A Study of Caspofungin (MK-0991) in Japanese Children and Adolescents With Documented Candida or Aspergillus Infections (MK-0991-074): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Caspofungin (MK-0991) in Japanese Children and Adolescents With Documented Candida or Aspergillus Infections (MK-0991-074) (NCT01165320), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With an Overall Favorable Response to Therapy.

2. Clinical Question

3. Trial Design

This was a phase 2, multicenter, noncomparative, open-label study. It used nonrandomized allocation and a parallel model, with caspofungin as the listed intervention. The planned focus was to estimate safety, efficacy, and pharmacokinetics among Japanese children and adolescents with documented Candida or Aspergillus infections. The registry record lists esophageal candidiasis, invasive candidiasis, and aspergillosis as conditions, but reports that no participants with esophageal candidiasis were identified for inclusion and response assessment.

The registry record reports enrollment of 20 participants. The study began on 2010-07-06, reached primary completion on 2013-09-17, and has completed status. These dates describe the registry timeline; they do not establish how long each participant was followed. The primary endpoint timeframe was up to 56 days for invasive candidiasis and up to 84 days for aspergillosis.

Because the study was nonrandomized and noncomparative, its design does not provide a randomized treatment-versus-control contrast. The infection groups have different eligibility and response definitions, and should not be read as interchangeable comparison groups. Open-label status means masking was absent; the record does not describe additional procedures intended to reduce assessment bias.

The study’s enrollment, allocation, and masking details are reported, but several design details are not reported in the registry record. These include the dose and schedule, the treatment duration, the number of participating centers, the eligibility criteria in full, and the rationale for the planned enrollment. The registry record also does not describe a control group or a prespecified statistical analysis plan.

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: Three participants were initially enrolled but were withdrawn when their suspected fungal infections were not confirmed. These 3 participants did not receive study drug. No participants with esophageal candidiasis were identified for inclusion in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The full analysis set included all enrolled participants who received \>=1 dose of study drug. No participants with esophageal candidiasis were identified for inclusion in the study and assessment for response to therapy. Participants whose overall response assessment was "unable to judge" were counted as having an unfavorable response.

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 Percentage of Participants With an Overall Favorable Response to Therapy, measured over Invasive candidiasis: up to 56 days; aspergillosis: up to 84 days.

The primary endpoint was the percentage of participants with an overall favorable response to therapy. This is a binary outcome at the participant level: each assessed participant is classified as having a favorable response or not, and the group result can be expressed as a percentage. The endpoint is intended to combine clinical status with other evidence relevant to the infection rather than relying on a single measurement.

The criteria differed by infection type. For invasive candidiasis, a favorable response required resolved clinical findings and a negative follow-up Candida culture. When Candida was not observed in the baseline blood culture, the definition instead required resolved clinical findings and resolved or improved radiographic findings. For aspergillosis, the definition allowed specified combinations of clinical and radiographic status, including resolved, improved, unchanged, or stable findings as described in the registry record.

General statistical context: composite response endpoints can capture more than one dimension of a condition, but their meaning depends on the components and decision rules. Here, the infection-specific definitions matter when interpreting any percentage, because a favorable response did not use an identical set of criteria across the two infection groups. The endpoint’s observed percentage and uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: a clinical study’s analysis should connect the outcome definition, the population being analyzed, and the method used to estimate the result. The registry record describes a binary primary endpoint—the presence or absence of an overall favorable response—but does not report a primary analysis estimate or statistical test. It also lists no analysis entries. The methods used to calculate the primary result, if it was calculated, are not reported in the registry record.

What does a percentage describe?

For a binary endpoint, the percentage describes the share of assessed participants classified in a particular category. For this study, the category of interest was overall favorable response. A percentage is easy to interpret as a summary, but it depends on which participants are included in the denominator and how each participant’s outcome is classified. The registry record defines the full analysis set as enrolled participants who received at least one dose of study drug. It does not report the primary result or the number of participants included in the response analysis.

The response rules were infection-specific. In invasive candidiasis, favorable response depended on clinical findings and follow-up culture, with a different rule when Candida was not observed in the baseline blood culture. In aspergillosis, the criteria used clinical and radiographic findings with several permitted combinations of status. These definitions are part of the measurement method: the endpoint is not a single laboratory result, and the same response label does not represent precisely the same criteria in each infection group.

Why does uncertainty matter?

General statistical context: a confidence interval communicates uncertainty around an estimate. A narrower interval indicates greater precision under the specified method; a wider interval indicates less precision. The width depends on factors such as the number of observations and the variability of the data. A point estimate alone does not show how stable an estimate may be in other samples. No confidence interval for the primary response is reported in the registry record, so the result’s precision cannot be assessed.

