Study Will Evaluate The Safety And Efficacy Of Anidulafungin In Patients With Candidemia Or Invasive Candidiasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Will Evaluate The Safety And Efficacy Of Anidulafungin In Patients With Candidemia Or Invasive Candidiasis (NCT00496197), a non-randomized phase 4 study. The primary outcome is Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Treatment (EOT).

2. Clinical Question

The clinical question is whether participants treated with the intravenous-to-oral regimen met the registry's combined definition of global response by end of treatment. Success required a clinical response of cure or improvement and a microbiological response of eradication or presumed eradication. Failure required clinical failure and microbiological persistence or presumed persistence. These categories combine assessments of symptoms and culture findings into a single outcome.

This is a description of response within one treated group, not a randomized estimate of comparative benefit. Without a control group, any outcome observed in the participants could not be separated from the course of illness, other care, or other influences using this study design alone. The registry record states that 282 participants were enrolled, but does not report how many were included in the primary analysis or how many had success or failure. It also does not report a numerical estimate of treatment response or its precision. The endpoint definition and treatment sequence establish what the study set out to assess; they do not establish the outcome.

3. Trial Design

This was a Phase IV, open-label, nonrandomized, single-group study sponsored by Pfizer. The record lists candidiasis as the condition and an enrollment of 282 participants. It reports a start date of 2007-07, primary completion in 2010-06, and a completed status. The official title identifies the study as an open-label, noncomparative trial of intravenous anidulafungin followed by oral azole therapy.

The intervention was a treatment sequence rather than a comparison of separate assigned regimens: intravenous anidulafungin followed by oral fluconazole or voriconazole. The study summary describes intravenous treatment for 5-28 days followed by oral antifungal medication. The primary endpoint was assessed at end of treatment, with the stated timeframe of Day 5 up to Day 42. The record also lists clinical, microbiological, and global response outcomes at end of treatment, end of intravenous treatment, and follow-up.

Open-label means the treatment was not masked according to the registry record. Nonrandomized allocation and the single-group model mean there was no randomized control arm. The record explicitly cautions that arms are not a like-for-like control comparison. In this design, response counts can describe what happened among analyzed participants, but the design does not provide the protection against confounding that random assignment can offer in a comparative trial.

The registry record does not report a sample-size justification, a detailed statistical analysis plan, planned interim analyses, or a numerical primary outcome result. The stated enrollment should not be treated as the primary analysis denominator: the primary population had additional eligibility conditions, and participants with missing outcome values were excluded. The number actually included in that endpoint analysis is 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent to Treat population (MITT): includes all participants who received at least 1 dose of study medication and with a positive baseline culture for a Candida spp. N=number of participants included in analysis (participants with missing outcome values were excluded from the 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 Number of Participants With Global Response of Success or Failure (Based on Clinical and Microbiological Response) at End of Treatment (EOT), measured over End of Treatment (Day 5 up to Day 42).

The primary endpoint counted participants with global response of success or failure at end of treatment, defined as Day 5 up to Day 42. It combined clinical and microbiological assessments. Clinical cure meant no signs or symptoms of Candida; improvement meant significant but incomplete resolution. Microbiological eradication meant a negative follow-up culture, while presumed eradication applied when a follow-up culture was unavailable and the clinical response was successful. Failure combined clinical failure with persistence or presumed persistence of Candida.

A composite endpoint is used to capture more than one aspect of response in a single classification. In this case, it requires clinical and microbiological information to align with the defined success or failure categories. This can make the outcome more comprehensive than either assessment alone, but it also means the overall category depends on the component definitions and on whether follow-up culture information is available.

The registry record describes the endpoint criteria and analysis population but does not report the number of participants with success or failure. It therefore does not establish how often either classification occurred. Nor does it report a confidence interval or another measure of uncertainty for the primary result. The endpoint definition explains what was to be counted; it is not itself evidence of the observed response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: each participant is classified as having global success or failure at end of treatment. Binary outcomes reduce a participant's response to a category, which can make results straightforward to count. They also discard detail about the degree or timing of change within each category. For this trial, the categories were based on combined clinical and microbiological criteria rather than on a single measurement.

What does a composite response mean?

A composite outcome combines multiple component outcomes into one overall classification. Here, the clinical component concerned signs and symptoms, while the microbiological component concerned follow-up culture and Candida persistence. The registry's success definition requires clinical cure or improvement together with eradication or presumed eradication. Its failure definition requires clinical failure together with persistence or presumed persistence. This makes the endpoint a rule-based combination, not a simple count of clinical improvement alone.

Composite outcomes can be useful when more than one aspect of a condition is relevant to the question. They can also conceal differences between components: the same overall classification may arise from different clinical and microbiological patterns. Separate component results can help explain the combined outcome, and the registry lists clinical and microbiological response outcomes separately. The numerical results for those outcomes are not reported in the registry record.

How should the denominator be understood?

