A Trial of Ferumoxytol for the Episodic Treatment of Iron Deficiency Anemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial of Ferumoxytol for the Episodic Treatment of Iron Deficiency Anemia (NCT01114217), a na phase 3 study. The primary outcome is Mean Change In Hemoglobin From TP Baseline To TP Week 5 Following The First Course Of Ferumoxytol.

2. Clinical Question

3. Trial Design

This was a Phase III, open-label extension trial of ferumoxytol for episodic treatment of iron deficiency anemia. The registry lists the design as single-group, with allocation recorded as NA and masking as none. The overall enrollment was 634. The listed intervention was ferumoxytol, and the trial status is completed.

The extension followed participants from AMAG-FER-IDA-301, in which participants had received ferumoxytol or placebo. Those who entered the extension were evaluated monthly and could receive ferumoxytol if they met criteria for persistent or recurrent iron deficiency anemia. The registry description of those criteria is incomplete, so the full treatment decision rules are not reported in the registry record. This is important context: extension treatment was conditional on eligibility, rather than assigned as part of a new randomized comparison.

The primary endpoint focuses on hemoglobin change after the first ferumoxytol course, from TP Baseline to TP Week 5. The analysis population includes participants who received at least one ferumoxytol dose and had evaluable hemoglobin data at both endpoint time points. This is the registry’s stated operational definition of the ITT Population for this endpoint.

The trial began on 2010-07-27 and had a primary completion date of 2012-09-24. The registry record does not report a sample-size justification, the planned statistical analysis in sufficient detail to reproduce it, or interim analyses. The design should therefore be interpreted as an open-label, single-group extension, not as a randomized trial comparing ferumoxytol with a concurrent control.

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: ITT Population: Participants who received at least 1 dose of ferumoxytol and had evaluable data for hemoglobin at TP Baseline and TP Week 5 in AMAG-FER-IDA-303.

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: All participants

6. Primary Endpoint

The registry lists the primary outcome as Mean Change In Hemoglobin From TP Baseline To TP Week 5 Following The First Course Of Ferumoxytol, measured over TP Baseline (Day 1), TP Week 5.

The primary endpoint is the mean change in hemoglobin from TP Baseline to TP Week 5 following the first course of ferumoxytol. Hemoglobin is measured in g/dL, and the registry defines change by subtracting the TP Baseline value from the TP Week 5 value. TP Baseline is the most recent measurement on or after screening, or the closest monthly evaluation visit before Day 1 dosing of Course 1.

As a continuous endpoint, the mean summarizes the average change across participants in the defined analysis population. The standard deviation describes how dispersed individual changes are around that average. Together, these quantities can describe both the average pattern and the variability in response, but they do not show how many participants had a particular change unless the results provide that information separately.

Hemoglobin is used as a laboratory measure of anemia-related change. The endpoint is focused on the period after the first course, rather than on a comparison between randomized treatment groups. The registry record does not report the numerical mean change or standard deviation, so it is not possible to state the direction, magnitude, or precision of the primary endpoint result from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods described in the registry record are limited. It defines the primary measure as mean change in hemoglobin, specifies the two time points, gives the endpoint population, and states how missing post-baseline values were handled. The detailed statistical analysis plan, including any model, test, confidence-interval method, or prespecified adjustment, is not reported in the registry record. The explanations below are general statistical context, not a claim about methods that were not documented.

What a mean change summarizes

For each participant with endpoint data, change is defined as the TP Week 5 hemoglobin value minus the TP Baseline value. The mean of those changes describes the average change in the analysis population. This is different from comparing the mean hemoglobin at TP Week 5 with the mean at baseline without accounting for which measurements belong to the same participant. A within-participant change retains that pairing.

The standard deviation describes the spread of participant-level changes around their mean. A small spread would indicate that changes cluster more closely around the average; a larger spread would indicate more variation. The registry identifies standard deviation as the dispersion measure, but does not report its numerical value for the primary endpoint. A standard deviation is not the same as a standard error or a confidence interval: it describes variation among participants, whereas uncertainty about the estimated mean depends on the analysis and amount of information available.

What a confidence interval would add

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity under a specified method. Its width reflects both the variability in the observations and the amount of information used in the estimate. A point estimate alone would not show that uncertainty. Neither a numerical confidence interval nor the method for constructing one is reported in the registry record for the primary endpoint, so no interval should be inferred.

Understanding the single-group setting

General statistical explanation: a single-group change analysis describes what happened in the observed group over the measured period. Without a concurrent comparison group, it cannot isolate the change that would have occurred in the absence of the intervention. The registry describes this as a single-group extension and records no masking. It also states that participants could receive ferumoxytol in the extension when they met criteria for persistent or recurrent iron deficiency anemia. Thus, treatment exposure and entry into a treatment course are part of the context for interpreting the observed changes.

