Evaluate the Utility of Serum Hepcidin Levels to Predict Response to Oral or IV Iron: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluate the Utility of Serum Hepcidin Levels to Predict Response to Oral or IV Iron (NCT01950247), a randomized phase 4 study. The primary outcome is Multidimensional Assessment of Fatigue (MAF) Scores.

2. Clinical Question

The trial’s broader objectives also included comparing safety, quality-of-life effects, and resource utilization for Injectafer versus IV iron SOC. Separately, it aimed to assess whether baseline serum hepcidin could predict a clinically meaningful hemoglobin response to oral or IV iron therapy. The posted primary result concerns MAF score change; it does not answer every objective in the trial description. The registry record does not report posted results for the hepcidin prediction objective, oral iron response, resource utilization, or the other quality-of-life measures.

3. Trial Design

This was a randomized, parallel-group, phase 4 trial with no masking reported. Its stated setting was an infusion center, and its condition of interest was iron deficiency anemia. The registry lists an enrollment of 1025 and marks the study as completed. The listed start date is 2013-08-15, and the listed primary completion date is 2015-05-20.

The two intervention arms were Injectafer and IV iron standard of care (SOC). Injectafer was described as two doses at 15 mg/kg, with a maximum single dose of 750 mg, given 7 days apart, for a total of up to 1500 mg. For SOC, the dose and administration regimen were determined by the study-site investigator. The registry record does not report further details of randomization, such as the sequence-generation or allocation-concealment procedures.

The primary outcome was the change in mean MAF score from baseline to Day 30. The posted outcome groups contain 264 participants for Injectafer and 269 for SOC. These outcome counts are not the same as the listed overall enrollment; the registry record does not explain the difference or detail which participants contributed to this outcome.

The registry record does not report the original trial sample-size justification, its planned statistical analysis methods, or an original design target for the primary comparison. It lists no posted analysis records and no posted secondary outcome results. Therefore, the posted primary comparison can be interpreted as reported, but details such as adjustment for baseline values, analysis-population definitions, and handling of missing outcome data are not available 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Change from baseline to Day 30

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 Multidimensional Assessment of Fatigue (MAF) Scores, measured over Baseline to Day 30.

The primary endpoint is the change in the Multidimensional Assessment of Fatigue (MAF) score from baseline to Day 30, summarized as a mean with a standard deviation. The registry describes this outcome as a change in score, rather than as the Day 30 score alone.

The MAF has 16 items. Items 1 through 15 contribute to the Global Fatigue Index (GFI), a composite score. Items 1 through 14 use a scale from 1 to 10, with 1 meaning “not at all” and 10 meaning “a great deal.” Items 15 and 16 use categorical responses from 0 to 4, where 0 means no days and 4 means every day. The GFI is calculated by summing specified items and averaging others. Its final score ranges from 1, indicating no fatigue, to 50, indicating severe fatigue.

Because lower scores on this scale correspond to less fatigue, a negative change indicates a lower score at follow-up than at baseline. The measure provides a way to summarize reported fatigue as a continuous outcome, and the mean change describes the average change among participants included in each arm’s posted result. The registry record does not report further details about questionnaire completion, scoring implementation, or the clinical threshold used to define a meaningful change.

7. Results Posted in the Registry

• Injectafer: mean -8.80 versus -8.10 on control; difference -0.70 (95% CI -2.62 to 1.22), standardized effect d = -0.06; z-test p = 0.476.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a comparison of a continuous outcome: change in MAF score. The registry reports a mean and standard deviation for each arm, followed by an unadjusted mean difference, an interval estimate, and a p-value. The difference is expressed in MAF score units, which keeps the comparison on the scale used by the endpoint.

What does a mean change represent?

For each participant with a usable baseline and follow-up score, change is the follow-up score relative to the baseline score. A mean change summarizes the average of these individual changes within an arm. It does not show how every participant changed: individuals may have changes above or below the arm mean. The standard deviation describes variability among the observed changes. It is not the standard error and does not directly express the precision of the estimated arm mean.

What does the mean difference compare?

