Pharmacokinetic Study of Liposomal Vincristine in Patients With Malignant Melanoma & Hepatic Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic Study of Liposomal Vincristine in Patients With Malignant Melanoma & Hepatic Dysfunction (NCT00145041), a na phase 1 study. The primary outcome is T 1/2.

2. Clinical Question

The study concerned vincristine sulfate liposome injection (VSLI) in people with malignant melanoma and hepatic dysfunction secondary to metastases. The registry describes the primary outcome as a pharmacokinetic measure of total plasma vincristine after an infusion. Its brief summary also describes assessing safety and whether VSLI might slow tumor growth or shrink tumors, but the registry record does not report numerical results for those aims.

This is a descriptive pharmacokinetic question, not a randomized comparison of VSLI with another treatment. With no control arm, the design cannot estimate a between-group treatment contrast. The registry describes three male and four female subjects in its pharmacokinetic description and specifies cycle 1 day 1 as the primary-outcome timeframe. It also says the infusion was given every 2 weeks, with one cycle described. The record does not report the individual concentration measurements, the timing of pharmacokinetic samples, or a numerical estimate and dispersion for T 1/2. Consequently, the intended question can be identified, but the posted registry information does not permit a reader to assess the magnitude or precision of the primary pharmacokinetic result.

3. Trial Design

The registry lists NCT00145041 as a completed phase 1 study sponsored by Acrotech Biopharma Inc. The recorded start was 2005-02, and primary completion was 2007-09. The design is single-group, with no allocation to competing arms and no masking. The arm description states that all subjects received VSLI. Enrollment was 7, and the registry identifies malignant melanoma as the condition.

The intervention is listed as vincristine sulfate liposomes injection. For the pharmacokinetic measurement, the description specifies a target dose of 1.0 mg/m2 administered by a single intravenous infusion lasting approximately 1 hour. It describes measurement of total plasma VCR pharmacokinetic profiles in three male and four female subjects with malignant melanoma and hepatic dysfunction secondary to metastases. The dosing description says administration occurred every 2 weeks and refers to one cycle; the primary-outcome timeframe is cycle 1 day 1.

Because this is a single-group study, the design is suited to describing observations among the treated participants, not to comparing outcomes against an untreated or differently treated group. The record lists allocation as not applicable and masking as none. It does not describe random assignment, a control group, or blinding. Those features matter when interpreting any apparent change in tumor status or safety experience: without a comparator, the registry cannot establish how such observations differ from what would have occurred under another treatment or no study treatment.

The registry lists three outcome measures and zero analyses. It does not report a full protocol, detailed statistical analysis plan, sample-size justification, interim-analysis plan, or numerical primary outcome result. Information about recruitment flow, treatment discontinuations, and the completeness of pharmacokinetic observations is also not reported in the registry record. The study's completed status indicates that the registry marks it completed; it does not, by itself, establish that every planned analysis or outcome is reported.

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.

Before assignment: Eligible subjects were to have liver metastases confirmed by computed tomography (CT) scan at screening. Categorization of hepatic dysfunction at screening included Child-Pugh System.

Overall Study

Analysis population for the primary outcome, as defined in the registry: all patients enrolled

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 T 1/2, measured over cycle 1 day 1.

The primary endpoint is titled T 1/2, with hours as its unit. It is specified as a mean with standard deviation, for cycle 1 day 1, in all patients enrolled. In pharmacokinetics, a half-life measure describes the time course of a substance's concentration in the body. For this study, the registry says the measure relates to total plasma VCR following a single intravenous infusion of VSLI. Such a measure is used to characterize drug disposition over time and to describe how concentrations change after administration. That is a general explanation of the endpoint's role, not a claim about the observed result in this study.

A mean gives a summary of the measured values, while a standard deviation describes the spread of individual observations around that mean. Reporting both can help distinguish the average profile from the degree of participant-to-participant variation. The registry identifies this summary format but does not report the mean, standard deviation, number of evaluable measurements, or a confidence interval. It also does not provide concentration-time data or further detail about how the half-life estimate was derived. Therefore, the endpoint's intended meaning can be described, but its value and precision cannot be assessed from the registry record.

