Busulfan, Cyclophosphamide, and Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Busulfan, Cyclophosphamide, and Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma (NCT00941720), a na phase 2 study. The primary outcome is Relapse-free Survival.

2. Clinical Question

The study's stated purpose was to examine outcomes and toxicity when busulfan was included in the preparative regimen for autologous transplantation. In statistical terms, the design can describe outcomes among the participants who received the regimen, but it does not provide a concurrent control group for estimating how those outcomes compare with a different regimen or with no treatment.

The primary outcome is titled “Relapse-free Survival,” while its definition is a count of participants without progressive disease at the end of the study period. The specified timeframe is at six months. The record does not include the observed count or a comparison estimate, so the primary question cannot be answered from the posted results. Pulmonary toxicity is listed as a secondary outcome, but its result is not reported in the registry record.

3. Trial Design

This completed study is listed as phase II and single-group. The intervention combines busulfan and cyclophosphamide with autologous hematopoietic stem cell transplantation. The treatment arm is called “Busulfan Treatment.” The record does not describe a separate control arm; allocation is recorded as NA, and masking is recorded as none.

The study enrolled 71 participants. Its recorded start date is 2009-06-11, and its primary completion date is 2013-02-28. These dates describe the registry record's study timeline; they do not establish the duration of follow-up for each participant. The primary outcome has a stated timeframe of six months, but the record does not report participant-level follow-up or the timing of outcome assessments beyond that definition.

The primary outcome is a count of participants without progressive disease at six months, according to the stated International Myeloma Working Group response and progression definitions. Pulmonary toxicity is named as a secondary outcome. The record indicates three outcome measures overall, but the details and results for all of them are not reported in the registry record. It lists zero analyses, and no primary-outcome result or statistical comparison is posted.

For a single-group study, the observed outcome can describe the treated group, subject to how complete and consistently assessed the outcome data are. Without a concurrent comparator, differences from another treatment cannot be separated from differences in patient characteristics, clinical setting, follow-up, or other factors. The registry record does not report a randomized allocation, a control group, eligibility details, or further information about the study's analysis plan.

The safety data are reported separately from the primary outcome. For the Busulfan Treatment group, 57 participants are listed as at risk for serious adverse events and 12 as affected; the corresponding figures for other adverse events are 57 at risk and 5 affected. These safety denominators are not the same as the overall enrollment figure. Why the safety population differs from enrollment is not reported in the registry 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:

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 Relapse-free Survival, measured over at 6 months.

The primary endpoint is titled “Relapse-free Survival,” but its registry definition is a participant count: the number without progressive disease at the end of the specified period, which is at six months. The definition refers to the International Myeloma Working Group criteria for complete response, partial response, and progressive disease. This wording makes the event classification criteria part of the endpoint: a participant's status depends on how disease response or progression is categorized under those definitions.

A status assessed at a fixed follow-up time can give a clinically interpretable snapshot of disease control in the study group. It differs from a time-to-event measure that uses the timing of progression or relapse and accounts for differing follow-up times. Although the endpoint title uses the phrase “relapse-free Survival,” the registry definition does not specify an event-time analysis, censoring rules, or a survival-curve method. Those details are not reported in the registry record.

The registry does not post the observed number of participants without progressive disease, the number assessed at six months, or an estimate of uncertainty around the outcome. It therefore does not permit an assessment of the primary endpoint's observed frequency or precision. The registry also does not report how missing or unevaluable disease assessments were handled. These omissions matter because a count at a fixed time can be interpreted only in light of the participants included in that count and the completeness of their assessments.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In a single-group study, the main direct statistical description is the outcome among participants who received the study regimen. That description may include a count or proportion at a specified assessment time, depending on what the study measures and reports. It is not inherently a comparison with an alternative regimen. A comparison requires a defined reference group and an analysis that accounts for how participants entered each group.

