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 Cerebrospinal Fluid (CSF) Pharmacokinetics of Antimicrobials in Children (NCT00991185), a registered phase not stated study. The primary outcome is CSF:Serum Ratio of Vancomycin.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00991185 |
| Phase | Phase not stated |
| Condition | Infections |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Duke University |
| Results posted | Yes |
2. Clinical Question
The study concerns how antimicrobial drugs used in children reach the central nervous system. Its stated purpose is to gather information about drug levels in cerebrospinal fluid (CSF), alongside information about how children handle these drugs in the body. The primary outcome listed for this record focuses specifically on vancomycin.
Population
Children receiving antimicrobial treatment as part of standard care are the population of interest. The record reports enrollment of 8 participants, but does not report participant ages, diagnoses, or other demographic details. The study description also discusses young children and babies, but does not say which age groups were represented among those enrolled.
Intervention
The study examines antimicrobials given as part of standard care, with vancomycin identified in the primary outcome and adverse-event information. The specific dosing regimens and the drugs received by each participant are not reported in the registry record.
Comparator
No control group or like-for-like comparator is identified. The registry record does not state an allocation method, and it does not describe this study as a randomized comparison.
Primary question
The primary measure is the CSF-to-serum ratio of vancomycin, summarized by its median and full range. It is intended to describe the relationship between vancomycin levels in CSF and in serum within 1 week of drug administration. The numerical median and range are not reported in the registry record.
This is therefore a pharmacokinetic question about drug distribution, not a comparison of clinical outcomes between treatment groups. The record does not identify an efficacy outcome or state that the study was designed to determine whether one treatment is better than another.
3. Trial Design
The record describes a study of antimicrobial pharmacokinetics in children, with a focus on drug levels in CSF during treatment that would ordinarily be part of standard care. The stated rationale is that the handling of these drugs by children and babies, including how they leave the circulation and how much enters the central nervous system, has not been extensively studied. The record describes information gathering rather than a treatment-assignment comparison.
The study is listed as completed, with a start date of 2009-07 and a primary completion date of 2014-04. Duke University is named as the sponsor. Enrollment is reported as 8. The condition listed is infections. The registry record does not report the study phase, detailed eligibility criteria, recruitment setting, or participant characteristics.
The primary outcome is the CSF:serum ratio of vancomycin, measured within 1 week of drug administration and described using a median and full range. One outcome measure is listed, and the record contains 0 analyses. It does not report the timing of specimen collection for individual participants, the exact drug regimens, or how many participants contributed CSF and serum measurements.
Allocation is not stated, and the record does not identify a control arm. The registry record therefore does not support treating the participants as randomized treatment groups or making a like-for-like comparison. Details of blinding, protocol deviations, interim analyses, and the statistical analysis plan are not reported in the registry record. The small enrollment and absence of posted numerical outcome results limit what can be concluded from the available record about the precision or distribution of CSF drug levels.
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 | Vancomycin |
|---|---|
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
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 | Vancomycin |
|---|---|---|
| Participants analysed | 8 | |
| Age, Continuous | years | 4 (0.2 to 17) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 4 |
| Region of Enrollment: United States | participants | 8 |
6. Primary Endpoint
The registry lists the primary outcome as CSF:Serum Ratio of Vancomycin, measured over within 1 week of drug administration.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | ratio |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the ratio of vancomycin concentration in cerebrospinal fluid to its concentration in serum. CSF is the fluid surrounding the brain and spinal cord; serum is the liquid component of blood. A ratio expresses the CSF level relative to the serum level, rather than reporting either level alone. It can therefore describe how drug exposure in CSF relates to drug exposure in the circulation.
The registry record specifies a median and full range for this ratio, with measurement within 1 week of drug administration. A median describes the central position of observed values, while the full range gives the lowest and highest observed values. These summaries can be useful for a small pharmacokinetic dataset because they describe the observed values without requiring a claim that they follow a particular distribution. In general, the range can be strongly affected by extreme observations, so it should be interpreted alongside the median and the underlying sample size.
The endpoint is a measure of drug distribution, not a direct measure of infection response, clinical benefit, or harm. The registry record does not give the median ratio, the range, concentration values, or the number of participants with paired CSF and serum measurements. Consequently, the listed endpoint identifies what was intended to be measured, but the posted results do not show the numerical finding.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a pharmacokinetic outcome but does not report its numerical result. It names the CSF:serum ratio of vancomycin and specifies that it is to be summarized by the median and full range within 1 week of drug administration. Neither the median nor the endpoints of the range appear in the record. There is therefore no reported estimate from which to describe the observed ratio, its spread, or its precision.
