HSCT for High Risk Inherited Inborn Errors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for HSCT for High Risk Inherited Inborn Errors (NCT00383448), a na phase 2 study. The primary outcome is Number of Patients With Donor Cell Engraftment.

2. Clinical Question

3. Trial Design

This was a phase 2, single-group trial, listed as completed. The registry gives enrollment as 38 and describes one group, “Treated Patients.” Allocation is listed as not applicable, and masking is listed as none. With no concurrent control group, the trial can describe outcomes among treated participants but cannot make a randomized comparison between the regimen and an alternative.

The trial evaluated reduced-intensity conditioning for hematopoietic stem cell transplantation in patients with high-risk inherited lysosomal and peroxisomal disorders. The registry’s rationale describes a regimen intended to decrease transplant-associated toxicity. It names clofarabine and other chemotherapy agents, total body irradiation, transplantation, mycophenylate mofetil, and cyclosporine A. The registry does not report which participants received each specific component beyond the group-level treatment description.

The primary outcome was the number of participants with donor-cell engraftment by day 100. Four secondary outcomes are listed: transplant-related death, concentrations of mycophenylate mofetil, acute graft-versus-host disease, and chronic graft-versus-host disease. Their results are not reported in the registry record. The registry lists five outcome measures overall, but records no analyses.

The record gives a start date of 2006-09 and a primary completion date of 2014-09. It does not report the sample-size justification, any planned interim analyses, or details of the statistical analysis plan. A planning illustration based on two-arm assumptions is not the design of this single-group trial and should not be read as a description of how the trial was planned or analyzed.

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

Analysis population for the primary outcome, as defined in the registry: One patient was not evaluable due to an early death.

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 Donor Cell Engraftment, measured over Day 100.

The primary endpoint is a count: the number of participants with donor-cell engraftment by day 100. The registry defines engraftment as the process by which transplanted stem cells reproduce new cells. It is therefore a measure of whether donor cells were reported to establish and reproduce in the recipient during the stated follow-up period.

Engraftment is relevant to a transplant study because the intervention includes donor stem-cell transplantation, and the registry’s stated aims include assessing whether engraftment can be achieved with the reduced-intensity protocol. The endpoint captures this transplant process directly. It does not, by itself, summarize every aspect of a participant’s health or establish the overall balance of benefits and harms.

The endpoint is specified at day 100, but the registry does not report why that time point was selected. It also does not report the number of participants who achieved engraftment. One patient was not evaluable for the primary outcome because of an early death. Without the observed count and the endpoint denominator or analysis-population details, the primary result’s magnitude and precision cannot be assessed from the registry record.

As a general statistical point, a count is easiest to interpret when its denominator and rules for handling unevaluable participants are clear. A count alone does not indicate the proportion of an eligible population with the outcome. The registry’s brief definition gives the biological meaning of engraftment, but additional endpoint specifications, including any assessment procedure or adjudication process, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is described as a single-group phase 2 study. This design means that participants received the study regimen, with no randomized control group listed. In a single-group study, outcome counts can characterize what happened among participants treated in the trial. They cannot, on their own, separate the effect of treatment from the course of the underlying disorders, other care, or participant characteristics. The registry lists allocation as not applicable and masking as none. It does not report further design features that would change this basic interpretation.

What does a count endpoint tell the reader?

The primary endpoint is the number of participants with donor-cell engraftment by day 100. A count states how many participants met the endpoint definition; it does not automatically communicate the proportion of participants who did so. Interpreting a count as a proportion requires a clearly specified denominator and rules for determining who was evaluable. The registry notes one patient was not evaluable because of an early death, but the number who achieved engraftment is not reported in the registry record. The endpoint’s denominator and any analysis-population definition are also not reported in the registry record.

As a general statistical explanation, a confidence interval describes a range of values compatible with the observed data under the method’s assumptions. Its width conveys precision: wider intervals indicate greater uncertainty. No confidence interval for engraftment is reported in the registry record, so the precision of that outcome cannot be assessed. No p-value or hypothesis-test result is reported either. Without an observed outcome and an inferential analysis, there is no basis for a statistical significance statement.

Why does the lack of a comparator matter?

A randomized comparison can help balance measured and unmeasured participant characteristics between treatment groups, making the treatment contrast easier to interpret. This trial has no comparator group identified, so there is no within-trial contrast. Even if a single-group outcome were available, it would describe the treated group rather than estimate a difference attributable to treatment. The registry does not report an external comparison or a prespecified historical control.

