A Study of Monthly Subcutaneous Mircera for the Treatment of Chronic Renal Anemia in Predialysis Patients Not Treated With ESA.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Monthly Subcutaneous Mircera for the Treatment of Chronic Renal Anemia in Predialysis Patients Not Treated With ESA. (NCT00661388), a na phase 3 study. The primary outcome is Mean Change in Hb Concentration Between Baseline and the Efficacy Evaluation Period.

2. Clinical Question

The study addressed hemoglobin correction and maintenance in a specific clinical setting: renal anemia before dialysis among patients not currently receiving ESA. Its primary measure focused on the difference between baseline hemoglobin and a time-adjusted average during the efficacy evaluation period. A positive change was defined in the registry as improvement, but no observed mean change, standard deviation, confidence interval, or test result is posted for this endpoint.

This is a question about the pattern of hemoglobin under treatment in one group, not a direct test of whether C.E.R.A. performs better than an alternative. Without a concurrent comparison group, the study cannot separate changes associated with treatment from changes that might have occurred over time for other reasons. The clinical question is therefore descriptive: what change was recorded during the specified period among the analyzed participants? The registry record does not report the result needed to answer even that question numerically.

3. Trial Design

This was a Phase 3, single-group, open-label study sponsored by Hoffmann-La Roche. The registry lists the study as completed, with a start date of 2008-08 and primary completion in 2010-12. Enrollment was 75. The study title and summary describe participants with chronic renal anemia before dialysis who were not currently treated with ESA.

Participants assigned to the sole treatment group were to receive C.E.R.A. by subcutaneous injection every 4 weeks for 44 weeks. The arm description gives an initial dose of 1.2 micrograms/kilogram and says subsequent doses would be adjusted to maintain hemoglobin within 10.0 and 12.0 grams/deciliter. The brief summary describes the anticipated time on study treatment as 3-12 months. These are planned treatment details, not a report of the actual dosing received by each participant.

There was no random allocation, masking, or separate control arm: the record identifies the model as single group, masking as none, and allocation as not applicable. Thus, the study could describe hemoglobin and safety outcomes over time in the treated group, but it was not structured to make a randomized treatment comparison. Open-label conduct also means participants and investigators were not masked to treatment.

The brief summary states a target sample size of 100-500 individuals, while the registry enrollment is 75. The reason for this difference and the statistical justification for the target are not reported in the registry record. Nor does the record report a detailed protocol for interim analyses or a full statistical analysis plan. Completion status indicates that the study is listed as completed; it does not by itself establish that every planned analysis or outcome result is available in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol (PP) population included all participants who received at least one dose of C.E.R.A. and had at least one follow-up. Participants with less than three recorded Hb values during EEP; missing administration of C.E.R.A. during weeks 28-36; having inadequate iron status, were excluded.

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 received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in Hb Concentration Between Baseline and the Efficacy Evaluation Period, measured over From Baseline (Week 0) to EEP (Week 29 to Week 36).

The primary endpoint was mean change in hemoglobin concentration between baseline and the efficacy evaluation period (EEP), specified as Week 29 to Week 36. Hemoglobin is a continuous measurement, so the endpoint summarizes the average change in that measurement rather than counting participants who did or did not cross a threshold. The registry defines the change as the time-adjusted average hemoglobin during the EEP minus hemoglobin at baseline (Week 0). Under that definition, a positive change indicates improvement.

Using an average across the EEP can describe the level maintained across a period rather than relying on one measurement at a single visit. The time adjustment is part of the endpoint definition; the registry record does not give further detail about the calculation procedure. The endpoint is relevant to the study’s stated objective of assessing hemoglobin correction and maintenance, while the secondary outcomes include measures relating to time in the target range, dose adjustment, transfusion, adverse events, and hematocrit.

