Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa (NCT00478244), a na na study. The primary outcome is Number of Patients With Detectable Collagen Type VII.

2. Clinical Question

The study rationale states that stem cells had been observed to home to skin and repair biochemical and structural abnormalities in animal models of RDEB. That background motivates the question but is not a result from this clinical study. The registry describes the purpose as determining the safety and effectiveness of stem cell infusion in RDEB; the reported design and missing endpoint result limit what can be concluded from this record.

3. Trial Design

The registry describes an open-label, single-group study of allogeneic hematopoietic cell transplantation for epidermolysis bullosa. Allocation is listed as NA, masking as NONE, and phase as NA. Because there is no reported randomized allocation or separate comparison group, the design does not support a direct comparison of treatment outcomes against an untreated or alternative-treatment group.

The listed group, “Epidermolysis Bullosa (EB) Patients,” received chemotherapy and stem cell transplant according to the study regimen. The listed drugs were busulfan, cyclophosphamide, and fludarabine phosphate, alongside hematopoietic bone marrow transplantation. Further details about the regimen, donor selection, eligibility criteria, or treatment delivery are not reported in the registry record.

Enrollment was 7. The study start is recorded as 2007-04 and primary completion as 2011-08. Its status is TERMINATED. The reason for termination and whether termination affected planned follow-up or outcome collection are not reported in the registry record. The registry lists the primary endpoint at Day 100 Post Transplant and includes secondary outcomes concerning donor chimerism, transplant-related mortality, engraftment, graft-versus-host disease, survival, donor-derived cells in skin, and resistance to blister formation.

The registry does not report a detailed statistical analysis plan, an intended analysis population, or a sample-size justification for the trial itself. Consequently, the design can be described from its registered features, but not supplemented with assumptions about how participants were to be analyzed or why enrollment was set at this level.

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: All subjects were registered with the BMT Biostatistical Support Group at the University of Minnesota.

Overall Study

Reasons for not completing this period:

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 Patients With Detectable Collagen Type VII, measured over Day 100 Post Transplant.

The primary endpoint is the number of participants with detectable collagen type VII at Day 100 Post Transplant. It is a participant count, rather than a continuous measurement of collagen concentration or a time-to-event outcome. The record does not specify a laboratory method, tissue collection procedure, threshold for detectability, or handling of samples that could not be assessed. Those details are not reported in the registry record.

The endpoint is biologically connected to the condition described in the registry: collagen type VII defects cause RDEB, which is characterized as a blistering skin disorder and is often accompanied by epidermal cancers. The study rationale proposes that donor stem cells might reach skin and help address biochemical and structural abnormalities. Detectable collagen type VII is therefore an indicator related to the proposed biological pathway. It should not be treated as equivalent to a measure of symptoms, skin integrity, cancer outcomes, or overall clinical benefit.

The registry’s endpoint description identifies the count to be assessed but does not provide the count observed at Day 100. The result, uncertainty around it, and the number of participants assessed for this endpoint are not reported in the registry record. Without those data, the endpoint’s observed frequency and precision cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is recorded as a participant count. In general, a count endpoint records how many people meet a defined outcome rather than measuring the outcome on a continuous scale. Here, the outcome is detectable collagen type VII at Day 100 Post Transplant. Although the registry specifies the endpoint and time point, it does not report the observed count, the number assessed, or the operational definition of “detectable.” A reader therefore cannot reconstruct the endpoint estimate from the registry record.

What does a count estimate mean?

For a binary outcome, each participant is classified according to whether the event or condition is present. A count can describe the number meeting the outcome in the group studied. A proportion would additionally relate that count to the number assessed, but the primary endpoint’s numerator and assessment denominator are not reported. No such proportion can be stated from this record. In general, uncertainty around a binary outcome can be substantial when the group is small; the registry’s enrollment of 7 makes the absence of an estimate and interval especially consequential for interpretation. This is a general statistical consideration, not a result calculated for this study.

A confidence interval, in general, describes a range of values compatible with the data and a specified method. It helps communicate estimation uncertainty and is not a guarantee that the true value lies within a particular range. The registry record does not report a confidence interval for the collagen endpoint. With no endpoint estimate or interval, precision cannot be assessed from the posted results.

Why does the single-group design matter?

The study is identified as SINGLE GROUP, with allocation listed as NA and masking as NONE. In general, a single-group design can describe what happened among participants receiving the regimen, but it does not directly estimate a contrast with a control group. Without a concurrent comparator, differences between outcomes over time or relative to expectations may reflect factors other than the intervention. This is a design limitation, not evidence for or against a treatment effect.

