A Study of Once Monthly Subcutaneous Mircera in Dialysis Patients With Chronic Renal Anemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Once Monthly Subcutaneous Mircera in Dialysis Patients With Chronic Renal Anemia (NCT00882713), a na phase 3 study. The primary outcome is Percentage of Participants Maintaining Mean Hemoglobin Concentration Within +/- 1 g/dL of Their Reference Hb and Between 10.5 and 12.5 g/dL During Efficacy Evaluation Period.

2. Clinical Question

This is a maintenance question, not a randomized comparison of alternative treatments. The design can describe the proportion meeting the defined hemoglobin criterion among the analyzed participants, if that result is reported. Without a control group and a reported primary estimate, the record does not establish the magnitude of maintenance achieved or whether it differs from another approach.

3. Trial Design

The registry describes a completed phase 3, open-label, single-group study sponsored by Hoffmann-La Roche. It was designed to assess the efficacy, safety and tolerability of once-monthly C.E.R.A. administration for maintaining hemoglobin levels in dialysis patients with chronic renal anemia. Enrollment is recorded as 202, and the brief summary gives a target sample size of 200. These enrollment figures describe the record; they do not establish how many participants contributed to each outcome analysis.

The brief summary describes subcutaneous Mircera at a starting dose of 120, 200 or 360 micrograms every 4 weeks. The starting dose was to be calculated from the last weekly dose of epoetin or darbepoetin alfa previously administered, with subsequent doses adjusted to maintain hemoglobin within the target range. The same summary states that treatment duration was 56 weeks. However, the arm description says C.E.R.A. was administered intravenously every 4 weeks for 44 weeks. These descriptions do not agree on route or duration, and the arm description is incomplete. The record does not clarify the discrepancy.

The primary outcome was assessed during the Efficacy Evaluation Period, identified as Week 17 to Week 24. The reference hemoglobin was calculated from assessments at Weeks -4, -3, -2, -1 and 0. The primary endpoint population is described as per-protocol, including participants from the intention-to-treat population who fulfilled protocol inclusion and exclusion criteria; the record states that this population included 123 participants.

Other listed outcomes include mean change in hemoglobin, maintenance within 10.5-12.5 g/dL throughout the Efficacy Evaluation Period, time spent in that range, adverse events, dose adjustment, red blood cell transfusions, and hemoglobin and hematocrit over time. The registry record lists 19 outcome measures and no analyses. A comparator, masking, a detailed statistical plan, and further operational details are not reported 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.

Before assignment: Of 202 participants, 8 participants did not complete the stability verification period (SVP) of 4 weeks. Overall, 194 participants entered dose titration period (DTP) of 16 weeks.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The per-protocol (PP) population included all participants from the intention-to-treat (ITT) population, who fulfilled inclusion/exclusion criteria as per the study protocol. A total of 123 participants were included in the PP population.

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: Safety population included all participants who have been treated with at least one dose of the study drug and a safety follow-up, whether withdrawn prematurely or not.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Maintaining Mean Hemoglobin Concentration Within +/- 1 g/dL of Their Reference Hb and Between 10.5 and 12.5 g/dL During Efficacy Evaluation Period, measured over EEP (Week 17 to Week 24).

The primary endpoint is the percentage of participants whose mean hemoglobin met both parts of the criterion during the Efficacy Evaluation Period: it had to remain within ±1 g/dL of that participant’s reference hemoglobin and fall between 10.5 and 12.5 g/dL. The period is defined as Week 17 to Week 24. The reference hemoglobin was based on the mean of assessments at Weeks -4, -3, -2, -1 and 0. Because the endpoint requires both conditions, being within the reference-based limit alone would not meet the stated definition if the absolute range criterion were not also met, and vice versa.

This endpoint focuses on maintaining hemoglobin within a prespecified range over an evaluation period, rather than reporting a single measurement at a single visit. A percentage expresses how often participants in the analyzed group met the combined criterion. The registry record specifies a 95% confidence interval as the measure of uncertainty, but neither the observed percentage nor its interval is reported in the registry record.

