A Study on The Safety of Administering Rituximab at A More Rapid Rate in Patients With Rheumatoid Arthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study on The Safety of Administering Rituximab at A More Rapid Rate in Patients With Rheumatoid Arthritis (NCT01382940), a na phase 4 study. The primary outcome is Percentage of Participants Experiencing Any Infusion-related Reaction (IRR) Associated With the Second Rituximab Infusion.

2. Clinical Question

In practical statistical terms, this is a safety description of a specified infusion schedule in a selected study population, rather than a randomized test of whether one infusion rate is safer than another. The registry also lists outcomes relating to reactions, severe adverse events, and infusion interruptions around later infusions.

3. Trial Design

The registry identifies this as a Phase 4, multicenter, open-label, single-arm study. It lists 351 participants as enrolled. The study status is completed, with a start date of 2011-07-26 and a primary completion date of 2013-01-06. Hoffmann-La Roche is listed as the sponsor.

All participants were assigned to the rituximab group in the registry description; there was no separate control arm. The infusion schedule included a 4.25-hour infusion on Day 1 and 2-hour infusions on Day 15 and Days 168 and 182. Participants continued methotrexate as directed by their treating physician. Although the record lists methylprednisolone, acetaminophen, and antihistamine among the interventions, the available description of premedication is incomplete, so its full regimen is not reported in the registry record.

The primary endpoint focused on infusion-related reactions associated with the Day 15 infusion, within 24 hours after the infusion began. The primary analysis population is described as participants who received the faster-rate infusion on Day 15. Four participants who received that infusion were excluded from this population because their infusion rates could not be determined.

The record contains a wording inconsistency relevant to design interpretation: the primary population description refers to “randomized participants,” while the study is also designated single-group, with allocation listed as not applicable. No randomized comparison is described. Accordingly, the record supports reading this as a single-group safety study, not as a randomized comparison of infusion rates. The registry lists six secondary outcomes, addressing serious reactions, any reactions, severe adverse events, and infusion stopping, slowing, or interruption around the second and third infusions.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received infusion at the faster rate on Day 15. Four participants who received the Day 15 rituximab infusion were excluded from the primary analysis population because their infusion rates could not be determined.

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 Percentage of Participants Experiencing Any Infusion-related Reaction (IRR) Associated With the Second Rituximab Infusion, measured over Within 24 hours of beginning infusion on Day 15.

The primary endpoint was the percentage of participants experiencing any infusion-related reaction associated with the second rituximab infusion. The specified observation window was within 24 hours of beginning the infusion on Day 15. The registry defines an infusion-related reaction as an adverse event within that window that matched a prespecified list of preferred terms from the Medical Dictionary for Regulatory Activities.

This endpoint is used to describe the frequency of reactions temporally associated with the infusion. Expressing the outcome as a percentage makes the event frequency interpretable relative to the participants included in the analysis. The registry also specifies a 95% confidence interval as the measure of uncertainty around this percentage. General statistical interpretation: a confidence interval conveys the range of values reasonably compatible with the observed data under the method used; it does not remove uncertainty or establish that an infusion caused an event.

The registry record does not report the observed percentage or its confidence interval. It also does not provide the numerator and denominator for the primary endpoint result. The stated analysis population excludes four Day 15 infusion recipients whose infusion rates could not be determined, but the resulting analysis denominator is not reported in the registry record. As a result, readers can identify what was intended to be measured and over what period, but cannot assess the reported frequency or its precision from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that can be described from this record are limited. It identifies a percentage endpoint, a 95% confidence interval, a single-group design, and a primary analysis population. It does not report the detailed analysis procedures or the numerical primary result. The explanations below distinguish what the record states from general statistical context.

What does a percentage endpoint describe?

