Vfend Special Investigation For Prophylaxis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vfend Special Investigation For Prophylaxis (NCT02674685), a registered phase not stated study. The primary outcome is Number of Participants With Adverse Drug Reactions.

2. Clinical Question

3. Trial Design

This is a completed special investigation of VFEND (voriconazole) used for prophylaxis. Its stated purpose was to examine safety and effectiveness under general clinical practices. The registry lists fungal infection as the condition. It reports enrollment of 241 and dates from 2016-03-11 to primary completion on 2019-07-03.

The available record does not identify a randomized allocation process. Allocation is not stated, and the registry explicitly cautions that the arms are not a like-for-like control comparison. Accordingly, the listed results should be read as safety observations for VFEND use, not as a randomized comparison with an untreated or alternative-treatment group. The record does not report a control group suitable for estimating a causal treatment effect.

The primary outcome is the number of participants with adverse drug reactions. Its timeframe is a maximum of 3 years. An adverse drug reaction was defined as an untoward medical occurrence attributed to VFEND in someone who received it; relatedness was assessed by the physician. A serious adverse drug reaction was defined by specified serious consequences or a physician assessment that it was significant for another reason.

The safety analysis set comprised participants who met the inclusion criteria and received VFEND at least once. The registry reports a safety denominator of 233 in the listed group. It does not explain the difference between enrollment and this safety denominator, nor does it report the inclusion criteria in the registry record for this account. Details such as masking, a protocol-defined comparison group, or a statistical analysis plan are not reported in the registry record.

Other listed outcomes include adverse drug reactions not expected from the approved local product document, adverse reactions by age and reason for use, invasive fungal infection rates and subgroups, and successful prophylaxis. Their presence in the outcome list does not establish that numerical results were reported for them.

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: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received VFEND at least once.

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.

Population: A total of 237 participants completed this study. Of the 237 participants, 4 participants were excluded from the safety analysis set due to the following reasons: Protocol violation (registration violation, 3; contract violation/deficiency, 1)

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Drug Reactions, measured over Maximum 3 years.

The primary endpoint counts participants with adverse drug reactions attributed to VFEND. It is a count of people experiencing an event, rather than a measure of the number of separate reactions or their duration. The registry defines an adverse drug reaction as an untoward medical occurrence attributed to VFEND among participants who received it. The physician assessed whether an occurrence was related to VFEND.

The endpoint also distinguishes serious adverse drug reactions by their consequences. These include death, a life-threatening experience, initial or prolonged inpatient hospitalization, persistent or significant disability or incapacity, or congenital anomaly. An event could also be considered serious for another significant reason. These criteria describe seriousness; they do not by themselves establish that VFEND caused an event.

Counting affected participants gives a direct way to describe the observed safety experience in the specified analysis set. It can communicate how many people had at least one qualifying reaction, but a participant count alone does not convey the number of events per person, timing, duration, severity beyond the serious classification, or certainty of causal attribution. The registry identifies the endpoint and its definition, but the numerical primary-endpoint result and its precision are not reported in the registry record.

The maximum follow-up timeframe is 3 years. Because participants may have differing exposure or observation time, a count alone should not be read as a rate over a uniform period unless the record reports the relevant time-at-risk information and method. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a participant-count endpoint and a safety analysis set. The key statistical distinction is between describing observed events and estimating a treatment effect. Since allocation is not stated and the registry cautions that the arms are not a like-for-like control comparison, the posted counts should be read descriptively. They do not provide a randomized estimate of what would have happened to the same population under another treatment or no prophylaxis.

What does a participant count measure?

A participant count records people who meet an event definition. It is not necessarily the same as a count of all event episodes: one participant can experience more than one event. The primary endpoint is defined as the number of participants with adverse drug reactions, and the reaction must be attributed to VFEND. Physician assessment determines relatedness under the registry definition. This attribution is a clinical judgment recorded in the study context, not a statistical test of causation.

The counts of 60 in the serious category and 153 in the other category are reported against 233 at risk in each category. These categories should be interpreted using the registry's classifications. They should not be combined into a total affected count, because the record does not establish whether the categories are mutually exclusive or whether participants can appear in both. The count of 19 deaths is also not, by itself, a count of deaths caused by treatment.

Why does the analysis population matter?

The safety set includes participants who met inclusion criteria and received VFEND at least once. A safety analysis based on exposure can describe events among those who actually began treatment, while an analysis based on all enrolled participants would answer a different question. The registry reports enrollment of 241 and a safety denominator of 233, but does not explain the difference. Reasons for exclusion, treatment exposure patterns, and the handling of participants with incomplete follow-up are not reported in the registry record. Without those details, readers cannot assess how the analyzed population differs from everyone enrolled.

