Pilot Study for Patients With Poor Response to Deferasirox: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study for Patients With Poor Response to Deferasirox (NCT00749515), a na phase 4 study. The primary outcome is Area Under the Curve of Deferasirox After a Dose of 35 mg/kg.

2. Clinical Question

The study’s stated purpose was to understand differences between people with good and poor responses when deferasirox is used for transfusion-dependent iron overload. Its hypothesis was that poor response might be associated with physiologic barriers, including absorption, drug metabolism, hepatic clearance, or genetic factors. Those possibilities are the investigators’ proposed explanations, not findings established by the record.

The record also lists a secondary outcome concerning participants with polymorphisms in genes known or potentially involved in deferasirox disposition. It does not report the result for that outcome. Consequently, the clinical question is about characterizing pharmacokinetics and exploring possible differences between pre-classified responder groups, rather than estimating a treatment effect against a randomized comparison group.

3. Trial Design

This was a completed phase 4 study sponsored by Boston Children's Hospital. The registry lists an enrollment of 15, a single-group model, no masking, and allocation as NA. The study started in 2008-03 and had primary completion in 2008-10. These design features describe a small pharmacokinetic investigation, not a randomized controlled trial.

According to the arm description, all patients received a deferoxamine challenge, a deferasirox dose with pharmacokinetic monitoring, and a HIDA scan. The comparison was made between patients already known to be slow responders to deferasirox and those known to be rapid responders, described as patients who chelated well. The labels “Inadequate Responders” and “Adequate Responders (Control)” identify these groups in the safety record. The word “control” does not make the groups randomized or otherwise equivalent at baseline.

The interventions listed in the registry are Deferoxamine, Deferasirox, and HIDA. The primary pharmacokinetic measure is the area under the curve after a deferasirox dose of 35 mg/kg. Its measurement timeframe lists 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose. The record lists six outcome measures and five analyses, but does not describe the full analysis methods or give the primary endpoint results.

The registry record does not report how responder status was defined, how participants were selected, whether there were eligibility restrictions beyond the listed conditions, or why the enrollment target was chosen. A sample-size justification for the trial itself is not reported in the registry record. The study’s design can support descriptive pharmacokinetic characterization and exploratory comparisons between the identified groups, but its nonrandomized structure does not isolate the effects of deferasirox or establish why participants differed in response.

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

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 Area Under the Curve of Deferasirox After a Dose of 35 mg/kg, measured over 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose.

The primary endpoint is the area under the curve (AUC) of deferasirox after a dose of 35 mg/kg. AUC from 0 to 24 hours represents drug exposure over the measurement period: it combines concentration information across the post-dose observation window rather than focusing on a single measurement time. The registry lists measurements at 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose.

Pharmacokinetic exposure is relevant to the study’s stated aim because the investigators wanted to explore whether people with poor responses differed from good responders in how deferasirox was handled in the body. AUC can describe overall exposure during the specified period, while the individual concentration measurements can characterize the time course used to assess that exposure. This is a general explanation of the measure; it does not establish what caused any observed response difference in this study.

The registry specifies that the endpoint is a mean, with standard deviation as the dispersion measure, and gives the unit as micromole/liter*hour. However, the mean and standard deviation are not reported in the registry record. Nor does the record state a numerical between-group contrast or a confidence interval for the primary endpoint. Without those results, the magnitude and precision of the measured exposure, and any difference between the responder groups, cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical concepts relevant to this study begin with the distinction between a measured value and an estimate of a group’s typical value. The primary endpoint is a continuous measure: AUC of deferasirox after a dose of 35 mg/kg. The registry specifies that it is summarized as a mean, with standard deviation describing dispersion. A mean gives a central summary of observed values. A standard deviation describes how spread out individual measurements are around that mean. These summaries answer different questions: the mean describes the group’s average exposure, while the standard deviation describes variability among participants.

The registry record does not report either summary for the primary endpoint. It also does not state whether the mean was estimated separately for each responder group or report a numerical contrast between them. Therefore, no conclusion about the direction or size of a group difference can be drawn from the endpoint description alone.

What does AUC represent?

AUC is a summary of drug exposure over a specified time window. In this study, the stated window is 0 to 24 hours post dose, with measurements listed at 0, 1, 2, 4, 6, 8, 12, and 24 hours. As a general concept, summarizing the concentration-time profile can capture exposure across the window rather than treating any one sampling time as a complete description. The registry record does not describe the specific computational procedure used to obtain AUC, so no particular interpolation or estimation method should be assumed.

The specified unit, micromole/liter*hour, reflects concentration accumulated over time. AUC is a pharmacokinetic endpoint, not itself a direct measurement of clinical response. The study’s question links pharmacokinetic characterization with known responder status, but a relationship between exposure and response would not alone identify its cause.

How should a mean and its uncertainty be read?