The record notes prior participation in AMAG-FER-IDA-301, where participants received ferumoxytol or placebo. That earlier study context does not turn this extension endpoint into a randomized comparison. The extension analysis population is defined by receiving at least one dose of ferumoxytol and having evaluable hemoglobin data at both time points. That population definition should be used when interpreting the endpoint, rather than assuming that all 634 enrolled participants contributed to it.

How the missing-value rule matters

For change from baseline, the registry says a missing post-baseline value was imputed as 0. In this endpoint’s change scale, that means a missing post-baseline observation was assigned no change from baseline for the calculation. General statistical explanation: this rule can affect the estimated mean, because an imputed value contributes to the result rather than being omitted or estimated using a model. The direction and size of any effect depend on how many values were missing and on the values that would otherwise have been observed. Those missing-data counts and further sensitivity analyses are not reported in the registry record.

This rule does not establish that missing outcomes truly represented no change. It is an analysis convention stated for the endpoint. Readers should distinguish the convention from observed measurements and should not interpret imputed values as measured hemoglobin values.

Over-dispersion and count outcomes

General statistical explanation: over-dispersion occurs when count data vary more than a statistical model’s assumptions allow. When present, it can make uncertainty estimates too optimistic if not accounted for. The primary endpoint is a continuous mean change, not a count outcome, and the registry does not report a model for it that would permit assessment of over-dispersion. This concept should not be attributed to the trial analysis without evidence that a relevant count model was used.

What the planning section represents

The sample-size section is a planning illustration based on the observed effect, rather than the trial’s own design rationale. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. These are hypothetical planning assumptions, not evidence that this single-group extension used two equally allocated arms. The registry does not report the trial’s sample-size justification. Planning figures should not be read as observed power, nor as a retrospective confirmation that the trial could answer its clinical question.

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("Ferumoxytol")
n   <- c(151)
m   <- c(2.6)
sp  <- c(1.55)
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  Ferumoxytol  151  2.600  1.550  2.351  2.849

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and one analysis. It identifies the primary hemoglobin change endpoint and names secondary outcomes covering repeated-course hemoglobin changes, hemoglobin thresholds, transferrin saturation, FACIT-Fatigue questionnaire change, and time to a hemoglobin outcome. However, the registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a detailed statistical analysis plan. It is therefore not possible to determine from this record how the chance of false-positive findings across multiple outcomes was addressed, if at all.

For the primary endpoint, the registry states that missing post-baseline values were assigned a change of 0. This is a specific imputation rule, not a description of the amount or pattern of missing data. The number of participants with missing measurements, reasons for missingness, and sensitivity analyses under alternative assumptions are not reported in the registry record. General statistical explanation: conclusions based on imputed values can depend on whether the imputation assumption is reasonable for the missing observations. The rule should therefore be kept visible when interpreting the endpoint.

The endpoint population is called the ITT Population in the record, but its operational definition is participants who received at least one ferumoxytol dose and had evaluable hemoglobin data at TP Baseline and TP Week 5 in AMAG-FER-IDA-303. This definition is narrower than the overall enrollment of 634. The registry does not report the number meeting this endpoint definition. Since this is a single-group extension, the label should be understood using the registry’s stated criteria rather than assuming an all-randomized analysis population.

These reporting gaps limit assessment of multiplicity, missing-data sensitivity, and analysis-population flow. They do not establish that no additional procedures were used; those details are simply not reported in the registry record.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure congestive (0.6%), colitis ulcerative (0.6%), gastrointestinal haemorrhage (0.6%), abortion spontaneous (0.6%), atrial fibrillation (0.3%).

The safety summary lists 337 participants at risk for serious adverse events and 22 affected. For other adverse events, it lists 337 at risk and 93 affected. These are counts in the posted results, not comparative estimates against a concurrent control group. The registry does not provide a randomized comparator for this extension.

The listed serious-event terms include cardiac failure congestive, colitis ulcerative, gastrointestinal haemorrhage, and abortion spontaneous, each reported as 0.6%. Atrial fibrillation and small intestinal stenosis are each reported as 0.3%. These percentages are reproduced as listed; they should not be treated as estimates of treatment-caused risk or compared with outside populations using this record alone. The registry does not report a causal attribution for these terms in the information.

The death field is null, so a death result is not reported in the registry record. A null field should not be interpreted as evidence that no deaths occurred. The available figures also do not describe event timing, recurrence, severity beyond the serious-event classification, or participant-level overlap between event categories. They provide a limited summary of reported safety counts, not a complete account of individual clinical histories.

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

This trial record is useful for understanding how an open-label extension evaluated episodic ferumoxytol treatment and defined its hemoglobin endpoint. It specifies that the primary measure was mean hemoglobin change from TP Baseline to TP Week 5 following the first course, and it identifies the population used for that measure. It also reports a rule for handling missing post-baseline values and presents selected adverse-event counts.

