Blinded Randomized Placebo-Controlled Study Efficacy and Safety of Injectafer in ID Patients With Fibromyalgia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Blinded Randomized Placebo-Controlled Study Efficacy and Safety of Injectafer in ID Patients With Fibromyalgia (NCT02409459), a randomized phase 2 study. The primary outcome is Proportion of Patients With a ≥13 Point Improvement in FIQR Score.

2. Clinical Question

3. Trial Design

This completed phase 2 trial, NCT02409459, was a randomized, double-masked, parallel-group, placebo-controlled study sponsored by American Regent, Inc. It enrolled 81 participants. The registry record lists the study start as 2015-03 and primary completion as 2015-10. Participants were randomized in a 1:1 ratio to Injectafer or placebo, with treatment scheduled on days 0 and 5. Follow-up for efficacy and safety continued for 42 days.

The Injectafer arm description specifies an intravenous dose of 15 mg/kg up to 750 mg, administered undiluted at 100 mg/minute. The placebo description specifies 15 cc of normal saline by intravenous push at 2 ml/minute. Both groups are described as blinded. The record identifies iron deficiency and fibromyalgia as the conditions under study.

The posted primary outcome counts use 39 participants in each arm. Those counts do not account for every participant in the enrollment figure; the registry record does not explain the difference or give a participant-flow account in the registry record. The safety results use separate at-risk counts, so their denominators should not be assumed to match the primary efficacy counts.

The planned follow-up was short, ending at Day 42. The listed outcomes include FIQR and Brief Pain Inventory measures, fatigue, and iron indices. The record does not report the original statistical analysis plan, sample-size justification, masking assessment, interim analyses, or details of treatment adherence. Those omissions limit assessment of how the reported outcomes relate to the trial’s prespecified design.

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

Analysis population for the primary outcome, as defined in the registry: The Safety population consisted of all subjects who received at least one dose of randomized treatment. The Efficacy Evaluable Population consisted of all subjects who received at least 1 dose of randomized treatment with at least 1 completed post treatment FIQR evaluation.

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 Proportion of Patients With a ≥13 Point Improvement in FIQR Score, measured over Day 42.

The primary endpoint is the proportion of participants with a ≥13-point improvement in Fibromyalgia Impact Questionnaire Revised (FIQR) score from baseline to Day 42. It is a responder outcome: each participant is classified according to whether their score change reaches the stated threshold, and the arm-level result is expressed as a count of participants meeting that criterion. The endpoint is not the average FIQR change, which is listed separately as a secondary outcome.

A responder threshold can make an outcome easier to interpret as the share of participants reaching a specified amount of improvement, rather than describing only an average change across a group. It also discards information about how far each participant’s change lies above or below the threshold. Participants just short of the criterion and those with little change are both counted as not meeting it, while the amount of improvement among responders is not conveyed by the count alone.

The registry record defines the efficacy-evaluable population as participants who received at least one dose of randomized treatment and had at least one completed post-treatment FIQR evaluation. It separately defines the safety population as all participants who received at least one dose. The posted primary counts are 30 of 39 for Injectafer and 26 of 39 for placebo. The registry record does not provide further detail about how missing Day 42 FIQR measurements were handled.

7. Results Posted in the Registry

• Injectafer: 76.9% (30/39) versus 66.7% (26/39) on control; risk difference 10.3 percentage points (95% CI -9.6 to 30.1), risk ratio 1.15 (0.87–1.53); unadjusted two-proportion z-test p = 0.314.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in BPI, Pain Interference

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Injectafer: mean -4.10 versus -2.30 on control; difference -1.80 (95% CI -3.13 to -0.47), standardized effect d = -0.61; z-test p = 0.008.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Injectafer than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in FIQR Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Injectafer: mean -45.00 versus -29.70 on control; difference -15.30 (95% CI -27.94 to -2.66), standardized effect d = -0.54; z-test p = 0.018.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Injectafer than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in BPI, Pain Severity

