A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA) (NCT00642460), a randomized phase 3 study. The primary outcome is Part I: Percentage of Participants With ≥30% Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, quadruple-masked, parallel-group study of tocilizumab versus placebo in patients with active systemic juvenile idiopathic arthritis. The registry record lists enrollment of 112 participants. Part I was the double-blind comparison, with intravenous study treatment given every 2 weeks and randomization in a 2:1 ratio. The brief description specifies weight-based tocilizumab dosing and continuation of stable NSAIDs and methotrexate.

The primary outcome was measured at Week 12. After 12 weeks of double-blind treatment, participants had the option to enter Part II for open-label tocilizumab treatment for a further 92 weeks. The study description then gives a 3-year continuation in Part III. For participants meeting specific criteria, an optional alternative dosing schedule decreasing administration frequency was to be introduced in Part III. Anticipated time on study treatment was up to 5 years. These extensions differ from the randomized placebo comparison: the primary efficacy result concerns the Part I comparison, while the safety group described in the registry combines Parts I, II and III.

The registry record marks the study completed and gives May 2008 as the start and September 2009 as the primary completion. The record does not report the random sequence-generation method, allocation concealment procedure, masking implementation, participant flow by treatment phase, or the number who entered each extension. The arm descriptions are not populated. Those omissions limit assessment of how the planned design was implemented and how many participants contributed to later follow-up.

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: This study consists of 3 parts. Part I: a 12 week double-blind placebo controlled study followed by Part II: a 92 week single arm open-label extension study followed by Part III: a 3 year open label continuation study.

Part I: 12 Week Double-Blind

Reasons for not completing this period:

Part II: Open-Label Up to Week 92

Reasons for not completing this period:

Part III: Open-Label Up to Week 260

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population includes all participants who had at least one dose of study drug.

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.

6. Primary Endpoint

The registry lists the primary outcome as Part I: Percentage of Participants With ≥30% Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever, measured over Baseline, Week 12.

The primary endpoint is the percentage of participants who met a combined response definition at Week 12. It required at least 30% improvement in the JIA ACR core set and absence of fever. The core set comprises 6 components: physician’s global assessment of disease activity, parent or patient global assessment of overall well-being, maximum number of joints with active arthritis, number of joints with limitation of movement, erythrocyte sedimentation rate, and the Childhood Health Assessment Questionnaire Disability Index. Fever absence was defined as no diary temperature recording of at least 37.5° Celsius in the preceding seven days.

A combined endpoint captures more than one aspect of disease status. A participant had to satisfy the improvement criterion and the fever criterion to count as a responder; improvement alone was not enough under this definition. This makes the outcome clinically interpretable as a response across disease assessment domains together with absence of recorded fever during the specified period. It also means that the percentage depends on how each component was assessed and on complete information needed to classify the combined response.

The endpoint is reported for the intent-to-treat population, defined in the registry record as participants who received at least one dose of study drug. The record does not report a more detailed missing-data rule for participants without an assessable Week 12 response.

7. Results Posted in the Registry

• Tocilizumab: 85.3% (64/75) versus 24.3% (9/37) on control; risk difference 61.0 percentage points (95% CI 45.0 to 77.0), risk ratio 3.51 (1.97–6.24); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Tocilizumab: 85.4% (35/41) versus 20.8% (5/24) on control; risk difference 64.5 percentage points (95% CI 45.0 to 84.1), risk ratio 4.10 (1.86–9.03); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Tocilizumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Part I: Percentage of Participants With Concomitant Corticosteroid Reduction

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Tocilizumab: 24.3% (17/70) versus 3.2% (1/31) on control; risk difference 21.1 percentage points (95% CI 9.2 to 32.9), risk ratio 7.53 (1.05–54.09); unadjusted two-proportion z-test p = 0.011.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Tocilizumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Tocilizumab: 77.3% (58/75) versus 18.9% (7/37) on control; risk difference 58.4 percentage points (95% CI 42.6 to 74.2), risk ratio 4.09 (2.07–8.05); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Tocilizumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes with numerical results cover fever among participants who had fever at baseline, concomitant corticosteroid reduction, and minimally important improvement in CHAQ-DI. Across these reported comparisons, the observed percentages are higher in the tocilizumab group than in the placebo group. This is directionally consistent with the primary comparison, which also favored a higher observed response proportion in the tocilizumab group. The secondary outcomes add context by addressing fever, steroid use, and functional impact rather than repeating the full combined primary definition.

