Safety and Efficacy of Deferasirox in Patients With Transfusion Dependent Iron Overload - a Non-comparative Extension Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Deferasirox in Patients With Transfusion Dependent Iron Overload - a Non-comparative Extension Study (NCT01033747), a non-randomized phase 2, phase 3 study. The primary outcome is The Relative Change From Baseline in Liver Iron Content (LIC) After Prolonged Use of Deferasirox.

2. Clinical Question

The study was intended to assess safety and the effects on liver iron during prolonged deferasirox treatment in people with transfusion-dependent iron overload. The primary outcome uses liver iron content measured by superconducting quantum interference device (SQUID), with a stated comparison between the start of deferasirox treatment and the end of the five-year extension. The registry record describes the outcome timeframe as baseline to 7 years.

The extension enrolled 70 participants and was non-randomized, open label, and single group in its design classification. Although the record distinguishes a Deferasirox group from a Deferasirox Crossover group, those groups arose from different earlier treatment assignments and histories. They do not provide a randomized comparison of deferasirox against an untreated or concurrently controlled group. The registry record does not report a numerical primary-outcome estimate, so the magnitude and precision of the liver iron change cannot be assessed from this record.

3. Trial Design

This was a non-randomized, open-label extension study listed as phase II and phase III. The registry classifies its model as single group and its allocation as non-randomized, with no masking. The study title describes a five-year extension following earlier studies. Enrollment was 70, and the record marks the study as completed.

The two listed groups represent treatment histories rather than newly randomized arms. The Deferasirox group includes participants initially randomized to 10 and 20 mg/kg/day deferasirox in the main study who remained on the same treatment during the comparative prolongation study and at the beginning of this extension. The Deferasirox Crossover group includes participants initially assigned to 40 mg/kg/day deferoxamine in the main and comparative prolongation studies who crossed over to deferasirox at the beginning of the extension. For the crossover group, the record describes deferasirox dosing as 5mg/kg/day to 30 mg/kg/day. The continuation group is described as receiving deferasirox orally daily; the crossover group is also described as receiving it orally daily.

These histories matter when interpreting any contrast between the groups. Their membership reflects previous treatment, continued treatment, and crossover, not a fresh random assignment within the extension. The record explicitly identifies the study as non-comparative and cautions that its arms are not a like-for-like control comparison. Accordingly, results from the groups can describe their observed experience, but the design does not establish a randomized treatment contrast for the extension itself.

The primary outcome is described for participants in the full analysis set who received deferasirox for more than 3.5 years. This eligibility condition means the primary-outcome population is narrower than the overall enrollment. The record does not report the number contributing to the primary analysis, the protocol’s sample-size justification, or the detailed analysis plan.

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 participants in the full analysis set treated with deferasirox for more than 3.5 years.

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 The Relative Change From Baseline in Liver Iron Content (LIC) After Prolonged Use of Deferasirox, measured over Baseline to 7 Years.

The primary endpoint is the relative change from baseline in liver iron content (LIC) after prolonged deferasirox use. LIC was assessed by superconducting quantum interference device (SQUID) and is expressed in milligrams of iron per gram of liver dry weight (mgFe/g dw). The stated timeframe is baseline to 7 years. The endpoint description compares LIC at the start of deferasirox treatment with LIC at the end of the five-year extension, for participants treated with deferasirox for more than 3.5 years.

LIC is a measure of iron in liver tissue, so change in LIC addresses the study’s stated interest in liver iron during long-term treatment. The registry describes the outcome as a mean percentage change and specifies full range as the dispersion measure. In general, a mean summarizes the average observed change, while a full range describes the span from the lowest to the highest observation; neither by itself conveys how uncertain the estimated mean is. The record gives the outcome definition but no numerical mean, range, or confidence interval. Therefore, it does not allow the size or precision of the reported primary result to be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The primary outcome is described as a mean percentage change in liver iron content. In general, a mean is an average across the observations included in an analysis. It can give a compact account of the group’s overall change, but it does not show how individual participants’ measurements were distributed. A small number of unusually large or small changes can influence a mean, and participants can have varied responses even when the mean is well defined.

The registry identifies full range as the dispersion measure. In general, the range gives the lowest and highest observed values and communicates the span of the data. It does not show how densely observations cluster within that span, and it can be sensitive to extreme values. A range is also not a confidence interval: a range describes observed values, whereas a confidence interval expresses uncertainty around an estimated quantity under a statistical model. No numerical range or confidence interval for the primary result is reported in the registry record.

How should the baseline comparison be understood?

The endpoint description compares LIC at the start of deferasirox treatment with LIC at the end of the extension. Its stated population consists of full-analysis-set participants treated with deferasirox for more than 3.5 years. This is a within-participant change question for people meeting that treatment-duration condition, rather than a direct randomized comparison between the two groups. In general, measuring participants at two times can account for their own starting measurement when describing change, but it does not by itself remove changes over time due to other causes or establish what would have happened under a different treatment.

