Eltrombopag for Fanconi Anemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Eltrombopag for Fanconi Anemia (NCT03206086), a na phase 2 study. The primary outcome is Proportion of Drug Responders.

2. Clinical Question

The study also aims to assess how long eltrombopag needs to be given to improve blood counts. Secondary outcomes address response at Month 3, relapse during the extension phase, clonal evolution, adverse events during extension, quality-of-life score changes, and Fanconi anemia-associated organ-system findings. These additional outcomes broaden the clinical questions, but the registry record does not report their results.

3. Trial Design

NCT03206086 is a phase 2, single-group study sponsored by the National Heart, Lung, and Blood Institute. The registry lists an enrollment of 25 and the condition as Fanconi anemia. Allocation is not applicable, and masking is none. There is no randomized or concurrent control arm in the design described by the registry record.

The study began on 2018-11-02. Its primary completion date is listed as 2025-08-01, and its status is active, not recruiting. Participants are screened with blood and urine tests and repeat testing before starting treatment. They take eltrombopag pills once daily for 24 weeks and are monitored for side effects, including blood tests every 4 weeks.

Visits are planned 3 months and 6 months after treatment starts. They include questions about medical history, how participants feel, and quality of life; a physical examination; blood and urine tests; and a bone marrow sample taken from the hip. Participants whose blood counts improve might enter the extension portion. The registry description says treatment may continue for up to 3 years, with dose adjustment, tapering, interruption, discontinuation, or re-initiation described as possible. Further details of the extension rules are not reported in the registry record.

The listed dose schedule for non-Asian populations is 75 mg daily for ages 6 to 11, with a possible increase to 150 mg during extension; for ages 12 and older, it is 150 mg daily, with a possible increase to 300 mg during extension. The record does not give a like-for-like comparator, so outcomes describe participants in this study rather than a comparative treatment effect. The sample-size justification and detailed statistical plan are 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.

Screening: Up to 16 Weeks

Reasons for not completing this period:

Initial: Day 0 to Month 6

Reasons for not completing this period:

Extended: M6 - Aug 1, 2025 Report Cutoff

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One non-treatment-related early discontinuation before the first scheduled on-treatment assessment was excluded from analysis.

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 Proportion of Drug Responders, measured over 6 months (+/- 14 day window).

The primary endpoint is the count of participants who meet the registry-defined criteria for a drug response at 6 months, allowing a 14-day window. The response definition combines several possible forms of improvement rather than requiring one specific blood-count change in every participant. Peripheral blood response may involve platelet improvement or stable platelets with transfusion independence, increased hemoglobin or reduced red-cell transfusion use, or specified increases in absolute neutrophil count. Bone marrow response may involve increased normal marrow CD34+ cells or increased normal marrow cellularity.

For some criteria, the definition compares measurements with a participant's baseline or pretreatment period. The record specifies thresholds and, for transfusion-related criteria, a period of at least 8 consecutive weeks. The response endpoint is therefore intended to capture more than one clinically relevant pattern of hematologic change in a population with varied blood-count problems. The primary endpoint title refers to a proportion, while its measurement is recorded as a count of participants; the registry description gives the response criteria but does not report the resulting count or proportion.

In general, a binary response endpoint classifies each participant as meeting or not meeting a predefined response rule at the assessment time. This can make results easier to interpret as the number or share meeting the rule, but it also compresses the magnitude and variety of individual changes into a category. Here, the actual response result and its uncertainty are not reported in the registry record, so the endpoint definition alone does not establish how often response occurred.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

This study's primary outcome is binary at the participant level: each person either meets the response definition at the specified assessment or does not. The registry records the endpoint as a count of participants and describes it as a proportion of drug responders. The response rule allows several ways to qualify, spanning peripheral blood measures and bone marrow findings. The result would therefore be a summary of how many participants satisfy at least one permitted response pathway, not a single continuous measure of blood-count change.

What does a response proportion tell the reader?

