Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome (NCT01165996), a na phase 1, phase 2 study. The primary outcome is Number of Patients With Response as Defined by IWG (International Working Group) Criteria for Myelodysplasia.

2. Clinical Question

The study’s stated rationale is that decitabine may help myelodysplastic cells become more like normal stem cells. That is the rationale for testing the treatment, not a finding established by the registry information. The listed conditions span several forms of myelodysplastic disease and related blood-count abnormalities. The record does not give a more detailed description of eligibility criteria or report how many enrolled patients received treatment and contributed to the endpoint analysis.

The clinical question is therefore descriptive: among the patients treated in this single-group study, how many met the specified response criteria at the formal assessment? Without a randomized control group, the study cannot directly estimate how outcomes would have differed under another treatment or no treatment. The registry record also does not report the observed response count, so the size and precision of the response estimate cannot be assessed from the posted information.

3. Trial Design

This completed study is registered as a phase 1 and phase 2 trial with a single-group model and no masking. Allocation is recorded as not applicable, consistent with the absence of randomized treatment groups. Enrollment was 25. The sponsor was Case Comprehensive Cancer Center. The recorded start was 2010-07, and primary completion was 2011-12.

The intervention arm description specifies subcutaneous decitabine during induction: twice weekly for 4 weeks or thrice weekly until bone marrow blasts were less than 5%. The maintenance phase then used subcutaneous decitabine twice weekly for up to 52 weeks, subject to the stated absence of disease progression or unacceptable toxicity. The record does not give further details about how patients were assigned between the induction schedules or how treatment duration was determined beyond those descriptions.

Laboratory procedures listed in the registry include flow cytometry, DNA methylation analysis, cytogenetic analysis, microarray analysis, gene expression analysis, pharmacological study, and polymorphism analysis. These procedures indicate that the study included biological and genetic assessments alongside the clinical response question. Their detailed timing, analysis methods, and results are not reported in the registry record.

A single-group design can describe outcomes observed in the treated participants, but it does not provide a randomized estimate of a treatment effect relative to a control group. The lack of masking also means that treatment and assessment were not described as blinded. The registry record does not report a protocol rationale for the sample size, a statistical analysis plan, or interim analyses. Although the study is marked completed, completion status alone does not establish that all planned assessments were reported.

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: All patients enrolled and that received any treatment.

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 Number of Patients With Response as Defined by IWG (International Working Group) Criteria for Myelodysplasia, measured over Formal assessment at week 12 for study primary end-point (hematologic improvement)..

The primary endpoint is titled as the number of patients with response according to International Working Group criteria for myelodysplasia. Its timeframe specifies a formal assessment at week 12 and calls the primary end-point hematologic improvement. The endpoint is expressed as a participant count rather than a continuous measurement, so its intended summary is the number meeting the specified response definition. The registry record does not report the observed count.

The description includes complete response, partial response, stable disease, disease progression, and hematologic improvement. Complete response requires less than 5% marrow blasts without evidence of dysplasia and normalization of peripheral blood counts, including hemoglobin of 110 g/L or more, neutrophils of 1.5 × 109/L or more, and platelets of 100 × 109/L or more. Partial response is described in relation to the complete-response criteria and pretreatment status, with specified alternatives involving marrow blasts or a less-advanced disease category. Stable disease means that partial response is not achieved and there is no evidence of progression. The record also describes progression criteria and hematologic improvement criteria involving blood counts and transfusions.

These clinical categories provide a framework for classifying disease status rather than relying on a single laboratory value. However, the endpoint title refers broadly to response, while the timeframe identifies hematologic improvement as the primary end-point. The record does not clarify how the categories were combined into the primary count or report the detailed operational analysis rules. Accordingly, the endpoint definition and the observed result cannot be fully evaluated from the registry information alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase 1 and phase 2 study, with no masking and allocation recorded as not applicable. In general, a single-group design follows outcomes in participants receiving the study intervention without random assignment to a separate comparison group. It can document what was observed in the enrolled group, but it does not directly estimate what would have happened to comparable participants under a different treatment. This distinction matters when interpreting response: a count of responders is a description of the treated group, not a randomized treatment contrast.

What does a participant count measure?

The primary endpoint is expressed as the number of patients meeting a response definition. In general, a count answers how many participants were classified as having an outcome, while a proportion relates that count to an explicitly defined group. The registry record states the endpoint population as all patients enrolled who received any treatment, but does not report the number in that population or the observed response count. It therefore does not permit the reader to verify the analysis denominator or derive an outcome proportion. No such calculation should be inferred from enrollment alone.

The criteria describe multiple clinical states. Complete response includes marrow, dysplasia, and peripheral blood count requirements. Partial response is defined in relation to complete-response criteria and changes from pretreatment status. Stable disease and disease progression are separate classifications, and hematologic improvement has its own blood-count and transfusion criteria. These definitions make classification depend on more than one measurement. In general, reproducible endpoint assessment requires clear rules for which criteria are applied, how missing components are treated, and how conflicting findings are resolved. Those operational details are not reported in the registry record.