The outcome description also states a formula for relative change. The registry calls the outcome a mean percentage change and specifies baseline and end-of-extension measurements. Because no numerical result is listed, the record does not permit checking how that formula was applied to individual observations or how the individual values were summarized. The stated timeframe is baseline to 7 years, while the description refers to the end of the five-year extension; those are both elements of the record’s endpoint description and should be retained when interpreting the outcome.

Why does the study design affect interpretation?

Random allocation, when used, is intended to make treatment groups comparable on average at the point of assignment. This extension is classified as non-randomized, open label, and single group. Its two group labels preserve different histories from earlier studies: continued deferasirox in one group and crossover from deferoxamine in the other. They therefore do not function as newly randomized intervention and control groups. General statistical reasoning indicates that treatment history, participant selection, and other differences between groups can complicate comparisons. The registry explicitly cautions that the arms are not a like-for-like control comparison.

Open-label means masking was absent, as the record states. In general, lack of masking can affect subjective assessments or behaviors, although the primary outcome is a measurement of liver iron assessed by SQUID. The record does not describe procedures for measurement assessment, safeguards against bias, or additional outcome adjudication, so those details cannot be characterized.

What can a planning illustration tell readers?

In general, a sample-size calculation is a planning exercise that relates an assumed effect, variability, allocation, significance level, and desired power to a target sample size. The stated planning assumptions for illustrations on the clinical page use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning illustrations based on an observed effect, not the trial’s original design. They must not be interpreted as observed power or as evidence that the study was designed around those assumptions.

For an event-time analysis, a planning method may count total events rather than participants per arm; for other outcomes, the stated convention is participants per arm. The registry record does not report the trial’s own sample-size justification, and the numerical observed primary effect needed to interpret an effect-based illustration is not reported in the registry record. No planning calculation can fill that gap or substitute for the study’s observed result.

What does the absence of an analysis listing mean?

The registry lists no analyses. This means there are no analysis entries in the registry record to explain model choice, covariate adjustment, uncertainty estimates, or handling of repeated measurements. It does not establish that investigators did not perform analyses; it limits what can be assessed from the registry entry. General statistical interpretation depends on knowing not only the outcome definition but also the analysis population, missing-data handling, and method used to estimate the result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary LIC outcome and a secondary outcome of relative change in serum ferritin from baseline to 3.5 years. It lists no analyses. The record does not report whether there was a prespecified hierarchy among outcomes, whether multiplicity was addressed, or whether additional outcomes were examined. When several outcomes or analyses are considered, general statistical practice recognizes that the chance of at least one apparently unusual result can increase unless the analysis plan accounts for multiple testing. Whether or how this issue was handled is not reported in the registry record.

The primary population is described as the full analysis set treated with deferasirox for more than 3.5 years. The record does not give the number in this population, define the full analysis set further, or state how participants with incomplete LIC measurements were handled. It also does not report a missing-data method, reasons for missing measurements, or sensitivity analyses. Those omissions prevent assessment of whether the analyzed participants differed from those without endpoint data and how that might affect the estimated change.

Enrollment was 70, but enrollment is not a substitute for the number analyzed. The record also does not report the original sample-size justification or a detailed statistical analysis plan. Consequently, the listed outcome definitions can be described, but the registry record does not permit a full assessment of multiplicity control, missing-data assumptions, or analysis-population implementation.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: renal colic (5.9%), gastroenteritis (5.3%), tendon injury (5.3%), headache (5.3%), paraesthesia (5.3%).

For serious adverse events, the Deferasirox group lists 51 participants at risk and 18 affected; the Deferasirox Crossover group lists 19 at risk and 2 affected. For other adverse events, the corresponding counts are 51 at risk and 50 affected in the Deferasirox group, and 19 at risk and 19 affected in the Deferasirox Crossover group. These are registry counts of participants affected, not necessarily counts of distinct event episodes. The categories should be read as the registry presents them rather than combined into a single measure.

The listed serious-event terms and percentages are renal colic, 5.9%; gastroenteritis, 5.3%; tendon injury, 5.3%; headache, 5.3%; paraesthesia, 5.3%; and abdominal pain, 3.9%. The record does not establish in these summaries how those terms are distributed between the two groups. The percentages should therefore not be assigned to a particular group based on these details alone.

Deaths are not reported in the registry record; a missing death count should not be interpreted as zero deaths. The groups also differ in their treatment histories and are not a like-for-like control comparison. These safety summaries are descriptive and do not establish that any event was caused by treatment or support a randomized comparison of safety.

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

The registry record is useful for understanding the purpose and structure of a long-term extension: it focused on safety and liver iron during prolonged deferasirox treatment in people with transfusion-dependent iron overload. It identifies LIC as the primary outcome, describes its measurement by SQUID, and defines a population treated for more than 3.5 years. It also records the groups’ previous treatment histories and gives participant counts for adverse-event summaries.