Enrollment was 8, and the registry record lists 0 analyses. Enrollment alone does not establish how many participants contributed usable measurements to the primary outcome. The number with paired CSF and serum specimens, the number excluded from the endpoint analysis, and the reasons for any unavailable measurements are not reported. No confidence interval or other uncertainty interval for the primary measure is reported either.
In general, a confidence interval describes the uncertainty around an estimate under the assumptions of the method used. Without a reported estimate and interval, readers cannot assess how narrowly or broadly the study may have estimated the CSF:serum ratio. A median and full range would describe the observed values, but they would not by themselves show the uncertainty around a population-level quantity. The registry record does not report inferential analyses that address that uncertainty.
The study is not presented as a randomized comparison, and allocation is not stated. Its outcome is a pharmacokinetic ratio rather than a contrast between treatment groups. The record therefore does not support claims about comparative effects, nor does it provide evidence about clinical outcomes. The study description frames the research as gathering information on antimicrobial handling in children; the available posted result information is insufficient to say what vancomycin ratio was observed.
The adverse-event record lists 8 participants at risk for serious events and 0 affected, and also lists 8 at risk and 0 affected for other adverse events. These counts are descriptive of the registry entries; they do not supply a detailed account of event monitoring, definitions, or follow-up. Deaths are not reported in the registry record, and no serious-event terms are listed. A count of zero affected in a small enrolled group should not be read as proof that an event cannot occur.
Overall, the record establishes the study's purpose, enrollment, completion status, and intended primary measure, but it does not report a numerical primary result. That absence prevents quantitative interpretation of the endpoint and makes it impossible to assess its observed variability or estimate precision from the registry record.
9. Statistical Methods Explained
The listed endpoint is a descriptive pharmacokinetic measure: the ratio of vancomycin in CSF to vancomycin in serum. The record specifies that the median and full range are the summary statistics. It does not report an inferential test, a model, an adjustment procedure, or a confidence interval. The following points explain the statistical meaning of the stated summaries and the limits of interpretation.
What does the ratio express?
A ratio compares two quantities by expressing one relative to the other. Here, the numerator is the vancomycin level in CSF and the denominator is the level in serum. The ratio is intended to describe the relationship between drug levels in those two compartments. It does not provide either concentration on its own. Interpretation also depends on the concentrations used to form the ratio and on whether the CSF and serum samples were collected at comparable times. The registry record does not report the sampling schedule, the assay details, or how paired samples were selected.
Ratios can vary for more than one reason: the numerator may vary, the denominator may vary, or both may vary. In general, a ratio can also be sensitive when its denominator is small. These are general statistical considerations, not findings about this study. The registry record does not give individual concentration values or enough detail to assess how these considerations affected the reported endpoint.
Why report a median and full range?
The median is the middle value when observations are ordered. It is a measure of the center that is less affected by an unusually high or low observation than the arithmetic mean. The full range reports the lowest and highest observed values and gives a direct view of the spread in the measured sample. As a general matter, the range is sensitive to extreme values and tends to depend on how many observations are available. For this study, enrollment was 8, but the number of participants contributing to the endpoint is not reported. The registry record also does not provide the median or range values themselves.
These descriptive summaries cannot establish that the observations represent all children receiving vancomycin. Generalizing from a small sample requires assumptions about how participants were selected and how their characteristics relate to the wider population. Recruitment methods and participant characteristics are not reported in the registry record. The median and range, even if available, would describe the observed measurements; they would not alone provide a formal estimate of uncertainty in a broader population.
What can be said about statistical testing?
The record lists 0 analyses and does not report a statistical test or model for the primary outcome. No p-value, confidence interval, adjusted estimate, or hypothesis test is reported. In general, a hypothesis test evaluates data against a specified null hypothesis, while an interval estimate conveys uncertainty about an estimate under stated assumptions. Since the registry record does not give a numerical outcome estimate or analysis method, neither a test result nor an interval-based interpretation can be reconstructed from the posted information.
The registry record also does not report whether the analysis plan specified transformations, handling of measurements below assay limits, covariate adjustment, or sensitivity analyses. Such choices can matter for pharmacokinetic measurements, but their use in this study is not reported. There is no basis in the record for assuming that a particular model or data-handling method was used.