A mean is an estimate from observed measurements. A confidence interval, when reported, communicates uncertainty around an estimate under the assumptions of the statistical method used. A relatively wide interval generally indicates less precision than a narrower interval. The registry record does not report a confidence interval for the primary endpoint or a group contrast. It also does not provide the individual observations needed to assess the distribution of AUC values.

Standard deviation and confidence interval should not be treated as interchangeable. Standard deviation describes variation among observations; a confidence interval describes uncertainty in an estimated quantity. The record names standard deviation as the dispersion measure but gives no numerical value. General explanations of uncertainty cannot substitute for those absent results.

What can the responder-group comparison establish?

The study uses a single-group model in which participants received the same interventions, then compares patients already known to be slow responders with those known to be rapid responders. This is an observational comparison based on response classification, not a randomized assignment to different treatments. In general, randomization can help balance measured and unmeasured characteristics across assigned groups. Because this study did not randomize patients to responder status, a difference between groups could reflect other characteristics as well as pharmacokinetic differences.

The registry record does not report the criteria used to define slow or rapid response, baseline characteristics by group, or an adjusted analysis. It therefore does not allow readers to determine whether the comparison accounted for other factors. The comparison can be interpreted as exploratory characterization of the groups, not as a causal estimate of the effect of a treatment or a mechanism.

What do the planning assumptions mean?

The record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For continuous outcomes, the illustration is expressed as participants per arm for 80% power or another stated planning level. Such calculations are hypothetical planning aids; they are not observed power and do not change the actual enrollment of 15.

The planning assumptions do not establish that the trial was designed with those assumptions. A trial-specific sample-size justification is not reported in the registry record. Nor are the numerical planning results stated in the record details available for this interpretation. The planning illustration should therefore be kept separate from the study’s observed data and from any inference about what the study could detect.

Over-dispersion is a general issue when a statistical model assumes less variability than the data contain. If variability is greater than assumed, standard errors may be too small and uncertainty may be understated. This concept is relevant to statistical interpretation generally, but the registry record does not report a model or an assessment of over-dispersion for this study. No claim about whether it occurred is warranted.

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("Inadequate Responders", "Adequate Responders (Control)")
n   <- c(10, 5)
m   <- c(479.59, 1123.11)
sp  <- c(259.42, 63.4)
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  Inadequate Responders  10  479.590  259.420  294.012  665.168
CARM  Adequate Responders (Control)  5  1123.110  63.400  1044.389  1201.831

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures and five analyses, but does not report the full analysis plan, the order of testing, or whether the analyses were considered confirmatory or exploratory. It does not state whether any adjustment was made for multiple outcomes or comparisons. When several outcomes or hypotheses are examined, the chance of a false-positive finding can increase if each is assessed without accounting for multiplicity. This is a general statistical concern; the record does not provide enough information to determine how it was addressed in this study.

The primary endpoint is identified as the mean AUC of deferasirox after a dose of 35 mg/kg, but its result is not reported in the registry record. The listed secondary outcome concerns the number of participants with polymorphisms in genes known or potentially involved in deferasirox disposition. Its result is also not reported in the registry record. The record does not provide a complete outcome-by-outcome account of estimates, uncertainty, or statistical tests.

Missing-data handling is not reported in the registry record. The record does not state whether all enrolled participants contributed to each analysis, whether any measurements were incomplete, how incomplete concentration profiles were handled, or how missing outcome values were treated. An analysis population, such as all enrolled participants or a subset with usable pharmacokinetic measurements, is not specified.

These omissions limit the ability to assess how robust the findings might be to incomplete data or multiple analyses. They do not prove that data were missing or that multiplicity was mishandled; they indicate that the registry record does not describe those methods or results. The number enrolled and the stated outcome schedule cannot establish how many observations were available at each time point.

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 0% reporting threshold.

The safety record lists 10 inadequate responders and 5 adequate responders (control). For the serious-event figures shown, 0 participants are recorded as affected in each group, and deaths are recorded as 0 in each group. The other affected figures are also 0 for both groups. These are the recorded counts, not evidence that the interventions carry no risk.

Counts need to be read alongside the numbers at risk: 10 in the inadequate-responder group and 5 in the adequate-responder group. With these group sizes, zero recorded events does not establish that an event could not occur, and it does not precisely characterize uncommon risks. The registry record does not report event descriptions, follow-up details, or a fuller safety analysis that would explain the scope of the counts. No serious adverse event terms are listed.

The responder groups were not randomized treatment arms. Their safety counts should not be interpreted as a comparative estimate of harm between treatments: all patients received the same interventions, and the groups differ by their pre-existing responder classification. The figures describe what was recorded for these groups in the registry, within the information reported there.

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

This study addresses a focused pharmacokinetic question: how deferasirox exposure was characterized in patients already classified as inadequate or adequate responders. Its primary endpoint is AUC from 0 to 24 hours after a dose of 35 mg/kg, summarized as a mean with standard deviation. The registry record gives the endpoint definition and sampling schedule, but does not report the numerical mean, standard deviation, or a between-group result. Consequently, it cannot establish from the posted registry information whether the groups differed in AUC or how precisely exposure was estimated.