The brief study description also mentions safety and tumor growth or shrinkage as aims. Those aims should not be confused with the named primary pharmacokinetic endpoint. Numerical results for those aims are not reported in the registry record in the information summarized for this study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study's main statistical task is descriptive: summarize a continuous pharmacokinetic endpoint in a single group. The registry labels T 1/2 as a mean with standard deviation and gives hours as the unit. In general, a mean is the arithmetic average of observed measurements. A standard deviation describes how dispersed measurements are around that average. Together, they answer different questions: the mean describes the center of the observed values, while the standard deviation describes their variability. Neither is reported numerically in the registry record for this endpoint.

What does a mean summarize?

For a continuous measurement, a mean offers a compact summary of the observations. It can be useful when the average value is scientifically meaningful and the measurement scale supports averaging. But a mean alone does not describe the shape of the data. Different distributions can share the same mean while differing in skewness, outliers, or clustering. These are general statistical points. The registry does not provide individual T 1/2 values or a distributional plot, so it is not possible to assess those features for this study.

What does the standard deviation add?

The standard deviation describes spread among measured values, rather than the precision of the estimated mean. A small standard deviation indicates less spread in the observed values; a larger one indicates more spread. It is not interchangeable with a standard error or confidence interval. A confidence interval is a range calculated to express uncertainty about an estimated quantity under a statistical model. It is not the range containing most individual measurements. No standard deviation, standard error, or confidence interval for T 1/2 is reported in the registry record, so neither observed variation nor uncertainty can be evaluated.

Why does the single-group design matter?

A single-group summary can describe the participants who received VSLI, but it does not estimate a contrast against a separate control group. Randomized comparisons can help balance measured and unmeasured factors across treatment groups, in expectation. That logic does not apply to this record as a between-arm comparison: allocation is listed as not applicable, masking as none, and the study model as single-group. The design therefore supports a descriptive pharmacokinetic objective, not a causal comparison of treatment effects. This is a general design interpretation, not a conclusion about the quality of any unreported analysis.

Why can variability matter for pharmacokinetic data?

Pharmacokinetic measurements describe concentrations over time, and individuals may differ in their observed profiles. In general, variability can affect how representative a group average is for a particular participant and how precisely the mean is estimated. If measurements are highly variable or have an asymmetric distribution, a mean and standard deviation may not convey all important features; other summaries or a model may also be useful. These are general considerations. The registry does not report the concentration measurements, distributional characteristics, or model used to derive T 1/2, so no claim can be made about whether additional methods were needed in this study.

Over-dispersion is a general concept most often discussed for data whose variability exceeds what a chosen model expects. It can make standard errors too small if a model fails to account for extra variation. It is not possible to diagnose over-dispersion from the registry description: no model specification, residual assessment, or numerical endpoint results are reported. It would be inappropriate to assume that the study used a particular distribution or model.

What do the planning assumptions mean?

The registry's planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect targeted in the illustration is a stated fraction of the observed effect. These are assumptions for planning calculations, not descriptions of an observed trial result. The description also distinguishes total events for time-to-event calculations from participants per arm for other calculations. The current trial is listed as single-group, so a hypothetical two-arm planning illustration should not be read as the study's actual allocation or design.

Sample-size planning asks how many participants a future study might need under specified assumptions. Its output depends on the assumed effect, variability, significance level, power target, allocation, and analysis method. Those calculated sample sizes are planning illustrations; they are not observed power. Observed power is not a substitute for an estimate and its uncertainty after data have been collected. The registry record does not report a numerical planning result or a sample-size justification for the original study, so the assumptions alone cannot establish why enrollment was 7.

What is unavailable for evaluating the analysis?

The registry lists zero analyses and does not provide a numerical endpoint estimate. It also does not describe a statistical model, transformation, handling of repeated observations, confidence-interval method, or diagnostic checks. The pharmacokinetic description refers to profiles following an infusion, but it does not provide enough detail to reconstruct an analysis. No recalculated estimate can be made from the registry record because the summary statistics required for a recalculation are absent. The record also does not identify any discrepancy between a sponsor analysis and a recalculation.

