Aromasin® As Adjuvant Treatment In Postmenopausal Women With Invasive, Estrogen Receptor Positive Early Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aromasin® As Adjuvant Treatment In Postmenopausal Women With Invasive, Estrogen Receptor Positive Early Breast Cancer (NCT01239745), a registered phase not stated study. The primary outcome is Number of Participants With Adverse Events (AEs).

2. Clinical Question

The study’s stated aims also included describing safety, tolerability, use in routine clinical practice, adherence, and reasons for early discontinuation. The listed secondary outcomes include concomitant morbidities and medications, discontinuation, time to discontinuation, recurrence-free survival, and overall survival. These aims do not make the study a randomized test of Aromasin against another treatment: allocation is not stated, and no control comparison is reported. The registry record lists 46 enrolled participants, but enrollment alone does not establish how many received treatment or contributed data to each outcome. The primary outcome’s safety analysis set has its own stated eligibility definition: receipt of at least one dose during the observation period.

The central statistical question is therefore descriptive: what adverse-event counts are recorded for the listed group, and what limits apply to interpreting those counts? The registry does not report comparative estimates for efficacy or safety. It also does not report outcome analyses for recurrence-free survival, overall survival, adherence, or discontinuation. Their presence among the outcomes describes what the study intended to assess, not what results are available in the registry record.

3. Trial Design

This is described as a non-interventional study of Aromasin as adjuvant treatment in postmenopausal women with invasive, estrogen receptor positive early breast cancer. Participants were to be disease-free after 2 to 3 years of initial adjuvant tamoxifen therapy. The brief summary describes treatment in routine clinical practice across several Eastern European countries and continuation with Aromasin until completion of 5 years of adjuvant hormonal therapy. These are descriptions of the study’s aims and intended setting; the registry does not provide details establishing how treatment decisions were made in practice.

The registry lists Pfizer as sponsor, an enrollment of 46, a start date of 2011-04, and a primary completion date of 2011-10. The status is TERMINATED. The reason for termination is not reported in the registry record. Although Aromasin is the listed intervention, the arm description is blank. Allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. The record therefore does not support interpreting the listed adverse-event counts as a randomized comparison between treatment groups.

The primary outcome is the number of participants with adverse events, with a timeframe from baseline up to Month 36. The safety analysis set is defined as participants who received at least one dose of study medication during the observation period. The outcome description specifies treatment-emergent events, investigator assessment of relatedness, and counting participants once within a category despite multiple occurrences of an event in that category.

The registry lists secondary outcomes concerning concomitant morbidities, concomitant medications, study-medication discontinuation and its reasons, time to discontinuation, recurrence-free survival, and overall survival. The methods for collecting or analysing these outcomes are not reported in the registry record. The record lists no analyses. It also does not report randomization, masking, a comparator protocol, a sample-size justification, interim analyses, or a detailed statistical plan. Those omissions limit how far the study design can be reconstructed from the registry information.

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 analysis set included participants who received at least one dose of the study medication during the observation period.

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 Adverse Events (AEs), measured over Baseline up to Month 36.

The primary outcome counts participants who experienced treatment-emergent adverse events. An event qualifies under the registry definition if it is newly occurring or worsens after the first dose. The timeframe is baseline up to Month 36. Relatedness to study drug was assessed by the investigator as Yes or No, and a participant with multiple occurrences of an adverse event within a category was counted once in that category.

This participant-count approach is useful for describing how many people experienced an event, rather than how many separate episodes occurred. It can make a safety summary easier to interpret when events recur, but it does not convey the number, duration, intensity, or clinical consequences of every episode. Nor does a count by itself establish that treatment caused an event. The registry’s description says investigators assessed relatedness; it does not provide a causal comparison against an untreated or alternative-treatment group.

The posted primary outcome is a count, not a time-to-event estimate or a comparative effect estimate. Its interpretation depends on who entered the safety analysis set, the period during which events were observed, and the completeness of event recording. The registry specifies the safety-set definition and the observation timeframe, but details about missing observations, follow-up completeness, and event ascertainment are not reported in the registry record. The count should therefore be read as a descriptive safety result within the listed study, not as a measure of comparative risk or evidence of treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The principal outcome is a binary event count at the participant level: each participant either had a qualifying event in a category or did not. The reported quantity is the number of participants with an event, rather than a mean, median, or rate. For this outcome, the registry says that multiple occurrences within the same category count once for a participant. This rule prevents repeated episodes in one category from inflating the participant count, but it also means the result does not describe how often each event recurred.

What does a participant count represent?

As a general statistical explanation, a participant count answers how many people met an outcome definition within an observed group. A proportion can sometimes help compare groups of different sizes, but the record’s posted outcome is expressed as counts and the explanatory details do not include a reported proportion. No new proportion should be inferred from the count. Counts also depend on the definition of an event, the period of observation, and which participants were included. Here, an event is treatment-emergent if newly occurring or worsening after the first dose, and the listed timeframe is baseline up to Month 36.