The posted mean difference compares the average change in the Injectafer arm with the average change in the SOC arm. A negative difference indicates a more negative mean change for Injectafer on the stated comparison scale. The registry labels the comparison unadjusted. An unadjusted comparison does not account for other measured variables through a reported statistical adjustment. Whether the trial’s original analysis used additional adjustment, or whether this comparison matches that analysis, is not reported in the registry record.

How should the p-value be read?

In general, a p-value measures how surprising data at least as incompatible with a specified null model would be if that model and the analysis assumptions were correct. It is not the probability that the null model is true, and it does not measure the clinical importance of an effect. The posted p-value is unadjusted. The registry record does not give the full test specification or analysis plan, so details such as the exact test and any planned covariate adjustment are not reported.

Why does the confidence interval matter?

In general, a confidence interval expresses uncertainty around an estimate and gives a range of values compatible with the data under a specified method. For this result, the interval spans negative and positive mean differences. That means the posted estimate does not precisely distinguish the direction of the between-arm difference. The interval’s confidence level and calculation method are not reported in the registry record, so the interval should be described using its posted endpoints without assuming those details.

What does the design tell us?

Random allocation is intended, in general, to support a fair comparison between intervention groups by distributing prognostic factors without systematic assignment. It does not ensure that groups are identical in every realized trial. No masking was reported, so participants and study personnel were not described as blinded to assignment. Knowledge of assignment can matter for outcomes involving participant-reported experience, such as fatigue, and for how care is delivered or recorded. The registry record does not report whether outcome assessors were masked separately.

Why might outcome counts differ from enrollment?

An overall enrollment count and the number contributing to a particular outcome can differ for reasons such as outcome availability or analysis-population definitions. Those explanations are general possibilities, not documented reasons for this trial. Here, the registry lists an enrollment of 1025 and posts primary-outcome counts of 264 for Injectafer and 269 for SOC. The reasons for the difference, the missing-data approach, and the analysis population are not reported in the registry record.

These distinctions matter when interpreting the result. The posted summary statistics describe the participants included in that outcome result, while the registry record does not provide enough detail to assess the handling of incomplete data or to reconstruct a full analysis. The comparison is useful as a description of the posted MAF change, but its statistical interpretation should remain limited to the methods and information that are actually recorded.

10. Confidence Intervals and Precision

The estimated unadjusted mean difference in MAF change is -0.7 units, with an interval from -2.624 to 1.224. The estimate is the central summary of the between-arm comparison; the interval indicates uncertainty around it. Because the interval includes differences in both directions, the data do not pin down a single direction of the between-arm contrast with precision.

In general, a confidence interval gives a range of values that are compatible with the observed data and the method used to construct the interval. It is not a guarantee that the true effect lies within the endpoints, and it does not show the range of individual participant responses. The posted interval is specific to the mean difference, whereas the arm-level standard deviations, 11.38 and 11.28, describe variability in participant-level changes.

The registry record does not report the confidence level or the method used to calculate this interval. It also does not describe whether the interval comes from the trial’s own analysis or from a separate unadjusted calculation. The p-value is reported as 0.476, but it should not replace attention to the interval: a p-value alone does not describe the range of plausible effect sizes. The interval’s breadth, spanning both negative and positive values, signals uncertainty about the direction and magnitude of the comparison.

Precision is also affected by which observations were included. The posted outcome counts are 264 for Injectafer and 269 for SOC, while the registry lists overall enrollment of 1025. The registry record does not explain the outcome counts or how missing data were handled. Without that information, the posted interval can be described, but the completeness of the analyzed outcome data cannot be assessed from the record.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They illustrate the sample size associated with detecting a specified fraction of the observed mean difference under the stated assumptions. For 100% of the observed effect, the figures are 4,113 participants per arm for 80% power and 5,506 participants per arm for 90% power. For planning at 75% of the observed effect, the figures are 7,311 participants per arm for 80% power and 9,787 participants per arm for 90% power. For 50% of the observed effect, they are 16,449 participants per arm for 80% power and 22,021 participants per arm for 90% power.

