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 the Effects of RoActemra/Actemra (Tocilizumab) on Neutrophils in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic and/or Non-biologic DMARDs. (NCT01195272), a non-randomized phase 4 study. The primary outcome is Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01195272 |
| Phase | Phase 4 |
| Condition | Rheumatoid Arthritis |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled people with active rheumatoid arthritis who had an inadequate response to current biologic or non-biologic disease-modifying antirheumatic drugs. The official title specifies background non-biologic DMARDs and inadequate response to current non-biologic DMARD and/or anti-TNF therapy. The registry lists 21 enrolled participants. Its primary-endpoint population was defined as participants in the Safety Population who had follow-up data for neutrophils or at least one efficacy variable; the number analyzed for a particular endpoint could depend on the visit.
Intervention
Participants received tocilizumab, also called RoActemra/Actemra, at 8 mg/kg intravenously every 4 weeks. The brief description says treatment could be given as monotherapy or with a participant’s current non-biologic DMARD. Anticipated time on treatment was 52 weeks. The registry describes the study as open-label, so treatment assignment was not masked.
Comparator
There was no randomized comparator group. The record describes a single-group, non-randomized study, and its arm description contains only the tocilizumab group. Outcomes during treatment therefore do not constitute a like-for-like comparison with an untreated group or another treatment group. Changes over time can be described, but the design alone cannot separate treatment-associated changes from other explanations.
Primary question
The primary question concerned neutrophil apoptosis, assessed by the mean percentage of cells staining positive for Annexin V binding. The endpoint was scheduled at baseline and Weeks 4, 12 and 24, with stimulated and control samples assessed at 4 hours and 20 hours. The registry record does not report the numerical endpoint results, so the magnitude, direction, and precision of any observed changes cannot be described from the posted information.
3. Trial Design
This was a Phase 4, single-center, open-label, single-group study of tocilizumab in active rheumatoid arthritis. Allocation was non-randomized, masking was absent, and the registry describes no control arm. The study is listed as completed, with 21 participants enrolled. The registered study start was 2010-08 and the primary completion was 2012-03.
The treatment description specifies tocilizumab at 8 mg/kg by intravenous infusion every 4 weeks. Participants could receive it alone or with their current non-biologic DMARD, and anticipated time on study treatment was 52 weeks. The official title likewise describes a 52 Week study in participants on background non-biologic DMARDs who had an inadequate response to current non-biologic DMARD and/or anti-TNF therapy. These descriptions characterize the intended treatment context; details of individual participants’ treatment combinations are not reported in the registry record.
The primary outcome focused on neutrophil function and survival-related biology, measured through Annexin V binding as an indicator of apoptosis. The listed endpoint visits were baseline and Weeks 4, 12 and 24. Secondary outcomes included the Disease Activity Score Based on 28-Joint Count and the percentage of participants with acceptable and not acceptable benefit-risk assessments. The registry lists 14 outcome measures and 66 analyses, but the numerical primary outcome results are not reported in the registry record.
Because this was an uncontrolled, open-label study, its design is suited to documenting measurements and safety observations in the enrolled group, not to establishing a randomized treatment contrast. The protocol’s detailed statistical analysis plan, sample-size justification, interim analyses, and procedures for handling deviations from the intended treatment schedule are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Tocilizumab 8 Milligrams Per Kilogram (mg/kg) |
|---|---|
| STARTED | 21 |
| COMPLETED | 17 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Tocilizumab 8 Milligrams Per Kilogram (mg/kg) |
|---|---|
| Adverse Event | 1 |
| Lack of Efficacy | 3 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) Population: all participants in the Safety Population who provided follow-up data for neutrophils or at least 1 efficacy variable. n (number) equals (=) number of participants analyzed for the specified parameter at a given visit.
