Evaluating the Safety and Effectiveness of Decitabine in People With Thalassemia Intermedia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Safety and Effectiveness of Decitabine in People With Thalassemia Intermedia (NCT00661726), a na phase 2 study. The primary outcome is Number of Evaluable Patients With an Increase From Baseline in Hemoglobin (Hb) of ≥1.5 g/dL.

2. Clinical Question

This framing matters because an observed change from baseline in a single group does not by itself establish that the intervention caused the change. There is no concurrent control group in the record to help distinguish a treatment-associated change from other influences, natural variation, or measurement variation. The study also lists secondary outcomes involving fetal hemoglobin and several blood-related laboratory measures. Their inclusion indicates a broader set of outcomes was considered, but their numerical findings are not reported in the registry record. The clinical question should therefore be read as a description of the outcome the study set out to assess, not as evidence of a demonstrated benefit.

3. Trial Design

The registry describes a phase II study with a single-group model, no masking, and allocation recorded as NA. It lists 6 enrolled patients and a completed status. The study began in 2008-01, and primary completion is recorded as 2010-05. These dates describe the registry record; they do not supply information about how long each participant was followed beyond the stated outcome timeframe.

The intervention was decitabine, described as injected and scheduled for 12 weeks. No comparator arm is listed. Because all participants were assigned to the single listed group, there is no randomized, like-for-like control comparison in this record. The absence of masking also means the record does not describe masking of participants, clinicians, or outcome assessors. Further details about how the intervention was administered are not reported in the registry record.

The primary endpoint is a count of evaluable patients meeting a specified hemoglobin-change threshold, assessed up to 12 weeks. The registry says one of 6 enrolled patients withdrew after week 2 and was not used for analysis. This makes the analysis population smaller than the enrolled population, but the record does not provide a separate numerical denominator for the primary result or explain how evaluability was otherwise determined.

The listed secondary outcomes cover absolute fetal hemoglobin, indirect bilirubin, serum lactate dehydrogenase, absolute reticulocyte count, erythropoietin, platelet count, neutrophil counts, and red blood cell deformability. Several are defined using a peak or nadir during follow-up. The record lists 12 outcome measures and 11 analyses, but further details on the analysis methods are not reported in the registry record. The trial’s statistical plan, including any prespecified handling of multiple outcomes, 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.

Before assignment: To be eligible, patients had to be \>=18 years of age and have beta thalassemia intermedia or beta thalassemia-HbE intermedia, no transfusions for 120 days, no hydroxyurea for 120 days, have RBC folate levels above the lower limit of normal, and steady-state anemia (post pt #2, the protocol was amended to define anemia hemoglobin level of \<10g/dl).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One of 6 enrolled patients withdrew from study after week 2 and was not used for analysis.

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 Evaluable Patients With an Increase From Baseline in Hemoglobin (Hb) of ≥1.5 g/dL, measured over up to 12 weeks.

The primary endpoint is the number of evaluable patients with an increase from baseline in hemoglobin (Hb) of at least 1.5 g/dL. The registry gives an assessment timeframe of up to 12 weeks. This is a binary response definition at the participant level: a patient either meets the stated threshold or does not. The endpoint is then expressed as a count of patients meeting that definition, rather than as the average change in hemoglobin across the group.

A threshold-based endpoint can make a study question concrete. It identifies a change that the study classifies as a response and focuses attention on how many evaluable patients crossed that boundary. It does not, on its own, describe the size of each patient’s change, the range of changes, or how close patients who did not meet the threshold came to it. Nor does a count alone convey the precision of the estimated response frequency; that requires a denominator and, typically, an uncertainty interval.

The registry’s primary outcome description does not give the observed count, an uncertainty interval, or a numerical denominator for the analysis. The numerical primary result is not reported in the registry record. One withdrawal after week 2 was excluded from the primary analysis, according to the record. How other incomplete measurements, if any, were treated is not reported in the registry record. The threshold and timeframe define what was intended to be measured; they are not themselves evidence that the threshold was met.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint count?

The endpoint counts evaluable patients whose hemoglobin increased from baseline by at least 1.5 g/dL, within a timeframe of up to 12 weeks. In general, a binary endpoint classifies each participant according to whether a defined event or threshold was met. A count of responses is easy to interpret in ordinary terms, but it needs a denominator to show how common the response was in the analyzed group. The primary result and its analysis denominator are not reported in the registry record.

In general, an estimate based on a small group can be imprecise: changing the classification of one participant can have a substantial influence on the reported response frequency. An uncertainty interval communicates the range of values compatible with the observed data under the chosen statistical method. Such an interval is not reported for this primary outcome in the registry record. Without the response count and denominator, no response frequency or interval can be interpreted.

What can a single-group design tell us?

This study is identified as single-group, with allocation recorded as NA and no comparator listed. In general, a before-and-after assessment describes change over time within the observed group. It does not isolate the effect of an intervention as well as a comparison that includes an appropriate control group, because other explanations for change remain possible. A randomized comparison can help balance known and unknown influences between groups; this record does not describe such a comparison.

