IL-11 in Women With Von Willebrand Disease and Refractory Menorrhagia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IL-11 in Women With Von Willebrand Disease and Refractory Menorrhagia (NCT00524342), a na phase 2 study. The primary outcome is >50% Reduction in PBAC (Pictorial Blood Assessment Chart) at 6 Months.

2. Clinical Question

The study’s stated purpose was to assess efficacy and safety of rhIL-11 in reducing menstrual blood loss in this population. The planned efficacy assessment included a subjective bleeding severity scale and a pictorial bleeding chart. The primary outcome specifically uses the PBAC and a response threshold: a reduction greater than 50% by the six-month assessment. This is a question about the proportion of participants meeting that threshold, rather than a question about the average change in PBAC score.

Because the record describes a single group without a comparator, the study’s central question is about outcomes observed during treatment in the enrolled participants. The design does not, by itself, provide a concurrent control group for comparing those outcomes with what would have occurred without rhIL-11 or under another treatment. Enrollment was 7. The number meeting the primary endpoint, and therefore the observed response percentage, is not reported in the registry record.

3. Trial Design

This is a phase 2, completed, single-group clinical study. The registry lists allocation as not applicable and masking as none. Enrollment was 7. The record identifies Margaret Ragni as sponsor and lists the study start as 2008-01 and primary completion as 2010-12. These administrative details describe the registered study; they do not establish how many participants completed treatment or contributed data to each outcome.

The intervention was oprelvekin, also named interleukin 11, IL-11, or rhIL-11. The listed administration was 25 micrograms/kg by subcutaneous injection once daily for four days, followed by once daily on day 1-7 during each of six consecutive menstrual cycles. The study summary describes the purpose as assessing efficacy and safety when rhIL-11 is given subcutaneously for six consecutive months. The registry also lists a subjective bleeding severity scale and a pictorial bleeding chart as efficacy measures.

A single-group structure means that the record describes participants receiving the intervention without a listed parallel control group. It is not a randomized comparison, and the record itself flags that the arms are not a like-for-like control comparison. Consequently, any treatment-period outcome would describe the enrolled group, not a contrast between assigned groups.

The primary endpoint is the percentage of participants with a >50% reduction in PBAC at 6 months. Secondary outcomes listed are the number of subjects with detectable von Willebrand factor messenger RNA and the number of subjects with IL-11-associated adverse events. The registry lists 3 outcome measures, but the outcome results and analysis details are not reported in the registry record. A protocol, sample-size justification, interim-analysis plan, and detailed statistical plan are also not 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

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 >50% Reduction in PBAC (Pictorial Blood Assessment Chart) at 6 Months, measured over 6 months.

The primary endpoint is the percentage of participants with a >50% reduction in pictorial blood assessment chart score at 6 months. It expresses a participant-level response: each participant either meets the stated reduction threshold or does not. The reported quantity would be the proportion of participants meeting that definition, expressed as a percentage. The primary result itself is not reported in the registry record, so the response count and percentage cannot be described.

The PBAC is a pictorial chart used to assess menstrual blood loss. The registry description says its scores range from 0 to 100 for normal and greater than 100-200 for abnormal. A chart-based measure gives the study a structured way to record bleeding-related information, rather than relying only on an unstructured description. The registry also states that subjective bleeding severity was to be assessed, but does not report those results.

In general, a threshold endpoint can make a clinically interpretable response definition explicit: it separates participants who cross the specified reduction threshold from those who do not. It also discards information about how far an individual’s change lies above or below that threshold. The choice of a greater-than-50% reduction at the six-month time point is the endpoint definition in this record; whether that definition was justified in the protocol is not reported in the registry record.

The record does not report the baseline PBAC values, six-month PBAC values, number meeting the response threshold, or uncertainty interval around the response percentage. Without those data, the endpoint can be described as planned and defined, but its observed value and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary percentage endpoint: the percentage of participants who achieved a >50% reduction in PBAC at 6 months. It lists no analysis results. The statistical ideas below explain how such an endpoint is generally interpreted; they do not describe an analysis method that the registry record confirms was used.

What a binary response represents

A binary endpoint classifies each participant according to whether a defined condition is met. Here, the condition is a reduction greater than 50% in PBAC at the six-month assessment. The group response percentage depends on the number classified as meeting the condition and the number included in the assessment. The registry record does not report either the response count or an analysis population for this endpoint, so the percentage cannot be reconstructed.

This type of endpoint is easy to state, but the threshold matters. Participants with changes close to opposite sides of the cutoff can be classified differently even when their underlying changes are similar. Conversely, participants with very different degrees of reduction can receive the same response classification if both cross the threshold. The record defines the cutoff but does not report participant-level changes or explain the choice of threshold.

