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 MabThera (Rituximab) in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate (NCT01000610), a na phase 4 study. The primary outcome is Number of Participants Reporting Adverse Events (AEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01000610 |
| Phase | Phase 4 |
| Condition | Rheumatoid Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 18 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled 18 participants with active rheumatoid arthritis who had an inadequate response to prior methotrexate treatment. The registry describes a safety population as participants who received any part of an infusion of study medication. Further eligibility details and participant characteristics are not reported in the registry record.
Intervention
Participants received rituximab, identified as MabThera or Rituxan, as an intravenous infusion of 1000mg on days 1 and 15, alongside background methotrexate at 10-25mg by mouth or under the skin weekly. The summary also describes possible re-treatment for eligible participants after the initial 24 weeks. The role and administration details of methylprednisolone are not reported in the registry record.
Comparator
There was no comparison group: the study is described as open-label and single-group, with allocation recorded as NA and masking as NONE. The registry therefore does not offer a concurrent control for separating treatment-associated changes from changes over time, background care, or other influences.
Primary question
The primary endpoint asks how many participants report adverse events during the specified follow-up. The registry also lists disease activity and bone-density outcomes, including DAS28 change through Week 24. However, outcome values and analysis results for these measures are not reported in the registry record. The posted figures describe safety counts, not a controlled test of efficacy.
3. Trial Design
This was a Phase 4, open-label, single-group study sponsored by Hoffmann-La Roche. The registry lists a start date of 2008-03-17, primary completion on 2012-05-16, a completed status, and enrollment of 18. With no random allocation or masking, participants and study personnel were not blinded to the treatment. No comparator arm is described.
The study summary describes rituximab infusions of 1000mg on days 1 and 15, with background methotrexate of 10-25mg weekly by mouth or under the skin. After the initial 24 weeks, eligible participants could receive up to 3 re-treatments. The anticipated time on study treatment is described as 1-2 years, while the primary endpoint timeframe gives scheduled safety assessments through a total of 104 weeks. These statements describe the registry summary; further details about treatment delivery, eligibility for re-treatment, or adherence are not reported in the registry record.
The primary outcome is the number of participants reporting adverse events in the safety population, defined as participants who received any part of an infusion of study medication. Listed secondary outcomes concern percentage change in DAS28 from baseline to Week 24, the percentage whose DAS28 improved by >1.2 at Week 24, and bone-density change among participants untreated with bisphosphonates. The registry gives no outcome analysis results for these measures. Because the design has no control group, it is primarily descriptive for the posted safety counts and cannot provide a like-for-like treatment comparison.
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 | Rituximab |
|---|---|
| STARTED | 18 |
| COMPLETED | 12 |
| NOT COMPLETED | 6 |
Reasons for not completing this period:
| Reason | Rituximab |
|---|---|
| Adverse Event | 1 |
| Lost to Follow-up | 4 |
| Treatment failure | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety Population: Included all participants who have received any part of an infusion of study medication.
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: Intent-to-Treat (ITT) population: All participants who received any part of an infusion have been included in the ITT analysis. Participants who prematurely withdrew from the study for any reason and for whom an assessment was not performed for whatever reason, were still included in the ITT analyses.
| Characteristic | Unit | Rituximab |
|---|---|---|
| Participants analysed | 18 | |
| Age, Continuous | years | 53.4 (SD 7.91) |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Reporting Adverse Events (AEs), measured over Days 1 and 15, every 8 weeks up to Week 24 and and then every 3 months up to 18 months for a total of 104 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | number of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants reporting adverse events. The registry defines the safety population as participants who received any part of an infusion of study medication. Its timeframe describes assessment on days 1 and 15, every 8 weeks up to Week 24, and then every 3 months up to 18 months for a total of 104 weeks. The registry wording repeats “and” before the later assessment schedule; further clarification is not reported in the registry record.
Counting participants with an event is a direct way to summarize how many people in the observed safety population experienced reported adverse events during follow-up. It is not the same as counting every event: a participant may have more than one event, and the endpoint as worded counts participants. The posted record does not give event-level timing or the number of events per participant.
In general, safety endpoints are used to describe harms observed during a study, alongside the treatment and follow-up context. Here, the endpoint is not a comparison of event risk against an untreated or active control group. It also does not by itself establish that treatment caused an event. The posted results include participant counts for serious and other adverse events, but an analyzed primary-endpoint result with an uncertainty interval is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety figures list 18 participants at risk for serious adverse events, with 6 affected, and 18 at risk for other adverse events, with 9 affected. These are descriptive counts from the single rituximab group. They show that adverse events were reported among participants in this study, but the registry record does not provide an inferential analysis, uncertainty intervals, or a comparator against which to assess the counts.
