A Study of Subcutaneous Mircera for the Treatment of Anemia in Pre-Dialysis Participants With Chronic Kidney Disease.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Subcutaneous Mircera for the Treatment of Anemia in Pre-Dialysis Participants With Chronic Kidney Disease. (NCT00462384), a na phase 3 study. The primary outcome is Mean Change in Hemoglobin Concentration Between Baseline and the Efficacy Evaluation Period (EEP).

2. Clinical Question

The study addresses a within-participant question: how hemoglobin concentration changed between a defined baseline period and a later evaluation period while participants received the study drug. The endpoint uses averages of hemoglobin assessments in each period, rather than a single measurement, as described in the registry. This makes the comparison about the average concentration in the specified periods.

The question is not whether the drug performed better than another treatment or than no treatment. With no concurrent comparator, observed change could reflect the study treatment, the course of participants’ illness, other care, measurement variation, or other influences. The registry record does not provide a numerical primary result that would allow readers to judge the size or precision of the change.

3. Trial Design

This was a Phase 3, open-label, multi-center study with a single-group design. The registry lists allocation as not applicable and masking as none. Participants received subcutaneous methoxy polyethylene glycol-epoetin beta; there was no control arm for a randomized or like-for-like comparison. The sponsor is Hoffmann-La Roche.

The study description focuses on participants with chronic kidney disease who were not on dialysis and were not treated with erythropoiesis-stimulating agents. The brief summary describes monthly injections, with a starting dose of 1.2 micrograms per kilogram of body weight. The arm description specifies administration every 4 weeks at Weeks 4, 8, 12, 16, 20, 24, 28 and 32. It also indicates that later dose adjustments depended on body weight, but the available description ends before giving the complete adjustment details.

The primary endpoint compares baseline hemoglobin, defined as the mean of assessments during Weeks -2 and 0, with EEP hemoglobin, defined as the mean of assessments during Weeks 29 to 36. The EEP is described as the first 8 weeks following a 28-week dose-titration period. The brief summary anticipates 3-12 months on study treatment; the endpoint timeframe itself is specified by study weeks.

The registry records enrollment of 39 and lists the study status as terminated. The brief summary describes a target sample size of 100-500 individuals. The reason for termination and whether the target changed are not reported in the registry record. The recorded start is 2008-02, and primary completion is recorded as 2011-04. The record does not establish why enrollment was below the stated target or how termination affected the 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: Intent to treat (ITT) population: included all participants who received at least one dose of methoxy polyethylene glycol-epoetin beta and for whom data for at least one study variable was available.

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 were treated with at least one dose of the study medication.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in Hemoglobin Concentration Between Baseline and the Efficacy Evaluation Period (EEP), measured over Baseline (Week -2 to 0) and EEP (Weeks 29 to 36).

The primary endpoint is the mean change in hemoglobin concentration between baseline and the Efficacy Evaluation Period, measured in grams per deciliter (g/dL). The registry defines baseline as the mean of assessments recorded during screening at Weeks -2 and 0. EEP hemoglobin is the mean of assessments during Weeks 29 to 36, the first 8 weeks following the 28-week dose-titration period.

Using a mean across assessments is intended to describe hemoglobin over a defined period rather than rely on a single reading. In general, averaging repeated measurements can reduce the influence of short-term measurement fluctuation, although it does not eliminate uncertainty or other sources of bias. The endpoint’s interpretation depends on consistent assessment and on having usable data in both periods.

The registry record specifies the endpoint, its unit, the summary measure and its timeframes, but does not report the numerical mean change, standard deviation, confidence interval or test result. Consequently, the magnitude and precision of the observed change cannot be assessed from the endpoint information recorded. The endpoint description alone does not establish whether a change occurred or what caused it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

The primary outcome is a continuous measure: hemoglobin concentration in g/dL. The registry defines a mean for baseline and a mean for the EEP. In general, a mean is a summary of the values in a group; a mean change summarizes the participant-level differences between the two periods. It answers a different question from comparing the average hemoglobin at the EEP with a separate group’s average, because this trial has no separate comparator group.