The record also cannot establish why a patient was a poor responder. The study description names possible physiologic and genetic explanations, but the registry does not report results that confirm any of them. The listed secondary outcome on genetic polymorphisms has no reported result in the registry record.

Because patients were classified by existing response status rather than randomized to groups, the comparison cannot isolate a causal effect of pharmacokinetic exposure or of any intervention. Even if a group difference were reported, other differences between patients could contribute. The record does not report baseline comparisons or an adjusted analysis that would help evaluate that possibility.

The total enrollment of 15 and the group counts of 10 and 5 describe a small study. They do not, on their own, tell readers the precision of the primary estimate; that requires the observed measurements and uncertainty estimates, which are not reported. The safety counts likewise describe recorded events in the listed groups, not proof of absence of risk.

In short, the registry establishes the study’s purpose, intervention sequence, responder-group comparison, and primary endpoint definition. It does not provide enough outcome information to draw a numerical conclusion about deferasirox exposure, responder differences, genetic findings, or the proposed mechanisms.

14. Why This Trial Matters Statistically

Pharmacokinetic studies can help characterize how drug exposure varies across patients and can generate questions about whether exposure is related to observed response. This study is statistically informative as an example of a design that examines that relationship through a comparison of patients already classified by response. The design and the endpoint need to be considered together: AUC summarizes exposure over the stated post-dose period, while responder status supplies the grouping for exploratory comparison.

The study’s small enrollment and unequal responder-group counts matter when interpreting estimates. In general, estimates from small groups can be imprecise, and the amount of uncertainty is best assessed from reported confidence intervals or other uncertainty measures. Those measures and the primary endpoint results are not reported in the registry record, so the precision cannot be evaluated directly.

The design also illustrates the difference between an exploratory association and a causal conclusion. Comparing existing responder groups may identify patterns worth investigating, but nonrandomized group membership does not ensure that the groups are comparable in other respects. The record does not report adjustment methods or baseline balance, so the comparison should not be treated as a causal test of the proposed explanations.

Finally, reporting completeness is central to statistical interpretation. A defined endpoint and a stated hypothesis are not substitutes for the numerical estimates and uncertainty needed to judge the evidence. The record’s missing primary and secondary outcome results prevent readers from evaluating whether the study’s statistical question was answered in a way that supports any particular conclusion. This is an important distinction between a clearly described research question and a report that contains enough results to assess it.

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.

Several limitations are specific to the information and design described in this registry record. The total enrollment was 15, with 10 inadequate responders and 5 adequate responders. The comparison groups are unequal in size, and no primary endpoint estimates or uncertainty measures are reported. Thus, the precision of any group-specific AUC estimate or comparison cannot be assessed.

The study is listed as a single-group model with allocation NA and no masking. All patients received the same interventions, and the groups were formed from known response status. This does not provide a randomized, like-for-like control comparison. The record does not report the criteria used to classify response, the timing or source of that classification, or baseline characteristics by group.

The record identifies deferoxamine, deferasirox, and HIDA as interventions and describes the sequence, but it does not provide detailed procedures for the pharmacokinetic analysis. The method used to calculate AUC, the handling of incomplete concentration profiles, and the analysis population are not reported in the registry record. The primary result and the result of the listed genetic outcome are not reported either.

The registry lists six outcome measures and five analyses but does not describe a multiplicity strategy or missing-data methods. A trial-specific sample-size justification is not reported in the registry record. The stated planning assumptions describe an illustration based on an observed effect; they do not establish the original design rationale or observed power.

These limitations concern what can be concluded from the record and the study structure. They do not establish that particular analyses were absent or that particular data were missing. The registry does not report enough detail to resolve those questions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study for Patients With Poor Response to Deferasirox — NCT00749515.
• Registry record last updated 2024-02-12; status last verified 2024-02.
• Results first posted 2019-02-06.
• 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

NCT00749515 is a completed phase 4, single-group pharmacokinetic study sponsored by Boston Children's Hospital. The registry lists enrollment of 15, no masking, and allocation as NA. The study began in 2008-03 and reached primary completion in 2008-10.

All patients received a deferoxamine challenge, a deferasirox dose with pharmacokinetic monitoring, and a HIDA scan. The primary endpoint was mean AUC of deferasirox after a dose of 35 mg/kg, measured over 0 to 24 hours. The intended comparison was between known inadequate and adequate responders, not randomized treatment groups.

The registry record does not report the primary endpoint values, the group comparison, or the result of the listed genetic polymorphism outcome. It also does not report the trial-specific sample-size justification, missing-data methods, analysis populations, or multiplicity approach. The posted information therefore describes the question and design, but does not permit a numerical assessment of the primary result.