Negative Beta Glucan in ICU Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Negative Beta Glucan in ICU Patients (NCT01734525), a na phase 4 study. The primary outcome is Evaluate the Ocurrence of Candidemia in Patients With Negative 1,3 Beta-D-glucan Who Discontinue Anidulafungin.

2. Clinical Question

The study’s broader objectives were to assess how often biomarkers were positive among ICU patients considered at high risk of invasive candidiasis or candidemia, and to test an approach to stopping antifungal therapy early when blood cultures and 1,3-beta-D-glucan remained repeatedly negative. These objectives connect a diagnostic marker with a treatment decision, but they are not equivalent to a randomized comparison of treatment strategies.

The primary outcome is specifically about candidemia after discontinuation among participants with negative biomarker results. It is not a general measure of all invasive candidiasis, nor does the registry description establish that every enrolled participant met the outcome’s biomarker and discontinuation conditions. The number of participants meeting those conditions, and the exact analysis population for the endpoint, are not reported in the registry record.

3. Trial Design

This is a completed prospective study registered as phase 4, with an enrollment of 85. Its start is recorded as 2012-11 and its primary completion as 2013-12. The sponsor is Universidade Federal do Rio de Janeiro. Candidemia is listed as the condition. The registry describes a single-group design, allocation as not applicable, and masking as none.

The intervention listed is anidulafungin, described for patients considered at risk. The study summary sets out a strategy of early initiation of antifungal treatment and proposes early discontinuation based on repeatedly negative blood cultures and serum 1,3-beta-D-glucan. The record does not provide a separate arm receiving usual care, another antifungal, or a different biomarker-guided strategy. The registry therefore does not describe a like-for-like comparison from which a relative treatment effect can be estimated.

The design is important for interpreting the primary outcome. The endpoint concerns candidemia among participants with negative 1,3-beta-D-glucan who discontinue anidulafungin, assessed over 30 days. In a single-group study, that outcome can describe what happened to the defined participants under the study strategy, if results are reported. It cannot by itself show what would have happened to comparable participants under an alternative strategy.

The registry lists one outcome measure, but no analysis is listed and no primary outcome result is reported in the registry record. Details such as eligibility criteria, the number who received treatment, the number who discontinued, biomarker testing schedules, and the specific procedures used to define repeated negative results are not reported in the registry record. These omissions limit how fully the strategy and its endpoint can be reconstructed from the record.

The single-group design and absence of masking do not automatically invalidate a descriptive study, but they affect what can be concluded. Without a comparison group, differences between possible treatment strategies are not identified by this design. With no masking, knowledge of the strategy could potentially affect care or outcome assessment; whether that occurred, and what steps were taken to limit it, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

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 Evaluate the Ocurrence of Candidemia in Patients With Negative 1,3 Beta-D-glucan Who Discontinue Anidulafungin, measured over 30 days.

The primary endpoint is the occurrence of candidemia among participants with negative serum 1,3-beta-D-glucan who discontinue anidulafungin. The registry specifies a count of participants and a 30-day timeframe. In plain terms, it is intended to count how many people in this defined group develop candidemia during the stated period after treatment is stopped.

This endpoint is relevant to the study’s stated question because the proposed strategy uses repeatedly negative blood cultures and 1,3-beta-D-glucan as a basis for stopping antifungal treatment early. Monitoring for candidemia after discontinuation addresses whether the outcome of interest is subsequently observed in that group. The endpoint is not itself a comparison of stopping treatment with continuing treatment, because no comparator group is described.

The registry record does not report the observed candidemia count, the number of participants who qualified for this endpoint, or an effect estimate with uncertainty. It also does not specify in the endpoint description how candidemia was defined, how outcomes were ascertained, or whether participants with incomplete follow-up were included in a particular way. Those details are not reported in the registry record.

As a general statistical point, a participant count is a direct description of how many people experience an event, but its interpretation depends on the population counted and the completeness of outcome ascertainment. Without the outcome count and the relevant denominator, the endpoint cannot be quantified from the registry record. Even when those quantities are available, a single-group count describes observed outcomes under that study context; it does not establish what an alternative treatment strategy would have produced.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group study estimate?

In general, a single-group study observes participants managed under a described strategy and summarizes outcomes within that group. It can provide a count of events or other descriptive measures when results and denominators are reported. The design does not directly compare the observed group with a concurrent group receiving an alternative strategy. This study is recorded as single-group, and no comparator arm is listed. Therefore, even if its candidemia outcome were reported, the design would not by itself estimate the difference between stopping anidulafungin and continuing it.

A treatment contrast asks how outcomes differ between strategies. In general, a randomized comparison can help make groups comparable with respect to factors that influence outcomes, while a single-group observation cannot ensure that observed outcomes are attributable to the strategy rather than other influences. No randomized allocation or comparator is described in this record. The record does not report an adjusted comparison or another design feature intended to estimate a counterfactual outcome.

What does a participant count mean?