The record lists six serious adverse-event terms, each with a reported frequency of 5.6%: Pulmonary embolism, Persistent thrombopenia, Rectal bleeding, Ventricular Extra systolebigeminy, Severe infusion reaction, and Dyspnea. Those entries should be read as listed terms and percentages, not as a complete account of all event detail. The registry does not state the event-level counts, whether a participant could contribute to more than one term, or the timing and duration of each event. The deaths field has no reported value, so deaths are not reported in the registry record; this does not establish that there were none.
The primary outcome is a participant count, but the registry does not show a formal primary-outcome analysis. It lists 4 outcome measures and 0 analysis entries. In particular, results for the listed DAS28 and bone-density outcomes are not reported in the registry record. The posted information therefore does not establish the magnitude or precision of change in disease activity or bone density. Nor does the safety summary answer whether any event was caused by rituximab, methotrexate, another factor, or a combination of factors.
In general, a confidence interval expresses the uncertainty around an estimate under a specified statistical model. No confidence interval for the posted safety counts is reported, so the precision of an estimated event frequency cannot be evaluated from an interval. Counts from a small enrolled group can also be sensitive to the experience of individual participants; this is a general interpretive concern, not a recalculation of these results.
The study’s open-label, single-group design matters to interpretation. Without a concurrent control, there is no like-for-like basis for comparing event frequency or disease activity under a different treatment. The record can describe what was reported in this group, but it cannot isolate a treatment effect from the course of rheumatoid arthritis, background methotrexate, other care, or reporting and follow-up influences. This is a limitation of the design, not a reason to disregard the observed counts.
9. Statistical Methods Explained
The registry identifies the study as open-label and single-group, with allocation recorded as NA and masking recorded as NONE. These design features shape which statistical questions the record can answer. The posted safety counts can describe events in the treated group, but there is no randomized comparator for estimating a between-group treatment contrast. The registry record does not report a statistical analysis plan or enough analysis detail to determine whether any additional modeling was planned or performed.
What does a participant count describe?
The primary endpoint is the number of participants reporting adverse events, rather than the total number of events. A participant-level count answers how many people were affected at least once under the endpoint definition. It does not indicate how many separate events occurred, how often events recurred, how severe each event was, or how long an event lasted. Those details are not reported in the registry record for the posted summary.
In general, a rate or proportion summarizes a count relative to a defined population at risk. The adverse-event section reports 18 at risk for each of the serious and other adverse-event categories, alongside 6 and 9 affected, respectively. The registry does not give confidence intervals or a model-based analysis for these counts. A reader should not treat the raw counts as a precise estimate of event frequency beyond the enrolled study group.
Why does the single-group design matter?
In a randomized controlled study, allocation can support a comparison between groups, subject to the design and analysis assumptions. Here there is only one group. Without a concurrent comparator, a change in disease activity or an adverse event cannot be contrasted with what would have occurred under another treatment condition within this study. Open-label conduct also means the treatment assignment was not masked. The record does not report whether outcome assessors were masked separately.
This does not make descriptive statistics inappropriate. Counts can still summarize what was observed in the enrolled group. It does mean that comparative language about treatment effects would go beyond the design and posted results. The registry record does not report adjusted estimates, hypothesis tests, or an inferential model for the listed outcomes.
How should precision be understood?
In general, an estimate is more informative when its uncertainty is also shown. A confidence interval gives a range of values compatible with the data under a statistical model and its assumptions; it is not a guarantee that the true value lies in that range. No interval estimates for the adverse-event counts are reported in the registry record. Therefore, readers cannot use posted interval bounds to judge how precisely an event frequency is estimated.
Over-dispersion is a general issue in count data: variation can exceed what a simple model assumes, for example when events cluster within participants. That distinction matters especially for total event counts. This primary endpoint is described as participants reporting events, and the record does not provide event-level data or a model that would allow assessment of clustering or over-dispersion. A more elaborate count model cannot be justified from the posted summary alone.
What do the planning illustrations represent?
The sample-size section is a planning illustration, not a report of the trial’s design justification or observed power. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event tables, the stated quantity is the total number of events using the Schoenfeld method; other tables express participants per arm. These assumptions describe the illustration, not this single-group study’s actual allocation or analysis.