This record lists one treatment group and no comparator. Consequently, it cannot estimate a randomized between-group treatment effect. Even if an outcome count were posted, interpreting it as evidence about what would have happened under another treatment would require assumptions that cannot be checked from a single-group result alone. The registry does not report an external comparison or a planned comparative analysis.

How should the primary endpoint wording be read?

The endpoint title is “Relapse-free Survival,” but the definition describes a count of participants without progressive disease at six months. A fixed-time count and a time-to-event analysis answer related but different questions. A fixed-time measure classifies participant status at the specified assessment. A time-to-event measure uses when an event occurred and may account for participants whose observation ends before the event or before the planned follow-up is complete.

General statistical interpretation: a time-to-event analysis usually requires a definition of the event, a time origin, follow-up information, and rules for censoring. The registry does not report these details for this endpoint. Nor does it report a survival curve or an event-time estimate. The endpoint definition should therefore be interpreted as written rather than expanded into an unreported analysis.

What would uncertainty measures add?

General statistical explanation: an estimate describes the observed data, while a confidence interval expresses the uncertainty associated with that estimate under a specified statistical method. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The interval does not resolve design limitations, such as the lack of a comparator, nor does it account automatically for selection, measurement, or missing-data problems.

No confidence interval or other uncertainty estimate for the primary endpoint is reported in the registry record. There is also no posted primary-outcome count from which to evaluate the result's precision. The registry's count outcome could be accompanied by an uncertainty interval in an analysis, but the method and estimate are not reported, so no particular interval or interpretation can be attributed to this study.

What can the safety counts tell readers?

The safety listing reports participants at risk and participants affected for serious and other adverse events. These are participant counts, not necessarily event counts. A participant may experience more than one event, and the registry record does not describe how repeated events were handled. Nor does it state whether the serious and other categories are mutually exclusive at the participant level.

General statistical explanation: event counts and participant counts answer different questions. Event counts can reflect repeated occurrences in a participant, whereas participant counts describe how many people had at least one recorded event. Rates also require a clearly defined denominator and, for incidence rates, an amount of time at risk. The registry provides at-risk participant counts for the safety categories, but does not give event-level timing or person-time. It is therefore not possible to infer an incidence rate or the frequency of recurrent events from these figures.

Why does over-dispersion matter?

General statistical explanation: over-dispersion occurs when count outcomes vary more than a chosen statistical model expects. If a model assumes less variability than the data contain, standard errors may be too small and uncertainty may be understated. A suitable analysis depends on the outcome distribution, study structure, and data available. The primary endpoint in this record is described as a count of participants meeting a status definition, but no analysis is posted. There is no basis for claiming that over-dispersion was present, that a particular count model was used, or that a model-based adjustment was made.

What do planning calculations mean?

General statistical explanation: sample-size planning illustrations ask how many participants might be required under stated assumptions to detect a specified effect with a chosen error rate and power. They are prospective planning exercises, not observed study outcomes. Their meaning depends on the assumed effect, allocation, statistical test, and other model conditions. A planning calculation based on an observed effect is especially dependent on that effect estimate and should not be described as observed power.

The registry record does not report the study's sample-size justification or its original design assumptions. It also does not report an observed primary-outcome effect from which to assess a recalculation. Any planning illustrations associated with an analysis should therefore be understood as hypothetical rather than as a statement about the trial's actual design or the certainty of its result. No sample-size target or power calculation is 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("Busulfan Treatment")
n      <- c(57)
events <- c(48)
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  Busulfan Treatment  57  48  84.2  72.1  92.5  72.6  91.5  72.6  91.4

11. Multiplicity, Missing Data and Analysis Populations

The record lists three outcome measures and identifies relapse-free survival as the primary outcome, with pulmonary toxicity named as a secondary outcome. The remaining outcome details and results are not reported in the registry record. It also lists zero analyses. No statistical analysis plan, hierarchy of secondary outcomes, or method for controlling the chance of false-positive findings across multiple outcomes is reported.