The primary outcome is the percentage of participants experiencing at least one qualifying infusion-related reaction associated with the second rituximab infusion. The registry defines qualifying reactions as adverse events occurring within 24 hours of the infusion beginning on Day 15 and included among a prespecified list of preferred terms from the Medical Dictionary for Regulatory Activities. General statistical explanation: for a binary outcome, each participant is classified according to whether the event occurred, and the percentage summarizes the event frequency in the analysis population. The event definition and observation window matter because changing either can change which events are counted.

The registry does not give the primary event count, the analyzed denominator, or the resulting percentage. Enrollment of 351 is the total enrolled count, not a substitute for the unreported primary analysis denominator. The primary-population description says four participants who received the Day 15 infusion were excluded because their infusion rates could not be determined. The resulting population size is not reported in the registry record.

What does the confidence interval add?

The primary endpoint specifies a 95% confidence interval. General statistical explanation: a confidence interval expresses uncertainty in an estimate, incorporating both the observed data and the method used to calculate the interval. A narrower interval generally indicates greater precision than a wider interval, while the location of the interval indicates the range of event frequencies compatible with the estimate under that method. A confidence interval is not a guarantee that the true value falls within the particular interval, and it does not establish causality.

Here, the interval's numerical limits are not reported in the registry record. Without those limits, or the underlying event count and denominator, readers cannot evaluate the precision of the primary estimate. The record does not state which specific confidence-interval calculation was used, so no more detailed description of that method is warranted.

Why does the single-group design matter?

The study is described as open-label and single-group, with allocation listed as not applicable and masking as none. There is no control group receiving a different infusion schedule. General statistical explanation: a single-group estimate can describe outcomes observed among participants receiving the study regimen, but it does not directly estimate a between-group treatment effect. In a randomized comparison, concurrent groups can help distinguish differences associated with assigned strategies from background event rates and other influences. That kind of comparison is not available.

Open-label conduct means the study is not described as masked. General statistical context: awareness of treatment or study procedures can affect how events are noticed, reported, assessed, or managed. The registry record does not specify procedures for blinded outcome assessment, so their use is not reported in the registry record.

What can be inferred from the listed event counts?

The adverse-event section lists 30 participants in the serious-event count and 37 in a separate other-event count, with 351 at risk for each. It also lists percentages for several serious-event terms. These figures are descriptive. They do not provide the primary infusion-reaction result, and the record does not describe a comparison group. General statistical context: counts and percentages answer different descriptive questions; counts show how many participants are represented, while percentages relate events to a stated denominator. The serious-event term percentages should be read as posted, without assuming unreported term counts or deriving new quantities.

The record does not report whether participants could contribute more than one event, how recurrent events were handled, or whether event counts refer to participants or episodes for each term. It also does not report the timing of the serious adverse events in relation to individual infusions. These details should not be inferred from the listed terms alone.

What analysis details are unavailable?

The registry lists seven outcome measures in total: one primary outcome and six secondary outcomes. It reports no analyses in the analysis listing. The record does not describe the statistical test or estimation procedure for the primary endpoint, a missing-data method, a multiplicity adjustment, or interim analyses. It also does not provide a sample-size justification or a prespecified precision target. These methods are not reported in the registry record.

The registry's primary-population description uses the phrase “randomized participants,” but the study design is also identified as single-group with allocation not applicable. Because no randomized comparison is described, the population wording should not be taken as evidence of a randomized design. The record does not explain this discrepancy.

General statistical context: safety results can be affected by the way events are defined, the population included, the observation window, missing information, and the analysis method. In this study, the endpoint definition and window are stated, but the numerical primary result and several analysis details are absent. The posted record therefore supports a description of the intended analysis, not a reconstruction or independent verification of its result.

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.

R code and output

arm    <- c("Rituximab")
n      <- c(337)
events <- c(22)
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  Rituximab  337  22  6.5  4.1  9.7  4.4  9.7  4.4  9.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcomes: one primary endpoint and six secondary outcomes. The secondary endpoints cover serious infusion-related reactions associated with the second infusion; any reaction or serious reaction associated with the third infusion; severe adverse events associated with the second and third infusions; and stopping, slowing, or interrupting the second and third infusions.