These findings should be treated as supportive rather than as separate proof of the primary result. Secondary endpoints are often numerous and may be evaluated for different purposes. The registry lists 33 secondary outcomes, while the posted endpoint details include results for only some of them. Numerical results for the other listed secondary measures are not reported in the registry record. This incomplete result set makes it difficult to assess the full pattern of outcomes or the possibility of selective emphasis.

The secondary comparisons include unadjusted p-values and confidence intervals for the risk differences, but the registry record does not report a multiplicity procedure or a prespecified hierarchy for testing them. When multiple outcomes are examined, isolated nominal p-values can overstate the strength of evidence if the chance of false-positive findings is not controlled. Effect estimates remain useful descriptions of the posted results, but should not be treated as confirmatory claims without knowing the analysis plan and multiplicity handling.

The secondary outcomes also use different analysis populations or time points, as indicated by their individual definitions. Their results therefore need not represent the same participants or estimand as the primary endpoint. They relate to the primary result by broad directional consistency, not by establishing that the entire treatment effect operates through any one secondary measure.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12
• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity
• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being
• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis
• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement
• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate
• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI)
• Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12

9. Statistical Interpretation

10. Statistical Methods Explained

What does the response percentage represent?

For a binary endpoint, each participant is classified into one of two categories: the defined event occurred or it did not. In this study, the event is meeting the combined primary response criterion. The percentage in each group represents the observed proportion classified as a responder among the participants included in that group’s analysis. It is not an average change in a continuous disease score, and it does not describe the size of response among responders.

The clinical definition matters because it determines what counts as an event. Here, response required both the specified improvement in the JIA ACR core set and absence of fever according to the diary-based definition. A participant who met one part but not the other would not meet the combined criterion. This creates a clear yes-or-no outcome but can conceal different component-level patterns behind the same overall classification.

What is a risk difference?

The risk difference compares the response proportions by subtracting the comparator-group proportion from the intervention-group proportion. It expresses the contrast on the absolute probability scale: a positive estimate means the observed response proportion was higher in the tocilizumab group. The registry-derived estimate is 0.610. Its confidence interval is 0.450 to 0.770. These estimates are reported as proportions; they should not be mistaken for relative risks or odds ratios, which use different scales.

An absolute contrast is often useful because it directly describes separation between group response probabilities. It remains tied to the outcome definition, study population, follow-up time, and analysis approach. It does not imply that every participant’s outcome would change in the same way under a different treatment assignment.

How should the confidence interval be understood?

A confidence interval gives a range of values compatible with the data under the statistical procedure used, reflecting sampling uncertainty. For the primary risk difference, the interval extends from 0.450 to 0.770. The interval does not describe variation in individual responses, guarantee that the true value lies inside it, or address every possible source of bias. In particular, a confidence interval does not correct for missing outcomes, selective reporting, or an analysis that was not prespecified.

The primary group percentages are reported without confidence limits in the registry record, while the risk-difference comparison has a reported interval. The interval is therefore the available precision summary for the contrast, not a substitute for intervals around each group’s response proportion.

What does the p-value say?

The registry lists an unadjusted p-value of <0.001 for the primary comparison. A p-value describes how incompatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, nor a measure of the clinical importance of the estimate. It also does not account for multiplicity unless the procedure explicitly incorporates such an adjustment; no such adjustment is reported in the registry record.

