A Study to Evaluate Efficacy and Safety of Epoetin Beta (NeoRecormon®) in Anemic Participants With Breast Cancer Undergoing Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Efficacy and Safety of Epoetin Beta (NeoRecormon®) in Anemic Participants With Breast Cancer Undergoing Chemotherapy (NCT02761642), a na phase 2 study. The primary outcome is Percentage of Participants With Response to Treatment Based on Hemoglobin Levels.

2. Clinical Question

The study addresses a biomarker-based question: whether participants receiving the study treatment met a prespecified hemoglobin response criterion during the treatment period. Response was defined as an increase in hemoglobin of at least 2 g/dL from baseline, or achieving a hemoglobin level of 12 g/dL after 12 weeks of treatment, in the absence of red blood cells transfusion.

This endpoint combines two ways of meeting the response criterion. One is a change relative to baseline; the other is reaching a specified hemoglobin level. Both are assessed at Week 12, and the transfusion condition is part of the definition. The registry record does not report how many participants met either part, the percentage who responded, or the confidence interval around that percentage.

Because the study has a single treatment group, it can describe outcomes among participants who received epoetin beta but cannot make a randomized, like-for-like comparison with an untreated or alternative-treatment group. The clinical question is therefore narrower than a comparative efficacy question. The record also lists secondary measures involving hemoglobin change, early hemoglobin increase, time to increase, and quality of life, but their observed results are not reported in the registry record.

3. Trial Design

This is a completed Phase 2, multicenter study of epoetin beta in anemic participants with breast cancer treated with chemotherapy. The registry record lists an enrollment of 200 and describes a single-group model. The allocation field is NA, and masking is listed as none. The intervention is epoetin beta, described as subcutaneous treatment for 12 weeks.

The record identifies Hoffmann-La Roche as the sponsor. The study start is listed as 2004-02-29, and primary completion as 2007-03-31. These dates describe the study timeline; they do not establish when particular analyses were conducted or when results were available. The status is completed.

The primary outcome is the percentage of participants with a hemoglobin response at Week 12, assessed in the safety population. Response requires an increase from baseline of at least 2 g/dL or a hemoglobin level of 12 g/dL after 12 weeks, without red blood cells transfusion. Secondary outcomes listed in the record include hemoglobin change overall and in subgroups defined by baseline hemoglobin, chemotherapy, and time spent on chemotherapy. Other listed outcomes concern early hemoglobin increase, time to increase, and FACT-An quality-of-life scores.

These design features determine what can be learned from the study. A single-group design can describe response and safety outcomes in the treated group, but does not separate treatment effects from other explanations such as the course of chemotherapy, changes over time, or participant characteristics. With no masking, knowledge of treatment may also affect some assessments or care decisions; whether and how that could affect a particular outcome depends on how it was measured. The record does not report further details about outcome assessment procedures.

The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or detailed procedures for conducting the study. Those features should not be inferred from the phase, enrollment, or completion status.

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: Safety population

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety population: included all enrolled participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Response to Treatment Based on Hemoglobin Levels, measured over Week 12.

The primary endpoint is a percentage: the proportion of participants in the safety population who met the study's hemoglobin response definition at Week 12. A response is an increase from baseline of at least 2 g/dL or a hemoglobin level of 12 g/dL after 12 weeks of treatment, provided there was no red blood cells transfusion.

A percentage expresses how common the defined outcome was in the assessed population. The accompanying 95% confidence interval, named as the measure of dispersion, is intended to communicate uncertainty around that estimated percentage. In general, a confidence interval gives a range of values compatible with the data under the assumptions of the analysis; it is not a guarantee that the true value lies in that particular interval.

This kind of endpoint is used to summarize how many participants crossed a clinically specified response threshold, rather than the average amount of hemoglobin change. Threshold outcomes can be straightforward to interpret, but they discard information about how far above or below the threshold each participant's measurement lies. The endpoint also combines a change-from-baseline criterion with an attained-level criterion, so the overall response percentage alone would not show which criterion participants met.

