A Post-Approval Pharmacokinetic Study of Bortezomib in Participants With Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Post-Approval Pharmacokinetic Study of Bortezomib in Participants With Multiple Myeloma (NCT01801436), a na phase 3 study. The primary outcome is Number of Participants With Response to Treatment at Day 1 of Cycle 5.

2. Clinical Question

The study’s stated purpose was to characterize plasma concentrations of unchanged bortezomib and assess its pharmacokinetic properties in the Taiwanese population. It also sought to provide expanded access. The listed primary outcome is an efficacy response measure, not a pharmacokinetic concentration measure. The registry record does not provide a primary pharmacokinetic result or a numerical primary response result, so the posted record cannot answer how often participants met the response definition or how precisely that frequency was estimated.

3. Trial Design

This is a completed, Phase 3, single-group study of bortezomib in participants with multiple myeloma. The record describes enrollment of 14 and lists Johnson & Johnson Taiwan Ltd as the sponsor. The study began in 2006-12 and primary completion was in 2008-04. The allocation field is not applicable, and masking is listed as none. These design features mean the record does not describe random assignment or a blinded comparison.

The intervention schedule was bortezomib 1.3 milligram per meter square on Days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles. The stated population had received at least two previous lines of therapy and was refractory to or had relapsed after the last therapy. The record’s summary describes both a post-marketing pharmacokinetic purpose and expanded access, while the listed primary outcome concerns treatment response at Day 1 of Cycle 5.

A single-group design can describe outcomes observed among treated participants, but it does not estimate a treatment contrast against a concurrent control group. Changes in an outcome over time, if reported, would not by themselves establish that the intervention caused those changes. The record does not report a protocol rationale for the design, details of an enrollment target, a sample-size justification, interim analyses, or the statistical analysis plan.

The registry record lists 29 outcome measures and zero analysis entries. This does not supply the missing numerical primary result. The response endpoint’s evaluated denominator is not reported in the registry record. Consequently, enrollment should not be treated as the denominator for every endpoint, and it does not establish how many participants contributed to the primary outcome.

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 full analysis set (FAS) population included all the participants who received 1 dose of study medication and had post-dose efficacy data. Here 'N' signifies those participants who were evaluated for this outcome measures.

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 Number of Participants With Response to Treatment at Day 1 of Cycle 5, measured over Day 1 of Cycle 5.

The primary endpoint is the number of participants with response to treatment at Day 1 of Cycle 5. The record says response was assessed from changes in monoclonal protein, or M-protein, in serum and urine. It lists complete response, response, partial response, minimal response, stable disease, and progression. The descriptions include complete clearance of M-protein for at least 6 weeks for complete response; at least 75 percent reduction for at least 2 determinations 6 weeks apart for response; 50 to 74 percent reduction for partial response; and 25 to 49 percent reduction for minimal response. Stable disease and progression are also described.

A categorical endpoint can make a clinically interpretable summary of how participants’ measured disease marker status was classified at a specified assessment. The timing matters: this endpoint concerns Day 1 of Cycle 5, rather than an unspecified point during follow-up. Its interpretation depends on the precise rule used to count a participant as having a response. The registry record does not clarify which of the listed categories were included in the primary response count, and it does not report the number meeting that count or the number evaluated. Thus, the endpoint’s definition is partly described, but its observed result cannot be interpreted quantitatively from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods describe how observations are turned into estimates and how uncertainty is assessed. The registry record gives the study structure and endpoint description, but it does not report the statistical analysis plan. It lists zero analysis entries. The following concepts are general explanations of how methods would be interpreted; they are not claims about methods used in this study.

What does a single-group result estimate?

In a single-group study, an outcome summary describes the participants observed under the study intervention. For a binary response outcome, a basic summary would state how many evaluated participants met the response rule and how many were evaluated. A proportion could then describe the observed share, with an uncertainty interval to show how imprecisely that share may be estimated. The registry record does not report the response numerator or evaluated denominator, so no such estimate or interval can be assessed from the posted results.

A single-group estimate is not a treatment comparison. To estimate a difference attributable to treatment, a design needs a suitable comparison and an analysis that accounts for how participants entered the groups. This record identifies no comparator group. A result among treated participants alone cannot separate treatment-associated change from other explanations, such as the natural course of disease or changes in care. This is a general limitation of interpretation, not a statement about what happened to participants in this study.

Why do outcome definitions matter?

A statistical endpoint is useful only when the rule for classifying observations is clear. The record describes several response categories based on M-protein changes and specifies timing or thresholds for several categories. It does not state which categories count as a response in the primary number. If category membership or the aggregation rule is unclear, readers cannot fully reproduce or interpret the endpoint even when a count is available. Here the count itself is also not reported.

