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 Impact of Proteasome Inhibition on Anti-Donor HLA Antibody Production After Kidney Transplantation (NCT01349595), a randomized phase 2 study. The primary outcome is The Incidence of a Combined Endpoint of Death-censored Graft Loss or Greater Than 50% Reduction in Estimated Glomerular Filtration (eGFR) in Study Subjects..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01349595 |
| Phase | Phase 2 |
| Condition | Disorder of Transplanted Kidney |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mark Stegall |
| Results posted | Yes |
2. Clinical Question
Population
Kidney transplant recipients with high levels of donor-specific alloantibodies after transplantation. The study concerned the potential development of transplant glomerulopathy and preservation of allograft function. The registry does not report further eligibility details or a more specific description of the participant group.
Intervention
Bortezomib, described in the registry as a type of targeted chemotherapy. The registry does not report a dosing schedule or additional intervention details.
Comparator
Standard post-transplant treatment, described as Mayo Clinic standard post-kidney-transplant follow-up. The registry does not give more detail about what that follow-up included.
Primary question
Whether the incidence of a combined endpoint—death-censored graft loss or a >50% reduction in estimated glomerular filtration rate—differed between study groups during the 60 months after enrollment. No participants were analyzed for this outcome in the registry results.
3. Trial Design
The registry describes a randomized, parallel-group, phase 2 study with no masking. The two listed groups were bortezomib and standard post-transplant treatment. Random allocation is intended, in general, to make group comparisons less vulnerable to systematic differences in who receives each intervention. With no masking, participants and study personnel may know the assigned treatment; whether that knowledge affected care, follow-up, or outcome assessment is not reported in the registry record.
The registry records enrollment of 4 and a status of terminated. It lists a start date of 2011-12 and primary completion of 2015-03. The primary outcome timeframe is 60 months after study enrollment. The registry states that results for zero participants were analyzed and that long-term follow-up evaluation was not possible because of discontinuation of funding. Consequently, the design description does not translate into an available randomized comparison of the primary endpoint.
The registry does not report the randomization procedure, allocation concealment, treatment dose or schedule, adherence, or the detailed conduct of follow-up. It also does not report a reason for termination beyond the funding-related limitation on long-term follow-up. These details matter when assessing how assignment was implemented and whether participants were followed in comparable ways, but their absence does not establish that any particular procedure was or was not used.
Enrollment is not the same as the number of participants with outcome data. The registry's primary-outcome entry explicitly states that zero participants were analyzed. The adverse-event entries separately list two participants at risk in each group; these safety denominators do not supply missing primary-outcome observations or establish that the primary comparison was performed.
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 | Bortezomib | Standard Post-transplant Treatment |
|---|---|---|
| STARTED | 2 | 2 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 2 | 2 |
Reasons for not completing this period:
| Reason | Bortezomib | Standard Post-transplant Treatment |
|---|---|---|
| Lack of funding | 2 | 2 |
Analysis population for the primary outcome, as defined in the registry: Results data for zero participants were analyzed; long-term follow-up evaluation of participants was not possible due to discontinuation of funding.
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 | Bortezomib | Standard Post-transplant Treatment | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 2 | 4 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 2 | 4 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 2 |
| Region of Enrollment: United States | participants | 2 | 2 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as The Incidence of a Combined Endpoint of Death-censored Graft Loss or Greater Than 50% Reduction in Estimated Glomerular Filtration (eGFR) in Study Subjects., measured over 60 months after enrollment in the study.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint combines death-censored graft loss with a >50% reduction in estimated glomerular filtration rate (eGFR). Graft loss concerns loss of function of the transplanted kidney. In general, death-censored graft loss treats death as a competing event rather than counting it as graft loss. eGFR is an estimate of kidney filtration based on clinical measurements; a large decline can be used as an indicator of worsening graft function. The registry does not give a more detailed definition of either component or specify how the combined endpoint was adjudicated.
A combined endpoint can capture more than one clinically important way an outcome may occur. In general, this can be useful when separate components are related or when a single component alone would not describe the full outcome of interest. Interpretation depends on knowing which components occurred and how they were defined. The registry gives the combined endpoint title and a timeframe of 60 months after enrollment, but no analyzed participant results or component-level results.
Because the registry reports zero participants analyzed for the primary endpoint, it provides no observed incidence for either group and no comparison of the combined endpoint. The endpoint's clinical rationale therefore does not establish what happened in the study groups. Detailed endpoint definitions, assessment procedures, and component counts are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical limitation is that the registry reports no analyzed participants for the primary outcome. It therefore supplies no observed primary-endpoint incidence by group, no treatment contrast, and no uncertainty interval for that contrast. The study's randomized design describes how groups were intended to be compared; it cannot substitute for outcome observations. In the absence of analyzed outcomes, the registry cannot show whether the groups differed on the combined endpoint.