The registry record does not report the observed response percentage, the confidence interval, or the number of participants meeting the definition. It therefore supports a description of what the endpoint was intended to measure, but not a conclusion about the observed response rate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the percentage measure?

The primary measure is a binary outcome at the participant level: each assessed participant either meets the stated response definition or does not. The percentage summarizes the frequency of response in the safety population. It is not the average change in hemoglobin. The distinction is important because people with different amounts of change can fall on the same side of a threshold, while a small change around the threshold can change a participant's classification.

The endpoint uses an “or” rule. A participant qualifies through an increase from baseline of at least 2 g/dL or through an achieved hemoglobin level of 12 g/dL after 12 weeks. The absence of red blood cells transfusion is also required. As a general matter, compound definitions should be read as written: the reported percentage would represent the combined rule, not separate response rates for each component. The registry record does not provide component-specific counts.

What does a confidence interval convey?

The primary endpoint names a 95% confidence interval. In general, an interval communicates the uncertainty associated with an estimate and depends on the data and the statistical method used. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The interval is not a measure of clinical importance and does not correct for design limitations, missing data, or bias.

No observed percentage or interval is reported in the registry record. Consequently, it is not possible to assess the precision of the primary estimate from this record. It is also not possible to evaluate whether an estimate would be compatible with a range of response rates, or to compare its uncertainty with a benchmark not stated in the record.

Why does the single-group structure matter?

In general, the outcome frequency in a treated group is descriptive. Without a concurrent comparator, there is no randomized between-group contrast to estimate how outcomes differ under alternative treatment conditions. Participants are receiving chemotherapy, and the study focuses on anemia during that care. The record does not provide a way to separate changes associated with epoetin beta from changes occurring over time or alongside chemotherapy and other care.

Randomization, when used, is a method for making comparison groups more alike on average with respect to measured and unmeasured characteristics. This study is not recorded as randomized: allocation is NA and the model is single group. Therefore, even a reported response percentage would not be a randomized estimate of treatment effect. Masking is recorded as none. In general, awareness of treatment assignment can influence some aspects of assessment or management, although the record does not establish that such influence occurred for any specific outcome.

What can be inferred from the sample-size assumptions?

The record includes assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. These assumptions describe hypothetical planning calculations, not the allocation or design of the single-group study. The statement that time-to-event calculations use the total number of events, while other calculations use participants per arm, is also a description of the illustration's conventions.

In general, a sample-size calculation explores how much information a hypothetical design might need under specified assumptions. Its result depends on those assumptions, including the effect size and statistical model. A planning illustration is not observed power: it does not quantify the probability that this completed study detected an effect after seeing its results. The registry record does not report the trial's own sample-size justification, and the illustration's assumptions should not be mistaken for the actual study design. The calculated sample-size values are not reported in the registry record.

What is not available about the analysis?

The registry record lists eight outcome measures and zero analyses. It does not report the primary outcome estimate, the statistical procedure used to calculate the confidence interval, or the participant counts underlying that estimate. It does not report how missing Week 12 hemoglobin measurements were handled, whether all eligible participants were included in the primary analysis, or how measurements after transfusion were treated beyond the transfusion condition in the response definition.

These omissions limit reproducibility and interpretation. In general, analysis choices can affect a percentage estimate when participants lack outcome measurements or when eligibility for an endpoint depends on events during follow-up. A confidence interval also depends on its calculation method. Without those details and the observed result, the primary endpoint cannot be independently assessed from the registry record.

