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 RoActemra/Actemra (Tocilizumab) Versus Placebo in Patients With Systemic Sclerosis (NCT01532869), a randomized phase 3 study. The primary outcome is Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01532869 |
| Phase | Phase 3 |
| Condition | Sclerosis, Systemic |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 87 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants with systemic sclerosis were eligible for this multicenter study. The primary analysis population was described as randomized participants who had received any study drug by the Week 24 cutoff date; the number analyzed for the primary endpoint included those evaluable for that outcome.
Intervention
Tocilizumab, identified in the registry as RoActemra/Actemra, was given as a 162 mg subcutaneous injection weekly during the randomized period.
Comparator
Participants assigned to the comparator received placebo during the randomized period. From Week 48 to Week 96, all participants were to receive open-label tocilizumab.
Primary question
The primary question was whether the mean change from baseline in modified Rodnan Skin Score (mRSS) at Week 24 differed between the tocilizumab and placebo groups. Because a negative change represents improvement, the direction and uncertainty of the between-group difference both matter when interpreting the result.
The registry describes a randomized, double-blind, placebo-controlled, parallel-group study in systemic sclerosis, with 87 participants enrolled. Its primary endpoint concerns skin thickness, assessed using mRSS. The scale combines ratings across 17 body sites, so the outcome reflects a structured clinical assessment rather than a single measurement at one site. The reported comparison estimates the difference in mean change between the randomized groups; it does not by itself describe every participant’s experience or establish how the result relates to other aspects of the condition.
3. Trial Design
The registry lists this as a Phase 3, randomized, double-blind, parallel-group study sponsored by Hoffmann-La Roche. The official title describes it as a Phase II/III study. It was multicenter and placebo-controlled, and enrollment was 87 participants. The registry status is completed. The recorded start was 2012-03 and primary completion was 2014-01.
During the first 48 weeks, participants were randomized to weekly subcutaneous tocilizumab at 162 mg or placebo. The study plan then described open-label tocilizumab for all participants from Week 48 to Week 96. Thus, the randomized placebo comparison applies to the initial treatment period; after Week 48, the planned treatment groups no longer represent a continuing blinded comparison of tocilizumab against placebo.
The primary outcome was change from baseline in mRSS at Week 24. The registry reports the primary estimate as a difference in least-squares means from a mixed models analysis, with a 95% confidence interval and p-value. The analysis population description refers to randomized participants who received any study drug by the Week 24 cutoff date, while the number analyzed was limited to those evaluable for the outcome. The precise number included in that endpoint analysis is not reported in the registry record as a single count.
Other listed outcomes address physical function, disability, clinician and patient global assessments, fatigue, itch, skin score at later follow-up, and maintenance or improvement in mRSS. The record lists 15 outcome measures and 23 analyses. It does not report enough detail to reconstruct the full protocol, the planned hierarchy among outcomes, or all analysis choices. Those omissions matter when interpreting secondary findings and the relationship between the registered plan and posted analyses.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Randomization was stratified by joint involvement at baseline (\>=4 or \<4 tender joints of 28 tender joint count \[TJC\]). The study consisted of double-blind (Week 0-Week 48) and open-label (Week 48-Week 96) periods. Data analyzed up to Weeks 24 and 48 (data cut-off: 11 July 2014), and up to Week 96 (data cut-off: 05 August 2015) are reported.
