MIRACLE Study: A Study of Once-Monthly Intravenous Mircera in Hemodialysis Participants With Chronic Renal Anemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MIRACLE Study: A Study of Once-Monthly Intravenous Mircera in Hemodialysis Participants With Chronic Renal Anemia (NCT00545571), a na phase 3 study. The primary outcome is Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb or Within Target Range During the Efficacy Evaluation Period (EEP).

2. Clinical Question

3. Trial Design

The MIRACLE study is registered as a Phase 3, interventional, multicenter, open-label, single-arm study sponsored by Hoffmann-La Roche. Its stated aim was to assess the efficacy, safety, and tolerability of once-monthly intravenous Mircera for maintenance of hemoglobin levels in hemodialysis participants with chronic renal anemia. The registry lists enrollment of 120. That registry enrollment figure does not establish how many participants contributed data to the primary endpoint or safety summaries.

Participants previously receiving maintenance darbepoetin alfa, epoetin alfa, or epoetin beta were to start Mircera at a dose selected according to their erythropoiesis-stimulating agent dose before treatment. The listed starting doses were 120, 200, or 360 micrograms per month. Subsequent doses were adjusted to maintain hemoglobin within the country-specific target range. The study description gives administration every 4 weeks for 52 weeks.

The primary endpoint focuses on average hemoglobin during the Efficacy Evaluation Period, which covered Weeks 18 to 24. The record describes blood sampling at Weeks 18, 20, 22, and 24, as well as sampling before dialysis sessions. The pretreatment reference hemoglobin was calculated individually from values collected during the stability assessment at Weeks -4 to 0. The applicable target range was 11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria.

Because the study has no concurrent comparator, it can describe outcomes among participants receiving Mircera but cannot provide a randomized estimate of how those outcomes differ from another treatment. The registry record does not report the detailed protocol, the criteria used to select the Per Protocol population, or the number of participants included in each endpoint analysis.

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: Per Protocol (PP) Population: All participants from the Intent-to-Treat (ITT) Population who fulfill select criteria per study protocol.

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: Intent-to-Treat (ITT) Population: All participants who received at least one dose of study drug and for whom data were available from at least one follow-up variable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb or Within Target Range During the Efficacy Evaluation Period (EEP), measured over At Weeks -4, -3, -2, -1, 0; pre-dose (0 hours) and immediately before dialysis (minimum 3 sessions per week) during Weeks 18, 20, 22, 24.

The primary endpoint is the percentage of participants whose average hemoglobin during the Efficacy Evaluation Period met two conditions: it was within the country-specific target range, and it was within ±1 g/dL of that participant’s reference hemoglobin. The reference was calculated for each participant as the average of hemoglobin values during the pretreatment stability assessment at Weeks -4 to 0. The endpoint therefore combines a study-defined target with a measure anchored to each participant’s own pretreatment level.

The Efficacy Evaluation Period covered Weeks 18 to 24. The registry describes four pre-dose blood samples during that period and additional sampling before dialysis sessions. These repeated measurements inform the average used for the endpoint; the endpoint itself is a participant-level classification, summarized as a percentage. The specified analysis population is the Per Protocol population, drawn from the Intent-to-Treat population according to selected protocol criteria.

A proportion is a direct way to express how many participants met the endpoint definition. The registry specifies an exact Pearson-Clopper confidence interval to communicate uncertainty around that proportion. However, neither the endpoint percentage nor its confidence limits are reported in the registry record. Consequently, the recorded endpoint definition can be explained, but its observed result and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a proportion: each participant in the analysis population is classified according to whether the average hemoglobin during the Efficacy Evaluation Period meets the endpoint definition. The reported percentage would summarize the share classified as meeting it. A percentage describes the observed study group; it does not, on its own, show why participants did or did not meet the definition.

What does the confidence interval add?

A confidence interval expresses the statistical uncertainty around an estimate. For a proportion, the interval reflects that the observed share is based on a finite group of participants and may differ from the underlying share in a broader population. A narrower interval indicates greater precision under the method’s assumptions; a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its limits, and it does not address systematic differences between this study and other settings.

The registry specifies a 95% confidence interval calculated with the Pearson-Clopper method for exact confidence bounds. This is an exact binomial interval method for a proportion, rather than an interval based on a simple normal approximation. The record does not report the estimated percentage or either confidence limit. Therefore, the degree of statistical precision cannot be judged from the registry entry.

Why define the endpoint using two criteria?

The endpoint requires the average hemoglobin during the Efficacy Evaluation Period to satisfy both the country-specific target range and the individual-reference condition of within ±1 g/dL. The target range provides a prespecified interval that differs by country. The individual reference condition anchors the assessment to each participant’s pretreatment hemoglobin. A participant who satisfies only one of the two conditions would not meet the endpoint as described in the primary endpoint details.

The reference value was based on all hemoglobin values collected during the pretreatment stability assessment at Weeks -4 to 0. During the Efficacy Evaluation Period at Weeks 18 to 24, the registry describes four pre-dose samples and sampling before dialysis sessions. Averaging multiple measurements can describe a period of treatment rather than relying on a single measurement. The registry does not report details such as the handling of missing measurements or the exact calculation rules when measurements were unavailable.

