Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients (NCT03318159), a na phase 2 study. The primary outcome is the Incidence of Proven/Probable/Possible Fungal Infection.

2. Clinical Question

The study is titled “Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients.” Its stated purpose is to investigate posaconazole as an antifungal prophylaxis agent for patients with aplastic anemia or hypoplastic myelodysplastic syndrome who are undergoing antithymocyte globulin treatment. The primary endpoint counts participants meeting the fungal-infection definition; it is not a comparison of infection rates between treatment arms.

That distinction matters for interpretation. A single-group study can describe outcomes in the participants who received the prophylaxis, but it does not provide a concurrent untreated or alternative-treatment group for estimating a comparative treatment effect. The registry record does not report the primary endpoint result, so the incidence observed in the study cannot be stated from this record. It also does not report a comparison with an external or historical group.

The record lists overall survival and any incidence of proven, probable, or possible fungal infection among the secondary outcomes. It does not provide results for those outcomes either. Thus, the registry description establishes the clinical question and outcome definitions, but does not establish the observed efficacy or survival findings.

3. Trial Design

This is a Phase II, open-label study with a single-group model. The listed intervention is posaconazole, and the described group consists of patients with aplastic anemia or hypoplastic myelodysplastic syndrome undergoing antithymocyte globulin treatment while receiving posaconazole prophylaxis. Enrollment is recorded as 20. The study is marked completed.

The registry lists the start as 2018-04-20 and primary completion as 2023-07-15. Seoul National University Hospital is named as the sponsor. Allocation is recorded as NA, and masking is recorded as NONE. These design details mean that the record does not describe a randomized, blinded, concurrent-arm comparison. In particular, the listed study group is not a like-for-like control comparison.

For the primary outcome, the registry specifies a participant count for proven, probable, or possible fungal infection during 4 weeks of posaconazole prophylaxis, with the timeframe also described as up to 4 weeks. The record refers to criteria from the Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. The registry does not report additional operational details about how those criteria were applied in this study.

The record lists three outcome measures and zero analyses. It does not report a statistical analysis plan, a sample-size justification, interim analyses, or an analysis population. Consequently, the design can be characterized from the registry’s study structure and outcome descriptions, but not from a detailed protocol-level account of its planned statistical procedures. Planning assumptions appearing in the record are described as illustrations rather than the trial’s own design.

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 the Incidence of Proven/Probable/Possible Fungal Infection, measured over during 4 weeks of posaconazole prophylaxis (i.e. upto 4 weeks).

The primary endpoint is the incidence of proven, probable, or possible fungal infection, measured as a count of participants. The registry defines the observation period as during 4 weeks of posaconazole prophylaxis, or up to 4 weeks. It refers to consensus guidelines for defining invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants.

In general, a participant-count endpoint records whether participants meet a specified event definition within a stated period. Such an endpoint can make the clinical event easier to interpret than a count of episodes, because the outcome is framed around participants who experienced an event. The registry record does not report whether recurrent episodes were assessed separately or how incomplete observation was handled.

For this study, the endpoint is relevant to the stated objective because it concerns fungal infection during the prophylaxis period. However, the registry record does not give the observed number of participants meeting the definition, an incidence estimate, or an uncertainty interval. It therefore does not show the primary endpoint result or how precisely that result was estimated. The endpoint definition alone is not evidence of the outcome achieved.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information available for this study is limited. The record identifies a binary participant-count primary endpoint and describes a single-group design, but it reports zero analyses. The statistical concepts below are general explanations of how such outcomes can be approached; they are not a claim that a particular method was used in this study.

What does a participant-count endpoint represent?

In general, a binary endpoint classifies each participant according to whether the defined event occurred during the specified observation period. A participant is counted as having the outcome if the study’s criteria are met; the endpoint is not a count of every infection episode. The registry’s primary endpoint is the incidence of proven, probable, or possible fungal infection during 4 weeks of prophylaxis, described as up to 4 weeks. It specifies participants as the unit of measurement.

For an observed binary endpoint, a basic descriptive summary would report the number meeting the definition and the number assessed. An estimated event proportion can then describe the frequency in the analyzed group. The registry record does not report the primary event count, the analyzed denominator, or an estimate. Those quantities cannot be recovered from enrollment alone, and the adverse-event counts are not substitutes for the primary fungal-infection outcome.

How should uncertainty be understood?

In general, an estimate from a study is subject to sampling uncertainty: a different set of participants from the same target population could produce a different observed result. A confidence interval expresses a range of values compatible with the observed data under a specified statistical procedure. Its width reflects the precision of the estimate, and its interpretation depends on the method and assumptions used.

No primary endpoint estimate or confidence interval is reported in the registry record. Accordingly, there is no primary-outcome precision to interpret. A confidence interval cannot be inferred from the enrollment count, and no interval should be presented as though it were an observed result. The record also does not state which interval method, if any, was planned for the primary endpoint.

