CU Programme of Idarucizumab for Japanese Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CU Programme of Idarucizumab for Japanese Patients (NCT02831660), a na phase 3 study. The primary outcome is Percentage of Subjects With Drug-related Adverse Events.

2. Clinical Question

The clinical context is urgent: patients were receiving dabigatran and required rapid reversal because of bleeding or a need for emergency surgery or an urgent procedure. The registry describes a compassionate-use program focused on safety collection. That context explains why the study question is framed around adverse events in treated patients rather than a randomized comparison of treatment strategies.

The question is narrow. It concerns the recorded occurrence of drug-related adverse events over the stated observation window in the treated set. It does not, by itself, ask whether idarucizumab changes the risk of an event relative to another treatment, nor does it establish how effectively anticoagulant effects were reversed. Those comparative or efficacy questions are not answered by the primary endpoint as described.

3. Trial Design

The registry identifies NCT02831660 as a completed phase 3 compassionate-use program of idarucizumab for Japanese patients. Its official title describes a program for patients treated with dabigatran who have uncontrolled bleeding or require emergency surgery or procedures. The brief summary also refers to life-threatening bleeding and the need for rapid reversal of dabigatran’s anticoagulant effects.

The design is recorded as single-group. Allocation is listed as not applicable, and masking is listed as none. There is no randomized allocation and no control arm in the record, so the study is descriptive rather than a like-for-like treatment comparison. The registry records enrollment as 1. The safety grouping is labelled “Idarucizumab 5 g”; the record does not give a further arm description.

The listed start date is 2016-07-22, and the primary completion date is 2016-09-16. The overall study status is completed. The sponsor is Boehringer Ingelheim. These administrative details describe the registry entry; they do not provide information about the clinical course or follow-up of the participant.

The primary outcome is the percentage of participants with drug-related adverse events in the treated set. Its timeframe begins with first drug administration and continues until 5 days after last drug administration, up to 6 days. The registry lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a sample-size justification, interim analyses, or details of how the study’s compassionate-use setting affected enrollment or follow-up.

Because the study has no comparator group and enrollment is recorded as 1, its design cannot estimate a between-group treatment effect. Its scope is the safety information collected in the treated set and the registry’s description of the program. The primary endpoint result itself is not numerically reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: Treated Set

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: Treated set (TS) comprised all patients who had been received at least 1 dose of the study medication.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects With Drug-related Adverse Events, measured over from first drug administration until 5 days after last drug administration, up to 6 days..

The primary endpoint is the percentage of participants in the treated set who had drug-related adverse events. The observation window runs from first drug administration until 5 days after last drug administration, up to 6 days. This endpoint is intended to describe the frequency of attributed adverse events during a defined period after exposure, rather than to compare outcomes between treatment groups.

A percentage is a binary-outcome summary: each participant is classified according to whether the specified event occurred, and the result expresses the affected participants relative to the relevant analysis population. In general, this kind of measure is straightforward to interpret when the event definition, attribution process, observation window, and population denominator are clear. The registry identifies the treated set and the timeframe, but does not report further operational details about event attribution or endpoint assessment.

The endpoint is relevant to the registry’s stated objective of collecting safety data in patients needing rapid reversal. However, a primary endpoint label is not itself a result. A numerical value for the percentage, its numerator and denominator, or an uncertainty interval for this endpoint is not reported in the registry record. The separate safety figures list serious and other adverse-event counts, but they do not supply a numerical result for the primary drug-related adverse-event endpoint. Those safety categories should therefore not be substituted for the primary endpoint.

The measure also has limits: it describes recorded events in the treated set over the specified window and does not, on its own, show how the event frequency compares with what would have occurred without idarucizumab.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A binary endpoint records whether a participant did or did not experience a defined event during a specified observation period. A percentage describes the share of an analysis population classified as having the event. This is a general explanation of the measure; it does not supply a result for this study. The registry names a percentage of participants with drug-related adverse events as its primary endpoint and defines the treated set as the population. It does not report the primary endpoint’s numerical value.

What does a percentage represent?

For a binary outcome, the percentage is based on an event count and a denominator. Interpretation requires knowing how the event was defined, which participants were included, and how missing outcome information was handled. The registry gives the endpoint label, population name, and timeframe, but does not report the event count, denominator for the primary result, or additional rules for classifying an event as drug-related. The separate adverse-event figures are not enough to reconstruct that primary endpoint because they are organized by seriousness and do not identify the drug-related endpoint count.