How should the assessment time be understood?

The formal assessment is stated to occur at week 12. In general, a fixed assessment time helps define when an outcome is evaluated and makes the endpoint interpretable as a status at that scheduled point. It does not, by itself, explain whether earlier observations can count, how participants who discontinue before assessment are handled, or whether later confirmation is required. The registry record does not report those rules. It also does not report whether response was centrally reviewed or whether assessors were unaware of treatment, which is pertinent in a study with no masking.

What can confidence intervals contribute?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but an interval does not correct weaknesses in design or establish causality. No confidence interval for the primary response result is reported in the registry record. Since the response count and analysis denominator are also absent, the precision of the primary estimate cannot be assessed from the posted results.

Why do over-dispersion and model choice matter?

In general, over-dispersion occurs when outcome variation is greater than a statistical model assumes. When relevant, failing to account for it can make uncertainty estimates too small. The endpoint is described as a participant count, but the registry record does not state a model, variance assumption, or inferential method for the primary outcome. There is therefore no basis to say that over-dispersion was assessed or that a particular model was used. For a simple count in one group, the choice of method would still need to be stated to understand any reported uncertainty or comparison.

What do planning calculations mean?

In general, sample-size calculations are planning tools that describe the sample size associated with specified assumptions, such as a target effect, significance level, allocation, and statistical method. They are not observed trial outcomes and do not show the probability that a completed study found a true effect. The registry record does not report a sample-size justification or the assumptions used to design this study. Any planning illustration based on an observed effect should therefore be distinguished from the original design rationale and should not be described as observed power. No such design rationale is established by the registry information.

How should the endpoint wording be read?

The endpoint title identifies the number of patients with response by International Working Group criteria, while the stated timeframe names hematologic improvement as the primary end-point. The description lists response categories and gives criteria for several of them. In general, a statistical analysis should specify which classifications count as the primary event and how each participant is assigned a final outcome. The record does not state those decisions clearly enough to reconstruct the primary analysis. It also reports no analysis results, so there is no estimate to interpret against the endpoint definition.

The registry lists secondary outcomes involving serious non-hematologic toxicity, cytogenetic response, pharmacodynamic evidence of drug effect, marrow evidence of cytotoxicity or terminal differentiation, and genetic abnormalities in relation to clinical response. The presence of these outcomes does not establish that each was analyzed or reported. The registry record reports zero analyses and does not give statistical methods for these outcomes. Their results, uncertainty estimates, and any handling of multiple comparisons are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcome measures, including the primary response endpoint and secondary assessments of toxicity, cytogenetic response, pharmacodynamic effects, marrow findings, and genetic abnormalities in relation to clinical response. When a study evaluates multiple outcomes, there are generally more opportunities for apparently notable results to arise by chance. A multiplicity strategy can specify whether and how statistical error is controlled across those outcomes. The registry record does not report a multiplicity adjustment, a testing hierarchy, or another prespecified approach.

The record reports zero analyses and does not provide inferential results for the primary or secondary outcomes. It therefore does not report p-values, confidence intervals, or analysis methods for those endpoints. The absence of posted analyses should not be interpreted as evidence that no analyses were conducted; the methods and results are simply not reported in the registry record.

The primary endpoint population is described as all patients enrolled who received any treatment. Enrollment is 25, but the number who received treatment, completed the week 12 assessment, or were included in the endpoint analysis is not reported. The record also does not describe how missing assessments, early discontinuation, or incomplete response measurements were handled. In general, missing outcomes can affect both the analysis denominator and the interpretation of an endpoint, particularly when the reason for missingness is related to health status or treatment continuation.

No intention-to-treat population, per-protocol population, or separate safety population is identified in the posted information. The stated primary population definition is the only explicit analysis-population description. Without participant flow and missing-data rules, the relationship between enrollment, treatment exposure, endpoint assessment, and the reported safety counts cannot be fully traced.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (40.0%), death (12.0%), bacterial infection (8.0%), neutropenic fever (8.0%), acute left popliteal dvt (4.0%).

The safety information reports 15 participants with a serious adverse event among 25 at risk in Arm I. It also reports 3 deaths. The listed serious-event terms and their reported percentages are febrile neutropenia, 40.0%; death, 12.0%; bacterial infection, 8.0%; neutropenic fever, 8.0%; acute left popliteal DVT, 4.0%; and aspiration pneumonia, 4.0%.

These figures should be read as registry safety reports, not as a randomized comparison or an estimate of excess risk attributable to treatment. The record does not state that the events were caused by decitabine, and the percentages do not establish causality. It does not provide event timing, duration, recurrence, severity details beyond the listed serious-event classification, or an attribution assessment. The listed terms may describe event categories rather than mutually exclusive groups of participants; the registry record does not explain their overlap. Accordingly, the figures describe the recorded safety experience but do not support a causal interpretation.