General statistical explanation: when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase if each is assessed independently at a conventional threshold. A multiplicity plan may specify which outcome is primary, how secondary outcomes are interpreted, or whether significance thresholds are adjusted. Without such details, readers cannot determine how any reported p-values would relate to an overall testing strategy. No p-values are posted for this study, so there is no basis for assessing multiplicity adjustment in practice.

The registry does not report how missing primary-outcome assessments were handled, how many participants were assessed at six months, or which participants were included in the primary analysis. It does not describe an intention-to-treat population, a per-protocol population, or another analysis population. The overall enrollment of 71 and the safety denominator of 57 do not, by themselves, explain the population used for the primary endpoint. Reasons for the difference are not reported in the registry record.

General statistical explanation: missing outcome data can affect interpretation when the probability of missingness is related to participants' health status or other factors. Approaches to missing data rely on assumptions, and those assumptions should be described alongside the analysis. The registry record does not state whether missing assessments occurred, how they were handled, or whether sensitivity analyses were conducted. It is therefore not possible to assess the impact of missing data or the robustness of an 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death nos (8.8%), adult respiratory distress syndrome (1.8%), allergic reaction - angioedemia due to ace inhibitors (1.8%), blood and lymphatic system disorders - other (relapsed disease) (1.8%), dyspenia (1.8%).

For the Busulfan Treatment group, the registry lists 57 participants at risk for serious adverse events and 12 affected. For other adverse events, it lists 57 at risk and 5 affected. These are separate safety categories. The counts describe participants recorded as affected; they do not tell how many event episodes occurred, whether events recurred, or how severe each event was beyond its classification.

The serious-event listing includes “Death NOS” at 8.8%, “Adult Respiratory Distress Syndrome” at 1.8%, “Allergic reaction - Angioedemia due to ACE Inhibitors” at 1.8%, “Blood and lymphatic system disorders - other (Relapsed disease)” at 1.8%, “Dyspenia” at 1.8%, and “Injury, poisoning and procedural complications - Other (patient fell and hit head. Never recovered)” at 1.8%. These percentages should be read as reported, not recalculated. The record does not state the denominator or counting method for each term.

Adverse events recorded during a study do not, by themselves, show that the intervention caused them. The record does not report event timing, individual attribution assessments, or detailed definitions for the listed terms. It also does not explain why the safety population is smaller than overall enrollment of 71. The figures describe what the registry reports, but do not support additional causal or comparative conclusions.

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

The record describes a phase II, completed, single-group study of busulfan and cyclophosphamide followed by autologous hematopoietic stem cell transplantation in patients with multiple myeloma. It identifies a primary endpoint at six months and reports safety counts for a treatment group. These details establish what the study was intended to examine and what types of outcomes the registry lists.

The primary endpoint result itself is not reported in the registry record. There is no posted count of participants without progressive disease at six months, no estimate of uncertainty, and no analysis. The record therefore cannot establish the observed outcome's magnitude or precision. The absence of a posted result should not be converted into a conclusion that the outcome was favorable, unfavorable, or unchanged.

The single-group design also limits what any outcome description could establish. Without a concurrent comparator, an outcome among treated participants cannot isolate the effect of the regimen from other explanations. The record does not present a randomized comparison or another controlled estimate. It would therefore be unwarranted to claim that the regimen caused a particular outcome or performed better or worse than an alternative.

The safety listing reports affected participant counts and selected serious adverse-event terms. These reports describe events recorded in the study, but do not establish that the regimen caused them. The registry does not provide enough detail to assess event timing, repeated events, attribution, or the relationship between the safety population and the overall enrolled group.

General statistical interpretation: a study's design and results answer only the questions supported by its measurements, follow-up, and analysis. A clearly defined endpoint can aid interpretation, but it does not substitute for a posted result. A reported count without a comparator is descriptive; a reported estimate without uncertainty can be difficult to assess for precision; and an adverse-event listing without attribution details does not establish causation. For this study, the posted record supports a description of design and selected safety data, not a conclusion about the primary outcome or comparative treatment effects.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint's operational definition matters as much as its title. “Relapse-free Survival” suggests an event-time outcome, yet the registry defines it as a count of participants without progressive disease at six months. Statistical interpretation depends on the measure actually specified and analyzed, not on a title alone. The difference affects what data are needed and which estimates would answer the clinical question.