The safety analysis set is defined by receipt of at least one dose during the observation period. This is an analysis-population rule, not a statement that all enrolled participants necessarily received treatment or completed the same follow-up. The registry does not report the number excluded from the safety set, the extent of follow-up for each participant, or how incomplete event records were handled. Those details matter because an event count is interpretable only in relation to the population and observation process that generated it.

How should uncertainty be understood?

As a general statistical explanation, an observed count is an estimate based on the study’s recorded experience, not a guarantee of the event frequency in other populations or settings. Confidence intervals are commonly used to express uncertainty around an estimate. Their width depends on factors such as the amount of information and the statistical method. The registry record does not report confidence intervals for the adverse-event counts, so their precision cannot be described with an interval based on the record. A zero observed count is not the same as proof that the underlying event risk is zero; it means no participants were recorded with that event category in the posted observation.

Some statistical analyses model event counts using assumptions about how variable observations are. As a general point, over-dispersion occurs when the observed variability is greater than a model assumes; ignoring it can make uncertainty estimates too narrow. That issue is relevant when modelling counts of episodes or rates, but the primary outcome is the number of participants with an event, with repeat occurrences within a category counted once. The registry does not report a model for this endpoint, so it is not possible to say whether over-dispersion was assessed or whether a particular count model was used.

What can an unadjusted or comparative analysis establish?

A comparison between treatments requires interpretable groups and an analysis that accounts for how people entered those groups. The registry describes a non-interventional study, does not state allocation, and cautions that the arms are not a like-for-like control comparison. Thus, no randomized treatment contrast is available in the record. Differences between groups, if displayed elsewhere in statistical results, would not automatically be attributable to treatment; confounding and selection can affect observational comparisons. The registry lists no analyses, and no adjusted or unadjusted comparative estimates are reported in the record.

Statistical significance and clinical importance are also different ideas. A p-value, as a general concept, measures how compatible data are with a specified null model under stated assumptions; it does not measure the size or importance of an effect, nor does it establish causality. No p-value for a treatment comparison is reported in the registry record. There is therefore no basis for describing a comparative result as statistically significant or not significant.

What do planning calculations mean?

Sample-size calculations are planning tools: under stated assumptions, they illustrate how much information a future study might need to detect a specified effect. They are not observed findings and are not evidence that a study achieved a particular level of power. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These assumptions are explicitly planning illustrations, not the trial’s own design. The registry does not report a sample-size justification for this study. Any planning illustration should therefore be kept separate from the observed adverse-event counts and should not be interpreted as observed power or as a reconstruction of the study’s analysis plan.

In short, the methods that can be described from the record are the participant-level event definition, the once-per-category counting rule, the safety-set definition, and the stated timeframe. The record does not report inferential methods, model specification, adjustment variables, uncertainty intervals, missing-data procedures, or multiplicity handling. General statistical concepts can clarify what such methods would mean, but they cannot fill in undocumented choices for this study.

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("Exemestane")
n      <- c(46)
events <- c(2)
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  Exemestane  46  2  4.3  0.5  14.8  1.2  14.5  1.3  14.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes in addition to the primary adverse-event outcome. They concern concomitant morbidities and medications, medication discontinuation and its reasons, time to discontinuation, recurrence-free survival, and overall survival. When a study evaluates multiple outcomes, the chance of at least one apparently unusual result can increase if many statistical tests are performed. As a general statistical principle, multiplicity procedures can control or describe that issue, but the appropriate approach depends on the prespecified questions and analysis plan. A multiplicity strategy is not reported in the registry record.

The record lists no analyses. It therefore does not report outcome-specific estimates, tests, confidence intervals, or adjustment for multiple comparisons. The presence of outcomes in the registry is not evidence that their results were analysed or that a particular hierarchy was used. No conclusions about the secondary outcomes can be drawn from the posted adverse-event counts.

Missing-data methods are also not reported in the registry record. The available description does not say how missing event reports, incomplete follow-up, or unavailable outcome measurements were handled. That matters because missing observations can affect both the numerator and the population understood to be at risk. The stated safety analysis set includes participants who received at least one dose during the observation period, but this definition does not specify how incomplete observations within that set were treated.

The registry’s primary outcome definition identifies the event period as baseline up to Month 36, yet the record does not report how consistently participants were observed across that period. No imputation method, sensitivity analysis, or missingness assumption is described. These omissions prevent assessment of whether the posted counts are robust to incomplete outcome information.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted adverse-event figures list 0 participants with serious adverse events among 46 at risk, and 2 participants with events in the other adverse-event category among 46 at risk. These are participant counts, consistent with the registry’s rule that multiple occurrences within a category count once for a participant. The serious adverse-event list contains no top serious terms.

These counts describe what was recorded in the listed group; they do not establish that the study medication caused an event or that no unrecorded event occurred. The registry describes investigator assessment of relatedness as Yes or No, but the posted figures do not include a breakdown by relatedness. Nor do the counts provide detail on event type, severity within the other category, duration, or clinical consequence.

