LATINO Study: A Study of Mircera for the Maintenance Treatment of Dialysis Patients With Chronic Renal Anemia.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for LATINO Study: A Study of Mircera for the Maintenance Treatment of Dialysis Patients With Chronic Renal Anemia. (NCT00517413), a na phase 3 study. The primary outcome is Percentage of Participants Maintaining Their Mean Hb Concentration Within ±1.0 Gram/Deciliter of Their Reference Hb and Between 10.5 and 12.5 Gram/Deciliter.

2. Clinical Question

The clinical question concerns maintenance of hemoglobin levels during monthly C.E.R.A. treatment after prior treatment with other erythropoiesis-stimulating agents. It is not a question of whether C.E.R.A. performs better than a concurrent alternative: the single-group design cannot directly estimate that comparative effect. The endpoint combines closeness to each participant’s reference hemoglobin with remaining within a stated absolute range. This makes the outcome a measure of maintenance within specified bounds rather than a measure of change alone.

The primary endpoint was assessed during the efficacy evaluation period (EEP), described as Week 16 to Week 24 after a 16-week dose titration period (DTP). Other registered outcomes included hemoglobin change, time within the target range, C.E.R.A. dose, dose adjustments, transfusions and adverse events. Numerical results for those outcomes are not reported in the registry record. The listed information therefore establishes the question the study set out to address, but does not show the observed primary endpoint estimate or how precisely it was estimated.

3. Trial Design

The LATINO Study (NCT00517413) is recorded as a Phase 3, completed, single-group, open-label study sponsored by Hoffmann-La Roche. The study start is listed as 2007-10 and primary completion as 2010-05. Enrollment was 163. Allocation is listed as not applicable, and masking as none; there was no randomized control group.

The intervention was methoxy polyethylene glycol-epoetin beta, referred to as C.E.R.A. or Mircera, given monthly by intravenous and/or subcutaneous administration. The brief summary says participants currently receiving maintenance epoetin alfa were to receive a starting dose of 120, 200 or 360 micrograms, derived from their epoetin alfa dose in the preceding week. The arm description also identifies prior treatment with epoetin beta or darbepoetin alfa. The registry record does not explain this difference in wording. The anticipated time on study treatment is described as 3-12 months.

The primary endpoint focused on hemoglobin maintenance during the EEP, which ran from Week 16 to Week 24 after completion of the 16-week DTP. Hemoglobin assessments were described from enrollment through Week 48, with a reference value based on assessments at Weeks -4, -3, -2, -1 and 0. The Week 0 assessment was taken before the first dose. These timings distinguish the dose adjustment period from the subsequent efficacy assessment.

A single-group design can describe outcomes among participants receiving the intervention, but it does not separate treatment effects from changes that might also occur over time or under other care. The open-label status means masking was not used, although the registry record does not describe how endpoint assessment or other study procedures were conducted. The protocol, detailed statistical analysis plan and sample-size justification 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Per-Protocol Population (PP) included all participants in the safety population except those who had \<3 recorded Hb values; withdrawn; inadequate iron defined as mean serum ferritin =\<100 nanogram/milliliter (ng/mL) or mean TSAT=\<20% or mean hypochromic RBCs\>=10%; or had missing administration of C.E.R.A. all during EEP (Week 16-24).

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: The Intention To Treat (ITT) population included participants who received at least 1 dose of C.E.R.A. (Week 0) and for whom data for at least one follow-up variable were available.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Maintaining Their Mean Hb Concentration Within ±1.0 Gram/Deciliter of Their Reference Hb and Between 10.5 and 12.5 Gram/Deciliter, measured over EEP (Week 16 to 24).

The primary endpoint is the percentage of participants whose mean hemoglobin concentration during the efficacy evaluation period remained within ±1.0 gram/deciliter of their reference hemoglobin and between 10.5 and 12.5 gram/deciliter. The registry defines the reference using each participant’s hemoglobin assessments at Weeks -4, -3, -2, -1 and 0; the Week 0 value was measured before the first dose. The EEP is described as Week 16 to Week 24, following a 16-week dose titration period.

