Efficacy and Safety Study of Deferasirox in Patients With Non-transfusion Dependent Thalassemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of Deferasirox in Patients With Non-transfusion Dependent Thalassemia (NCT01709838), a na phase 4 study. The primary outcome is Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline.

2. Clinical Question

The study also described further assessment of long-term efficacy and safety for up to 260 weeks. Its listed secondary outcomes include LIC thresholds and time to those thresholds, health-related outcomes, LIC over time, serum ferritin in relation to LIC, and correlations between changes in LIC and serum ferritin. These are different questions from the primary 52-week change: some concern levels, some concern time to an event or threshold, and others concern patient-reported measures or relationships between laboratory measures.

Because there is no concurrent comparator, the primary question is descriptive within the treated group. Change from baseline can show how the measured outcome moved during follow-up, but alone it cannot distinguish treatment effects from other influences on change over time. The numerical result needed to describe the observed direction and size of change is not reported in the registry record.

3. Trial Design

This is a completed Phase 4, open-label, multicenter, single-group study of deferasirox in patients with non-transfusion dependent thalassemia. The registry lists enrollment of 134. Allocation is recorded as NA, and masking as none. The record therefore describes treatment without random assignment to a separate comparison group and without masking.

All patients in the described treatment arm received deferasirox, with an initial dose of 10mg/kg/day. Dose adjustments after 4 weeks were made according to baseline LIC. The record does not describe a control arm receiving placebo or another treatment. Comparing follow-up values with baseline is not equivalent to comparing randomized groups: it measures within-group change, not a treatment contrast protected by concurrent randomization.

The primary endpoint was absolute change in LIC from baseline at 52 weeks, measured by MRI. The listed primary analysis population was the Full Analysis Set, defined as all patients assigned at least one dose of study drug. The registry summary also describes further long-term assessment for up to 260 weeks among patients with iron overload, specified as LIC ≥ 5 mg Fe/g liver dw and SF ≥ 300 ng/mL. The record does not provide further detail on how that long-term group was selected or analyzed.

The study start is recorded as 2012-12-06, and primary completion as 2015-01-03; status is completed. These dates identify the registry milestones but do not give individual follow-up durations or establish that every participant contributed data at each assessment. The registry record does not report the protocol’s rationale for the sample size, details of treatment adherence, or the statistical analysis plan. Since there is no randomized comparator, any planning illustration based on two arms should not be mistaken for the design actually used in this study.

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: At least 117 patients were planned to be enrolled; 134 patients were enrolled.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

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: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline, measured over Baseline, 52 weeks.

The primary endpoint is absolute change in liver iron concentration from baseline after 52 weeks of treatment. LIC is expressed in mg Fe/g dw, and the record says it was measured by MRI. The endpoint is continuous: it retains the magnitude of measured change rather than reducing every observation to whether a threshold was crossed.

Change endpoints use a baseline measurement as a reference and describe how the outcome differs at follow-up. This can be useful when the scientific question concerns the course of a measured quantity during treatment. The mean summarizes the average change across the analysis population, while the standard deviation describes variation in individual changes around that mean. Neither summary alone describes the full distribution or the precision of the estimated mean.

The choice of LIC is consistent with the registry’s stated focus on iron overload and with its other listed outcomes involving LIC levels and thresholds. The record also lists serum ferritin and health-related outcomes, but they are not the primary endpoint. Keeping the primary endpoint distinct from secondary measures matters when interpreting evidence: a result for one measure does not automatically answer questions about the others.

The registry record does not report the mean change, its standard deviation, a confidence interval, or a statistical test for this primary endpoint. As a result, the endpoint definition is available, but the posted results do not establish the observed direction, magnitude, or precision of the 52-week change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

The primary endpoint is a continuous measure expressed as change from baseline. A mean change is the arithmetic average of participant-level changes in the analysis population. It gives a concise summary of the group’s average movement, but does not imply that every participant changed by that amount or in the same direction. Individual responses can vary around the mean.

The record identifies standard deviation as the dispersion measure. Standard deviation describes spread among observations; it is not the same as the standard error or a confidence interval. A confidence interval, in general, expresses uncertainty around an estimated quantity under the assumptions of the analysis. It helps readers assess precision, while the mean alone describes the point estimate. The registry record does not report the primary mean change, its standard deviation, or a confidence interval, so those quantities cannot be interpreted for this study from the record summarized.

Why does the single-group design matter?

A single-group before-and-after analysis can describe how a measured outcome changes among participants who receive the study treatment. It does not supply the treatment contrast available from a randomized comparison. A baseline value is a participant’s earlier measurement, not an untreated outcome observed at the same time as the follow-up value. General causal interpretation must therefore allow for other reasons that measurements can change, including natural course, concurrent care, measurement variability, and changes in who remains observed at follow-up.

Here, allocation is listed as NA, masking as none, and the model as single group. The record identifies an open-label study, meaning treatment was not masked as described in the registry. These are design characteristics, not proof that any particular bias occurred. They indicate why a within-group change should be read as descriptive evidence unless a suitable comparison and additional assumptions support a causal conclusion.

