Immunophenotyping of Peripheral T Cells After T Cell Depletion With Alemtuzumab: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunophenotyping of Peripheral T Cells After T Cell Depletion With Alemtuzumab (NCT01213329), a na phase 4 study. The primary outcome is The Effect of T Cell Depletion on Phenotypic & Functional Profiles of Peripheral Blood Mononuclear Cells in Steroid-free Kidney Transplant Recipients..

2. Clinical Question

The clinical question is biological and descriptive: the study aimed to characterize peripheral immune cells following alemtuzumab, rather than report a treatment comparison on a clinical outcome. The primary outcome description lists circulating CD4 and CD8 positive T cells, B cells, natural killer cells, naive and memory cells, activated T cells, and regulatory cells. It also identifies the intended population as steroid-free kidney transplant recipients.

The record's summary says the study was intended to check T and B cells in newly transplanted patients and examine how standard-of-care anti-rejection medication affects those cells. That rationale does not establish what the measurements showed. Because the blood samples were lost and no analysis was performed, the record cannot answer whether the measured cell profiles changed, by how much they may have changed, or how precisely any change could be estimated.

3. Trial Design

This is a Phase 4, single-group study of alemtuzumab in kidney transplant recipients. The registry lists allocation as not applicable and masking as none. The Phase I arm description states that each kidney transplant recipient received one 30mg dose by intravenous push in the operating room, per standard of care. The record does not describe a randomized treatment assignment or a masked assessment.

The planned primary outcome was assessment of peripheral blood leukocytes before transplant and at 6 months and 12 months after transplant. The listed measures include absolute counts of CD4 and CD8 positive T cells, B cells and natural killer cells, together with naive and memory, activated, and regulatory cell populations. Although the primary outcome title includes functional profiles, the registry description does not specify the functional assays in detail.

The record lists enrollment as 52. Separately, the brief summary describes 50 recipients and 50 donors as anticipated participants, while the primary outcome population description says samples from 26 recipient/donor pairs were collected, for 52 collected samples. These entries refer to different record statements; they should not be treated as interchangeable measures of analyzed participants. The record says no analysis was performed because samples were lost after a liquid nitrogen tank malfunction during a power loss.

The study status is terminated. The registry record gives a start of 2006-02 and primary completion of 2009-04. It does not report the reason for termination beyond the stated sample loss, nor does it provide a detailed statistical analysis plan, sample-size justification, or planned interim analysis. The donor comparison group listed in the adverse-event information does not turn this single-group study into a randomized treatment comparison.

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: The first year of the study was specimen collection only. Group assignment (phase 2) was intended to begin after 12months of sample collection and there were not any subjects who continued into phase 2. An additional pair enrolled compared to the number that started this study. This is due to a loss of samples from a processing inconsistency

Screening

Phase 2

Analysis population for the primary outcome, as defined in the registry: samples from 26 recipient/donor pairs were collected = 52 collected but no analysis was performed because samples were lost.

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 The Effect of T Cell Depletion on Phenotypic & Functional Profiles of Peripheral Blood Mononuclear Cells in Steroid-free Kidney Transplant Recipients., measured over Pre-transplant, 6months & 12 months post-transplant.

The primary outcome concerns phenotypic and functional profiles of peripheral blood immune cells in steroid-free kidney transplant recipients after T-cell depletion. Blood was planned for collection before transplant and at 6 months and 12 months after transplant. The listed cell measures include absolute counts of CD4 and CD8 positive T cells, B cells and natural killer cells, and characterization of naive and memory cells, activated T cells, and regulatory cells.

These measurements are used to describe which immune-cell populations are present and how their profiles may vary over time. Such measurements address a biological question about the immune system after alemtuzumab; they are not themselves a direct measure of graft survival, rejection, or another clinical benefit. The registry record does not specify the functional assays in detail, despite the outcome title's reference to functional profiles.

No endpoint estimates are reported. The outcome description states that blood samples were lost because a liquid nitrogen tank stopped working during a power loss, and that no analysis was performed. Consequently, the record provides no cell counts, changes over time, uncertainty estimates, or test results for this primary outcome. The planned timing and the list of cell types define what the study intended to measure, but they do not establish what the measurements would have shown.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the study as single-group, with allocation not applicable and masking none. These labels describe the broad design: it was not a randomized, masked comparison of assigned treatments. The Alemtuzumab (Phase I) arm description says recipients received one 30mg dose in the operating room per standard of care. A donor comparison group appears in the adverse-event information, but the record does not present it as a randomized treatment control.

What does a single-group design allow?

In general, a single-group design can describe measurements collected from participants over time. If measurements are available before and after an intervention, the observed pattern can be reported, but a change alone does not establish that the intervention caused it. Other factors that vary with time may also contribute. A randomized comparison can help distinguish treatment effects from such influences by comparing groups assigned to different approaches. That design is not described in this registry record.