Secondary outcomes may involve different types of analysis. A mean change summarizes the average numerical difference from baseline; a percentage above a threshold summarizes a binary outcome; time to a threshold concerns the timing of an event; and questionnaire scores represent a measured quality-of-life construct. Those general distinctions do not establish which models or methods were used in this study. The statistical procedures for these outcomes are 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("Epoetin Beta")
n      <- c(197)
events <- c(91)
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  Epoetin Beta  197  91  46.2  39.1  53.4  39.4  53.2  39.4  53.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists eight outcome measures, including the primary hemoglobin response endpoint and secondary outcomes covering hemoglobin changes, early response, time to response, and FACT-An questionnaire scores. It records zero analyses. The record does not report a multiplicity strategy, such as a testing hierarchy, adjustment procedure, or distinction between confirmatory and exploratory analyses.

In general, when several outcomes or subgroup comparisons are tested, the chance of at least one apparently unusual result can increase if each is assessed separately without accounting for the collection of tests. Multiplicity procedures can address that issue, but their relevance depends on the planned claims and analysis structure. The presence of multiple registered outcomes alone does not show that statistical tests were performed or that multiplicity affected any result. No such conclusion can be drawn because analyses and results are not reported.

Missing-data handling is also not reported. The record does not describe the number of participants with an available Week 12 hemoglobin measurement, how incomplete follow-up was treated, or whether any imputation or sensitivity analysis was used. In general, missing outcome data can affect both the estimated response percentage and its precision, particularly when the probability of missingness is related to participants' outcomes or clinical course. The impact cannot be assessed without the relevant counts and methods.

The primary outcome names the safety population. The record does not further define that population or report its analysis procedures. It does not identify an intention-to-treat population or describe how participants were handled if they did not complete treatment or lacked endpoint data. These details are not reported in the registry record, so the population underlying an observed primary estimate cannot be reconstructed from the 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: disease progression (1.0%), deep vein thrombosis (1.0%), neutropenia (0.5%), pancytopenia (0.5%), fatigue (0.5%).

The adverse-event figures describe the Epoetin Beta group. The record lists 197 participants at risk for serious adverse events and 17 affected, and 197 at risk for other adverse events and 85 affected. The serious-event terms listed with percentages are disease progression, 1.0%; deep vein thrombosis, 1.0%; neutropenia, 0.5%; pancytopenia, 0.5%; fatigue, 0.5%; and general physical health deterioration, 0.5%.

These are descriptions of recorded safety events, not estimates of comparative risk. The study is single group, and the registry record does not provide a control group for comparison. The figures do not establish that epoetin beta caused an event, nor do they show what would have happened under another treatment. In general, safety interpretation also depends on how events were defined, collected, and assessed; these procedures are not reported in the registry record.

The affected-participant figures should not be treated as totals of event occurrences: the record reports participants affected, and one participant could potentially contribute to more than one event category. The registry record does not report deaths in the adverse-event field. That absence is not evidence that no deaths occurred; the death value is not reported in the registry record.

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

The study record establishes that epoetin beta was evaluated in anemic participants with breast cancer receiving chemotherapy, using a single-group design and a Week 12 hemoglobin response endpoint. It also gives the response definition and selected safety figures. These details clarify the scope of the intended assessment, but they are not a substitute for the outcome results.

The primary response endpoint would describe the percentage of the safety population meeting a defined hemoglobin threshold, including the requirement concerning red blood cells transfusion. It would not, by itself, describe all changes in hemoglobin, all aspects of anemia, or quality of life. The listed secondary endpoints address some of these distinct questions, but their results are not reported in the registry record.

No observed primary response percentage or confidence interval is reported. Accordingly, the record does not show the size or precision of the response estimate. It also does not support a conclusion that treatment did or did not produce a response. Such conclusions would go beyond the information recorded.

Even if the response result were available, the single-group design would remain an important limit on causal interpretation. A percentage in the treated group does not estimate the difference between epoetin beta and no epoetin beta, or between epoetin beta and another treatment. Without a comparator, changes over time and other aspects of participants' care cannot be separated from a treatment effect using this design alone.