Blinded-Treatment Period (Up to Week 24)
| Stage | Placebo | Tocilizumab |
|---|---|---|
| STARTED | 44 | 43 |
| COMPLETED | 36 | 35 |
| NOT COMPLETED | 8 | 8 |
Reasons for not completing this period:
| Reason | Placebo | Tocilizumab |
|---|---|---|
| Death | 0 | 1 |
| Adverse Event | 2 | 3 |
| Lost to Follow-up | 0 | 1 |
| Non-compliance | 1 | 0 |
| Lack of Efficacy | 1 | 1 |
| Withdrawal by Subject | 4 | 2 |
Blinded-Treatment Period (Up to Week 48)
| Stage | Placebo | Tocilizumab |
|---|---|---|
| STARTED | 44 | 43 |
| COMPLETED | 33 | 30 |
| NOT COMPLETED | 11 | 13 |
Reasons for not completing this period:
| Reason | Placebo | Tocilizumab |
|---|---|---|
| Death | 0 | 3 |
| Adverse Event | 4 | 5 |
| Lost to Follow-up | 0 | 1 |
| Non-Compliance | 1 | 0 |
| Lack of Efficacy | 0 | 1 |
| Withdrawal by Subject | 5 | 3 |
| Physician Decision | 1 | 0 |
Open-label Period (Week 48 to Week 96)
| Stage | Placebo | Tocilizumab |
|---|---|---|
| STARTED | 31 | 30 |
| COMPLETED | 24 | 27 |
| NOT COMPLETED | 7 | 3 |
Reasons for not completing this period:
| Reason | Placebo | Tocilizumab |
|---|---|---|
| Adverse Event | 4 | 1 |
| Non-compliance | 1 | 0 |
| Lack of Efficacy | 1 | 1 |
| Withdrawal by Subject | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population included all participants randomized who had received any study drug at the time of the Week 24 cutoff date (14 January 2014). Here, number of participants analyzed included only those participants who were evaluable for this outcome measure at any time point up to Week 24.
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 included all participants who received any study drug and provided at least one post-dose safety assessment (withdrawal, adverse event \[AE\], death, laboratory assessment, vital signs).
| Characteristic | Unit | Placebo | Tocilizumab | Total |
|---|---|---|---|---|
| Participants analysed | 44 | 43 | 87 | |
| Age, Continuous | years | 48.1 (SD 12.9) | 51.2 (SD 11.7) | 49.6 (SD 12.3) |
| Sex: Female, Male: Female | Participants | 35 | 32 | 67 |
| Sex: Female, Male: Male | Participants | 9 | 11 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24, measured over Baseline, Week 24.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | unit on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline in modified Rodnan Skin Score (mRSS) at Week 24. The mRSS assesses skin thickness at 17 body sites. Each site is rated from 0, meaning normal, to 3, meaning severe skin thickening; the total is the sum of the site scores and ranges from 0-51 units. The registry describes the scale as validated for participants with systemic sclerosis.
Change from baseline makes the endpoint a measure of movement in skin score over the assessment period, rather than a comparison of final scores alone. The registry specifies that a negative change indicates improvement. A group mean change therefore summarizes average movement across participants, while a between-group contrast asks whether that average movement differs between randomized assignments.
The endpoint is relevant to the study question because it quantifies skin thickening using a defined multi-site assessment. It remains a particular measure of disease status: it does not represent every symptom, function, or aspect of health. Nor does a group average show how changes are distributed among individuals. The estimate should therefore be read alongside its confidence interval, the analysis population, other outcomes, and the limitations of the registry’s reporting.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
At Week 24, the reported least-squares mean change was -1.22 in the placebo group, with a 95% confidence interval from -3.42 to 0.98, and -3.92 in the tocilizumab group, with a 95% confidence interval from -6.17 to -1.67. Since negative change indicates improvement on mRSS, the group estimates are in the direction of a larger average decrease with tocilizumab. These are estimates of group means, not statements that each participant improved.
The reported between-group difference in least-squares means was -2.70, with a 95% confidence interval from -5.85 to 0.45 and p = 0.091. The point estimate is consistent with a greater decrease in mRSS in the tocilizumab group, but the confidence interval includes zero. Thus, the reported data remain compatible with no between-group difference as well as with effects in either direction within the interval. The p-value is not, on its own, a measure of effect size or the probability that a treatment effect exists.
The confidence interval conveys uncertainty about the estimated contrast under the reported analysis. Its lower and upper limits indicate that the point estimate is not precise enough to exclude a zero difference. The interval also includes values that would correspond to a more favorable average change for either group, given the outcome’s direction. This uncertainty should temper any interpretation based solely on the negative point estimate.