The at-risk entries should be read alongside the stated safety-set definition: participants had to receive at least one dose during the observation period. The record does not report how much follow-up each participant contributed or how missing safety information was handled. Accordingly, the counts are descriptive and should not be treated as a comparative risk estimate or as proof that serious events cannot occur.

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

The posted results show a descriptive safety summary for the listed Exemestane group: 0 participants with serious adverse events among 46 at risk, and 2 participants with events in the other adverse-event category among 46 at risk. The outcome counts participants, not every episode, and applies the registry’s definition of treatment-emergent events. These observations provide a record of what was counted within the specified study context.

They do not show whether Aromasin is safer or less safe than another treatment, because no like-for-like control comparison is reported and allocation is not stated. They do not prove that the medication caused an event, since an event following treatment is not by itself evidence of causation. They also do not establish that a serious event is impossible: a count of zero is an observation in this record, not a claim that the underlying risk is absent.

The figures do not answer the study’s other stated questions about adherence, discontinuation, recurrence-free survival, or overall survival. Those outcomes are listed, but their results and analyses are not reported in the registry record. The status TERMINATED does not explain why the study ended, and the registry does not report a reason for termination.

More broadly, interpretation is constrained by missing information about follow-up completeness, missing-data handling, statistical analysis, and uncertainty intervals. The record’s enrollment figure does not, on its own, establish complete outcome ascertainment for every enrolled participant. The results should therefore be understood as limited descriptive counts, not as a comparative estimate, an efficacy finding, or a basis for causal conclusions.

14. Why This Trial Matters Statistically

This study illustrates a distinction that is central to clinical biostatistics: recording an outcome and estimating a treatment effect are different tasks. A count of participants with adverse events can describe observed safety experience. Without a like-for-like comparison and a reported analysis, it cannot establish how that experience differs from what would have occurred under another treatment or under no treatment.

The record also shows why outcome definitions matter. Treatment-emergent events are defined by timing relative to the first dose, relatedness is assessed by the investigator, and repeat occurrences within a category do not increase the participant count. Those choices determine what the count means. They also define what it leaves out: the participant count does not summarize episode frequency or provide detailed information about event duration and consequences.

Another statistical lesson is that enrollment, analysis population, and follow-up are not interchangeable. The registry lists 46 enrolled participants and separately defines the safety analysis set by receipt of at least one dose. It does not report complete follow-up or missing-data procedures. Readers need those details to judge how well an observed count reflects the intended population and observation period.

Finally, a study’s aims and its reported results must be kept distinct. The registry lists outcomes related to adherence, discontinuation, recurrence-free survival, and overall survival, but does not report their analyses. Outcomes being named in a registry does not mean that estimates are available or that hypotheses were tested. In this record, the strongest interpretation stays close to the descriptive safety counts and acknowledges the limits created by absent comparative analyses, uncertainty estimates, and methodological detail.

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 registry record identifies the study as non-interventional, does not state allocation, and cautions that the arms are not a like-for-like control comparison. This limits causal interpretation and prevents a treatment-versus-control conclusion from the posted counts. The arm description is blank, and no comparator protocol is reported.

The study status is TERMINATED, but the reason is not reported in the registry record. The record lists enrollment as 46, but does not explain how many participants contributed to each outcome beyond the at-risk entries for the adverse-event categories. The safety-set definition requires at least one dose during the observation period; the record does not report details of treatment exposure, adherence, or participant-level follow-up.

The primary outcome covers baseline up to Month 36, but the record does not describe event ascertainment procedures, missing-data handling, or completeness of follow-up. It also does not report confidence intervals or a statistical analysis plan. The listed secondary outcomes include discontinuation and survival outcomes, but their results and analyses are absent from the registry record.

The study’s stated routine-practice setting across several Eastern European countries may be relevant to how its intended context differs from a controlled comparison, but the registry does not provide enough detail about participating sites or practice patterns to assess generalizability. The enrollment figure and descriptive counts alone cannot establish how representative the recorded participants were. These limitations make the posted safety figures informative as a narrow description, while leaving uncertainty about precision, completeness, and applicability.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Aromasin® As Adjuvant Treatment In Postmenopausal Women With Invasive, Estrogen Receptor Positive Early Breast Cancer — NCT01239745.
• Registry record last updated 2012-10-31; status last verified 2012-10.
• Results first posted 2012-10-31.
• 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

The registry record identifies a non-interventional study of Aromasin as adjuvant treatment for postmenopausal women with invasive, estrogen receptor positive early breast cancer who were disease-free after 2 to 3 years of initial tamoxifen. It lists Pfizer as sponsor, an enrollment of 46, a start date of 2011-04, a primary completion date of 2011-10, and status TERMINATED.

The primary outcome counts participants with treatment-emergent adverse events from baseline up to Month 36. The posted safety figures list 0 participants with serious adverse events among 46 at risk and 2 with events in the other category among 46 at risk. The registry lists secondary outcomes concerning concomitant conditions and medications, discontinuation, recurrence-free survival, and overall survival, but their analyses are not reported. Allocation, a like-for-like control comparison, missing-data methods, and a detailed statistical plan are not reported in the registry record.