The record does not report the exact test or model used for the sponsor’s primary comparison, nor whether any covariate adjustment was part of the sponsor’s analysis. The displayed recalculated comparison is an unadjusted calculation from posted summary statistics. There is no discrepancy flagged between that calculation and the posted summaries, but a sponsor-reported analysis would take precedence if a discrepancy were present.

Why does the analysis population matter?

The primary population is called intent-to-treat in the registry record, with a definition that includes participants who received at least one dose of study drug. This operational definition is important to preserve when interpreting the results. The record does not provide a participant-level accounting of randomization, treatment received, exclusions, or missing Week 12 outcome data. It therefore does not allow a full assessment of whether the analyzed population followed the intended randomized comparison in every respect.

In general, intention-to-treat analysis aims to retain participants in their randomized groups, reducing bias that can arise when people are excluded after assignment. The registry’s stated definition should not be expanded beyond what it says: it specifies at least one dose, and does not describe handling of every possible post-randomization event.

Why can secondary results be less conclusive?

Secondary outcomes can provide context on different facets of disease and treatment, but evaluating many endpoints increases the chance that some will appear notable by chance. A multiplicity procedure can control the overall error rate when several hypotheses are tested, but the registry record does not report whether one was used. The secondary p-values are unadjusted in the posted comparisons. Their estimates can still be informative descriptively, but their inferential weight is lower when the analysis hierarchy and multiplicity handling are unknown.

The registry record lists no reported analysis entries for the secondary outcomes. The absence of a reported analysis plan means the chosen tests, covariates, missing-data rules, and handling of repeated assessments cannot be verified from the record. These uncertainties do not erase the observed values; they qualify how strongly those values can support confirmatory claims.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.610, and its confidence interval runs from 0.450 to 0.770. This interval indicates that the estimated contrast is subject to sampling uncertainty, while remaining on the positive side of zero. The reported p-value is <0.001. The interval and p-value address related but distinct aspects of the comparison: the interval conveys a range of effect estimates compatible with the data under the method, while the p-value summarizes evidence against a null comparison under that method’s assumptions.

The arm-level primary response proportions are 85.3% for tocilizumab and 24.3% for placebo. No confidence intervals for those primary arm proportions are reported in the registry record. The interval posted for the risk difference does not give the uncertainty for either arm separately, and the displayed percentages should not be read as exact population values.

Precision is also affected by the number of observations contributing to the endpoint and by how outcomes are distributed. The registry lists 75 participants in the tocilizumab primary analysis group and 37 in the placebo group. It does not report the number with missing Week 12 data or the rule used to classify missing outcomes. Without that information, the reported interval cannot address uncertainty introduced by missingness or possible departures from the stated population definition.

Confidence intervals quantify statistical uncertainty under the analysis assumptions; they do not resolve questions about generalizability, measurement quality, bias, or multiplicity. The interval should therefore be read alongside the study design and reporting limitations rather than as a complete summary of certainty.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations use participants per arm for the binary outcomes in this study; they are not total event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. These are retrospective planning illustrations based on the observed result, not the trial’s original design assumptions. The original sample-size justification and assumptions are not reported in the registry record.

The 80% power column describes the illustrative number of participants per arm needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column gives the corresponding planning number for a 90% chance. Power is a design property calculated under assumptions; it is not the probability that the result is true, and it does not measure the evidential strength of the completed trial.

Rows planning for 100% of the observed effect use the observed contrast as the target. Rows planning for 75% or 50% of the observed effect use smaller target effects. Smaller effects are harder to distinguish from random variation and therefore require more participants per arm in these illustrations. For example, the primary outcome’s planning figures increase as the target moves from the full observed effect to a smaller fraction. The same pattern is presented for the secondary outcomes with comparisons.