The study is also listed as unmasked. In general, masking can reduce the possibility that knowledge of treatment assignment influences behavior, clinical decisions, or outcome assessment. The record does not specify which people, if any, were masked in particular parts of the study, and no masking is recorded. It is therefore not possible to assess from this record how outcome assessment was conducted or whether any safeguards were used.

How should the safety counts be understood?

In general, an adverse-event count and an at-risk denominator describe how many participants in a group were reported to have an event. A serious adverse event is a registry category; the count is not, by itself, proof of a causal relationship to the intervention. For this study, the serious-event figures are reported for the Decitabine group as 3 affected among 5 at risk, and other adverse events as 4 affected among 5 at risk. The record also lists High Platelets Count at 60.0% among the top serious terms. Event timing, causal attribution, and further clinical detail are not reported in the registry record.

What do the planning assumptions mean?

The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s original design. The assumptions specify a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are assumptions for an illustrative planning exercise, not evidence about the design choices used when this study was planned.

In general, a significance level sets a decision threshold for a statistical test under a specified model. A two-sided test allows evidence in either direction to count against the null hypothesis. Equal allocation is a planning choice that assigns the same intended number of participants to each hypothetical arm. A normal approximation uses a mathematical distribution to make an estimate or test tractable; its suitability depends on the outcome and data structure. The record does not report a trial-specific statistical plan or sample-size justification. No planning illustration should be read as observed power or as a result from the study.

For a binary outcome, planning sample sizes depend on the assumed response frequency in each group, the difference the study aims to detect, the chosen significance level, desired power, and analysis method. Those quantities are not all reported as trial design details. Because this is a single-group study, a hypothetical equal-allocation, two-arm planning calculation does not turn the actual trial into a controlled comparison. The planning calculations are illustrations rather than a description of the study’s enrollment decision.

What is not described statistically?

The registry lists 12 outcome measures and 11 analyses. It does not report the methods used for the primary analysis, any model or test, or the approach used to calculate uncertainty. The record also does not report a statistical analysis plan, interim analyses, or a rationale for the sample size. Those details should not be inferred from the endpoint wording or from the planning assumptions.

In general, a statistical method should correspond to the outcome type, study design, and assumptions about the data. For a count of participants meeting a binary threshold, an analysis can estimate the response frequency and its uncertainty. But the specific estimator and interval method matter, particularly when the dataset is small. Since those methods and the primary numerical result are not reported in the registry record, there is no basis to evaluate their implementation for this study.

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("Decitabine")
n      <- c(5)
events <- c(2)
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  Decitabine  5  2  40.0  5.3  85.3  11.8  76.9  11.8  77.7

11. Multiplicity, Missing Data and Analysis Populations

The study lists 12 outcome measures and 11 analyses, including a primary hemoglobin endpoint and secondary laboratory outcomes. The numerical results for the primary and secondary outcomes are not reported in the registry record. The record does not explain the difference between the number of measures and analyses, nor does it describe whether every listed outcome was analyzed or how outcome selection was handled.

In general, testing multiple outcomes creates more opportunities for a result to appear noteworthy by chance. A prespecified hierarchy, adjustment procedure, or clear distinction between confirmatory and exploratory outcomes can help readers understand how to interpret multiple findings. The registry record does not report whether such an approach was used. No adjustment or multiplicity strategy should be assumed.

For missing data and analysis populations, the record states that one of 6 enrolled patients withdrew after week 2 and was not used for the primary analysis. The reason for withdrawal, the handling of any measurements after withdrawal, and the rules defining an evaluable patient beyond this statement are not reported in the registry record. It is not reported whether other outcome-specific data were missing or how any such data were handled.

In general, excluding participants with incomplete follow-up can affect interpretation if the reasons for missingness are related to outcomes or treatment experience. The registry’s note identifies an exclusion but does not supply enough information to assess its consequences. The record does not state whether sensitivity analyses or alternative analysis populations were used. Accordingly, conclusions should remain limited to the stated endpoint definition and the available enrollment and withdrawal information.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: high platelets count (60.0%).

The registry reports adverse-event counts for the Decitabine group. Serious adverse events affected 3 of 5 participants at risk; other adverse events affected 4 of 5 at risk. High Platelets Count is listed among the top serious terms at 60.0%. These are descriptive registry figures and should be read according to their stated categories and denominators.

A serious adverse event is not synonymous with an event caused by the intervention. In general, safety counts describe events reported during a study, while causal attribution requires further assessment. The record does not report event-level attribution, timing, or additional details for these figures. The listed term and percentage do not establish whether the event was persistent, clinically consequential, or related to decitabine.