What does the analysis population specify?

The primary population is the Full Analysis Set, defined in the record as all patients assigned at least one dose of study drug. This definition states who qualifies for the primary analysis at a broad level. It does not say how missing follow-up measurements were handled, whether all eligible participants contributed to the 52-week estimate, or how deviations from treatment were addressed. Those details are not reported in the registry record.

For a continuous endpoint, missing follow-up values can affect both the number of observations used and the estimate. General approaches differ in their assumptions about why data are missing and what unobserved values might have been. A complete-case analysis, for example, summarizes observed outcomes among those with available measurements, while other approaches may use models or imputation. No such method can be attributed to this study from the registry entries available.

How should the secondary outcome types be distinguished?

The listed threshold outcomes concern whether LIC is above or below a specified value, while time-to-achievement outcomes consider when a participant reaches that threshold. Time-to-event methods generally account for the fact that some participants may not experience the event during observed follow-up, using censoring to retain partial follow-up information. Their interpretation depends on the event definition, follow-up rules, and analysis method. Those details and numerical results are not reported in the registry record.

Other listed outcomes concern health-related measures, LIC measurements over time, serum ferritin in relation to LIC, and correlations between changes in LIC and serum ferritin. Correlation is a measure of association; it does not show that changes in one measure cause changes in another. Repeated measurements also raise questions about how within-participant dependence is handled. The registry record does not state the statistical methods used for these secondary analyses.

Why can over-dispersion matter?

In general, count outcomes can vary more than a simple statistical model expects. This is called over-dispersion. If a model assumes less variability than the data actually contain, estimated uncertainty can be too small, making intervals or tests look more decisive than warranted. Methods designed for over-dispersed counts can better reflect that extra variation. This concept is relevant generally to count data, but the primary endpoint in this study is a continuous change measure, and the registry record does not report a count-model analysis.

What can planning illustrations say?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it defines the target effect as a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is total events; for other illustrations, it is participants per arm. These are planning assumptions, not the observed design of this single-group study, and the illustrations are not observed power. The registry record does not report the values needed to interpret a particular illustration here, nor does it state that this was the trial’s own sample-size justification. The sponsor’s own analysis would take precedence if a recalculated result differed from it; no such discrepancy is stated in the record details.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Deferasirox")
n   <- c(134)
m   <- c(-6.68)
sp  <- c(7.018)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Deferasirox  134  -6.680  7.018  -7.879  -5.481

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 0 analyses. The outcomes span different measurement types, including continuous changes, thresholds, times to thresholds, health-related measures, and associations between LIC and serum ferritin. The registry record does not report a multiplicity adjustment, a hierarchy of confirmatory outcomes, or which secondary outcomes were treated as exploratory. When many outcomes are examined, the chance of at least one apparently notable result can increase; general methods such as prespecifying a primary question or adjusting for multiple testing can address that concern. No particular approach should be attributed to this study without a stated analysis plan.

The primary population is defined as all patients assigned at least one dose of study drug. That identifies the population intended for the primary analysis, but does not explain how missing LIC measurements were handled. The record does not report the number with an observed 52-week value, reasons for missingness, imputation, sensitivity analyses, or rules for excluding measurements. Missing-data methods rely on assumptions, and different assumptions can produce different estimates. Without the analysis details and numerical results, the effect of missing data cannot be assessed.

The long-term summary refers to patients meeting LIC and serum ferritin thresholds, but the registry record does not describe in detail how entry into that assessment was determined or how incomplete follow-up was addressed. It also does not report interim analyses or stopping rules. Those aspects are not inferable from the study’s completed status or the list of registered outcomes.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (6.1%), gastroenteritis (6.1%), pneumonia (6.1%), pyrexia (4.5%), cholelithiasis (4.5%).

The registry reports safety counts by Chinese, Non-Chinese, and All Patients groups. In the All Patients group, 45 were recorded as affected by serious adverse events, and 84 were recorded as affected by other adverse events; 2 deaths are listed. The corresponding counts for Chinese participants are 15 affected by serious adverse events, 26 by other adverse events, and 2 deaths. For Non-Chinese participants, the counts are 30, 58, and 0, respectively. These are descriptive registry counts, not comparisons with an untreated or alternative-treatment group.

The listed serious adverse event terms and percentages are Anaemia, 6.1%; Gastroenteritis, 6.1%; Pneumonia, 6.1%; Pyrexia, 4.5%; Cholelithiasis, 4.5%; and Urinary tract infection, 4.5%. The record does not give further context for these terms in the registry record, including timing, duration, severity beyond the serious classification, or attribution to treatment. A listed percentage should not be interpreted as a comparative risk without an appropriate comparator and fuller analysis.

Safety counts can describe what was recorded, but they do not alone establish whether treatment caused an event or how event risk compares with another option. The registry record does not report the causes or timing of the deaths. These figures should therefore be read as descriptive safety reporting, with the limits of the single-group design kept in view.