The endpoint definition does not establish what change occurred. The registry record does not report a primary mean change, its standard deviation, or an interval estimate. Consequently, the size and precision of the hemoglobin change cannot be assessed from the posted results. A mean change also does not show how individual participants’ values varied around the average; that requires participant-level or distributional summaries that are not reported for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure: hemoglobin concentration, expressed in g/dL. A mean summarizes the central level of a set of measurements. The standard deviation describes how dispersed individual observations are around that mean; it is not the same as the uncertainty in the estimated mean. Although the endpoint lists standard deviation as its dispersion measure, no numerical mean or standard deviation is reported in the registry record.

What does the change from baseline represent?

The registry defines change as the time-adjusted average hemoglobin during the EEP minus the baseline hemoglobin at Week 0. This makes the sign interpretable: a positive value is a higher average hemoglobin during the EEP than at baseline, according to the stated definition. The reported time window for the EEP is Week 29 to Week 36. “Time-adjusted average” is part of the registry’s description, but the exact calculation method and handling of measurements within that period are not reported in the registry record. No additional computational details should be inferred from the label alone.

A confidence interval, if reported, would express the uncertainty around an estimated mean change under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The registry record does not report a confidence interval for the primary endpoint, so the precision of any estimated change cannot be assessed. A p value, if available, would address a specified statistical hypothesis under a model; it would not by itself convey the size or clinical importance of a change. No primary endpoint p value is reported.

Why does the single-group design matter?

In a single-group study, the principal comparison is within participants over time, rather than between groups treated differently. That can document a before-and-after pattern, but it does not provide the counterfactual needed to identify what would have happened to comparable participants without the study treatment. A change may reflect treatment, the natural course of the condition, other care, measurement variability, or a combination. Randomized allocation to a concurrent comparator can reduce some sources of systematic difference between groups; this study did not have such a comparator.

Open-label status means treatment assignment was not masked. For a laboratory measure such as hemoglobin, the measurement itself may be more objective than a subjective rating, but the registry record does not report whether laboratory assessments were centrally processed or otherwise protected from potential bias. Open-label conduct can also affect treatment adjustment and co-interventions. The available record does not allow the extent of any such influence to be assessed.

What does the analysis population mean?

The primary endpoint population is described as the per-protocol (PP) population. It included participants who received at least one dose of C.E.R.A. and had at least one follow-up. Participants were excluded if they had fewer than three recorded hemoglobin values during the EEP, missed C.E.R.A. administration during weeks 28-36, or had inadequate iron status. These criteria define a selected analysis population based on treatment exposure, follow-up, measurement availability, and iron status. The registry does not report how many participants met the criteria or how many were excluded for each reason.

Per-protocol analyses can describe outcomes among participants who meet specified study requirements, but exclusion after enrollment can affect how representative the analyzed group is of everyone who entered the study. For example, participants with incomplete endpoint measurements may differ from those with measurements available. This general concern does not establish that bias occurred; it means the counts, reasons for exclusion, and handling of missing data are important for assessing the estimate. Those details and the numerical primary result are not reported in the registry record.

How should the secondary outcomes be understood?

The listed secondary outcomes include mean time to response, the percentage remaining within the stated hemoglobin target range throughout the EEP, time spent in that range, dose adjustment, red blood cell transfusions, adverse events and serious adverse events, and changes in hemoglobin and hematocrit over time. These outcomes address different aspects of response, treatment management, and safety. A measure of time to an event differs from a continuous mean change, and a proportion within a range differs from both. Each requires its own definition of eligible participants, observation window, and approach to incomplete follow-up.

The record lists 18 outcome measures and 0 analyses. Numerical results for the primary endpoint and the listed secondary outcomes are not reported in the registry record. The record does not describe a multiplicity adjustment or identify which outcomes were treated as confirmatory versus exploratory. When several outcomes are evaluated, the chance of at least one apparently unusual result can increase if each is tested separately without accounting for the family of tests. This is a general statistical issue, not evidence about what analyses were performed in this study.

What can safety counts and planning calculations say?

The adverse-event summaries count participants recorded as affected within the treatment group. They do not compare event rates against a control group, and they do not establish causation. The listed percentages for serious-event terms are descriptive summaries in the registry record. The methods used to attribute events, determine severity, or handle repeated events are not described in the information available.

