A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes (NCT00384956), a na phase 2 study. The primary outcome is Rate of Complete Remission (CR) and Partial Remission (PR).

2. Clinical Question

3. Trial Design

This was a phase II study of intravenous azacitidine alone in patients with myelodysplastic syndromes. The registry lists a single-group model, allocation as not applicable, and no masking. The study therefore has no randomized control arm and cannot directly compare outcomes between azacitidine and another treatment within this trial. The registry reports an enrollment of 25 and lists Washington University School of Medicine as the sponsor.

The recorded study start was 2006-08, primary completion was 2008-08, and status is completed. These administrative milestones describe the trial's progress, but completion does not itself indicate that outcome results were reported. In this registry record, there are no analysis entries, and the primary outcome result is absent.

The intervention description gives a starting dose of 75 mg/m2 intravenously on days 1-5 of each 28 day cycle. It says the dose would increase to 100 mg/m2 for patients who did not respond after two cycles. Patients achieving complete remission were described as receiving three additional 28 day cycles and then moving to treatment on days 1-5 of a 56 day cycle. The arm description ends mid-sentence, so further treatment details are not reported in the registry record.

The primary outcome is assessed after four cycles of therapy, with the timeframe described as up to 112 days after treatment began. The brief summary emphasizes morphologic complete remission, while the registered primary outcome title includes complete and partial remission. The record does not clarify whether the intended primary quantity was complete remission alone, either response category, or separate rates for both. Secondary outcomes listed include hematologic improvement, transfusion independence, cytogenetic response, overall survival, and relapse after hematopoietic stem cell transplant in individuals treated with 5-azacitidine before transplant.

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.

Population: 25 patients were enrolled and 22 were evaluable (3 patients had acute myeloid leukemia according to the FAB classification on enrollment bone marrow biopsy review and were removed from the study)

6. Primary Endpoint

The registry lists the primary outcome as Rate of Complete Remission (CR) and Partial Remission (PR), measured over After 4 cycles of therapy (up to 112 days after start of treatment).

The registry defines the primary outcome as the rate of complete remission and partial remission, measured in participants after four cycles of therapy, up to 112 days after the start of treatment. The response definitions refer to modified International Working Group response criteria for myelodysplasia from 2006. Complete remission requires bone marrow with <5% myeloblasts and 0% peripheral blasts, hemoglobin ≥11g/dL, platelets ≥ 100 x 10^9/L, and neutrophils ≥1.0 x 10^9/L; residual dysplasia is allowed. Partial remission requires the complete remission criteria that were abnormal before treatment, except that bone marrow blasts must decrease by ≥50% from pretreatment while remaining >5%.

A response endpoint is used to describe whether participants meet specified disease-related criteria at a defined assessment time. Requiring explicit criteria makes the outcome more reproducible than an unstructured judgment, although its interpretation still depends on how assessments were performed and how missing assessments were handled. Those details are not reported in the registry record.

The brief summary says the primary endpoint is to estimate morphologic complete remission rate, whereas the registered primary outcome title combines complete and partial remission. This distinction matters because a complete-remission rate and a rate including partial remission represent different response summaries. The registry record does not resolve the difference or provide an observed result. It therefore supports describing the endpoint and its criteria, but not reporting the trial's remission rate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a phase II, single-group study and lists no outcome analyses. It does not report a statistical analysis plan, the method used to estimate the primary outcome, or a confidence interval. Statistical concepts can help explain what an analysis might communicate, but they cannot be attributed to this trial unless the registry record reports them.

What would a response rate describe?

In general, a response rate is a proportion: the number of participants meeting a response definition relative to the number included in the analysis. For this trial, the response criteria distinguish complete remission from partial remission. A complete-remission result and a result that includes partial remission answer different questions. Reporting each category separately, or clearly defining a combined outcome, would make the estimand—the precise quantity the analysis aims to estimate—more interpretable. The registry record does not specify how its brief-summary wording and primary-outcome title were reconciled.

The denominator is as important as the response count. It might be all enrolled participants or a defined subset with an assessment, depending on the analysis population. These choices can produce different estimates when participants do not complete treatment or lack an outcome assessment. The registry lists enrollment of 25 but does not report the primary analysis denominator, the number assessed after four cycles, or how missing assessments were treated. No assumption about those choices is warranted.

How should precision be understood?

In general, a confidence interval gives a range of values compatible with the observed data under the method used to calculate it. It describes statistical uncertainty, not every source of uncertainty. A wide interval indicates limited precision; a narrow interval indicates greater precision under the analysis assumptions. A confidence interval does not account automatically for bias from selection, incomplete follow-up, measurement, or an unsuitable analysis population. The registry record reports no primary-outcome estimate or interval, so precision cannot be assessed for remission.