These figures are planning illustrations, not observed power. They do not show what power the completed study actually had, and they do not validate the original trial size. Results depend on the assumed effect and statistical conditions, which may differ from those used in the trial’s design.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.243; treatment proportion p₁ = 0.853; average p̄ = 0.548.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7038 = 1.3794.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5561 = 0.4680.
4. n = (1.3794 + 0.4680)² / (0.6101)² = 9.2, rounded up to 10 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.243243243243243                          # control proportion
p1 <- 0.853333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(642460)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 10 (80% power), 12 (90% power)
 75% of observed effect: n per arm = 18 (80% power), 23 (90% power)
 50% of observed effect: n per arm = 40 (80% power), 52 (90% power)
power.prop.test: 9.2 
Simulated power at n = 10 per arm: 0.826 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record does not report whether the primary endpoint was part of a prespecified testing hierarchy, whether secondary outcomes were adjusted for multiple comparisons, or whether interim analyses were planned or conducted. The posted comparisons identify p-values as unadjusted. Without a reported multiplicity strategy, the secondary p-values should be read as nominal results rather than as evidence that controls the overall probability of a false-positive conclusion across outcomes.

The record lists 35 outcome measures and 33 posted secondary outcomes. A number of measures address related but nonidentical aspects of disease response. Testing several outcomes can be informative, but it creates choices about which results to emphasize and how to control error rates. The record does not report the statistical analysis plan needed to evaluate those choices. The formal analysis entries are not reported in the registry record.

The primary population is described as intent-to-treat, including participants who received at least one dose of study drug. The registry record does not report how missing Week 12 measurements were handled, whether missingness differed by group, or whether sensitivity analyses were performed. It also does not give a participant flow accounting sufficient to reconcile randomized participants, treated participants, and those with endpoint data. Missing-data methods can influence a binary response result because each unclassified outcome must be handled according to an explicit rule.

The study has an initial double-blind placebo-controlled period followed by optional open-label and continuation periods. The record does not report how many participants entered each extension or the statistical methods for longer-term efficacy analyses. It also does not report details of interim monitoring or the original sample-size justification. These missing details limit assessment of analysis planning and of how the reported endpoint results fit into the full study program.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2.68% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: histiocytosis haematophagic (4.5%), gastroenteritis (4.5%), pneumonia (4.5%), varicella (4.5%), herpes zoster (2.7%).

The serious adverse event summary covers the group titled All Tocilizumab (Part I, Part II and Part III). The registry lists 112 participants at risk and 48 with a serious adverse event. This is a broad study-period summary across the tocilizumab treatment phases, not a randomized Part I comparison with a placebo safety group. It should not be interpreted as a comparative estimate of risk between randomized treatments.

The registry also lists 112 participants at risk for other adverse events and 112 affected. These categories are reported separately from the serious-event count. The record does not provide a placebo-group safety summary in the details, nor does it establish that reported events were caused by treatment. Adverse events recorded during a trial can have multiple possible causes.

The listed serious-event terms include histiocytosis haematophagic, gastroenteritis, pneumonia, and varicella, each reported at 4.5%; herpes zoster at 2.7%; and lower respiratory tract infection at 1.8%. The registry record does not report deaths in the safety summary. Event-term percentages describe the posted safety listing and should not be treated as a complete account of event timing, severity, recurrence, or causal attribution.

16. What the Result Does, and Does Not, Mean

The primary result shows a higher observed Week 12 response proportion in the tocilizumab group than in the placebo group for the combined criterion of at least 30% improvement in the JIA ACR core set and absence of fever. The estimated risk difference is 0.610, with a confidence interval from 0.450 to 0.770 and an unadjusted p-value of <0.001. This is evidence of a separation between the observed group proportions in the Part I comparison.

The result does not mean that every participant receiving tocilizumab met the response criterion, or that no participant receiving placebo did so. It does not identify which core-set components account for the combined response, or show the extent of change among participants who did not meet the binary threshold. A group-level percentage cannot describe every individual’s experience.

The estimate applies to the study’s defined population, treatment regimen, comparator, outcome definition, and Week 12 assessment. It does not by itself establish effects beyond that setting or demonstrate persistence after the double-blind comparison. The later study periods were open-label or continuation phases, and their safety summary is not a randomized placebo comparison.

