Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes (NCT00045305), a na phase 2 study. The primary outcome is Complete Response Rate.

2. Clinical Question

This design can describe outcomes among people who received the study approach, but it cannot by itself separate the effects of individual regimen components or establish how outcomes compare with another treatment strategy. The listed follow-up schedule for the primary endpoint begins monthly for the first 3 months from study entry, continues every 3 months for the first two years from study entry, and then every 6 months for years 3-5. The record does not report the completeness of this follow-up or how many participants contributed endpoint data.

3. Trial Design

The registry classifies this as a phase II study with a single-group model. Allocation is listed as not applicable and masking as none. The record therefore describes an open, nonrandomized treatment group rather than a blinded comparison between allocated arms. Enrollment was 17, and the study status is completed. The listed start date is 2006-10-24, with primary completion in 2014-02.

The study concerned a reduced-intensity preparative regimen before donor bone marrow transplant for myelodysplastic syndromes. The intervention list includes photopheresis, pentostatin, total-body irradiation, allogeneic bone marrow and peripheral blood stem cell procedures, as well as cyclosporine, methotrexate and mycophenolate mofetil. The available arm description says photopheresis was performed on two consecutive days, followed by pentostatin at 4 mg/m2/d for two consecutive days, for a total dose of 8 mg/m2. It describes total-body irradiation on two consecutive days following pentostatin, but the regimen description ends before giving further details. Specific dosing or use of other listed interventions is not reported in the registry record.

Without a comparator, the study can estimate outcomes in the enrolled group if those results are reported, but it cannot directly estimate a treatment contrast with usual care or another regimen. Differences between this group and a separate population could reflect factors other than treatment. The registry record does not report a randomized design, a control group, or a masking procedure. It also does not report a detailed rationale for the planned enrollment, so the adequacy of the sample size for a target precision or treatment effect cannot be assessed from the record.

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: eligible and treated patients

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.

Population: eligible and treated patients

6. Primary Endpoint

The registry lists the primary outcome as Complete Response Rate, measured over Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5..

The primary endpoint is the complete response rate, expressed as the percentage of participants. Its stated population is eligible and treated patients. Complete response is a composite clinical and laboratory definition: repeat bone marrow evaluation must show less than 5% myeloblasts with normal maturation of all cell lines and no evidence of dysplasia, with a dysplasia qualifier linked to the peripheral blood evaluation. The peripheral blood requirements include hemoglobin greater than 11 g/dl without transfusion or erythropoietin, neutrophils listed at 1500/mm3 without a myeloid growth factor, platelets listed at 100,000/mm3 without a thrombopoietic agent, blasts at 0%, and no dysplasia. If a cytogenetic abnormality was present before treatment, no detectable abnormality is required.

The record says absolute peripheral blood values must last at least 2 months. This duration requirement makes the endpoint more than a single measurement and is intended to distinguish a sustained response from a transient finding. In general, a complete response endpoint combines several features so that a response requires meeting the specified criteria across disease and blood measures. The record does not report the observed number or percentage meeting the definition, the timing of any responses, or a confidence interval. The neutrophil and platelet thresholds are printed without a visible comparison operator in the endpoint description, so their precise threshold direction is not clear from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information describes a phase II, single-group study without masking. A single-group design follows participants receiving a study approach without a concurrent control group. In general, it can describe outcomes in that group, but it does not provide the randomized treatment contrast needed to distinguish a treatment effect from other explanations for an observed outcome. Since allocation is listed as not applicable and no comparator is described, comparisons with an external group would require additional assumptions and are not reported in the registry record.

What does a response rate estimate?

For a binary endpoint such as complete response, the underlying quantity is the proportion of participants who meet the response definition during the specified assessment process. A point estimate gives one summary of that proportion, while a confidence interval conveys uncertainty around it. In general, the interval depends on the number of participants with evaluable data, the number meeting the endpoint and the method used. The registry specifies a 90% confidence interval, but it does not report the estimate, interval limits, or calculation method. No response proportion can therefore be interpreted from the record.

The endpoint definition includes several criteria rather than one measurement. Such a composite definition generally means every required component must be satisfied for a participant to count as a complete response. The registry describes bone marrow and peripheral blood requirements, a duration requirement for absolute blood values, and a cytogenetic condition for patients with a preexisting abnormality. It does not report the number of participants meeting each component or identify any adjudication process. The printed neutrophil and platelet threshold entries also lack a visible comparison operator, which leaves those parts of the definition ambiguous.

Why does the study design matter?