For a single-group study, a response estimate is descriptive of the participants included in the analysis. There is no randomized concurrent group in this study to provide a treatment contrast. In general, random allocation can help balance prognostic factors across comparison groups, while a single-group design cannot use that mechanism to make groups comparable. This does not make descriptive estimation impossible; it limits causal and comparative interpretation.

What do the design labels imply?

The single-group model means the registry does not define separate study arms for a head-to-head comparison. Allocation is listed as not applicable, and masking as none. These labels are consistent with a study that reports outcomes under one intervention rather than a masked randomized comparison. The record does not provide further details about assessment procedures or whether response assessments were independently reviewed.

The stated intervention includes dose escalation for participants who did not respond after two cycles, and a different cycle schedule for those achieving complete remission. Thus, the described regimen includes treatment adjustments based on response. The registry record does not report how many participants received each dose or schedule, so subgroup outcomes by treatment course cannot be described.

What can planning calculations tell a reader?

In general, sample-size planning calculations are conditional illustrations: they estimate the number of participants needed under specified assumptions about the effect to detect, the significance level, allocation, and statistical method. They are not observed trial outcomes and are not a measure of the probability that a study's finding is true. Planning illustrations based on an observed effect are especially dependent on the estimate chosen as their starting point. The registry record does not report a trial-specific sample-size justification, and the primary observed effect is not reported, so such illustrations should not be mistaken for the study's original design rationale.

A significance test, when used, evaluates the compatibility of data with a specified null model under its assumptions. A p-value is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The registry record does not report a primary-outcome p-value or state that a particular test was used. No test result should be inferred from the study's phase, enrollment, or completed status.

Count data and proportions are also affected by the way events cluster or vary across participants. In general, over-dispersion means that observed variation exceeds what a model assumes; ignoring it can make uncertainty estimates too optimistic. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not describe a model for the primary endpoint, and its outcome title is a participant count rather than a reported modeled rate. Therefore, no model-specific assumption can be assigned to the trial.

Finally, a statistical analysis is only interpretable alongside its outcome definition, assessment time, analysis population, missing-data handling, and uncertainty estimate. The registry provides a response definition and timeframe, but not the count, denominator, method, or interval. Those omissions leave the primary outcome statistically unquantified in this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, including hematologic improvement, transfusion independence, cytogenetic response, overall survival, and relapse after hematopoietic stem cell transplant for individuals treated with 5-azacitidine before transplant. It reports nine outcome measures overall, but does not provide outcome analyses. The statistical plan is not reported in the registry record.

When a study evaluates multiple outcomes or performs multiple tests, the chance of at least one apparently notable result can increase. In general, a prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory analyses can help readers interpret a collection of results. The record does not state whether multiplicity was addressed, whether secondary outcomes were intended to be confirmatory or descriptive, or how the different response categories were handled.

The primary outcome itself has a wording discrepancy: the brief summary emphasizes morphologic complete remission, while the registered primary outcome title includes both complete and partial remission. The record does not explain whether these were analyzed separately, combined, or prioritized. This uncertainty affects what a primary result would represent even if a result were available.

Missing-data procedures and analysis populations are not reported. The registry does not give the number assessed for the primary outcome, the number with incomplete assessments, reasons for missingness, or any method for handling missing values. It also does not specify whether the analysis included all enrolled participants or a subset. Enrollment of 25 cannot substitute for a reported denominator.

These gaps prevent assessment of whether outcome reporting followed a prespecified plan, whether missing observations could have influenced estimates, or how secondary findings should be weighed. No interim analysis plan is reported in the registry record.

11. 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: neutropenic fever (20.8%), dyspnea (8.3%), cough (8.3%), fever (8.3%), pneumonia (4.2%).

The adverse-event fields list 24 participants at risk for serious adverse events, of whom 12 were affected. For other adverse events, the record lists 24 at risk and 24 affected. These are separate categories; the figures should not be combined into a single count of participants with any adverse event. The registry does not provide further detail about event counts per participant or how repeat events were summarized.

The listed serious adverse-event terms and percentages are neutropenic fever, 20.8%; dyspnea, 8.3%; cough, 8.3%; fever, 8.3%; pneumonia, 4.2%; and infection with unknown neutrophils (sepsis), 4.2%. The registry record does not specify whether participants could be represented in more than one term, so the percentages should not be added to estimate a total affected proportion.

The deaths field is not reported in the registry record. That absence should not be interpreted as evidence that no deaths occurred. The record also does not provide event timing, duration, severity grades, attribution, or a comparison group. These figures describe the safety entries recorded for this single-group study; they do not establish a comparative safety difference.