A percentage is also an estimate, not a complete account of uncertainty. A confidence interval is a general statistical method for expressing the range of values compatible with the observed data under a specified method. It is especially important to consider precision when the available information is sparse: a small amount of data can leave substantial uncertainty even when the observed count is clear. No confidence interval for the primary endpoint is reported in the registry record, and none can be inferred from the endpoint description alone.

Why does the design matter?

In a randomized comparison, treatment groups can support an estimate of the difference between strategies, subject to the study’s design and analysis. This program is recorded as single-group, with allocation not applicable and masking none. It therefore provides no concurrent control group. Its safety observations describe what was recorded among treated participants; they do not estimate the contrast between idarucizumab and an alternative. In general, a single-group design also makes causal attribution difficult because the study cannot distinguish the intervention’s contribution from the clinical circumstances that led to treatment.

The registry records enrollment as 1, while the safety record lists 1 at risk in each of the serious and other adverse-event categories. These entries describe separate categories and should be read as recorded, not combined. The record does not provide enough information to establish how the primary endpoint population corresponds to each safety category or to reconstruct any unreported endpoint percentage.

What can be said about analysis?

The registry lists zero analyses. It does not report a statistical analysis plan, a hypothesis test, an adjusted model, or an uncertainty interval. The absence of listed analyses means there is no reported inferential procedure to interpret. It does not establish which procedures might have been contemplated or why results were not listed; those details are not reported in the registry record.

The record includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. Such calculations are general planning exercises, not observed power and not evidence that this single-group program was designed with those assumptions. They do not convert the program into a comparative trial, and no planning illustration values should be treated as results from participants.

Why does over-dispersion matter generally?

Over-dispersion is a general concern when data vary more than a statistical model assumes. If a model underestimates variability, it can make uncertainty appear smaller than it is. It often arises in settings involving counts, clustering, or repeated observations. The registry information does not describe a count model, repeated-measures analysis, or an over-dispersion assessment, so this concept is not a reported method used in this program. It is relevant as a general reminder that statistical uncertainty depends on assumptions, and those assumptions need to be stated before model-based results can be evaluated.

For this record, the most defensible reading is consequently descriptive. The primary endpoint and observation window are specified, but its numerical result is not. The safety counts can be reported as recorded, while causal, comparative, and precision claims remain unsupported by the information in the registry record.

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("Idarucizumab 5 g")
n      <- c(1)
events <- c(0)
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  Idarucizumab 5 g  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. It identifies the primary endpoint as the percentage of participants with drug-related adverse events in the treated set. The record does not describe a family of inferential tests, a hierarchy of secondary outcomes, or a multiplicity adjustment. With no analyses listed, there are no reported p-values or multiple-comparison procedures to evaluate. Whether any other analyses were planned or conducted is not reported in the registry record.

Missing-data methods are also not reported in the registry record. There is no description of how missing event assessments, incomplete follow-up, or unavailable safety information would be handled. The stated endpoint timeframe is from first drug administration until 5 days after last drug administration, up to 6 days, but the registry does not give participant-level follow-up completeness or explain how the window was applied if follow-up ended early.

The endpoint population is named as the treated set, but its operational definition is not reported in the registry record. The record does not explain whether all participants who received any amount of study drug were included, how treatment exposure was verified, or whether any additional eligibility rules applied to the analysis set. The enrollment entry and the safety at-risk counts do not replace those definitions.

These omissions matter because endpoint estimates depend on which observations enter the denominator and how unavailable outcomes are treated. Without the analysis population rules and missing-data approach, a reader cannot fully assess the risk of bias or reproduce the primary endpoint. The absence of a numerical primary result makes that assessment still more limited.

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 non-serious adverse event terms

The registry’s safety record lists the “Idarucizumab 5 g” group with 1 participant at risk in the serious adverse-event category and 0 affected. For other adverse events, it lists 1 at risk and 1 affected. These category-specific figures are reported separately; they should not be added or treated as interchangeable outcomes. The “other” adverse-event count does not establish that the event was drug-related and is not a reported value for the primary endpoint.

The deaths field is not reported in the registry record. The list of top serious adverse-event terms is empty, which means the record gives no serious-event terms to describe. It should not be read as additional evidence about the primary endpoint or as a detailed account of how safety events were collected.

Counts with such limited information require caution. They describe the registry entries for this group, not a stable estimate of event frequency in a wider population. No uncertainty interval or more detailed safety narrative is reported in the registry record, and there is no comparator group for contextualizing the counts.

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

The record identifies a compassionate-use safety program in Japanese patients treated with dabigatran who required rapid reversal in the setting of uncontrolled or life-threatening bleeding, emergency surgery, or an urgent procedure. It specifies a primary endpoint, the treated set, and an observation window. It also records separate serious and other adverse-event figures for the idarucizumab 5 g group.