The disease list includes several inherited disorders, and the record does not report how many participants had each diagnosis or whether outcome summaries were stratified by diagnosis. As a general matter, combining distinct diagnoses into an overall count can conceal variation between groups. Whether that occurred in this trial cannot be assessed from the posted record.

How should planning estimates be understood?

The registry record does not report the trial’s sample-size justification. A separate planning illustration uses two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions are planning conventions, not evidence that the trial itself used them. They also describe a two-arm framework, whereas this trial is recorded as single-group. Any such participant-per-arm estimates are planning illustrations, not observed results and not observed power.

As a general statistical point, power is a property of a design under specified assumptions about the effect, variability, significance level, and sample size. It is not a measure of whether a completed study “had enough power” based on the observed result. A planning calculation based on an observed effect can be especially sensitive to uncertainty in that effect. The registry does not report a protocol-based power calculation, design assumptions, or the planned sample size rationale.

What does the absence of analyses imply?

The registry lists five outcome measures and no analyses. This indicates that analyzed results are not posted in the record, not that no analysis was ever conducted. Statistical methods for the primary endpoint, secondary outcomes, subgroup assessments, or safety outcomes are not reported in the registry record. In particular, the record does not state whether an inferential model was used, how missing observations were handled, or whether any adjustment for multiple outcomes was planned.

For a binary outcome, general methods may estimate the event probability and its uncertainty, but the choice of method depends on the sample, the endpoint definition, and analysis assumptions. No such estimate is available for engraftment in the registry record. General concepts explain how results could be analyzed; they do not fill in the missing trial results or establish which methods investigators used.

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("Treated Patients")
n      <- c(37)
events <- c(26)
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  Treated Patients  37  26  70.3  53.0  84.1  54.2  82.5  54.1  82.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and four secondary outcomes: donor-cell engraftment, transplant-related death, mycophenylate mofetil concentrations, acute graft-versus-host disease, and chronic graft-versus-host disease. It records five outcome measures and no analyses. Results for the secondary outcomes are not reported in the registry record.

When a study examines multiple outcomes, the chance of at least one apparently notable result can increase if each is tested separately. Statistical approaches to multiplicity may control that risk or clarify which outcomes are confirmatory and which are exploratory. Whether any multiplicity procedure was planned or used is not reported in the registry record. No p-values are posted, so there is no multiplicity-adjusted or unadjusted significance result to interpret.

For the primary endpoint, one patient was not evaluable because of an early death. The registry does not report how the primary analysis handled that participant, nor whether any other observations were missing. It does not report an intention-to-treat, per-protocol, or other analysis population. These omissions matter because the definition of the population included in an analysis can affect both the reported count and its denominator.

As a general principle, missing outcomes should not be presumed to have a particular statistical mechanism. The registry does not state whether data were considered missing at random, whether sensitivity analyses were conducted, or whether the early death was handled in a prespecified way. Those details are not reported in the registry record. The available information establishes the existence of one unevaluable primary outcome, but does not establish how it was incorporated into the analysis.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: disease progression (10.5%), graft failure (10.5%), death due to disease progression (5.3%), infection with grade 3 or 4 neutrophils (2.6%).

The adverse-event record lists 38 treated patients at risk for serious adverse events and 10 affected. It also lists 38 at risk for other adverse events and 33 affected. These are descriptive counts recorded for the treated group, not comparisons between treatment groups. The registry does not report a control group or a comparative safety estimate.

The listed serious-event terms include Disease Progression (10.5%), Graft Failure (10.5%), Death Due to Disease Progression (5.3%), and Infection with Grade 3 or 4 Neutrophils (2.6%). These percentages are reproduced as recorded; the registry excerpt does not provide further details about their denominators, timing, recurrence, or whether a participant could contribute to multiple terms. The list should not be treated as a complete account of every event or as a ranking of treatment-related risks.

As a general statistical point, counts of affected participants and counts of event episodes are not necessarily interchangeable. The record does not clarify the event-counting detail for these terms. It also does not report how investigators judged causality or distinguish events caused by disease progression from events attributed to treatment. The listed figures therefore describe reported safety observations, but do not establish comparative risk or causation.

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

The record establishes that a phase 2, single-group trial evaluated a reduced-intensity hematopoietic stem cell transplantation regimen in patients with high-risk inherited disorders. It identifies donor-cell engraftment by day 100 as the primary endpoint and reports that one patient was not evaluable for that endpoint because of an early death. It also provides treated-group adverse-event counts and lists several serious-event terms.

