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 to Assess the Effect of Tocilizumab Plus Methotrexate on Safety and Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis (NCT00754572), a non-randomized phase 3 study. The primary outcome is Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00754572 |
| Phase | Phase 3 |
| Condition | Rheumatoid Arthritis |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 418 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants with moderate to severe active rheumatoid arthritis. The primary endpoint population is described as the ITT population, defined in the record as participants with endpoint values collected at Week 24.
Intervention
Tocilizumab in combination with methotrexate. The study summary describes tocilizumab 8mg/kg intravenously every 4 weeks and methotrexate 10-25mg weekly.
Comparator
No control group is listed. This is a single-group, non-randomized study, so the registry record does not support a like-for-like comparison with another treatment group.
Primary question
What percentage of participants had an American College of Rheumatology 50 response at Week 24 during treatment with tocilizumab plus methotrexate? The registry record names this outcome but does not report its result.
The study addresses a response outcome based on changes in joint counts and other assessments of rheumatoid arthritis activity. ACR50 requires improvement in both swollen and tender joint counts, as well as improvement in a specified set of other assessments. It is therefore a composite response criterion rather than a measure of a single symptom or laboratory value.
The registry lists safety and reduction of signs and symptoms as study aims. However, because the design has no comparator and is open-label, the study question is descriptive: it concerns outcomes observed among people receiving the combination, rather than a randomized estimate of what would have happened under another treatment. The record gives no Week 24 ACR50 percentage or confidence interval. That prevents interpretation of the observed response level or its precision from the registry record.
3. Trial Design
This is a Phase 3, single-group, non-randomized, open-label study listed as completed. The registry record describes 418 participants and identifies rheumatoid arthritis as the condition. The study is sponsored by Hoffmann-La Roche. The record lists the study start as 2009-02 and primary completion as 2012-10.
Participants were to receive tocilizumab with methotrexate. The study summary specifies tocilizumab 8mg/kg intravenously every 4 weeks and methotrexate 10-25mg weekly. It gives an anticipated time on study treatment of 3-12 months and a target sample size of <500 individuals. These statements describe the study plan in the record; they do not establish how long each participant received treatment or what treatment exposure was observed.
There is no randomized allocation, masking, or listed comparator group. The open-label, single-group structure means that the registry outcomes describe participants treated in the study, without a contemporaneous control group to separate treatment-associated changes from other influences. The study can report observed response and safety events, but a treatment contrast against an alternative is not available from this design.
The primary outcome is the percentage of participants with an ACR50 response at Week 24. The registry also lists secondary outcomes concerning ACR20 and ACR70 response at Week 24, time to ACR20, ACR50, and ACR70 response, hemoglobin, swollen and tender joint counts, pain, and global assessment of disease activity. The registry record lists 24 outcome measures, but it does not report a primary endpoint result in the information available for interpretation.
The design information does not report a protocol-level statistical analysis plan, a sample-size justification, or whether interim analyses were conducted. Those details should not be inferred from the study phase, enrollment, or outcome list.
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 | 418 |
| COMPLETED | 347 |
| NOT COMPLETED | 71 |
Reasons for not completing this period:
| Reason | Tocilizumab |
|---|---|
| Adverse Event | 19 |
| Other | 39 |
| Protocol Violation | 3 |
| Withdrawal by Subject | 3 |
| Lack of Efficacy | 2 |
| Death | 1 |
| Administrative Reason | 3 |
| Lost to Follow-up | 1 |
Analysis population for the primary outcome, as defined in the registry: ITT Population; All participants with endpoint values collected at Week 24 were included in the analysis.