In general, a sample-size calculation asks what study size would be needed under specified assumptions to detect a chosen effect with a stated power. It does not establish that the trial had that power, and it cannot replace a report of observed outcomes or uncertainty. The registry record does not report the study’s sample-size justification, a power target, or a planned effect size. The posted enrollment is 18; it should not be interpreted as proof that the study was sized adequately for any particular safety or efficacy question.
What analyses are available?
The record lists 0 analysis entries. It identifies 4 outcome measures, including the primary adverse-event endpoint and the listed secondary outcomes, but does not report analysis methods or outcome estimates for the DAS28 and bone-density measures. The sponsor’s inferential analysis, if any, is not reported in the registry record. Consequently, no recalculated comparative estimate or test can be discussed from the available information. Any planning values displayed elsewhere on the page should be read as illustrations based on their stated assumptions, not as observed trial findings.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety endpoint and secondary outcomes covering DAS28 change, DAS28 improvement by >1.2 at Week 24, and bone-density change among participants untreated with bisphosphonates. It reports 4 outcome measures and 0 analysis entries. A multiplicity strategy—such as prioritizing outcomes, adjusting significance thresholds, or specifying a testing sequence—is not reported in the registry record. Since outcome analysis results are also not reported, readers cannot assess how multiple comparisons were handled or whether any reported finding was prespecified.
Missing-data methods are not reported in the registry record. The posted description does not explain how participants with incomplete follow-up, missed visits, treatment discontinuation, or unavailable outcome measurements were handled. The safety population definition includes participants who received any part of an infusion, but it does not explain how missing safety assessments were addressed. The record also does not describe imputation, censoring, or sensitivity analyses.
The primary safety population is defined, but analysis populations for the secondary efficacy outcomes are not reported in the registry record. Details such as whether analyses followed all enrolled participants, only participants with available measurements, or another specified group are unavailable. These gaps limit assessment of how representative the outcome summaries would be of all enrolled participants and how robust they are to missing observations. No assumptions about missingness or multiplicity should be inferred from the absence of posted analysis details.
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 |
|---|---|---|---|
| Rituximab | 6 | 18 | 33.3% |
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 |
|---|---|
| Rituximab | 9 of 18 |
Most frequent serious adverse event terms
| Event term | Organ system | Rituximab |
|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 1 of 18 |
| Persistent thrombopenia | Blood and lymphatic system disorders | 1 of 18 |
| Rectal bleeding | Gastrointestinal disorders | 1 of 18 |
| Ventricular Extra systolebigeminy | Cardiac disorders | 1 of 18 |
| Severe infusion reaction | Injury, poisoning and procedural complications | 1 of 18 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 18 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rituximab |
|---|---|---|
| Hypertension | Blood and lymphatic system disorders | 2 of 18 |
| Blurred Vision | Eye disorders | 1 of 18 |
| Hyperglycemia | Endocrine disorders | 1 of 18 |
| Multi-sensitive Streptococcus Cystitis | Infections and infestations | 1 of 18 |
| Keratitis Secca | Skin and subcutaneous tissue disorders | 1 of 18 |
| Red Throat | General disorders | 1 of 18 |
| Vertigo | Ear and labyrinth disorders | 1 of 18 |
| Somnolence | General disorders | 1 of 18 |
| Influenza | Infections and infestations | 1 of 18 |
| Muscular Pain | Musculoskeletal and connective tissue disorders | 1 of 18 |
Serious events with the highest arm-level rate: pulmonary embolism (5.6%), persistent thrombopenia (5.6%), rectal bleeding (5.6%), ventricular extra systolebigeminy (5.6%), severe infusion reaction (5.6%).
The safety section reports 18 participants at risk for serious adverse events and 6 affected; for other adverse events, it reports 18 at risk and 9 affected. These are participant counts in the rituximab group, not a comparison with another treatment. The registry does not clarify whether the serious and other categories are mutually exclusive, so the counts should not be added together to estimate a total number of participants with any event.
The serious-event term list gives 5.6% for each of Pulmonary embolism, Persistent thrombopenia, Rectal bleeding, Ventricular Extra systolebigeminy, Severe infusion reaction, and Dyspnea. The registry does not provide further event-level details, including whether terms refer to distinct participants or to repeated events. The percentages are reported as written and should not be treated as proof of causation.
The deaths field has no reported value. Deaths are therefore not reported in the registry record; an empty value should not be interpreted as a confirmed absence of deaths. The counts describe the safety information posted for this study and do not by themselves quantify comparative risk or establish why an event occurred.