The baseline mean uses assessments from Weeks -2 and 0. The EEP mean uses assessments from Weeks 29 to 36. Taking the mean of assessments within each period can make the period summary less dependent on any single reading. It does not remove uncertainty, ensure that assessments are complete, or address potential influences that change over time. The registry does not report how many assessments each participant contributed or how missing measurements were handled.

How should standard deviation be understood?

The endpoint lists standard deviation as its dispersion measure. In general, standard deviation describes how spread out individual observations are around a mean. For a mean-change outcome, it can help show whether participant-level changes were relatively similar or varied substantially. It is not the same as the uncertainty around the mean estimate: a confidence interval is a separate summary used to express uncertainty in an estimated quantity.

The standard deviation value for the primary outcome is not reported in the registry record. Neither a confidence interval nor a p-value for the primary comparison is reported there. Without these quantities, the record does not show the spread of participant-level changes or how precisely the mean change was estimated.

What can a before-and-after design establish?

In general, a before-and-after analysis describes change over time within the observed participants. A concurrent comparison group can help distinguish change associated with treatment from change that might have occurred over the same period for other reasons. This study has a single-group design and no comparator. Accordingly, even a reported change would be a descriptive within-group finding, not a randomized estimate of the treatment’s effect relative to an alternative.

The study is open-label, and masking is listed as none. This means the registry does not describe blinded treatment assignment or outcome assessment. For an objective laboratory measure, the observed value remains a measurement, but study conduct and participant care can still be influenced by knowledge of treatment. The record does not detail laboratory procedures or safeguards against measurement bias.

What is the role of the EEP?

The EEP is the first 8 weeks during Weeks 29 to 36 after the 28-week dose-titration period. The endpoint therefore focuses on a later evaluation window rather than the full treatment period. The registry separately identifies secondary outcomes about response and hemoglobin maintenance during the EEP. In general, defining an evaluation window makes clear which observations contribute to an endpoint; it does not by itself show that the window was reached or fully observed by every participant.

The registry does not report the number of participants contributing baseline and EEP data, the timing of individual discontinuations, or the handling of participants without measurements in both periods. Those details matter because an analysis based only on participants with complete measurements may differ from one using a prespecified approach to incomplete data. The registry record does not describe which approach was used.

How should planning illustrations be interpreted?

In general, sample-size calculations estimate how many participants a future study might need under stated assumptions about the effect, variability, significance level, allocation and analysis method. They are planning illustrations, not observed findings and not evidence that a study had a particular probability of detecting an effect. The planning assumptions associated with the record describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. For non-time-to-event outcomes, the stated convention is participants per arm for 80% power or 90% power; time-to-event calculations use total events.

Those assumptions describe hypothetical two-arm planning, while the actual study is a single-group study. They must not be mistaken for the trial’s design or for observed power. The registry record does not report the trial’s own sample-size justification or a numerical planning result. The stated target of 100-500 in the brief summary and the recorded enrollment of 39 are study-record details, not a substitute for a documented design calculation.

Why does over-dispersion matter in general?

For count outcomes, over-dispersion means that observed variability exceeds what a simple model assumes. In general, failing to account for over-dispersion can make standard errors too small and confidence intervals too narrow. This primary endpoint is continuous and summarized by a mean and standard deviation, so that general issue is not a basis for interpreting the unreported primary result. The registry does not describe a model for the primary endpoint.

The listed secondary outcomes include time to response and time spent in a hemoglobin range. Such outcomes can require methods tailored to time or repeated observations. The registry record does not report analysis methods, model specifications, or numerical analyses for these outcomes, so no particular statistical procedure should be inferred.