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: Intention to treat (ITT) population: All participants who received at least one dose of study drug and who had at least one effectiveness measurement performed after baseline.
| Characteristic | Unit | Tocilizumab |
|---|---|---|
| Participants analysed | 418 | |
| Age, Continuous | years | 48.69 (SD 12.36) |
| Sex: Female, Male: Female | Participants | 371 |
| Sex: Female, Male: Male | Participants | 47 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 24, measured over Week 24.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with an American College of Rheumatology 50 response at Week 24. ACR50 is defined in the registry as 50 percent improvement in both swollen joint count and tender joint count, together with improvement in three of the following five assessments: participant global assessment of pain by visual analog scale; participant global assessment of disease activity by visual analog scale; investigator or physician global assessment of disease activity by visual analog scale; participant disability measured by the Health Assessment Questionnaire Disability Index; and an acute phase reactant, erythrocyte sedimentation rate or C-reactive protein.
This is a composite response definition. It requires improvement in joint counts and across several additional domains, rather than relying on a change in only one measure. Such response criteria can provide a consistent way to classify whether participants meet a defined threshold of improvement. The percentage expresses how common that defined response was among the participants included in the endpoint analysis.
The endpoint is assessed at Week 24, a specified time point that makes the outcome interpretable relative to the study schedule. The registry identifies the analysis population as participants with endpoint values collected at Week 24. It does not give the number with observed endpoint values, the ACR50 response percentage, or its 95% confidence interval. The endpoint definition is reported, but its result and precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central result needed to interpret this study statistically would be the observed percentage meeting the ACR50 definition at Week 24, together with its confidence interval and the number of participants included in that analysis. The registry record specifies the endpoint and the analysis population, but does not report the response percentage, a confidence interval, or the endpoint denominator. Consequently, it is not possible to describe the observed response level or how precisely it was estimated from the registry record.
This absence matters for both the size and the uncertainty of the result. A percentage alone would describe the observed frequency in the analysis population; a confidence interval would communicate sampling uncertainty around that estimate. A narrow interval would indicate greater precision than a wide interval, but neither can be assessed when the estimate and interval are not reported. No inference about the endpoint’s statistical significance can be made from the endpoint definition, study phase, or enrollment alone.
The design also limits what any observed percentage could establish. Because the study is single-group, non-randomized, and open-label, an ACR50 response percentage would describe outcomes among participants receiving the combination. It would not by itself estimate the difference between the combination and a control treatment. Without a control group, observed change can also reflect factors other than treatment, including the course of disease, expectations, and other influences on assessment. This is a general limitation of interpreting uncontrolled treatment outcomes, not a claim that any such factor affected this study.
The registry lists 418 participants enrolled, but enrollment is not necessarily the same as the number with Week 24 endpoint values. The record defines the endpoint analysis population as participants with those values collected. It does not report the number lacking endpoint data or how missing values were handled. Therefore, the enrolled count cannot be used as the endpoint denominator, and the potential for missing-data bias cannot be evaluated from the record.
The adverse-event information reports 30 participants with a serious adverse event among 418 at risk, and 324 with another adverse event among 418 at risk. These are separate registry summaries; the counts should not be added together, and the record does not establish whether the groups overlap. The listed serious adverse-event terms have percentages, but the registry does not provide enough information in this record to interpret them as a complete account of risk across treatment or against a comparator. Deaths are not reported in the registry record.
Overall, the available information describes the study design, endpoint definition, and selected safety counts, but not the primary efficacy result. Any conclusion about the frequency or precision of ACR50 response would require results not reported in the registry record.
9. Statistical Methods Explained
Statistical methods are useful only when the reported estimate, its uncertainty, the population analyzed, and the design are considered together. In this study, the registry identifies a binary percentage endpoint: whether each participant met the ACR50 response definition at Week 24. It also identifies a 95% confidence interval as the measure of dispersion. However, the registry record does not report the endpoint estimate or interval, and it does not describe the method used to calculate the interval.
What does a percentage endpoint represent?
For a binary outcome, each participant either meets the response criterion or does not meet it at the specified assessment. The percentage is a summary of the proportion meeting that criterion in the analyzed population. It does not describe the size of improvement among those who responded, nor does it capture every possible change in the underlying measures. Here, the response criterion combines joint-count improvement with improvement in additional disease assessments.