In general, a response proportion describes the observed frequency of participants who meet a stated outcome definition in the analyzed group. It is an estimate for that group and does not, on its own, show what would have happened to the same participants without treatment. In a single-group study, the proportion is descriptive of outcomes under the study conditions. A control group is needed for a direct comparison of response frequencies between treatment strategies.

In general, a confidence interval expresses uncertainty around an estimate. For a response proportion, it helps show how compatible the observed data are with a range of underlying response frequencies. Wider intervals indicate less precision, while narrower intervals indicate greater precision. The registry record does not report a confidence interval for the primary endpoint, and it does not report the response estimate itself. Consequently, neither the observed response frequency nor its precision can be evaluated from this record.

Why is the endpoint definition important?

The registry criteria set thresholds for several response pathways. These include platelet count increases or transfusion independence under specified conditions; hemoglobin increase or a reduction in packed red blood cell transfusions; absolute neutrophil count improvement for participants meeting the baseline criteria; and increases in normal marrow CD34+ cells or marrow cellularity. The definition also refers to pretreatment comparisons and specified assessment periods. These details matter because changing thresholds, timing, or the way response pathways are combined could change who is classified as a responder.

When an endpoint can be met through different components, a single overall result may conceal variation in the types of response. In general, reporting component-level results alongside a composite can clarify which findings contributed to the overall classification. The registry record lists the composite definition, but component-specific primary results are not reported in the registry record.

How should the analysis population be understood?

The record states that one non-treatment-related early discontinuation before the first scheduled on-treatment assessment was excluded from the primary analysis. This statement identifies an exclusion, but it does not describe every analysis-population rule. The registry record does not report whether the main analysis otherwise included all enrolled participants, how participants with later missing assessments were classified, or what sensitivity analyses were used. In general, excluding participants can affect an estimated response frequency if those who are excluded differ from those who remain in the analysis. The direction and size of any such effect cannot be determined without the relevant participant-level information and analysis details.

Missing outcome data can matter when participants do not complete the assessment needed to classify response. In general, analyses may use different assumptions about whether missing outcomes count as nonresponse or are handled through another method. Those choices can alter the estimate and its uncertainty. The specific missing-data approach is not reported in the registry record, so no assumption about it should be attributed to this study.

What can the design establish?

The study is single-group, with no allocation to a comparator and no masking. In general, a single-group design can describe whether participants meet a prespecified outcome after receiving the study intervention. It cannot provide the same direct treatment contrast as a randomized controlled design. Changes may reflect the intervention, the natural course of the condition, other care, measurement variability, or combinations of these factors. This is a design limitation, not a statistical adjustment that can be resolved from the response definition alone.

Masking is listed as none. In general, unmasked assessments can be more vulnerable to expectations influencing subjective judgments or decisions. The primary endpoint includes laboratory and marrow criteria, as well as transfusion-related criteria; the registry record does not explain what safeguards were used to reduce assessment or classification bias. The extent of any influence cannot be determined from the record.

What does the sample-size illustration mean?

The registry information 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. It states that the illustrated effect is a specified fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that a trial had a particular probability of success. The stated assumptions describe a hypothetical two-arm calculation; they do not change the fact that this study is single-group and has no like-for-like control comparison. The registry record does not report the trial's own sample-size justification.

In general, planning calculations depend on choices about the target effect, statistical error rates, allocation, and analysis method. If those assumptions differ from the actual study design or the clinically relevant question, the resulting participant counts may not be applicable. The illustration should not be treated as an additional observed finding or as a substitute for the missing primary outcome estimate.

How should multiple outcomes be considered?

The registry lists 8 outcome measures and 1 analysis. Outcomes include the primary Month 6 response and several secondary measures, among them Month 3 response, relapse, clonal evolution, safety during extension, quality of life, and organ-system findings. In general, evaluating multiple outcomes raises a multiplicity question: repeated opportunities to identify a statistically notable result can increase the chance of at least one apparently notable finding. Statistical approaches may adjust for multiplicity or define a hierarchy of outcomes, but the plan for doing so is not reported in the registry record. No adjustment or hierarchy should be assumed.