Timing is another part of endpoint definition. The primary assessment is at Day 1 of Cycle 5. A result at that scheduled point would answer a different question from a best response during the full course of treatment or a response measured at another time. The record does not report a numerical result at this assessment or a separate time-to-event analysis.

What does a confidence interval convey?

General explanation: a confidence interval presents a range of estimates compatible with the observed data under a specified statistical procedure. A narrow interval generally indicates greater precision than a wide interval, while neither width nor statistical significance alone establishes clinical importance. For a binary endpoint, the interval’s interpretation depends on the number evaluated and the observed response count, as well as the chosen method. Because the registry record does not report the primary count or evaluated denominator, a confidence interval for the primary endpoint cannot be interpreted from the posted information.

Why can an analysis population differ from enrollment?

The record defines the full analysis set as participants who received at least one dose of study medication and had post-dose efficacy data. It says that the N for the primary outcome signifies participants evaluated for that outcome, but it does not report that N. This definition indicates that enrollment and endpoint evaluation are not necessarily the same population. In general, excluding participants without post-dose data can affect an estimate if the reasons for missing assessments are related to outcome status. A clear report would describe the numbers assessed and missing, reasons for missingness, and the analysis used to address missing outcomes. Those details are not reported in the registry record.

What do the planning assumptions mean?

General explanation: sample-size calculations describe the size of a future study under chosen assumptions; they do not describe an observed treatment effect or prove that an existing study had adequate power. The planning illustration associated with the posted material assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a stated fraction of an observed effect. That is a hypothetical two-arm planning framework, not the design described in this registry record, which is single-group. The record does not report a study-specific sample-size justification or an observed-effect calculation that can be interpreted as an analysis of this trial.

For count outcomes, variation can exceed the amount assumed by a simple model; this is called over-dispersion. General explanation: when data vary more than the model expects, standard errors may be too small if the extra variation is ignored, making intervals appear more precise than warranted. The primary endpoint is described as a participant count, but the registry does not report a model, dispersion estimate, or analysis for it. No claim about an over-dispersion adjustment can therefore be made.

Multiplicity concerns arise when many outcomes or comparisons are examined. The registry lists 29 outcome measures, but the existence of multiple measures alone does not establish how multiplicity was handled or whether adjustments were planned. The statistical plan, hierarchy of outcomes, and any multiplicity procedure are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 29 outcome measures, while the primary endpoint is the number of participants with response at Day 1 of Cycle 5. The record does not report how the primary endpoint was prioritized relative to other outcomes, whether outcomes were prespecified in a hierarchy, or whether any adjustment for multiple testing was planned. A list of multiple outcomes is not, by itself, evidence that a multiplicity correction was or was not used. The statistical plan is not reported in the registry record.

The efficacy population is defined as participants who received at least one dose and had post-dose efficacy data. The record says the N for the endpoint refers to those evaluated, but it does not report the evaluated number or primary response count. It also does not describe the amount or pattern of missing efficacy data, reasons for missing assessments, or a method for handling missing outcomes. These details matter because an analysis based only on observed assessments may represent a different set of participants from the enrolled group.

The enrollment figure is 14, but it should not be substituted for the primary endpoint denominator. Nor does the definition of the full analysis set establish that every enrolled participant had an evaluable result. The registry record does not describe a per-protocol population, an imputation approach, sensitivity analyses for missing data, or the treatment of participants who discontinued before the scheduled assessment. These are unreported details, not evidence that a particular method was used or omitted from the underlying study.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (28.6%), platelet count decreased (28.6%), blood potassium decreased (14.3%), blood sodium increased (14.3%), pancytopenia (7.1%).

The registry’s serious adverse-event summary lists pneumonia and platelet count decreased at 28.6% each, blood potassium decreased and blood sodium increased at 14.3% each, and pancytopenia and gastritis at 7.1% each. These are the listed top serious-event terms. The record does not provide event counts for each term, so the percentages should be read as the reported summaries rather than converted into counts. It does not describe the event-level criteria or provide a comparator group for assessing relative safety.

The safety summary lists 14 at risk and 14 affected for both serious and other adverse events. The death count is not reported in the registry record. These overall entries do not supply detail about the timing, duration, severity, or outcome of individual events. A participant may also experience more than one event, so event terms should not be treated as mutually exclusive categories or added together. The safety figures describe what the registry lists; they do not establish whether bortezomib caused an event or how its frequency compares with another treatment.

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

The record documents a completed, single-group post-approval study with a stated pharmacokinetic purpose and an expanded-access purpose for participants with multiple myeloma. It also identifies a primary response endpoint at Day 1 of Cycle 5 and describes response categories based on M-protein changes. This information clarifies the intended population, treatment schedule, and outcome timing.