The primary analysis used a mixed models analysis, and the estimate is reported as a difference in least-squares means. Such an estimate is model-based and need not be identical to a simple subtraction of the two arm summaries. The record does not provide sufficient detail to identify all model terms or assumptions, so the reported analysis is the principal basis for interpreting the primary result.
The registry also reports a secondary binary outcome: the proportion who maintained or improved in mRSS from Week 24 to Week 48. Its posted group percentages and logistic regression result do not replace the Week 24 primary endpoint. They concern a different time period and a different outcome definition. The presence of a secondary result that may appear more favorable does not remove uncertainty in the primary comparison, particularly when the record does not report a multiplicity plan.
Overall, the primary estimate points toward a larger mean decrease in mRSS with tocilizumab, but its confidence interval includes zero and the reported p-value is 0.091. The registry result is therefore best described as an uncertain estimate, not as conclusive evidence of a between-group difference. This statistical interpretation does not establish clinical importance, durability, or effects on outcomes beyond the measures reported.
9. Statistical Methods Explained
The primary endpoint is continuous: mRSS change is measured on a numerical scale, and the registry reports a group mean estimate. The reported arm values are least-squares means, a model-based form of mean that accounts for the analysis model. The registry names a mixed models analysis for the primary comparison and reports the difference in least-squares means, its confidence interval, and a p-value. The model’s full specification, including all covariates and assumptions, is not reported in the registry record.
What does the confidence interval describe?
A confidence interval expresses uncertainty around an estimated effect under the statistical method used. Here, the interval for the between-group difference runs from -5.85 to 0.45. Because it includes zero, the posted estimate does not rule out no difference between the groups. The interval is also informative about precision: a range spanning values on both sides of zero signals that the direction and size of the underlying contrast are not tightly determined by this result alone. A confidence interval is not a range containing every individual participant’s outcome.
How should the p-value be read?
The reported p-value for the primary comparison is 0.091. In general, a p-value describes how unusual data at least as inconsistent with a specified null model would be if that model and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, and it does not quantify the chance that the result will replicate. The registry’s sample-size planning illustration names a two-sided significance level of 0.05, but the record does not report the trial’s full statistical analysis plan or whether other decision criteria were prespecified.
Why report a model-based difference?
The two arm estimates describe average change within each assigned group. The between-group estimate targets the contrast between those averages, as estimated by the mixed model. Least-squares means and their difference can depend on model structure and the data included in the analysis. A simple contrast calculated from summary values would not necessarily match the model-based estimate. For the primary endpoint, the registry’s mixed-model result is the relevant reported comparison; the model details needed for independent reconstruction are not reported in the registry record.
How do the binary secondary statistics differ?
The secondary outcome of maintaining or improving mRSS is binary: each participant is classified according to whether the specified outcome occurred. A risk difference expresses the difference between group proportions, whereas an odds ratio compares the odds of the outcome between groups. These measures have different scales and should not be treated as interchangeable. The registry’s secondary analysis reports a logistic regression odds ratio of 2.39, with a 95% confidence interval from 0.60 to 9.50 and p = 0.216. A separate unadjusted recalculation reports a risk difference of 0.241, with a confidence interval from 0.035 to 0.447 and p = 0.026. They answer related but not identical statistical questions and use different methods.
For binary outcomes, uncertainty can be substantial when the number of participants is limited. General statistical principle: estimates based on a finite sample vary from sample to sample, and a wide confidence interval indicates that many effect sizes remain compatible with the data. The confidence interval for the posted logistic regression odds ratio includes the value representing no association, while the reported interval for the unadjusted risk difference does not include zero. The difference in conclusions across these methods is a reason to give priority to the sponsor’s reported analysis rather than select whichever result appears more favorable.
What do the planning illustrations mean?