Masking is listed as NONE. In general, lack of masking can affect outcomes that depend on judgment or reporting, while laboratory-based measurements may have different susceptibility to observer expectations depending on how they are collected and assessed. The registry does not report whether collagen testing or outcome assessment was blinded, so the potential influence of assessment procedures cannot be determined.

What can be inferred from the planning assumptions?

The planning illustrations are described as hypothetical calculations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For non-time-to-event outcomes, they are expressed as participants per arm; time-to-event illustrations are described in terms of total events. These are planning illustrations, not evidence that the trial enrolled two groups or was designed using those assumptions. The actual registry design is single-group. The calculations are not observed power, and the registry does not report the trial’s own sample-size justification.

In general, planning calculations ask how much information might be needed to detect a chosen effect under stated assumptions. They depend on the effect used, the outcome’s variability or event rate, the analysis method, and the design. A planning illustration based on a fraction of an observed effect explores hypothetical targets; it does not demonstrate that an effect exists, that the study was adequately powered, or that the trial’s data support the assumed effect. The registry record does not report the primary endpoint effect needed to assess those calculations in context.

How should event rates and dispersion be understood?

For a binary outcome, the basic observed information is the event count and the number of participants assessed. General methods may model such outcomes using a binomial distribution. Over-dispersion is a general concern when observed variability exceeds what a chosen model assumes; it can make standard errors too small if ignored. The registry record does not report a model, a dispersion assessment, or an analysis for the primary endpoint. It would therefore be inappropriate to claim that a particular model or correction was used.

Time-to-event outcomes, such as overall survival, require information about event timing and censoring as well as event status. The registry lists Overall Survival as a secondary outcome but does not report its analysis or result in the registry record recorded. General methods for time-to-event data account for varying follow-up and censoring; no method or follow-up details are reported in the registry record. These concepts should not be mistaken for analyses documented for this study.

Finally, an analysis result requires more than an endpoint definition: it depends on collected observations, participant inclusion rules, missing-data handling, and a prespecified or otherwise documented statistical method. The registry reports none of these details for the primary endpoint, and lists zero analyses. The methods that were actually used to analyze the endpoint are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Evaluable Patients")
n      <- c(6)
events <- c(5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Evaluable Patients  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary outcomes covering donor chimerism, transplant-related mortality, platelet engraftment, acute and chronic graft-versus-host disease, overall survival, donor-derived cells in skin, and resistance to blister formation. It reports 10 outcome measures and zero analyses. The record does not identify which secondary outcomes were analyzed or give results for them in the information available.

When multiple outcomes are assessed, general statistical practice considers whether repeated testing raises the chance of finding an apparently noteworthy result by chance. A prespecified hierarchy, adjustment method, or explanation of how multiple outcomes were handled would help readers understand the evidential status of any findings. No multiplicity strategy is reported in the registry record. Because no analyses are reported, there are no posted statistical tests to interpret as primary or secondary evidence.

Missing-data methods are not reported. The record does not state how participants without an endpoint measurement, incomplete follow-up, or unevaluable samples were handled. It also does not report an analysis population, such as whether the primary endpoint was intended to include all enrolled participants or only those with an available measurement. Enrollment of 7 does not establish how many contributed data to the Day 100 endpoint.

These omissions prevent assessment of the impact of missing outcome data, exclusions, or analytical choices. They do not prove that data were missing or that any particular method was used; those details are simply not reported in the registry record.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: bacterial infection (85.7%), hyperbilirubinemia (57.1%), fungal infection (28.6%), renal insufficiency (28.6%), acute respiratory distress syndrome (14.3%).

For the group “Epidermolysis Bullosa (EB) Patients,” the registry reports 7 participants at risk for serious adverse events and 6 affected. It reports 7 participants at risk for other adverse events and 0 affected. These are the posted group-level figures; they should not be treated as a comparison between treatments because the study has no reported control group.

The serious-event terms with the highest listed percentages are bacterial infection at 85.7%, hyperbilirubinemia at 57.1%, fungal infection at 28.6%, renal insufficiency at 28.6%, acute respiratory distress syndrome at 14.3%, and Death at 14.3%. The registry also identifies transplant-related mortality, acute and chronic graft-versus-host disease, and other outcomes as secondary measures, but does not report their results in the record.

Serious adverse events are event categories, and a participant may have more than one event. Their percentages should not be added to obtain a total or interpreted as mutually exclusive categories. The death field is null, while Death appears among the serious-event terms; a separate death count is therefore not reported in the registry record. These listings describe reported safety information but do not establish causation or provide a comparison with background risk.

