Clinical Evaluation of Eltrombopag in Chronic Idiopathic Thrombocytopenic Purpura (ITP): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Evaluation of Eltrombopag in Chronic Idiopathic Thrombocytopenic Purpura (ITP) (NCT00828750), a non-randomized phase 3 study. The primary outcome is Number of Participants Experiencing an Adverse Event (AE) and/or Serious Adverse Event (SAE) Within the Indicated Category.

2. Clinical Question

3. Trial Design

This was a completed Phase III extension study of eltrombopag in participants with ITP who had previously enrolled in TRA108109 (NCT00540423). The registry describes it as open-label and dose-adjusted. Participants received eltrombopag oral tablets once daily. The study used a single-group model, non-randomized allocation, and no masking, so there was no concurrent control arm for a randomized comparison.

The registry reports enrollment of 19. The primary outcome was a count of participants experiencing an AE and/or SAE within the indicated category. Its observation period ran from baseline (Day 1) to the last dose of eltrombopag or an early withdrawal visit, up to 981 days. The Safety Population was defined as participants who received at least one dose of study medication.

The listed secondary outcomes address platelet-count thresholds and patterns over time, bleeding episodes after dosing, reduction in baseline ITP medication, and initiation of rescue medication or treatment during on-therapy follow-up. These outcomes indicate that the study considered both safety and measures related to disease management. Numerical results for those secondary outcomes are not reported in the registry record.

Because the study enrolled people previously involved in an eltrombopag study and continued their treatment in an extension, its setting differs from a trial that begins with a newly recruited population and assigns participants to alternative treatments. The registry record does not report a concurrent comparison group, random assignment, or masking. It also does not report the dose-adjustment rules or detailed statistical analysis plan. The registry lists the study as completed.

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 is an open-label, dose-adjustment extension study to evaluate the safety and efficacy of eltrombopag for the treatment of participants with idiopathic thrombocytopenic purpura (ITP) who had previously been enrolled in eltrombopag trial TRA108109 (NCT00540423).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population (SP): all participants who received at least one dose of study medication

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 Number of Participants Experiencing an Adverse Event (AE) and/or Serious Adverse Event (SAE) Within the Indicated Category, measured over From Baseline (Day 1) to last dose of eltrombopag/early withdrawal visit (up to 981 days).

The primary endpoint counts participants who experienced an adverse event (AE) and/or serious adverse event (SAE) within the indicated category. The observation window began at baseline (Day 1) and continued to the last eltrombopag dose or an early withdrawal visit, up to 981 days. The Safety Population includes participants who received at least one dose of study medication.

The registry defines an AE as an untoward medical occurrence temporally associated with use of a medical product, whether or not it is judged related to that product. An SAE is an event meeting specified seriousness criteria, including death, a life-threatening event, hospitalization or its prolongation, disability or incapacity, a congenital anomaly or birth defect, or another event considered serious. Drug-related AEs are those judged by the investigator to have a relationship with study medication; severity is based on the investigator’s clinical judgment.

A participant count is useful for describing how many people in the safety population experienced an event during the stated observation period. It is not, by itself, a measure of treatment effect: without a concurrent comparator, the count cannot distinguish events associated with treatment from events that would have occurred for other reasons. The registry’s definition also makes clear that an AE does not automatically mean the medication caused the event.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count: the number of participants with an AE and/or SAE in an indicated category. The registry presents the safety results as counts with participants at risk. This is a descriptive way to report how many people in the defined Safety Population had events during the stated follow-up period. It should not be confused with a comparison of event rates between treatment groups, because the trial had a single-group design and no concurrent comparator.

What does a count tell the reader?

A count communicates the number of participants recorded as having an event. The at-risk count gives the corresponding group size used for that reporting. In this study, the registry reports 6 participants with serious adverse events among 19 at risk, and 19 participants with other adverse events among 19 at risk. These figures describe the registry’s reported categories. They do not identify how many individual events occurred, since one participant may have more than one event; the registry entries do not report event totals or participant-level overlap.

Counts also depend on how events are defined and collected. Here, the registry defines an AE as an untoward medical occurrence temporally associated with use of a medical product, whether or not related to it. An SAE is classified according to the stated seriousness criteria. Investigator judgment determines whether an AE is considered drug-related and how severe it is. These definitions guide classification, but they do not establish causation on their own.

Why does the design affect interpretation?

Random allocation in a controlled trial is generally used to create groups that can be compared while reducing systematic differences in treatment assignment. This study was non-randomized and single-group, so it does not offer that comparison. Open-label status means masking was absent. Without a concurrent control group, observed event counts cannot isolate the effect of study medication from other explanations, such as participants’ underlying condition or events occurring over time. This is a general limitation of single-group safety descriptions, not a claim about the cause of any particular event in this study.

