This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Post-marketing Surveillance Study of Invasive Mycosis With Posaconazole (Study P04641) (NCT00726609), a registered phase not stated study. The primary outcome is Number of Participants Reporting Adverse Drug Reactions..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00726609 |
| Phase | Phase not stated |
| Condition | Mycoses |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 214 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
The registry record concerns 214 participants in a post-marketing surveillance study of invasive mycosis. It does not report detailed eligibility criteria, participant characteristics, or the specific fungal conditions represented beyond the broad condition category of Mycoses. The record describes data collection in everyday practice rather than a tightly specified experimental setting.
Intervention
Participants received posaconazole, identified in the record as NOXAFIL® (posaconazole). The treatment was for invasive fungal infection or for prophylaxis of invasive fungal infection. The physician assigned treatment in normal practice; the record does not specify dosing or duration.
Comparator
No comparison group is listed. The record therefore does not describe a like-for-like control group or a randomized treatment comparison. It is not possible to interpret the reported counts as a difference between posaconazole and another treatment or no treatment.
Primary question
The named primary outcome is the number of participants reporting adverse drug reactions before starting posaconazole, during treatment, and until 100 days after treatment. The outcome description classifies reaction severity as mild, moderate, or severe. A numerical result for this primary outcome is not reported in the registry record. The posted safety summaries list participants affected by serious and other adverse events, but the record does not establish that these are the same as the primary endpoint of adverse drug reactions.
3. Trial Design
This was a completed post-marketing surveillance study sponsored by Merck Sharp & Dohme LLC. The registry record lists 214 participants and describes the purpose as collecting data in a large patient population in everyday life to investigate the safety and efficacy of posaconazole in invasive fungal disease. The study started in 2006-01, and primary completion was recorded in 2008-07.
The listed treatment was posaconazole, assigned by a physician in normal practice. Its recorded uses included treatment of invasive fungal infection and prophylaxis of invasive fungal infection. The record does not give a separate participant count for these uses, nor does it describe how the physician chose a use, dose, or duration. Further details of the clinical setting and eligibility criteria are not reported in the registry record.
Only one treatment group is listed, and the record does not describe a control arm. Allocation is not stated as randomized; the arm description instead says that the physician assigned treatment in normal practice. This is therefore not a randomized comparison, and the listed group cannot serve as a like-for-like control for estimating a treatment contrast.
The registry record lists one outcome measure and zero analyses. The named primary measure concerns participants reporting adverse drug reactions over a timeframe spanning before treatment, during treatment, and until 100 days after treatment. Although the study purpose mentions safety and efficacy, the record does not include a comparative efficacy result or an analysis plan. Details such as blinding, monitoring procedures, and protocol-defined analysis populations 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
| Stage | Posaconazole (Assigned by Physician in Normal Practice) |
|---|---|
| STARTED | 214 |
| COMPLETED | 116 |
| NOT COMPLETED | 98 |
Reasons for not completing this period:
| Reason | Posaconazole (Assigned by Physician in Normal Practice) |
|---|---|
| Adverse Event | 10 |
| Withdrawal by Subject | 2 |
| Lack of Efficacy | 25 |
| Other | 16 |
| Missing | 42 |
| Other | 3 |
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.
| Characteristic | Unit | Posaconazole (Assigned by Physician in Normal Practice) |
|---|---|---|
| Participants analysed | 214 | |
| Age, Continuous | years | 55.6 (SD 12.77) |
| Sex: Female, Male: Female | Participants | 79 |
| Sex: Female, Male: Male | Participants | 135 |
| Region of Enrollment: Germany | participants | 214 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Reporting Adverse Drug Reactions., measured over Before starting treatment with posaconazole, during treatment, and until 100 days after treatment..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled “Number of Participants Reporting Adverse Drug Reactions.” It is a participant count, not a measure of the number of separate reaction episodes. The stated observation period begins before posaconazole treatment, continues during treatment, and extends until 100 days after treatment. The description distinguishes mild reactions, which are noticed but well tolerated; moderate reactions, which impair normal activities and may require intervention; and severe reactions, which significantly impair clinical status, prevent normal activity, and require intervention.
A count of participants experiencing a reaction can describe the observed safety burden in the population under surveillance. This kind of measure is useful in post-marketing observation because it can capture events recorded during routine care, beyond the narrower circumstances of a controlled trial. The endpoint title alone, however, does not specify how a suspected reaction was attributed to treatment, how repeated events in the same person were handled, or what rules were used to determine severity. Those details are not reported in the registry record.