The registry record does not report whether statistical testing across these outcomes was planned, whether any adjustment for multiple comparisons was used, or how outcome priority was handled beyond identifying a primary endpoint. It also does not report interim analyses. These procedures are not reported in the registry record. General statistical context: when several outcomes are examined, the chance of observing an apparently notable result by chance can be affected by how many analyses are conducted and how they are interpreted. A prespecified primary endpoint can help organize interpretation, but it does not reveal whether a multiplicity procedure was used.

The primary analysis population is described as participants who received the faster Day 15 infusion, excluding four participants whose infusion rates could not be determined. The final denominator and the number of primary endpoint events are not reported. The record does not explain how other missing outcome information, if any, was handled, or whether all enrolled participants contributed to each secondary endpoint.

There is also a design-description inconsistency: the primary population wording refers to randomized participants, whereas the study is listed as single-group with allocation not applicable. No randomized comparison is described, and the registry does not explain the wording. The record identifies 351 enrolled participants, but does not provide a flow of participants through each infusion or analysis population.

Because the analysis results are not listed, the record does not allow readers to assess the effect of missing observations or any multiplicity approach on the reported estimates. The statistical plan and detailed analysis populations are not reported in the registry record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (1.1%), atrial fibrillation (0.6%), hip fracture (0.6%), rheumatoid arthritis (0.6%), febrile neutropenia (0.3%).

The adverse-event section lists a rituximab group with 351 participants at risk for serious adverse events and 351 at risk for the separate other adverse-event count. It reports 30 participants under the serious-event count and 37 under the other-event count. These are descriptive counts from the posted results; they are not the primary endpoint result and do not compare infusion rates.

The record also lists serious-event terms with percentages: pneumonia, 1.1%; atrial fibrillation, 0.6%; hip fracture, 0.6%; rheumatoid arthritis, 0.6%; febrile neutropenia, 0.3%; and cardiac failure congestive, 0.3%. The registry does not provide corresponding term counts in this record. These listed percentages should not be converted into counts or treated as evidence about whether an event was caused by rituximab or by a particular infusion rate.

The deaths value is not reported in the registry record. This should not be read as a reported count of zero. The record also does not specify event timing, recurrence, or how the serious-event terms relate to the infusion windows. General statistical context: safety listings summarize events observed during study follow-up, but interpretation depends on definitions, timing, exposure, and the population monitored. The available entries do not establish a causal relationship.

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

This trial is relevant as a registry record of a specified faster rituximab infusion schedule in people with rheumatoid arthritis. It describes a single-group safety study, including a primary endpoint focused on infusion-related reactions within 24 hours of the Day 15 infusion. The record also lists outcomes addressing reactions, severe adverse events, and infusion interruptions at later infusions.

What the record does not show is the numerical primary endpoint result. The observed percentage, its 95% confidence interval, and the primary analysis denominator are not reported. Consequently, readers cannot determine from this record how frequently the defined Day 15 reactions occurred or how precisely their frequency was estimated. The adverse-event section provides some overall counts and serious-event term percentages, but these do not fill that gap.

The study design also limits what its results could establish. There was no concurrent comparator group, and the study was open-label. Even a reported event percentage would describe observations in this group under the study schedule; on its own, it would not quantify the difference between a faster and slower infusion strategy. It would not establish that the infusion rate caused or prevented a particular event.

The record identifies 351 participants enrolled, but not every enrolled participant is necessarily represented in the primary analysis population. Four Day 15 infusion recipients were excluded because their infusion rates could not be determined, and the final primary analysis denominator is not reported. The record does not describe how missing information was handled for the other outcomes.

In general, safety findings are interpreted in the context of event definitions, observation periods, exposed populations, and the completeness of follow-up. Here, the primary event definition and time window are available, but the corresponding result and several analysis details are not. The registry record therefore supports a description of the question and study structure, but not a quantitative conclusion about the primary endpoint or a comparative conclusion about infusion rates.