Sample-size planning illustrations, when based on an observed effect, are hypothetical calculations that show how a design might be sized under stated assumptions. They are not observed power and do not supply evidence about a treatment effect. The registry record does not report its sample-size justification, and it does not report a primary endpoint estimate from which to assess an observed effect. Any planning illustration should therefore be kept separate from the study’s observed results.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("C.E.R.A")
n   <- c(41)
m   <- c(1.99)
sp  <- c(0.74)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  C.E.R.A  41  1.990  0.740  1.756  2.224

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, spanning hemoglobin response, time in a target range, dose adjustment, transfusion, adverse events, and hematocrit. Evaluating several outcomes can create a multiplicity issue: if many separate statistical tests are considered, the chance of at least one result appearing notable by chance may be higher than for a single prespecified test. This is a general statistical concern. The registry record does not report whether the study adjusted for multiplicity, which outcomes were designated as confirmatory, or how the outcome hierarchy was specified.

The record lists 0 analyses and does not post the numerical primary endpoint result. The analysis methods, any interim analyses, and the full statistical analysis plan are not reported in the registry record. No claim about which procedures were actually used can be made from the outcome list alone.

For the primary endpoint, the PP population excluded participants with fewer than three hemoglobin values in the EEP, missed C.E.R.A. administration during weeks 28-36, or inadequate iron status. This makes missing endpoint measurements and post-enrollment exclusions relevant to interpretation. The record does not report the number of participants with missing measurements, the reasons for missingness, the number excluded under each rule, or any imputation or sensitivity analysis. These details are needed to understand whether the analyzed participants could differ systematically from those not included in the PP analysis.

The record also does not report a separate intention-to-treat analysis or a comparison of results across analysis populations. The absence of such information in the registry record does not establish that no additional analysis was performed elsewhere; it means those details are unavailable in the posted record.

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: metabolic acidosis (8.0%), angina pectoris (2.7%), blood creatine increased (2.7%), thrombocytosis (1.3%), coronary artery disease (1.3%).

The registry safety summary lists 75 participants at risk for serious adverse events, with 24 affected, and 75 at risk for other adverse events, with 38 affected. These are counts within the single C.E.R.A. group. They should be read as descriptive participant counts, not as comparative treatment effects. The study had no separate control group, so the record cannot show whether these counts were higher or lower than they would have been under another treatment or without treatment.

The listed serious-event terms include metabolic acidosis (8.0%), angina pectoris (2.7%), blood creatine increased (2.7%), thrombocytosis (1.3%), coronary artery disease (1.3%), and atrial septal defect (1.3%). These percentages are reported for the named terms. A term’s appearance in the list does not mean that treatment caused the event. Nor do the listed terms necessarily represent every event observed; the record identifies them as the top serious terms.

Event counts and affected-participant counts are not interchangeable when a participant can experience more than one event. The registry summary does not provide further detail about repeat events, event timing, or attribution. The number of deaths is not reported in the registry record. These limitations prevent a complete comparative safety assessment from the posted summaries.

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

The study was designed to assess hemoglobin correction and maintenance during monthly subcutaneous C.E.R.A. treatment in predialysis patients with renal anemia who were not currently treated with ESA. It specifies a primary measure based on mean change from baseline to the EEP, defined as Week 29 to Week 36. The registry record also describes dosing, a target hemoglobin range, secondary outcomes, and the PP population criteria.

However, the registry record does not report the primary endpoint’s numerical result. It therefore does not establish the average hemoglobin change, its direction, its magnitude, or its precision. The definition that a positive change indicates improvement should not be mistaken for a finding that the mean change was positive. Missing numerical results are not evidence of no effect; they leave the result undetermined from the posted record.

Even if a within-group change were available, this design would not establish that C.E.R.A. caused it. Without a concurrent control group, changes over time cannot be separated from other influences with the same confidence as in a randomized comparison. The open-label, single-group design is useful for describing experience in the enrolled group, but it does not support a direct estimate of comparative benefit or harm.

