A Study of Intravenous Mircera in Dialysis Patients With Chronic Renal Disease and Anemia.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Intravenous Mircera in Dialysis Patients With Chronic Renal Disease and Anemia. (NCT00576303), a na phase 3 study. The primary outcome is Percentage of Participants Maintaining Average Hemoglobin Concentration Within +\- 1 Gram/Deciliter of Their Reference Hb and Between 10.5 and 12.5 Gram/Deciliter During EEP.

2. Clinical Question

The study focused on maintenance rather than describing a comparison between alternative regimens. Participants entered while receiving epoetin alfa or beta, and the intervention was a monthly intravenous regimen whose starting dose depended on their preceding epoetin dose. The primary endpoint combined two conditions: proximity to each participant's reference hemoglobin and location within the stated target range. Both conditions matter to the endpoint as defined; it is not simply the average hemoglobin value for the group.

The registry describes the study as Phase 3, open label, multicenter and single group. These design features frame what the question can establish. The endpoint can describe the proportion meeting the specified hemoglobin criteria in the analysis population during the stated period, but without a concurrent comparator it cannot by itself isolate a treatment effect relative to another regimen. The outcome estimate is not reported in the registry record, so the primary question cannot be answered from the posted results summarized in the record.

3. Trial Design

The study is listed as a completed Phase 3, open-label, multicenter, single-group trial with enrollment of 200. Allocation is listed as not applicable, and masking as none. Participants were dialysis patients with chronic renal disease and anemia who were receiving epoetin alfa or beta. The trial evaluated monthly intravenous RO0503821, identified in the registry as C.E.R.A. and Mircera.

The intervention description specifies a starting dose of 120, 200 or 360 micrograms every four weeks, selected according to the epoetin dose in the week before study start. The dose bands described in the registry are less than 8000 IU/week, 8000-16000 IU/week and greater than 16000 IU/week, respectively. The brief study description gives an anticipated treatment duration of 3-12 months. That is an anticipated duration, not a reported duration for every participant.

The registry dates the study start to 2008-04 and primary completion to 2010-06. These are registry dates, not a description of each participant's treatment or follow-up schedule. The primary evaluation period is identified as EEP, Week 16 to Week 24. Other listed outcomes include change in hemoglobin from baseline, maintenance within the 10.5-12.5 g/dL range, days within that range, dose adjustment, and red blood cell transfusion. Their presence in the outcome list does not establish what their results were.

Because the trial had one group and no allocation to concurrent arms, changes observed during treatment have no randomized control group for comparison. An open-label design also means masking was absent. The registry record does not report additional design details such as the precise visit schedule, handling of treatment discontinuation, or a statistical analysis plan. Those details should not be inferred from the brief description.

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 the 241 screened participants, 200 participants received the study drug and 41 participants were early withdrawals during the stability verification period (SVP)

Dose Titration Period

Reasons for not completing this period:

Efficacy Evaluation Period

Reasons for not completing this period:

Long Term Safety Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol (PP) population included participants except who didn't meet inclusion criterion relative to consent, stable baseline Hb values, iron status, epoetin maintenance, and who met exclusion criterion of hemoglobinopathies/hemolysis, bleeding, \>3 recorded Hb, missing drug administration, other ESA, blood transfusion during the DTP or EEP.

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 Percentage of Participants Maintaining Average Hemoglobin Concentration Within +\- 1 Gram/Deciliter of Their Reference Hb and Between 10.5 and 12.5 Gram/Deciliter During EEP, measured over EEP (Week 16 to Week 24).

The primary endpoint is the percentage of participants whose average hemoglobin concentration during the evaluation period met both stated conditions: it was within 1 g/dL of that participant's reference hemoglobin and between 10.5 and 12.5 g/dL. The evaluation period was Week 16 to Week 24. The registry's description says mean hemoglobin values during the evaluation period were calculated and compared with the participant's mean baseline hemoglobin value. The endpoint is therefore a participant-level maintenance measure summarized as a percentage, rather than a comparison of group mean hemoglobin alone.

This kind of endpoint is used to express how many participants met a prespecified clinical range over a defined period. It can be easier to interpret as a maintenance target than a single average value, because a group mean can conceal variation among individuals. Conversely, converting measurements into a criterion met or not met discards some information about how far each person's values were from the limits. That is a general property of threshold-based outcomes, not a result specific to this study.