The group is small, so the counts provide limited information about the range and frequency of possible safety outcomes beyond the participants observed. The registry does not provide a control group for comparing event rates. These registry entries are therefore best interpreted as a description of reported events in this study group, not as a comparative safety estimate or a complete characterization of risk.

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

The record establishes that a phase II, single-group study evaluated injected decitabine in people with thalassemia intermedia and defined a primary outcome based on a hemoglobin increase of at least 1.5 g/dL from baseline. It also records a 12-week intervention period, a primary assessment timeframe of up to 12 weeks, a withdrawal excluded from analysis, and adverse-event counts for the Decitabine group. These details clarify what the study set out to examine and what information the registry reports.

The record does not report the numerical result for the primary endpoint. It therefore cannot show how many evaluable patients met the hemoglobin threshold, nor quantify the uncertainty around a response estimate. The listed secondary outcomes also lack numerical results in the registry record. Without these results, the endpoint definitions should not be mistaken for findings.

Even if a numerical within-group change were available, a single-group study could not by itself distinguish an intervention-associated effect from other possible explanations for change over time. There is no control group in the record, and no randomized comparison. The study’s unmasked status is also part of the context in which outcomes were assessed, while further details of assessment procedures are not reported.

The adverse-event counts show that events were recorded among participants in the listed group. They do not establish that decitabine caused the reported events, and the record does not provide detailed attribution or timing. The figures also do not offer a comparison against another group. Thus, the available information supports careful description of the study and reported safety counts, but does not support a definitive causal or comparative conclusion about effectiveness or safety.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions, analysis populations, and design structure all matter when interpreting clinical results. The primary endpoint is not a general measure of hemoglobin change; it is a count of evaluable patients who crossed a prespecified threshold from baseline within the stated timeframe. That definition gives the outcome a clear clinical interpretation, but a count still requires a reported denominator and uncertainty estimate to convey how precisely the response frequency is known. Those numerical primary results are not reported in the registry record.

The withdrawal note also shows why enrollment and analysis populations should not be treated as interchangeable. One enrolled patient withdrew after week 2 and was not included in analysis. The record does not describe the reason or broader missing-data procedures, so readers cannot judge whether exclusion may have influenced the result.

Statistically, the single-group model is a key limitation on causal interpretation. Within-group observations can describe what happened among participants, but without a concurrent comparator they cannot separate treatment effects from other changes over time. This distinction remains important even when a study has a specific threshold-based outcome and multiple laboratory measures.

The safety figures provide concrete descriptive information, but they also demonstrate the limits of interpreting event counts without a control group, detailed attribution, or timing. More broadly, the record lists multiple outcomes without reporting a multiplicity strategy or numerical findings for the outcomes discussed. The study is therefore informative as a record of a small phase II investigation and its intended measures, while its available registry information does not permit a robust estimate of treatment effect or comparative safety.

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.

Enrollment was 6, and one patient withdrew after week 2 and was not used for the primary analysis. The record does not report why the patient withdrew, how evaluability was otherwise defined, or how incomplete follow-up was handled for the primary or secondary outcomes. This limits assessment of the analyzed population and the potential influence of missing information.

The study has a single-group design, with no comparator listed, and masking is recorded as none. Consequently, the record does not support a randomized comparison or a direct estimate of differences between treatment and control. Further information about outcome assessment procedures and possible safeguards is not reported in the registry record.

The numerical primary result and numerical secondary-outcome findings are not reported in the registry record. The record also does not report uncertainty estimates, statistical tests, the statistical analysis plan, sample-size justification, or interim analyses. It lists 12 outcome measures and 11 analyses but does not explain the difference or state how multiplicity was handled. These omissions prevent assessment of the reported statistical findings and their precision.

Safety reporting includes counts and a listed serious-event term, but event-level details, timing, and causal attribution are not reported in the registry record. Since no comparator group is described, the safety counts cannot serve as comparative rates. The planning assumptions refer to a hypothetical two-arm calculation and should not be mistaken for the trial’s original design or for evidence that the actual study was powered to answer a comparative question.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluating the Safety and Effectiveness of Decitabine in People With Thalassemia Intermedia — NCT00661726.
• Registry record last updated 2014-04-25; status last verified 2014-02.
• Results first posted 2014-04-08.
• 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.

19. Record Summary

NCT00661726 is a completed phase II, single-group study of decitabine in people with thalassemia intermedia. The registry records enrollment of 6, no masking, and no comparator group. The intervention was injected decitabine for 12 weeks; the recorded study start is 2008-01 and primary completion is 2010-05.

The primary outcome counts evaluable patients whose hemoglobin increased from baseline by at least 1.5 g/dL, assessed up to 12 weeks. One patient withdrew after week 2 and was not used for analysis. The numerical primary result is not reported in the registry record. Safety counts list serious adverse events affecting 3 of 5 at risk, other adverse events affecting 4 of 5 at risk, and High Platelets Count at 60.0% among the top serious terms. The record does not report a comparative treatment estimate or detailed causal attribution for adverse events.