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 TCR Alpha/Beta Depletion for HSCT From Haploidentical and Unrelated Donors in the Treatment of PID (NCT02327351), a na phase 2, phase 3 study. The primary outcome is Overall Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02327351 |
| Phase | Phase 2, Phase 3 |
| Condition | Primary Immune Deficiency Disorder, Hematopoietic Stem Cell Transplantation |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 98 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Federal Research Institute of Pediatric Hematology, Oncology and Immunology |
| Results posted | Yes |
2. Clinical Question
Population
Pediatric patients with primary immunodeficiency diseases undergoing hematopoietic stem cell transplantation. The registry record lists enrollment of 98.
Intervention
A graft treated with TCR alfa beta T cell depletion, followed by infusion. The record describes the graft as undergoing depletion after leukapheresis.
Comparator
There is no separate comparator group in the registry design. The study is listed as single-group, with allocation recorded as NA.
Primary question
What is the probability of overall survival at 1 year after HSCT among the treated patients? The registry record names this as the primary endpoint but does not report the survival estimate or its 95% confidence interval.
The clinical question concerns outcomes after a transplant using a TCR alfa beta-depleted graft, with haploidentical and unrelated donors identified in the study title. The available design does not describe a randomized comparison between donor types, graft approaches, or another treatment. It therefore addresses the observed outcome in the study group rather than a relative treatment effect against a control group.
The registry also lists transplant-related mortality, acute and chronic graft-versus-host diseases, cellular immunological reconstitution, full donor chimerism, and viral infections after transplant as secondary outcomes. These outcomes add context to the transplant experience, but their definitions and numerical results are not reported in the registry record summarized by the registry entries. The central question remains the one-year survival probability, for which the result itself is not reported in the registry record.
3. Trial Design
The registry identifies this as a phase II/III study with a single-group model. Allocation is recorded as NA, and masking as none. Enrollment is listed as 98. The study status is completed; the recorded start is 2012-07 and primary completion is 2017-12. The sponsor is the Federal Research Institute of Pediatric Hematology, Oncology and Immunology.
The intervention is TCR alfa beta T cell depletion. The arm description states that the leukapheresis product undergoes TCR alfa beta depletion following a standardized protocol and that the depleted graft is infused. The title identifies transplantation from haploidentical and unrelated donors. Donor-specific results, or a comparison between those donor sources, are not reported in the registry record.
A single-group design describes outcomes in the enrolled group but does not, by itself, estimate what would have happened under a different treatment or without the intervention. Because there is no separate control group described, differences in outcomes cannot be attributed to the depletion procedure through a randomized between-group contrast. The record does not report a comparison group or a randomization scheme.
The primary endpoint is overall survival probability at 1 year after HSCT, estimated by the Kaplan-Meier method, with a 95% confidence interval specified as the measure of dispersion. The registry lists secondary outcomes covering transplant-related mortality, graft-versus-host diseases, immune reconstitution, donor chimerism, and viral infections. Although the record notes seven outcome measures and two analyses, further details about how those analyses were conducted are not reported in the registry record.
The protocol’s sample-size justification, statistical analysis plan, interim analyses, and rules for analysis populations are not reported in the registry record. The listed planning framework is an illustration based on an observed effect, not evidence that the study was designed using those assumptions. It should not be mistaken for a description of the study’s actual enrollment plan or for observed power.
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 | TCR Alfa Beta Depletion |
|---|---|
| STARTED | 98 |
| COMPLETED | 98 |
| NOT COMPLETED | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | TCR Alfa Beta Depletion |
|---|---|---|
| Participants analysed | 98 | |
| Age, Categorical: <=18 years | Participants | 98 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 4.2 (SD 2) |
| Sex: Female, Male: Female | Participants | 23 |
| Sex: Female, Male: Male | Participants | 75 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: Russia | participants | 98 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival, measured over 1 year after HSCT.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of survival probability |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is overall survival probability at 1 year after HSCT. Overall survival is a time-to-event outcome: the event is death, and the endpoint asks what proportion of the study group is estimated to remain alive at the specified time after transplantation. The registry specifies the Kaplan-Meier method and a 95% confidence interval.
In general, a time-specific survival estimate can make use of information from participants whose observed follow-up does not extend to the endpoint time. The Kaplan-Meier method accounts for the time each participant is observed and the timing of events; participants whose later status is not known are censored at their last observed time. This interpretation relies on assumptions about censoring, and details about follow-up and censoring in this study are not reported in the registry record.
