Non-Myeloablative Conditioning and Bone Marrow Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Non-Myeloablative Conditioning and Bone Marrow Transplantation (NCT01850108), a na na study. The primary outcome is Transplant-related Mortality (TRM).

2. Clinical Question

In statistical terms, the study’s central question is about the occurrence of a defined event in a group receiving the transplant approach, rather than a difference between randomized groups. The record also lists outcomes concerning acute graft-vs.-host disease, donor hematopoietic chimerism, and toxicities. These add information about events after transplantation, but they do not create a control comparison. Because the primary outcome count is not reported, the registry record does not establish the observed frequency of transplant-related mortality under its definition.

3. Trial Design

The registry identifies NCT01850108 as a single-group study titled “Non-Myeloablative Conditioning and Bone Marrow Transplantation.” Its official title describes non-myeloablative conditioning and transplantation of partially HLA-mismatched and HLA-matched bone marrow for patients with sickle cell disease and other hemoglobinopathies. The listed enrollment is 26. The study start is recorded as 2013-05, primary completion as 2023-11, and status as unknown.

There is no randomized allocation: allocation is recorded as NA, masking as none, and the study model as single group. These design features mean there is no concurrent trial arm against which to estimate a treatment contrast. The record gives no arm-specific description beyond the single arm’s title, and its arm description is blank. Phase is listed as NA. More detailed information about eligibility, recruitment, treatment delivery, follow-up procedures, and protocol deviations is not reported in the registry record.

The intervention list includes several drugs, bone marrow transplantation, and total body irradiation. The registry record does not specify their timing, dose, sequence, or whether each intervention applied to every participant. Those details should not be inferred from the list alone.

The primary outcome is transplant-related mortality, assessed at 1 year after BMT. The registry also lists secondary outcomes for grade I-IV acute graft-vs.-host disease, donor hematopoietic chimerism in peripheral blood below 95% at 6 months after mini-haploBMT, and hematologic and non-hematologic toxicities following minihaploBMT. The record lists four outcome measures overall, but does not report outcome results for the primary endpoint. It lists no analyses. The sponsor is Vanderbilt-Ingram Cancer Center.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: participants in this study

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 Transplant-related Mortality (TRM), measured over at 1 year after BMT.

The primary endpoint is transplant-related mortality (TRM), reported as a count of participants. The registry defines TRM as death in the absence of recurrent sickle cell disease or hemoglobinopathy, with assessment at 1 year after BMT. This definition makes the outcome more specific than an all-cause death count: it requires both death and the absence of recurrent underlying disease according to the registry wording.

Counting participants with a defined event is useful because it gives a direct description of how often that event was recorded in the study group. For a binary outcome, each participant is classified as having or not having the event under the stated definition. The count is interpretable only alongside a clear denominator and consistent event ascertainment. The registry identifies the outcome population as participants in the study, but the primary result and its analyzed denominator are not reported in the registry record.

The endpoint’s timing matters. It addresses mortality by the specified follow-up point, not mortality over every possible period after transplantation. Nor does the definition by itself establish a cause of death or a causal link to a particular component of conditioning or transplantation. The record does not report the number meeting the TRM definition, a corresponding uncertainty interval, or details about how deaths and recurrence were adjudicated. Consequently, the endpoint is defined, but its observed result cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as a count of participants with transplant-related mortality. General statistical explanation: a participant-level event outcome is often treated as binary, with each participant classified according to whether the defined event occurred during the stated period. The event count describes the number meeting the definition; a denominator is needed to describe the event frequency. Here, the primary endpoint result and analyzed denominator are not reported in the registry record, so no primary-outcome frequency can be interpreted.

What does a count measure?

A count and a rate or proportion answer related but different questions. A count gives the number of recorded events or affected participants. A proportion relates that count to an eligible or analyzed group. Comparisons of proportions also require a clearly specified comparison group and compatible outcome definitions and follow-up. For this study, the registry’s design is single group, and no control arm is listed. The posted primary outcome is a count, not a reported comparative treatment effect.

General statistical explanation: uncertainty in an event estimate depends in part on how many observations contribute and how frequently the event occurs. A confidence interval is a range of values compatible with the observed data under the assumptions of a chosen method. It is not a guarantee that the true value lies within the interval, and it does not address biases caused by missing data, selection, or outcome misclassification. The registry record does not report a confidence interval for the primary outcome or identify an interval method.

Why does the single-group design matter?

A single-group design can describe outcomes in participants who received the study approach. It does not provide a randomized estimate of the difference between that approach and another treatment. Random allocation, when used, helps balance measured and unmeasured characteristics across comparison groups on average. Since allocation is listed as NA and the model is single group, that protection is not part of this study design. An external comparison could be considered in other analyses, but none is identified in the registry record.

Masking is listed as none. In general, masking means keeping treatment or outcome information from specified people involved in a study or assessment. The record does not identify which roles, if any, were unmasked, or describe outcome adjudication. It is therefore not possible to assess from the registry record whether knowledge of treatment could have influenced event reporting or classification.