The record identifies a planned follow-up horizon of 60 months after enrollment, but it also states that long-term follow-up evaluation was not possible because funding was discontinued. This is important context for the missing primary-outcome results. It does not reveal what the outcome would have been for participants had follow-up continued, nor does it establish the direction or size of any difference between groups.
The registry lists enrollment of 4. That enrollment figure should not be mistaken for a primary-outcome analysis population: the outcome entry expressly reports that zero participants were analyzed. The adverse-event figures have their own denominators and do not fill this gap. No primary-outcome effect estimate, confidence interval, or p-value is reported in the registry record. Without these results, the precision of a possible treatment comparison cannot be assessed.
In general, a confidence interval describes a range of values compatible with the data and analysis under stated assumptions. When no primary-outcome observations are analyzed, there is no outcome-based interval to interpret from the registry results. Likewise, a p-value would address compatibility between observed data and a specified statistical model or null hypothesis; no such primary-endpoint result is reported. Neither a positive nor a null treatment effect can be inferred from the absence of an analysis.
The safety entries report no serious adverse events in either group, while other adverse events are listed in the bortezomib group and not in the standard-treatment group. These are descriptive counts, not a comparison that establishes a treatment effect. The numbers are small, and the record does not provide event descriptions, timing, severity beyond the serious-versus-other categorization, or a causal assessment. Death counts are not reported in the registry record.
Overall, the posted information documents the study question, group assignments, enrollment, termination status, and limited adverse-event counts, but not the primary outcome results. Any conclusion about relative efficacy, graft preservation, or the incidence of the combined endpoint would go beyond what the registry record reports. This is a limitation of the available results, not evidence that the treatments produced equal outcomes.
9. Statistical Methods Explained
Statistical methods are not reported in the registry record. The explanation below is general and describes how methods commonly used in randomized studies relate to the information available for this trial; it does not assert that these methods were used.
What randomization contributes
In general, randomization assigns participants to groups by chance. This helps prevent deliberate or systematic selection from determining who receives each treatment and supports a fair comparison. In expectation across repeated randomized trials, measured and unmeasured characteristics are balanced between groups. It does not guarantee that groups will be identical in any one trial, especially when enrollment is limited. It also does not ensure that outcomes are observed or analyzed. Here, the registry identifies randomized allocation, but reports zero participants analyzed for the primary outcome.
Masking is a separate design feature. In general, masking can reduce the influence of knowledge about treatment assignment on participant behavior, clinical management, or outcome assessment. The registry lists no masking. It does not report which people, if any, knew assignments in practice or whether any outcome assessments were conducted in a blinded manner. These details are not reported in the registry record.
What a group comparison would require
For a binary composite endpoint, a usual comparison would begin with the number of participants who experienced the endpoint and the number assessed in each group, along with a defined analysis population and follow-up approach. An effect estimate could then describe the difference or ratio between group outcomes, depending on the chosen method. A confidence interval would communicate uncertainty around that estimate. The registry does not report the primary endpoint counts, an analysis population, or a comparative estimate, so these quantities cannot be interpreted from the posted outcome results.
The endpoint is time-framed at 60 months after enrollment. In general, when time to an event matters and participants have different lengths of observation, an analysis may account for follow-up time and censoring rather than treating all participants as if observed for the same duration. Competing events can also matter: death may prevent later observation of graft loss. The registry's term “death-censored” signals that death is treated distinctly in defining the graft-loss component, but the statistical method for handling time, censoring, and competing events is not reported in the registry record.
Why uncertainty matters
General statistical interpretation distinguishes an estimate from its precision. An estimate summarizes an observed contrast; its confidence interval indicates how uncertain that estimate is under the chosen model and assumptions. A wide interval often indicates substantial uncertainty, while a narrow interval indicates greater precision. No primary-outcome estimate or interval is reported. It is therefore not possible to assess precision, and the absence of an estimate should not be described as a precise finding of no difference.
A p-value is also not a measure of effect size or clinical importance. In general, it assesses how unusual the observed data would be under a specified null hypothesis and model. Its interpretation depends on the study design, analysis choices, and data quality. No primary-outcome p-value or analysis method is reported in the registry record, so no significance claim can be made from the primary results.
Small studies and variability
In general, limited enrollment can make estimates unstable and confidence intervals broad, because each participant's outcome can have substantial influence on the group summary. Randomization does not remove this uncertainty. It is also possible for baseline characteristics to differ by chance. The registry's enrollment figure and absence of primary-outcome analysis mean that no primary-endpoint estimate or precision measure is available to evaluate in this study.