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: Safety Population: all participants who received at least 1 dose of tocilizumab treatment and had at least 1 post-baseline safety assessment.
| Characteristic | Unit | Tocilizumab 8 mg/kg |
|---|---|---|
| Participants analysed | 21 | |
| Age, Continuous | Years | 49.2 (SD 11.2) |
| Sex: Female, Male: Female | Participants | 18 |
| Sex: Female, Male: Male | Participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Percentage of Cells Staining Positive for Annexin V Binding in Apoptosis, measured over Visits 2, 3, 5, and 8 (Baseline and Weeks 4, 12 and 24).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage of cells staining positive |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the mean percentage of cells staining positive for Annexin V binding, reported as a percentage of cells staining positive, with standard deviation as the listed measure of dispersion. The registry describes the endpoint at baseline and Weeks 4, 12 and 24. Neutrophils were assessed in stimulated and control samples at 4 hours and 20 hours.
The biological rationale in the registry is that aging neutrophils move phosphatidylserine from the inner to the outer leaflet of the plasma membrane during early apoptosis. FITC-labeled Annexin V binds exposed phosphatidylserine; cells staining positive for Annexin V binding are treated as apoptotic in this assay. Thus, the endpoint measures the proportion of analyzed cells showing this apoptosis-associated staining, rather than a clinical symptom or a direct measure of disease activity.
In general, a mean summarizes the average observed value in an analyzed group, while the standard deviation describes the spread of individual measurements around that mean. These summaries do not by themselves show how precisely a group mean is estimated or whether a change is attributable to treatment. The numerical mean and standard deviation results for the primary endpoint are not reported in the registry record, so the actual values and their time pattern cannot be interpreted from the posted information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive constraint is that the registry identifies the primary endpoint and its planned measurement schedule but does not report numerical endpoint values. It is therefore not possible to state whether the mean percentage of Annexin V-positive cells rose, fell, or remained similar over the listed visits, nor to describe the size or precision of any change. The endpoint’s stated unit and dispersion measure do not substitute for the observed results.
The study enrolled 21 participants and used a single-group, open-label design. Measurements from the same participants across visits can describe how the recorded endpoint varied during follow-up, but there is no randomized comparison group against which to assess what might have happened without tocilizumab or under another treatment. In general, changes over time in an uncontrolled study can also reflect participant characteristics, concurrent care, measurement variability, or other changes during follow-up. The design does not isolate the contribution of any one explanation.
The registry’s description of the primary endpoint distinguishes stimulated and control samples and measurements at 4 hours and 20 hours. These conditions define different assay observations, not independent treatment arms. Without the numerical results for these conditions, their relative values and any differences across visits cannot be assessed. The number analyzed for a given parameter at a given visit is defined as the number of participants analyzed for that parameter; those visit-specific counts are not reported in the registry record.
Other registered outcomes include DAS28 and benefit-risk assessments, but the registry entries available for interpretation do not include their numerical findings. The safety information does report serious adverse events in the tocilizumab group: 4 participants were listed as affected among 21 at risk. Four serious-event terms are each listed with 4.8%. These are descriptive observations in a small, single-group study and do not establish comparative risk. The registry does not report deaths in the posted adverse-event details; deaths are not reported in the registry record as a numerical result.
Any sample-size calculations associated with the posted materials should be read as planning illustrations, not as evidence about the trial’s power after completion. The stated illustration assumptions are two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. That hypothetical two-arm planning setup is distinct from this trial’s actual single-group design. Sample-size illustrations are not observed power and do not recover missing endpoint estimates or uncertainty.
Overall, the record establishes the study question, design, population, and measurement approach, along with selected safety counts. It does not supply the primary endpoint values needed to judge the size, direction, variability, or precision of the measured neutrophil response.
9. Statistical Methods Explained
The registry identifies the primary outcome as a mean of a continuous measure: the percentage of cells staining positive for Annexin V binding. It lists standard deviation as the measure of dispersion. The endpoint was assessed at baseline and Weeks 4, 12 and 24, with stimulated and control samples measured at 4 hours and 20 hours. The registry record does not report the analysis model used to combine or compare these measurements.