The record also illustrates the limits of interpreting a single-group study. Such a design can describe outcomes among participants who received a regimen, but does not provide a concurrent treatment comparison. This distinction is central when readers move from describing observed outcomes to asking whether an intervention caused them. Statistical methods cannot create a control group that the design did not include.

Reporting completeness is another statistical issue. The registry identifies enrollment, the primary endpoint definition, the study status, and some safety figures, but does not post the primary outcome result or an analysis. Without the outcome count and its analysis, readers cannot assess the endpoint's observed magnitude or precision. Without details on analysis populations and missing data, readers also cannot determine how the observed population was formed.

The safety figures show why denominators and event definitions matter. The registry lists a safety population of 57 for each category, alongside an overall enrollment of 71, and gives selected serious-event percentages. Those details should not be silently combined or treated as interchangeable measures. Clarifying participant counts, event counts, time at risk, and attribution would support a more complete statistical reading.

These features make the record useful as an example of the boundary between study description and evidence about outcomes. The design and endpoint can be characterized, and the posted safety information can be read as recorded. The missing primary result and absence of a comparator prevent stronger conclusions. Recognizing those boundaries is an essential part of responsible analysis in clinical research.

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 main limitation for interpreting efficacy is that no primary-outcome result is reported in the registry record. Although the endpoint is defined as a count of participants without progressive disease at six months, the observed count, analysis population, and uncertainty estimate are absent. The record lists zero analyses, so no inferential result can be evaluated.

The single-group design has no separate comparator, and allocation is recorded as NA. This prevents a direct controlled comparison within the study. The registry does not report an external control or analysis that would support a comparative estimate. Any causal interpretation would go beyond the design information recorded.

The primary endpoint's title and definition are not fully aligned in their statistical implications. The title uses a time-to-event term, while the definition describes a fixed-time participant count. The record does not report event times, censoring rules, or a survival-analysis method. Readers cannot determine whether the posted analysis, if any, treated the endpoint as a fixed-time status or as a time-to-event outcome.

There is limited information about the analysis population and missing data. The record does not identify the number assessed at six months, explain how unavailable assessments were handled, or describe an intention-to-treat or other analysis set. The overall enrollment of 71 differs from the safety denominator of 57, but the reason is not reported. These gaps limit assessment of follow-up completeness and potential selection in the analyzed group.

Safety interpretation is also constrained. The record reports affected participants and selected serious-event terms, but does not provide event-level timing, recurrence, attribution, or the denominator method for each listed percentage. It does not explain whether participants could appear in both safety categories. The registry also does not report the study's sample-size justification, analysis plan, multiplicity strategy, or interim analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Busulfan, Cyclophosphamide, and Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma — NCT00941720.
• Registry record last updated 2020-07-24; status last verified 2020-07.
• Results first posted 2014-04-02.
• 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 identifies NCT00941720 as a completed phase II study sponsored by Case Comprehensive Cancer Center. It enrolled 71 participants with multiple myeloma or plasma cell neoplasm and evaluated busulfan and cyclophosphamide followed by autologous hematopoietic stem cell transplantation. The design is single-group, allocation is recorded as NA, and masking is none.

The primary endpoint is titled “Relapse-free Survival” and is defined as the number of participants without progressive disease at six months using International Myeloma Working Group definitions. Pulmonary toxicity is listed as a secondary outcome. The primary result and statistical analysis are not reported in the registry record, which lists zero analyses.

For the Busulfan Treatment group, the safety listing records 12 of 57 participants affected by serious adverse events and 5 of 57 affected by other adverse events. Selected serious adverse-event terms and percentages are also listed. The registry does not report details needed to explain the safety denominator, the missing primary result, or how participants with unavailable outcome assessments were handled.