Over-dispersion is a general issue for some count outcomes: observed variation can exceed what a simple statistical model assumes. When that occurs, a model that accounts for the extra variation may better represent uncertainty. The registry does not report a count-outcome analysis for the primary endpoint, and over-dispersion is not a reported feature of these results. This concept therefore cannot be used to infer an analysis or finding for the trial.
Planning calculations versus trial findings
In general, sample-size calculations are planning tools based on assumptions about an effect, variability, allocation, and a chosen statistical threshold. They are not observed outcomes and do not establish that a study had adequate precision after the fact. The registry describes planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also states that the relevant effect is a stated fraction of the observed effect. However, the registry reports no analyzed primary-outcome participants and no observed primary-endpoint comparison from which to interpret an effect. Any planning illustration should therefore not be read as evidence of an actual treatment effect, a completed analysis, or observed power. The registry's own sample-size justification is not reported in the registry record.
These general principles clarify why the primary finding cannot be reconstructed from the design description or safety counts. A valid estimate requires outcome data and a specified analysis. Neither is reported for the primary endpoint. The record supports description of the intended comparison and its limitations, but not a quantitative efficacy conclusion.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies one primary endpoint: a combined outcome of death-censored graft loss or a >50% reduction in eGFR. A multiplicity strategy—such as how the analysis would account for multiple endpoints, time points, or comparisons—is not reported in the registry record. The primary-outcome entry is not reduced to a single comparison, and its detailed categories or time-point structure are not reported in the registry record. No inferential results are available to assess whether multiplicity affected interpretation.
Missing outcome information is central to this record. The registry reports results for zero participants analyzed for the primary outcome and states that long-term follow-up evaluation was not possible because funding was discontinued. It does not report which participants, if any, had partial follow-up, when observations ended, or whether any missing outcomes were imputed. Reasons for missing data beyond the funding-related follow-up limitation are not reported in the registry record.
In general, missing outcome data can affect a comparison if the likelihood of missingness is related to treatment assignment or outcome status. Different assumptions about unobserved outcomes can lead to different estimates, so analysts often describe their missing-data methods and assess how robust results are to assumptions. No such methods or sensitivity analyses are reported. The record also does not report whether an intention-to-treat, per-protocol, or other analysis population was specified or used. Without analyzed primary outcomes and a stated analysis population, neither the impact of missing data nor the handling of the randomized groups can be evaluated.
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 |
|---|---|---|---|
| Bortezomib | 0 | 2 | 0.0% |
| Standard Post-transplant Treatment | 0 | 2 | 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 |
|---|---|
| Bortezomib | 2 of 2 |
| Standard Post-transplant Treatment | 0 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bortezomib | Standard Post-transplant Treatment |
|---|---|---|---|
| nausea/vomiting | Gastrointestinal disorders | 2 of 2 | 0 of 2 |
| fatigue | General disorders | 2 of 2 | 0 of 2 |
| Pain at injection site | General disorders | 1 of 2 | 0 of 2 |
| Injection site reaction | Skin and subcutaneous tissue disorders | 1 of 2 | 0 of 2 |
| dehydration | Metabolism and nutrition disorders | 1 of 2 | 0 of 2 |
| joint pain | Musculoskeletal and connective tissue disorders | 1 of 2 | 0 of 2 |
| Pain | General disorders | 1 of 2 | 0 of 2 |
The registry separates serious adverse events from other adverse events. For serious events, it lists 0 affected among 2 at risk in the bortezomib group and 0 affected among 2 at risk in the standard post-transplant treatment group. For other adverse events, it lists 2 affected among 2 at risk in the bortezomib group and 0 affected among 2 at risk in the standard-treatment group. These are registry counts and should be read as descriptive entries, not as proof of a treatment-related cause.
The record does not provide the terms for the serious events; no serious-event terms are listed. It does not report death counts, and death counts should not be inferred from the serious-event figures. The registry also does not provide event timing, duration, severity details beyond its categories, or information about whether events led to treatment changes. These limitations restrict interpretation of the safety entries.
In general, adverse-event counts describe events recorded under the registry's categories; they do not by themselves establish comparative risk. The small denominators make each recorded event consequential to the descriptive pattern, and no adjusted analysis or uncertainty interval is reported. The safety information does not replace the missing primary-outcome analysis.
12. What the Result Does, and Does Not, Mean
The registry establishes that this was a randomized, parallel-group, phase 2 study comparing bortezomib with standard post-transplant treatment in kidney transplant recipients with high levels of donor-specific alloantibodies. It also records enrollment of 4, a terminated status, and a primary endpoint defined over 60 months after enrollment. These details describe the intended study question and the context in which the results were expected.