These details do not amount to a numerical result for the primary endpoint. The percentage of treated-set participants with drug-related adverse events is not reported in the registry record. Nor does the record provide a confidence interval or a detailed account of endpoint adjudication. The separate count for other adverse events cannot fill that gap because the record does not establish that this event was drug-related.

The program’s single-group design can describe safety observations recorded among those treated, but it cannot estimate a comparative effect against an untreated or alternative-treatment group. Because the clinical circumstances prompting treatment are serious and urgent, observed events could reflect the underlying condition, the treatment context, or other factors. The registry does not report a method that separates these possible explanations.

The safety record lists 0 serious adverse events among 1 at risk and 1 other adverse event among 1 at risk. These entries are useful as a narrow description of what the registry records, but they are not a basis for generalizing event frequencies. The enrollment entry is 1, and the record does not provide enough methodological detail to assess how complete the outcome data were or how adverse-event relatedness was determined.

Accordingly, the record documents a small safety experience and the question the program set out to address. It does not establish a comparative safety profile, quantify the primary endpoint, or answer an efficacy question. The stated objective and observed safety categories should be kept distinct from claims about treatment effect.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a stated endpoint and a reported endpoint result. The registry clearly names a primary safety measure and defines its population and observation window. Yet it does not give a numerical result for that measure. Without the event count and denominator for the primary endpoint, the central safety question cannot be summarized as a percentage or assessed for precision.

It also illustrates the limits of a single-group record. Compassionate-use programs can collect safety information in a clinical setting where a comparison group is not part of the design. Such observations may be valuable as a record of experience, but they cannot provide a randomized contrast. In this study, allocation is not applicable, masking is none, and the model is single-group. The design therefore defines what the data can answer: a descriptive account, not a comparative estimate.

The separate safety categories further show why outcome definitions matter. The record lists serious and other adverse-event counts, while the primary endpoint concerns drug-related adverse events. Those labels are not interchangeable. Without a documented link between the categories and the primary endpoint, a reader should not substitute one for the other or infer attribution.

Finally, sparse enrollment and limited analysis detail make precision and reproducibility central concerns. The registry lists zero analyses and does not report missing-data handling, endpoint assessment procedures, or a confidence interval. Those omissions constrain statistical interpretation independently of the clinical importance of the setting. The record is most informative when read as a narrowly scoped description of a program and its recorded safety categories, with the missing primary numerical result kept explicit.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation is that the registry does not report a numerical result for the primary endpoint. Although it names the endpoint, treated-set population, and timeframe, it gives no primary event count, denominator, percentage, or confidence interval. The separate adverse-event counts do not establish the primary endpoint result.

Enrollment is recorded as 1, and the design is single-group. This leaves very limited information for describing event occurrence and no concurrent comparator for estimating relative safety or attributing differences to treatment. The registry also does not report detailed eligibility criteria, participant characteristics, treatment administration details beyond the 5 g group label, or further follow-up information.

Key methods details are absent. The record does not describe how drug-relatedness was assessed, how adverse events were collected, how missing observations were handled, or how the treated set was defined operationally. It lists zero analyses and provides no statistical analysis plan, interim-analysis information, or sample-size justification. These gaps prevent a reader from assessing the planned analysis or reproducing the primary endpoint.

The safety record’s serious and other adverse-event categories are sparse and should be interpreted independently. The deaths field is not reported in the registry record, and no serious-event terms are listed. These details do not establish that all relevant safety information was captured or that the primary endpoint was fully assessed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CU Programme of Idarucizumab for Japanese Patients — NCT02831660.
• Registry record last updated 2018-03-20; status last verified 2018-03.
• Results first posted 2018-03-20.
• 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

NCT02831660 is a completed phase 3 compassionate-use program of idarucizumab for Japanese patients treated with dabigatran who required rapid reversal because of bleeding or a need for emergency surgery or procedures. The registry records a single-group design, no masking, allocation not applicable, enrollment of 1, and sponsor Boehringer Ingelheim. The listed start date is 2016-07-22, and the primary completion date is 2016-09-16.

The primary endpoint is the percentage of treated-set participants with drug-related adverse events from first drug administration until 5 days after last drug administration, up to 6 days. Its numerical result is not reported in the registry record. The safety record lists 0 serious adverse events among 1 at risk and 1 other adverse event among 1 at risk for the idarucizumab 5 g group. These categories do not replace the missing primary endpoint result. No analyses are listed, and important details about endpoint assessment and missing data are not reported.