The extension setting matters as well. Participants had previously enrolled in TRA108109, and the study continued eltrombopag treatment in an extension. The results therefore describe participants entering this extension context. The registry does not report enough detail to assess how participants who entered the extension compare with people who did not, or how their prior study experience may relate to the observed outcomes.

What can be said about precision?

A confidence interval is a general statistical tool for expressing uncertainty around an estimate. It helps show which values are reasonably compatible with the observed data under a specified method. No confidence interval is reported in the registry record. Without an interval or an inferential analysis, the precision of the serious-event count cannot be judged from the count alone. The reported count remains a direct description of the enrolled safety population, but it should not be mistaken for a precise estimate of risk in a broader population.

For event counts that are compared over differing follow-up periods, analysts may use time-to-event or rate-based methods. In general, these approaches can account for the amount of time participants are observed or the timing of events. The registry entries do not report participant-level event times, individual follow-up, or such an analysis, so no time-adjusted comparison can be described. The overall observation window is stated as baseline to last dose or early withdrawal, up to 981 days.

What does the registry report about analysis?

The record lists 8 outcome measures and no analyses. It provides the primary outcome definition and adverse-event summaries, but the registry entries do not report a statistical analysis plan, adjustment model, hypothesis test, p-value, or confidence interval. This absence means the narrative should remain descriptive rather than imply that a formal comparative test was conducted.

The record also describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are assumptions for a hypothetical planning exercise, not evidence of the trial’s own design or an observed-power calculation. The study itself was single-group and non-randomized, so an equal-allocation, two-arm illustration does not describe its actual allocation. The record does not report a sample-size justification for the extension study.

Over-dispersion is a general issue in count data: observed variability can exceed what a simple model assumes, which may make standard errors too small if the model is not appropriate. It is not possible to assess over-dispersion for this study from the reported participant counts alone. The registry does not report a count model or the event-level data needed to examine this feature. In keeping with the available information, the results are best read as descriptive safety counts rather than model-based estimates.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the primary AE/SAE count and secondary outcomes related to platelet counts, bleeding, medication use, and rescue treatment. It reports no analyses. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a statistical analysis plan specifying which outcomes were intended for confirmatory inference. When many outcomes are examined, general statistical practice recognizes that the chance of at least one apparently notable result can increase unless the analysis plan addresses multiple testing. That concern cannot be evaluated for this study from the information.

The registry defines the Safety Population as all participants who received at least one dose of study medication. It reports 19 participants at risk in the adverse-event summaries. The registry entries do not describe how missing outcome data were handled, whether participants had incomplete follow-up, or whether any imputation or sensitivity analysis was used. Individual follow-up duration and the reasons for early withdrawal are not reported in the registry record.

The outcome list includes platelet-count and other clinical measures, but numerical results for those secondary outcomes are not reported in the registry record. Without those results, their completeness, denominators, and analysis populations cannot be assessed. The listed sample-size planning assumptions are not a report of the study’s own statistical plan. In particular, the record does not report the extension study’s sample-size justification or any interim analyses. These gaps limit assessment of how analyses were selected and how missingness or multiple outcomes might affect interpretation.

11. 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: cataract (10.5%), abdominal pain (5.3%), mallory-weiss syndrome (5.3%), lumbar spinal stenosis (5.3%), osteonecrosis (5.3%).

The registry reports serious adverse events in 6 participants among 19 at risk in the eltrombopag group. It reports other adverse events in 19 participants among 19 at risk. These are participant counts in the registry’s categories, not counts of every individual event. The record lists cataract at 10.5% among the top serious-event terms; abdominal pain, Mallory-Weiss syndrome, lumbar spinal stenosis, osteonecrosis, and spinal osteoarthritis are each listed at 5.3%. The term percentages should be read as reported; further details about event overlap or the underlying event records are not reported in the registry record.

An AE is not necessarily caused by the study medication. The registry’s definition includes an untoward medical occurrence temporally associated with use of a medical product whether or not it is related. Drug relatedness is based on the investigator’s judgment, and the registry entries do not report how many events were judged drug-related. An SAE is classified using seriousness criteria, not simply by whether an event is considered related to treatment.

Because the study had no concurrent comparator, these counts cannot establish whether event occurrence differed from another treatment or from no study treatment. They describe reported safety experience in this extension population over the stated observation period.

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

The results establish that adverse events were recorded in this extension study and that the registry reports serious adverse events in 6 participants among 19 at risk. The registry also reports other adverse events in 19 participants among 19 at risk. The listed serious-event terms and their reported percentages provide additional descriptive detail. These observations concern participants who entered the eltrombopag extension and the registry’s defined safety categories.