In general, an analysis plan helps clarify which outcomes and methods were intended before results are examined. Without the plan, it is harder to assess whether analyses were selected after data were seen or whether multiple outcomes were handled as intended. The registry does not report the protocol or full statistical analysis plan, so these questions remain unresolved. This absence does not prove that a plan did not exist; its details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and zero analyses. The primary endpoint is identified as T 1/2, but the numerical result is not reported in the registry record. The record does not identify which analyses correspond to the other outcome measures, whether they were tested inferentially, or whether any multiplicity adjustment was planned or used. A multiplicity strategy matters when several outcomes or repeated tests are considered, because the chance of at least one apparently unusual result can increase as testing expands. That is a general statistical explanation, not a statement that this study conducted multiple tests.

The primary outcome population is stated as all patients enrolled, and enrollment was 7. The registry does not report how many participants contributed usable pharmacokinetic observations, whether any measurements were missing, or how missing values were handled. It does not describe exclusions, imputation, sensitivity analyses, or reasons for missingness. These details are not reported in the registry record; their absence should not be interpreted as evidence that no data were missing or that a particular method was used.

The record also does not specify an analysis population beyond identifying all patients enrolled for the primary outcome. It does not say whether the full enrolled group, a treated group, or a group with evaluable pharmacokinetic profiles was used for each of the other outcomes. There is no reported protocol or statistical analysis plan to clarify planned populations or multiplicity procedures. As a result, the stated outcome count and the absence of listed analyses do not allow readers to determine how outcome selection, missingness, or analysis populations affected the results.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: malignant melanoma (42.9%), cardiac arrest (14.3%), dyspnoea (14.3%), disseminated intravascular coagulation (14.3%), multi-organ failure (14.3%).

The registry's overall study safety group lists 7 participants at risk and 7 affected for serious adverse events. For other adverse events, it also lists 7 at risk and 7 affected. These entries describe the registry's participant-level safety fields; they do not by themselves provide event counts, timing, severity grades, or judgments about whether an event was caused by VSLI. The record does not give a comparator group, so these figures are not comparative estimates.

The serious-event terms listed include malignant melanoma at 42.9%, and cardiac arrest, dyspnoea, disseminated intravascular coagulation, multi-organ failure, and ascites each at 14.3%. The registry does not provide further detail in this summary about the circumstances or timing of these terms. A term appearing in a safety list is not, on its own, evidence of treatment causation. The deaths field is null, so a death count is not reported in the registry record.

With enrollment of 7, the safety summary concerns a small group. In general, percentages based on small groups can change substantially when the status of a participant differs, and should not be treated as precise population-level rates. The record does not provide confidence intervals for these safety percentages or a detailed account of event collection. These limitations prevent a fuller assessment of frequency and uncertainty.

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

The registry record establishes that this was a completed phase 1, single-group study of VSLI in patients with malignant melanoma and hepatic dysfunction secondary to metastases. It identifies a pharmacokinetic objective and names T 1/2 in hours as the primary endpoint, summarized as a mean with standard deviation. It also describes the intended infusion and timing of the primary measurement. Those details explain what the study set out to measure.

The record does not report the numerical T 1/2 mean or standard deviation. It therefore does not show the observed average, how much participant values varied, or how precisely the average was estimated. No confidence interval or underlying concentration data are listed. Without these quantities, the primary pharmacokinetic result cannot be quantified or evaluated for precision from the registry information.

The design does not include a comparator. Thus, the study does not provide a randomized estimate of how VSLI compares with another treatment. The brief summary mentions safety and tumor growth or shrinkage as aims, but numerical tumor results are not reported in the registry record. The safety summary lists serious and other adverse-event fields, but it does not include enough detail to establish causality, timing, severity, or comparative risk.