What can a single-group design estimate?

In general, a single-group study can estimate the frequency of an outcome among the participants observed, subject to its measurement, follow-up, and missing-data limitations. It does not directly estimate a contrast between posaconazole and another treatment because no comparator group is listed. Differences from an expected or historical rate would require a defined reference and assumptions about comparability; neither is reported in this registry record.

Randomization is useful in comparative studies because it can help balance measured and unmeasured factors between groups on average. This study is not described as a randomized comparison: allocation is listed as NA and the model is single group. Open-label status means masking is recorded as NONE. These design characteristics do not establish that outcome assessment was biased, but the registry record does not report additional procedures for blinded outcome assessment.

What do the planning assumptions mean?

The record describes sample-size calculations as planning illustrations based on the observed effect, rather than the trial’s own design. It states assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event illustrations, it states that the total number of events is used; other illustrations report participants per arm.

These are planning assumptions, not evidence that the study used a two-arm design. The actual study is listed as single group. Planning calculations ask what size a hypothetical study might require under specified assumptions; they do not report how many events occurred in the completed study. The record’s description also explicitly distinguishes planning illustrations from the trial’s design. Any such sample-size value should be understood as a planning illustration, never as observed power.

In general, power is a design property calculated for a specified effect, variability, significance level, and analysis. Once a study is completed, an observed result and its uncertainty are more informative than a retrospective power calculation. The record does not report the primary endpoint result needed to interpret an observed effect, and no analysis is listed. Therefore, planning assumptions cannot be used to infer the study’s efficacy finding or the precision of its estimate.

Do over-dispersion or survival methods apply?

In general, over-dispersion is a concern when count data vary more than a model assumes. It can affect standard errors and intervals if a model does not account for that extra variation. The primary endpoint is described as a participant count for a binary event, rather than a recurrent-event rate or an episode count. The registry record does not report a model or a dispersion parameter, so there is no basis for saying that over-dispersion was assessed or was a concern in the analysis.

Overall survival is listed as a secondary outcome. In general, time-to-event methods can account for differing follow-up times and participants whose event time is not observed during the study, using censoring assumptions. The record does not report survival results, follow-up details, censoring rules, or a time-to-event analysis. It is therefore not possible to describe how survival was analyzed in this study.

Finally, a complete interpretation of any statistical analysis depends on the prespecified outcome definition, analysis population, missing-data procedures, and methods for handling multiple outcomes. Those details are not reported in the registry record. The listed outcome definitions and study structure provide useful context, but they do not replace a reported analysis plan or endpoint results.

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("Posaconazole Prophylaxis Group")
n      <- c(20)
events <- c(20)
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  Posaconazole Prophylaxis Group  20  20  100.0  83.2  100.0  83.9  100.0  83.9  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: the primary fungal-infection endpoint and the secondary outcomes overall survival and any incidence of proven, probable, or possible fungal infection. It reports zero analyses. The record does not describe a multiplicity procedure, such as an adjustment to account for testing several outcomes, or state how the primary and secondary outcomes would be prioritized for inferential claims. That information is not reported in the registry record.

In general, testing several hypotheses can increase the chance of at least one apparently notable result if each is interpreted without accounting for the set of tests. The extent of that concern depends on which analyses were planned and how conclusions were to be drawn. Since no analysis is listed, no multiplicity-adjusted or unadjusted inference can be evaluated from this record.

The registry record does not report how missing outcome data were handled, whether participants with incomplete follow-up were excluded or retained in an analysis, or which analysis population was intended. It also does not report whether endpoint status was available for every enrolled participant. These are important details for a participant-count endpoint because the observed proportion depends on who was assessed and how missing status is treated.

General statistical practice distinguishes the population enrolled from the population included in a particular analysis. The enrollment figure alone does not establish the denominator used for the primary endpoint or secondary outcomes. Since the record does not provide an analysis population or missing-data approach, the representativeness and completeness of any endpoint estimate cannot be assessed from the posted results.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: herpes zoster (5.0%), neutropenia (5.0%), cellulitis (5.0%), cardiac arrest (5.0%).

For the Posaconazole Prophylaxis Group, the registry reports 20 participants at risk and 4 affected for serious adverse events. It separately reports 20 at risk and 4 affected for other adverse events. The record lists 6 deaths. These are registry-reported safety figures; they do not establish that an event or death was caused by posaconazole.

The listed serious adverse-event terms are Herpes zoster, Neutropenia, Cellulitis, and Cardiac arrest, each reported as 5.0%. The registry does not provide additional details in this record about event timing, severity beyond the serious-event classification, duration, or attribution. It also does not report whether the same participant experienced more than one listed term or whether participants in the serious and other adverse-event counts overlap.

The death count should be interpreted separately from the affected-participant counts. The registry record does not report the causes of death, their timing, whether they were considered treatment-related, or their overlap with adverse events. These safety figures describe what is recorded, but without those details they cannot establish a causal relationship or provide a complete account of safety.