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Injectafer: mean -3.10 versus -1.80 on control; difference -1.30 (95% CI -2.38 to -0.22), standardized effect d = -0.54; z-test p = 0.019.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Injectafer than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted numerical secondary results follow a consistent direction for the three outcomes with available summaries: mean changes in BPI pain interference, FIQR score, and BPI pain severity are more negative in the Injectafer arm than in the placebo arm. Their unadjusted recalculated mean-difference intervals do not include zero. This pattern offers contextual evidence alongside the primary responder comparison, but it does not erase the uncertainty in that primary result or establish that the outcomes were planned as confirmatory tests.

The secondary FIQR result is related to the primary outcome because both use FIQR, but they answer different questions. The primary endpoint counts participants who pass a specified improvement threshold; the secondary endpoint compares average score changes. A difference in average change does not tell how many participants crossed the responder threshold, and a responder count does not describe the size of mean change. The two summaries should therefore be interpreted as complementary descriptions, not as interchangeable tests.

The registry lists additional secondary measures for fatigue and iron indices, including serum ferritin and transferrin saturation. Numerical results for those measures are not reported in the registry record. The record identifies six secondary measures, but only three have numerical summaries in the results. Their absence from the posted numerical results cannot be taken as evidence of no change or no difference.

Unadjusted secondary results carry less weight because several outcomes are examined and no multiplicity adjustment is reported. Without a stated testing hierarchy or correction procedure, nominal p-values do not account for the broader set of comparisons. The registry record also does not provide sponsor analyses for these outcomes. Accordingly, the secondary pattern can be described as supportive context, while keeping the primary endpoint and its uncertainty central to interpretation.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in BPI, Pain Interference
• Change in FIQR Score
• Change in BPI, Pain Severity
• Change in Fatigue Visual Numeric Scale
• Change in Iron Indices, Serum Ferritin
• Change in Iron Indices - Transferrin Saturation

9. Statistical Interpretation

10. Statistical Methods Explained

The posted comparisons can be read as simple, unadjusted comparisons between the Injectafer and placebo arms. For the primary binary outcome, the recalculated measure is a risk difference: the proportion meeting the responder criterion in one arm minus the proportion in the other. A value of zero corresponds to equal proportions. The confidence interval describes a range of values compatible with the observed counts under the calculation’s assumptions; it is not a guarantee that the true effect lies within that range.

What does the primary comparison measure?

The primary comparison is based on the counts meeting the ≥13-point FIQR improvement threshold and the arm denominators. The posted counts are 30 of 39 and 26 of 39. The recalculated risk difference is 0.103, with a 95% confidence interval from -0.096 to 0.301. Because the interval crosses zero, it does not rule out equal response proportions. The unadjusted p-value is 0.314. This p-value describes how unusual the observed data would be under a null model of no difference, subject to the calculation assumptions; it is not the probability that the null hypothesis is true.

How should mean differences be read?

The secondary continuous outcomes are reported as mean changes from baseline. Their recalculated comparisons subtract the placebo mean change from the Injectafer mean change. Negative values indicate a more negative mean change in the Injectafer arm, given the direction of the posted scores. For example, the posted BPI pain interference means are -4.1 and -2.3, and the recalculated mean difference is -1.8. The corresponding 95% confidence interval is -3.129 to -0.471. The estimate describes a difference between group means; it does not show the distribution of individual participant changes.

The registry reports standard deviations for the continuous arm summaries. Standard deviation describes spread among participant measurements, rather than uncertainty in the estimated group mean. A standard error, by contrast, describes the estimated uncertainty of a statistic. The recalculated mean-difference intervals use the posted group summaries and sample sizes. They are not adjusted for covariates or other analysis features, because no such analysis is reported in the registry record.

What do the p-values and intervals contribute?