The primary population was the modified Intent to Treat population. It included participants who received at least one dose of study medication and had a positive baseline culture for a Candida species. The record further states that participants with missing outcome values were excluded from the analysis. Thus, enrollment is not a substitute for the endpoint denominator. The number in the primary analysis is not reported in the registry record, so the proportion classified in either category cannot be recovered from the enrollment figure.

In general, a proportion is interpreted in relation to its denominator, and uncertainty around that proportion depends in part on the amount of information in the analysis. A confidence interval is a range of values compatible with the observed data under a specified statistical method; it communicates precision as well as the estimate. The registry record does not report a primary estimate or confidence interval, so neither the outcome level nor its precision can be assessed.

Why does the study design matter?

Random assignment, when used, is intended to make comparison groups similar on average with respect to measured and unmeasured factors. This study was nonrandomized and single-group, with no comparator. Therefore, its design supports a descriptive account of outcomes in the analyzed group but not a randomized treatment contrast. General concerns for a single-group study include changes over time, differences in participant prognosis, and other care or circumstances that may influence outcomes. The record does not establish that any of these factors affected the results.

Open-label status means masking was absent. In general, knowledge of treatment can influence clinical judgments, reporting, or decisions about assessment. The extent to which that could matter depends on how outcomes were assessed and the procedures used. The registry record does not report further details of assessor masking or the statistical procedures used to mitigate assessment bias. The global response endpoint includes clinical judgments as well as culture-based criteria, which makes the assessment process relevant to interpretation.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variation is greater than a statistical model expects. It is relevant to some count-data models, where assuming too little variation can make uncertainty estimates too narrow. The primary outcome in this record is a participant count for a binary classification, and no over-dispersion assessment or count-model specification is reported. This general concept should not be mistaken for a finding about this trial.

How should planning calculations be read?

The stated sample-size illustrations are planning calculations based on an observed effect, not the trial's own design justification. The assumptions include 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. The record says that time-to-event illustrations use a total event count, while other illustrations use participants per arm. These are hypothetical planning quantities, not observed power and not a description of the actual single-group study allocation. No trial-specific sample-size justification is reported in the registry record.

A significance level is a threshold used in a testing procedure to control the chance of a false positive under specified assumptions. It does not measure the probability that a treatment effect is real, nor does it describe the size or importance of an effect. A power calculation concerns the chance of detecting an assumed effect under a design and model; it is not a measure of the probability that a completed study's result is correct. Because no primary numerical result or detailed test procedure is reported, significance testing cannot be reconstructed from this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 24 outcome measures and 16 analyses. It includes the primary global response at end of treatment and additional clinical, microbiological, and global response assessments at end of treatment, end of intravenous treatment, and follow-up. When several outcomes or analyses are considered, the chance of at least one false positive can increase if each is tested independently at the same threshold. Statistical approaches to multiplicity can address this concern, but the appropriate approach depends on which outcomes are confirmatory and how the analyses were planned. The registry record does not report a multiplicity adjustment, hierarchy, or detailed testing strategy.

Missing data also affect interpretation. The primary analysis population excluded participants with missing outcome values, according to the registry description. The record does not report how many primary outcome values were missing, why they were missing, or whether analyses assessed the effect of missingness. Excluding participants with missing outcomes can be straightforward to describe, but if missingness is related to prognosis or response, the analyzed participants may differ systematically from those excluded. That is a general methodological concern, not a claim about what occurred in this study.

The endpoint definition allows presumed eradication or presumed persistence when follow-up culture is unavailable, conditional on the clinical result. This rule addresses one form of unavailable component information, but the registry record does not report the number classified using either presumed category. It also does not report additional missing-data sensitivity analyses.

The modified Intent to Treat population required treatment exposure and a positive baseline Candida culture. The record does not report the number analyzed under this definition. Enrollment of 282 should therefore not be used as the endpoint denominator. A complete accounting of analyzed, excluded, and missing participants is not reported in the registry record.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (4.6%), septic shock (3.2%), respiratory failure (2.5%), cardiac arrest (2.1%), pneumonia (2.1%).

For the anidulafungin group, the registry lists 282 participants at risk for serious adverse events and 134 affected. It lists 282 at risk for other adverse events and 132 affected. These are counts of participants recorded in the relevant categories; they should not be combined into a single total, since the categories are distinct registry summaries and a participant may be represented in more than one safety category.

The serious adverse event terms listed with percentages are sepsis, 4.6%; septic shock, 3.2%; respiratory failure, 2.5%; cardiac arrest, 2.1%; pneumonia, 2.1%; and renal failure, 2.1%. These terms describe reported serious events, not necessarily events judged to be caused by study treatment. The registry record does not report causal attribution for these terms in the information summarized.

The record does not report a death count for the safety group. The listed term percentages should be read as registry-reported values; they do not establish how the events were distributed over time or whether participants experienced more than one event. Because this was a single-group study, these safety figures do not provide a controlled comparison with another treatment.

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

The record establishes that a completed Phase IV study evaluated an intravenous anidulafungin regimen followed by oral fluconazole or voriconazole in participants with candidemia or invasive candidiasis. It describes a primary endpoint combining clinical and microbiological response and specifies the modified Intent to Treat population used for analysis. It also reports safety counts and selected serious adverse event terms.