The maximum endpoint timeframe is 3 years. In general, counts and rates answer different questions. A count gives the number of affected participants; a rate incorporates a denominator and, where relevant, time at risk. If exposure or follow-up differs among participants, a simple count may not capture those differences. The record does not report the participant-level follow-up or time-at-risk methods needed to interpret the endpoint as a rate.

What can confidence intervals and tests add?

In general, a confidence interval describes the statistical uncertainty around an estimate under stated assumptions. It can show whether the data are compatible with a range of values, but it does not correct bias from selection, confounding, missing follow-up, or an unsuitable comparator. No confidence interval or statistical test for the primary endpoint is reported in the registry record. Therefore, the affected counts should not be interpreted as precise estimates of risk or evidence of a difference from another group.

The registry lists 11 outcome measures and 0 analyses. That listing does not supply a detailed analysis plan, methods for subgroup comparisons, adjustment procedures, or a strategy for controlling false positive findings across multiple outcomes. These statistical-plan details are not reported in the registry record. In general, when many outcomes or subgroup analyses are considered, each result needs to be interpreted in light of how many questions were examined and whether analyses were planned in advance.

How should planning calculations be read?

The sample-size assumptions describe planning illustrations based on an observed effect, not the investigation's own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the detectable effect is expressed as a stated fraction of the observed effect. The illustrations are not observed power and do not establish that the study was designed to detect a particular effect. The registry does not report a sample-size justification for this investigation. The listed caution about non-comparable arms also means that planning assumptions for a two-arm comparison should not be mistaken for evidence that the actual investigation used such a comparison.

In general, over-dispersion matters when event counts vary more than a model assumes; ignoring it can make uncertainty look too small. No dispersion value or count-model analysis is reported, and the endpoint is described as a participant count. The relevant interpretation therefore remains descriptive unless further analysis details are available in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures and 0 analyses. It names the primary adverse drug reaction endpoint and several secondary outcomes, including reactions by age, reason for use, and long-term use; invasive fungal infection outcomes and subgroup results; and successful prophylaxis. The numerical results for these secondary outcomes are not reported in the registry record.

When several outcomes or subgroup questions are considered, the chance of seeing an apparently notable finding by chance can increase. In general, a statistical plan may address this through prespecification, adjustment, or a clearly exploratory interpretation. The registry record does not report a multiplicity strategy, identify which subgroup tests were prespecified, or provide enough analysis detail to determine whether any adjustment was used. No significance tests for these outcomes are reported in the registry record.

The safety analysis set is defined as eligible participants who received VFEND at least once. The registry reports enrollment of 241 and 233 at risk for each listed adverse-event category, but does not explain the difference or give a participant flow account. Missing outcome data, loss to follow-up, and the methods used to handle incomplete observations are not reported in the registry record. The maximum timeframe of 3 years does not establish that each participant was observed for that full period.

The record does not report an intention-to-treat population, a per-protocol population, or an analysis population for efficacy outcomes. Nor does it report methods for imputation, censoring, or sensitivity analyses. These omissions limit assessment of selection and missing-data bias. They also mean the listed event counts should be understood as reported safety observations, not as a complete account of every enrolled participant's outcome.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: graft versus host disease (5.2%), febrile neutropenia (2.1%), renal impairment (1.7%), pneumonia (1.3%), acute graft versus host disease (1.3%).

The listed safety data give a denominator of 233 at risk for the serious-event category and 233 at risk for the other-event category. The corresponding affected counts are 60 and 153. These are participant counts in the reported categories; the registry does not establish that the categories are mutually exclusive, so they should not be added together or treated as a count of unique people across categories.

The serious-event term list includes graft versus host disease (5.2%), febrile neutropenia (2.1%), renal impairment (1.7%), pneumonia (1.3%), acute graft versus host disease (1.3%), and blood bilirubin increased (1.3%). A term's appearance in this list does not alone establish that VFEND caused it. The registry states that relatedness was assessed by the physician, while the available term listing does not give individual causality assessments.

The record lists 19 deaths. It does not report causes or state how many, if any, were considered related to VFEND. The serious adverse drug reaction definition includes death among the possible serious outcomes, but that criterion is not evidence that the listed deaths were treatment-related. The reported safety data should therefore be read as event descriptions and counts, not as proof of causation or a comparison with background risk.

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

The investigation documents the registry's stated aim: examining VFEND (voriconazole) for prophylaxis under general clinical practices. It defines adverse drug reactions, describes a safety analysis set, and reports participant counts in serious and other adverse-event categories. Those details can help readers understand what safety experience the registry records and how the endpoint was defined.

The counts do not establish that VFEND caused the events. The physician assessed relatedness, but the available record does not report the individual assessments or a comparison that can separate drug effects from the underlying condition, other care, or other causes. Allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. As a result, the counts do not estimate a causal difference between treatments.