The analysis population matters because the percentage depends on who is included. The registry says the ITT population includes all participants with endpoint values collected at Week 24. This wording defines the reported endpoint population by availability of endpoint values. It does not give the number analyzed or explain how the label ITT was operationalized beyond that definition. The record also does not describe whether participants without observed Week 24 values were excluded, imputed, or handled by another method.
What does a confidence interval add?
General explanation: a confidence interval describes uncertainty around an estimated quantity under the assumptions of the statistical method. For a response percentage, it helps readers judge how compatible the data are with a range of underlying response frequencies. It is not a guarantee that the true value lies within the interval, nor is it a measure of clinical importance. The registry specifies a 95% confidence interval for the primary endpoint, but the endpoints of that interval are not reported in the registry record. Its width and the precision of the estimate therefore cannot be assessed.
A confidence interval for a single-group percentage would address uncertainty in that group’s response frequency. It would not create a control comparison. To estimate a treatment difference, a study needs an appropriate comparative design and a contrast defined between treatment groups. This study is listed as single-group and non-randomized, with no comparator, so the registry’s design does not provide such a contrast.
Why does the design affect inference?
General explanation: random assignment can help balance measured and unmeasured characteristics between treatment groups, while masking can reduce some influences on treatment delivery or assessment. Neither feature is listed for this study. In an open-label, single-group study, outcomes can be described, but attribution of observed changes to the treatment combination is more limited. This does not invalidate a descriptive response estimate; it defines what that estimate can support.
The endpoint is assessed at Week 24, while the study summary describes anticipated treatment duration of 3-12 months. The registry does not explain how participants with treatment exposure differing from that schedule were handled in the primary analysis. Nor does it report the exact timing rules, assessment windows, or statistical method for the primary outcome. Those details are not reported in the registry record.
How should planning illustrations be read?
The study record contains a general description of planning illustrations based on the observed effect. It states that these use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. The record distinguishes participants per arm for non-time-to-event outcomes from total events for time-to-event outcomes.
These are planning illustrations, not observed trial results and not observed power. The described equal-allocation, two-arm framework does not match the single-group design listed for this study. The registry record does not report the numerical planning results or the observed effect needed to assess such illustrations. They should not be interpreted as evidence about the study’s precision, its statistical power after completion, or a treatment effect against a control.
More generally, sample-size planning depends on assumptions about the effect to detect, variability or event frequency, significance threshold, power target, allocation, and analysis method. These are general statistical considerations; the registry record does not report a trial-specific sample-size justification or enough information to reconstruct one. The target sample size in the study summary is not itself a justification or a result.
What can be concluded from the posted methods?
The record supports a description of the primary outcome, its assessment time, the stated endpoint population, and the intended confidence-interval presentation. It does not provide the primary numerical result, the interval, the endpoint denominator, missing-data procedures, or a detailed statistical analysis plan. Those omissions prevent a full evaluation of precision, robustness, and the assumptions behind the endpoint analysis. They also make it important not to infer efficacy or comparative effectiveness from the study design or from the presence of an endpoint definition alone.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Tocilizumab | 381 | 279 | 73.2% | 68.5% to 77.6% | 68.6% to 77.4% | 68.6% to 77.4% |
R code and output
arm <- c("Tocilizumab")
n <- c(381)
events <- c(279)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Tocilizumab 381 279 73.2 68.5 77.6 68.6 77.4 68.6 77.411. Multiplicity, Missing Data and Analysis Populations
The registry lists numerous secondary outcomes, including ACR20 and ACR70 response, time to response, hemoglobin, joint counts, pain, and global assessment. It lists 24 outcome measures overall. When a study evaluates multiple outcomes, the chance of finding an apparently notable result among them can increase unless the analysis plan accounts for multiplicity. General approaches include prioritizing outcomes, adjusting inference, or treating secondary findings as exploratory. The registry record does not report whether multiplicity was addressed, how outcomes were prioritized, or whether any adjustment was planned.
The primary outcome population is described as participants with endpoint values collected at Week 24. The record does not report how many participants had those values, how many were missing, why values might be missing, or how missing data were handled. It does not state whether any imputation, sensitivity analysis, or alternative missing-data analysis was used. These details are needed to evaluate whether the analyzed participants could differ from those without observed endpoint values.
