods, and sensitivity analyses are not reported.
Third, the single-group design has no randomized comparator. Any reported within-group change would not by itself establish the change that would have occurred under a different treatment or without study treatment. The open-label design is recorded, while image-reader masking or other assessment safeguards are not described.
Fourth, the registry does not report a detailed statistical analysis plan, a sample-size justification, or a multiplicity strategy. It lists 20 outcome measures and 1 analysis, but those counts do not establish how outcomes were prioritized or tested. No confidence interval or hypothesis-test result for the primary outcome is reported.
Finally, the safety record provides affected-participant counts and selected serious adverse event terms, but not detailed event narratives, timing, relatedness, or a death count. These limits apply to what can be concluded from the registry record; they do not indicate what might be available in other materials.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Open-Label Study of RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Active Rheumatoid Arthritis — NCT01951170.
- Registry record last updated 2016-09-21; status last verified 2016-08.
- Results first posted 2016-09-21.
- 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 record describes NCT01951170, a completed Phase 3, open-label, single-group study sponsored by Hoffmann-La Roche. It enrolled 52 participants with moderate to severe active rheumatoid arthritis. Participants received subcutaneous tocilizumab, described as 162 mg once weekly for 24 weeks. The study began in 2013-11 and reached primary completion in 2015-08.
The primary endpoint was change from baseline to Week 24 in Genant-modified Total Sharp Score, summarized by a median and full range. The endpoint combines bone erosion and joint-space narrowing scores. The registry does not report the primary numerical result or the number analyzed for that endpoint.
Secondary outcomes cover disease activity, response criteria, patient and physician assessments, disability, and fatigue. The safety record lists 3 participants affected by serious adverse events and 35 by other adverse events, each among 52 at risk. A death count is not reported in the registry record. The record does not describe a randomized comparator, a detailed analysis plan, a multiplicity approach, or methods for handling missing data.