Most importantly, the record does not report a numerical result for this named primary endpoint. The separately posted adverse-event summaries give counts of participants affected by serious and other adverse events. The record does not establish that those categories are interchangeable with adverse drug reactions, so those summaries should not be presented as the primary endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record reports 33 participants affected by serious adverse events among 214 at risk, and 49 participants affected by other adverse events among 214 at risk. These are descriptive counts from the posaconazole group. They do not provide an estimate of how outcomes would differ under another treatment, because no comparator group is listed and treatment assignment was by physician in normal practice.
The named primary endpoint is the number reporting adverse drug reactions, but its result is not reported in the registry record. The posted serious and other adverse-event counts should therefore be read as distinct safety summaries, not as a substitute for a missing primary endpoint result. The record also does not provide an analysis of efficacy, despite describing efficacy as part of the study purpose.
The serious-event terms listed include STAPHYLOCOCCAL SEPSIS (2.8%), CYTOMEGALOVIRUS INFECTION (1.9%), LUNG INFILTRATION (1.4%), HAEMORRHOIDS (0.9%), DEATH (0.9%), and DISEASE PROGRESSION (0.9%). The record does not explain whether these percentages refer to participants, events, or another denominator. They are therefore best read as reported term-level figures, without converting them into participant risks or comparing them directly with the group counts.
These observations describe events recorded in a population receiving posaconazole in routine practice. They do not, by themselves, identify whether an event was caused by treatment. The underlying invasive fungal disease, other illnesses, and clinical decisions may also be relevant, but the record does not provide data that separate their contributions. A physician-assigned, uncontrolled design also cannot distinguish treatment effects from differences in who received treatment or how care was delivered.
No confidence intervals, hypothesis tests, or adjusted estimates are reported in the registry record. Consequently, the precision of the posted counts cannot be assessed from an interval estimate in the record, and no statistical evidence for a comparative effect is presented. The number of participants at risk supplies context for the counts, but without a reported analysis it does not resolve uncertainty about the event frequency or its cause.
9. Statistical Methods Explained
The registry describes a post-marketing surveillance study in which posaconazole was assigned by a physician in normal practice. This setting is different from a randomized trial: treatment choice was not described as being allocated by a random process, and no control group is listed. The resulting summaries can describe what was recorded among the participants in the treatment group, but they do not isolate a causal treatment effect.
What do the counts represent?
The safety summaries identify participants affected, with 214 at risk for each of the serious and other adverse-event categories. A participant count is a person-based summary, so it is conceptually different from counting all event episodes. A person may experience multiple events, but the record does not state how repeat events were handled or whether the term-level list counts people or episodes. The named primary outcome is also participant-based, but it concerns adverse drug reactions rather than the posted serious and other adverse-event categories.
For a binary outcome, the underlying observation for each participant can be thought of as whether the specified event occurred or did not occur during the defined observation period. Descriptive reporting then gives the number with the event and the population at risk. A percentage or risk estimate can aid interpretation, but it should be tied to a clearly specified event definition, denominator, and time window. The registry record does not provide a numerical primary-endpoint result or the additional detail needed to reconcile that endpoint with the separately listed safety summaries.
What does a confidence interval add?
In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a stated analysis. It is not a guarantee that the true value lies within the displayed limits, and it does not address biases caused by study design or data collection. No confidence interval for the listed safety counts or the primary endpoint is reported in the registry record. As a result, the record does not show how precisely the event frequency was estimated.
Why does the absence of a comparator matter?
A treatment comparison asks how outcomes differ between groups that received different interventions. Here, the registry lists only a posaconazole group and says treatment was assigned by a physician in normal practice. Without a comparator, no between-group contrast can be estimated. Even if a comparison group had been present, nonrandom treatment choice could produce confounding: the reasons a physician selects a treatment may also be associated with the outcome. Adjustment can address measured factors under suitable assumptions, but the registry record reports zero analyses and gives no adjusted estimates.
The purpose of surveillance is to observe treatment in routine settings, which may capture clinical experience not represented in a controlled experiment. At the same time, routine-care data can have variation in event recognition, documentation, follow-up, and attribution. The record does not describe the procedures used to standardize these elements. These are general considerations for interpreting observational safety data, not claims about procedures known to have occurred in this study.
How should the planning illustration be understood?
The planning assumptions describe an illustrative calculation based on an observed effect, not the study's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The assumptions also distinguish participant-per-arm quantities from total-event quantities for time-to-event settings. These are planning conventions and do not establish that the surveillance study had two arms, used equal allocation, or planned its enrollment through that calculation.
Sample-size planning asks how much information a future study might need under chosen assumptions. It does not establish what was observed, and a planning calculation is not observed power. The record does not report the original sample-size justification. The illustrative assumptions should not be interpreted as evidence that this study was designed to test a comparative hypothesis or that its actual precision met a prespecified target.