14. Why This Trial Matters Statistically

This study illustrates why the statistical design and the completeness of a registry result matter alongside the stated clinical question. The record defines a specific safety endpoint: any qualifying infusion-related reaction associated with the Day 15 rituximab infusion, occurring within 24 hours after it began. It also identifies a 95% confidence interval as the intended expression of uncertainty. Those details help readers understand what the primary result was meant to summarize.

However, the primary estimate and interval are not reported in the registry record. Without them, the endpoint definition cannot be translated into an estimate of event frequency or precision. The overall enrollment of 351 does not resolve this, because the primary analysis population was narrower and excluded four participants whose Day 15 infusion rates could not be determined. Its final size is not reported.

The single-group design provides no concurrent control for interpreting observed safety events. General statistical context: a descriptive event frequency can be useful for understanding what was observed in a study population, but it does not by itself estimate a contrast between treatment strategies. This distinction is especially important when a trial's question concerns a change in how an intervention is administered.

The record also lists six secondary outcomes and some broader adverse-event counts. These show that safety assessment extended beyond the primary reaction endpoint, but the secondary results and multiplicity procedures are not reported. A complete interpretation would need the results, analysis populations, and relevant methods, not only the list of outcomes.

Statistically, the record is useful for identifying the target population, infusion schedule, endpoint definition, and limitations of the design. It also demonstrates that a stated confidence-interval plan is not enough to evaluate precision if the interval itself is absent. The posted information cannot support a full quantitative assessment of the primary safety question.

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 central limitation of this registry record is that it does not report the primary endpoint estimate or its 95% confidence interval. It also does not report the primary analysis event count or final analysis denominator. The record states that four participants who received the Day 15 infusion were excluded because their infusion rates could not be determined, but does not report the resulting population size.

The study has no concurrent comparator group and is described as open-label and single-group. It therefore cannot provide a like-for-like comparison of faster and slower infusion rates. The record's use of the phrase “randomized participants” in the primary population description is not reconciled with the single-group design and allocation listed as not applicable.

The registry lists six secondary outcomes but does not report their results. It does not describe a multiplicity adjustment, interim analyses, missing-data procedures, or the detailed statistical analysis method. A sample-size justification is not reported in the registry record. These omissions prevent assessment of how the analysis was planned and how incomplete observations may have affected results.

The adverse-event section reports 30 participants under serious adverse events and 37 under a separate other-event count, with 351 at risk for each. It lists percentages for several serious-event terms, but does not provide term counts, event timing, or details about recurrent events. The deaths value is not reported in the registry record, so it cannot be interpreted as zero. The premedication description is incomplete, and the record does not give a full account of concomitant treatment procedures.

These limitations apply to interpretation of the registry record and should not be taken as evidence that unreported analyses or information were absent from other study materials. They mean that the posted information alone does not allow a complete evaluation of the primary endpoint's frequency, precision, or comparative meaning.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study on The Safety of Administering Rituximab at A More Rapid Rate in Patients With Rheumatoid Arthritis — NCT01382940.
• Registry record last updated 2017-08-01; status last verified 2017-07.
• Results first posted 2014-02-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This Phase 4 study was a multicenter, open-label, single-group evaluation of a faster rituximab infusion schedule in people with moderate to severe rheumatoid arthritis. The registry lists 351 participants enrolled and describes infusions over 4.25 hours on Day 1 and over 2 hours on Day 15 and Days 168 and 182. Participants continued methotrexate as prescribed by their treating physician.

The primary endpoint was the percentage experiencing any qualifying infusion-related reaction associated with the Day 15 infusion, within 24 hours of its beginning. Four participants were excluded from the primary analysis population because their infusion rates could not be determined. The primary percentage, confidence interval, and final analysis denominator are not reported in the registry record.

The registry lists six secondary safety outcomes and reports group-level counts of 30 serious adverse events and 37 in a separate other-event category, each among 351 at risk. The study has no concurrent comparator, and the posted record does not include the primary or secondary outcome results needed for a full quantitative interpretation.