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("Methoxy Polyethylene Glycol-epoetin Beta")
n   <- c(39)
m   <- c(1.32)
sp  <- c(0.88)
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  Methoxy Polyethylene Glycol-epoetin Beta  39  1.320  0.880  1.035  1.605

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary hemoglobin mean-change outcome and secondary outcomes concerning time to response and maintenance or time spent within the hemoglobin range 11.0 to 13.0 g/dL during the EEP. When a study evaluates several outcomes, multiplicity is a general concern: repeated statistical testing can increase the chance of finding an apparently notable result by chance. Whether and how that concern was addressed depends on the prespecified statistical plan. The multiplicity approach is not reported in the registry record.

The record reports 0 analyses. It does not provide numerical primary or secondary outcome analyses, p-values, confidence intervals, or a statistical analysis plan. It is therefore not possible to determine whether testing was planned, adjusted for multiple outcomes, or conducted according to a prespecified hierarchy. The absence of analyses in the record should not be interpreted as proof that no analyses were performed outside the registry.

The primary analysis population is defined as the intent-to-treat population: participants who received at least one dose of methoxy polyethylene glycol-epoetin beta and had data for at least one study variable. This definition describes eligibility for that population; it does not establish how many participants met the definition or contributed to the primary endpoint. The record does not report the number with usable baseline and EEP hemoglobin assessments.

Missing-data methods, reasons for missing measurements, and sensitivity analyses are not reported in the registry record. In general, incomplete outcome data can affect a mean-change estimate if the participants with observed measurements differ from those without them. The record does not allow assessment of the extent or likely direction of any such effect. The stated enrollment and analysis-population definition cannot substitute for outcome-specific data availability.

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: angina pectoris (2.6%), arteriosclerosis coronary artery (2.6%), atrial fibrillation (2.6%), bronchitis (2.6%), otitis media chronic (2.6%).

The registry safety summary lists 39 participants at risk for serious adverse events and 11 affected, and 39 at risk for other adverse events and 11 affected. These are separate recorded safety counts. The record also lists serious-event terms with a percentage of 2.6% for each: angina pectoris, arteriosclerosis coronary artery, atrial fibrillation, bronchitis, otitis media chronic and pneumonia.

In general, a serious adverse event is a safety category, while an adverse event is an event recorded during a study; a recorded event does not, by itself, establish that treatment caused it. The listed terms and counts provide descriptive information from a single-group study without a concurrent comparator. They cannot establish whether event frequency differed from what would have occurred without treatment or under another treatment.

The registry record does not report a death count. It also does not provide event-level timing, duration, outcome, participant overlap across terms, or an assessment of causality. The listed percentages should be read as recorded and not converted into a comparative risk estimate. The safety summary is therefore useful as a description of reported events, but limited for attributing events to the study drug or comparing safety with another option.

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

The record establishes that a Phase 3, open-label, single-group study was designed to assess hemoglobin change and safety in pre-dialysis participants with chronic kidney disease. It identifies the intervention, the baseline and EEP definitions, and selected safety counts. It also records enrollment of 39 and a terminated study status. These registry entries describe the study and its registry entry; they do not provide a numerical primary outcome result.

The primary endpoint is a within-participant comparison between mean hemoglobin during baseline and mean hemoglobin during the EEP. Its numerical mean change and standard deviation are not reported in the registry record. Without those results, readers cannot assess the observed direction or magnitude of change, the variability among participants, or the precision of the estimate. No conclusion about statistical significance can be drawn from the information recorded.

Even if a mean change were available, the single-group design would not provide a concurrent estimate of what would have happened without the study treatment. Before-and-after change may reflect treatment exposure along with other influences over time. The design also offers no randomized comparison with another treatment. The record therefore does not support a comparative treatment-effect conclusion.

The safety counts document recorded events among participants at risk, but they do not establish causation or comparative safety. The registry does not report a death count, and the listed serious-event terms are not a substitute for a complete event-level account. The termination status also does not identify why the study ended. Its reason is not reported in the registry record.