Survival is often used in transplant studies because it summarizes whether participants are alive over a defined follow-up period. It is a broad endpoint: by itself, it does not describe complications, immune recovery, graft function, or the reasons for deaths. The registry lists several such outcomes separately as secondary measures.
Although the endpoint definition includes a 95% confidence interval, neither the one-year survival estimate nor its interval is reported in the registry record. The endpoint definition therefore identifies what was intended to be measured, but does not establish the observed result or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record specifies a clinically interpretable primary outcome: overall survival probability at 1 year after HSCT. It also identifies the Kaplan-Meier method and a 95% confidence interval. However, it does not report the numerical survival probability or the interval. The primary result and its precision therefore cannot be assessed from the registry information available for this analysis.
This absence matters for interpretation. A survival estimate describes the observed group at a specified follow-up time; its confidence interval communicates uncertainty around that estimate. Without either value, readers cannot determine the level of survival recorded, how precise the estimate was, or whether the study result is compatible with a broad or narrow range of outcomes. The registry’s endpoint definition is not a substitute for the result.
The study is listed as single-group, with allocation recorded as NA. As a result, there is no concurrent control estimate described in the record against which to judge the observed survival. Even if a group-level survival result were available, it would describe outcomes in this study group rather than isolate the effect of TCR alfa beta depletion from other influences on transplant outcomes. The record does not report a randomized comparison or a like-for-like control group.
The safety entries list 17 participants with serious adverse events among 98 at risk, 0 in the other affected category among 98 at risk, and 13 deaths. The registry also lists serious-event terms with percentages. These entries describe recorded events, but do not establish whether an event was caused by the intervention, whether event categories overlap, or how deaths relate to the primary endpoint. Those details are not reported in the registry record.
The secondary outcome list suggests that the study tracked transplant-related mortality, acute and chronic graft-versus-host diseases, immune reconstitution, donor chimerism, and viral infections. Numerical results and detailed definitions for these measures are not reported in the registry record. They cannot fill the gap in the primary survival result or support a comparison of benefit and harm.
Accordingly, the record supports a description of the study question, design, endpoint definition, and selected safety entries. It does not support a conclusion about the observed one-year survival probability, the certainty of that result, or a causal treatment effect. General statistical interpretation must remain separate from outcome claims that the record does not report.
9. Statistical Methods Explained
What does the Kaplan-Meier method estimate?
The registry states that overall survival at 1 year after HSCT was to be estimated by the Kaplan-Meier method. In general, this method estimates the probability of remaining free of the event over time. For overall survival, the event is death. The method uses the observed event times and the time participants remain under observation, rather than treating every participant as if follow-up ended at the same moment.
Some participants may have no recorded event before their last observed contact. In time-to-event analysis, their follow-up is generally censored at that point: their observed time contributes information up to the last known status, while their later event status is unknown. Censoring is not itself an event. The method depends on assumptions about how censoring relates to the outcome. The registry record does not report follow-up completeness, censoring details, or checks of these assumptions for this study.
What does the confidence interval add?
The specified 95% confidence interval expresses statistical uncertainty around the estimated survival probability. In general, an interval reflects how much the estimate might vary because the study observes a finite group rather than every person from a broader population of interest. A narrower interval indicates greater precision under the method’s assumptions; a wider interval indicates less precision. It does not describe the range of individual outcomes, and it does not remove limitations from the study design or data collection.
The registry names a 95% confidence interval but does not report its endpoints or the underlying survival estimate. Thus, the level of uncertainty cannot be evaluated from the available record. The stated confidence level alone does not indicate whether the estimate is precise.
Why does the single-group design matter?
A single-group analysis can describe outcomes observed among participants receiving the specified intervention. It does not create a counterfactual comparison: there is no observed control group in the registry design to show outcomes under an alternative approach in otherwise comparable participants. General statistical adjustment cannot recover the protection of random allocation if no appropriate comparison data exist. The record does not report a comparator or randomized treatment allocation.
Consequently, a group outcome would be descriptive rather than a direct estimate of the causal effect of graft depletion. The design also does not support a direct comparison between haploidentical and unrelated donors unless results and a suitable analysis by donor source are reported. Such donor-specific results are not reported in the registry record.
What can be learned from the planning assumptions?
The planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It uses the stated fraction of the observed effect as the effect to detect. These are assumptions for a planning calculation, not a statement of the trial’s own design: the registry describes a single-group study. The illustrations should not be interpreted as observed power. Sample-size calculations used for planning do not show that an effect was detected, and they do not supply the missing survival estimate.