Finally, statistical methods depend on explicit choices: the outcome definition, follow-up window, treatment of missing observations, analysis population, and handling of multiple outcomes. The registry record does not report those choices in sufficient detail. The available summaries should therefore be interpreted descriptively, with uncertainty about the endpoint definition and analysis procedures kept distinct from the event counts themselves.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or any procedure for handling multiple statistical tests. The primary endpoint is named, but no numerical result for it is reported. The listed serious and other adverse-event summaries do not establish whether they were prespecified endpoints, additional safety summaries, or derived through another reporting process.
Multiplicity refers generally to the interpretive problem that arises when many outcomes, subgroups, or hypotheses are examined: the chance of seeing an apparently notable result can increase unless the analysis plan accounts for the number and structure of comparisons. Since no tests or analysis plan are reported, there is no basis to assess multiplicity adjustment or to interpret a reported significance finding; no significance finding is posted in the record.
Missing-data handling is also not reported in the registry record. The record does not say whether all enrolled participants completed the observation period, how incomplete follow-up was addressed, or whether any participants were excluded from the safety summaries. It does not define an intention-to-treat, per-protocol, or other analysis population. The listed at-risk counts give the denominator for the reported safety categories, but do not answer these questions about follow-up or missing observations.
These omissions limit assessment of how complete and comparable the underlying observations were. They do not show that data were missing or that an inappropriate analysis was used; they mean that the registry record does not report the information needed to evaluate those possibilities.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Posaconazole (Assigned by Physician in Normal Practice) | 33 | 214 | 15.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Posaconazole (Assigned by Physician in Normal Practice) | 49 of 214 |
Most frequent serious adverse event terms
| Event term | Organ system | Posaconazole (Assigned by Physician in Normal Practice) |
|---|---|---|
| STAPHYLOCOCCAL SEPSIS | Infections and infestations | 6 of 214 |
| CYTOMEGALOVIRUS INFECTION | Infections and infestations | 4 of 214 |
| LUNG INFILTRATION | Respiratory, thoracic and mediastinal disorders | 3 of 214 |
| HAEMORRHOIDS | Gastrointestinal disorders | 2 of 214 |
| DEATH | General disorders | 2 of 214 |
| DISEASE PROGRESSION | General disorders | 2 of 214 |
| MULTI-ORGAN FAILURE | General disorders | 2 of 214 |
| CHOLECYSTITIS | Hepatobiliary disorders | 2 of 214 |
| ESCHERICHIA SEPSIS | Infections and infestations | 2 of 214 |
| INFECTION | Infections and infestations | 2 of 214 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Posaconazole (Assigned by Physician in Normal Practice) |
|---|---|---|
| PYREXIA | General disorders | 27 of 214 |
| DIARRHOEA | Gastrointestinal disorders | 19 of 214 |
| NAUSEA | Gastrointestinal disorders | 12 of 214 |
| C-REACTIVE PROTEIN INCREASED | Investigations | 11 of 214 |
Serious events with the highest arm-level rate: staphylococcal sepsis (2.8%), cytomegalovirus infection (1.9%), lung infiltration (1.4%), haemorrhoids (0.9%), death (0.9%).
The registry record lists 33 participants affected by serious adverse events, with 214 at risk, and 49 participants affected by other adverse events, also with 214 at risk. These are counts of participants in the posaconazole group, not a comparison with participants receiving another treatment. They should not be combined, because the record does not describe whether the categories overlap or how they were defined in relation to one another.
The serious-event terms include STAPHYLOCOCCAL SEPSIS (2.8%), CYTOMEGALOVIRUS INFECTION (1.9%), LUNG INFILTRATION (1.4%), HAEMORRHOIDS (0.9%), DEATH (0.9%), and DISEASE PROGRESSION (0.9%). The registry record does not state the denominator or counting method for these term-level percentages. It also does not report a separate overall death count; the listed DEATH term should not be treated as that count.
Serious adverse events are not automatically adverse drug reactions. An event can be serious without being judged related to treatment, and the record does not give the attribution rules or event narratives needed to determine causality. These summaries describe reported safety events in the observed group; they do not establish that posaconazole caused them or provide a comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The posted results show that serious and other adverse events were recorded among participants in the posaconazole group. The registry gives counts of 33 and 49 participants, respectively, each with 214 at risk. It also lists several serious-event terms with percentages. These registry entries describe the reported safety experience in this surveillance group; they do not establish the cause of any event.
The named primary endpoint concerns participants reporting adverse drug reactions from before treatment through the period ending 100 days after treatment. Its numerical result is not reported in the registry record. This absence matters: the separate event counts cannot be assumed to answer the primary question, because adverse events and adverse drug reactions are not necessarily the same category. The record also does not report an efficacy result, a comparison with another treatment, or an estimate adjusted for participant characteristics.
