High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma (NCT00349778), a na phase 2 study. The primary outcome is Number of Participants With Pulmonary Toxicity.

2. Clinical Question

The clinical question is therefore about the frequency of a specified toxicity during a treatment sequence, rather than a comparative effect against another regimen. The study summary says the treatment was evaluated for efficacy and side effects, and that the regimen was designed to reduce the risk of interstitial pneumonitis. That statement describes the study’s aim; it is not evidence that the risk was reduced, because no before-and-after or concurrent comparator is recorded.

The registry lists overall participant survival and the number of participants who relapse after autologous transplantation as secondary outcomes. Their outcome results are not reported in the registry record. The record also does not specify the enrolled participants’ clinical characteristics, how toxicity was defined beyond the interstitial pneumonitis description, or whether every enrolled participant contributed to the primary outcome. Consequently, the clinical question can be identified, but its answer and the breadth of the population to which it might apply cannot be established from the recorded outcome information.

3. Trial Design

This completed Phase 2 study is recorded as a single-group trial with 102 participants enrolled. Stanford University is listed as the sponsor. The record gives a start date of 2006-08 and a primary completion date of 2009-04. Allocation is listed as NA, and masking as none. These entries describe a design without a randomized allocation or masking procedure recorded.

The intervention group is titled High-Dose Sequential Therapy. Its description names cyclophosphamide, etoposide, melphalan and carmustine with filgrastim. The study summary also describes a stem cell transplant, and the listed secondary outcome includes relapse after autologous transplantation. This is a treatment sequence, not a comparison between independently assigned arms. The registry’s design labels do not provide the timing, doses, sequencing details, or supportive-care protocol; those details are not reported in the registry record.

The primary outcome is the number of participants with pulmonary toxicity, defined in the description as incidence of interstitial pneumonitis, with a timeframe of 2 years. The record lists overall participant survival and relapse after autologous transplantation as secondary outcomes. It reports three outcome measures in total, but numerical results for these outcomes are not reported in the registry record. There are no analyses listed.

Because there is no control group, the recorded design can describe outcomes observed in participants receiving the regimen but cannot by itself separate treatment effects from the course of disease, participant characteristics, other care, or chance. The record does not report a protocol, a statistical analysis plan, or details of how participants were followed for each outcome. Any interpretation must therefore distinguish the study’s stated purpose from outcome evidence and avoid treating this single-group experience as a controlled comparison.

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

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: all patients who proceeded to transplant on trial

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Pulmonary Toxicity, measured over 2 years.

The primary endpoint is the number of participants with pulmonary toxicity during a timeframe of 2 years. The registry description specifies that pulmonary toxicity was assessed as the incidence of interstitial pneumonitis. This makes the endpoint a count of participants meeting the study’s toxicity definition over the stated period, rather than a continuous measurement or a time-to-event estimate as described in the record.

Tracking a prespecified toxicity can help characterize a regimen’s safety profile. In this study, the summary identifies reducing the risk of interstitial pneumonitis as a design aim, so the endpoint addresses a concern relevant to the treatment being studied. In general, an endpoint is most interpretable when the case definition, surveillance procedures, follow-up completeness and analysis population are clear. Those operational details are not reported in the registry record.

The registry names the endpoint and its timeframe but does not give a primary-outcome count or an analysis. The serious adverse event listing separately includes interstitial pneumonitis at 1.0%. That listing should not automatically be treated as the primary endpoint result: a serious adverse event category and a prospectively defined endpoint may use different collection rules or populations, and the record does not establish that they are identical. Thus the primary measure is identifiable, while its numerical finding and its relationship to the adverse-event listing remain unclear.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a single-group Phase 2 design and lists no analyses. That distinction matters: the design describes how participants were assigned or observed, while an analysis describes how outcome data were turned into estimates and statistical comparisons. The record gives no statistical analysis plan, model specification, or test results. The discussion below explains general statistical concepts relevant to the outcomes without attributing unreported methods to this trial.

What does a participant count represent?