The posted findings also do not establish a complete benefit-risk balance. The serious adverse event summary spans tocilizumab exposure across Parts I, II and III and lacks a corresponding placebo safety summary in the record details. The registry does not report causal attribution, missing-data handling, multiplicity adjustment, or the complete statistical analysis plan. Those limitations qualify how broadly or definitively the results can be interpreted.

Statistical significance is not equivalent to proof of a mechanism, certainty about every outcome, or a statement about what any individual should do. The defensible interpretation is narrower: the posted Week 12 data show a higher proportion meeting the specified response definition in the tocilizumab group than in the placebo group, with uncertainty summarized by the reported confidence interval.

17. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions matter in clinical research. The primary outcome is not a single laboratory measure or a general judgment of improvement; it combines at least 30% improvement across the JIA ACR core set with a specified fever criterion. The resulting percentage is straightforward to compare, but its meaning depends on the full rule for classifying response. Readers need both the statistical estimate and the operational definition to understand what the comparison represents.

The example also distinguishes an absolute effect measure from a significance test. The risk difference describes separation in observed response proportions, while the p-value addresses compatibility with a null hypothesis under statistical assumptions. The confidence interval adds information about precision. None of these measures alone addresses missing data, multiplicity, outcome selection, or generalizability.

Finally, the study’s phases highlight the importance of matching a result to its design. The primary efficacy contrast comes from the randomized, placebo-controlled Part I period. The safety group covers tocilizumab exposure across Parts I, II and III. Treating those summaries as if they shared one comparison would blur the difference between controlled efficacy evidence and longer-term event reporting. Careful reading keeps the endpoint, population, follow-up period, and analysis aligned.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the original sample-size justification, the exact statistical test or model used for the sponsor’s primary analysis, or a detailed analysis plan. Although the posted comparison has an unadjusted p-value and a confidence interval, the record does not explain covariate adjustment, the planned handling of multiplicity, or whether interim analyses were considered. These omissions restrict evaluation of the prespecification and robustness of the analyses.

The primary population is defined as participants who received at least one dose, but the record does not give a complete flow from randomized assignment through treatment and Week 12 assessment. It also does not report the missing-outcome rule or sensitivity analyses. The primary arm percentages are not accompanied by arm-specific confidence intervals in the registry record, even though an interval is reported for the risk difference.

The Part I result concerns a single Week 12 assessment and a composite binary endpoint. The record does not provide the component-level primary results in the endpoint details, so the combined response cannot show which elements contributed to the group contrast. The secondary findings are unadjusted, and numerical results are not reported for every listed secondary outcome.

Safety information is aggregated across all tocilizumab treatment parts and lacks a placebo-group comparison in the details available. The record does not give event timing, causal attribution, or deaths in the safety summary. These limitations mean that efficacy and safety summaries should be read as separate descriptions with different populations and follow-up, rather than combined into a single comparative assessment.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA) — NCT00642460.
• Registry record last updated 2016-07-25; status last verified 2016-06.
• Results first posted 2011-10-26.
• 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.

22. Record Summary

The registry record describes a completed Phase 3, randomized, quadruple-masked, parallel-group study of tocilizumab versus placebo for active systemic juvenile idiopathic arthritis. Part I was a 12-week double-blind comparison. The primary endpoint was the percentage meeting at least 30% improvement in the JIA ACR core set and absence of fever at Week 12.

The posted primary response proportions were 85.3% with tocilizumab and 24.3% with placebo. The risk-difference estimate was 0.610, with a confidence interval from 0.450 to 0.770 and an unadjusted p-value of <0.001. Secondary results with posted values were directionally consistent, but multiplicity handling and missing-data methods are not reported in the registry record.

The study included optional open-label and continuation phases. The listed serious adverse events summarize tocilizumab exposure across Parts I, II and III and do not constitute a randomized safety comparison.