The endpoint is stated to have a 95% confidence interval, but neither the percentage nor its interval is reported in the registry record. The record identifies the analysis population as per protocol and lists eligibility and treatment or measurement conditions used to define it. The population description is incomplete, so the exact set of participants contributing to this endpoint cannot be fully reconstructed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical details in the registry record are limited. It identifies a percentage endpoint, a 95% confidence interval, an evaluation period and a per-protocol analysis population. It does not report the numerical endpoint estimate or the interval limits. The concepts below explain what those methods ordinarily mean; they are general explanations, not additional details about the study's unreported analysis procedures.

What does a percentage endpoint represent?

For a binary participant-level outcome, each participant is classified according to whether the stated criteria were met. The percentage then describes the share of the analysis population classified as meeting those criteria. Here, the criteria are a mean hemoglobin within 1 g/dL of the reference hemoglobin and within the range of 10.5 to 12.5 g/dL during EEP, Week 16 to Week 24. The registry labels the primary outcome as a percentage of participants, but does not post the percentage or the number of participants contributing to its calculation.

Reducing a continuous measurement to a binary outcome can make the result straightforward to interpret against a target. It also removes information: two participants on opposite sides of the threshold may be classified differently even if their measurements are close, while values at different distances from the threshold may receive the same classification. This is a general consequence of threshold-based endpoints. The endpoint's two conditions should be considered together; meeting one condition alone does not meet the definition described in the registry.

What does a confidence interval add?

A confidence interval is an estimate of statistical uncertainty around an outcome estimate. In general, it is affected by the amount of information available and by the method used to calculate it. A confidence interval is not a guarantee that the true value lies within its limits, nor is it a substitute for understanding the design and analysis population. The registry states that the primary percentage is accompanied by a 95% confidence interval, but does not report the interval's endpoints. It is therefore not possible to assess its width or use it to judge how precisely the percentage was estimated.

The interval also cannot address design limitations such as the lack of a concurrent randomized comparator. Statistical precision and causal interpretation are different matters: an estimate can be precise yet remain descriptive of a single group. Conversely, a comparison design does not remove uncertainty from an estimate. In this trial, the single-group design is a central constraint on comparative inference, irrespective of what the unreported interval might have shown.

Why does the analysis population matter?

The primary endpoint is associated with a per-protocol population. In general, a per-protocol analysis focuses on participants meeting specified eligibility and study-conduct requirements. The registry description refers to consent, stable baseline hemoglobin, iron status and epoetin maintenance, and exclusions involving hemoglobinopathies or hemolysis, bleeding, more than 3 recorded hemoglobin measurements, or missing drug administration. The description ends incompletely, so further criteria are not reported in the registry record.

Population definitions affect the denominator and the interpretation of a percentage. If participants are excluded after enrollment, the analyzed group may differ from the full enrolled group. That can affect how representative an estimate is of everyone who started the study. The registry record does not report the size of the per-protocol population, the reasons for exclusions by count, or a complementary analysis of all enrolled participants. It is not possible to determine from the record how those issues affected the endpoint estimate.

How do study design and dosing shape interpretation?

There was one treatment group, no allocation to a control group and no masking. A single-group study can describe outcomes under the observed regimen, but a change from baseline is not equivalent to a randomized treatment contrast. Without a concurrent control group, observed changes may also reflect time, background care, participant selection or measurement variation. These are general considerations for interpreting an uncontrolled study and should not be mistaken for explanations demonstrated in this trial.

The starting dose varied according to the preceding epoetin alfa or beta dose. That is part of the intervention strategy described in the registry; it does not imply that the three starting-dose groups were randomized or intended as a comparison. The registry does not report comparative estimates by starting dose, adjustment rules beyond the listed outcomes, or analyses examining dose subgroups.

What about over-dispersion and other models?

For count outcomes, over-dispersion means that variability exceeds what a chosen probability model expects. In general, accounting for over-dispersion can affect estimated uncertainty. The primary endpoint in this record is a participant percentage, and no model or over-dispersion adjustment is reported. It would be inappropriate to claim that a particular model, adjustment or diagnostic procedure was used. The record also does not report a model for the primary endpoint, covariate adjustment, or any alternative analysis.

For a binary percentage, general methods may estimate a proportion and its uncertainty using different assumptions. The registry's confidence-interval label alone does not identify which method was used. No method for calculating the interval is reported in the registry record. Likewise, no details are given about handling repeated hemoglobin measurements beyond the endpoint description that refers to mean values during the evaluation period.

