A Study to Evaluate Safety and Tolerability in Patients With Metastatic Breast Cancer Receiving Treatment With Caelyx (Study P04878)(COMPLETED): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Safety and Tolerability in Patients With Metastatic Breast Cancer Receiving Treatment With Caelyx (Study P04878)(COMPLETED) (NCT00736333), a registered phase not stated study. The primary outcome is Number of Participants With Infusion Reactions (IR).

2. Clinical Question

The study title and brief description frame the work as a safety and tolerability evaluation in metastatic breast cancer. Its primary outcome is a participant count, rather than a comparison of outcomes between treatment groups. The program also lists complete response or partial response as a secondary outcome, but does not report its result in the registry record.

These questions describe what the program set out to observe, not what its results establish. Without a reported primary endpoint count, an uncertainty estimate, or a suitable comparator, the registry record does not show how often infusion reactions occurred relative to another treatment or to an untreated group. The record also does not provide an outcome result for PPE.

3. Trial Design

The record describes an observational program of Caelyx in metastatic breast cancer, focused on prevention and treatment of PPE and infusion reactions. Pegylated liposomal doxorubicin is the listed intervention, and the arm description identifies subjects with metastatic breast cancer. The record does not describe a randomized treatment assignment. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison.

Enrollment is reported as 167. The study is marked completed. Its recorded start is 2006-11, and its primary completion is 2010-06. These dates and enrollment describe the registered study; they do not establish how many participants contributed data to each outcome. The primary endpoint uses the safety population, defined as participants who received at least one dose of study medication. The registry record does not report the primary endpoint’s participant count.

The primary outcome is the number of participants with infusion reactions, assessed from Day 1 up to Week 24. The record also lists complete response or partial response as a secondary outcome and identifies six outcome measures in total. It does not give results for the secondary outcome in the information recorded. Nor does it describe the full schedule of visits, treatment administration, follow-up procedures, or eligibility criteria; those details are not reported in the registry record.

The observational framing matters for interpretation. Without a stated allocation process or a suitable control group, differences between any listed groups cannot be treated as evidence of a causal treatment effect. Observational findings can describe what was recorded among participants, but comparisons may reflect differences in who received which care or how events were documented. The registry record does not provide enough detail to assess those possibilities. It also does not report a sample-size justification or a statistical analysis plan.

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 (those who received at least one dose of study medication)

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Infusion Reactions (IR), measured over Day 1 up to Week 24.

The primary endpoint is the number of participants with infusion reactions in the safety population, from Day 1 up to Week 24. The safety population is defined as those who received at least one dose of study medication. An infusion reaction is defined in the record as an allergic or anaphylactoid reaction characterized by shortness of breath, hypotension, back pain, chest pain, chills, flush, sweating, fever, nausea, dizziness, rash, pruritis, or tachycardia.

As a general statistical concept, a participant-count endpoint records whether each person experienced the event during the specified observation period. It is useful for describing the frequency of a defined safety event in the population being assessed. The event definition matters: a broad list of symptoms can group together presentations that may differ in nature or severity. The registry record supplies the definition but does not report the primary endpoint count, event rate, severity breakdown, or uncertainty around the result.

The endpoint does not by itself show whether a treatment caused an event. That interpretation depends on study design, comparisons, and how completely events were captured. The observational program has no stated allocation method and no identified like-for-like control comparison. The registry record also does not report an endpoint result for PPE, despite naming PPE as a focus of the program. Thus, the registered endpoint establishes what was to be counted, not the frequency or comparative risk of infusion reactions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in this record is limited. It names a participant-count primary endpoint and defines the population and observation window, but provides no primary outcome count or analysis. The concepts below explain how such data are generally interpreted; they are not claims about analyses performed in this program.

What does a participant count represent?

For a binary event outcome, each participant is classified according to whether the event occurred during the specified period. The count of participants with the event describes the observed number, while the number at risk describes the population used as its denominator. A rate or proportion requires both quantities and a clear definition of the analysis population. Here, the primary endpoint title gives the event count as its measure, and the safety population is defined as participants who received at least one dose. The primary event count and its denominator are not reported in the registry record.

Binary outcomes can be summarized with a proportion and an uncertainty interval. In general, a confidence interval describes the range of values compatible with the observed data under the method’s assumptions; it is not a guarantee that the true value lies in that range. With few events, estimates can be imprecise, and the choice of interval method can matter. No primary endpoint estimate or interval is reported in the registry record, so these properties cannot be assessed for the infusion-reaction outcome.

Why does the event definition matter?

The registry defines an infusion reaction as an allergic or anaphylactoid reaction characterized by a listed set of symptoms. A prespecified, consistent definition helps determine which observations count as events. A definition that includes varied symptoms can encompass events with different presentations. General statistical interpretation therefore depends not only on a count, but also on consistent event identification, adequate follow-up, and clarity about how events were classified. The registry record does not report event-level details, adjudication procedures, or symptom-specific results for the primary outcome.

What can an observational design establish?