A p-value and a confidence interval answer related but different questions. The p-value summarizes compatibility with a specified null model; the confidence interval displays a range of effect values compatible with the data and calculation method. Neither alone establishes clinical importance. Interpretation also depends on the outcome definition, study design, data completeness, and the range of effects considered meaningful. The registry record does not report a threshold for a clinically important between-arm difference.

The comparisons are unadjusted, and the registry record lists several outcomes. When multiple outcomes are tested, the chance of observing at least one apparently notable result can increase. An adjustment procedure may address that issue, but no multiplicity procedure is reported. The listed unadjusted p-values should therefore be treated as descriptive evidence rather than as a complete confirmatory analysis. The primary responder comparison remains the designated primary efficacy endpoint, while the secondary outcomes can provide supporting context without superseding it.

Why do analysis populations matter?

The registry record defines both a safety population and an efficacy-evaluable population. The safety population includes all participants who received at least one dose; the efficacy-evaluable definition additionally requires at least one completed post-treatment FIQR evaluation. These definitions affect which participants contribute to each analysis. The record does not state whether the primary counts use the efficacy-evaluable population exactly as defined, nor does it describe an intention-to-treat analysis or a method for handling missing outcome values. Those details matter because exclusions and missing measurements can affect the estimated comparison.

All recalculated comparisons are unadjusted summaries of the posted data. No sponsor-reported analyses are listed for the primary outcome or the posted secondary outcomes. The registry record does not report the trial’s statistical analysis plan, so it is not possible to determine whether the recalculated methods reproduce the planned analysis. The posted results should be read as the available summary evidence, not as a substitute for unreported analysis details.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.103, and its 95% confidence interval ranges from -0.096 to 0.301. The interval crosses zero and spans values on both sides of no difference. Its width signals substantial uncertainty about the magnitude and direction of the comparison. The estimate is not precise enough to distinguish clearly among the range of effects represented by the interval.

Confidence intervals are useful because they show uncertainty around an estimate rather than presenting a point estimate alone. In general, an interval reflects both the observed data and the method used to calculate it. A wider interval indicates less precision, while a narrower interval indicates more precision. The interpretation depends on the assumptions of the calculation and on whether the analysis matches the study design. For the primary result, the registry record does not provide a sponsor analysis or additional details that would resolve those limitations.

The recalculated continuous-outcome intervals are also relevant to precision. Their ranges are -3.129 to -0.471 for BPI pain interference, -27.94 to -2.66 for FIQR score, and -2.382 to -0.218 for BPI pain severity. These intervals do not include zero under the unadjusted calculations, but they still represent ranges of plausible mean differences, not exact values. Their interpretation should account for multiple outcomes and the absence of reported multiplicity adjustment.

Precision is not the same as importance. A result can be estimated with uncertainty even when its point estimate appears notable, and a narrow interval would not by itself establish that an effect matters to patients. The registry record does not report a clinically important difference threshold for these measures. It also does not report enough information about missing-data handling or the planned analysis to evaluate how those choices might affect interval estimates.

12. 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 sample-size figures are planning illustrations based on the observed effect, not the original trial’s design calculations. They are expressed as participants per arm, rather than total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row considers detecting the stated fraction of the observed effect: 100%, 75%, or 50%.

The 80% power column gives the planned number of participants per arm for a design that would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true effect. The 90% power column represents a higher chance of detection under the same assumptions and therefore requires a larger planned sample. Smaller effects need more participants to detect because they are harder to distinguish from random variation. These entries are planning estimates, not a report of the number actually enrolled or analyzed.

The original design’s sample-size assumptions and justification are not reported in the registry record. The displayed calculations use the observed estimates, which themselves are uncertain; they do not establish that the trial was planned around those effects. They are not observed power. Observed power is not a substitute for reading the effect estimate and its confidence interval, and the planning illustrations should not be used to claim that the trial did or did not have adequate power for its original question.