What does the mean describe?
In general, a mean is the arithmetic average of observed measurements in the group being analyzed. For this endpoint, the measurement is a percentage of cells staining positive, so the mean describes the average percentage across the analyzed observations under a particular visit and assay condition. It is not the percentage of participants who had a particular outcome. The exact way cell-level readings were summarized within participants is not reported in the registry record.
In general, the standard deviation describes how spread out measurements are around their mean. A larger standard deviation indicates more variability among the measurements, while a smaller one indicates that measurements are more clustered. Standard deviation is not the same as a confidence interval: it describes observed dispersion, whereas a confidence interval is used to express uncertainty about an estimated quantity. No confidence intervals for the primary endpoint are reported in the registry record.
Why do repeated visits matter?
Measurements at multiple visits create a longitudinal structure: observations from one participant across time may be related to one another. In general, methods for repeated measurements need to account for that dependence when estimating changes or uncertainty. Treating all observations as independent when they are correlated can produce misleading uncertainty estimates. The registry lists visits and endpoint definitions but does not report whether a repeated-measures model, a visit-by-visit analysis, or another method was used.
The assessment also distinguishes stimulated from control samples and 4-hour from 20-hour measurements. These are assay conditions, and interpretation would depend on how the reported analysis handled them. The statistical approach to these conditions, including whether they were analyzed separately or jointly, is not reported in the registry record. No particular model or adjustment should therefore be assumed.
How should uncertainty be considered?
In general, an estimate describes the observed data, while an uncertainty interval describes a range of values compatible with those data under an analysis framework. A p-value, when reported, addresses compatibility with a specified null hypothesis under stated assumptions; it does not measure the size or clinical importance of an effect. The registry information does not include a primary-endpoint estimate, confidence interval, or p-value, so none can be interpreted for this endpoint.
The study’s single-group, non-randomized design is also relevant to statistical interpretation. Within-group summaries can describe measurements in participants who were analyzed, but they do not create a randomized contrast. Statistical adjustment, if used, could address only modeled factors and would not turn the design into a randomized comparison. Whether any adjustment was planned or applied is not reported in the registry record.
What do the planning illustrations represent?
The stated planning illustration assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It defines the effect to detect as a stated fraction of the observed effect. For time-to-event settings, the stated output is a total number of events; for other settings, it is participants per arm. These are planning assumptions rather than observed trial findings. They do not describe the actual allocation in this study, which was single-group and non-randomized, and they are not observed power. A sample-size justification for the actual trial is not reported in the registry record.
General caution applies when a planning illustration uses an effect observed in the same study as its reference. Such an effect can be uncertain, and a planning calculation under specified assumptions does not demonstrate that an analysis had a particular probability of detecting an effect after the study was completed. The actual planning inputs beyond the stated assumptions, and any protocol-based rationale for enrollment, are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary endpoint and secondary outcomes, as well as 14 outcome measures and 66 analyses. When many outcomes, time points, or assay conditions are examined, the chance of obtaining apparently notable findings by chance can increase. In general, multiplicity procedures can control error rates across a defined family of tests, but their use and the definition of any test family need to be specified. A multiplicity strategy is not reported in the registry record.
The primary outcome has measurements at baseline and Weeks 4, 12 and 24, with stimulated and control samples and assessments at 4 hours and 20 hours. Those dimensions create multiple possible comparisons. The registry record does not report which contrasts were primary for statistical testing, whether a hierarchy or adjustment was used, or whether analyses were prespecified beyond the endpoint description. The number of outcome measures and analyses alone does not establish that a particular multiplicity method was applied.
The primary-endpoint population is described as all participants in the Safety Population who provided follow-up data for neutrophils or at least one efficacy variable. The number analyzed for a parameter at a visit is the number of participants analyzed for that specified parameter and visit. This definition indicates that available follow-up data determine inclusion for the particular measure, but the actual visit-specific analysis counts and the extent of missing data are not reported in the registry record.