How should event counts be read?

General statistical explanation: event counts can be analyzed with methods appropriate to the outcome and study design. For a binary participant-level endpoint, methods may estimate an event proportion and its uncertainty. Other count models may be used when the outcome represents repeated events or count variation, but their assumptions differ. Over-dispersion is a general concern when count data vary more than a model assumes; accounting for it can prevent uncertainty from being understated. The registry record does not report a statistical model, a test, an interval method, or an adjustment for over-dispersion. No such method should be attributed to this study.

The registry lists four outcome measures and no analyses. This does not establish what analyses were performed outside the registry record; it means the record does not document them. It also does not identify a statistical analysis plan, whether analyses were adjusted for covariates, or how competing events were handled. For a mortality outcome defined by absence of recurrent disease, those details could matter to the operational classification, but they are not reported.

What does the planning illustration represent?

The accompanying sample-size illustration is a planning exercise, not an observed analysis and not observed power. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; its effect to detect is a stated fraction of the observed effect. Such assumptions describe a hypothetical design calculation. They do not convert this single-group study into a randomized two-arm trial, and they do not indicate that the study was designed with those assumptions. The registry record does not report its own sample-size justification or statistical design calculations.

General statistical explanation: a planning calculation estimates how many participants might be needed under specified assumptions to detect a target effect with a chosen operating characteristic. Results depend on the assumed effect, outcome variability or event frequency, allocation, and analysis method. A calculation based on an observed effect should not be read as evidence that the study had a particular probability of detecting a true effect. Nor does a planning figure correct for the lack of a control group or fill in an unreported endpoint result.

Interpretation therefore begins with what is documented: the endpoint definition, follow-up time, study structure, and reported counts. Where an estimate, uncertainty interval, analysis method, or denominator is absent, the appropriate conclusion is that it is not reported in the registry record, rather than to reconstruct it from other entries.

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("Non-Myeloablative Conditioning and Bone Marrow Tra")
n      <- c(16)
events <- c(0)
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  Non-Myeloablative Conditioning and Bone Marrow Tra  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and no analyses. It does not identify a prespecified hierarchy among the outcomes, distinguish confirmatory from exploratory analyses, or report a multiplicity adjustment. Multiplicity refers generally to the increased chance of a misleading positive finding when several hypotheses are tested. Whether an adjustment is appropriate depends on the study questions and analysis plan; no plan is reported in the registry record. The absence of a reported adjustment should not be interpreted as evidence that one was or was not performed.

The record defines the primary outcome and its assessment time, but does not report its result, denominator, or statistical analysis. It also does not report results for the listed secondary outcomes. It therefore does not allow readers to evaluate whether all prespecified outcomes were reported or whether outcome definitions changed during the study. Protocol amendments and a statistical analysis plan are not reported in the registry record.

Missing-data handling is also not reported. There is no description of incomplete follow-up, withdrawals, exclusions from analysis, imputation, or sensitivity analyses. In general, missing outcomes can affect an estimate if the participants without recorded outcomes differ systematically from those with complete data. The impact depends on the amount and pattern of missingness and the assumptions used to handle it. Since those details are absent, the extent of any missing-data concern cannot be assessed.

The record names participants in the study as the primary-outcome population, but does not specify an analysis population such as all enrolled participants or a subset meeting particular criteria. The listed enrollment is 26; this should not be assumed to be the denominator for every endpoint. The registry does not report how participants were counted for each outcome or whether follow-up was complete through the stated time points.

12. Safety Results

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

Deaths

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: reversible posterior leukoencephalopathy syndrome (7.7%), fever (7.7%), seizure (7.7%), kidney injury (7.7%), sepsis (7.7%).

The registry safety summary lists 9 participants affected by serious adverse events among 26 at risk, and 0 affected by other adverse events among 26 at risk. It separately lists 1 death. The record does not explain whether that death meets the primary endpoint definition of transplant-related mortality, which requires death in the absence of recurrent sickle cell disease or hemoglobinopathy. The relationship between the death and the serious-event summary is not reported.

The listed serious adverse event terms and registry-reported percentages are: reversible posterior leukoencephalopathy syndrome, 7.7%; fever, 7.7%; seizure, 7.7%; kidney injury, 7.7%; sepsis, 7.7%; and duodenal hemorrhage, 3.8%. The registry record does not give event counts for these individual terms or explain the denominator and counting rules behind the percentages. These percentages should therefore be read as registry entries rather than recalculated or combined.

Serious adverse event summaries describe reported events; they do not by themselves establish causation. The record does not state whether events were judged related to conditioning or transplantation, how events were collected, or whether the listed terms represent unique participants. The figures should not be added together because a participant may have more than one event. They also should not be treated as a comparison with another treatment, since no control group is listed.