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

The trial record documents a completed, single-group evaluation of decitabine with a formal week 12 assessment intended to address response under International Working Group criteria. It describes the induction and maintenance schedule, the enrolled population size, the planned endpoint criteria, and selected serious adverse event information. Those details help explain what the study set out to examine and what safety events were recorded.

The record does not report the observed primary response count. It also does not give a confidence interval, an analysis denominator, or the methods used to produce an efficacy estimate. As a result, the posted information does not establish how many treated participants met the response definition, how precise such an estimate might be, or how response categories were combined for the primary outcome. The wording difference between the endpoint title and the timeframe adds uncertainty about the exact primary outcome rule.

Even if a response count were available, this design would describe outcomes in one treated group rather than compare decitabine with a randomized control. The single-group structure cannot separate treatment-associated changes from other explanations. The absence of masking is another feature relevant to interpretation, particularly where response classification involves clinical and laboratory criteria.

The safety data document serious events and deaths in the study group, but the registry record does not establish that treatment caused them. Nor do the posted safety figures alone determine the overall balance of benefits and harms. The information does not support a conclusion that treatment works or does not work, and it cannot answer comparative questions about alternative care. The most defensible reading is that the registry describes the study plan and selected safety counts, while the principal efficacy result and several key analysis details are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable because its clinical question depends on a defined response classification, while the registry record does not report the resulting response count. The endpoint description encompasses marrow findings, peripheral blood counts, disease status, and transfusion-related criteria. Such a composite clinical framework can be meaningful for describing disease response, but it requires clear rules about which categories count as the primary event and how incomplete or discordant information is handled. The registry wording does not fully resolve those details.

The single-group design is also central to the statistical interpretation. A treated-group response count can describe what occurred among participants, but it does not estimate a comparative effect against a concurrent randomized control. This distinction is especially important when a study’s rationale concerns a potential treatment mechanism: a biological rationale motivates investigation, but the design and reported outcomes determine what conclusions the data can support.

The record also illustrates why enrollment and completion status do not substitute for results reporting. Enrollment is 25 and the trial is marked completed, yet the primary response result, confidence interval, analysis denominator, missing-data approach, and statistical analysis plan are not reported in the registry record. Without those details, readers cannot assess the magnitude or precision of the endpoint or reconstruct how the analysis was conducted.

Finally, the safety counts are interpretable as descriptive observations but not as causal estimates. Their statistical meaning depends on the event definitions, participant follow-up, overlap among categories, and attribution, details not fully reported in the record. Separating descriptive counts from comparative inference is therefore essential to reading this trial carefully.

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 principal limitation for interpreting efficacy is that the registry record does not report the observed primary endpoint result. It supplies neither the response count nor an analysis denominator, and it does not report an uncertainty estimate. The endpoint population is described as enrolled patients who received any treatment, but the number meeting that definition is not stated. The number assessed at week 12 is also not reported.

The primary endpoint description is not fully operationally clear. The title refers to response according to International Working Group criteria, while the timeframe calls hematologic improvement the primary end-point. The criteria description includes complete response, partial response, stable disease, disease progression, and hematologic improvement, but the record does not specify which classifications contributed to the primary count or how final classifications were assigned. No details are reported about independent assessment or adjudication.

The single-group, unmasked design provides no randomized control comparison and leaves the interpretation of observed outcomes vulnerable to influences that cannot be separated from treatment. The registry record does not report a sample-size justification, interim analysis plan, statistical analysis plan, missing-data handling, or multiplicity strategy. It also does not report statistical results for the listed secondary outcomes.

The treatment description gives an induction schedule and a maintenance phase, but does not provide further information about treatment exposure or adherence. For safety, the record reports serious-event counts and selected terms but does not provide timing, event-level detail, overlap among terms, or causal attribution. These omissions limit interpretation of both the clinical outcome and the safety profile without changing what the registry explicitly records.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome — NCT01165996.
• Registry record last updated 2019-03-04; status last verified 2019-02.
• Results first posted 2013-02-26.
• 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

NCT01165996 is a completed phase 1 and phase 2, single-group, unmasked study sponsored by Case Comprehensive Cancer Center. Enrollment was 25. The study evaluated subcutaneous decitabine using an induction phase followed by a described maintenance phase. The primary endpoint was titled as the number of patients with response by International Working Group criteria, with formal assessment at week 12.

The registry record does not report the primary response count, an analysis denominator, or inferential results. It reports 15 participants with a serious adverse event among 25 at risk and 3 deaths, alongside selected serious-event terms and percentages. The single-group design supports descriptive interpretation of the posted information but not a randomized treatment comparison. Key statistical methods, including missing-data handling and multiplicity procedures, are not reported in the registry record.