Anidulafungin In Treatment Of Candidemia In Asian Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anidulafungin In Treatment Of Candidemia In Asian Subjects (NCT00537329), a non-randomized phase 3 study. The primary outcome is Number of Subjects With Global Response of Success at End of Treatment.

2. Clinical Question

The clinical question is descriptive: it concerns response and safety during treatment in the enrolled study population, rather than a randomized estimate of the difference between treatments. The trial record describes a Phase IIIB pilot study evaluating anidulafungin in subjects with candidemia. Its stated purpose was to assess safety and efficacy in Asian subjects. The primary endpoint links clinical status with microbiological evidence, so success required criteria from both response domains rather than a clinical assessment alone.

The endpoint timeframe was end of treatment, defined as Day 5 up to Day 42. This range is the registry's stated endpoint window; the record does not provide further details about how the time point was selected for each participant. Eleven outcome measures and 28 analyses are recorded. Those counts describe the scope of the registered outcomes and analyses, but do not establish which analyses were prespecified as primary or how results were adjusted for multiple comparisons. Such details are not reported in the registry record.

Because there is only one study group, the principal interpretive question is what response and safety counts were observed among the treated participants. The absence of a comparator limits what can be concluded about outcomes relative to another treatment or to no study treatment. The primary response count itself is not reported in the registry record, so the magnitude and precision of response cannot be assessed from the reported details.

3. Trial Design

This was a Phase IIIB, open-label, non-randomized, single-group pilot study of anidulafungin for candidemia in Asian subjects. The arm description calls it a multicenter, non-comparative 12 week study evaluating efficacy and safety. Enrollment was 43, and the registry status is completed. The listed start was 2008-01 and primary completion was 2009-03.

There was no random allocation and no masking. Participants and clinicians therefore knew the treatment being administered. There is no concurrent control arm against which to compare the response or adverse-event counts. The registry specifically characterizes the arms as not being a like-for-like control comparison; for this single-group study, the anidulafungin group is the only described treatment group.

The word “Phase” identifies the study's recorded development phase, while “pilot” describes the study in its official title and arm description. Neither label supplies the missing details of the protocol or statistical plan. The rationale for choosing a single-group pilot design, any planned precision target, and any sample-size justification are not reported in the registry record. Nor are dose, treatment schedule, eligibility criteria beyond the primary population description, or center-level details reported in the registry record.

The primary endpoint was the number of MITT subjects with global response success at end of treatment. Its timeframe was Day 5 up to Day 42. The MITT definition requires receipt of at least one treatment dose, confirmed documented candidemia, and receipt of the initial loading dose, in addition to membership in the Full Analysis Set. Enrollment and analysis-population size are not interchangeable: the number of enrolled subjects who met this definition is not reported in the registry record.

The record lists 11 outcome measures and 28 analyses, including global, clinical and microbiological response outcomes, time to death outcomes, and β-D-glucan assay outcomes. A list of outcomes does not by itself identify the statistical methods used for each analysis, the order of testing, or any hierarchy among endpoints. Those details are not reported in the registry record. Accordingly, the design supports a descriptive account of one treated group, but not a controlled estimate of comparative treatment effect.

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: Approximately 100 eligible subjects from 22 centers were planned to be enrolled. However, due to slow enrollment, 46 subjects were screened and 43 subjects were assigned to treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent to Treat (MITT): includes all Full Analysis Set (FAS) subjects (received at least 1 dose of study treatment) with confirmed, documented diagnosis of candidemia and had received the initial loading dose of study treatment.

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 Subjects With Global Response of Success at End of Treatment, measured over End of treatment (EOT) = Day 5 up to Day 42.

The primary endpoint is the number of subjects with global response success at end of treatment. It applies to the Modified Intent to Treat population and covers end of treatment from Day 5 up to Day 42. Global success combines two components. The clinical component is cure, meaning resolution of signs and symptoms of Candida infection, or improvement, meaning significant but incomplete resolution. The microbiological component is eradication, based on a negative follow-up culture for Candida species, or presumed eradication when a follow-up culture is unavailable and the clinical outcome is defined as success.