The safety figures similarly describe events in the treated group and do not establish causation or comparative safety. The statistical meaning of the record is therefore bounded: it documents a treatment evaluation, an endpoint definition, and selected event counts, while leaving the efficacy result and important analysis details unreported.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a clearly defined primary endpoint and the absence of a reported primary result in the registry record. The endpoint is expressed as a percentage and includes a specified confidence interval, so the intended summary combines an estimate of response frequency with a measure of precision. Without either the estimate or the interval, neither the observed frequency nor its uncertainty can be evaluated.

The single-group model is also essential to the interpretation. Descriptive response rates can characterize outcomes among treated participants, but a comparative treatment effect requires a meaningful comparator. The record lists no comparator group and records allocation as NA. It is therefore important not to read a potential within-group change as a controlled estimate of benefit or harm.

The outcome list illustrates that different statistical questions were contemplated: threshold response, mean change from baseline, subgroup descriptions, time to a threshold, and a quality-of-life questionnaire. These measures do not answer interchangeable questions. In general, a threshold percentage communicates how many participants crossed a criterion, while a mean change retains information about the scale of change. The registry record does not report analyses for these outcomes.

The safety information makes another useful distinction: affected-participant counts and percentages describe recorded events, but do not establish their cause. A single-group record cannot provide a like-for-like comparative safety estimate. The record also does not give detailed event definitions or handling procedures, limiting further interpretation.

Finally, the planning assumptions should not be confused with the actual study's design or its evidential strength. The illustration assumes equal allocation between two arms, whereas the registered study is single group. Recognizing that distinction helps prevent a hypothetical sample-size calculation from being treated as observed power or as a justification documented for this trial.

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 direct limitation of the registry record for statistical interpretation is that it does not report the observed primary endpoint result. The Week 12 response percentage and its 95% confidence interval are absent, as are the corresponding participant counts. The secondary outcome results are also not reported.

The single-group design has no concurrent comparator. This limits causal interpretation because observed outcomes cannot be contrasted with outcomes under an alternative condition within the study. Allocation is listed as NA and masking as none. The record does not report additional design or assessment details that could clarify the role of potential sources of bias.

The record does not report a statistical analysis plan, analysis procedures, missing-data methods, or a sample-size justification. It does not explain how participants with incomplete Week 12 measurements were handled, how the safety population was defined, or how the secondary outcomes were analyzed. The registry lists eight outcome measures and zero analyses, which further limits the available information about the intended and completed statistical work.

The primary endpoint combines two hemoglobin criteria and conditions response on the absence of red blood cells transfusion. The record does not provide separate results for the endpoint components or further detail on outcome ascertainment. Thus, even if an overall response estimate were reported elsewhere, the registry record as described would not show which criterion accounted for responses.

For safety, the record gives participant counts and selected serious-event terms but does not describe event definitions, collection methods, or comparative rates. Deaths are not reported in the adverse-event field. These limitations mean the listed figures should be read as recorded descriptive information, not as complete evidence about causation or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate Efficacy and Safety of Epoetin Beta (NeoRecormon®) in Anemic Participants With Breast Cancer Undergoing Chemotherapy — NCT02761642.
• Registry record last updated 2018-08-24; status last verified 2018-08.
• Results first posted 2018-08-24.
• 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

NCT02761642 is a completed Phase 2, multicenter, single-group study of subcutaneous epoetin beta in anemic participants with breast cancer undergoing chemotherapy. The arm description specifies 12 weeks of treatment. Enrollment is listed as 200; the sponsor is Hoffmann-La Roche. The study start and primary completion dates are 2004-02-29 and 2007-03-31.

The primary endpoint is the percentage of the safety population with a hemoglobin response at Week 12, defined by an increase from baseline of at least 2 g/dL or a hemoglobin level of 12 g/dL after 12 weeks, without red blood cells transfusion. The registry record does not report the observed primary estimate or its confidence interval.

Listed secondary outcomes cover hemoglobin changes, early and timed hemoglobin response, and FACT-An scores. The record lists serious and other adverse-event figures for the Epoetin Beta group. It does not report a comparator, statistical analysis plan, missing-data procedures, or outcome analyses.