As a general statistical rationale, a range-based maintenance endpoint can capture whether measurements stay near an individual reference while also meeting a clinically specified interval. It does not, by itself, describe the full pattern of hemoglobin measurements, the reasons for any departures from range, or the comparative effect of treatment. The registry lists related secondary outcomes, including mean change and time spent in the target range, but their results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary percentage represent?

The primary outcome is a binary participant-level classification: each participant either met the stated hemoglobin maintenance criterion during the Efficacy Evaluation Period or did not. The reported measure is the percentage meeting it. The criterion combines closeness to a reference hemoglobin with an absolute hemoglobin interval of 10.5-12.5 g/dL. The reference is the mean of assessments at Weeks -4, -3, -2, -1 and 0; the evaluation period is Week 17 to Week 24.

As a general explanation, converting a participant-level outcome into a percentage provides a summary of how common the defined outcome was in the analyzed population. It necessarily reduces detail: the percentage alone does not show how far outside the criterion other participants were, how their measurements changed across visits, or whether departures were brief or persistent. The registry lists related secondary outcomes that address some of these dimensions, but those results are not reported in the registry record.

What would a confidence interval add?

The registry specifies a 95% confidence interval for the primary percentage, but does not report the interval itself or the endpoint estimate. In general, a confidence interval expresses statistical uncertainty around an estimate, reflecting the variability that can arise when results are estimated from a sample rather than a full target population. A narrower interval indicates greater precision under the assumptions of the analysis; a wider interval indicates less precision. The interval does not correct for bias, resolve missing data, or make a single-group study comparative.

The observed percentage and its interval are needed together for an informative account of the endpoint. The percentage would describe the estimated share meeting the criterion in the analysis population; the interval would indicate how precisely that share was estimated. Since neither is reported in the registry record, the endpoint’s observed magnitude and precision cannot be assessed.

Why does the analysis population matter?

The primary endpoint is specified for a per-protocol population of 123 participants. The record defines that population as participants from the intention-to-treat population who fulfilled inclusion and exclusion criteria. This is a record-specific definition; the registry does not provide the full details of which protocol requirements were applied or explain why other enrolled participants were not included.

As a general statistical consideration, estimates can depend on who is included in the analysis. A per-protocol analysis may describe outcomes among participants meeting protocol criteria, but it may be less representative of all enrolled participants if exclusion is related to prognosis, treatment exposure, or outcome availability. The registry record does not provide enough information to assess whether such selection affected this endpoint. The enrollment figure of 202 and the stated primary population of 123 should therefore be understood as separate descriptions, not combined or substituted for one another.

What does the single-group design allow?

The study is recorded as single-group, with allocation not applicable and masking none. It can describe outcomes among participants receiving the recorded intervention. It cannot estimate a randomized difference against a concurrent control because no comparison group is listed. In general, observed changes over time in a single group may reflect treatment as well as other influences, and the design does not separate those possibilities by itself.

The open-label designation means masking is listed as none. The registry record does not explain whether or how outcome assessment was independently reviewed. Hemoglobin is a measured laboratory outcome, but this fact alone does not establish how collection, handling, or analysis was conducted. Those details are not reported in the registry record.

How should the planning illustration be understood?

The record describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions, not evidence that the trial used a two-arm design: the actual study is recorded as single-group. The record does not give the calculated planning values in the information available for this analysis. Such illustrations, when reported, are hypothetical estimates of participants per arm under their stated assumptions; they are not observed power and do not establish the adequacy of this study’s enrollment.

In general, a planning calculation depends on assumptions about the effect to detect, variability, significance level, and allocation. A calculation based on an observed effect is especially dependent on that estimate and should not be read as an independent confirmation of the effect. The registry record does not report a sample-size justification for the actual single-group study, so the rationale for the target sample size is not reported in the registry record.

What analysis details remain unknown?

The registry lists 19 outcome measures and no analyses. It specifies a 95% confidence interval for the primary endpoint but does not report the method used to calculate it. The analysis model, any adjustment for covariates, handling of repeated hemoglobin assessments, missing-data procedures, sensitivity analyses, and any interim analyses are not reported in the registry record. These details matter because different choices can affect which observations contribute to an estimate and how its uncertainty is quantified.