Combining clinical and microbiological criteria is intended to describe response across both how the infection presents clinically and the culture evidence. This is a general explanation of composite response endpoints: requiring multiple aspects to be considered can make the outcome more comprehensive, while also making its interpretation depend on each component's definition and assessment. In this endpoint, the “presumed eradication” rule means the endpoint can include a microbiological success classification when a follow-up culture is unavailable, provided the clinical outcome meets the stated success condition.

The endpoint is expressed as a count of subjects, not as a continuous measurement or time-to-event value. A count can describe how many participants met the criteria, but interpretation also depends on the size and definition of the analysis population. The MITT population criteria are stated in the registry record, while its size and the primary response count are not reported in the registry record. Thus, neither the observed response proportion nor its precision can be evaluated in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count endpoint tell the reader?

The primary outcome is a count of participants who met the global success definition. In general, a count is directly interpretable as the number meeting a criterion in the analysis population, but it depends on the denominator and the rules used to classify each participant. For a binary response, analysts may also describe a proportion or an interval around that proportion. These are general statistical concepts, not claims about methods used in this study. The primary result, denominator, and interval are not reported in the registry record.

The endpoint has two linked components: a clinical response and a microbiological response. In general, a composite endpoint can capture more than one dimension of a condition. Its meaning depends on the definitions of each component and on the rule that combines them. Here, the record defines success through cure or improvement together with eradication or presumed eradication. The absence of follow-up culture can therefore be treated according to a specified presumed-eradication rule when the clinical outcome meets the success definition. How often each component occurred separately is not reported in the registry record.

Why does a confidence interval matter?

As a general statistical concept, a confidence interval expresses uncertainty around an estimate under a specified statistical procedure. It helps readers distinguish the point estimate from the range of values that may be reasonably compatible with the data and method. An interval does not remove design limitations, and it cannot account automatically for bias, missing information, or differences between study groups. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated.

A p-value, when used, addresses compatibility of data with a specified statistical hypothesis under a model; it is not a direct measure of clinical importance or the probability that a hypothesis is true. The registry entries do not report a primary endpoint p-value or identify a hypothesis test. It would therefore be inappropriate to characterize the primary response as statistically significant or not statistically significant.

What does over-dispersion mean?

Over-dispersion is a general concern for count data when variation is greater than a chosen model expects. If a model assumes a particular relationship between the average count and its variability, extra variation can make standard errors too small and intervals or tests misleading. This concept is relevant when count outcomes are modeled, but the primary endpoint is described as a number of participants with a binary response, not a rate of recurrent events. The registry entries do not say that an over-dispersion model was used. It should not be assumed to have been part of the analysis.

How should a single-group result be understood?

In a single-group study, a response count describes the participants observed under the study conditions. General statistical methods can quantify uncertainty around that description, but they do not create a concurrent counterfactual group. Randomization is one way to support a comparative interpretation by balancing, on average, factors that could affect outcomes. This study is recorded as non-randomized and non-comparative, with one group, so no randomized treatment contrast is available from the design.

The open-label nature is also relevant as general context. When outcome assessment includes clinical judgment, awareness of treatment may influence assessment or reporting. This does not establish that bias occurred; it identifies a possible source of measurement influence. Whether the study used blinded endpoint review, independent adjudication, or other assessment safeguards is not reported in the registry record.

What do the planning illustrations represent?

The sample-size assumptions describe planning illustrations computed from an observed effect, rather than the trial's own design. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event tables, the stated quantity is total events, while other illustrations are expressed as participants per arm. These are planning conventions, not results from the single-group study.

In general, a sample-size calculation estimates the amount of information a hypothetical design would need for a chosen target under specified assumptions. It is sensitive to the effect size, allocation, outcome variability, significance level and power target. A calculation based on an observed effect is particularly dependent on that effect estimate and is not evidence that a trial had a particular probability of success. It is not observed power. Here, the stated illustration uses a two-arm equal-allocation setup even though the actual study is single-group and non-comparative. The illustration should therefore be read as a hypothetical planning exercise, not as a description of the actual study design or a justification for its enrollment. A trial-specific sample-size justification is not reported in the registry record.