The record does not report the number of participants with donor-cell engraftment. It therefore does not show, in the posted results, how often the primary endpoint occurred or how precisely it was estimated. Results for the listed secondary outcomes are also not reported in the registry record. The information cannot support a numerical conclusion about the primary endpoint or the secondary endpoints.

Because there is no comparator group, the registry record cannot establish how outcomes under this regimen compare with another approach. An outcome observed in a treated group is not, by itself, an estimate of what treatment changed. The record also does not provide enough detail to assess outcomes by diagnosis or other participant characteristics.

The safety information can be read as a description of reported adverse-event counts among treated participants. It does not establish that the regimen caused each event, nor does it estimate how those events compare with risks under another treatment. Event definitions, timing, and participant-level overlap are not reported in the registry record.

As a general principle, the absence of a posted result is not evidence that an outcome did or did not occur. It means the registry record does not provide the result needed to quantify it. Statistical interpretation should therefore remain limited to the design features, the one stated unevaluable primary outcome, and the descriptive safety counts that are actually recorded.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between evaluating whether a treatment process can be achieved and determining whether a treatment improves outcomes compared with an alternative. Engraftment by day 100 is a direct process-oriented endpoint for a transplant study. In a single-group design, however, even a reported engraftment count would primarily describe what happened among treated participants; it would not provide a randomized treatment contrast.

The trial also concerns several inherited disorders rather than one diagnosis. This makes clear reporting of the enrolled population important: the number of participants with each condition, their disease status, and any diagnosis-specific outcomes could shape interpretation of an overall result. Those details are not reported in the registry record.

The record illustrates how missing outcome results constrain statistical interpretation. Enrollment and endpoint definitions do not substitute for an observed endpoint count. Without the primary result, its denominator, and an uncertainty estimate, readers cannot evaluate the magnitude or precision of engraftment in the trial. The same limitation applies to the listed secondary outcomes, for which results are not reported.

Finally, the safety counts underscore the distinction between descriptive surveillance and comparative safety evidence. Counts can signal which events were recorded in the treated group, but without a control group and fuller event details they do not quantify excess risk or establish causality. These design and reporting features make the trial a useful example of why endpoint results, analysis populations, and uncertainty measures are central to interpreting clinical evidence.

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 principal limitation for statistical interpretation is that the primary endpoint result is not reported in the registry record. The record gives the endpoint definition and timeframe, and notes one patient was not evaluable due to an early death, but does not give the number with engraftment or an analysis denominator. There is consequently no reported estimate or measure of precision for the primary outcome.

The single-group design has no concurrent control group. It can describe outcomes among treated participants, but does not support a randomized estimate of treatment effect. Allocation is listed as not applicable and masking as none. The registry does not report additional details that would allow assessment of outcome assessment procedures or potential measurement bias.

The study includes a range of inherited disorders, but the number of participants with each condition and diagnosis-specific results are not reported in the registry record. Without those details, the extent to which an overall summary represents the different disorders cannot be assessed. Further participant characteristics and disease-severity details are also not reported.

The record lists four secondary outcomes but does not report their results, and it records no analyses. The statistical analysis plan, sample-size justification, interim analyses, missing-data methods, and analysis-population definitions are not reported in the registry record. One early death made a participant unevaluable for the primary endpoint, but how this was handled is not stated.

Safety information is limited to event counts and selected serious-event terms. The record does not report a comparator, event timing, participant-level overlap, or further details on causality. These limitations prevent comparative safety conclusions and restrict interpretation to the descriptive information posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: HSCT for High Risk Inherited Inborn Errors — NCT00383448.
• Registry record last updated 2019-07-11; status last verified 2019-07.
• Results first posted 2019-07-11.
• 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

This completed phase 2 trial enrolled 38 participants and evaluated reduced-intensity hematopoietic stem cell transplantation in a single treated group with high-risk inherited disorders. The primary endpoint was the number with donor-cell engraftment by day 100. One patient was not evaluable because of an early death, but the engraftment result is not reported in the registry record.

Four secondary outcomes are listed, with no results reported. The registry records no analyses, and does not report the trial’s sample-size justification or statistical analysis plan. Safety entries include 10 participants affected by serious adverse events and 33 affected by other adverse events among 38 at risk in each category. The single-group design does not provide a randomized comparison, so the posted information supports descriptive interpretation only.