Are there planning calculations?

Any sample-size illustration associated with the posted material is a planning exercise based on an observed effect, not the trial's original design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Those assumptions do not describe the actual single-group design. The registry record does not report the trial's own sample-size justification. Planning illustrations are not observed power, and they do not show the probability that this completed study detected an effect.

The record contains no analysis records for the listed outcomes. In particular, it does not report a fitted model, a test statistic, a p-value, or a numerical primary endpoint estimate. The absence of these details means statistical methods beyond the endpoint and interval labels cannot be reconstructed. General statistical principles can clarify what the stated measures mean, but cannot replace outcome estimates or an analysis plan that is not reported in 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("RO0503821 (1x/4 Weeks)")
n      <- c(145)
events <- c(79)
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  RO0503821 (1x/4 Weeks)  145  79  54.5  46.0  62.8  46.4  62.4  46.4  62.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary hemoglobin-maintenance percentage and secondary measures of hemoglobin change, time in the target range, dose adjustment and transfusion. Listing several outcomes raises a general question about multiplicity: when multiple hypotheses are tested, the chance of at least one apparently unusual result can increase if no adjustment or interpretation strategy is used. Whether any adjustment is needed depends on which outcomes were formally tested and how confirmatory claims were planned.

The registry record does not report a multiplicity strategy, a hierarchy of secondary outcomes, or whether any adjustment was applied. It also does not report interim analyses or a statistical analysis plan. The absence of those details in the registry record should not be taken as proof that none existed; their status is not reported in the registry record.

Missing-data handling is also not reported. The endpoint population description mentions missing drug administration among exclusion conditions and refers to hemoglobin measurement requirements, but the record does not describe a general missing-data method, imputation, sensitivity analysis or rules for measurements unavailable during the evaluation period. Nor does it report how many observations or participants had missing data.

The primary analysis population is described as per protocol, but its complete definition and size are not reported. The registry record does not provide an intention-to-treat analysis or a comparison of analysis populations. These gaps matter because exclusions and missing measurements can change the population represented by a percentage estimate. Without counts and handling rules, the potential influence of missing data or exclusions cannot be assessed.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: arteriovenous fistula thrombosis (7.0%), peritonitis (2.0%), cardiac failure acute (1.5%), cholecystitis acute (1.5%), anaemia (1.0%).

The registry safety summary lists 200 participants at risk for serious adverse events and 45 participants affected. For other adverse events, it lists 200 at risk and 78 affected. These figures count participants with at least one event in each category, rather than the total number of event episodes. A participant may experience more than one event, and the affected-participant counts do not show the number or timing of all episodes.

The listed serious adverse-event terms and percentages are arteriovenous fistula thrombosis, 7.0%; peritonitis, 2.0%; cardiac failure acute, 1.5%; cholecystitis acute, 1.5%; anaemia, 1.0%; and duodenal ulcer, 1.0%. These are the terms and percentages reported in the registry record. The record does not provide additional context in this summary about event timing, individual participants, or whether events were considered related to the intervention. The death count is not reported in the registry record.

These safety counts come from a single-group study. Without a concurrent comparator, they cannot by themselves establish how event occurrence compares with another treatment or with no study intervention. They should be read as descriptive counts in the registry's safety summary, not as proof of causation or as a treatment comparison.

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

The study's central question concerns maintenance of hemoglobin within a defined range during Week 16 to Week 24 among dialysis patients with chronic renal anemia receiving monthly intravenous C.E.R.A. The registry record reports the endpoint definition, study design and intended analysis population. It does not report the percentage meeting the primary criteria, the 95% confidence interval, or the final per-protocol denominator. The primary outcome result is therefore not reported in the registry record.

The design was single group, open label and without allocation to a concurrent control. If an outcome estimate were available, it would describe the observed participants under the study regimen, subject to the population definition and missing-data handling. It could not, on its own, show what would have happened to the same participants under a different regimen. The study record does not support a randomized comparative conclusion.

The endpoint itself is a threshold-based summary. It tells whether participants met both the reference-relative and target-range conditions, rather than detailing every hemoglobin value or the path taken over time. The registry lists other outcomes that could add context, including change from baseline, days within the target range, dose adjustment and transfusion, but their numerical results are not reported in the registry record. Their listed names alone cannot establish the direction or size of any finding.