In a randomized comparison, allocation can help balance known and unknown prognostic characteristics between groups. This study has no randomized comparison group, so outcome percentages would be descriptive of the participants treated in the study. General statistical adjustment cannot recreate the protection of randomization without suitable data and assumptions, and no adjusted treatment contrast is reported. The trial's phase and single-group classification do not, on their own, establish the precision or reliability of any particular result.

The registry lists enrollment of 17. Enrollment is not necessarily the same as the number included in each endpoint analysis. In general, participants may have incomplete assessments, may not meet an analysis population definition, or may have insufficient follow-up. The record does not report endpoint-specific denominators or missing outcome counts, so it is not possible to tell whether all enrolled participants contributed to the primary endpoint.

How should the planning assumptions be read?

The planning information describes illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. These are planning assumptions, not a report of the trial's actual design: the registry describes a single group and no two-arm allocation. No planning sample-size values or observed effect estimate are reported in the record. Accordingly, the illustrative framework cannot be used to infer the study's original sample-size justification or its ability to detect an effect. A calculation based on an observed effect would also be conditional on that effect estimate and would not show that a study had a particular probability of detecting it.

In general, normal approximations can be less reliable when samples or event counts are small, depending on the statistic and method. Equal allocation is a hypothetical design feature for a two-group calculation and does not describe enrollment in this single-group study. If a count outcome has variability greater than a simple model assumes, over-dispersion can make standard errors too small and intervals or tests misleading; this is a general statistical concern, not a reported finding about this trial. No over-dispersion assessment or count-model analysis is reported.

What does the record say about analyses?

The record lists no analysis entries. It does not report an estimation procedure for the primary endpoint, any adjustment for covariates, interim analyses, or a statistical analysis plan. The endpoint description includes scheduled assessments, but an assessment schedule does not specify how repeated assessments were summarized or which assessment determined response. The registry also does not report how death, disease progression, transplant complications, or missing visits were handled in the primary endpoint analysis. These details are necessary to interpret a numerical endpoint estimate, but no such estimate is posted 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("Arm I")
n      <- c(17)
events <- c(6)
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  Arm I  17  6  35.3  14.2  61.7  17.3  58.7  17.3  59.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures: complete response rate and five secondary outcomes covering disease progression after complete response, overall survival, graft-versus-host disease, and neutrophil and platelet engraftment. Examining multiple outcomes can create multiplicity: in general, when many hypotheses are tested, the chance of at least one apparently unusual result can increase if each test is interpreted independently. The registry record does not report a multiplicity adjustment, a hierarchy of outcome testing, or which secondary outcomes were considered confirmatory versus exploratory. It also does not report p-values or analysis entries from which the approach could be assessed.

Missing data are important for a response endpoint because the percentage depends on both the response count and the analysis denominator. The registry identifies eligible and treated patients as the primary endpoint population, but does not state how many were evaluable, whether assessments were missing, or how missing response status was handled. It does not report whether participants who died, progressed, or stopped follow-up were counted as nonresponders or treated another way. These decisions can change the interpretation of a response rate and its precision.

The record does not give a detailed analysis population definition beyond eligible and treated patients. It does not say whether all enrolled participants were analyzed, whether any participants were excluded, or how protocol deviations were handled. The assessment schedule is stated, but the record does not describe how multiple assessments were combined or which time point was used for the primary summary. These missing details limit reproducibility and make it difficult to judge the potential impact of incomplete follow-up or selective reporting.

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: white blood cell decreased (100.0%), neutrophil count decreased (100.0%), platelet count decreased (100.0%), anemia (82.4%), febrile neutropenia (35.3%).

The registry lists serious adverse-event terms with reported percentages: white blood cell decreased, neutrophil count decreased and platelet count decreased at 100.0% each; anemia at 82.4%; febrile neutropenia at 35.3%; and blood bilirubin increased at 35.3%. These are percentages, not a comparison with an untreated or alternative-treatment group. The safety record also lists 17 participants at risk and 17 affected for both serious and other adverse-event categories in Arm I. The entry does not explain whether the affected counts refer to participants with any event or to a particular event grouping.

In general, an adverse-event percentage describes how often an event was recorded within the specified safety population; it does not by itself establish that the study regimen caused the event. The record does not provide timing, duration, recurrence, severity grades, participant-level overlap, or event-specific counts alongside the percentages. It is therefore not possible to tell from these terms whether one participant experienced multiple events or how the events were distributed over the study period. These figures should be read as registry safety descriptions, not as comparative risk estimates.