However, the registry record does not report the number of participants with a primary response or the number evaluated for that endpoint. It therefore does not show the observed response frequency or its precision. The response rule is not fully explicit because the record does not state which of the listed categories were counted as a response in the primary number. The stated pharmacokinetic purpose is also not accompanied by a numerical pharmacokinetic result in the record.

The design has no comparator group, so the record cannot support a randomized comparison or a treatment-effect estimate against another option. Even if a treated-group outcome were available, a single-group result would describe the observed participants rather than isolate the causal effect of treatment. This is a general design interpretation, not a conclusion that the intervention did or did not affect outcomes.

The listed serious adverse-event terms provide descriptive safety information, but they do not establish causality or comparative risk. The registry does not report a death count, event-level detail, or a control group. In general, a complete interpretation of safety also depends on how events were defined, collected, followed, and attributed; those methods are not reported in the registry record.

The appropriate reading is therefore limited: the registry establishes that these outcomes and safety terms were recorded, but it does not provide enough numerical primary efficacy information to quantify the response result. It also does not report the statistical plan, endpoint-specific missing-data handling, or sample-size rationale. No conclusion about comparative benefit or harm can be drawn from the posted record alone.

13. Why This Trial Matters Statistically

This study is statistically notable because its stated purposes and its listed primary endpoint address different kinds of questions. The brief summary describes pharmacokinetic assessment of unchanged bortezomib in a Taiwanese population and expanded access, while the primary endpoint is a treatment-response count at Day 1 of Cycle 5. Pharmacokinetic concentration summaries and categorical response outcomes require different reporting and interpretation. The registry record does not provide a numerical pharmacokinetic result or the primary response count.

The single-group structure is also important. It can describe observations among participants who received the intervention, but it does not provide a concurrent benchmark for interpreting those observations as a comparative treatment effect. Recognizing this distinction prevents an observed outcome from being mistaken for evidence from a randomized comparison.

The record further illustrates why an endpoint needs both a clear classification rule and a reported denominator. It lists detailed thresholds for several M-protein response categories, yet does not specify which categories form the primary response count. It also defines the efficacy population but does not report the number evaluated. Without those details, the primary result cannot be reconstructed or judged for precision from the registry record.

Finally, the safety percentages are descriptive entries rather than comparative estimates. They can identify terms recorded among serious adverse events, but the record does not provide a control group, term-specific counts, or the death count. Together, these features make the study useful for understanding the structure of a post-approval record while underscoring how design, endpoint specification, analysis populations, and transparent result reporting determine the strength of statistical 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 most important limitation for interpreting the posted results is that the registry record does not report the primary response count or the number evaluated. The enrollment figure does not resolve this gap because the endpoint population is defined by receipt of study medication and availability of post-dose efficacy data. The record also does not clearly state which response categories were included in the primary count.

The study is single-group, with no comparator and no masking. It therefore cannot provide a direct comparative estimate, and any descriptive outcome among treated participants would not by itself establish a treatment effect. The record does not report a protocol rationale, a sample-size justification, interim analyses, or a statistical analysis plan.

The study’s stated pharmacokinetic purpose is not accompanied by a numerical pharmacokinetic result in the registry record. Although 29 outcome measures are listed, the record does not explain their hierarchy or report a multiplicity approach. It does not describe missing efficacy data, reasons for missing assessments, sensitivity analyses, or endpoint-specific analysis populations beyond the full analysis set definition.

Safety reporting is also limited in the posted record. Serious-event terms are accompanied by percentages, but term-specific counts and event-level details are not reported. The death count is not reported, and the absence of a comparator limits comparative safety interpretation. These limitations concern the registry information; they do not establish what may have been reported elsewhere or what analyses may have been performed outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Post-Approval Pharmacokinetic Study of Bortezomib in Participants With Multiple Myeloma — NCT01801436.
• Registry record last updated 2013-05-16; status last verified 2013-03.
• Results first posted 2013-05-16.
• 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.

18. Record Summary

The registry record describes a completed Phase 3, single-group, unmasked study of bortezomib in participants with multiple myeloma. Enrollment was 14. The treatment schedule was 1.3 milligram per meter square on Days 1, 4, 8, and 11 of each 3-week cycle, for up to 8 cycles. The stated study purposes included pharmacokinetic assessment and expanded access.

The primary endpoint was the number of participants with response at Day 1 of Cycle 5, assessed from M-protein changes in serum and urine. The primary response count and evaluated denominator are not reported in the registry record. The record lists serious adverse-event terms and percentages, but does not report the death count or term-specific event counts. It also does not report a statistical analysis plan, sample-size justification, or missing-data methods. The single-group design provides no concurrent comparator for a treatment-effect estimate.