For a binary endpoint, each participant is generally classified according to whether the event occurred under a defined outcome rule. A count is the number classified as having the event; its interpretation depends on the denominator, the event definition, and the observation window. Here, the primary endpoint is described as the number of participants with pulmonary toxicity, assessed as interstitial pneumonitis, over 2 years. The registry record does not report the endpoint count, its denominator, or details of the classification and follow-up procedures.

A participant count is not interchangeable with an event count. One participant might have more than one event, while a count of affected participants counts that person once under the endpoint definition. The adverse-event listing reports participants affected for serious and other adverse events, but the registry does not explain how repeated events were handled or how the safety categories map to the primary endpoint. Those distinctions matter when interpreting the serious adverse event figures.

Why does a comparator matter?

In a randomized comparison, allocation is intended to make treatment groups comparable in expectation, supporting an estimate of the difference between assigned strategies. This record lists a single group and allocation as NA. It therefore offers no randomized control arm against which to estimate a treatment contrast. The observed outcomes, even if fully reported, would characterize participants in the treatment group and would not alone show what would have occurred under another regimen.

General explanation: an uncontrolled outcome count can reflect treatment, underlying disease, participant factors, concurrent care, and chance. A treatment effect requires a meaningful counterfactual comparison: an estimate of outcomes under the treatment compared with outcomes under an alternative. A single-group record does not supply that contrast. Comparing its outcomes with results from a different study would require careful consideration of differences in populations, follow-up, event definitions and clinical context.

What would a confidence interval add?

General explanation: a confidence interval expresses uncertainty around an estimated effect or event frequency under a specified statistical procedure. A narrow interval indicates greater precision under that procedure; a wide interval indicates less precision. An interval does not resolve bias from the design, incomplete follow-up, or inconsistent measurement. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated from the posted results.

For event counts, uncertainty depends on the number of observed events and the analysis approach. If events are uncommon, the estimate may be particularly imprecise, even when the enrolled group is sizable. This is a general statistical point, not a claim about the unreported primary outcome in this study. The record’s serious adverse-event entries should not be used to construct an interval for the primary outcome without confirming that the endpoint and adverse-event definitions and denominators match.

How should time-to-event outcomes be understood?

Overall survival and relapse after autologous transplantation are listed as secondary outcomes. Time-to-event methods can account for the time until an event and for participants whose event time is not observed during follow-up, if censoring and other assumptions are handled appropriately. A survival curve can describe the pattern of event-free follow-up over time, while a hazard ratio can compare event rates between groups when a suitable comparison exists. These are general descriptions, not methods reported for this trial. The registry record does not provide survival estimates, relapse results, censoring details, or analyses.

Follow-up duration and completeness are important for interpreting either event counts or time-to-event estimates. The primary endpoint has a stated timeframe of 2 years, but the record does not say how many participants completed that follow-up, how missing outcome assessments were handled, or whether all participants entered follow-up at the same point. Those omissions limit interpretation of any frequency, even if a count were available.

What do planning calculations mean?

The planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is the total number of events; other illustrations refer to participants per arm. These assumptions are hypothetical planning choices, not evidence that the original study used a two-arm design or planned a particular sample size.

General explanation: a sample-size calculation estimates the number of participants or events that a proposed design would need to detect a specified effect under stated assumptions. Its output depends on the target effect, variability or event frequency, significance level, power target, allocation, follow-up and analysis method. If an illustration uses an effect estimated from observed data, it remains a planning exercise, and its result should not be described as observed power. It cannot establish that the completed single-group trial was adequately powered for an unreported endpoint.

The registry record does not report the trial’s sample-size justification, interim analyses, or statistical plan. Consequently, planning assumptions associated with hypothetical calculations should not be attributed to the original protocol. They also cannot fill the gap left by the missing primary outcome result.