This endpoint is used to represent maintenance within a clinically defined hemoglobin range while also accounting for each participant’s own reference level. The absolute range gives a common threshold, while the reference-based condition limits how far an individual’s mean can move from their starting reference. It is therefore different from reporting only an average change in hemoglobin: a group average could conceal how many participants remained within the specified bounds.

The endpoint’s value depends on its measurement period, reference definition and analysis population. The record describes a Per-Protocol Population and some of its exclusion criteria, but the population description is incomplete. Most importantly, the registry record does not report the primary endpoint percentage or its 95% confidence interval. Without those results, the stated endpoint defines what was intended to be measured but does not establish how many participants met it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods concepts relevant to interpreting the LATINO Study begin with its single-group design. Participants received monthly C.E.R.A.; there was no randomized comparator, and masking was listed as none. In a comparative trial, random assignment can help make groups similar in expectation with respect to both measured and unmeasured characteristics. A single-group study does not have that protection against alternative explanations for observed changes. Its outcomes can describe what occurred among participants, but do not by themselves isolate the effect of treatment from time trends, co-interventions or other influences.

What does the primary percentage represent?

The endpoint is a proportion: the percentage of participants whose mean hemoglobin during the EEP met both parts of the definition. Participants had to remain within ±1.0 gram/deciliter of their reference hemoglobin and within the absolute range of 10.5 to 12.5 gram/deciliter. Because both conditions are part of the definition, satisfying only one condition would not meet the stated endpoint. A proportion is a useful way to express how often a defined target is met, but its interpretation depends on the population included and the rules used to classify participants.

The reference hemoglobin was based on assessments at Weeks -4, -3, -2, -1 and 0, with the Week 0 assessment occurring before the first dose. The EEP was Week 16 to Week 24 after the 16-week DTP. This timing matters: the endpoint describes maintenance after dose titration rather than a single measurement immediately after treatment begins. The registry record says hemoglobin was recorded at different points through Week 48, but that broader assessment schedule does not change the primary endpoint’s stated evaluation period.

How should a confidence interval be understood?

A confidence interval communicates uncertainty around an estimated quantity. For a percentage, it indicates a range of values compatible with the observed data under the method used to calculate the interval. It is not a guarantee that the true value lies within the particular interval, and it does not correct limitations in the design, population definition or data collection. A narrower interval generally indicates greater statistical precision, while a wider one indicates more uncertainty. The registry specifies a 95% confidence interval for the primary percentage, but the numerical estimate and its interval are not reported in the registry record, so precision cannot be assessed.

Precision and clinical meaning are distinct. A precisely estimated percentage could still be difficult to interpret without a comparator or context for what would happen under another treatment. Conversely, a point estimate without its interval would not convey how much sampling uncertainty surrounds it. Here, neither the primary estimate nor its interval is available in the registry record.

Why do the analysis population and missing observations matter?

The endpoint description identifies the Per-Protocol Population and says that it excluded participants for several reasons, including having fewer than three recorded hemoglobin values, withdrawal, inadequate iron measures or missing administration information. The record’s population description is truncated, so a complete account of eligibility and exclusions is not available. A per-protocol analysis can focus on participants meeting specified study requirements, but excluding participants after enrollment may affect how representative the analyzed group is of everyone enrolled. Interpretation requires knowing who was excluded, why, and how many participants remained; these details are not fully reported.

Missing observations can affect a repeated-measure endpoint because a participant’s mean over the EEP depends on the available measurements and on rules for handling absent values. The registry record does not report a complete missing-data method, such as how incomplete endpoint measurements were handled. It is therefore not possible to determine from the record whether the analysis used all available measurements, imputation, or another approach. No method should be assumed.

What does over-dispersion mean in general?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. For count or proportion data, an overly restrictive model may make uncertainty appear smaller than it is. Methods that allow extra variability can produce more realistic standard errors or intervals when the data are more heterogeneous than the basic model expects. The registry record does not identify a model for the primary endpoint or report whether over-dispersion was assessed. This general concept therefore explains a possible statistical concern, not a claim about the analysis performed in this study.