The registry entries do not identify the estimator, confidence-interval method, hypothesis test, covariate adjustment, or model used for the primary endpoint. They also do not report whether results were adjusted for site or other factors. Those are not details that can be inferred from the endpoint definition or from the design label. The defensible statistical reading is to distinguish clearly between the outcome definition, the design, any reported result, and general methods concepts. In this record, the primary definition and design are described, while the primary result and analysis method are not reported in the registry record.

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("Anidulafungin")
n      <- c(42)
events <- c(31)
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  Anidulafungin  42  31  73.8  58.0  86.1  58.9  84.7  58.8  84.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 11 outcome measures and 28 analyses. The outcomes include global, clinical and microbiological response at endpoints, time to death from any cause, time to death due to candidemia, and β-D-glucan assay measures related to response status. This breadth creates a general multiplicity consideration: when many outcomes or analyses are examined, the chance of finding an apparently notable result can increase if each is tested separately. Whether and how that issue was handled is not reported in the registry record.

The registry entries identify a primary endpoint, but do not provide the complete statistical analysis plan, a testing hierarchy, an adjustment method, or details on which analyses were confirmatory versus exploratory. The count of analyses alone does not establish that every analysis was a hypothesis test or that any particular multiplicity correction was required. It does mean that individual results should be interpreted in light of the full analysis plan, which is not reported in the registry record.

The primary population is defined as MITT, with eligibility tied to treatment exposure and confirmation of candidemia. The number included in that population is not reported in the registry record, nor are numbers excluded or reasons for exclusion. Missing outcome handling, imputation, censoring rules, and sensitivity analyses are also not reported in the registry record. These details matter because participants without an assessable follow-up outcome may be handled in different ways, potentially changing a count-based response estimate.

The secondary outcomes include time-to-event measures and laboratory measures. Their analysis populations, endpoint-specific missingness, and statistical methods are not reported in the registry record. No assumptions about those methods should be inferred from the outcome names. Without the analysis plan and outcome counts, multiplicity and missing-data effects cannot be quantified from the record details.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: septic shock (4.7%), cardiac failure congestive (2.3%), cardio-respiratory arrest (2.3%), myocardial infarction (2.3%), upper gastrointestinal haemorrhage (2.3%).

The registry safety figures list 43 subjects at risk for serious adverse events, of whom 16 were affected, and 43 at risk for other adverse events, of whom 30 were affected. These are descriptive counts from the anidulafungin group. They are not comparative risk estimates, because the study has no concurrent control group. The registry entries do not state whether participants affected by serious events also appear among those affected by other events; the two counts should not be added together.

The listed serious-event terms are septic shock (4.7%), cardiac failure congestive (2.3%), cardio-respiratory arrest (2.3%), myocardial infarction (2.3%), upper gastrointestinal haemorrhage (2.3%), and chills (2.3%). These are the terms and percentages recorded in the registry entries. They should be read as listed event information, not as proof that an event was caused by the study drug. The registry entries do not specify the number of events versus the number of affected participants for each term, nor whether the list is exhaustive.

The death count is not reported in the registry record. Its absence from these registry entries should not be interpreted as zero deaths. Safety assessment also depends on definitions, follow-up duration, ascertainment and coding; those details are not reported in the registry record. The counts therefore describe reported safety information but do not establish comparative safety or causality.

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

The record establishes that an open-label, single-group study evaluated anidulafungin in Asian subjects with candidemia, with enrollment of 43 and a primary endpoint based on global response at end of treatment. It also identifies the response criteria and provides descriptive adverse-event counts. These registry entries clarify what the study was designed to assess and what safety information is listed.

The primary endpoint count is not reported in the registry record. As a result, the central response finding cannot be described from these registry entries, and neither the size of the response estimate nor its statistical precision can be assessed. A defined outcome and a stated study purpose do not substitute for a posted result. The MITT population size, primary endpoint estimate, and confidence interval are likewise not reported in the registry record.

Even if a response count were available, the single-group design would limit causal interpretation. Without randomization and a concurrent comparator, the study cannot establish how outcomes compare with another treatment or what would have happened to similar participants without the study treatment. Open-label assessment is also relevant because the primary outcome includes clinician judgment. These are design constraints, not evidence that the findings are necessarily biased.

The safety counts show how many subjects are recorded as affected in the stated categories, and the serious-event list supplies terms and percentages. They do not establish that an event was caused by anidulafungin, and without a comparator they cannot show whether risks differ from those under another treatment. The death count is not reported in the registry record.