The primary outcome was intended to characterize peripheral blood immune cells before transplant and at 6 months and 12 months after transplant. It includes counts and categories of T cells, B cells, natural killer cells, naive and memory cells, activated T cells, and regulatory cells. The outcome title also mentions functional profiles, but the registry description does not specify the functional measurements or a method for summarizing them.

What would estimates and uncertainty describe?

In general, an estimate summarizes the measured value or change in the study sample, while a confidence interval describes the uncertainty around an estimate under the assumptions of the analysis. A narrow interval generally indicates greater precision than a wide interval, but neither precision nor a confidence interval establishes that an association is causal. Here, the record reports no primary outcome analysis, so it provides no estimate or confidence interval for the immune-cell measurements. No primary outcome test statistic or p-value is reported either.

The registry reports that samples from 26 recipient/donor pairs were collected, corresponding to 52 collected samples, but no analysis was performed because the samples were lost. Collection is not equivalent to having usable outcome observations. It is therefore not possible to infer from the collection statement how many measurements would have been available at each planned timepoint or what the distribution of any cell measure would have been.

What role does over-dispersion play?

In general, over-dispersion means that observed variability is greater than a statistical model assumes. When it is present, standard errors can be too small if the model does not account for the extra variability, making results appear more precise than they are. This is a general consideration for count outcomes and other variable measurements, not a reported feature of this study. The registry record does not describe a model, distributional assumption, over-dispersion assessment, or variance adjustment for the primary outcome. With no analysis, there is no basis for assessing whether over-dispersion occurred.

How should the planning illustration be read?

The registry's sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. This is a planning exercise, not the trial's original design rationale and not observed power. The record does not report the original sample-size justification.

There is an important distinction between a planning illustration and the trial as registered. The registered study is single-group, while the illustration assumes equal allocation between two arms. Also, the primary outcome was not analyzed and no observed primary outcome effect is reported. Thus, the illustration's assumptions should not be mistaken for an analysis of this study's immune-cell data, a prospectively specified design, or evidence that the study had a particular probability of detecting an effect.

The record reports zero analyses. It does not state which statistical tests or models were planned, how repeated measurements would have been handled, how missing values would have been handled in an analysis, or whether adjustment for multiple comparisons was intended. Those methodological details are not reported in the registry record and cannot be inferred from the outcome list alone.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome encompasses multiple immune-cell populations and planned assessments before transplant and at 6 months and 12 months afterward. In general, testing many outcomes or timepoints can increase the chance of finding an apparently notable result by chance. An analysis plan may address this with a prespecified primary contrast, adjustment procedures, or a descriptive approach. The registry record does not report a multiplicity strategy or identify a single cell measure as the sole statistical contrast.

Multiplicity is not the main barrier to interpretation in this record: no primary analysis was performed. The stated reason is that blood samples were lost after a liquid nitrogen tank malfunction during a power loss. There are no reported cell measurements, missing-data methods, or sensitivity analyses. The record does not say whether any partial measurements were available or how each planned timepoint was affected beyond the statement that the samples were lost.

The outcome population description reports collection from 26 recipient/donor pairs, with 52 collected samples, and explicitly says no analysis was performed. The brief summary separately describes 50 recipients and 50 donors as anticipated. Registry enrollment is listed as 52. These statements should remain distinct: the record does not indicate that the anticipated enrollment, registry enrollment, and collected-sample description all refer to the same analysis population.

The registry does not report a primary analysis population definition, exclusions, or an approach to missing outcomes. It therefore does not establish an intention-to-treat or per-protocol analysis population for the primary endpoint. The sample-loss statement explains why results are absent, but it does not provide enough detail to evaluate whether the loss could have affected some participants or timepoints differently.

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 00% reporting threshold.

The adverse-event information lists the Alemtuzumab (Phase I) group and a Donor Comparison group. For serious adverse events, the record reports zero among 26 at risk in the Alemtuzumab group and zero among 25 at risk in the Donor Comparison group. For other adverse events, it also reports zero among 26 at risk and zero among 25 at risk, respectively.

These are recorded counts for the groups and categories as entered in the registry. Zero reported events does not establish that the underlying risk was zero. Interpretation depends on how events were defined, collected, and followed; those details and the safety follow-up period are not reported in the registry record. The listed at-risk counts also should not be treated as the number contributing primary immune-cell outcome data, because the outcome samples were lost and no analysis was performed.

Death counts are not reported in the registry record. The safety entries do not provide enough information to compare risks between groups, and the donor group is not described as a randomized, like-for-like treatment control. These counts should therefore be read as limited registry safety reporting, not as a controlled estimate of treatment-related risk.