The primary endpoint is defined as a count of participants with candidemia in a particular group over a stated timeframe. A count is interpretable only alongside the number of participants who could have experienced the event and the rules for deciding who belongs in that group. Here, the endpoint group is participants with negative 1,3-beta-D-glucan who discontinue anidulafungin. The registry does not report how many participants met those conditions or the observed event count. Enrollment of 85 describes study enrollment, not necessarily the number in the endpoint population.

As a general concept, a denominator identifies the population to which an event count refers. A count without a clear denominator cannot convey an event frequency, and a denominator that includes participants who did not meet the endpoint definition can misrepresent the population being described. No event frequency should be inferred from the registry’s enrollment alone. The endpoint is also limited to candidemia as named in the outcome, rather than every possible form of invasive candidiasis.

Why does uncertainty matter?

General statistical inference distinguishes an estimate from its precision. A confidence interval is a range calculated by a statistical procedure to express uncertainty around an estimate; its width depends on factors such as the amount of information and variability in the data. A p-value, when used, addresses how compatible data are with a specified null model under the assumptions of the test. Neither type of result is reported for the primary outcome in this registry record. There is consequently no reported interval or test result to interpret, and no basis for describing the endpoint as statistically significant or not statistically significant.

Even when a count is available, the observed value is not the complete account of uncertainty. In general, event counts from limited populations may be compatible with a range of underlying event rates. A precise numerical interval would require the relevant outcome count, denominator, and a stated method. Since the registry does not report those endpoint data, no interval or rate can be reconstructed without adding information not in the record.

How should the design and biomarker strategy be separated?

The study summary describes serum 1,3-beta-D-glucan as a biomarker considered alongside blood cultures in an early-discontinuation strategy. In general, a biomarker can be used to classify or inform decisions, but a biomarker’s role in a protocol is distinct from evidence that a decision based on it improves outcomes. Assessing a decision strategy requires clear information about who was tested, how results were interpreted, what actions followed, and the outcomes observed. The record states the strategy’s broad aim but does not report the testing schedule, exact decision rules, or outcome data needed to evaluate performance.

Negative predictive value is the probability that the condition of interest is absent among people with a negative test result, under a specified population and testing context. As a general concept, this value depends on the population and the frequency of the condition in that setting; it cannot be inferred from a biomarker rationale alone. The registry summary mentions the potential usefulness of negative predictive value, but the record does not report a calculated predictive value or the data needed to assess it.

What do planning assumptions tell us?

The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. This is a planning framework, not a description of the actual single-group trial design. It does not establish that the study was planned as a two-arm trial, and it does not report the trial’s own sample-size justification.

In general, a sample-size calculation asks how much information a hypothetical design would need to detect a specified effect under assumptions about the analysis and error rates. A planning illustration is conditional on those assumptions and should not be interpreted as observed power or as evidence that the study did or did not detect an effect. The registry record does not report numerical outputs for the planning illustration in the registry record for this analysis, and no sample-size result should be inferred.

Overall, the available information identifies the design and intended outcome but leaves the core endpoint results, uncertainty, analysis choices, and biomarker performance unreported. Statistical interpretation must remain descriptive and limited to those recorded details.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or a procedure for addressing multiplicity. Multiplicity arises in general when several outcomes, timepoints, subgroups, or statistical tests are examined: the chance of at least one apparently notable result can increase as the number of analyses grows. Whether that issue affected this study cannot be assessed from the registry record because the analysis details are not reported.

The study summary names two objectives: assessing biomarker positivity frequency among ICU patients considered at high risk and testing early discontinuation based on repeatedly negative blood cultures and 1,3-beta-D-glucan. The registry lists the candidemia outcome as the primary outcome measure, but does not provide results for either objective. It does not report whether additional exploratory analyses were conducted or how outcomes beyond the listed measure were handled.

Missing-data methods and follow-up completeness are not reported in the registry record. The number of participants with missing biomarker results, incomplete blood-culture information, incomplete follow-up, or unavailable candidemia status is not reported. The registry also does not state whether any analysis excluded participants or used an imputation method.

Analysis populations are not described. In particular, the record does not state how many enrolled participants received anidulafungin, discontinued it, met the negative-biomarker condition, or contributed to the primary endpoint. Without these details, the enrollment count cannot be treated as the endpoint denominator. The missing analysis and population information prevent a full assessment of selection, missingness, and the relationship between the stated strategy and the primary outcome.

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 0% reporting threshold.

The registry’s adverse-event figures list one arm, with 85 participants at risk and zero affected for serious adverse events. For other adverse events, it also lists 85 participants at risk and zero affected. No serious adverse-event terms are listed. The deaths field is not reported; that is different from a reported count of zero deaths.

These figures describe what the registry reports in its adverse-event fields. They do not establish that no adverse events occurred beyond what was captured or reported, and they do not provide details about event definitions, collection methods, observation periods, or completeness of safety reporting. Those details are not reported in the registry record.

In general, safety counts are interpreted in relation to the population monitored, the event definitions, and the duration and completeness of observation. A zero reported count is not proof that the underlying risk is zero. The safety figures should also be kept separate from the primary endpoint: candidemia among participants with negative 1,3-beta-D-glucan who discontinued anidulafungin. That endpoint result is not reported in the registry record.