How should the planning illustration be read?
The record's planning assumptions describe an illustration based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions are not a report of this study's design or an observed analysis. The study is not identified as a randomized comparison, and allocation is not stated; the record also warns that arms are not a like-for-like control comparison. A hypothetical two-arm calculation therefore does not describe the enrollment plan for this pharmacokinetic study.
In general, a sample-size calculation estimates how many observations a specified design might need under chosen assumptions about the effect, variability, significance level, and allocation. It is a planning illustration, not observed power. Any rows framed around fractions of an observed effect remain hypothetical planning scenarios; they do not show the probability that the completed study detected an effect. The registry record does not report a sample-size justification for the study's enrollment of 8, and no numerical effect estimate is posted for assessing the illustration's assumptions.
In general, over-dispersion means that variability in the data is greater than a model expects. If that occurs, a model that understates variability can make uncertainty look too small. No model or dispersion assessment is reported for this endpoint, so over-dispersion cannot be evaluated from the registry record. More broadly, the absence of an analysis description and numerical result means the endpoint's descriptive intent is clearer than the statistical procedure actually used.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure: the CSF:serum ratio of vancomycin. It also lists 0 analyses. The presence of one listed outcome does not establish that no additional outcomes, subgroup analyses, or exploratory comparisons were considered; the registry record does not report a complete analysis plan. No multiplicity adjustment or strategy for controlling the interpretation of multiple analyses is reported.
Multiplicity is a general concern when many hypotheses or outcomes are examined: the chance of a seemingly notable result can increase as more analyses are performed. Adjustment methods or a prespecified hierarchy can address this in some settings, but the registry record does not say whether either was used. Since no inferential results are reported, there are no posted p-values or sets of comparisons to interpret for multiplicity in this record.
Missing-data handling is also not described. The record does not report whether all enrolled participants posted paired CSF and serum samples, whether any measurements were unavailable, or how unavailable values would be handled. The stated enrollment of 8 should not be assumed to equal the number included in the endpoint summary. Imputation, exclusion rules, and sensitivity analyses are not reported in the registry record.
The population used for analysis is not specified. The primary outcome's population field is empty, and no analysis population is described. The record does not report whether analysis was limited to participants meeting particular criteria or whether protocol deviations affected inclusion. These omissions leave the relationship between enrollment and any analyzed measurements unclear. They also limit assessment of whether the intended endpoint was calculated consistently across participants.
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 |
|---|---|---|---|
| Vancomycin | 0 | 8 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Vancomycin | 0 of 8 |
The registry record lists the Vancomycin group with 8 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 8 at risk and 0 affected. These are event-count entries, not a comparison with another group. The record does not report the definitions, observation period, or collection procedures behind these categories, so the counts should be read narrowly as the figures entered in the registry.
No serious adverse-event terms are listed. The deaths entry is not reported in the registry record. An empty list of terms and an unreported death count do not establish that no events or deaths occurred; they indicate that the registry record does not provide those details. The record also does not describe whether the adverse-event entries cover all enrolled participants for the same duration.
In general, zero events observed in a small group do not demonstrate that an event is impossible or that risk is absent. The reported count of 0 affected among 8 at risk is descriptive and does not provide a precise estimate of how often events might occur in a broader population. No uncertainty interval or comparative safety analysis is reported. These registry entries should not be used to make a treatment recommendation or to draw a conclusion about safety beyond what the record documents.
12. What the Result Does, and Does Not, Mean
The study's stated contribution is a focus on antimicrobial pharmacokinetics in children, particularly the amount of vancomycin measured in CSF relative to serum. This question addresses drug distribution between the circulation and the central nervous system. The registry record documents a completed study with enrollment of 8 and identifies the intended primary summary as a median and full range within 1 week of drug administration.
The posted record does not give the actual median, the range, individual measurements, or an uncertainty interval. It therefore does not show the numerical relationship between CSF and serum vancomycin levels in the participants. Without those results, the reader cannot assess the observed central value, variability, or precision. The registry record also does not report how many participants contributed paired samples, which further limits interpretation of the listed enrollment.
This measure is pharmacokinetic, not a clinical outcome. A CSF:serum ratio does not by itself establish whether an infection improved, whether a drug was effective, or whether treatment was safe. The record does not identify a randomized comparator or state allocation. It should not be read as a comparison of treatment strategies, nor as evidence for a causal effect of vancomycin.