Likewise, a sample-size calculation is a planning exercise, not a study result. It asks how much information a design might need under stated assumptions about the effect, variability, significance level and allocation. A planning illustration based on an observed effect is not the trial’s original design justification and is not observed power. The registry record does not report the protocol’s sample-size justification or the assumptions used for such planning. No inference about the adequacy of enrollment can be made from enrollment alone.

The record lists 18 outcome measures and zero analyses. This means that the posted registry information does not include analysis entries for the outcomes. Without an analysis plan, endpoint results and details of model specification, it is not possible to verify which statistical procedures were used, whether they matched a prespecified plan, or how uncertainty was calculated. Statistical interpretation should remain limited to the information the record actually reports.

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(103)
events <- c(45)
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  103  45  43.7  33.9  53.8  34.5  53.3  34.5  53.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, including a primary hemoglobin-maintenance endpoint and secondary outcomes covering hemoglobin change, time in range, dose, dose adjustments, transfusions, and adverse events. Testing or interpreting many outcomes can raise a multiplicity issue: the more questions examined, the greater the chance that some findings may appear notable by chance alone. In general, a prespecified hierarchy or an adjustment procedure can help address this concern. The registry record does not report a multiplicity strategy, endpoint hierarchy beyond identifying the primary measure, or detailed statistical analysis plan.

The record lists zero analyses, and numerical results for the primary and secondary efficacy outcomes are not reported in the registry record. It is therefore not possible to assess whether the analyses followed a prespecified plan, whether all outcomes were reported, or how multiple comparisons were handled. No adjustment method should be inferred from the presence of a stated 95% confidence interval for the primary endpoint.

Missing-data handling is also not fully described. The primary endpoint is based on repeated hemoglobin measurements, while the Per-Protocol Population description excludes participants with fewer than three recorded hemoglobin values and other specified circumstances. The available description is truncated, and the registry record does not report a complete account of missing measurements, imputation, or sensitivity analyses. The number of participants included in the primary analysis is not reported in the registry record. These gaps limit assessment of both the analysis population and the potential influence of incomplete follow-up.

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: pneumonia (3.1%), arteriovenous fistula thrombosis (3.1%), gastrointestinal haemorrhage (1.9%), acute myocardial infarction (1.2%), sudden death (1.2%).

The adverse-event entry lists 162 participants at risk in the C.E.R.A. group, with 53 participants recorded with serious adverse events and 40 with other adverse events. These are participant counts, not counts of all individual event episodes. A participant may experience more than one event; the registry record does not specify whether the two participant groups are mutually exclusive, so the counts should not be added or interpreted as distinct people across categories.

The most frequently listed serious-event terms include pneumonia at 3.1%, arteriovenous fistula thrombosis at 3.1%, gastrointestinal haemorrhage at 1.9%, acute myocardial infarction at 1.2%, sudden death at 1.2%, and dyspnoea at 1.2%. These are event-term percentages as listed; the registry record does not provide fuller details on event timing, recurrence, adjudication, or the calculation basis for each term. It also does not report a death count in the adverse-event group.

Safety counts in an uncontrolled study describe events recorded among treated participants. Without a concurrent comparison group, they do not show whether event frequency differs from another treatment or from the background risk in a similar population. The registry record’s adverse-event information is therefore descriptive and should not be read as a comparative safety estimate.

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

The registry record establishes that LATINO was a Phase 3, open-label, single-group study of monthly C.E.R.A. In dialysis patients with chronic renal anemia. Its primary question was whether participants maintained mean hemoglobin within a reference-based margin and a specified target range during the EEP. The endpoint definition, assessment schedule and some features of the analysis population are described.

However, the numerical primary outcome is not reported in the registry record. The stated 95% confidence interval is also not accompanied by an estimate or interval limits. The record therefore does not establish what percentage met the endpoint or how precisely that percentage was estimated. It also does not report numerical findings for the listed secondary outcomes. Missing results must not be interpreted as evidence for either success or failure.

Even if a primary percentage were available, the single-group design would support a description of outcomes among participants, not a direct estimate of comparative treatment effect. There was no concurrent control group, and masking was not used. The observed course could not be separated from other influences by a randomized comparison. The registry record also does not include the complete analysis plan or full details of missing-data handling, making it difficult to evaluate the analysis beyond the endpoint definition.