How missing measurements were handled—such as whether any imputation, complete-case analysis, or other method was used—is not reported in the registry record. The record also does not specify whether the primary analysis followed a prespecified intention-to-treat strategy, beyond the operational population description. Without those details and numerical results, it is not possible to assess the potential effect of missingness on the estimates or to determine how multiplicity was addressed.
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 8 mg/kg | 4 | 21 | 19.0% |
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 |
|---|---|
| Tocilizumab 8 mg/kg | 21 of 21 |
Most frequent serious adverse event terms
| Event term | Organ system | Tocilizumab 8 mg/kg |
|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 1 of 21 |
| Pneumonia Viral | Infections and infestations | 1 of 21 |
| Hip Fracture | Injury, poisoning and procedural complications | 1 of 21 |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | 1 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tocilizumab 8 mg/kg |
|---|---|---|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 10 of 21 |
| Lower respiratory tract infection | Infections and infestations | 9 of 21 |
| Nasopharyngitis | Infections and infestations | 8 of 21 |
| Diarrhea | Gastrointestinal disorders | 7 of 21 |
| Constipation | Gastrointestinal disorders | 4 of 21 |
| Dry mouth | Gastrointestinal disorders | 4 of 21 |
| Dyspepsia | Gastrointestinal disorders | 4 of 21 |
| Fatigue | General disorders | 4 of 21 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 4 of 21 |
| Back pain | Musculoskeletal and connective tissue disorders | 4 of 21 |
Serious events with the highest arm-level rate: neutropenia (4.8%), pneumonia viral (4.8%), hip fracture (4.8%), pulmonary embolism (4.8%).
The adverse-event information lists a tocilizumab 8 mg/kg group with 21 participants at risk for serious adverse events and 4 affected. It also lists 21 participants at risk for other adverse events and 21 affected. These are descriptive counts for the enrolled group; there is no randomized comparator from which to estimate a comparative safety difference.
The listed serious-event terms are Neutropenia, Pneumonia Viral, Hip Fracture, and Pulmonary Embolism, each reported as 4.8%. The registry record does not give further detail in the registry record about event timing, recurrence, severity criteria, individual participant overlap, or causal attribution. The percentages should therefore be read as registry-listed event figures, not as proof that tocilizumab caused an event or as a comparison with another treatment.
Deaths are not reported in the registry record as a numerical result. A missing death value should not be interpreted as confirmation that no deaths occurred. The small enrolled group and absence of a control arm also limit what these figures can establish about uncommon events or relative safety.
12. What the Result Does, and Does Not, Mean
This trial’s primary question was about a laboratory measure of neutrophil apoptosis during tocilizumab treatment in people with active rheumatoid arthritis and an inadequate response to prior DMARD therapy. The registry defines how Annexin V binding relates to exposed phosphatidylserine and specifies the visits and assay conditions. However, it does not report the numerical primary endpoint findings. The posted information therefore does not establish the direction or size of any change in the measured cell-staining percentage.
The registry does document a completed, Phase 4, single-center, open-label, single-group study with 21 enrolled participants and a planned treatment period of 52 weeks. It also lists secondary outcomes related to disease activity and benefit-risk assessment, but numerical results for those outcomes are not reported in the registry record as part of the registry entries described for interpretation. The study design can describe what was measured in its participants, but without a randomized comparator it cannot establish how those observations would differ from outcomes under another treatment or no treatment.
The safety record lists 4 participants affected by serious adverse events among 21 at risk, with four serious-event terms each listed at 4.8%. This information describes reported events in the study group. It cannot establish comparative event risk, causation, or the frequency of unlisted events. Deaths are not reported in the registry record.