The registry does not report the protocol’s sample-size justification or a statistical analysis plan. It is therefore not possible to determine from the record whether the planning illustration matches any decisions made before enrollment, or how the primary analysis was specified beyond the endpoint and method named in the registry.
How should event counts be interpreted?
Event counts and percentages can describe recorded safety outcomes, but their meaning depends on how events were defined, collected, and attributed. Participants can experience more than one event, and a participant may appear in more than one event category. Without rules for counting and grouping events, counts should not be treated as independent observations or added together. The registry record does not report the relevant definitions, attribution rules, or whether categories overlap.
For time-to-event outcomes, event counts alone also do not reproduce a Kaplan-Meier estimate. That estimate depends on event timing and how long participants were observed. The recorded death count therefore cannot be converted into the one-year survival probability from the information. The one-year survival estimate and confidence interval remain not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes in addition to overall survival: transplant-related mortality, acute graft-versus-host diseases, chronic graft-versus-host diseases, cellular immunological reconstitution, full donor chimerism, and viral infections after transplant. It records seven outcome measures and two analyses. The definitions, analysis methods, and results for the listed secondary measures are not reported in the registry record available for this analysis.
When a study examines multiple outcomes or performs multiple statistical tests, the chance of at least one apparently notable result can increase. A prespecified multiplicity strategy can address that issue, for example by controlling the overall error rate or identifying which outcomes are confirmatory and which are exploratory. Whether any such strategy was used is not reported in the registry record. No adjustment should be assumed.
The registry record does not report how missing outcome data were handled, how follow-up ended, or whether participants were excluded from particular analyses. It also does not describe an intention-to-treat or other analysis population. These details are important for understanding who contributed to each estimate and whether missing status could affect interpretation. They should not be inferred from the enrollment entry or the at-risk figures.
The primary endpoint definition names a Kaplan-Meier estimate and a 95% confidence interval, but the estimate, interval, and analysis details are not reported in the registry record. The record also does not report an interim-analysis plan or stopping rules. Without these details, readers cannot evaluate the prespecification of outcome analyses, the handling of missing data, or the extent to which reported analyses may have been selected after results were known.
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 |
|---|---|---|---|
| TCR Alfa Beta Depletion | 17 | 98 | 17.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| TCR Alfa Beta Depletion | 13 of 98 |
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 |
|---|---|
| TCR Alfa Beta Depletion | 0 of 98 |
Most frequent serious adverse event terms
| Event term | Organ system | TCR Alfa Beta Depletion |
|---|---|---|
| Bacterial sepsis | Blood and lymphatic system disorders | 7 of 98 |
| CMV pneumonia | Respiratory, thoracic and mediastinal disorders | 6 of 98 |
| ADV hepatitis | Hepatobiliary disorders | 2 of 98 |
| TMA | Renal and urinary disorders | 2 of 98 |
Serious events with the highest arm-level rate: bacterial sepsis (7.1%), cmv pneumonia (6.1%), adv hepatitis (2.0%), tma (2.0%).
The registry lists 17 participants with serious adverse events among 98 at risk. It lists 0 in the other affected category among 98 at risk, and 13 deaths. These are separate entries in the record; they should not be treated as mutually exclusive categories or combined. The relationship between the death entry and the adverse-event categories is not reported in the registry record.
The listed serious-event terms and percentages are bacterial sepsis, 7.1%; CMV pneumonia, 6.1%; ADV hepatitis, 2.0%; and TMA, 2.0%. The record does not report the denominator used for these term-specific percentages, whether participants could contribute to more than one term, or whether the events were considered related to the intervention. The percentages therefore should be read as registry entries, not recalculated rates or evidence of causation.
Adverse-event counts describe events recorded under the study’s reporting approach. Their clinical and statistical interpretation depends on definitions, observation time, severity criteria, and attribution rules. Those details are not reported in the registry record. The entries do not by themselves compare safety with another treatment, and they do not establish that the intervention caused or prevented any event.
12. What the Result Does, and Does Not, Mean
The registry record establishes the study’s focus: TCR alfa beta-depleted grafts for HSCT in pediatric patients with primary immunodeficiency diseases. It defines overall survival at 1 year after HSCT as the primary endpoint and names the Kaplan-Meier method with a 95% confidence interval. It also records selected safety entries and a range of secondary outcomes.
It does not report the numerical primary endpoint result or its confidence interval. Without those values, the observed survival probability and its precision cannot be judged. A defined endpoint is not itself evidence of an outcome, and a method named in the record does not supply a result that is absent.