The registry’s planning illustrations use the observed secondary effect as a reference and show hypothetical participants per arm for specified fractions of that effect. They are not the trial’s observed power and are not evidence about what the original investigators used to design the study. The assumptions listed are a two-sided significance level of 0.05, equal allocation, and a normal approximation. For planning for 100% of the observed effect, the illustration gives 66 participants per arm for 80% power and 87 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 119 participants per arm for 80% power and 158 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 269 participants per arm for 80% power and 360 participants per arm for 90% power. These are illustrative assumptions based on an observed result, not a justification for the study’s enrollment.
More generally, over-dispersion occurs when observed variability is greater than a model assumes. When present, it can make uncertainty estimates too small if the model does not account for it. The registry record does not report whether over-dispersion was assessed or relevant to these analyses. Likewise, details about missing-data methods, interim analyses, and any sensitivity analyses are not reported in the registry record, so their influence cannot be assessed from the posted results.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Mixed Models Analysis | Difference in Least Square (LS) mean -2.70 | -5.85 to 0.45 | 0.091 |
The registry’s sponsor-reported primary analysis is a mixed models analysis of the difference in least-squares mean mRSS change. It gives a difference of -2.70, a 95% confidence interval from -5.85 to 0.45, and p = 0.091. The record does not present an alternative recalculated primary comparison in the posted statistics described for this analysis, so there is no separate primary re-calculation to set against the sponsor result.
For the secondary outcome of maintaining or improving mRSS, the sponsor-reported analysis is logistic regression, with an odds ratio of 2.39, a 95% confidence interval from 0.60 to 9.50, and p = 0.216. The unadjusted recalculation instead expresses the contrast as a risk difference of 0.241, with a 95% confidence interval from 0.035 to 0.447 and p = 0.026. These results differ in both effect measure and analysis method. The risk-difference calculation is a simple unadjusted comparison; it does not reproduce the sponsor’s regression model.
The registry does not flag a discrepancy. The sponsor’s own reported analysis therefore remains the principal result for interpretation, while the unadjusted calculation is best treated as a sensitivity in presentation rather than a substitute. The registry record does not explain the model specification or provide enough detail to determine why the estimates and inferential results differ.
11. Multiplicity, Missing Data and Analysis Populations
The primary analysis population is described as the intent-to-treat population, comprising randomized participants who had received any study drug by the Week 24 cutoff date, identified as 14 January 2014. The registry further says that the number analyzed included only participants evaluable for the outcome measure at any time point up to the cutoff. The primary endpoint’s arm summaries list 43.0 participants for placebo and 41.0 for tocilizumab. The record does not provide a complete account of how all randomized participants were handled in the endpoint analysis or identify the number with missing Week 24 measurements.
Missing outcome data can affect estimates when the availability of measurements is related to participants’ outcomes or treatment assignment. General statistical principle: different assumptions about unobserved outcomes can lead to different estimates, so methods for handling missingness and sensitivity analyses are important to interpretation. The specific missing-data method, reasons for missing measurements, and sensitivity analyses are not reported in the registry record. It is therefore not possible to assess how robust the primary result is to alternative assumptions about missing data.
The registry lists multiple outcomes and analyses, including secondary measures across function, disability, global assessments, fatigue, itch, and skin score. It does not report a multiplicity plan, such as a hierarchy of tests or an adjustment procedure. When many hypotheses are examined, the chance of at least one apparently unusual result can increase. This general concern does not establish that a particular result is false; it means that isolated secondary findings require caution unless the testing strategy is documented.
The record also does not report the full statistical analysis plan, sample-size justification, interim analyses, or the complete model specifications. The planning illustrations associated with the observed secondary effect are not evidence of the trial’s original design rationale. These gaps limit assessment of prespecification, analysis choices, and the consequences of missing observations. They do not change the numbers reported for the primary comparison, but they restrict how confidently the analysis process can be evaluated.