The description calls the population ITT but defines it by collection of endpoint values. The registry record does not provide further detail about this analysis-population label or how participants without Week 24 measurements were treated. It is therefore not possible to assess the impact of missing endpoint data or to establish whether the analysis followed a particular estimand or missing-data strategy.
The record lists no analysis entries. The statistical analysis plan, any interim analyses, and the handling of multiplicity and missing data are not reported in the registry record. These gaps do not establish that such procedures were absent; they mean the registry record does not document them.
12. 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 | 30 | 418 | 7.2% |
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 | 324 of 418 |
Most frequent serious adverse event terms
| Event term | Organ system | Tocilizumab |
|---|---|---|
| Pneumonia | Infections and infestations | 3 of 418 |
| Cellulitis | Infections and infestations | 3 of 418 |
| Leukopenia NOS | Blood and lymphatic system disorders | 2 of 418 |
| Hypersensitivity | Immune system disorders | 1 of 418 |
| Constipation | Gastrointestinal disorders | 1 of 418 |
| Anaemia | Blood and lymphatic system disorders | 1 of 418 |
| Bradicardia | Cardiac disorders | 1 of 418 |
| Bronchitis | Infections and infestations | 1 of 418 |
| Chronic gastrointestinal bleeding | Gastrointestinal disorders | 1 of 418 |
| Gastritis | Gastrointestinal disorders | 1 of 418 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tocilizumab |
|---|---|---|
| Hypercholesterolemia | Metabolism and nutrition disorders | 71 of 418 |
| Hepatic enzyme increased | Investigations | 70 of 418 |
| Headache | Nervous system disorders | 41 of 418 |
| Urinary tract infection | Infections and infestations | 41 of 418 |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | 39 of 418 |
| Hypertension | Vascular disorders | 32 of 418 |
| Influenza | Infections and infestations | 32 of 418 |
| Pharyngitis | Infections and infestations | 30 of 418 |
| Leukopenia NOS | Blood and lymphatic system disorders | 25 of 418 |
| Back pain | Musculoskeletal and connective tissue disorders | 22 of 418 |
Serious events with the highest arm-level rate: pneumonia (0.7%), cellulitis (0.7%), leukopenia nos (0.5%), hypersensitivity (0.2%), constipation (0.2%).
The registry reports 30 participants with a serious adverse event among 418 at risk. It also reports 324 participants with another adverse event among 418 at risk. These are counts from the tocilizumab group in this single-group study. The registry record does not provide a control group, so these counts cannot be used to estimate a comparative safety difference.
The listed serious adverse-event terms are pneumonia (0.7%), cellulitis (0.7%), leukopenia NOS (0.5%), hypersensitivity (0.2%), constipation (0.2%), and anaemia (0.2%). These entries describe selected terms as recorded; they are not a complete substitute for the overall serious adverse-event count. The record does not explain whether participants could have more than one event or how the term percentages were calculated. The term percentages should not be summed to create a total.
The registry record does not report deaths. It also does not provide, in this information, details about event timing, severity beyond the serious classification, duration, treatment relatedness, or the number of events per participant. These limitations matter when interpreting safety summaries. The counts describe reported events in the study group; without a comparator and fuller event context, they do not establish a causal treatment effect or a comparative risk.
13. What the Result Does, and Does Not, Mean
The study record establishes that the trial was designed to assess safety and signs and symptoms during treatment with tocilizumab plus methotrexate in participants with moderate to severe active rheumatoid arthritis. It identifies an ACR50 response at Week 24 as the primary endpoint and gives the response definition. It also reports selected adverse-event counts and lists serious adverse-event terms.
The primary endpoint result itself is not reported in the registry record. There is no ACR50 response percentage, endpoint denominator, or confidence interval to interpret. It is therefore not possible to say from this record how frequently participants met the response definition or how precisely that frequency was estimated. The study’s completion status and enrollment do not supply the missing endpoint result.