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("High-Dose Sequential Therapy")
n      <- c(102)
events <- c(32)
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  High-Dose Sequential Therapy  102  32  31.4  22.5  41.3  23.2  40.9  23.2  40.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record names a primary outcome and two secondary outcomes: overall participant survival and relapse after autologous transplantation. It reports three outcome measures in total and lists no analyses. Numerical results for the primary and secondary outcomes are not reported in the registry record. The multiplicity strategy, including whether any adjustment or hierarchy was planned for testing multiple outcomes, is not reported in the registry record.

General explanation: when several outcomes or hypotheses are tested, the chance of at least one apparently unusual result can increase if every test is interpreted independently. A prespecified hierarchy or multiplicity adjustment can help control that issue, but the appropriate method depends on the scientific aims and analysis plan. There is no basis in the registry record to say whether such a method was used.

Information about missing data and analysis populations is also limited. The record does not report how many participants had assessable primary outcome data, whether follow-up was complete through the 2-year timeframe, how missing or unevaluable outcomes were handled, or whether any participants were excluded from particular analyses. The record lists 102 enrolled participants, but enrollment alone does not establish the denominator used for every endpoint.

General explanation: missing outcome data can affect an estimate if participants with missing assessments differ systematically from those with observed data. The impact depends on why data are missing and how the analysis handles them. Without participant flow, endpoint-specific denominators, and missing-data methods, it is not possible to assess that risk for this study. The posted record also does not specify an intention-to-treat, per-protocol, or safety population. These analysis-population details are not reported in the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: cardiogenic shock (1.0%), fungal infection (1.0%), aspergillus infection (1.0%), interstitial pneumonitis (1.0%), infection (1.0%).

The safety entry is for the High-Dose Sequential Therapy group. It lists 102 participants at risk for serious adverse events and 5 affected. For other adverse events, it lists 102 at risk and 0 affected. The record also lists 22 deaths. These are the recorded figures; the registry does not give the timing, event-level detail, or cause-of-death information needed to interpret the death count further.

The top serious adverse event terms are cardiogenic shock, fungal infection, aspergillus infection, interstitial pneumonitis, and infection, each listed at 1.0%. These are serious-event terms, not necessarily mutually exclusive categories: one participant may have experienced more than one type of event, and the record does not explain how categories were counted. The terms should not be added together or treated as a complete description of all safety outcomes.

The primary endpoint is pulmonary toxicity assessed as interstitial pneumonitis over 2 years. Its outcome count is not reported in the registry record. Although the serious adverse event list includes interstitial pneumonitis, the record does not establish that this serious-event entry represents every case meeting the primary endpoint definition. The adverse-event summary therefore provides safety context, but cannot substitute for the missing primary endpoint result or establish causation.

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

The registry record supports a limited description of the study: it was a completed Phase 2, single-group study enrolling 102 participants with multiple myeloma, evaluating high-dose sequential therapy with autologous transplantation. It identifies pulmonary toxicity, assessed as interstitial pneumonitis over 2 years, as the primary endpoint. The record also identifies survival and post-transplant relapse as secondary outcomes and contains a serious adverse-event summary.

It does not report the numerical result for the primary endpoint, numerical results for the secondary outcomes, or statistical analyses. Consequently, readers cannot determine the recorded frequency of primary-endpoint pulmonary toxicity from the primary outcome entry, assess its precision, or evaluate survival and relapse results. The serious adverse event listing includes interstitial pneumonitis at 1.0%, but the registry does not establish that this listing uses the same definition, timeframe, or population as the primary endpoint. It should not be presented as the primary outcome estimate.

The single-group design also limits what can be inferred. Without a concurrent comparison group, the record cannot estimate how outcomes differ from another treatment strategy or from no treatment. It cannot establish that the regimen reduced toxicity, improved survival, or changed relapse risk. The study summary’s stated aim to reduce the risk of interstitial pneumonitis is a study rationale, not a finding.