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

The registry record establishes that this study examined non-myeloablative conditioning and bone marrow transplantation in a single group of participants with sickle cell disease and other hemoglobinopathies. It specifies transplant-related mortality at 1 year after BMT as the primary outcome and defines the event as death in the absence of recurrent sickle cell disease or hemoglobinopathy. This clarifies the outcome the study intended to describe.

What the record does not establish is the observed primary outcome result. No count meeting the TRM definition, analyzed denominator, or uncertainty interval is reported. The safety summary lists serious and other adverse events and a death, but does not say whether the death meets the primary endpoint definition. These safety data cannot substitute for the missing primary outcome result.

Because the study has one group and no randomized comparator, its design cannot estimate a causal difference between the transplant approach and an alternative. A descriptive result, even if reported, would concern outcomes in this study group; it would not by itself show what would have happened to the same participants under different care. The record also does not provide details needed to assess selection, outcome ascertainment, or completeness of follow-up.

General statistical explanation: estimates are more informative when their uncertainty and the number of observations contributing to them are clear. A confidence interval can communicate statistical precision, while transparent reporting of denominators and missing data helps readers judge how representative the analyzed participants are. Those details are not reported for the primary endpoint. No conclusion about treatment efficacy, comparative safety, or the certainty of a treatment effect can be drawn from the registry entries.

The appropriate reading is therefore narrow: the registry describes a transplant study, identifies its outcome definitions, and includes safety counts and terms. It does not report the primary endpoint result or a comparative analysis. The listed design and results do not establish that the intervention works or does not work.

14. Why This Trial Matters Statistically

This trial is statistically notable because it asks a consequential outcome question in a single-group design. Transplant-related mortality is defined at a specific follow-up time and with a specific condition concerning recurrent disease. Clear definitions are essential for reproducible outcome classification, particularly when a death count may include events that do not meet the endpoint definition.

The single-group structure also illustrates the distinction between describing outcomes and estimating treatment effects. A group’s outcome experience can be summarized, but without a concurrent comparator the study cannot directly estimate a randomized contrast. This distinction is especially important when readers encounter a safety count or an outcome label and are tempted to interpret it as evidence about what would happen under another treatment.

The registry record also demonstrates why result completeness matters. It identifies the primary outcome and its timing, yet does not report the event count, analyzed denominator, or uncertainty for that endpoint. A precise definition without a reported result is not enough to evaluate the outcome. Similarly, adverse-event counts are more interpretable when event definitions, denominators, attribution, and overlap among terms are clear.

Finally, the record lists multiple outcomes but no analyses and does not report its statistical analysis plan, multiplicity approach, or missing-data methods. These omissions limit assessment of how results were selected and analyzed. The study remains informative as a record of its design and stated outcomes, while its missing primary result and lack of a control group constrain the statistical conclusions that can be drawn.

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 is that the primary endpoint result is not reported in the registry record. The event count, analyzed denominator, and uncertainty are absent, so the primary outcome cannot be quantified or assessed for precision. The listed enrollment of 26 does not establish the denominator used for the endpoint or confirm complete follow-up.

The single-group design, with allocation recorded as NA, provides no randomized control comparison. This limits the ability to separate outcomes associated with the study approach from outcomes that could have occurred under another approach. Masking is listed as none, but the registry does not describe outcome adjudication or specify which people knew treatment information.

The arm description is blank, and the registry does not detail how the listed drugs, radiation, and transplant procedure were scheduled or delivered. Eligibility criteria, participant characteristics, adherence, follow-up completeness, and reasons for exclusion or withdrawal are not reported in the registry record. These gaps limit assessment of who the findings would describe and how outcomes were ascertained.

The safety summary lists serious adverse events, other adverse events, and a death, but does not state attribution to treatment or explain the individual term denominators and counting rules. The record also lists four outcome measures and no analyses, without documenting a statistical analysis plan, multiplicity handling, or missing-data methods. Status is recorded as unknown. Together, these limitations mean the registry record supports a description of study structure and selected safety entries, but not a complete evaluation of the primary outcome or a comparative treatment effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Non-Myeloablative Conditioning and Bone Marrow Transplantation — NCT01850108.
• Registry record last updated 2024-01-10; status last verified 2024-01.
• Results first posted 2024-01-10.
• 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

NCT01850108 is a single-group study of non-myeloablative conditioning and bone marrow transplantation for sickle cell disease and other hemoglobinopathies. The listed enrollment is 26; allocation is NA, masking is none, and phase is NA. The registry records a study start of 2013-05, primary completion of 2023-11, and status as unknown.

The primary outcome is transplant-related mortality at 1 year after BMT, defined as death in the absence of recurrent sickle cell disease or hemoglobinopathy. Its result is not reported in the registry record. Listed safety information includes 9 participants affected by serious adverse events, 0 affected by other adverse events, and 1 death. The record lists four outcome measures and no analyses. It does not report a control comparison, primary-outcome denominator, statistical analysis plan, or missing-data approach.