13. 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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.667; treatment proportion p₁ = 0.769; average p̄ = 0.718.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6364 = 1.2473.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6322 = 0.5321.
4. n = (1.2473 + 0.5321)² / (0.1026)² = 301.0, rounded up to 302 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
p0 <- 0.666666666666667                          # control proportion
p1 <- 0.769230769230769                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2409459)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 302 (80% power), 403 (90% power)
 75% of observed effect: n per arm = 551 (80% power), 737 (90% power)
 50% of observed effect: n per arm = 1,271 (80% power), 1,701 (90% power)
power.prop.test: 301 
Simulated power at n = 302 per arm: 0.801 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record designates one primary efficacy endpoint and lists multiple secondary outcomes. The primary endpoint is the proportion with a ≥13-point FIQR improvement at Day 42. Secondary outcomes include pain interference, FIQR score, pain severity, fatigue, serum ferritin, and transferrin saturation. Testing several outcomes raises a multiplicity issue: when many comparisons are examined, the chance of at least one result appearing notable by chance can increase.

No multiplicity adjustment, testing hierarchy, or other strategy for controlling the interpretation of multiple outcomes is reported in the registry record. The unadjusted p-values accompanying the recalculated comparisons should therefore not be read as if they accounted for all outcomes. This does not make the results unusable; it means their evidential weight should reflect the number of comparisons and the absence of a reported adjustment plan. The primary endpoint remains distinct from the secondary outcomes, but its own analysis details are also limited.

The registry record defines the safety population as participants who received at least one dose of randomized treatment. It defines the efficacy-evaluable population as those participants with at least one completed post-treatment FIQR evaluation in addition to receiving treatment. The record does not report whether missing Day 42 values were imputed, treated as nonresponse, excluded, or handled by another method. It also does not specify which population was used for each posted efficacy result beyond the population definitions.

The record lists no reported analyses for the primary or secondary outcomes. It does not report the trial’s statistical analysis plan, covariate adjustment, interim analyses, or the original rationale for the sample size. As a result, the recalculated comparisons provide unadjusted readings of posted summary statistics, but cannot establish whether they reproduce the sponsor’s planned procedures. Missing analytic details and missing-data methods are important limits on interpretation, particularly for a trial with separate safety and efficacy population definitions.

15. 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.

Most frequent non-serious adverse event terms

The posted serious adverse event figures show zero serious adverse events in the Injectafer group among 41 participants at risk and zero in the placebo group among 40 participants at risk. The registry record also reports zero deaths in both groups. These are counts over the period represented by the safety results; the record does not provide serious-event terms or further event-level details.

Other adverse events are reported for 16 of 41 participants in the Injectafer group and 2 of 40 in the placebo group. These counts should be read separately from serious adverse events, since the categories are not interchangeable. The results are descriptive counts in groups with limited size and do not, by themselves, determine whether an event was caused by treatment or establish a comparative safety profile.

The safety denominators differ from the primary efficacy denominators. The registry record defines the safety population as participants who received at least one dose, but does not supply additional detail about event timing, severity classifications for other events, or the sponsor’s comparative safety analysis. The absence of reported serious events in these counts is not evidence that serious events are impossible or that the treatments have equivalent safety.

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

The posted primary counts favor a higher observed responder proportion in the Injectafer arm, but the recalculated risk difference has a confidence interval that includes zero and a p-value of 0.314. The estimate is uncertain and does not establish a clear between-arm difference. The secondary continuous outcomes have more negative mean changes in the Injectafer group and unadjusted confidence intervals that do not include zero, but they remain secondary comparisons with no reported multiplicity adjustment.

These results do not establish that Injectafer works or does not work for fibromyalgia. A registry summary provides limited information about analysis choices, missing data, and the relation between the reported populations and the endpoint counts. The registry record does not report a sponsor analysis for the primary or posted secondary results. The recalculated comparisons are therefore best treated as descriptive statistical readings of the posted summaries.