General explanation: a registry entry is most informative when it reports outcome definitions, denominators, estimates, uncertainty, analysis populations and methods. Missing detail does not show that an outcome did not occur or that an analysis was not conducted outside the record; it means the result is not reported in the registry record. The conclusions should therefore remain bounded by the documented design and safety entries, rather than extending to efficacy or comparative safety claims that the record cannot support.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its stated clinical objective and its recorded design answer different kinds of questions. The study summary describes an interest in efficacy and side effects, with a specific aim related to interstitial pneumonitis. The registry describes a single-group study, however, so its design does not provide a randomized contrast between this regimen and an alternative. That distinction is central to reading treatment studies: an observed outcome count is not the same as an estimate of treatment effect.

The primary endpoint is clearly named and has a defined timeframe of 2 years, but its numerical result is not reported in the registry record. The record separately lists serious adverse events, including interstitial pneumonitis, yet does not establish that this safety category and the primary outcome share their definitions and ascertainment. This illustrates why outcome labels alone are not enough: denominators, event rules, follow-up, and analysis populations determine what a count represents.

Another statistical lesson is that design information and analysis information should be read separately. The record identifies enrollment and the single-group structure, but lists no analyses or statistical plan. As a result, readers cannot assess estimates, uncertainty, multiplicity handling, missing-data methods, or endpoint-specific populations. A registry record may identify what investigators intended to study without documenting enough outcome evidence to answer the scientific question.

Finally, planning calculations must not be confused with evidence from the completed study. A hypothetical calculation using two arms and an assumed effect can illustrate design requirements, but it does not convert a single-group trial into a comparative study or supply missing results. Keeping these distinctions explicit helps prevent overinterpretation and makes clear which conclusions are supported by the recorded design and which require outcome data that are not reported.

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 consequential limitation in the registry record is the absence of numerical results for the primary endpoint. Although pulmonary toxicity is defined as incidence of interstitial pneumonitis over 2 years, no primary outcome count, denominator, estimate of uncertainty, or analysis is reported. Secondary outcomes are named, but their numerical results are also not reported. This prevents assessment of the intended clinical outcomes from the outcome entries.

The single-group design provides no concurrent control. Any observed outcomes would be descriptive of the treated group and could not isolate the effect of the regimen from other influences. The record also does not describe participant eligibility details, baseline characteristics, treatment timing or doses, follow-up procedures, or endpoint adjudication. These omissions limit assessment of clinical comparability, reproducibility, and the extent to which the enrolled group represents other populations.

The adverse-event entry does not resolve the missing primary result. It lists serious events and a separate other-event count, but does not report how serious events were defined, how often participants were assessed, or how adverse-event categories relate to the primary endpoint. The 22 deaths are listed without timing or cause details in that summary. They cannot be interpreted as a survival analysis or attributed to treatment from the record alone.

The registry record lists no analyses and does not report the statistical plan, sample-size justification, interim analyses, missing-data handling, analysis populations, or multiplicity approach. It also does not give endpoint-specific follow-up completeness. These gaps leave uncertainty about the precision and potential biases of any unreported estimates. The record supports a description of the study design and listed safety terms, but not an efficacy conclusion or a quantified primary-outcome conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma — NCT00349778.
• Registry record last updated 2017-12-12; status last verified 2017-11.
• Results first posted 2017-12-12.
• 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

NCT00349778 is a completed Phase 2, single-group study sponsored by Stanford University, with 102 participants enrolled. It studied high-dose sequential therapy and autologous transplantation for multiple myeloma. The regimen description lists cyclophosphamide, etoposide, melphalan and carmustine with filgrastim.

The primary outcome was the number of participants with pulmonary toxicity, assessed as interstitial pneumonitis over 2 years. Overall participant survival and relapse after autologous transplantation were listed as secondary outcomes. Numerical results for these outcomes and statistical analyses are not reported in the registry record.

The adverse-event entry lists 5 participants affected by serious adverse events among 102 at risk, 0 affected by other adverse events among 102 at risk, and 22 deaths. Interstitial pneumonitis appears among the top serious-event terms at 1.0%. The record does not establish that this safety listing is equivalent to the primary endpoint. The single-group design does not provide a randomized comparator for estimating treatment effects.