However, the record does not report a numerical LIC estimate, its full range, or an uncertainty interval. It therefore does not show how large the mean change was, how variable individual changes were, or how precisely the mean was estimated. The secondary serum ferritin outcome is named, but its numerical result is not reported in the registry record either. The study’s completed status does not replace those missing results.

The extension also does not answer a randomized comparison question between deferasirox and deferoxamine. The crossover participants had received deferoxamine earlier and then changed to deferasirox; the other group continued prior deferasirox treatment. Because allocation in the extension was non-randomized, differences between the groups cannot be attributed to treatment alone. The record explicitly identifies the arms as not being a like-for-like control comparison.

Safety counts describe participants affected in the registry summaries, while the listed serious-event percentages describe terms without a stated group assignment in the available details. The counts do not establish causation, and deaths are not reported in the registry record. Overall, the available information supports a careful account of design, outcome definitions, and selected safety summaries. It does not support a conclusion about the size or precision of the liver iron change, a causal treatment effect, or a comparative safety effect.

13. Why This Trial Matters Statistically

Long-term extensions address a different statistical question from the randomized comparisons that may precede them. They can describe outcomes and safety during continued treatment, but eligibility and continued participation can select a population that differs from the original study population. In this record, the primary outcome is restricted to full-analysis-set participants treated with deferasirox for more than 3.5 years. That treatment-duration condition is important: the result, if reported, would describe this defined group rather than automatically representing everyone enrolled or all people with transfusion-dependent iron overload.

The study also illustrates why treatment history matters when a registry lists multiple groups. One group continued deferasirox, while the crossover group had earlier deferoxamine treatment before starting deferasirox in the extension. Those histories are not interchangeable, and the extension did not randomize participants between the groups. The record’s explicit warning against treating them as like-for-like controls is central to interpreting any observed contrast.

Outcome definition is another important statistical feature. The primary endpoint is a mean relative change in LIC, with a stated measurement method, timeframe, and dispersion measure. Yet an outcome definition alone is not an outcome result. Without the estimate and uncertainty, readers cannot judge its magnitude, variability, or precision. Similarly, safety counts need denominators and clear definitions, and should be interpreted descriptively when the design does not support a causal comparison.

The record therefore demonstrates the value of separating three questions: what was measured, who was included, and what the data estimate. Here, the first is described, the target primary population is specified in broad terms, and selected safety counts are listed. Numerical efficacy results and detailed analysis methods are not reported in the registry record. Keeping those distinctions clear prevents study design and endpoint labels from being mistaken for evidence about the size of an effect.

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 for interpreting the primary endpoint is that its numerical result is not reported in the registry record. The mean relative change, full range, and any confidence interval are not available in the record, so neither the observed magnitude nor its precision can be assessed. The secondary serum ferritin outcome is named but also has no numerical result in the available details.

The primary outcome applies to participants in the full analysis set treated with deferasirox for more than 3.5 years. The number meeting that condition and the number with an evaluable LIC measurement are not reported in the registry record. The record does not describe how incomplete follow-up or missing measurements were handled. Thus, the extent to which the analyzed population represents all enrolled participants cannot be assessed.

The design is non-randomized and non-comparative, despite the presence of two group descriptions. The groups have different prior treatment histories, and the record cautions that they are not a like-for-like control comparison. This limits any interpretation of differences between groups as treatment effects. The study is also open label, and the record does not describe measurement blinding or other safeguards that might clarify how outcome assessment was conducted.

The registry record does not report the protocol’s sample-size justification, detailed analysis plan, multiplicity approach, or statistical methods used for the primary estimate. It lists no analyses. The adverse-event summaries do not report deaths, and the serious-event terms are not explicitly assigned to groups in the details available. These limitations constrain interpretation of efficacy, precision, missing-data effects, and comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of Deferasirox in Patients With Transfusion Dependent Iron Overload - a Non-comparative Extension Study — NCT01033747.
• Registry record last updated 2011-08-11; status last verified 2011-07.
• Results first posted 2011-08-11.
• 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

NCT01033747 is a completed, open-label, non-randomized extension study of prolonged deferasirox treatment for transfusion-dependent iron overload. Enrollment was 70. The study is listed as phase II and phase III, with a single-group design classification and no masking.

The primary outcome is relative change in LIC, assessed by SQUID, for participants in the full analysis set treated with deferasirox for more than 3.5 years. The record describes the timeframe as baseline to 7 years and identifies full range as the dispersion measure. A secondary outcome is relative change in serum ferritin from baseline to 3.5 years. Numerical outcome results and analysis entries are not reported in the registry record.

The group descriptions distinguish continued deferasirox treatment from crossover to deferasirox after earlier deferoxamine treatment. The registry cautions that the groups are not a like-for-like control comparison. It reports participant counts for serious and other adverse events, but deaths are not reported in the registry record.