They do not establish that eltrombopag caused the reported events. The registry definition of an AE explicitly allows an event to be temporally associated with use of a medical product without being judged related to it. The registry entries do not give the number of events judged drug-related. The counts also do not describe the number of individual events, their timing, duration, recurrence, or clinical course.

The findings do not show how safety compares with another treatment, usual care, or no treatment, because the study was non-randomized and had a single group without a concurrent comparator. The open-label design and the extension setting are additional context for reading these observations. The results describe the enrolled extension population; they cannot on their own establish what would happen in a different population or under a different treatment approach.

The registry lists secondary outcomes involving platelet counts, bleeding, ITP medication reduction, and rescue treatment, but numerical results for those outcomes are not reported in the registry record. Their titles do not establish whether any particular outcome changed. No statistical analyses, confidence intervals, or p-values are reported in the available record. Thus, the posted safety counts can be interpreted as descriptive evidence of recorded events, while comparative effects, precision, and efficacy-related outcomes remain unestablished by the information.

13. Why This Trial Matters Statistically

This study is statistically informative because it illustrates the difference between describing safety experience and estimating a comparative treatment effect. The registry reports participant counts for serious and other adverse events in a defined safety population. Those counts can document what was recorded during the extension’s observation period, but a single-group design cannot provide a direct contrast with a concurrent control group.

The study’s extension setting is also important. Participants had previously enrolled in another eltrombopag study, and the extension evaluated continued treatment with dose adjustment. That context defines the population to which the reported observations apply. It also means the findings should not be treated as interchangeable with results from a study that recruits a different population or assigns participants to randomized treatment groups.

The record distinguishes event occurrence from investigator-assessed relatedness and seriousness. This distinction matters when reading safety data: an adverse event is not automatically an adverse reaction, and seriousness is a classification based on specified criteria. The posted counts are therefore useful as a registry description, while questions about causality require evidence that this design does not supply through a controlled comparison.

Finally, the registry lists a range of platelet-count and clinical outcomes, yet numerical results for those secondary measures are not reported in the record. The distinction between an outcome being listed and its result being available is essential. Statistical interpretation should be anchored in the reported counts and design, not inferred from outcome titles or from planning assumptions that do not represent the study’s own design.

14. 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 principal limitation for interpreting treatment effects is the absence of a concurrent comparator. The study was single-group, non-randomized, and open-label. As a result, the registry’s event counts cannot separate treatment effects from other influences or estimate a contrast with another treatment. No randomized comparison is available to support a causal conclusion.

The extension population had previously enrolled in TRA108109. This limits the scope of inference to the population entering this extension context; the record does not report how that population compares with people who did not enter the extension. The registry entries also do not describe dose-adjustment rules, individual exposure, adherence, or variation in follow-up. The stated outcome period could extend to 981 days, but participant-specific observation time is not reported.

The reported safety summaries do not provide event-level detail, timing, duration, recurrence, participant overlap across event terms, or the number of events judged drug-related. The registry definition relies on investigator judgment for relatedness and severity. No confidence intervals, p-values, or statistical analyses are reported in the registry record, so statistical precision and adjusted estimates cannot be assessed.

Although secondary outcomes are listed, numerical results for them are not reported in the registry record. The record also does not report how missing data were handled, whether interim analyses occurred, or the statistical plan and sample-size justification. These omissions restrict assessment of outcome completeness and analysis choices. The planning assumptions described for an illustrative sample-size exercise are not evidence of the trial’s actual design or a substitute for a reported analysis plan.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Clinical Evaluation of Eltrombopag in Chronic Idiopathic Thrombocytopenic Purpura (ITP) — NCT00828750.
• Registry record last updated 2018-09-17; status last verified 2011-10.
• Results first posted 2011-12-01.
• 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.

18. Record Summary

The registry describes a completed Phase III, open-label, dose-adjustment extension study of eltrombopag oral tablets once daily in participants with ITP who had previously enrolled in TRA108109 (NCT00540423). The study was non-randomized, used a single-group model, and had no masking. Enrollment was 19.

The primary outcome counted participants experiencing an AE and/or SAE from baseline (Day 1) to the last dose or early withdrawal visit, up to 981 days. The Safety Population comprised participants who received at least one dose of study medication. The registry reports serious adverse events in 6 participants among 19 at risk and other adverse events in 19 participants among 19 at risk. It lists 8 outcome measures and no analyses; numerical results for the secondary outcomes are not reported in the registry record.

These are descriptive safety findings from a single-group extension, not a randomized comparison. The record does not report comparative estimates, confidence intervals, p-values, or a statistical analysis plan.