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 |
|---|---|---|---|
| Placebo (up to 24 Weeks) | 11 | 44 | 25.0% |
| Tocilizumab (up to 24 Weeks) | 9 | 43 | 20.9% |
| Placebo (up to 48 Weeks) | 15 | 44 | 34.1% |
| Tocilizumab (up to 48 Weeks) | 14 | 43 | 32.6% |
| Placebo to Tocilizumab (up to 96 Weeks) | 22 | 44 | 50.0% |
| Tocilizumab to Tocilizumab (up to 96 Weeks) | 17 | 43 | 39.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo (up to 24 Weeks) | 26 of 44 |
| Tocilizumab (up to 24 Weeks) | 28 of 43 |
| Placebo (up to 48 Weeks) | 32 of 44 |
| Tocilizumab (up to 48 Weeks) | 34 of 43 |
| Placebo to Tocilizumab (up to 96 Weeks) | 39 of 44 |
| Tocilizumab to Tocilizumab (up to 96 Weeks) | 38 of 43 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo (up to 24 Weeks) | Tocilizumab (up to 24 Weeks) | Placebo (up to 48 Weeks) | Tocilizumab (up to 48 Weeks) | Placebo to Tocilizumab (up to 96 Weeks) | Tocilizumab to Tocilizumab (up to 96 Weeks) |
|---|---|---|---|---|---|---|---|
| Osteomyelitis | Infections and infestations | 0 of 44 | 2 of 43 | 1 of 44 | 2 of 43 | 2 of 44 | 2 of 43 |
| Skin ulcer | Skin and subcutaneous tissue disorders | 0 of 44 | 1 of 43 | 1 of 44 | 2 of 43 | 1 of 44 | 2 of 43 |
| Infected skin ulcer | Infections and infestations | 0 of 44 | 1 of 43 | 0 of 44 | 1 of 43 | 2 of 44 | 2 of 43 |
| Systemic sclerosis | Musculoskeletal and connective tissue disorders | 1 of 44 | 0 of 43 | 1 of 44 | 1 of 43 | 1 of 44 | 1 of 43 |
| Scleroderma renal crisis | Renal and urinary disorders | 1 of 44 | 0 of 43 | 1 of 44 | 0 of 43 | 2 of 44 | 0 of 43 |
| Haemolytic uraemic syndrome | Blood and lymphatic system disorders | 0 of 44 | 1 of 43 | 0 of 44 | 1 of 43 | 0 of 44 | 1 of 43 |
| Iron deficiency anaemia | Blood and lymphatic system disorders | 1 of 44 | 0 of 43 | 1 of 44 | 0 of 43 | 1 of 44 | 0 of 43 |
| Acute myocardial infarction | Cardiac disorders | 1 of 44 | 0 of 43 | 1 of 44 | 0 of 43 | 1 of 44 | 0 of 43 |
| Cardiac failure | Cardiac disorders | 1 of 44 | 0 of 43 | 1 of 44 | 0 of 43 | 1 of 44 | 0 of 43 |
| Cyanosis | Cardiac disorders | 1 of 44 | 0 of 43 | 1 of 44 | 0 of 43 | 1 of 44 | 0 of 43 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo (up to 24 Weeks) | Tocilizumab (up to 24 Weeks) | Placebo (up to 48 Weeks) | Tocilizumab (up to 48 Weeks) | Placebo to Tocilizumab (up to 96 Weeks) | Tocilizumab to Tocilizumab (up to 96 Weeks) |
|---|---|---|---|---|---|---|---|
| Pruritus | Skin and subcutaneous tissue disorders | 3 of 44 | 7 of 43 | 4 of 44 | 8 of 43 | 9 of 44 | 12 of 43 |
| Skin ulcer | Skin and subcutaneous tissue disorders | 6 of 44 | 6 of 43 | 7 of 44 | 7 of 43 | 9 of 44 | 8 of 43 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 6 of 44 | 6 of 43 | 8 of 44 | 6 of 43 | 10 of 44 | 6 of 43 |
| Diarrhoea | Gastrointestinal disorders | 4 of 44 | 6 of 43 | 4 of 44 | 7 of 43 | 5 of 44 | 12 of 43 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 4 of 44 | 4 of 43 | 5 of 44 | 5 of 43 | 7 of 44 | 5 of 43 |
| Back pain | Musculoskeletal and connective tissue disorders | 3 of 44 | 5 of 43 | 3 of 44 | 6 of 43 | 3 of 44 | 8 of 43 |
| Nasopharyngitis | Infections and infestations | 2 of 44 | 3 of 43 | 4 of 44 | 5 of 43 | 5 of 44 | 8 of 43 |
| Headache | Nervous system disorders | 2 of 44 | 3 of 43 | 3 of 44 | 5 of 43 | 5 of 44 | 8 of 43 |
| Fatigue | General disorders | 2 of 44 | 4 of 43 | 2 of 44 | 5 of 43 | 3 of 44 | 6 of 43 |
| Urinary tract infection | Infections and infestations | 3 of 44 | 2 of 43 | 3 of 44 | 3 of 43 | 5 of 44 | 6 of 43 |