The registry lists invasive fungal infection rates, success of prophylaxis, and related subgroup outcomes, but their numerical results are not reported in the registry record. The stated aim includes effectiveness, but the available outcome listings alone cannot establish the effectiveness of prophylaxis. The primary endpoint is a safety count; it does not directly measure whether fungal infection was prevented.

Likewise, the event counts do not provide a complete picture of event timing, duration, recurrence, severity beyond the serious classification, or differences in observation time. The maximum timeframe is 3 years, but the record does not state that each participant was followed for the full period. It also does not report a confidence interval for the primary outcome, a missing-data strategy, or a detailed analysis plan.

In general, a descriptive registry result can characterize events recorded in a defined population, while a comparative clinical conclusion requires appropriate design and analysis. Here, the available information supports reading the counts as reported safety observations among the listed VFEND group. It does not support a firm conclusion about comparative safety, causal risk, or prophylaxis benefit.

13. Why This Trial Matters Statistically

This investigation is statistically informative in part because it makes the safety endpoint definition explicit. The primary outcome counts participants with reactions attributed to VFEND, and the registry explains how it defines seriousness. Such definitions matter: an event count is interpretable only in relation to who was eligible for analysis, what qualified as an event, and how relatedness was assessed.

The record also illustrates why analysis populations and denominators deserve attention. Enrollment is reported as 241, while the safety set is defined by eligibility and receipt of at least one dose, and the listed adverse-event categories each have 233 at risk. The registry does not explain the difference between the enrollment and safety denominator. That gap leaves an important question about participant flow unanswered and cautions against assuming all enrolled participants contributed to the safety counts.

Another statistical lesson is the distinction between safety description and causal comparison. The registry does not state allocation and warns that the arms are not a like-for-like control comparison. Without a suitable comparator, observed event counts cannot isolate treatment effects from other explanations. This remains true even when the event definitions and counts are clearly stated.

The outcome list also includes several secondary and subgroup questions. In general, multiplicity and selective reporting matter when many outcomes are considered, yet the registry record does not report a detailed analysis plan or multiplicity approach. The numerical outcomes for invasive fungal infection and successful prophylaxis are not reported in the registry record. Readers therefore need to distinguish the stated aims and registered outcomes from demonstrated results.

Finally, planning calculations are not evidence of observed power or proof that a study can answer every clinical question. The stated planning assumptions are illustrations, whereas the study's own sample-size justification is not reported. Together, these features make the record a useful example of careful interpretation: endpoint definitions and counts are valuable, but design, completeness, and uncertainty determine what conclusions they can support.

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 registry record does not state allocation, and it cautions that the arms are not a like-for-like control comparison. This limits any comparison across groups and prevents interpreting the counts as a randomized treatment effect. Details of a comparator, treatment assignment, masking, and a statistical analysis plan are not reported in the registry record.

Enrollment is 241, while the listed safety denominator is 233. The record defines the safety analysis set but does not explain the difference, describe participant flow, or report how missing outcomes were handled. It also does not give participant-level follow-up or time-at-risk information. Although the primary endpoint timeframe is a maximum of 3 years, the record does not establish that every participant had the same observation period.

The event data include affected counts and selected serious-event terms, but the record does not provide a primary-endpoint estimate with a confidence interval, event timing, recurrent-event detail, or the relatedness assessment for each event. The count of 19 deaths is not accompanied by causes or attribution information. The serious-event terms and percentages do not establish treatment causality.

Although the registry lists invasive fungal infection and successful prophylaxis outcomes, their numerical results are not reported in the registry record. There is also no reported multiplicity strategy or detailed account of which subgroup analyses were prespecified. The sample-size justification for the investigation is not reported; the stated sample-size assumptions describe planning illustrations rather than the study's own design.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vfend Special Investigation For Prophylaxis — NCT02674685.
• Registry record last updated 2023-04-25; status last verified 2023-03.
• Results first posted 2020-07-23.
• 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.

18. Record Summary

NCT02674685 is the completed VFEND Special Investigation For Prophylaxis. It examined prophylactic voriconazole use under general clinical practices, with a primary endpoint of the number of participants with adverse drug reactions. The endpoint timeframe was a maximum of 3 years, and the safety analysis set included eligible participants who received VFEND at least once.

The registry reports enrollment of 241. The listed adverse-event categories each have 233 at risk, with 60 affected in the serious category and 153 in the other category. It also lists 19 deaths and selected serious-event terms with percentages. Allocation is not stated, and the record cautions that arms are not a like-for-like control comparison.

The record lists 11 outcome measures and 0 analyses. Numerical results for the listed invasive fungal infection and prophylaxis success outcomes are not reported in the registry record. Missing-data methods, multiplicity procedures, and the investigation's sample-size justification are also not reported.