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

The record documents a planned study of peripheral immune-cell profiles after alemtuzumab in kidney transplant recipients, including measurements intended before transplant and at 6 months and 12 months afterward. It also documents that blood samples were lost after a liquid nitrogen tank malfunction during a power loss and that no analysis was performed. Those are the main details needed to interpret the posted results: the biological question was specified, but the intended measurements did not yield analyzable primary outcome findings in the registry record.

Accordingly, no change in CD4 or CD8 positive T cells, B cells, natural killer cells, naive or memory cells, activated T cells, or regulatory cells can be estimated from the posted results. The absence of estimates does not show that the cell populations did not change. Nor can the record establish that alemtuzumab caused a change in any cell population. It reports no primary outcome effect size, confidence interval, or inferential test.

The study's single-group classification and lack of masking also matter. A before-and-after pattern, if it had been observed, would be descriptive and would not by itself isolate the effect of alemtuzumab from other changes over time. The donor comparison entries are not described as a randomized treatment comparison. The registry record does not report enough information to support a causal comparison based on those groups.

The zero adverse-event counts are limited to the categories and at-risk groups entered in the record. They do not establish absence of risk, and details of ascertainment and follow-up are not reported. The safety entries do not make up for the lack of analyzed primary outcome data.

The study's status is terminated. The record gives enrollment as 52, while the brief summary describes anticipated participation of 50 recipients and 50 donors, and the outcome description reports collection from 26 recipient/donor pairs. These figures describe registry and study-record statements, not an analyzed sample for the primary endpoint. Overall, the record supports a description of the study's aims, design, sample loss, and limited safety counts, but not a conclusion about measured immune-cell changes or a treatment effect.

13. Why This Trial Matters Statistically

This study illustrates why a clearly stated biological question and a planned measurement schedule do not guarantee an interpretable outcome. The registry describes which immune-cell populations were intended for assessment and when blood was to be collected. But because the samples were lost and no analysis was performed, the planned measurements produced no reported estimates. Statistical interpretation depends on usable data as well as on a defined outcome.

It also highlights the distinction between descriptive follow-up and a controlled treatment comparison. The study is classified as single-group, with allocation not applicable and masking none. Repeated measurements can characterize patterns over time, but without a randomized comparison those patterns do not by themselves separate treatment effects from other changes. The donor comparison information in the safety entries does not change the registered design classification.

The record further shows why counts at different stages must be kept conceptually separate. It lists enrollment as 52, describes anticipated participation of 50 recipients and 50 donors, and reports collection from 26 recipient/donor pairs. The latter statement is accompanied by an explicit note that no analysis was performed. Collected samples therefore cannot be treated as analyzed outcomes.

Finally, a sample-size planning illustration is not evidence of the original design rationale or of observed power. This distinction is especially important when the primary outcome has no reported analysis. The record does not provide an observed primary effect, and it does not report the original sample-size justification or detailed statistical plan. These limitations make it essential to separate what the study intended to learn from what the registry record can actually establish.

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 loss of the blood samples: the registry states that a liquid nitrogen tank malfunctioned during a power loss and that no primary outcome analysis was performed. There are consequently no reported values for the planned immune-cell outcomes and no estimates of their changes over time. The record does not report whether any samples or timepoints remained usable.

The endpoint description lists a broad set of cell types and phenotypes, but it does not specify the functional assays in detail, despite the outcome title's reference to functional profiles. The registry record also does not describe the statistical tests, models, repeated-measures approach, missing-data method, or multiplicity strategy that would have been used.

The design is single-group, allocation is listed as not applicable, and masking is none. The donor comparison information appears in the safety entries and is not described as a randomized, like-for-like treatment control. This limits any causal interpretation even apart from the loss of the primary outcome data.

The record contains distinct statements about enrollment, anticipated recipients and donors, and collected recipient/donor pairs. It does not explain their relationship in detail or identify an analyzed population; indeed, it states that no analysis was performed. The status is terminated, but the registry record does not report a termination reason beyond the stated sample loss. Safety follow-up details and death counts are also not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunophenotyping of Peripheral T Cells After T Cell Depletion With Alemtuzumab — NCT01213329.
• Registry record last updated 2019-04-10; status last verified 2019-03.
• Results first posted 2011-07-04.
• 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 describes a Phase 4, single-group study of alemtuzumab in kidney transplant recipients, with no masking and allocation listed as not applicable. The Phase I arm description states that recipients received one 30mg dose by intravenous push in the operating room per standard of care. The primary outcome was intended to assess peripheral blood immune-cell profiles before transplant and at 6 months and 12 months afterward.

The record states that samples from 26 recipient/donor pairs were collected, but no analysis was performed because samples were lost following a liquid nitrogen tank malfunction during a power loss. No primary outcome estimates are reported. The study status is terminated; the registry lists enrollment as 52, a start of 2006-02, and primary completion of 2009-04.

The safety entries report zero serious and other adverse events in the listed groups. Death counts are not reported in the registry record. The record does not provide a detailed statistical analysis plan or the original sample-size justification.