The endpoint also has a specific scope: it captures whether a participant met the stated FIQR improvement threshold by Day 42. It does not describe duration beyond that follow-up, outcomes not measured in the trial, or the experience of people outside the studied population. The average FIQR change and the responder count provide related but distinct views of the same measure. Neither alone describes every aspect of participant-level response.

The result should be read together with the confidence intervals, the outcome definitions, the study design, and the limits of registry reporting. The short follow-up, modest posted efficacy groups, unreported missing-data handling, and unreported multiplicity strategy all constrain conclusions. These findings are evidence about the outcomes and period recorded in this trial, not a general conclusion about all patients or all treatment settings.

17. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition matters. A responder analysis answers how many participants reached a specified improvement threshold, whereas a comparison of mean change describes the average difference between groups. The primary FIQR responder result and the secondary mean FIQR result can therefore produce different statistical impressions without being contradictory. They summarize different features of the outcome distribution.

It also demonstrates the distinction between an estimate and its precision. The primary point estimate is positive, yet its confidence interval spans zero and includes a broad range of possible differences. Looking only at the arm counts or the point estimate would omit important uncertainty. The interval gives readers a more complete account of what the posted data can support.

The registry lists several secondary measures, while numerical results are available for only some of them. With multiple outcomes and no reported multiplicity procedure, secondary p-values need cautious interpretation. This is a practical reminder that nominal statistical significance is not the same as a prespecified, multiplicity-controlled confirmatory finding.

Finally, the record distinguishes safety and efficacy populations but gives limited detail on missing measurements and analysis choices. Those details can affect who contributes to each result and how robust a comparison is. A registry record can support transparent reading of posted summaries, while still leaving key statistical questions unanswered.

18. 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 registry record does not report the original sample-size justification or the assumptions used to design the trial. The planning illustrations are based on observed effects and cannot be treated as evidence about the study’s original power. The record also does not report the statistical analysis plan, so it is not possible to confirm that the recalculated unadjusted comparisons match the planned analyses.

Posted primary outcome counts include 39 participants per arm, while enrollment is 81. The record does not explain participant flow or the difference between enrollment and the posted primary denominators. Safety at-risk counts are different, and the record does not provide more detail connecting these denominators to the defined populations. This limits assessment of exclusions and analysis-set membership.

The registry record does not describe missing-data handling for the Day 42 endpoint or state how participants without post-treatment FIQR evaluations were treated. That is especially relevant because the efficacy-evaluable population definition requires a completed post-treatment FIQR evaluation. No sponsor-reported analysis is listed for the primary outcome or the secondary comparisons, and no multiplicity adjustment is reported.

Numerical results are not reported for all listed secondary outcomes. Follow-up for efficacy and safety was 42 days, so the record does not address outcomes beyond that period. The posted summaries also provide limited detail about participant-level distributions and adverse-event terms. These trial-specific gaps restrict interpretation of robustness, outcome completeness, and the broader reach of the results.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Blinded Randomized Placebo-Controlled Study Efficacy and Safety of Injectafer in ID Patients With Fibromyalgia — NCT02409459.
• Registry record last updated 2018-02-20; status last verified 2018-01.
• Results first posted 2017-12-13.
• 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.

22. Record Summary

NCT02409459 is a completed phase 2 randomized, double-masked, parallel-group, placebo-controlled study of Injectafer versus placebo in iron-deficient patients with fibromyalgia. Enrollment was 81, with dosing on days 0 and 5 and efficacy and safety follow-up for 42 days.

The primary Day 42 outcome was the proportion with a ≥13-point FIQR improvement. Posted counts were 30 of 39 with Injectafer and 26 of 39 with placebo. The recalculated risk difference was 0.103, with a 95% confidence interval from -0.096 to 0.301 and p = 0.314. Several secondary outcomes have numerical summaries, but no sponsor analyses or multiplicity procedure are reported. The registry record also does not report missing-data methods or the original sample-size assumptions.