12. What the Result Does, and Does Not, Mean
The posted information supports a limited descriptive reading: in the enrolled single-group study, the registry reports adverse-event counts among participants in the rituximab group. It also lists serious-event terms and their reported percentages. These details give readers a view of what was recorded in the registry, but they do not provide a controlled estimate of how event frequency would differ under another treatment or no treatment.
The record does not report analyzed results for the listed disease activity or bone-density outcomes. It therefore cannot establish from the posted information whether DAS28 changed, how many participants met the stated improvement threshold, or what bone-density changes were observed. The record’s title and study objective refer to safety and efficacy, but an objective is not itself a result. The absence of posted results should not be converted into a claim of benefit or lack of benefit.
Nor do the adverse-event counts establish causality. In general, an event occurring during a study may have multiple possible explanations, and a single-group design offers no concurrent comparison to help distinguish them. The record does not provide detailed clinical adjudication, event timing, or participant-level histories for the listed terms. Conclusions should therefore remain close to the reported counts and avoid attributing each event to a particular cause.
These limitations do not make the registry entry useless. It records the study design, enrolled group, planned outcome domains, safety population definition, and selected safety information. But the registry record does not report the statistical analysis plan, uncertainty intervals, or outcome analyses needed for a fuller assessment. The appropriate interpretation is that these are descriptive posted data from a small, open-label, single-group study, with important efficacy and analysis details not reported.
13. Why This Trial Matters Statistically
This study illustrates a basic distinction in clinical-trial interpretation: a registry can describe observations without supporting a comparative treatment conclusion. The design is open-label and single-group, so the safety counts document what was reported in that cohort but do not estimate a contrast against another treatment. This distinction is important when a study’s title or objective includes both safety and efficacy, while the posted record contains only selected safety figures.
The endpoint also demonstrates why the unit being counted matters. The primary outcome concerns the number of participants reporting adverse events, whereas event terms may refer to individual events or participants. Without event-level detail, repeated events and overlap between categories cannot be assessed. Careful wording keeps the interpretation aligned with the participant-count endpoint rather than implying a complete accounting of all event occurrences.
Finally, the entry highlights the role of transparent analysis reporting. The registry lists secondary outcomes but no analysis entries, and it does not describe missing-data or multiplicity procedures. Without estimates and uncertainty measures, readers cannot judge the precision of results or how outcome selection and incomplete observations were handled. The study is therefore useful for teaching how to separate design, outcome definitions, raw safety summaries, and inferential claims—especially when not all planned information is posted.
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 enrollment was 18, and the study had a single group with no randomized comparator. As a result, the posted counts are descriptive and do not provide a controlled estimate of comparative safety or efficacy. Open-label conduct may also affect reporting or assessment, but whether and how this influenced the study is not reported in the registry record.
Although the registry names disease activity and bone-density outcomes, their results are not reported in the registry record. The absence of analysis entries also leaves the statistical methods, outcome estimates, and uncertainty unavailable. A sample-size justification, interim-analysis plan, and prespecified statistical analysis plan are not reported in the registry record.
The safety summary does not provide event-level descriptions, participant-level overlap, timing, duration, or attribution for the serious-event terms. The deaths field has no reported value. Missing-data handling and the analysis populations for the secondary outcomes are also not reported in the registry record. These omissions limit assessment of the completeness and precision of the posted findings.
The treatment summary describes background methotrexate and possible re-treatment, but further details about treatment exposure, adherence, and the use of methylprednisolone are not reported in the registry record. The timeframe wording also combines scheduled assessments through Week 24 and later follow-up through 18 months, while stating a total of 104 weeks. These registry entries do not resolve how individual follow-up varied. Together, the design and reporting limitations call for a narrow reading of the posted safety counts rather than broad conclusions about treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate — NCT01000610.
- Registry record last updated 2017-08-16; status last verified 2017-06.
- Results first posted 2015-03-19.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes NCT01000610, a completed Phase 4, open-label, single-group study sponsored by Hoffmann-La Roche. It enrolled 18 participants with active rheumatoid arthritis and an inadequate response to prior methotrexate. The summary describes rituximab infusions on days 1 and 15 with background methotrexate, and possible re-treatment for eligible participants after the initial 24 weeks.
The primary endpoint is the number of participants reporting adverse events in a safety population defined by receipt of any part of an infusion. Posted safety figures include 6 of 18 participants affected by serious adverse events and 9 of 18 affected by other adverse events. The registry lists serious-event terms but does not report an analysis of the listed disease activity or bone-density outcomes. Analysis methods, missing-data handling, and uncertainty estimates are not reported in the registry record.