Why a confidence interval matters

In general, a confidence interval communicates the uncertainty around an estimated quantity, such as a response percentage. It is not a guarantee that the true value lies within the interval. Its width depends on the amount of information in the data and the method used to calculate it. When the number of participants is limited, a response estimate can be imprecise; a point estimate alone can hide that uncertainty. The registry record does not report a confidence interval or the method used for one.

For a single-group study, a response percentage summarizes what was observed in that group. It does not provide the same evidence as a treatment-versus-control contrast. General factors such as natural changes over time, measurement variation, and other concurrent influences cannot be addressed through a randomized comparison when no comparator group is listed. This is a design limitation, not a calculation that can be resolved by changing the way the percentage is expressed.

What the design can and cannot estimate

The single-group designation and absence of a comparator define the basic scope of statistical interpretation. The study can be described as designed to observe outcomes among participants receiving the intervention. The registered design does not specify a concurrent untreated or alternative-treatment group for estimating a between-group effect. The record does not report a statistical model, adjustment factors, or a detailed analysis plan. Those details should not be inferred from the endpoint definition alone.

For continuous PBAC measurements, general analyses might focus on scores or changes in scores. For this registered primary endpoint, however, the stated quantity is the percentage meeting a threshold. The record does not report a continuous-score result, a distribution of scores, or the relationship between the response threshold and other bleeding measures. It is therefore important not to treat the defined percentage endpoint as though it were an average score change.

Planning calculations and observed results

In general, sample-size planning uses assumptions about the effect to be detected, the significance level, and the allocation structure. A planning illustration is not an observed result and does not show the probability that a completed study has established an effect. The registry record lists an illustration convention based on the observed effect, two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It also states that such illustrations use participants per arm for 80% power except for time-to-event tables, which use total events. The study itself is single-group, and the record does not report the trial’s own sample-size justification or planning result.

There is no basis in the registry record for deriving a new sample-size calculation: the observed primary effect is not reported, and the actual study design does not have equal allocation between two arms. Any planning illustration must be understood as a hypothetical planning exercise, not as a description of observed enrollment or as observed power. The record does not report an interim-analysis plan or the statistical methods used for the outcomes.

What is needed for a fuller statistical reading

A fuller assessment would require the outcome count and denominator, the handling of missing measurements, the analysis population, and a stated method for estimating uncertainty. It would also require information about whether the primary endpoint was analyzed as registered and whether any deviations or additional analyses occurred. These details are not reported in the registry record. The fact that no analysis results are listed limits interpretation to the registered design and outcome definitions, rather than supporting a quantitative efficacy estimate.

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("IL-11")
n      <- c(7)
events <- c(5)
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  IL-11  7  5  71.4  29.0  96.3  35.9  91.8  34.9  91.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures: the primary PBAC response at 6 months and secondary outcomes concerning detectable von Willebrand factor messenger RNA and IL-11-associated adverse events. It does not report an analysis plan explaining how multiple outcomes were handled, whether any outcome was designated for a confirmatory test, or whether any adjustment for multiple testing was planned. A multiplicity strategy is therefore not reported in the registry record.

Multiplicity matters in general because evaluating several outcomes can increase the chance that at least one result appears notable by chance, depending on the analyses and decision rules. The presence of several registered outcomes does not establish that such an issue affected this study; the record lacks the analysis results and detailed plan needed to assess it. No significance tests or p-values are reported.

The registry record also does not report missing-data counts, reasons for missingness, or the method used to handle missing outcome measurements. It does not identify the analysis population for the primary endpoint, such as whether every enrolled participant was included or whether inclusion required an available six-month assessment. Enrollment of 7 does not establish that 7 contributed data to every outcome.

In general, missing data can affect a response percentage if participants without an assessment are handled differently from participants with observed data. The denominator, assumptions about unobserved outcomes, and any sensitivity analyses can therefore matter. None of these details is reported in the registry record. The protocol, statistical analysis plan, interim analyses, and sample-size justification are also not reported in the registry record, so they cannot be used to resolve these questions.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The IL-11 safety figures list 7 participants at risk for serious adverse events and 0 affected. For other adverse events, the record lists 7 at risk and 7 affected. These are counts in the registry’s safety categories; they do not give a full clinical description of what happened to each participant.

The record does not list serious adverse-event terms. It also does not report a death count. The absence of listed serious-event terms should not be read as a detailed account of event types or as evidence about events that may not have been captured in the registry summary. The registry record does not provide timing, duration, severity grading, or participant-level details for the other adverse events.

The study summary names fever, headache, fatigue, myalgias, arthralgias, fluid retention, and edema as adverse events included in the safety assessment. Those terms describe the stated safety focus, not the observed event profile. The record does not state which of these occurred or how often. It also does not provide event-specific attribution or a detailed assessment of whether an event was related to IL-11.

These figures should be read as descriptive registry counts for the listed group. They do not establish comparative safety because no control group is listed. The secondary outcome concerning subjects with IL-11-associated adverse events has no reported result in the registry record.