Serious events with the highest arm-level rate: infected skin ulcer (4.7%), osteomyelitis (4.7%), skin ulcer (4.7%), scleroderma renal crisis (4.5%), haemolytic uraemic syndrome (2.3%).
The registry reports serious and other adverse-event counts for treatment periods up to 24 weeks, up to 48 weeks, and up to 96 weeks. Up to 24 weeks, serious adverse events affected 11 participants in the placebo group and 9 in the tocilizumab group; other adverse events affected 26 and 28 participants, respectively. Up to 48 weeks, the corresponding serious-event counts were 15 and 14, and other-event counts were 32 and 34.
For the period up to 96 weeks, the listed groups are placebo to tocilizumab and tocilizumab to tocilizumab. Serious adverse events affected 22 and 17 participants, respectively, while other adverse events affected 39 and 38. These longer-period groups include treatment sequences, not a continuing randomized comparison of placebo against tocilizumab. Event counts across these periods should not be treated as directly comparable rates: the periods differ in duration and, after Week 48, the planned treatment assignment changes.
The record also lists serious adverse-event terms and percentages, including infected skin ulcer, osteomyelitis, skin ulcer, scleroderma renal crisis, haemolytic uraemic syndrome, and arrhythmia. The reported percentages are tied to the registry’s adverse-event reporting and should not be converted into conclusions about comparative risk without fuller context. Death counts are not reported in the registry record. These figures describe posted events; they do not by themselves establish causation or determine an individual’s risk.
13. What the Result Does, and Does Not, Mean
The primary result is an estimate of the difference between randomized groups in mean mRSS change at Week 24. The point estimate is negative, which is in the direction of a larger average decrease in skin score with tocilizumab because the registry defines negative change as improvement. The confidence interval includes zero, and the reported p-value is 0.091. The data therefore leave substantial uncertainty about the size and direction of the between-group difference.
This finding does not establish that every participant experienced a change matching the group mean. A mean can conceal varied individual responses, and mRSS captures skin thickness rather than every feature of systemic sclerosis. The result also does not, on its own, establish whether any estimated difference is clinically important. A clinical-importance threshold is not reported in the registry record.
The primary comparison relates to Week 24 and the randomized, blinded period. The study plan describes open-label tocilizumab for all participants from Week 48 to Week 96, so later outcomes do not represent an ongoing placebo-controlled comparison. The registry’s secondary outcome at Week 48 uses a different definition from the primary endpoint, and the available secondary results cannot resolve the uncertainty in the primary analysis.
Statistical uncertainty is not the same as proof of no effect. A confidence interval that includes zero indicates that the posted analysis does not exclude no between-group difference; it does not show that the groups are identical. Conversely, a point estimate in a favorable direction is not sufficient to establish a reliable or clinically meaningful effect. The proper reading is bounded by the estimate, its interval, the reported analysis, and the limitations of the record.