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

The record establishes that this was a completed phase II study of intravenous azacitidine in a single group of patients with myelodysplastic syndromes. It describes the planned treatment schedule and response criteria, and it lists selected serious adverse-event terms. It does not report the primary remission count or rate. Therefore, the registry record cannot show how many participants met the response criteria or how precisely any response rate was estimated.

The endpoint is also not described consistently across the record: the brief summary identifies morphologic complete remission as the primary endpoint, while the registered primary outcome title includes complete and partial remission. The outcome definition supplies criteria for both categories, but the record does not say how they relate to the primary analysis. This makes the intended primary quantity uncertain.

Even if a response estimate were available, a single-group study would describe outcomes in the treated participants, not provide a randomized comparison with another treatment. A response rate on its own cannot establish what would have happened to similar participants under a different treatment or without the study intervention. The design does not include a concurrent control group.

Likewise, the listed adverse-event entries are descriptive. They identify reported events in the study group, but there is no control group for comparison and no detailed information about event timing, severity, or attribution. The deaths field is not reported, which is distinct from a report of no deaths.

Accordingly, the registry supports discussion of the study's design, intended outcomes, response definitions, and recorded safety entries. It does not support a numerical conclusion about remission, a comparative efficacy claim, or a complete assessment of benefit and harm. The status of completed indicates a study milestone, not that outcome findings are present in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a registry record must be read as more than a study title and enrollment figure. The design, endpoint wording, outcome definition, analysis population, and posted result each contribute different information. Here, the record describes a phase II single-group study and gives detailed remission criteria, but it does not report the primary outcome result. As a result, the endpoint can be explained without being estimated.

The discrepancy between the brief summary's focus on morphologic complete remission and the registered outcome title's inclusion of complete and partial remission is also statistically important. A clearly defined estimand tells readers which response category is being counted, at what time, and among which participants. Without clarification, even a hypothetical reported count could be ambiguous about what it represents.

The trial also demonstrates the limits of interpreting single-group results. Such a design can describe outcomes in participants receiving a treatment regimen, but it does not offer a randomized concurrent contrast. Statistical precision around a response proportion, if reported, would not by itself solve that design limitation; precision and causal interpretation are different issues.

Finally, safety records require denominators and definitions just as efficacy outcomes do. The adverse-event entries identify affected participants and selected event terms, but do not supply all details needed for comparative safety interpretation. A completed registry entry with incomplete outcome reporting is therefore not equivalent to a complete statistical account of the trial. Readers need both the design context and the limits of what the record quantifies.

14. 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 of the registry record is that it does not report the primary remission result. The number achieving complete remission, the number achieving partial remission, and the primary analysis denominator are not reported. Although enrollment is listed as 25, that figure does not establish how many participants were assessed after four cycles or included in an outcome analysis.

The primary outcome has inconsistent wording across the record. The brief summary describes estimation of morphologic complete remission rate, while the registered primary outcome title refers to complete remission and partial remission. The record does not explain whether these categories were separate outcomes or how they were intended to contribute to the primary endpoint.

Further limitations are the absence of a reported statistical analysis plan, analysis method, confidence interval, and p-value. The analysis population, missing-data handling, and any interim analyses are not reported in the registry record. The arm description is truncated, leaving the remainder of the treatment description unavailable.

The single-group design has no randomized concurrent comparator, so any reported response rate would be descriptive rather than a direct estimate of a treatment contrast. The safety information is also limited: deaths are not reported, and details such as timing, severity, attribution, and repeat events are not given. These constraints limit interpretation of both efficacy and safety from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes — NCT00384956.
• Registry record last updated 2016-12-12; status last verified 2016-10.
• Results first posted 2014-09-08.
• 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.

18. Record Summary

NCT00384956 is a completed phase II, single-group study of intravenous azacitidine in patients with myelodysplastic syndromes, sponsored by Washington University School of Medicine. The record lists enrollment of 25, a study start of 2006-08, and primary completion in 2008-08. Allocation is recorded as not applicable, and masking as none.

The primary outcome is described as complete and partial remission after four cycles, up to 112 days after treatment starts, with criteria based on modified International Working Group response definitions. The brief summary instead emphasizes morphologic complete remission. The primary outcome result, analysis denominator, statistical method, and missing-data handling are not reported in the registry record.

Selected adverse-event entries include serious-event and other-event participant counts, along with listed serious-event terms. The record does not report deaths. Without a reported primary outcome result or a comparator group, the record supports design and endpoint description but not a comparative efficacy conclusion.