However, the primary outcome count and response estimate are not reported in the registry record. The number included in that analysis is also not reported. Consequently, the posted record does not show how many participants met the success definition, how many met the failure definition, or how precisely either result was estimated. It cannot support a conclusion about the frequency of response based on the endpoint description alone.

The design further limits what can be inferred. The study was open-label, nonrandomized, and single-group, with no comparator. Even if a response estimate were available, it would describe outcomes in the analyzed group and would not by itself establish how outcomes would compare under another treatment. A causal treatment contrast requires a suitable comparison and assumptions that this design does not supply through randomization.

The safety counts show participants recorded as affected in the registry's serious and other adverse event categories, and the selected serious event terms are accompanied by percentages. These observations are descriptive. They do not establish that treatment caused any particular event or allow a direct safety comparison against another regimen.

Accordingly, the most defensible reading is limited to the study's design, intended outcome definition, analysis-population criteria, and the safety summaries recorded. The registry record does not report enough numerical efficacy information to quantify the primary response or its uncertainty. No treatment recommendation or comparative conclusion follows from these posted data alone.

13. Why This Trial Matters Statistically

Statistically, the trial is useful for illustrating the difference between describing outcomes and estimating a comparative effect. A single-group study can document outcomes among participants who received a defined treatment sequence, but without a control group it cannot provide a randomized estimate of how those outcomes differ from an alternative. The nonrandomized, open-label design is therefore central to interpretation, not a minor detail.

The primary outcome also illustrates how a composite endpoint depends on operational definitions. Success and failure combine clinical findings with microbiological evidence, and the definitions include presumed categories when culture results are unavailable. Readers need to know these rules to understand what the endpoint counts. A single global result, even if reported, would not replace examination of the clinical and microbiological components.

The registry record distinguishes total enrollment from the modified Intent to Treat analysis population and notes exclusion of participants with missing outcome values. This is a reminder that analysis denominators are part of the result: enrollment alone does not tell readers how many participants contributed to a particular endpoint. Here, that analysis count and the primary result are not reported in the registry record, limiting both interpretation and assessment of precision.

The record's safety summaries provide a descriptive account of affected participants and selected serious event terms, but the lack of a comparator limits comparative safety inference as well. Finally, planning calculations based on an observed effect must remain separate from trial results and from the trial's own design rationale. The registry record does not report a sample-size justification or enough primary outcome data to evaluate the endpoint statistically. These distinctions make this study a clear example of why design, outcome definitions, denominators, and reported uncertainty all matter alongside an enrollment total.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most consequential limitation for statistical interpretation is that the registry record does not report the primary outcome result. It gives the success and failure definitions but no count, proportion, or uncertainty estimate. The primary analysis denominator is also not reported, so the enrolled total of 282 cannot be used to reconstruct the endpoint result.

The study had no randomized comparator: it was nonrandomized, open-label, and single-group. Its design therefore cannot separate outcomes under the treatment sequence from the course of illness or other influences through a randomized contrast. This limits comparative and causal interpretation, even if complete response results were available.

The primary population was restricted to participants who received at least one dose and had a positive baseline Candida culture, while participants with missing outcome values were excluded. The record does not report the number excluded, the reasons for missing outcomes, or sensitivity analyses addressing missingness. It also does not state how many participants were classified through presumed eradication or presumed persistence.

The endpoint combines clinical and microbiological response. This provides a joint classification but can mask differences between its components, and the registry record does not report the numerical component results. The record lists multiple outcome measures and analyses but does not report a detailed statistical plan or a multiplicity strategy. It also does not report a sample-size justification, planned interim analyses, or a primary result with which to assess precision.

These limitations describe what is absent or constrained in the registry record; they do not establish that the study was conducted improperly. They define how narrowly its posted information can be interpreted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Will Evaluate The Safety And Efficacy Of Anidulafungin In Patients With Candidemia Or Invasive Candidiasis — NCT00496197.
• Registry record last updated 2011-10-03; status last verified 2011-08.
• Results first posted 2011-10-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes NCT00496197, a completed Phase IV, open-label, nonrandomized, single-group study sponsored by Pfizer. Enrollment was 282 participants, and the study evaluated intravenous anidulafungin followed by oral fluconazole or voriconazole for candidemia or invasive candidiasis. Intravenous treatment was described as lasting 5-28 days.

The primary endpoint counted participants with global success or failure at end of treatment, defined as Day 5 up to Day 42. The analysis population required treatment exposure and a positive baseline Candida culture; participants with missing outcome values were excluded. The primary outcome count, analysis denominator, and uncertainty estimate are not reported in the registry record.

The record lists additional response outcomes and safety summaries, including 134 participants affected by serious adverse events and 132 affected by other adverse events, each among 282 at risk. With no comparator group and no reported primary outcome result, the record supports a description of the study design and recorded safety counts, but not a comparative estimate of efficacy.