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

The record establishes that a completed prospective, single-group study enrolled 85 participants and examined an anidulafungin strategy in ICU patients considered at risk for invasive candidiasis. Its primary question concerns candidemia within 30 days among participants with negative 1,3-beta-D-glucan who discontinue treatment. These are design and endpoint details, not evidence of the outcome.

The registry does not report how many participants met the endpoint conditions or how many developed candidemia. It also does not report an estimate, confidence interval, p-value, or analysis of the primary outcome. It is therefore not possible to state from this record how often candidemia occurred after discontinuation, how precisely that occurrence was estimated, or whether the stated strategy was associated with a particular outcome.

The single-group design does not include a concurrent comparison strategy. In general, an observed outcome within one group cannot establish what would have happened to similar participants under continued treatment or another approach. The record does not support a comparative treatment-effect claim, nor does it establish that a negative biomarker result is sufficient to guide treatment decisions in other settings.

The adverse-event fields report zero affected among 85 at risk for serious events and zero affected among 85 at risk for other events. These registry counts are not the primary candidemia outcome and do not prove the absence of harm. The deaths field is not reported. Safety interpretation is limited by the lack of further reporting detail.

The most defensible conclusion is narrow: the registry documents the study’s intended strategy, design, enrollment, and outcome definition, but does not report the outcome results needed to judge candidemia occurrence or precision. The record also does not provide the data needed to evaluate biomarker performance, missingness, or treatment differences. No inference about an alternative strategy can be made from the single-group design alone.

13. Why This Trial Matters Statistically

This study raises a statistically important distinction between evaluating an outcome under a strategy and comparing strategies. The research question links negative biomarker results and blood cultures to early discontinuation of antifungal therapy, then focuses on candidemia after discontinuation. Such questions require clear reporting of who met the decision rule, what happened afterward, and how completely outcomes were observed. The registry record gives the intended endpoint but not those results or denominators.

The distinction matters because a biomarker-guided approach has several components: the test result, the population in which it is used, the decision based on the result, and the subsequent clinical outcome. As a general statistical principle, evidence about one component does not automatically answer questions about the full strategy. A rationale for using a negative result is not the same as a measured predictive value or an outcome comparison.

The single-group design is also important. A descriptive count, if reported, could characterize observed candidemia in the defined group. It would not directly reveal whether the outcome would differ under continued treatment or another management strategy. A concurrent comparison is often needed to estimate such a contrast, though its value depends on design and analysis quality.

Finally, the record illustrates why complete outcome reporting matters. An enrollment count cannot substitute for the endpoint denominator, and an endpoint definition cannot substitute for the observed count. Without the result and an account of uncertainty, readers cannot assess the magnitude or precision of the finding. The posted record is useful for identifying the question and design, while leaving the principal statistical result unresolved.

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.

Several limitations are specific to what the registry record reports. First, the primary candidemia result is absent. The record gives a 30-day timeframe and defines the outcome population in terms of negative 1,3-beta-D-glucan and discontinuation of anidulafungin, but does not report the number of participants who met that definition or the event count. This prevents calculation or interpretation of an outcome frequency.

Second, the study is single-group, with no comparator listed. The record cannot establish a relative difference between the early-discontinuation strategy and another treatment approach. The absence of masking is recorded, but the record does not describe outcome-assessment procedures or safeguards against bias.

Third, important procedural details are not reported in the registry record. These include eligibility criteria, biomarker and blood-culture schedules, the precise discontinuation rule, follow-up completeness, candidemia definitions, and how participants with missing information were handled. The analysis population and missing-data methods are also not reported.

Fourth, although the study summary describes objectives related to biomarker positivity and early discontinuation, results for those objectives are not reported. The record does not provide a predictive-value estimate or other evaluation of biomarker performance. It also does not report a statistical analysis plan, inferential results, or multiplicity procedures.

The adverse-event fields list zero affected for serious and other adverse events among 85 at risk, but event definitions and collection details are not reported. The deaths field is not reported. These limitations mean the safety counts should not be treated as a comprehensive account of all safety outcomes. Together, the absent endpoint results and limited methodological detail constrain interpretation to the study’s stated aims and design.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Negative Beta Glucan in ICU Patients — NCT01734525.
• Registry record last updated 2019-07-08; status last verified 2019-04.
• Results first posted 2019-07-08.
• 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 a completed, prospective, phase 4, single-group study sponsored by Universidade Federal do Rio de Janeiro. Enrollment was 85. The recorded start is 2012-11 and primary completion is 2013-12. The intervention is anidulafungin for patients considered at risk of invasive candidiasis or candidemia.

The study’s stated aims include assessing biomarker positivity and testing early discontinuation of antifungal therapy based on repeatedly negative blood cultures and serum 1,3-beta-D-glucan. The primary outcome is a participant count for candidemia among participants with negative 1,3-beta-D-glucan who discontinue anidulafungin, over 30 days.

No analysis is listed, and the primary outcome result is not reported in the registry record. The adverse-event fields report zero affected among 85 at risk for both serious and other adverse events; the deaths field is not reported. The record does not describe a comparator group, analysis populations, missing-data methods, or inferential results.