A small study can be useful for describing observations and informing further research, but its estimates may be uncertain. This is especially important when outcomes are expressed as percentages in relatively small groups. The registry record reports an overall enrollment of 20 and gives safety group sizes, but it does not report the number of primary endpoint responders. No primary-response percentage should be inferred from the enrollment or safety information.

What can nonrandomized, open-label design establish?

General statistical context: random allocation is used to support comparable treatment groups, on average, for a causal comparison. This study was nonrandomized and noncomparative, with no masking. The record does not describe a control treatment. Accordingly, the design does not provide a randomized contrast that separates a treatment effect from differences in participants, disease presentations, clinical care, or outcome assessment. The different infection groups are not substitutes for a control group, since their conditions and endpoint criteria differ.

Open-label assessment means treatment masking was absent. General statistical context: when outcome classification involves clinical judgment, knowledge of treatment can potentially influence assessment. The extent of any such influence cannot be determined from the design label alone. The registry record does not report additional safeguards, such as blinded adjudication, so none should be assumed.

What do the planning assumptions mean?

General statistical context: a sample-size calculation is a planning exercise that estimates how many observations may be needed under stated assumptions. It is not evidence that a study had a particular probability of finding a result, and it is not an observed result. The registry record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. For time-to-event outcomes, the stated convention is a total number of events; for other outcomes, it is participants per arm.

Those assumptions describe an illustration rather than the trial’s own design. The study was nonrandomized and noncomparative, and the registry record does not report a sample-size justification for this study. Any planning figures associated with such an illustration should therefore not be interpreted as the observed enrollment requirement, as a prespecified target, or as observed power. The registry record does not report an interim analysis plan, a statistical analysis plan, or the methods used for the primary endpoint.

How should missing analysis details be read?

General statistical context: interpretation of a clinical result often depends on knowing the analysis population, handling of missing outcomes, and approach to uncertainty. The registry record identifies the full analysis set as all enrolled participants who received at least one dose. It says participants whose response assessment was “unable to judge” were counted, but the remainder of that description is not reported in the registry record. The handling of missing assessments, exclusions after enrollment, and any sensitivity analyses is therefore unclear.

Without the endpoint numerator, denominator, analysis method, and uncertainty estimate, the primary result cannot be reconstructed from the information in the registry record. No independent recalculation is possible from the posted data. The safety percentages can be reported as registry findings, but they do not reveal the missing response analysis.

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 Invasive Candidiasis", "Participants With Aspergillosis")
n      <- c(12, 8)
events <- c(8, 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  Participants With Invasive Candidiasis  12  8  66.7  34.9  90.1  39.1  86.2  38.6  86.1
ARM  Participants With Aspergillosis  8  5  62.5  24.5  91.5  30.6  86.3  29.9  86.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and no analysis entries. It does not report a multiplicity strategy, such as whether any formal adjustment was planned for multiple outcomes or comparisons. It also does not report a hierarchy of endpoints or identify which analyses, beyond the stated primary outcome, were prespecified. Without those details, the role of any secondary outcome in formal inference cannot be assessed.

The primary analysis population is described as the full analysis set: enrolled participants who received at least one dose of study drug. The record states that no participants with esophageal candidiasis were identified for inclusion in the study and response assessment. It also refers to participants whose overall response was “unable to judge,” but the remainder of the handling description is not reported in the registry record. The number of such assessments and how they were treated in the analysis are not reported.

Missing outcome data can affect a response percentage if participants with unavailable assessments are excluded or classified in a particular way. General statistical context: transparent reporting of the number assessed, the number with missing outcomes, and the handling rule helps readers judge whether the analysis could be sensitive to those decisions. Those details are not reported in the registry record.

The record does not report an interim analysis plan, a statistical analysis plan, or sensitivity analyses. It also does not state whether analyses were adjusted for other factors. These omissions do not establish that such procedures were or were not used; their status is not reported in the registry record.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (12.5%), sepsis (12.5%), hyperventilation (12.5%).

The registry record reports safety groups for invasive candidiasis and aspergillosis. In the invasive candidiasis group, 1 of 12 participants had a serious adverse event; the other-adverse-event figures are 10 of 12. In the aspergillosis group, 2 of 8 participants had a serious adverse event; the other-adverse-event figures are 5 of 8. These are descriptive counts within the listed groups, not estimates from a randomized comparison.

The top serious adverse-event terms are pneumonia, sepsis, and hyperventilation, each reported at 12.5%. The registry record does not report a death figure. It also does not give further detail in the posted safety information about event timing, duration, severity grading beyond the serious classification, or whether an event was considered related to treatment.

General statistical context: adverse-event percentages describe the frequency recorded in a defined group; they do not by themselves establish that treatment caused an event. Interpretation depends on the study design, event definitions, follow-up, and completeness of reporting. Because the groups had different infections and there was no randomized control group, their adverse-event figures should not be treated as a comparative safety estimate. The registry record’s safety data do not answer the missing primary response question.