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

The study record documents a phase II investigation of a reduced-intensity regimen before donor transplant, with complete response rate as its primary endpoint. It gives a detailed response definition and a schedule for assessing the endpoint. It also records enrollment of 17, the single-group design, and several serious adverse-event percentages. Those details describe what the study set out to examine and what safety terms were recorded.

The record does not include a primary response estimate or confidence interval. It also lacks posted results for the listed secondary outcomes. Therefore, the available information cannot establish how many participants achieved complete response, how precise a response estimate would be, or what the study found for survival, disease progression, graft-versus-host disease or engraftment. The absence of these results is not evidence of a zero response rate or of no secondary outcomes.

Even with complete outcome results, a single-group study would not offer a randomized comparison with another strategy. A percentage observed among treated participants would be a description of that study group, not an estimate of the difference caused by the regimen relative to a control. Other features of care and participant characteristics could also contribute to outcomes. The registry record does not report analyses that address those issues.

The safety terms likewise have limits: they are not compared with a separate group, and event timing, severity and overlap are not described. The listed percentages should not be interpreted as a causal estimate of risk. Overall, the record supports a description of trial design, endpoint criteria and recorded safety terms, but not a conclusion about comparative efficacy or safety.

14. Why This Trial Matters Statistically

This trial illustrates how statistical interpretation depends on more than an endpoint name. Complete response is defined through bone marrow, blood, dysplasia and cytogenetic criteria, with blood values required to persist for at least 2 months. A response percentage would only be interpretable alongside its denominator, assessment timing and a clear account of how each criterion and missing assessment was handled. Those elements are not all reported in the registry record.

The study also highlights the distinction between describing an outcome and estimating a treatment contrast. In a single-group study, a reported response proportion could characterize participants who received the regimen, but it would not show what would have happened to comparable participants under another approach. That distinction is central to avoiding causal claims from a design without a concurrent control.

Small enrollment makes transparent reporting especially useful. With 17 participants, the number contributing to each outcome and the uncertainty around estimates would be important for readers. The record specifies a 90% confidence interval for the primary endpoint but does not post its estimate or interval. It also lists several secondary outcomes, without analysis entries or results. This leaves readers unable to assess precision, outcome completeness, or how multiple endpoints were handled.

Finally, the safety percentages demonstrate why event definitions and denominators matter. Percentages alone do not show timing, severity, recurrence, or whether different event terms occurred in the same participants. The registry entry is useful for identifying the planned question and recorded safety terms, while also showing how absent outcome and analysis details constrain statistical interpretation.

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.

A key limitation of the available record is that it does not report the primary endpoint result, despite specifying complete response rate and a 90% confidence interval. No interval limits, response count, endpoint-specific denominator or primary analysis method are given. The registry record also lists no analysis entries, so there is no posted quantitative result for the primary or secondary outcomes to interpret.

The single-group design has no concurrent control group and no randomized allocation. Any outcome among participants receiving the study approach would therefore be descriptive rather than a direct comparison with another strategy. The registry does not report a detailed sample-size justification, interim-analysis approach, or statistical analysis plan. Although planning assumptions are described for a hypothetical two-arm illustration, the actual study is listed as single-group, and no numerical planning output or observed effect is reported.

The primary response definition is detailed but contains an ambiguity: the neutrophil and platelet values are written without visible comparison operators. The record does not clarify how this was resolved. It also does not state how missing assessments, progression, death, withdrawal, or incomplete follow-up were handled, nor does it give an analysis population count beyond the eligible and treated population description.

The intervention description is incomplete: it ends after stating that total-body irradiation was administered on two consecutive days following pentostatin. Although several transplant and post-transplant interventions are listed, the record does not state which participants received each option. Safety information lacks event timing, severity grading, recurrence and overlap details. These limitations prevent a fuller assessment of treatment exposure, outcome precision and the context of the reported adverse-event percentages.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes — NCT00045305.
• Registry record last updated 2023-06-28; status last verified 2023-06.
• Results first posted 2015-01-19.
• 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

The registry describes a completed phase II, single-group study of a reduced-intensity preparative regimen before donor transplant for myelodysplastic syndromes. Enrollment was 17. The primary endpoint was complete response rate among eligible and treated patients, assessed on a stated schedule and defined using bone marrow, peripheral blood and cytogenetic criteria.

The record specifies a 90% confidence interval for the primary endpoint but does not report a response estimate or interval. It lists five secondary outcomes but provides no results or analysis entries. Serious adverse-event terms are reported with percentages, but event timing, severity, overlap and comparative safety are not described. The absence of a control group, missing endpoint results and limited analysis details restrict what can be concluded statistically from the registry record.