In general, an observational study records care or outcomes without a stated randomized assignment. It can describe events among the participants observed, but comparisons between groups may be affected by differences in participant characteristics, treatment selection, follow-up, or event detection. Random assignment is one way to balance measured and unmeasured factors on average, but the registry record does not identify such an assignment. It explicitly warns that the arms are not a like-for-like control comparison. A causal contrast should not be inferred from the registered information.

Even a clear difference in observed event counts would need interpretation in relation to group sizes, follow-up duration, and baseline differences. Raw counts alone can mislead if the groups have different denominators or observation time. The registry record does not describe a comparative primary analysis, and the primary endpoint result is absent. Thus, no comparison can be reconstructed from the recorded details.

How should uncertainty and testing be understood?

General inferential methods use estimates and uncertainty measures to distinguish a potentially meaningful pattern from variation expected from sampling. A confidence interval conveys precision, while a p-value, when used, addresses compatibility with a specified null hypothesis under model assumptions. Neither measure on its own establishes causality, clinical importance, or freedom from bias. The registry record reports no primary endpoint confidence interval, p-value, or analysis.

The record identifies six outcome measures. When several outcomes are tested, the chance of at least one apparently unusual result can increase if each is assessed separately without accounting for multiplicity. General approaches include prespecifying a primary outcome, adjusting for multiple tests, or interpreting secondary results as exploratory. The registry record does not report how multiplicity was handled or a statistical analysis plan. It lists complete response or partial response as a secondary outcome but gives no result for it.

What do the sample-size illustrations mean?

The accompanying planning assumptions describe an illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. This is a planning exercise, not the program’s design description. It should not be read as observed power or as evidence that the study was planned with those assumptions. The registry record does not report the protocol’s sample-size justification, and the effect estimate used for the illustration is not reported in the registry record.

In general, a planning calculation asks how many participants would be needed under chosen assumptions to detect a specified effect with a chosen probability. Its answer depends on the assumed effect, variability or event frequency, allocation, test, and target power. If the assumed effect is based on an observed estimate, that estimate may itself be uncertain. Such a calculation cannot repair the lack of a reported primary result, establish the study’s original intent, or demonstrate that the observed study had adequate power.

Finally, the presence of an adverse-event denominator does not fill in the primary endpoint analysis. The adverse-event summary lists 160 at risk, while the primary endpoint is defined for the safety population; the record does not state that these are identical analysis sets. Outcome-specific denominators, missing-data handling, and the completeness of follow-up are not reported in the registry record. Any interpretation beyond the specific descriptive entries would require information not recorded.

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("Pegylated Liposomal Doxorubicin")
n      <- c(160)
events <- c(7)
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  Pegylated Liposomal Doxorubicin  160  7  4.4  1.8  8.8  2.1  8.8  2.2  8.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures and identifies infusion reactions as the primary outcome. Complete response or partial response is listed as a secondary outcome. It does not report results for that secondary outcome, and it records no analyses. A multiplicity strategy—such as adjustment of statistical tests or a hierarchy for interpreting outcomes—is not reported in the registry record.

As a general statistical matter, examining multiple outcomes can increase the likelihood of an apparently notable result arising by chance when each is tested separately. Prespecifying a primary outcome can help focus interpretation, but it does not remove the need to understand how other outcomes were selected and analyzed. Since no analyses or analysis plan are recorded, it is not possible to determine whether multiplicity was addressed or how secondary findings were intended to be interpreted.

Missing-data methods are also not reported in the registry record. The record defines the primary endpoint population as participants who received at least one dose, but it does not state how missing outcome assessments, incomplete follow-up, or participants without an evaluable result were handled. The enrollment figure and the denominator in the adverse-event summary do not establish the primary outcome’s denominator or completeness.

In general, missingness can affect a safety estimate if participants with unavailable assessments differ from those with recorded outcomes. The direction and size of any effect depend on why information is missing and what assumptions are used. Without outcome-specific denominators, missing-data procedures, and the primary result, the extent of this concern cannot be quantified for this program.

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: general physical health deterioration (1.2%), leukopenia (0.6%), bone pain (0.6%), urticaria (0.6%).

The adverse-event summary for pegylated liposomal doxorubicin lists 160 participants at risk, 5 with serious adverse events, and 9 with other adverse events. The record also lists serious adverse-event terms with percentages: general physical health deterioration (1.2%), leukopenia (0.6%), bone pain (0.6%), and urticaria (0.6%). These are descriptive entries; the registry does not provide further detail about event timing, duration, severity beyond the serious-event classification, or attribution.

The serious and other adverse-event counts should not be mistaken for the primary infusion-reaction count. The registry record does not identify either count as the primary endpoint result. Nor does it explain whether a participant could appear in both categories or whether serious-event terms overlap. The percentages attached to the listed terms should be read as recorded, without inferring additional counts or a denominator not explicitly stated alongside each term.