In general, a treatment effect is a comparison between outcomes under alternative treatment strategies. This registry record does not supply that comparison. Physician assignment in normal practice means that the observed participants may differ in clinically relevant ways from people who would have received another treatment, and there is no control group to account for those differences. The reported data therefore do not support a causal conclusion about the effect of posaconazole on safety or efficacy.
Nor do the counts alone indicate how precisely event frequencies were estimated. No confidence intervals or other uncertainty measures are reported. The term-level percentages also lack a stated denominator in the record, so they should not be used to infer participant risks beyond their presentation as listed figures.
The study can be understood as a record of post-marketing surveillance in routine practice, with safety summaries for a group receiving posaconazole. Its value for interpretation is bounded by the information recorded: the primary endpoint result, detailed analysis methods, follow-up completeness, and comparative data are not reported. That distinction keeps descriptive observations from being mistaken for proof of benefit, harm, or equivalence.
13. Why This Trial Matters Statistically
Post-marketing surveillance addresses a different statistical question from a randomized treatment comparison. It records clinical experience in routine practice, where treatment is assigned by physicians and care may vary. Such data can describe events in the population observed, while the design also makes causal interpretation more difficult. This study provides an example of why the distinction between a safety count and a comparative treatment effect matters.
The record has a clear numerical feature that is easy to misread: it reports participant counts for serious and other adverse events, but does not report a result for its named primary endpoint of adverse drug reactions. These outcomes are related in subject matter but are not interchangeable without definitions and attribution rules. Keeping the endpoint label separate from the additional safety summaries is essential for statistical interpretation.
The study also illustrates the limits of an uncontrolled group. A count within a treatment group may be useful for describing observed events, but it does not tell what would have happened to comparable participants under another treatment. Physician assignment can be related to patient condition and clinical judgment, creating potential confounding. A comparator and a prespecified analysis would be needed to support a clearer treatment contrast, though no such analysis is reported in this record.
Finally, the registry record documents a completed study but leaves important analytic details unreported: the result for the primary outcome, uncertainty estimates, missing-data handling, and the original sample-size justification. Recognizing what is and is not reported is itself a core statistical skill. It prevents descriptive safety information and hypothetical planning calculations from being presented as confirmatory evidence.
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 direct limitation is the absence of a reported result for the named primary endpoint. The endpoint concerns adverse drug reactions over a defined treatment-related observation period, while the posted summaries describe serious and other adverse events. The registry record does not explain how these categories relate or provide enough detail to treat one as a substitute for the other.
The study lists only a physician-assigned posaconazole group. Allocation is not stated as randomized, and no control group is described. The reported counts therefore cannot show how event occurrence compares with another treatment or with no treatment. Confounding by clinical condition, treatment choice, and other aspects of routine care cannot be evaluated from the information in the registry record.
Reporting details are limited. The record does not provide the primary endpoint value, confidence intervals, an analysis plan, event-attribution rules, or a definition of the denominator for the serious-event term percentages. It does not report how repeated events were counted, how complete follow-up was, or how missing observations were handled. Nor does it give detailed participant characteristics, eligibility criteria, dose, or treatment duration.
The study purpose refers to both safety and efficacy, but no efficacy result is reported. The term DEATH appears with a percentage in the serious-event list, while a separate death count is not reported. These entries should not be treated as a complete mortality summary. In addition, the sample-size assumptions describe a planning illustration rather than the original design; the study's own sample-size justification is not reported in the registry record.
These limitations constrain what can be concluded from the record. They do not demonstrate that the underlying study lacked procedures or data; they indicate that the registry record does not report enough information to assess those matters.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Post-marketing Surveillance Study of Invasive Mycosis With Posaconazole (Study P04641) — NCT00726609.
- Registry record last updated 2015-03-05; status last verified 2015-02.
- Results first posted 2009-09-22.
- 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.
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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
This completed post-marketing surveillance study examined posaconazole in invasive fungal disease. It enrolled 214 participants and listed treatment assigned by a physician in normal practice, for treatment or prophylaxis of invasive fungal infection. The study started in 2006-01 and reached primary completion in 2008-07.
The named primary endpoint was the number of participants reporting adverse drug reactions before, during, and until 100 days after treatment. Its numerical result is not reported in the registry record. The posted safety summaries list 33 participants affected by serious adverse events and 49 affected by other adverse events, each among 214 at risk. Serious-event terms and percentages are also listed, but their denominator is not specified.
No control group, randomized comparison, or statistical analysis is reported. The record does not provide an efficacy result, confidence intervals, missing-data procedures, or the study's original sample-size justification. The available results are descriptive safety information from the observed treatment group and do not establish a causal treatment effect.