The registry record supplies no primary response estimate, interval, or test result. Statistical concepts can explain how such results would be interpreted, but they cannot fill the missing result. The posted information supports a description of the trial's design and endpoint rules, not a numerical assessment of efficacy or a comparative treatment effect.

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("Participants With Fanconi Anemia Receiving Eltromb")
n      <- c(21)
events <- c(21)
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  Participants With Fanconi Anemia Receiving Eltromb  21  21  100.0  83.9  100.0  84.5  100.0  84.6  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the primary response endpoint and secondary outcomes addressing response at Month 3, relapse during extension, clonal evolution, adverse events during extension, quality-of-life scores, and organ-system findings. It also records 1 analysis. These counts do not establish how outcomes were prioritized or whether statistical adjustment was planned.

In general, multiplicity arises when several outcomes, time points, or statistical tests are considered. Without a prespecified strategy, the chance of at least one result appearing notable can increase as more comparisons are examined. A study may address this by defining a primary outcome, controlling an error rate, or specifying a hierarchy. The statistical plan for multiplicity is not reported in the registry record. No particular correction or testing sequence can therefore be attributed to this study.

The primary analysis population description excludes one non-treatment-related early discontinuation before the first scheduled on-treatment assessment. The record does not report the full analysis-population definition, how missing primary assessments were handled, or whether sensitivity analyses were performed. In general, incomplete outcome data can affect both the estimated response frequency and its uncertainty, particularly if missingness is related to a participant's outcome. The registry record does not describe the reasons for other missing data or the assumptions used in analysis.

The primary response count, proportion, confidence interval, and p-value are not reported in the registry record. Results for the listed secondary outcomes are also not reported there. The registry record does not report a statistical analysis plan or sample-size justification, so neither multiplicity handling nor missing-data methods should be inferred.

12. Safety Results

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

Deaths

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: febrile neutropenia (18.2%), bronchopulmonary hemorrhage (9.1%), karyotypic abnormality (monosomy 7) (4.5%), sinus bradycardia (4.5%), diarrhea (4.5%).

The registry lists 22 participants at risk for the adverse-event summaries. Serious adverse events were recorded for 10 participants; other adverse events were recorded for 22 participants. The record also lists 2 deaths. These are counts in the study group, not comparisons with another group.

The listed serious-event terms and percentages are febrile neutropenia, 18.2%; bronchopulmonary hemorrhage, 9.1%; karyotypic abnormality (monosomy 7), 4.5%; sinus bradycardia, 4.5%; diarrhea, 4.5%; and dysphagia, 4.5%. The percentages are registry entries for the listed terms. The record does not provide further details about event timing, duration, recurrence, or attribution.

In general, an adverse event occurring during a study is not necessarily caused by the study treatment. The absence of a control group also means these counts cannot show whether the observed event frequency differs from another treatment or from the underlying condition and its course. The record does not state that the 2 deaths were caused by eltrombopag. They should be read as deaths listed in the study record, without assuming causation.

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

The registry record establishes that NCT03206086 is a phase 2, single-group study of eltrombopag in participants with Fanconi anemia and reduced blood cell counts. It describes a daily oral treatment period, follow-up assessments, an extension possibility, and a primary response definition at 6 months. It also lists several secondary outcomes and adverse-event summaries.

The record does not report the primary response count or proportion. It therefore does not show how many participants met the response criteria, how often response occurred, or how precisely that frequency was estimated. The listed response thresholds describe what would count as a response; they are not themselves evidence that a response occurred. Secondary outcome results are not reported in the registry record either.

Even if a response result were available, a single-group study would describe outcomes among treated participants rather than provide a direct comparison with an untreated or differently treated group. It could not, by design alone, establish that the treatment caused observed changes. The absence of a comparator is especially relevant when interpreting changes over time, since other influences may also affect measured outcomes.

The safety counts likewise describe events recorded among study participants. They do not identify which events were caused by treatment, and they do not provide comparative risk estimates. The registry lists 2 deaths but does not attribute them to the intervention. Careful interpretation requires separating an event occurring during a study from an event caused by the study drug.