What can a single-group study estimate?

In general, a single-group study can estimate the proportion meeting a defined endpoint among participants with evaluable data, subject to how participants were selected and followed. It has no concurrent control group for estimating a treatment contrast. Without random allocation to a comparator, observed outcomes cannot isolate the treatment’s effect from other influences. This is a design limitation, not a statistical flaw that can be resolved by a confidence interval around the single-group proportion.

The registry describes the primary analysis population as Per Protocol: participants in the Intent-to-Treat population who fulfill selected protocol criteria. The exact criteria and the number included in that population are not reported in the registry record. In general, a Per Protocol analysis can focus on participants meeting specified study requirements, but its interpretation depends on those requirements and on how exclusions relate to outcomes. The record does not provide enough detail to assess that issue for this study.

How should repeated outcomes be understood?

The listed secondary outcomes include mean change in time-adjusted hemoglobin from baseline to the end of the Efficacy Evaluation Period, time spent in the target range, the percentage maintaining average hemoglobin within range, measurements above or below range, excursions, dose-adjustment patterns, and mean dose. These outcomes address different aspects of hemoglobin control and treatment management. A mean change, a proportion within a range, and time spent outside a range are not interchangeable summaries; each answers a different question.

Repeated measurements may also be correlated because values from the same participant tend to share participant-specific features. In general, statistical analyses of repeated data need to account for that dependence when estimating uncertainty. The registry record names the outcomes but does not report the corresponding analysis methods or numerical results. It is therefore not possible to determine from the record how dependence was handled for secondary analyses.

In general, over-dispersion occurs when observed variability in count or proportion data exceeds what a simple model assumes. If present, it can make standard errors and confidence intervals based on that simple model too optimistic. The registry’s stated exact method applies to the primary proportion’s confidence bounds; the record does not report a broader modeling plan from which to assess methods for other outcomes.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Mircera in Renal Anemia")
n      <- c(45)
events <- c(34)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Mircera in Renal Anemia  45  34  75.6  60.5  87.1  61.3  85.8  61.2  85.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including the primary hemoglobin-maintenance endpoint and secondary measures of hemoglobin change, time in or outside the target range, excursions, dose adjustments, and dose. Considering several outcomes creates a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase. In general, a statistical plan may address this through a prespecified hierarchy, adjustment, or descriptive interpretation. The registry record does not report a multiplicity strategy, a testing hierarchy, or an inferential plan for the secondary outcomes.

The record lists 0 analyses. This does not establish that no analyses were conducted; it means that analysis records are not present in the registry entry. Numerical results for the primary endpoint and the named secondary outcomes are not reported in the registry record. The record also does not describe interim analyses or provide a statistical analysis plan.

Missing-data handling is not reported in the registry record. The primary endpoint depends on hemoglobin measurements across a defined pretreatment period and the Efficacy Evaluation Period. Without the missing-data rules, it is not possible to assess how incomplete sampling affected inclusion in the endpoint analysis or the resulting estimate. The record does not state whether missing observations were imputed, whether participants with incomplete measurements were excluded, or what sensitivity analyses were used.

The registry defines the primary population as Per Protocol participants drawn from the Intent-to-Treat population who fulfill selected protocol criteria. The exact criteria, the number in each population, and the handling of participants who did not satisfy the criteria are not reported in the registry record. These details matter because the population used for analysis can affect both the estimate and its relevance. No assumptions about the sample-size justification or analysis population should be inferred from the enrollment figure alone.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: haemoglobin decreased (4.4%), gastrointestinal haemorrhage (4.4%), pneumonia (3.3%), acute myocardial infarction (2.2%), cardiac failure (2.2%).

The safety record lists 91 participants at risk for the serious adverse-event summary and 91 at risk for the other adverse-event summary. It reports 43 participants affected by serious adverse events and 62 affected by other adverse events. These are the recorded counts for the single study group; they are not comparisons between treatments. The registry does not report a death count.

The listed serious adverse-event terms and percentages are haemoglobin decreased, 4.4%; gastrointestinal haemorrhage, 4.4%; pneumonia, 3.3%; acute myocardial infarction, 2.2%; cardiac failure, 2.2%; and myocardial infarction, 2.2%. These percentages are term-specific entries. The registry record does not give enough information to determine from these entries whether a participant could contribute to more than one term, or how terms were grouped for summary purposes.

In general, adverse-event counts describe events reported under a study’s safety collection and coding procedures; they do not establish that the study treatment caused an event. Without a concurrent comparator, the listed counts cannot quantify a relative difference in risk. The registry record does not report event timing, exposure-adjusted rates, severity details beyond the serious-event classification, or a comparison that would support causal attribution. The safety entries should therefore be read as descriptive findings for this study group, not as a treatment-effect estimate.

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

The record identifies a specific maintenance question and a participant-level endpoint: whether average hemoglobin during the Efficacy Evaluation Period was both within the applicable target range and within ±1 g/dL of an individual pretreatment reference. It also describes the once-monthly intravenous dosing approach, dose adjustment toward country-specific ranges, and several additional outcomes related to hemoglobin control and dosing.