In plain terms, the 80% power column gives the planning count per arm for an analysis with an 80% chance of detecting the specified effect under the assumptions used. The 90% power column gives the corresponding count for a 90% chance. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is the stated fraction of the observed effect.

Smaller effects require more participants to detect under these assumptions, which is why the planning figures increase as the target fraction decreases. These are planning illustrations calculated from the observed effect, not observed power for the trial. The registry record does not report the trial’s own original sample-size justification or design assumptions.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.700; pooled standard deviation σ = 11.330.
2. n = 2 × (1.96 + 0.842)² × 11.330² / -0.700² = 4,112.2, rounded up to 4,113 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.700000000000001                      # observed difference in means
sigma <- 11.3296395110389                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1950247)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 4,113 (80% power), 5,506 (90% power)
 75% of observed effect: n per arm = 7,311 (80% power), 9,787 (90% power)
 50% of observed effect: n per arm = 16,449 (80% power), 22,021 (90% power)
power.t.test: 4113.2 
Simulated power at n = 4,113 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The trial description includes several objectives: comparing safety, quality-of-life effects, and resource utilization for Injectafer versus IV iron SOC, and assessing whether baseline serum hepcidin predicts a clinically meaningful hemoglobin response to oral or IV iron therapy. The posted primary outcome result concerns MAF score change from baseline to Day 30. The registry record lists no posted secondary outcome results and no analysis records.

When a study assesses multiple outcomes, time points, subgroups, or comparisons, the chance of finding at least one apparently notable result can increase. Statistical procedures for addressing that issue are generally called multiplicity adjustments or multiplicity strategies. The registry record does not report whether any such procedures were planned or used, how outcomes were prioritized, or whether the primary comparison was the only confirmatory analysis. No multiplicity adjustment should therefore be assumed from the posted unadjusted p-value.

The registry record also does not report how missing MAF data were handled, what analysis population was used, or whether participants were analyzed according to randomized assignment. These details can affect which observations contribute to the arm means and comparison. The posted outcome counts are 264 for Injectafer and 269 for SOC, while overall enrollment is listed as 1025; the reason for this difference is not reported in the registry record.

These omissions do not change the values posted for the primary result, but they limit assessment of how the result was derived and how it relates to the broader study objectives. The record supports describing the stated comparison and its uncertainty. It does not provide enough information to reconstruct the complete statistical analysis plan, evaluate missing-data assumptions, or determine how multiple outcomes were handled.

14. 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: cardiac disorders (0.8%).

The registry lists serious adverse events for 513 participants at risk in the Injectafer arm, with 4 serious adverse events recorded. For IV iron SOC, it lists 512 participants at risk and 1 serious adverse event. Other adverse events are listed for 28 participants in the Injectafer group and 21 in the SOC group, with 513 and 512 participants at risk, respectively. One death is listed in each arm.

These are counts as recorded, not estimates of comparative risk. The registry record does not provide a statistical comparison, confidence intervals, event-level timing, or further details about how adverse events were collected or attributed. It lists “Cardiac disorders” at 0.8% among the top serious adverse-event terms; the denominator and further context for that percentage are not reported in the registry record.

Counts should be read with their corresponding at-risk group and with the limitations of the posted safety information in mind. The registry record does not report whether participants could experience more than one event or how event terms were grouped. These figures describe the posted safety entries and do not, by themselves, establish a causal difference between the arms.

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

The primary result describes average change in fatigue scores through Day 30 among the participants included in the posted outcome analysis. Mean MAF scores decreased from baseline in both arms, and the posted unadjusted comparison estimated a mean difference of -0.7 units for Injectafer relative to IV iron SOC. The interval extends from -2.624 to 1.224, so it is compatible with a difference in either direction as well as no between-arm difference.

This does not establish that the treatments have the same effect. An inconclusive comparison can reflect uncertainty about the effect, and the posted interval does not tightly determine the direction or magnitude of the difference. Nor does the result establish that one treatment is superior. The registry record does not report a clinical threshold for interpreting the size of a MAF change, so the clinical importance of the numerical difference cannot be judged from the posted result alone.