What the record does not show is the numerical primary endpoint result. The mean change and standard deviation are not reported in the registry record, and no confidence interval or endpoint-specific test result is available. Without those results, it is not possible to say how large the average observed change was, what its direction was, or how precise the estimate may have been. The secondary outcome definitions likewise do not establish their numerical findings.

The design also limits what an observed change could establish. This was a single-group extension with no concurrent control in the extension analysis, and treatment could be received when participants met criteria for persistent or recurrent iron deficiency anemia. A before-and-after change can describe the observed course in the analyzed group, but it is not by itself a randomized estimate of the difference attributable to treatment.

The safety counts should be read as the registry’s reported numbers, not as proof that events were caused by the intervention or as a comparison with another treatment. The listed serious adverse-event terms and percentages provide a summary, while the record does not report a death result or detailed event-level context.

In short, the record supports a careful account of design, endpoint definitions, handling of missing post-baseline data, and selected safety summaries. It does not support a numerical efficacy conclusion or a causal comparison. Those boundaries matter when reading the tables, plots, and planning illustrations elsewhere on the page.

14. Why This Trial Matters Statistically

This record illustrates why design labels and analysis populations matter as much as outcome names. The trial is a Phase III extension, but its extension analysis is single-group, open-label, and not a concurrent randomized comparison. The primary endpoint is a within-participant hemoglobin change after the first ferumoxytol course. Readers therefore need to distinguish a descriptive change over time from a treatment contrast between groups.

It also illustrates how population definitions can narrow the interpretation. Overall enrollment was 634, while the primary endpoint population was defined by treatment receipt and evaluable hemoglobin measurements at two time points. The registry does not report how many participants met that definition. A trial-wide enrollment figure should not automatically be treated as the sample size for every endpoint.

Missing-data handling is another statistically consequential detail. The registry states that missing post-baseline values were assigned a change of 0. That explicit rule is more informative than a generic statement that missing data were handled, but the extent of missingness and sensitivity to alternative assumptions are not reported. Readers can identify the method but cannot assess its impact from the registry record.

Finally, the case separates endpoint plans from endpoint findings. The record gives a clearly defined hemoglobin measure and lists several secondary measures, yet does not report the numerical primary result or the secondary results. The calculated displays and sample-size illustrations may support statistical learning, but they cannot fill in missing trial outcomes. This is a useful reminder that a method can be described without enough posted results to judge the estimate’s magnitude or precision.

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 most important limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. The mean change and standard deviation are identified as measures, but their values are absent. A confidence interval, p-value, and detailed analysis method are also not reported. This prevents assessment of the endpoint’s magnitude and precision.

The single-group extension design does not provide a concurrent control comparison. The lack of masking and the conditional opportunity to receive treatment are relevant features of the setting. Participants entered from a parent study in which they had received ferumoxytol or placebo, and extension treatment was available when persistent or recurrent iron deficiency anemia criteria were met. The complete criteria are not reported in the registry record.

The endpoint population is defined by having received at least one dose and having evaluable measurements at both specified time points. The number meeting that definition, the participant flow into the analysis, and the quantity of missing data are not reported. The imputation rule assigning a change of 0 to a missing post-baseline value is stated, but its impact cannot be evaluated without further information or sensitivity analyses.

The registry record does not report the sample-size justification, interim analyses, multiplicity procedure, or a complete statistical analysis plan. It lists adverse-event counts and selected serious-event terms, but the death result is not reported and the available summary does not establish causality. These limitations apply to interpretation of this registry record; they do not establish what may have been documented elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Trial of Ferumoxytol for the Episodic Treatment of Iron Deficiency Anemia — NCT01114217.
• Registry record last updated 2022-04-21; status last verified 2022-03.
• Results first posted 2018-06-11.
• 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.

19. Record Summary

NCT01114217 is a completed Phase III, open-label extension trial evaluating episodic ferumoxytol treatment for iron deficiency anemia. The registry describes a single-group design, enrollment of 634, and an intervention of ferumoxytol. Participants in the extension were evaluated monthly and could receive treatment when criteria for persistent or recurrent iron deficiency anemia were met.

The primary endpoint was mean hemoglobin change from TP Baseline to TP Week 5 after the first course. Its analysis population required at least one dose and evaluable hemoglobin values at both time points. Missing post-baseline values were assigned a change of 0. The numerical primary result is not reported in the registry record.

The record lists 337 participants at risk for serious adverse events, with 22 affected, and 337 at risk for other adverse events, with 93 affected. The death result is not reported in the registry record. Overall, the available information describes the study design, endpoint rules, and selected safety data, but does not provide the numerical efficacy results needed to characterize the primary estimate.