The safety counts and listed serious-event terms describe events recorded in the C.E.R.A. group. They do not show how those counts compare with another treatment, and they do not establish that treatment caused an event. The record does not report the number of deaths or the statistical methods used for safety analyses.

In short, the posted record documents a study question and design, along with selected safety summaries, but leaves the primary efficacy result unreported. It does not support a conclusion about the size or certainty of hemoglobin change, nor a treatment comparison or causal claim. The difference between a study being completed and its numerical results being available in the registry is important for interpretation.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between defining an outcome and reporting its result. The registry gives a detailed primary endpoint: mean change in hemoglobin from baseline to a specified efficacy evaluation period, with a stated sign convention. But without the mean, its dispersion, and an uncertainty interval, readers cannot evaluate the size, direction, or precision of the result. A clear endpoint definition is necessary for interpretation, but it cannot substitute for an estimate.

The single-group design also highlights why a before-and-after change is not the same as a treatment effect. A longitudinal pattern can be informative about what happened in an enrolled group, yet it does not show what would have happened to similar participants under a comparator. This distinction is central when interpreting studies that lack randomization and a control arm.

The population rules matter as well. The primary analysis was defined as per protocol and excluded participants on the basis of treatment exposure, follow-up, available hemoglobin measurements, and iron status. Without counts for those exclusions or a comparison across analysis populations, readers cannot assess how closely the analyzed group represents all enrolled participants.

Finally, the record combines a relatively broad set of outcome measures with no posted analysis entries. That makes transparency about prespecified hypotheses, multiplicity, missing-data handling, and the analysis plan especially relevant. The study is statistically instructive not because the registry resolves those questions, but because it shows how design, population selection, result availability, and uncertainty all shape what can be concluded from a clinical trial record.

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 most consequential limitation for interpreting this trial record is the absence of a numerical primary endpoint result. The endpoint is described, but the mean change, standard deviation, confidence interval, and p value are not reported in the registry record. The primary outcome’s magnitude and precision therefore cannot be evaluated.

The single-arm, open-label design provides no concurrent comparator. Any observed change during follow-up would be a within-group pattern and could not by itself isolate a treatment effect. The record also does not report a detailed statistical analysis plan, sample-size justification, interim analyses, or multiplicity procedures.

The primary endpoint uses a per-protocol population with exclusions tied to follow-up, hemoglobin measurement availability, dosing during weeks 28-36, and iron status. The numbers excluded under these criteria and the treatment of missing observations are not reported in the registry record. Without those details, the impact of exclusions on the analyzed population cannot be assessed.

The registry describes a target sample size of 100-500 individuals in the brief summary and records enrollment of 75; the reason for this difference is not reported. The listed serious and other adverse-event counts are not comparative, and the number of deaths is not reported. These limitations concern the information available in the registry record and should not be read as proof that additional analyses or documentation do not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Monthly Subcutaneous Mircera for the Treatment of Chronic Renal Anemia in Predialysis Patients Not Treated With ESA. — NCT00661388.
• Registry record last updated 2025-09-11; status last verified 2016-07.
• Results first posted 2016-07-22.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00661388 is a completed Phase 3, single-group, open-label study sponsored by Hoffmann-La Roche. It enrolled 75 predialysis patients with renal anemia who were not currently treated with ESA. The intervention was subcutaneous C.E.R.A. (Mircera), described as given every 4 weeks for 44 weeks, with an initial dose of 1.2 micrograms/kilogram and later adjustment to maintain hemoglobin within 10.0 and 12.0 grams/deciliter.

The primary endpoint was mean hemoglobin change from baseline (Week 0) to the EEP (Week 29 to Week 36), analyzed in a defined PP population. The numerical primary endpoint result is not reported in the registry record. The record lists 18 outcome measures and 0 analyses. Safety summaries list 24 of 75 participants affected by serious adverse events and 38 of 75 affected by other adverse events; the number of deaths is not reported. The single-group design does not provide a like-for-like control comparison.