The safety summary reports affected participants and selected serious-event terms. Those descriptive data do not establish that the intervention caused the events, and without a comparator they do not provide a relative safety estimate. The death count is not reported in the registry record. Efficacy and safety interpretations must therefore remain separate, and neither can fill the missing primary endpoint estimate.

In general, interpreting a clinical trial requires the outcome estimate, its uncertainty, the population analyzed, and the design context. For this record, the design and endpoint definition are available, but key result and analysis details are absent. The appropriate statistical conclusion is limited: the study was designed to assess maintenance of hemoglobin under a single-group monthly regimen, while the registry record does not report the numerical primary endpoint result needed to quantify that outcome.

14. Why This Trial Matters Statistically

This trial illustrates why the design label matters as much as the outcome definition. A single-group study can describe what was observed among participants receiving a regimen, but it does not create a concurrent randomized contrast. When the scientific question is comparative, a descriptive percentage cannot by itself distinguish an intervention-related change from changes that might occur over time or alongside other care. That is a general issue in interpretation, not a claim about what happened to participants in this study.

The endpoint also shows how a clinically recognizable target can become a statistical definition. It combines a participant-specific reference hemoglobin condition with an absolute range of 10.5 to 12.5 g/dL, then summarizes the proportion meeting both during EEP, Week 16 to Week 24. Such an endpoint is interpretable as a maintenance criterion, while still depending on the chosen thresholds, averaging window and analysis population. The registry record does not provide the estimate needed to see how many participants met it.

The distinction between enrolled and analyzed participants is important. Enrollment was 200, while the primary endpoint is assigned to a per-protocol population whose description includes exclusions. The exact population size and complete criteria are not reported. A percentage without its denominator and population definition would be difficult to evaluate for representativeness, and the registry record does not provide those endpoint details.

Finally, the record separates the existence of a planned outcome from evidence about its result. It identifies several secondary outcomes and reports some safety counts, but the primary outcome estimate and its interval are absent. This is a useful reminder that a trial's statistical question, its design, its analysis population and its posted results are distinct parts of the evidence. Missing numerical results limit interpretation regardless of the amount of descriptive design information available.

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.

A central limitation for interpretation is the absence of the numerical primary endpoint result in the registry record. Although the endpoint is defined and a 95% confidence interval is specified, neither the percentage nor the interval limits are reported. The endpoint analysis denominator is also not given. Consequently, the magnitude and precision of the primary outcome cannot be assessed from the record.

The single-group design lacks a concurrent control and is listed as open label with no masking. It can support descriptive reporting, but it cannot provide a randomized comparison. The registry does not report a comparative analysis or an adjustment that would create one. Any causal interpretation would therefore go beyond what the design described in the record can establish.

The per-protocol population is described through a series of eligibility and study-conduct criteria, but that description is incomplete. The number of participants excluded and the reasons by count are not reported. The registry record also does not report the missing-data strategy, imputation, sensitivity analyses, or a full analysis plan. These omissions make it difficult to assess how exclusions or missing measurements may have affected the endpoint.

The registry lists secondary outcomes without posting their numerical results in the record. It also does not report multiplicity procedures, interim analyses, or the trial's sample-size justification. The stated expected treatment duration of 3-12 months does not establish the actual duration for each participant, and individual follow-up details are not reported. The death count is not reported, and the safety summary does not establish event relatedness. These are limitations of the information available in the registry record, not evidence that a particular event, analysis or procedure did or did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Intravenous Mircera in Dialysis Patients With Chronic Renal Disease and Anemia. — NCT00576303.
• Registry record last updated 2016-05-26; status last verified 2016-04.
• Results first posted 2016-05-26.
• 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

NCT00576303 is a completed Phase 3, open-label, multicenter, single-group study sponsored by Hoffmann-La Roche. Enrollment was 200. It evaluated once-monthly intravenous RO0503821, known as C.E.R.A. or Mircera, in dialysis patients with chronic renal disease and anemia who had been receiving epoetin alfa or beta. Starting doses were 120, 200 or 360 micrograms every four weeks, based on the preceding epoetin dose.

The primary endpoint was the percentage maintaining average hemoglobin within 1 g/dL of reference hemoglobin and within 10.5 to 12.5 g/dL during Week 16 to Week 24. The registry record does not report the primary endpoint estimate, its confidence interval limits, or the per-protocol analysis denominator. It reports 45 participants with serious adverse events and 78 with other adverse events, among 200 at risk in each category. The death count is not reported in the registry record.