The single-group design also limits what the study can establish statistically. Outcomes in the treated group, even if fully reported, would not provide a randomized estimate of the difference between graft depletion and another approach. The record does not describe a comparator, and the donor sources named in the title are not presented as comparative arms. Thus, the record does not support a causal claim about the intervention or a donor-source comparison.
The adverse-event entries provide some information about recorded safety events, but event attribution, overlap, follow-up, and term-specific denominators are not reported in the registry record. The entries should not be interpreted as a complete accounting of risk or as a comparison with another treatment.
Overall, the available information is useful for understanding the study question, design, and intended endpoint. It does not establish the one-year survival result, its statistical precision, or the effect of the intervention relative to an alternative. The secondary outcome results and key analysis details are also not reported in the registry record.
13. Why This Trial Matters Statistically
This study raises a difficult statistical question in a population undergoing HSCT for primary immunodeficiency diseases: how should outcomes after a complex transplant approach be described when the registry records a single-group design? The design can characterize outcomes among treated participants, but it cannot by itself distinguish the intervention’s contribution from other influences on those outcomes. Recognizing that distinction is essential when interpreting survival or safety data.
The primary endpoint is time-to-event rather than a simple count at a single visit. The registry’s use of Kaplan-Meier estimation and a confidence interval reflects the need to account for event timing and follow-up. For readers, this makes the absence of the numerical estimate particularly important: without the estimate and its interval, neither the observed survival level nor its precision can be evaluated.
The record also illustrates why safety entries require careful reading. Counts and event-term percentages are not automatically comparable rates, and they do not establish causation. Definitions, denominators, overlap, follow-up, and attribution influence their meaning. Those details are not reported in the registry record.
Finally, the planning illustration should be separated from the study design and observed results. Its assumptions describe a planning calculation based on an observed effect; they do not turn a single-group study into a two-arm comparison and do not represent observed power. Keeping design, planning, endpoint definition, and reported outcomes distinct helps prevent stronger conclusions than the record can support.
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 of the available registry information is that it does not report the primary endpoint result. Although overall survival at 1 year after HSCT is defined and a 95% confidence interval is specified, neither the estimate nor the interval is reported in the registry record. The primary outcome’s magnitude and precision therefore cannot be evaluated.
The listed single-group design has no separate comparator. It can describe outcomes in the study group but cannot, on its own, estimate a causal contrast against an alternative treatment. The title refers to haploidentical and unrelated donors, but donor-specific outcomes and comparisons are not reported in the registry record.
Further limitations concern interpretability of follow-up and safety information. Details of censoring, follow-up completeness, missing outcome data, adverse-event definitions, attribution, overlap, and term-specific denominators are not reported in the registry record. The recorded deaths cannot be used to reconstruct the Kaplan-Meier estimate without event timing and follow-up information.
The record names several secondary outcomes, but their numerical results and detailed analysis methods are not reported. It also does not report the protocol’s statistical analysis plan, sample-size justification, analysis populations, multiplicity strategy, interim analyses, or stopping rules. These omissions limit assessment of prespecification and the way available data were analyzed.
The safety entries should therefore be interpreted narrowly as registry-recorded counts and percentages. They do not establish completeness of safety ascertainment, causal attribution, or comparative safety. The planning illustration is not a substitute for the trial’s design rationale or observed results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: TCR Alpha/Beta Depletion for HSCT From Haploidentical and Unrelated Donors in the Treatment of PID — NCT02327351.
- Registry record last updated 2021-02-26; status last verified 2021-02.
- Results first posted 2021-02-26.
- 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
NCT02327351 is a completed phase II/III, single-group study of TCR alfa beta-depleted grafts for HSCT in pediatric patients with primary immunodeficiency diseases. The registry lists enrollment of 98, allocation as NA, and masking as none. The recorded start is 2012-07 and primary completion is 2017-12. The sponsor is the Federal Research Institute of Pediatric Hematology, Oncology and Immunology.
The primary endpoint is overall survival probability at 1 year after HSCT, estimated by Kaplan-Meier with a 95% confidence interval. The numerical estimate and interval are not reported in the registry record. Secondary outcomes include transplant-related mortality, graft-versus-host diseases, immune reconstitution, full donor chimerism, and viral infections.
The safety entries list 17 participants with serious adverse events among 98 at risk, 0 in the other affected category among 98 at risk, and 13 deaths. Serious-event terms are listed with percentages, but further details needed to interpret attribution, overlap, and denominators are not reported in the registry record. The single-group design does not provide a randomized comparator.