The primary analysis excluded one non-treatment-related early discontinuation before the first scheduled on-treatment assessment. Details about other missing assessments and the full analysis population are not reported. These limits, along with the lack of a control group and the absence of primary outcome results, mean the registry record supports a description of the design and planned measures but not a conclusion about treatment effect.

14. Why This Trial Matters Statistically

This study raises a statistical question that is important in a condition with several possible patterns of blood-count impairment: how to define response so that it reflects more than one relevant hematologic change. The endpoint permits peripheral blood and bone marrow response pathways and specifies thresholds and assessment timing. Those rules make clear what classification is intended, while also making transparent that an overall response can arise through different components.

The trial also illustrates the distinction between measuring change and estimating a comparative treatment effect. A single-group study can record outcomes after treatment and describe safety events, but without a comparator it cannot establish how those outcomes differ from another care strategy. This distinction matters for interpreting both favorable and unfavorable observations; a within-study outcome is not automatically a causal treatment effect.

Precision is another central issue. A primary response estimate would need to be read with its uncertainty, and interpretation would depend on the analysis population and handling of missing assessments. The registry record gives an exclusion for one early discontinuation but does not report the full analysis rules, a primary estimate, or an uncertainty interval. Thus, a clear endpoint definition is not a substitute for a reported result and its precision.

Finally, the registry lists several secondary outcomes that address durability, clonal evolution, safety, quality of life, and organ-system findings. These dimensions can complement a response measure, but interpretation depends on the outcomes being reported and on how multiplicity and missing data were handled. The statistical plan for those issues is not reported in the registry record. The study is therefore informative as a design description, while its posted outcome information remains insufficient for judging the frequency, precision, or comparative meaning of response.

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 for interpreting outcomes is that the primary response result is not reported in the registry record. There is no primary response count or proportion, confidence interval, or p-value in the information described. The response criteria are detailed, but they do not show how many participants met them or the precision of any estimate.

The study has a single-group design, with no comparator and no masking. This prevents a direct comparison with another treatment strategy and limits causal interpretation of changes observed during follow-up. The registry record does not describe safeguards for outcome assessment or provide enough detail to assess the influence of unmasked assessment.

The endpoint combines different response pathways. An overall response result, if reported, would not by itself show whether participants responded through peripheral blood criteria, bone marrow criteria, or both. Component-level primary results are not reported in the registry record. The record also does not report the full analysis-population definition, the handling of missing primary assessments, or sensitivity analyses. It notes that one non-treatment-related early discontinuation before the first scheduled on-treatment assessment was excluded.

The registry lists secondary outcomes but does not report their results or the plan for controlling multiplicity. It does not report the trial's sample-size justification or full statistical analysis plan. The safety record gives group counts and selected serious-event terms, but does not report timing, duration, or attribution for individual events. These gaps limit assessment of precision, robustness, outcome selection, and causal interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Eltrombopag for Fanconi Anemia — NCT03206086.
• Registry record last updated 2026-09-16; status last verified 2026-08.
• Results first posted 2026-09-16.
• 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

NCT03206086, titled Eltrombopag for Fanconi Anemia, is a phase 2 single-group study sponsored by the National Heart, Lung, and Blood Institute. The registry lists an enrollment of 25, no allocation, and no masking. The study began on 2018-11-02, has a primary completion date of 2025-08-01, and is listed as active, not recruiting.

Participants with Fanconi anemia and reduced blood cell counts receive daily oral eltrombopag. The primary endpoint counts participants meeting protocol-defined peripheral blood or bone marrow response criteria at 6 months, within a 14-day window. One non-treatment-related early discontinuation before the first scheduled on-treatment assessment was excluded from the primary analysis.

The primary response result and its uncertainty are not reported in the registry record. The design has no comparator, and the registry does not report the full statistical plan, missing-data methods, multiplicity approach, or sample-size justification. Adverse-event summaries list 22 participants at risk, 10 with serious adverse events, 22 with other adverse events, and 2 deaths.