The results also do not establish a comprehensive safety comparison. Adverse-event counts are reported over different periods and treatment sequences, and deaths are not reported in the registry record. Taken together, the posted data describe specific efficacy and safety outcomes but do not support broader claims beyond those measures and analyses.
14. Why This Trial Matters Statistically
This trial is statistically informative because it makes the distinction between an estimated effect and the certainty around that estimate visible. The primary point estimate favors a larger average reduction in mRSS in the tocilizumab group, but the confidence interval includes zero. Reading the point estimate without its interval would overstate how firmly the result identifies a between-group difference.
The design also illustrates why the time window matters. Randomization and blinding support a direct placebo comparison during the initial treatment period, whereas the planned switch to open-label tocilizumab after Week 48 changes what later comparisons can answer. A result from a later period cannot automatically be interpreted as though the original placebo comparison had continued unchanged.
The secondary binary result highlights another statistical issue: conclusions can depend on whether an effect is expressed as a risk difference or an odds ratio and whether the calculation is unadjusted or model-based. Those methods target related but distinct summaries. The sponsor’s reported analysis and the unadjusted recalculation should not be presented as interchangeable versions of one number.
Finally, the record lists many outcomes but does not report a multiplicity strategy or full analysis plan. That makes restraint important when interpreting isolated secondary findings. The trial is a useful example of reading outcome definitions, estimates, uncertainty, analysis methods, and reporting gaps together rather than relying on a single p-value or a favorable point estimate.
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 registry does not report the full statistical analysis plan, the primary sample-size justification, interim analyses, or all details of the mixed model. Without those details, readers cannot fully assess which model terms were prespecified, how the analysis handled departures from assumptions, or how closely the posted analysis followed the original plan.
The primary population description refers to randomized participants who had received any study drug by the Week 24 cutoff, and it says that analyzed counts include participants evaluable for the outcome. A complete participant flow and a specific missing-data strategy are not reported in the registry record. The number of participants with missing primary endpoint data, reasons for missingness, and sensitivity analyses are also not reported.
The trial enrolled 87 participants, while the primary arm summaries list 43.0 and 41.0 participants. The registry’s description does not provide a single complete account reconciling enrollment, randomization, treatment, and endpoint evaluability. This limits assessment of exclusions and analysis-population differences.
The primary endpoint is a clinical score that summarizes skin thickness across multiple sites. Although the registry describes the scale as validated, a clinical-importance threshold for the observed change is not reported in the registry record. The mean change also does not show the distribution of individual responses.
For secondary outcomes, results for the full set are not reported in the registry record, and no multiplicity approach is described. The secondary binary outcome has a sponsor-reported logistic regression analysis and a distinct unadjusted recalculation, making it important not to treat those estimates as equivalent. Safety counts span different durations and treatment sequences, and deaths are not reported in the registry record. These limitations constrain broad comparisons and conclusions from the posted information.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study of RoActemra/Actemra (Tocilizumab) Versus Placebo in Patients With Systemic Sclerosis — NCT01532869.
- Registry record last updated 2016-09-23; status last verified 2016-08.
- Results first posted 2015-11-05.
- 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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19. Record Summary
NCT01532869 is a completed randomized, double-blind, placebo-controlled, parallel-group study of tocilizumab in systemic sclerosis. The registry lists Phase 3, while the official title describes Phase II/III. Enrollment was 87. Participants were assigned to weekly subcutaneous tocilizumab at 162 mg or placebo during the first 48 weeks, followed by planned open-label tocilizumab for all participants through Week 96.
The primary endpoint was change from baseline in mRSS at Week 24. The reported mixed-model difference in least-squares means was -2.70, with a 95% confidence interval from -5.85 to 0.45 and p = 0.091. Negative change indicates improvement; the interval includes zero, leaving uncertainty about the between-group contrast.
The registry lists multiple secondary outcomes and adverse-event counts, but does not report the full analysis plan, multiplicity strategy, or missing-data methods. The posted results should be interpreted as outcome-specific estimates with the uncertainty and reporting limitations.