Deaths are not reported in the registry record. The adverse-event entries alone do not establish that the treatment caused an event, and the observational program does not provide a like-for-like control comparison. They describe selected safety information in the recorded group, not a comparative estimate of harm.

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

The registry record shows that an observational program was registered to evaluate the safety and tolerability of Caelyx in metastatic breast cancer, with a particular focus on infusion reactions and PPE. It defines the primary endpoint as the number of participants with infusion reactions during Day 1 up to Week 24, among those who received at least one dose. It also records adverse-event counts and selected serious-event terms.

The record does not report the primary endpoint count, an estimate of its frequency, or an uncertainty interval. It therefore does not establish how common infusion reactions were in the safety population or how precisely their frequency was estimated. The record lists complete response or partial response as a secondary outcome, but its result is not reported. PPE is described as a program focus, but a PPE outcome result is not reported in the registry record.

These omissions also limit what can be said about treatment effects. The program is observational, allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. The registered information does not support a causal claim or a reliable comparison with another treatment. The adverse-event figures are descriptive and do not substitute for the missing primary endpoint result.

In general, a safety study can contribute useful information by defining events and recording their occurrence in a treated population. The strength of that information depends on clear outcome ascertainment, complete follow-up, a well-described analysis population, and, for comparative claims, an appropriate comparison design. The registry record supplies the endpoint definition and population description, but does not report several of these details. Its entries should therefore be read as a limited account of the registered question and selected safety data, not as a complete evaluation of risk or benefit.

14. Why This Trial Matters Statistically

This program raises an important statistical distinction: defining an outcome is not the same as reporting its result. The registry specifies an infusion-reaction endpoint, its observation period, and the safety population, which helps readers understand what the primary question concerned. Yet the participant count for that endpoint is not reported. Without that result, readers cannot estimate the event frequency or judge its precision.

The record also illustrates why a denominator must be tied to a clearly defined population. Enrollment is reported as 167, while the adverse-event summary gives 160 participants at risk. The primary endpoint population is defined by receipt of at least one dose. The record does not explain how these populations relate, so the enrollment figure cannot be used as the primary endpoint denominator. This is a general issue in clinical reporting: counts are meaningful only when their analysis populations and follow-up are clear.

The observational design description also matters. Without a stated allocation method and a like-for-like control comparison, observed events can describe the participants recorded but cannot, by themselves, isolate a treatment effect. This distinction is central to interpreting safety findings, especially when a registry record presents adverse-event counts without a comparative analysis.

Finally, the record lists several outcomes but no analyses. That makes it impossible to evaluate uncertainty, multiplicity handling, or missing-data methods. The statistical lesson is not that the recorded adverse events are uninformative; it is that descriptive entries answer narrower questions than a complete comparative analysis. Clear endpoint reporting, denominators, follow-up, and analysis methods are needed to judge how much a safety result can support.

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 is that the registry record does not report the primary endpoint result. Although it defines infusion reactions and specifies the safety population and observation window, it gives no participant count, estimate, or interval for that outcome. The record also does not report the PPE outcome result, despite naming PPE as a focus.

The observational design limits causal interpretation. Allocation is not stated, and the record explicitly warns that the arms are not a like-for-like control comparison. No comparative estimate is reported. The registry information therefore cannot establish whether an observed event was caused by treatment or how outcomes compare across equivalent groups.

Important details for interpreting the data are absent. The registry record does not report outcome-specific denominators, completeness of follow-up, missing-data handling, event adjudication procedures, treatment dosing, or a statistical analysis plan. It does not give the protocol’s sample-size justification or describe interim analyses. The record lists six outcome measures and no analyses, leaving multiplicity handling and the analysis of secondary outcomes unclear.

The adverse-event summary has a denominator of 160 at risk, but the record does not explain its relationship to the enrollment figure of 167 or to the primary endpoint population. It also does not state whether serious and other adverse-event categories overlap, or whether the serious-event terms overlap. Deaths are not reported in the registry record. These limitations prevent a fuller assessment of the completeness and scope of the reported safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate Safety and Tolerability in Patients With Metastatic Breast Cancer Receiving Treatment With Caelyx (Study P04878)(COMPLETED) — NCT00736333.
• Registry record last updated 2014-11-05; status last verified 2014-10.
• Results first posted 2011-07-07.
• 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

NCT00736333 is an observational program of Caelyx, identified as pegylated liposomal doxorubicin, in metastatic breast cancer. The record lists enrollment of 167, marks the study completed, and gives 2006-11 as the start and 2010-06 as primary completion. Its stated focus is safety and tolerability, especially infusion reactions and PPE.

The primary endpoint is the number of participants with infusion reactions from Day 1 up to Week 24 in the safety population, defined as those who received at least one dose. The primary endpoint result is not reported in the registry record. The record lists complete response or partial response as a secondary outcome, but does not report its result. It records 6 outcome measures and 0 analyses.

The adverse-event summary lists 160 at risk, 5 with serious adverse events, and 9 with other adverse events. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. A sample-size justification, statistical analysis plan, and missing-data methods are not reported in the registry record.