This page separates reported trial results from statistical interpretation. Numerical trial results on this page are restricted to the information reported in the ClinicalTrials.gov record.
1. Trial at a Glance
FACE was a randomized, parallel-group, phase 3 trial comparing letrozole with anastrozole in the adjuvant treatment of postmenopausal women with hormone receptor and node positive breast cancer. The registered primary endpoint was disease-free survival over a time frame of 84 months.
| Feature | FACE |
|---|---|
| Trial name | FACE |
| Brief title | Comparison Trial of Letrozole to Anastrozole in the Adjuvant Treatment of Postmenopausal Women With Hormone Receptor and Node Positive Breast Cancer |
| Phase | Phase 3 |
| Condition | Breast Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 4172 |
| Interventions | Letrozole; Anastrozole |
| Primary endpoint | Disease Free Survival |
| Primary endpoint type | Time-to-event |
| Hypothesis type | Superiority |
| Reported statistical method | Log-rank test |
| Results posted | Yes |
| ClinicalTrials.gov | NCT00248170 |
2. Clinical Question
The FACE trial addressed whether letrozole and anastrozole differed with respect to disease-free survival when used in the adjuvant treatment of postmenopausal women with hormone receptor and node positive breast cancer.
Population
Postmenopausal women with hormone receptor and node positive breast cancer.
Intervention
Letrozole.
Comparator
Anastrozole.
Primary question
Under a superiority framework, does disease-free survival differ between letrozole and anastrozole over the registered 84-month time frame?
3. Trial Design
Letrozole
- Letrozole
- Adjuvant treatment setting
- Primary comparison: disease-free survival
Anastrozole
- Anastrozole
- Adjuvant treatment setting
- Primary comparison: disease-free survival
The registry describes the allocation as randomized, the design model as parallel, and masking as none. This means the statistical comparison is based on randomized assignment to two parallel intervention groups, without masking reported in the registry.
| Design feature | Registry information |
|---|---|
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Arms | 2 |
| Enrollment | 4172 |
| Study start | December 2005 |
| Primary completion | September 2014 |
| Status | Completed |
| Lead sponsor | Novartis Pharmaceuticals |
| Sponsor type | Industry |
4. Endpoints
The registry lists one primary endpoint and classifies it as a time-to-event outcome. The registered time frame is 84 months.
| Endpoint | Registry definition | Time frame | Type |
|---|---|---|---|
| Disease Free Survival | Disease-free survival was defined as the time from the date of randomization to the date of the first documentation of re-occurrence of invasive breast cancer in local, regional or distant sites, new invasive breast cancer in the contra-lateral breast, or death from any cause. | 84 months | Time-to-event |
What makes disease-free survival a time-to-event endpoint?
The endpoint records when the first qualifying event occurs rather than simply whether an event occurred. Participants who have not experienced a qualifying event by the end of their observed follow-up may contribute censored survival information. This is why survival-analysis methods are appropriate for the endpoint.
5. Statistical Methodology
Primary analysis: log-rank test
The registry reports a log-rank test as the statistical method for the primary disease-free survival analysis. The analysis compares the observed pattern of event timing between the letrozole and anastrozole groups across the follow-up period.
Under a superiority hypothesis, the analysis asks whether the observed time-to-event experience differs between the randomized treatment groups.
Intention-to-treat analysis
The posted analysis identifies its analysis population as Intent-to-treat (ITT). The registry specifies that the ITT population contained randomized participants who had no protocol deviations. For this trial, the reported primary statistical analysis therefore uses the registry-defined ITT population rather than defining the analysis according to treatment received.
Superiority hypothesis
The registry classifies the hypothesis type as Superiority. This distinguishes the statistical question from a non-inferiority framework: the analysis was intended to evaluate whether the disease-free survival distributions differed between letrozole and anastrozole, rather than whether one treatment was no worse than another by a prespecified margin.
No estimate or confidence interval posted in the ClinicalTrials.gov record
The statistical analysis record posted on ClinicalTrials.gov for the primary endpoint reports the method, analysis population, groups compared, hypothesis type, and p-value of 0.3150. It does not provide a hazard ratio, confidence interval, median disease-free survival, event counts, or Kaplan-Meier estimates.
6. Primary Results: Disease-Free Survival
ClinicalTrials.gov reports a formal statistical analysis for the registered primary endpoint, Disease Free Survival, at 84 months. The analysis compares letrozole with anastrozole using a log-rank test in the registry-defined ITT population.