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

The registry record describes a study designed to estimate safety, efficacy, and pharmacokinetics of caspofungin in Japanese children and adolescents with documented Candida or Aspergillus infections. It identifies an overall favorable response as the primary endpoint and explains different response criteria for invasive candidiasis and aspergillosis. It also reports enrollment, the endpoint assessment windows, and several safety findings.

However, the primary endpoint result is not reported in the registry record. There is no reported favorable-response percentage, responder count, confidence interval, or primary analysis estimate in the information available. Therefore, the endpoint’s observed magnitude and precision cannot be described from this record. No conclusion about the size of a treatment effect can be drawn from the endpoint definition alone.

The design also sets limits on what the study can establish. It was nonrandomized, open-label, and noncomparative, and no control treatment is described. The record therefore does not offer a randomized comparison that would estimate how outcomes differ between caspofungin and another treatment. Comparing the infection groups would not fill that gap, because they represent different conditions and use different response criteria.

The reported safety figures show that serious adverse events were recorded in both infection groups and identify pneumonia, sepsis, and hyperventilation among the top serious event terms. These observations are descriptive and do not establish whether events were caused by treatment or how safety compares with another treatment.

General statistical context: absence of a reported estimate is not evidence that the outcome was zero or that no analysis occurred. It means the registry record does not provide enough information to quantify that outcome. The appropriate interpretation is limited to the design, definitions, and findings that are actually reported.

14. Why This Trial Matters Statistically

This study is statistically notable because it illustrates the distinction between describing a clinical study and estimating a comparative treatment effect. The registry record describes a phase 2, noncomparative, open-label design intended to estimate safety, efficacy, and pharmacokinetics. Such a design can organize observations in a defined treated population, but it does not create a randomized control contrast.

The primary endpoint also highlights the importance of outcome definition. “Overall favorable response” combined clinical findings with culture or imaging evidence, and the criteria differed between invasive candidiasis and aspergillosis. A response percentage would need to be interpreted in light of those disease-specific rules rather than as a uniform outcome across all infection types.

The record states that no participants with esophageal candidiasis were identified for inclusion in the study and response assessment, despite listing esophageal candidiasis among the conditions. This distinction matters for defining the population to which any study estimate could apply. The overall enrollment does not mean that every listed infection was represented in the response analysis.

Finally, the registry record demonstrates why outcome reporting is essential. It provides an endpoint definition and safety information but does not report the primary response result or its precision. Without those quantities, readers cannot assess the magnitude or uncertainty of the main outcome. The study can be characterized by its design and recorded safety findings, but the registry information does not permit a quantitative appraisal of its primary response endpoint.

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 main objective is that the primary favorable-response result is not reported in the registry record. The responder count, percentage, and uncertainty estimate are also not reported. As a result, the primary endpoint’s magnitude and precision cannot be assessed.

The study was nonrandomized, noncomparative, and open-label. No control treatment is described, so the record does not support a randomized estimate of comparative benefit or harm. The different infection groups do not provide an appropriate substitute for a control group: they represent different conditions and have different response definitions.

The registry record reports enrollment of 20 and identifies no participants with esophageal candidiasis for inclusion in the study and response assessment. This limits the relevance of the record to that listed condition. The number of participants in each primary response analysis is not reported, and the handling of “unable to judge” assessments is incompletely described. Missing assessments and their analysis could affect an endpoint percentage, but the information needed to evaluate that possibility is not reported.

Further details important to interpretation are not reported in the registry record, including the dose and schedule, treatment duration, full eligibility criteria, sample-size justification, statistical analysis plan, interim analyses, and any multiplicity procedure. Safety reporting also lacks a death figure and additional detail about event timing and treatment relatedness. These are limitations of the available registry information; they do not establish what was or was not done outside the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Caspofungin (MK-0991) in Japanese Children and Adolescents With Documented Candida or Aspergillus Infections (MK-0991-074) — NCT01165320.
• Registry record last updated 2018-08-27; status last verified 2018-07.
• Results first posted 2014-04-23.
• 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

This completed phase 2 study evaluated caspofungin in Japanese children and adolescents with documented Candida or Aspergillus infections. It was multicenter, nonrandomized, noncomparative, open-label, and used a parallel model. Enrollment was 20. The primary endpoint was the percentage of participants with an overall favorable response, assessed up to 56 days for invasive candidiasis and up to 84 days for aspergillosis. Its result is not reported in the registry record.

No participants with esophageal candidiasis were identified for inclusion in the study and response assessment. Safety groups included 12 participants with invasive candidiasis and 8 with aspergillosis. Serious adverse events were reported for 1 of 12 and 2 of 8, respectively. Pneumonia, sepsis, and hyperventilation were each reported at 12.5% among the top serious event terms. The registry record does not report a death figure or a comparative treatment effect.