These limitations do not make the study question unimportant; they define what can be concluded from the record. In general, biological measurements can help characterize a process, but their interpretation depends on numerical estimates, uncertainty, analysis methods, and the design used to support comparisons. Those elements are not all. The results should therefore be read as incomplete for assessing the primary endpoint rather than as evidence for or against a treatment effect.
13. Why This Trial Matters Statistically
Statistically, this study connects a biological question—neutrophil apoptosis—to a continuous endpoint measured repeatedly over time. Its endpoint description is specific about Annexin V binding, assay conditions, and scheduled visits. That specificity helps clarify what the measurement represents, but meaningful interpretation still requires the observed values, their variability, and the analysis used to compare them. Those numerical primary results are not reported in the registry record.
The design also illustrates why the type of comparison matters. A single-group study can document measurements and adverse events among participants receiving treatment, but it does not provide a randomized counterfactual. Even if follow-up measurements differ from baseline, the design cannot by itself distinguish treatment-associated change from other influences. This matters especially when the scientific question concerns change over time rather than a simple description at one visit.
Repeated visits and multiple assay conditions introduce analytical choices: how correlated observations are handled, which contrasts are emphasized, and how multiple analyses are interpreted. The registry lists the measurement schedule and the number of outcomes and analyses, but the statistical plan for those choices is not reported in the registry record. This makes clear that a well-described endpoint is not the same as a fully reported statistical analysis.
The safety details are also useful as descriptive reporting, while illustrating the limits of small uncontrolled datasets for comparative risk assessment. Counts and listed percentages can characterize what the record reports, but cannot establish causal attribution or compare safety with another group. Overall, the trial is statistically informative about the structure of the question and the limits imposed by design and reporting; its missing primary numerical results prevent a quantitative assessment of the endpoint itself.
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 principal trial-specific limitation is the lack of numerical primary-endpoint results in the registry record. Although the endpoint, units, dispersion measure, and visit schedule are specified, the observed means and standard deviations are not reported. This prevents assessment of direction, magnitude, variability, and precision.
The study was open-label, non-randomized, and single-group. It therefore has no randomized control group for distinguishing treatment-period observations from changes that might have occurred for other reasons. Its single-center setting and enrollment of 21 participants also define a limited study population; the registry entries do not support generalizing beyond the described participants.
The primary endpoint population depends on follow-up availability for neutrophils or at least one efficacy variable, and the number analyzed is defined separately for each parameter and visit. Actual visit-level counts, missingness patterns, and methods for handling missing data are not reported in the registry record. The statistical methods for repeated measurements, assay conditions, and multiple analyses are also not reported in the registry record.
The treatment description allows monotherapy or combination with a current non-biologic DMARD, but participant-level treatment details are not reported in the registry record. Thus, the registry entries do not establish how treatment combinations were distributed. Finally, the safety information is descriptive and has no comparison group; the registry does not provide details about event timing, recurrence, or causal attribution. Deaths are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of the Effects of RoActemra/Actemra (Tocilizumab) on Neutrophils in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic and/or Non-biologic DMARDs. — NCT01195272.
- Registry record last updated 2014-11-13; status last verified 2014-11.
- Results first posted 2014-11-13.
- 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 completed Phase 4, single-center, open-label, non-randomized, single-group study of tocilizumab in active rheumatoid arthritis. It enrolled 21 participants, with treatment described as 8 mg/kg intravenously every 4 weeks and anticipated study treatment for 52 weeks. The primary endpoint was the mean percentage of cells staining positive for Annexin V binding, assessed at baseline and Weeks 4, 12 and 24, using stimulated and control samples measured at 4 hours and 20 hours.
The numerical primary-endpoint results, analysis methods, sample-size justification, multiplicity strategy, and missing-data procedures are not reported in the registry record. The safety listing reports 4 participants affected by serious adverse events among 21 at risk, and four serious-event terms each at 4.8%. These findings are descriptive and do not provide a randomized treatment comparison.