Thus, the record supports an account of the study design, endpoint definitions, enrollment, and listed safety information. It does not support a conclusion about the magnitude or precision of the primary response, a randomized comparative treatment effect, or causal attribution of adverse events. Any planning illustrations are hypothetical and should not be mistaken for observed trial findings or observed power.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and endpoint definitions shape interpretation. Its primary endpoint combines a clinician-assessed clinical response with a microbiological response. That structure makes the success definition more specific than a single clinical assessment, but it also means that interpretation depends on multiple criteria, including the stated rule for presumed eradication when a follow-up culture is unavailable.

The study is recorded as non-randomized, open-label, single-group and non-comparative. That design can describe experience in the treated group, but it cannot provide the protection against confounding that random allocation is intended to offer in a comparative trial. A clinician-assessed endpoint in an open-label study also illustrates why outcome assessment methods matter. Whether any independent review was used is not reported in the registry record.

The registry's outcome list includes response measures, time-to-death outcomes and β-D-glucan assay measures. The number of outcomes and analyses makes it important to distinguish a prespecified primary question from exploratory or secondary analyses and to understand any multiplicity strategy. The relevant analysis-plan details are not reported in the registry record, so the analysis count cannot be interpreted as a testing hierarchy.

The sample-size assumptions also illustrate why planning calculations must be read in context. The stated illustrations use a hypothetical two-arm equal-allocation setup, while the actual study is one-group and non-comparative. They are based on an observed effect and are not the trial's design or a trial-specific justification. Such calculations are planning illustrations, not observed power.

Finally, the distinction between outcome definitions and outcome results is essential. The registry record defines the primary response carefully, but its response count is not reported in the registry record. This leaves the central efficacy result and its precision unavailable in the registry record recorded. The example underscores that statistical interpretation requires both a clear estimand and the numerical result, along with enough information about population, missing data and analysis methods to understand how the estimate was obtained.

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 response count and its analysis-population denominator are not reported in the registry record. The enrollment of 43 therefore cannot be treated as the number analyzed for the primary endpoint. The record defines the MITT population but does not report how many subjects met its criteria, whether any were excluded, or why.

The design is single-group, non-randomized, open-label and non-comparative. It has no concurrent control for interpreting response or safety differences. The clinical component of the primary endpoint is clinician assessed, and the record details do not state whether endpoint assessment was independently reviewed or whether other steps were used to reduce assessment bias. The number of centers is not reported in the registry record, although the arm description calls the study multicenter.

The endpoint timeframe is stated as end of treatment, Day 5 up to Day 42, while the arm description calls the study a 12 week study. Further details about individual assessment timing or follow-up windows are not reported in the registry record. Dose and administration schedule are also not reported in the registry record for this analysis.

Statistical methods for the response endpoint, uncertainty estimates, missing-data handling, and analysis-plan details are not reported in the registry record. The record lists 11 outcome measures and 28 analyses, but does not specify a multiplicity procedure or a hierarchy among analyses. The death count is not reported. Serious-event term percentages are listed, but the registry entries do not clarify whether those terms count participants or events or whether the list is exhaustive. These limits restrict both efficacy interpretation and safety comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Anidulafungin In Treatment Of Candidemia In Asian Subjects — NCT00537329.
• Registry record last updated 2010-03-09; status last verified 2010-03.
• Results first posted 2010-02-17.
• 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 describes a completed Phase IIIB pilot study of anidulafungin for candidemia in Asian subjects. It was open-label, non-randomized, single-group and non-comparative, with enrollment of 43. The arm description characterizes it as a multicenter 12 week study. The listed start was 2008-01 and primary completion was 2009-03.

The primary endpoint was the number of MITT subjects with global response success at end of treatment, defined as Day 5 up to Day 42. Success required a qualifying clinical response together with eradication or presumed eradication. The primary response count and MITT population size are not reported in the registry record.

Safety details list 16 subjects affected by serious adverse events and 30 affected by other adverse events, each among 43 at risk. Serious-event terms and percentages are recorded, but the death count is not reported. The record lists 11 outcome measures and 28 analyses; further statistical-plan and missing-data details are not reported in the registry record.