As a general matter, repeated measurements can be summarized in different ways, and participant-level range criteria depend on which visits and measurements are included. The endpoint description identifies the reference visits and evaluation period, but it does not describe all rules for incomplete or out-of-window measurements. Without the analysis details and the numerical result, no reanalysis or assessment of the primary estimate is possible from the registry record.

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("C.E.R.A.")
n      <- c(123)
events <- c(64)
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  C.E.R.A.  123  64  52.0  42.8  61.1  43.3  60.7  43.3  60.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, including the primary hemoglobin maintenance percentage and secondary outcomes covering hemoglobin change, time in range, adverse events, dose adjustment, transfusions, and hemoglobin and hematocrit over time. It does not report the results of analyses, and no analyses are listed in the record. A multiplicity strategy—such as a hierarchy among outcomes or an adjustment for testing multiple outcomes—is not reported in the registry record.

As a general statistical issue, examining several outcomes can increase the chance that at least one appears notable by chance, particularly when many tests are interpreted together. A prespecified analysis plan can clarify which outcome is primary and how other results are to be treated. Here, the primary endpoint is identified, but the record does not state whether secondary outcomes were formally tested, how their results would be interpreted, or whether any multiplicity adjustment was planned.

The primary population is described as per-protocol and includes 123 participants who fulfilled inclusion and exclusion criteria. The registry record does not give participant flow, reasons for exclusion from that population, or the number with endpoint data available. The method for handling missing data, including missing hemoglobin assessments or incomplete follow-up, is not reported in the registry record. It is also not stated whether any sensitivity analyses assessed the effect of missing observations.

These omissions limit the ability to judge how robust a reported estimate would be to choices about analysis populations and missing outcomes. They do not show that a particular method was or was not used; the details are simply not reported in the registry record. The primary percentage and confidence interval are also not reported, so the endpoint’s result cannot be evaluated alongside these uncertainties.

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: hypertension (2.1%), arteriovenous fistula thrombosis (1.5%), angina pectoris (0.5%), cardiac disorder (0.5%), coronary artery stenosis (0.5%).

The registry lists 194 participants at risk for serious adverse events and reports 19 participants affected. For the other adverse-event category, it also lists 194 at risk and 15 affected. These are descriptive counts from the C.E.R.A. group. Deaths are not reported in the registry record.

The listed serious adverse event terms include hypertension at 2.1%, arteriovenous fistula thrombosis at 1.5%, and angina pectoris, cardiac disorder, coronary artery stenosis, and hyperparathyroidism, each at 0.5%. These listed percentages describe the registry’s event-term entries; they do not establish that the intervention caused the events. The record does not provide a comparison group for assessing whether event occurrence differed from another treatment or from usual care.

As a general statistical point, safety counts depend on the recorded definitions, follow-up, and method for counting participants and events. The registry information does not provide further detail on event ascertainment or attribution. The counts should therefore be read as a description of reported events in this study, not as a comparative estimate of risk or a complete account of safety.

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

The primary endpoint is designed to summarize maintenance of hemoglobin within a specified range during the Efficacy Evaluation Period. It combines a limit relative to each participant’s reference hemoglobin with an absolute interval of 10.5-12.5 g/dL. The record identifies the analysis population and the confidence interval intended for the primary percentage, but the percentage and interval are not reported in the registry record. Consequently, the posted information does not reveal how many participants met the endpoint in percentage terms or how precisely that result was estimated.

The study’s single-group design means that outcomes can be described for participants receiving the intervention as recorded, but no randomized treatment contrast is available. Even if the primary result were reported, it would not by itself show what would have happened in a comparable group receiving another treatment or no study intervention. The record therefore does not support a causal comparison or a conclusion about relative effects.

The endpoint is also narrower than a complete account of treatment experience. It does not, on its own, describe each participant’s trajectory, the number or timing of dose changes, transfusions, or adverse events. The registry lists several secondary outcomes intended to address other aspects of hemoglobin control and safety, but their results are not reported in the registry record.