In sum, the registry provides design and outcome definitions but not the primary numerical efficacy result or a reported statistical analysis. Its entries should be read as a description of the study record rather than as a complete account of efficacy, uncertainty, or comparative safety.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and result reporting need to be considered separately. The registry specifies a continuous primary measure, the unit, the dispersion measure, the baseline period and the EEP. Those details make the intended comparison understandable. But a well-defined endpoint is not itself a result: the mean change and standard deviation are not reported in the registry record, so the central statistical finding cannot be evaluated from this entry.

The single-group structure also clarifies the boundary between describing change and estimating a comparative effect. A within-group before-and-after contrast can describe how measured hemoglobin changed over the specified periods. It cannot, on its own, determine how much of that change was attributable to treatment rather than other time-related influences. The open-label design and lack of a comparator are therefore central to interpretation, not minor reporting details.

The record further shows why enrollment, a stated target and analysis populations should not be conflated. It lists enrollment of 39, a target sample size of 100-500 in the brief summary, and an ITT population definition. It does not report the endpoint-specific analysis count, missing-data handling, or the reason the study was terminated. Those gaps limit assessment of how the design translated into the reported analysis.

Finally, safety summaries require the same distinction between recorded events and treatment attribution. Counts and listed event terms are informative descriptions, but without a comparator and fuller event detail they cannot establish relative risk. These features make the record a useful example of how design, endpoint reporting, uncertainty, missing-data information and safety context jointly determine what statistical conclusions are supportable.

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 efficacy is that the registry record does not report the numerical mean change in hemoglobin or its standard deviation. No confidence interval or test result is reported. As a result, the endpoint’s observed magnitude, participant-level variability and precision cannot be assessed. The endpoint definition alone does not show the outcome.

The study has no concurrent comparator and is open-label. It can describe change between baseline and the EEP, but the record cannot isolate the effect of treatment from other influences over time or support a randomized comparison. There is no basis in the registry record for estimating relative benefit or harm against another treatment or no treatment.

Enrollment is recorded as 39, while the brief summary states a target sample size of 100-500. The study status is terminated, but the reason for termination, any changes to the target, and the relationship between termination and the final analysis are not reported in the registry record. These registry entries raise questions about completeness and study conduct that cannot be resolved from this entry alone.

The record does not state how many participants had usable measurements in both baseline and the EEP, how missing measurements were handled, or whether sensitivity analyses were conducted. The ITT population definition includes participants with at least one dose and data for at least one study variable, but does not establish endpoint-specific completeness. The statistical analysis plan and multiplicity approach are also not reported.

For safety, the record gives aggregate counts and selected serious-event terms, but not a death count, event timing, participant overlap, or causal assessment. Without a comparator, these summaries cannot establish comparative safety. The limitations are specific to the information recorded and should not be mistaken for proof that unreported procedures or analyses did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Subcutaneous Mircera for the Treatment of Anemia in Pre-Dialysis Participants With Chronic Kidney Disease. — NCT00462384.
• Registry record last updated 2016-04-01; status last verified 2016-03.
• Results first posted 2016-04-01.
• 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

NCT00462384 is a Phase 3, open-label, multi-center, single-group study of subcutaneous methoxy polyethylene glycol-epoetin beta in pre-dialysis participants with chronic kidney disease and anemia. The registry records enrollment of 39, status as terminated, a start of 2008-02 and primary completion in 2011-04. The brief summary states a target sample size of 100-500.

The primary endpoint is mean change in hemoglobin concentration from baseline, defined using Weeks -2 and 0, to the EEP during Weeks 29 to 36. The numerical primary result and its variability are not reported in the registry record. The study has no comparator, and the record does not report the reason for termination, missing-data methods, or a statistical analysis plan.

The safety summary lists 11 participants with serious adverse events and 11 with other adverse events, among 39 at risk for each category. A death count is not reported. These descriptive data do not establish causality or comparative risk.