The registry does not establish whether bortezomib changed the incidence of death-censored graft loss or a >50% reduction in eGFR. No participants were analyzed for that primary outcome, and long-term follow-up evaluation was not possible because funding was discontinued. There is no reported endpoint estimate, uncertainty interval, or p-value to support a conclusion about the direction, size, or precision of a group difference.
This absence of a primary-outcome analysis is not evidence that the treatments had the same results. It is also not evidence that one treatment was better or worse. The study's randomized design does not overcome the lack of analyzed outcome data. Nor can the adverse-event counts answer the primary efficacy question; they describe separate registry categories and do not provide a graft-function comparison.
The safety counts should likewise be interpreted narrowly. They indicate what the registry lists for the reported categories, but the record does not provide event details or a causal assessment. These entries cannot establish overall safety, exclude unrecorded harms, or characterize longer-term outcomes.
The appropriate reading is therefore descriptive and cautious: the registry records the design and a limited set of safety counts, while the planned long-term primary outcome is unavailable for analysis. Any stronger statement about prevention of transplant glomerulopathy, preservation of allograft function, or clinical benefit would exceed the posted results.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a randomized design and an analyzable randomized comparison. Randomization is an important protection against selection bias, but it cannot produce an effect estimate when outcome data are not analyzed. The registry reports the intended comparison clearly enough to identify the clinical question, yet it also reports zero participants analyzed for the primary outcome.
The record also highlights the role of follow-up in time-framed outcomes. A question about a combined endpoint over 60 months requires outcome observation across the relevant period or a clearly specified approach to incomplete follow-up. The registry states that long-term follow-up evaluation was not possible because of discontinuation of funding. Without the resulting primary-endpoint observations, no incidence estimate or comparison can be interpreted.
For biostatistical interpretation, this distinction prevents a common mistake: treating a missing result as a null result. No reported estimate is not an estimate of no effect. It leaves the treatment contrast unknown in the registry results. Similarly, a design label, a planning assumption, or adverse-event counts cannot stand in for primary-outcome analysis.
The study also shows why results require more than event counts. Definitions, analysis populations, handling of follow-up, and uncertainty measures are necessary to understand how a comparison was produced. Those details are not reported for the primary endpoint. The record's limitations therefore concern both the unavailable outcome data and the lack of analytic detail needed to assess a completed comparison.
Its statistical importance is not a positive or negative efficacy finding. Rather, it is a clear example of how discontinuation and missing long-term outcome assessment can prevent a planned randomized question from yielding an interpretable treatment-effect estimate.
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 consequential limitation is the absence of analyzed primary-outcome data. The registry explicitly reports results for zero participants analyzed, despite recording enrollment of 4. Therefore, no primary-endpoint incidence or treatment comparison is available. Long-term follow-up evaluation was not possible because of discontinuation of funding, according to the registry.
The registry marks the study as terminated but does not report a detailed account of the termination beyond the funding-related limitation on long-term follow-up. It does not describe the timing or completeness of follow-up for individual participants, or whether any partial primary-outcome data were collected. Such details are not reported in the registry record.
Important design and analysis information is also absent. The registry does not report the randomization procedure, allocation concealment, dosing schedule, adherence, endpoint adjudication process, analysis population, missing-data method, or primary-outcome statistical method. It does not provide a primary-outcome effect estimate, confidence interval, or p-value. These omissions prevent assessment of the execution and precision of the intended comparison.
The safety entries are limited to category counts and denominators. Serious-event terms are not listed, death counts are not reported in the registry record, and details such as timing and causal assessment are unavailable. These counts should not be treated as a complete account of harms or as a substitute for long-term outcome evaluation.
Finally, enrollment of 4 and the safety denominators are not interchangeable with the primary-outcome analysis population. The record gives no basis to infer primary outcomes for participants who were not analyzed. Taken together, the limitations leave the intended clinical question unanswered by the posted primary results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Impact of Proteasome Inhibition on Anti-Donor HLA Antibody Production After Kidney Transplantation — NCT01349595.
- Registry record last updated 2015-10-28; status last verified 2015-10.
- Results first posted 2015-09-09.
- 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 describes a randomized, unmasked, parallel-group, phase 2 study of bortezomib versus standard post-transplant treatment in kidney transplant recipients with high levels of donor-specific alloantibodies. Enrollment is recorded as 4, and the status is terminated. The primary endpoint was death-censored graft loss or a >50% reduction in eGFR during the 60 months after enrollment.
The registry reports that zero participants were analyzed for the primary outcome and states that long-term follow-up evaluation was not possible because of discontinuation of funding. No primary-endpoint comparison, effect estimate, confidence interval, or p-value is reported. Safety entries list no serious adverse events in either group and other adverse events in the bortezomib group; death counts are not reported in the registry record. The posted information describes the study and its limitations but does not establish a comparative primary-outcome result.