These limits should not be mistaken for evidence that the treatment did or did not have a particular effect. They describe what can be interpreted from the registry record. The absence of reported endpoint estimates means the size and precision of the primary result remain unknown in this record. Likewise, completion status and the presence of safety terms do not resolve efficacy or causal questions. Any stronger conclusion would require outcome data and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between identifying a measurement and reporting a result. The registry gives a clear primary-outcome label, unit, summary format, population, and timeframe: T 1/2 in hours, expressed as a mean with standard deviation, for all patients enrolled at cycle 1 day 1. Those specifications identify the kind of quantity intended for analysis. They do not substitute for the numerical estimate and its uncertainty, which are not reported in the registry record.

The design also illustrates the distinction between descriptive and comparative questions. A single-group pharmacokinetic study can characterize measured profiles among participants receiving an intervention. It cannot, without a comparator, estimate a treatment difference between groups. That distinction is important when readers encounter a trial record that also mentions safety or tumor-related aims: the intended aims do not change the design's capacity for causal comparison.

The enrollment of 7 makes careful reporting of individual variation and uncertainty especially important as a general statistical matter. A group average alone can conceal how much observations differ, while a standard deviation alone does not show uncertainty in the average. The registry specifies both as the intended format but reports neither numerical value. The reader is therefore left without the information needed to assess the magnitude, spread, or precision of the primary endpoint.

Finally, the registry lists three outcome measures and zero analyses, while the safety record gives percentages and affected-participant fields without fuller event detail. This makes the boundary between recorded design information and interpretable results especially important. Statistical transparency depends not only on naming outcomes but also on reporting estimates, uncertainty, analysis populations, and missing-data handling. Those details are not reported in the registry record for this study.

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 main limitation for interpreting this trial record is that the primary endpoint is named but its numerical result is absent. The mean and standard deviation for T 1/2 are not reported, and no confidence interval or individual pharmacokinetic measurements are available in the registry record. This prevents assessment of the observed magnitude, variability, or precision of the intended primary measure.

Enrollment was 7, and the study had a single group in which all subjects received VSLI. There is no control arm or randomized treatment comparison. This limits the design to describing observations in the study group and prevents a direct estimate of comparative treatment effects. It also means that the safety percentages cannot be interpreted as differences from another group.

The pharmacokinetic description specifies total plasma VCR after an infusion, but the record does not provide the concentration-time data, sampling schedule, detailed derivation of T 1/2, or analysis model. It does not report the number of participants with evaluable measurements or how missing observations were handled. The registry lists three outcome measures but zero analyses; it does not explain the absence of listed analyses or give results for the additional aims mentioned in the brief summary.

Safety information is limited to participant fields and a list of serious-event terms with percentages. The record does not report event timing, severity grading, attribution, or event-level counts in this summary. The deaths field is null, so a numerical death result is not reported. The protocol, full statistical analysis plan, and original sample-size justification are not reported in the registry record. These limitations concern the available record and do not establish what information may exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pharmacokinetic Study of Liposomal Vincristine in Patients With Malignant Melanoma & Hepatic Dysfunction — NCT00145041.
• Registry record last updated 2019-12-12; status last verified 2019-12.
• Results first posted 2012-01-05.
• 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

NCT00145041 is listed as a completed phase 1 study of VSLI in patients with malignant melanoma and hepatic dysfunction secondary to metastases. The design is single-group, with no allocation to a comparator and no masking. Enrollment was 7. The recorded start was 2005-02, and primary completion was 2007-09.

The named primary endpoint is T 1/2 in hours, summarized as a mean with standard deviation for cycle 1 day 1. The pharmacokinetic description concerns total plasma VCR after a target dose of 1.0 mg/m2 by intravenous infusion for approximately 1 hour. The numerical endpoint result is not reported in the registry record. The record lists three outcome measures and zero analyses.

The safety summary lists 7 participants at risk and 7 affected for both serious and other adverse events. Serious-event terms and percentages are reported, but the deaths field has no numerical value. The registry does not report a comparator, numerical tumor results, missing-data methods, or a full analysis plan.