What the record does not provide is the observed primary endpoint percentage or its 95% confidence interval. Without those results, it is not possible to state how often participants met the endpoint or how precise that estimate was. The secondary outcome names likewise do not indicate their observed values; their numerical results are not reported in the registry record. The safety summaries provide selected counts and serious-event term percentages, but the record does not include a concurrent control group for comparison.

Even if the primary endpoint result were available, a single-arm study would describe the outcome in the treated group rather than provide a randomized comparison. The confidence interval around a proportion would quantify sampling uncertainty, not remove the limitations of the design. It would not account for differences from an untreated or differently treated group, because no such group is registered for this study.

The endpoint’s use of both an individual reference and a country-specific range is important to its interpretation. Meeting the endpoint means satisfying the combined study definition; it is not the same as reporting only a change from baseline or only whether a value fell within a target range. The record also specifies a Per Protocol analysis population, but does not report its exact size or selection criteria.

Accordingly, this registry record supports understanding of the study question, design, endpoint construction, and some safety observations. It does not support a numerical conclusion about the primary endpoint, the magnitude or precision of a treatment effect, or a comparison of safety with another treatment.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of a maintenance endpoint that combines a population-level clinical target with an individualized reference. The country-specific hemoglobin ranges define a common target within each country, while the individual reference condition asks whether a participant’s average remained close to their own pretreatment level. Those criteria capture related but distinct ideas, so the endpoint definition is central to interpreting any eventual percentage.

The study also illustrates the distinction between measuring an outcome and estimating a comparative treatment effect. Repeated hemoglobin measurements can support a period-based average and several secondary summaries, such as time in range or excursions outside it. Yet a single-group design provides no randomized contrast. Statistical precision around a treated-group proportion cannot substitute for a control group when the question concerns differences attributable to treatment.

Another important statistical point is the choice of analysis population. The registry specifies a Per Protocol population drawn from the Intent-to-Treat population, subject to selected criteria. That choice can shape the population represented by the endpoint estimate. Without the criteria, population counts, and missing-data approach, readers cannot fully assess who contributed to the result or how incomplete measurements were handled.

Finally, the registry distinguishes a clearly specified endpoint from a reported numerical finding. Here, the primary endpoint definition and exact confidence-interval method are recorded, but the endpoint estimate and interval are not reported in the registry record. This distinction matters: a protocol-like description explains what was intended to be measured, while an observed result is needed to assess the data and their precision. The record therefore teaches as much about the limits of registry interpretation as about endpoint construction.

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 main limitation for interpreting efficacy is that the primary endpoint result is not reported in the registry record. The percentage meeting the endpoint and its 95% confidence interval are unavailable, as are numerical results for the listed secondary outcomes. The endpoint definition alone cannot establish the observed level of hemoglobin maintenance or the precision of any estimate.

The study is single-arm and open-label, with no concurrent comparator. Any observed outcome would be descriptive of the participants receiving the study treatment and would not provide a randomized estimate of a difference from another approach. The lack of a comparator also limits interpretation of adverse-event counts as treatment-related differences.

The registry lists enrollment of 120, but reports 91 at risk for each of the two safety summaries. The primary Per Protocol population size and the number contributing to each outcome are not reported. The criteria for entering the Per Protocol population are only described as selected protocol criteria; their details are not reported in the registry record. Reasons for differences between enrollment, analysis populations, and safety denominators are therefore unclear.

The registry does not report missing-data handling, a detailed statistical analysis plan, a multiplicity strategy, or interim-analysis information. It also does not provide numerical secondary results or details that would permit assessment of repeated-measures methods. These omissions constrain evaluation of analysis choices and robustness. The listed safety terms provide percentages but not fuller event context, and the death count is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: MIRACLE Study: A Study of Once-Monthly Intravenous Mircera in Hemodialysis Participants With Chronic Renal Anemia — NCT00545571.
• Registry record last updated 2016-06-24; status last verified 2016-05.
• Results first posted 2016-05-18.
• 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

The MIRACLE Study is registered as a Phase 3, multicenter, open-label, single-arm study of once-monthly intravenous Mircera in hemodialysis participants with chronic renal anemia. The listed enrollment is 120. Participants previously receiving specified erythropoiesis-stimulating agents were assigned a starting dose based on prior treatment, with later doses adjusted toward country-specific hemoglobin ranges.

The primary endpoint is the percentage of Per Protocol participants whose average hemoglobin during Weeks 18 to 24 was within the applicable target range and within ±1 g/dL of their individual pretreatment reference. The registry specifies an exact Pearson-Clopper 95% confidence interval, but the primary endpoint estimate and interval are not reported in the registry record. Secondary outcomes are listed without numerical results.

The safety record reports 43 participants with serious adverse events and 62 with other adverse events, each among 91 at risk. It lists selected serious-event terms and percentages. No death count is reported. The single-group design permits descriptive interpretation but provides no randomized treatment comparison.