The result also does not answer every objective described for the trial. The registry record does not post secondary outcome results for safety comparisons, resource utilization, other quality-of-life measures, or the ability of baseline serum hepcidin to predict response to oral or IV iron. The adverse-event counts are descriptive entries without a posted comparative analysis. No conclusions about those broader outcomes can be drawn from the primary MAF comparison.

Finally, the registry record does not report the missing-data approach, analysis-population definition, or original statistical analysis plan. Those omissions limit assessment of how the comparison was produced and how representative it is of all enrolled participants. The most defensible reading is therefore restricted to the posted mean changes, their unadjusted contrast, and the uncertainty expressed by the interval.

16. Why This Trial Matters Statistically

This trial illustrates why a difference in group means should be read alongside its uncertainty. The arm-level average changes are both negative, while the estimated difference between them is small relative to the uncertainty represented by its interval. Looking only at the direction of the means or at a p-value would not convey the full range of comparisons compatible with the posted result.

It also highlights the distinction between variability and precision. The standard deviations describe how much individual change scores vary within each arm; the confidence interval concerns uncertainty in the estimated difference between arm means. These answer different statistical questions and should not be treated as interchangeable measures.

The registry record presents a useful example of the limits of registry summaries. It identifies a randomized, parallel, open-label design and reports an outcome comparison, but does not report the detailed analysis plan, missing-data methods, or reasons the outcome counts differ from enrollment. Statistical interpretation depends not only on the numerical estimate, but also on understanding how the analysis population was formed and how the data were handled.

Finally, the trial’s stated objectives were broader than its posted primary result. Keeping the MAF comparison separate from unreported safety, resource-use, and hepcidin-prediction results prevents a single endpoint from being treated as a summary of every study question. The planning illustrations also show that sample-size requirements depend on the target effect: smaller target effects require more participants under the stated planning assumptions. Those calculations are distinct from the design rationale for the completed trial, which is not reported in the registry record.

17. 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 outcome counts are 264 for Injectafer and 269 for IV iron SOC, while the registry lists overall enrollment of 1025. The registry record does not explain the difference, state how many participants had complete MAF data, or describe any exclusions from the outcome analysis. This limits assessment of how the posted results relate to the full enrolled population.

The registry record does not report the missing-data method, analysis-population definition, or detailed statistical analysis plan. It also does not report whether the primary comparison was adjusted for baseline MAF score or other variables. The posted mean difference is labeled unadjusted, but the relationship between that comparison and any original trial analysis is not described.

The study was not masked. Since MAF is a participant-reported measure, knowledge of treatment assignment could generally influence reporting or experience; the registry record does not report any separate masking of outcome assessors. This is a design consideration, not evidence that reporting was biased in this trial.

The record posts no secondary outcome results and no analysis records. It also does not report the confidence interval method or confidence level, the clinical threshold for a meaningful MAF change, or the original sample-size justification. These limitations restrict assessment of the result’s precision, clinical importance, and relationship to the wider objectives. They do not alter the posted values, but they constrain what can be inferred from them.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Evaluate the Utility of Serum Hepcidin Levels to Predict Response to Oral or IV Iron — NCT01950247.
• Registry record last updated 2025-05-22; status last verified 2024-11.
• Results first posted 2025-05-22.
• 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.

21. Record Summary

NCT01950247 is a completed, randomized, parallel, open-label phase 4 trial of Injectafer versus IV iron standard of care for iron deficiency anemia in an infusion-center setting. The registry lists enrollment of 1025, a start date of 2013-08-15, and a primary completion date of 2015-05-20.

The posted primary outcome is mean change in MAF score from baseline to Day 30. The mean change was -8.8 in the Injectafer arm and -8.1 in the SOC arm; the unadjusted mean difference was -0.7, with an interval from -2.624 to 1.224 and an unadjusted p-value of 0.476. The registry record lists no analysis records or secondary outcome results. Details of the original sample-size justification, missing-data handling, and analysis populations are not reported in the registry record.