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

The record establishes that a completed, open-label, single-group Phase II study investigated posaconazole prophylaxis during antithymocyte globulin treatment for patients with aplastic anemia or hypoplastic myelodysplastic syndrome. It identifies a primary endpoint focused on proven, probable, or possible fungal infection during up to 4 weeks of prophylaxis, and it lists overall survival and fungal infection among secondary outcomes.

It does not report the primary endpoint result, the secondary outcome results, or any analysis. As a result, the record does not establish the observed incidence of fungal infection, the precision of an estimate, or a comparative treatment effect. The study’s completed status and enrollment figure do not supply these missing results. No conclusion about whether posaconazole did or did not prevent infection follows from the endpoint description alone.

The single-group design is important to the scope of inference. In general, outcomes observed in one group may reflect the intervention and other factors, but a concurrent comparator is needed to make a direct between-group contrast. No comparator is listed in this record. Thus, the available design description does not support a comparative claim about posaconazole versus another prophylaxis strategy or no prophylaxis.

The adverse-event counts and listed serious-event terms provide a limited safety description. They should not be read as proof of treatment causality, and the record does not provide information about timing, attribution, overlap, or causes of death. The record also does not report missing-data procedures or analysis populations, which would be relevant to judging how complete and representative endpoint results are if they were available.

Overall, the registry record documents the study question, intervention, design, outcomes, and selected safety figures. It does not provide enough outcome or analysis information to determine what the study observed on its primary efficacy endpoint or how precisely that outcome was estimated.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why a clearly stated clinical question and a reported result are separate parts of trial evidence. The registry identifies a focused participant-count endpoint and a defined observation period, but does not report the primary result or an analysis. Without those elements, readers cannot assess the event frequency or its uncertainty, even though the study is marked completed.

The single-group structure also makes the estimand—the quantity the study can address—important. In general, a single-group study can describe outcomes in the observed group, while a comparative trial can estimate a contrast between groups under its design assumptions. The registry lists no comparator and records allocation as NA. The stated study question is therefore about the incidence observed during prophylaxis, not a randomized comparison of prophylaxis strategies.

Its planning illustrations raise a related distinction. A planning calculation depends on assumptions about the effect and design; it does not show what the completed study observed. The record explicitly describes its calculations as illustrations rather than the trial’s own design. Separating planning quantities from observed results helps avoid treating a hypothetical sample-size calculation as evidence of efficacy or as observed power.

The record also illustrates the importance of reporting the analysis population, missing-data approach, and multiplicity handling. Those elements affect how an endpoint estimate should be interpreted, but are not reported. For biostatisticians and clinical researchers, this is a reminder that outcome definitions and enrollment information alone are not enough to reconstruct an analysis or assess its robustness.

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 for interpreting the study from this registry record is that it does not report the primary fungal-infection result, despite marking the study completed. No primary event count, estimate, confidence interval, or analysis is listed. Secondary outcome results are also not reported. As a result, outcome frequency and statistical precision cannot be assessed.

The study is described as open-label and single group, with no comparator arm listed. This limits comparative interpretation: the record does not provide a concurrent control against which to estimate a treatment contrast. The record does not report randomization or a blinded assessment process, and additional procedures for outcome adjudication are not reported in the registry record.

The primary endpoint’s timeframe is described as during 4 weeks of prophylaxis, or up to 4 weeks, but further follow-up details are not reported. The registry record does not state how missing or incomplete outcome observations were handled, which participants were included in each analysis, or whether the endpoint definition was applied consistently throughout the study. It also does not report the analysis plan, sample-size justification, interim analyses, or multiplicity procedures.

The safety record supplies affected counts, serious-event terms, and a death count, but not event attribution, timing, overlap, or causes of death. Consequently, those data cannot establish treatment causality or provide a complete account of safety. The limited reporting means the design and recorded safety information can be described, while efficacy, survival, and the full safety interpretation remain undetermined from this registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients — NCT03318159.
• Registry record last updated 2024-12-20; status last verified 2024-11.
• Results first posted 2024-12-20.
• 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

The registry record describes NCT03318159, “Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients,” an open-label, single-group Phase II study sponsored by Seoul National University Hospital. The listed population is patients with aplastic anemia or hypoplastic myelodysplastic syndrome undergoing antithymocyte globulin treatment and receiving posaconazole prophylaxis. Enrollment is recorded as 20, and the study is marked completed.

The primary endpoint is the incidence of proven, probable, or possible fungal infection during 4 weeks of prophylaxis, described as up to 4 weeks. Overall survival and fungal infection are listed as secondary outcomes. The record does not report endpoint results or an analysis; it lists zero analyses.

For safety, the record reports 4 affected participants for serious adverse events and 4 for other adverse events, with 20 at risk in each category, and lists 6 deaths. It does not report the primary outcome result, comparative treatment effect, or the details needed to establish event causality.