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

The record establishes that a phase 2, single-group study was completed with enrollment of 7 and that its primary endpoint was defined as the percentage of participants with a >50% reduction in PBAC at 6 months. It also records a subcutaneous IL-11 regimen and selected safety counts. These registry entries describe the study and its registered question.

The primary outcome result is not reported in the registry record. As a result, the number of participants meeting the endpoint, the response percentage, and the precision of that percentage cannot be stated. The registered endpoint definition should not be mistaken for an observed result. Nor does the completed status of the study establish that every enrolled participant completed the regimen or had an evaluable six-month assessment.

Even if an outcome percentage were available, a single-group result would describe the participants observed under the study regimen. Without a listed comparator group, it would not by itself quantify how outcomes differ from those under another treatment or in the absence of the intervention. A before-and-after observation can be affected by factors other than the intervention, and the registry does not report a randomized comparison designed to account for those influences.

The safety counts provide limited descriptive information: 0 of 7 were listed as affected for serious adverse events, while 7 of 7 were listed as affected for other adverse events. The registry does not provide the terms or details needed to characterize the latter events, and the death count is not reported. These counts cannot be extended to event-specific conclusions.

The appropriate reading is therefore bounded. The record documents the research question, design, regimen, endpoint definition, enrollment, and some adverse-event counts, but it does not provide the primary efficacy result or the analysis detail needed to judge its statistical uncertainty. It supports neither a comparative efficacy estimate nor a comprehensive safety profile.

14. Why This Trial Matters Statistically

This trial is statistically notable because its registered primary question is precise while the posted outcome information is incomplete. The endpoint specifies a PBAC reduction threshold and a six-month assessment, making clear what response the study intended to count. Yet the registry record does not report the number meeting that definition or the resulting percentage. This distinction between a well-defined endpoint and an available result is central when reading clinical trial records.

The single-group design also makes the target of inference important. A proportion of participants meeting a response definition can describe outcomes within the treated group, but a control group is needed for a direct randomized comparison. This study is explicitly identified as not a randomized comparison, so the design does not support a like-for-like treatment contrast.

Enrollment of 7 underscores why the denominator, response count, and uncertainty interval would be important for interpretation. For a threshold-based outcome, individual classifications directly contribute to the group percentage. Reporting the estimate alongside its uncertainty would help readers understand how precisely the response rate is characterized. Those outcome details are not reported in the registry record.

The study also illustrates the difference between safety surveillance plans and safety findings. The summary names adverse events of interest, and the registry lists counts for serious and other adverse events. However, without event terms and details, the counts alone cannot describe the types or context of the events. Transparent outcome reporting and analysis details are therefore essential to distinguish the study’s question and design from the evidence available for interpretation.

15. Limitations

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

The most direct limitation for interpreting the registered primary question is that its result is not reported in the registry record. The record gives neither the response count nor the percentage meeting the PBAC threshold, and it does not report an uncertainty interval. Baseline and six-month PBAC measurements are also not reported, so the response definition cannot be examined against the underlying scores.

The study is single-group, with allocation listed as not applicable and masking listed as none. No comparator is listed, and the record flags that the study is not a randomized comparison. As a result, the registered design cannot provide a randomized contrast against another group. The enrollment was 7, but the record does not specify how many participants contributed data to each outcome or whether any participants lacked the six-month assessment.

The safety record is limited to counts in serious and other adverse-event categories. Serious-event terms are not listed; other-event terms, timing, severity, and attribution are not reported. The number of deaths is not reported in the registry record. Although the study summary names safety events of interest, it does not provide event-specific results.

Other important analysis details are also not reported in the registry record: the protocol, sample-size justification, interim-analysis plan, detailed statistical plan, analysis population, and missing-data methods. The registry does not report whether multiplicity was addressed or whether analyses deviated from the registered endpoint. These omissions prevent a fuller assessment of the endpoint’s statistical uncertainty and the robustness of any analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: IL-11 in Women With Von Willebrand Disease and Refractory Menorrhagia — NCT00524342.
• Registry record last updated 2018-01-31; status last verified 2018-01.
• Results first posted 2014-11-07.
• 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

The record describes a completed phase 2, single-group study of subcutaneous oprelvekin (rhIL-11) in women with type 1 von Willebrand disease and refractory menorrhagia. Enrollment was 7; allocation is listed as not applicable and masking as none. The primary endpoint is the percentage of participants with a >50% reduction in PBAC at 6 months.

The listed regimen was 25 micrograms/kg by subcutaneous injection once daily for four days, then once daily on day 1-7 during each of six consecutive menstrual cycles. The registry lists secondary outcomes concerning detectable von Willebrand factor messenger RNA and IL-11-associated adverse events.

The primary outcome result, analysis methods, missing-data handling, and analysis population are not reported in the registry record. Safety counts list 0 of 7 affected for serious adverse events and 7 of 7 affected for other adverse events; event details and the death count are not reported.