In general, pharmacokinetic observations can help describe how a drug is distributed and can inform further research questions. The extent to which findings apply beyond the participants depends on study methods, participant characteristics, and the completeness of the measurements. Those details are not reported in the registry record, and the numerical outcome is absent. The appropriate interpretation is consequently limited: the study was intended to characterize a drug-level ratio, but the registered information does not make the observed result available.
The adverse-event entries likewise have a narrow meaning. They report 0 affected among 8 at risk in each listed event category, with no serious-event terms and no reported death count. They do not establish the absence of risk, particularly without event definitions and follow-up details. Neither the primary endpoint nor these safety entries justify a broader conclusion about treatment effects.
13. Why This Trial Matters Statistically
This study highlights a statistical distinction between defining a useful measurement and reporting an interpretable result. The registry record identifies a clear pharmacokinetic quantity—the ratio of vancomycin measured in CSF and serum—and states that it is to be summarized by a median and full range. Yet it does not report the numerical summary. Readers can identify the intended question but cannot evaluate the observed estimate or its variability.
That distinction is important in small studies. With enrollment of 8, the number of participants who contributed usable paired measurements would be particularly relevant, but it is not reported. In general, descriptive estimates from a small sample can be uncertain, and clear reporting of the analysis population, individual observations or summaries, and uncertainty is important for judging precision. Those details are not present in this registry record.
The record also illustrates why generic sample-size planning scenarios must be separated from the design and results of an individual study. The planning assumptions describe equal allocation to two arms and a normal approximation, while this study is not identified as a randomized comparison and allocation is not stated. Such scenarios are not evidence that the study had a particular power, nor do they replace a study-specific design justification. No sample-size justification is reported for the enrollment of 8.
Finally, safety counts need context. A registry entry of 0 affected among 8 at risk is a descriptive count, not proof of no risk. Event definitions, follow-up, and the death count are not reported. Together, these features make the study statistically instructive: the research question and endpoint are identifiable, but result completeness and methods reporting determine whether a reader can draw a quantitative interpretation.
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 central limitation of the registry record is that it does not report the numerical primary outcome. The intended CSF:serum ratio is identified, along with its summary form and timeframe, but the median and full range are absent. No confidence interval or other uncertainty measure is reported. As a result, the primary pharmacokinetic finding cannot be quantitatively assessed.
Enrollment is reported as 8, but the registry record does not state how many participants had usable paired CSF and serum measurements. The analysis population, exclusions, missing specimens, and handling of unavailable measurements are not described. This prevents readers from determining whether the endpoint reflects all enrolled participants or a subset.
Participant characteristics are not reported, including the ages and diagnoses represented. The study description refers to young children and babies as the population of interest, but does not establish which ages were enrolled. The exact antimicrobial regimens, vancomycin dose and administration details, specimen collection times, assay methods, and timing of samples within the stated window are also not reported. These details would be important for understanding variation in measured drug levels.
The record does not state allocation and does not identify a like-for-like control group. It therefore offers no basis for a randomized or comparative interpretation. The analysis methods, sample-size justification, missing-data plan, multiplicity approach, and any interim analyses are not reported in the registry record. Finally, safety-event definitions, observation duration, and deaths are not reported in sufficient detail. These limitations concern what can be learned from the registry record and should not be mistaken for evidence that the study did or did not collect information that is not posted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Cerebrospinal Fluid (CSF) Pharmacokinetics of Antimicrobials in Children — NCT00991185.
- Registry record last updated 2024-04-15; status last verified 2014-06.
- Results first posted 2014-07-16.
- 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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18. Record Summary
The registry record describes a completed study of antimicrobial pharmacokinetics in children, sponsored by Duke University. It lists infections as the condition, enrollment of 8, a start date of 2009-07, and a primary completion date of 2014-04. Its stated purpose is to gather information about antimicrobial handling and drug levels in CSF among children receiving drugs as part of standard care.
The primary outcome is the CSF:serum ratio of vancomycin, summarized by the median and full range within 1 week of drug administration. The numerical outcome is not reported in the registry record. One outcome measure is listed, with 0 analyses. Allocation is not stated, and the record does not describe a like-for-like control comparison.
For Vancomycin, the safety entries list 0 affected among 8 at risk for serious adverse events and 0 affected among 8 at risk for other adverse events. Serious-event terms are not listed, and deaths are not reported in the registry record. The available information defines the intended question and the scope of the study, but does not supply a numerical primary result or enough analysis detail to assess its precision.