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

The registry record establishes that a single-group study of allogeneic hematopoietic cell transplantation for epidermolysis bullosa was registered, enrolled 7 participants, and was marked TERMINATED. It specifies a primary endpoint: the number of participants with detectable collagen type VII at Day 100 Post Transplant. It also records serious adverse-event information for the study group.

The record does not report the primary endpoint result or an analysis. It therefore cannot show from the posted results how many participants had detectable collagen type VII, how uncertain an estimate would be, or whether the endpoint differed from any comparator. The registry’s rationale links collagen type VII to RDEB and describes a biological hypothesis involving stem cells and skin. That rationale is not a clinical outcome result.

Nor does the record establish that transplantation caused any listed event or outcome. A single-group study has no concurrent comparison group in the registry entry, so outcomes cannot be contrasted with what would have occurred under another treatment or without treatment. The serious adverse-event listings are important descriptions of events reported in the treated group, but they are not a comparative risk estimate.

In general, statistical significance, clinical importance, and precision are distinct considerations. A result may be estimated imprecisely even when a test is reported, and the size or relevance of an effect cannot be determined from a test alone. In this case, the primary result and its uncertainty are not reported, so those questions cannot be assessed from the registry record. The appropriate conclusion is limited to what the entry documents: a registered study, its design and endpoint, and the listed safety events. The record does not support a conclusion about treatment effectiveness.

14. Why This Trial Matters Statistically

This study raises a statistically important distinction between a biologically motivated endpoint and an interpretable clinical estimate. Detectable collagen type VII is connected to the condition’s described biochemical defect, and the endpoint is specified at Day 100 Post Transplant. Yet the registry does not report the observed endpoint count or its uncertainty. A clearly stated endpoint is not, by itself, evidence about the outcome.

The single-group design also matters. It can organize observations among participants receiving a regimen, but it cannot provide the same comparative evidence as a randomized control group. This distinction is especially important when a study purpose includes safety and effectiveness: descriptions of events and biological measurements do not establish what would have happened under another strategy.

The record further illustrates why registry completeness is part of statistical interpretation. Without posted analyses, analysis populations, missing-data methods, or a multiplicity plan, readers cannot determine how the listed outcomes were evaluated. The status TERMINATED and the serious-event information add context, but the reason for termination and the primary endpoint result are not reported in the registry record.

For biostatistical readers, the key lesson is to separate the scientific rationale, the design, the observed results, and the uncertainty attached to those results. Here, the rationale and endpoint are described, while the primary result and analysis are absent. That distinction prevents a mechanistic hypothesis or a planning illustration from being mistaken for a clinical finding.

15. 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 direct limitation of the registry entry is that it does not report the primary endpoint result, despite specifying the endpoint and its assessment time. The registry reports zero analyses. The number of participants assessed for detectable collagen type VII, the endpoint estimate, and any uncertainty interval are not reported in the registry record.

The study is single-group, with allocation listed as NA and masking listed as NONE. There is no reported control group for a comparative estimate. Enrollment was 7, so the study record concerns a limited group, but the endpoint-specific denominator and participant characteristics are not reported. No inference about representativeness or generalizability can be made from enrollment alone.

The registry marks the study TERMINATED but does not give the reason. It does not report whether the planned endpoint collection was completed, whether follow-up differed across participants, or how incomplete measurements were handled. The protocol details, including assay method and detectability threshold for collagen type VII, are also not reported in the registry record.

The adverse-event information lists serious events and percentages, but the record does not provide event-level timing, attribution, or a separate death count. The death field is null. These limitations restrict interpretation of both safety and endpoint findings and cannot be resolved by treating the stated purpose or biological rationale as evidence of an observed effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa — NCT00478244.
• Registry record last updated 2017-12-28; status last verified 2017-12.
• Results first posted 2013-02-11.
• 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.

19. Record Summary

NCT00478244 is a registered study titled “Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa.” It is described as a single-group, open-label study with phase listed as NA. Enrollment was 7, and status is TERMINATED. The registry records the study start as 2007-04 and primary completion as 2011-08.

The regimen included busulfan, cyclophosphamide, fludarabine phosphate, and hematopoietic bone marrow transplantation. The primary endpoint was the number of participants with detectable collagen type VII at Day 100 Post Transplant. Its result and an analysis are not reported in the registry record.

The registry reports serious adverse events for the study group, including 6 of 7 affected participants, and lists event terms with percentages. It reports zero analyses. The reason for termination, detailed analysis methods, missing-data handling, and the primary endpoint findings are not reported in the registry record.