Even if a response percentage were available, this study’s single-group, non-randomized, open-label design would support a description of outcomes in the treated group rather than a randomized comparison. A response observed during treatment does not, by itself, show what would have happened under another treatment or without the study treatment. The registry record does not establish comparative benefit or harm.
The serious and other adverse-event counts are descriptive summaries among participants at risk in the listed group. The record offers no control-group safety data and does not report deaths. The listed serious-event terms provide additional context but do not constitute a complete accounting of all possible safety outcomes.
Accordingly, the record is useful for understanding the study question, design, endpoint definition, and some safety reporting. It does not contain the primary response estimate or enough comparative information to determine treatment effects. Those boundaries are important: a planned outcome is not a result, and descriptive observations in a single group should not be read as proof of a causal effect.
14. Why This Trial Matters Statistically
This trial is statistically instructive because its endpoint is clearly defined while the registry record lacks the numerical result needed to interpret it. The distinction between an outcome definition and an observed estimate is fundamental. Knowing that ACR50 was assessed at Week 24 does not reveal how many participants met the criterion, the denominator used, or the uncertainty around the percentage.
The design also highlights the difference between descriptive and comparative evidence. A single-group study can report the frequency of an outcome among participants receiving the study regimen. Without a comparator, however, it cannot directly estimate a difference between the regimen and another strategy. Open-label assessment and non-randomized allocation further limit causal interpretation. These are design constraints, not numerical findings about the treatment.
The record’s endpoint-population definition makes missingness a central interpretive issue. It refers to participants with endpoint values collected at Week 24 but does not report how many had those values or how missing measurements were handled. Without that information, readers cannot assess the relationship between enrollment and endpoint analysis or judge the possible influence of missing data.
Finally, safety summaries illustrate why counts and event terms need context. The record reports serious and other adverse-event counts, but no comparator, and lists selected serious-event terms without a full account of event overlap or calculation details. Reporting the counts accurately while avoiding unsupported comparisons is part of sound statistical interpretation.
15. 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 primary limitation for interpreting the main study question is that the registry record does not report the Week 24 ACR50 estimate or its 95% confidence interval. It also does not report the endpoint denominator, so the stated enrollment of 418 cannot be treated as the number analyzed for that outcome.
The study has a single-group, non-randomized, open-label design and no listed comparator. Consequently, the record cannot support a randomized treatment contrast. Observed outcomes among participants receiving the combination cannot alone establish that the treatment caused those outcomes or show how results compare with an alternative.
The registry defines the endpoint analysis population as participants with Week 24 endpoint values collected, but does not report missing-data counts, reasons for missingness, or handling methods. The statistical analysis plan, trial-specific sample-size justification, multiplicity procedures, and interim analyses are not reported in the registry record. The record also does not describe the method used to calculate the confidence interval.
Safety interpretation is limited by the absence of a control group and by the lack of detail about event timing, participant overlap, and the method used for the percentages attached to selected serious adverse-event terms. Deaths are not reported in the registry record. These limits do not show that outcomes were absent; they identify information that the registry record does not report.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study to Assess the Effect of Tocilizumab Plus Methotrexate on Safety and Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis — NCT00754572.
- Registry record last updated 2015-05-15; status last verified 2015-05.
- Results first posted 2015-05-15.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry describes a completed Phase 3, open-label, non-randomized, single-group study of tocilizumab plus methotrexate in moderate to severe active rheumatoid arthritis. It lists enrollment of 418 and names the percentage of participants with ACR50 response at Week 24 as the primary endpoint. The record defines ACR50 and describes the endpoint population as participants with Week 24 endpoint values collected.
The registry record does not report the primary endpoint percentage, its 95% confidence interval, or the endpoint denominator. It reports 30 participants with a serious adverse event and 324 with another adverse event, each among 418 at risk. A control group is not listed, and deaths are not reported in the registry record. Thus, the available record supports description of the study design and selected safety information, but not a numerical interpretation of the primary efficacy endpoint or a comparative treatment effect.