In general, statistical evidence depends both on the estimate and on its uncertainty, as well as on the design and analysis population. Here, the primary estimate, its confidence interval, missing-data approach, and detailed statistical plan are not reported in the registry record. The enrollment and per-protocol figures alone cannot substitute for those results or establish that the endpoint was met.

The intervention description also contains unresolved differences: the brief summary describes subcutaneous administration and a 56-week treatment duration, whereas the arm description specifies intravenous administration for 44 weeks. The record does not explain these differences. This uncertainty should be kept in mind when interpreting what treatment exposure the results would represent.

14. Why This Trial Matters Statistically

This trial raises several important statistical interpretation issues for a maintenance endpoint. The primary outcome is based on repeated hemoglobin assessments over a defined evaluation period and requires participants to meet both a reference-based criterion and an absolute range. That definition is more informative than a single hemoglobin reading, but it also makes the analysis dependent on how measurements across visits are summarized and how incomplete assessments are handled. The registry gives the period and reference assessments, but not the full analysis rules.

The single-group design is central to interpretation. It can describe the observed proportion meeting the endpoint in the study population, but it cannot provide a randomized comparison. This distinction prevents a descriptive maintenance estimate from being treated as an estimate of a comparative treatment effect. The record’s open-label status and lack of a comparator also underscore why outcome definitions and analytic procedures matter.

The endpoint population is described as per-protocol and includes 123 participants, while enrollment is recorded as 202. Understanding how those populations relate would require participant-flow information and reasons for exclusion, which are not reported in the registry record. Missing-data methods are also not reported, even though the endpoint depends on hemoglobin assessments across an evaluation period.

Finally, the registry record does not report the primary percentage or its 95% confidence interval. Without those values, the result’s magnitude and precision cannot be judged. The record also gives conflicting intervention route and duration descriptions. Together, these limitations illustrate why a clearly defined endpoint is only part of statistical interpretation: the result, analysis population, missing-data approach, and study design must all be considered.

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 primary limitation for interpreting the efficacy endpoint is that its numerical result is not reported in the registry record. Although the endpoint definition, per-protocol population, and intended 95% confidence interval are stated, the primary percentage and interval are absent. The listed secondary outcomes also have no reported analyses in the record, so they cannot fill this gap.

The study has no comparison group. It is recorded as single-group, open-label, and with allocation not applicable. This supports description of outcomes within the study group but does not permit a randomized comparison. The record does not report a detailed statistical analysis plan, method for calculating the confidence interval, covariate adjustment, or approach to repeated measurements.

The participant populations are not fully reconciled. Enrollment is recorded as 202, while the primary per-protocol population is described as 123. The registry record does not report participant flow, reasons for exclusion, endpoint-data availability, or methods for handling missing measurements. Those omissions make it difficult to judge the potential impact of selection and missingness on the primary estimate.

There are also inconsistencies in the intervention description. The brief summary says subcutaneous administration and a 56-week treatment duration; the arm description says intravenous administration every 4 weeks for 44 weeks. The arm description is incomplete, and the record does not resolve the route or duration discrepancy. The registry also does not report a sample-size justification for this single-group design. These are limitations of the information recorded, not evidence about what occurred beyond the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Once Monthly Subcutaneous Mircera in Dialysis Patients With Chronic Renal Anemia — NCT00882713.
• Registry record last updated 2016-10-07; status last verified 2016-08.
• Results first posted 2016-10-07.
• 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

NCT00882713 is recorded as a completed phase 3, open-label, single-group study sponsored by Hoffmann-La Roche. It enrolled 202 dialysis patients with chronic renal anemia and assessed once-monthly C.E.R.A. (Mircera) for hemoglobin maintenance. The primary endpoint was the percentage meeting a combined hemoglobin criterion during Week 17 to Week 24, analyzed in a per-protocol population described as 123 participants.

The registry specifies a 95% confidence interval for the primary percentage but does not report the estimate or interval. It lists 19 outcome measures and no analyses. There is no comparator, and the record does not report a detailed statistical plan or missing-data methods. Descriptions of route and treatment duration differ between the brief summary and arm description. Safety counts and event terms are recorded, but they are descriptive and do not establish causation.