The safety entry reports serious and other adverse-event participant counts in the C.E.R.A. group, along with selected event-term percentages. These are descriptive counts without a randomized comparator, and the record does not provide a death count. They do not establish comparative risks or explain causation. In statistical terms, the available information is most useful for understanding what the study set out to measure, its design constraints, and the safety summaries posted. It does not support a conclusion about treatment efficacy or comparative safety, and it is not a basis for medical advice.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of a maintenance question expressed through a target-based endpoint. Rather than focusing only on mean hemoglobin change, the primary outcome asks what percentage of participants remained within a range that combines an individual reference value and an absolute hemoglobin interval. Such an endpoint can reflect whether a target is maintained across a defined period, but its interpretation depends closely on how the reference, assessment window and analysis population are defined.

The study also illustrates the limits of a single-group design. A measured percentage can describe the treated participants, but without a concurrent comparator there is no direct randomized contrast. This distinction is important when reading efficacy claims: an outcome observed during treatment is not, on its own, an estimate of what treatment changed relative to an alternative.

The record gives a detailed endpoint definition and identifies a Per-Protocol Population, yet omits the numerical primary result, its confidence interval and the complete analysis population details. It lists 18 outcome measures and zero analyses. These omissions show why registry design information and posted results must be considered separately. Knowing what was intended to be measured does not reveal the observed estimate or its uncertainty.

Finally, safety listings are also best read in context. Participant counts and selected event-term percentages provide descriptive information, but the absence of a control group and fuller event detail limits comparisons. The statistical value of the record lies in clarifying the study question and identifying what remains unavailable for a full assessment.

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 principal trial-specific limitation is the absence of the numerical primary endpoint result and its 95% confidence interval in the registry record. The same record lists zero analyses, and numerical secondary outcome results are not reported. This prevents evaluation of the size and precision of the primary estimate or review of the other outcome findings.

The single-group, open-label design has no concurrent randomized comparator. As a result, outcomes during C.E.R.A. treatment cannot be directly contrasted with outcomes under another treatment or a control condition. Allocation is listed as not applicable and masking as none. The record does not explain additional procedures that might address bias in measurement or conduct.

The primary endpoint’s Per-Protocol Population description is incomplete. It identifies some exclusions, including insufficient recorded hemoglobin measurements, withdrawal, inadequate iron measures and missing administration information, but the full population definition and analyzed participant count are not reported. The registry record also does not give a complete missing-data strategy, sensitivity analyses or a detailed statistical analysis plan. The sample-size justification is not reported in the registry record.

There is also a difference in how prior treatment is described: the brief summary refers to current maintenance epoetin alfa, while the arm description names prior epoetin alfa, epoetin beta or darbepoetin alfa. The registry record does not explain that wording difference. Finally, the adverse-event listing gives participant counts and selected event terms but does not report a death count or provide detailed event-level context. These limitations constrain interpretation of both efficacy and safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: LATINO Study: A Study of Mircera for the Maintenance Treatment of Dialysis Patients With Chronic Renal Anemia. — NCT00517413.
• Registry record last updated 2016-04-29; status last verified 2016-03.
• Results first posted 2016-04-29.
• 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

NCT00517413, the LATINO Study, is recorded as a completed Phase 3, single-group, open-label study sponsored by Hoffmann-La Roche. The listed enrollment was 163; the study start was 2007-10 and primary completion was 2010-05. Participants received monthly methoxy polyethylene glycol-epoetin beta (C.E.R.A./Mircera) by intravenous and/or subcutaneous administration.

The primary endpoint was the percentage maintaining mean hemoglobin within ±1.0 gram/deciliter of reference and between 10.5 and 12.5 gram/deciliter during the EEP. The registry record describes the reference assessments and evaluation period but does not report the numerical primary result or its confidence interval. It lists 18 outcome measures and zero analyses.

The adverse-event group lists 162 participants at risk, 53 with serious adverse events and 40 with other adverse events. Selected serious-event terms and percentages are reported, but there is no death count. The registry record does not provide a concurrent comparison, complete analysis details or numerical efficacy results.