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

The registry record identifies a focused primary question: the mean absolute change in MRI-measured LIC from baseline at 52 weeks among patients assigned at least one dose of study drug. It also documents an open-label, single-group study of deferasirox and lists longer-term outcomes and safety summaries. These registry entries explain what was studied and how the primary outcome was framed.

The record does not report the numerical primary change, its variability, or a confidence interval. It therefore does not support a statement about the direction or size of the observed 52-week change, or its precision. Completion status and an efficacy-oriented title cannot replace those results. The listed secondary outcomes likewise do not establish their findings without numerical estimates and analysis details.

Even if a within-group change estimate were available, a before-and-after result in a single-group study would describe change during follow-up, not necessarily the causal effect of treatment. Without a concurrent comparison group, other changes over time cannot be separated from treatment effects using the design description alone. The absence of masking is also relevant to how subjective measurements or reporting might be interpreted, though the record does not establish that bias occurred.

The safety counts provide descriptive information about adverse events and deaths recorded in the registry. They do not by themselves establish causation or comparative safety. The record does not provide the additional context needed to interpret the deaths or to assess event timing and attribution.

In short, the entry supports an account of the trial design, endpoint definition, analysis population, and certain safety counts. It does not support a numerical conclusion about the primary endpoint’s result or its statistical precision. The distinction between what the study set out to measure and what the registry record reports is essential to a careful reading.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between defining an endpoint and reporting its result. The registry specifies a continuous primary outcome, its MRI measurement method, a 52-week time point, and a Full Analysis Set definition. These details allow readers to understand the intended estimand at a broad level. But without a mean estimate and a measure of uncertainty, the central efficacy result cannot be evaluated quantitatively.

The single-group design also makes the target of inference important. A change from baseline can describe the course of LIC among treated participants, but it is not the same as a randomized treatment contrast. This is a general design distinction: within-group change and between-group effect answer different questions. It matters when interpreting efficacy claims, particularly when there is no concurrent control group to help account for time-related changes and other influences.

The range of registered outcomes highlights how one study can generate distinct statistical questions. Continuous change, threshold achievement, time to an event, health-related measures, and correlation each call for different summaries and assumptions. They should not be treated as interchangeable confirmations of a single effect. The registry lists 15 outcome measures and 0 analyses, while the registry entries do not describe multiplicity handling or the methods used for the secondary outcomes.

The safety record similarly illustrates the boundary between event counts and comparative inference. Counts of affected participants and deaths can describe recorded events, but a single-group record cannot directly compare those counts with an alternative treatment group. Taken together, these features make the registry useful for understanding the study’s framework while underscoring why transparent numerical results and analysis details are needed for statistical interpretation.

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 primary limitation for interpreting efficacy is that the registry record does not report the numerical 52-week LIC change. It also does not report the associated standard deviation, confidence interval, or p-value. Without an estimate and uncertainty measure, the direction, size, and precision of the primary outcome cannot be assessed from the record.

The single-group, open-label design provides no concurrent randomized comparison. Baseline measurements are not a substitute for outcomes in a control group followed over the same period, so change during follow-up cannot by itself isolate a treatment effect. The record does not describe procedures for masking outcome assessment or other safeguards against bias.

The Full Analysis Set definition is given, but the registry record does not report the number with a measured primary outcome at 52 weeks, reasons for missing data, or the method used to handle missing measurements. It also does not provide details about adherence, protocol deviations, or sensitivity analyses. These omissions limit assessment of how representative the analyzed observations were of the intended population.

Further details are not reported for the long-term assessment, including how participants entered that assessment, how follow-up was handled, and what statistical methods were used. The record lists multiple secondary outcomes but does not state a multiplicity strategy or identify which analyses were confirmatory. Safety counts are available, but the registry entries do not include causes or timing of deaths, event attribution, or a comparator for interpreting event frequency.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of Deferasirox in Patients With Non-transfusion Dependent Thalassemia — NCT01709838.
• Registry record last updated 2019-10-02; status last verified 2019-09.
• Results first posted 2019-08-28.
• 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

This completed Phase 4 study was an open-label, multicenter, single-group assessment of deferasirox in patients with non-transfusion dependent thalassemia. Enrollment is listed as 134. The treatment description gives an initial dose of 10mg/kg/day, with dose adjustments after 4 weeks according to baseline LIC.

The primary endpoint was mean absolute change in MRI-measured LIC from baseline at 52 weeks, in the Full Analysis Set of patients assigned at least one dose of study drug. The registry summary also describes longer-term efficacy and safety assessment for up to 260 weeks in patients meeting stated LIC and serum ferritin thresholds. Listed secondary outcomes include threshold, time-to-event, health-related, longitudinal LIC, ferritin, and correlation measures.

The registry reports safety counts, including 2 deaths in the All Patients group. It does not report the numerical primary endpoint result or its uncertainty, and the available record does not describe the statistical analysis methods, missing-data handling, or multiplicity approach.