Primary log-rank comparison
Method: Log Rank · Hypothesis: Superiority
Analysis population: Intent-to-treat (ITT) — randomized participants who had no protocol deviations.
| Primary endpoint | Time frame | Groups compared | Method | P-value |
|---|---|---|---|---|
| Disease Free Survival | 84 months | Letrozole vs Anastrozole | Log-rank test | 0.3150 |
The reported p-value of 0.3150 is the probability, under the statistical null hypothesis used for the log-rank comparison, of observing a difference in the time-to-event data at least as incompatible with that null as the one observed, according to the test framework.
The p-value is not an estimate of treatment effect. It does not say that letrozole has a particular percentage increase or decrease in disease-free survival, and it does not give the probability that either treatment is effective or ineffective.
The registry analysis does not report a hazard ratio or confidence interval. Consequently, the precision and magnitude of the treatment difference cannot be quantified from the posted statistical-analysis record alone.
For a time-to-event endpoint, the log-rank test compares the survival experience over follow-up. It does not by itself describe the size of the difference, the absolute probability of remaining event-free at a particular time, or the median event-free time.
7. How to Interpret the P-value
The FACE primary analysis illustrates an important distinction between statistical evidence against a null hypothesis and the size of a treatment effect.
What 0.3150 tells us
The reported log-rank test produced a p-value of 0.3150 under the registered superiority framework.
What 0.3150 does not tell us
It does not quantify the treatment effect, provide an effect-size estimate, or establish the probability that one treatment is better.
What is missing for effect size
The ClinicalTrials.gov record does not report a hazard ratio, confidence interval, median disease-free survival, or treatment-specific event count.
Why the endpoint still matters
Disease-free survival incorporates the timing of qualifying events and therefore requires time-to-event methods rather than a simple comparison of event proportions.
8. Statistical Methods Explained
Why was a log-rank test used?
Disease-free survival is a time-to-event endpoint. Participants can experience a qualifying event at different times, while others may be censored before an event is observed. A log-rank test is designed to compare the survival distributions of two groups while incorporating the timing of observed events and the risk set at each event time.
What does the log-rank test actually compare?
At each observed event time, the log-rank framework compares the number of events observed in each group with the number that would be expected under the null hypothesis of equal survival experience. These contributions are combined over follow-up to produce the test statistic and p-value.
Why is the analysis population important?
The registry identifies the primary analysis population as ITT and specifically describes it as randomized participants who had no protocol deviations. Defining the population matters because excluding participants can change the composition of the comparison and therefore the interpretation of the resulting test.
What is the difference between a p-value and a hazard ratio?
A p-value addresses evidence against a statistical null hypothesis. A hazard ratio is an effect-size measure that describes the relative event hazard under a specified survival model. The registry-reported FACE statistical analysis reports the former but not the latter.
Why would Kaplan-Meier estimation normally accompany a log-rank test?
A log-rank test provides a formal comparison, whereas Kaplan-Meier estimation provides a descriptive picture of disease-free survival over time. A Kaplan-Meier curve can show when events accumulate, where censoring occurs, and how the two groups' estimated survival functions evolve. The ClinicalTrials.gov record does not provide enough information to reproduce such a curve.
Why does censoring matter?
In time-to-event analysis, a participant may reach the end of observed follow-up without a qualifying event or may leave observation before an event is documented. Such a participant can still contribute information up to the censoring time. Correct handling of censoring is therefore central to the interpretation of a disease-free survival analysis.
What does a superiority hypothesis mean here?
The registered hypothesis type is superiority. Conceptually, the analysis is asking whether disease-free survival differs between letrozole and anastrozole. This is different from a non-inferiority design, where the principal question would be whether the new treatment is not unacceptably worse than a comparator by a prespecified margin.
9. Randomization and Causal Interpretation
Randomization is a central statistical feature of FACE. When participants are randomly allocated to treatment groups, treatment assignment is intended to be independent of measured and unmeasured baseline characteristics, apart from chance imbalance. This provides the foundation for interpreting between-group differences as treatment comparisons within the trial population.
The statistical analysis then compares disease-free survival according to randomized treatment assignment using the registry-specified analysis population and log-rank method.
The registry does not report stratification factors in the ClinicalTrials.gov record. It therefore would not be appropriate to add specific stratification variables or claim that the log-rank analysis was stratified.
10. Safety
The ClinicalTrials.gov record reports serious adverse events by treatment arm as affected participants divided by the corresponding at-risk denominator.
| Safety measure | Letrozole | Anastrozole |
|---|---|---|
| Serious adverse events | 486/2049 | 520/2062 |
The serious-adverse-event denominators shown above should not be treated as the overall randomized enrollment counts without additional evidence. The trial enrollment was 4172, whereas the registry's serious-adverse-event field gives separate at-risk denominators of 2049 and 2062.
11. What the Registry Does and Does Not Report
The ClinicalTrials.gov record contains a formal primary statistical analysis but only a limited set of numerical results. Maintaining that boundary is important when interpreting registry-based evidence.
| Information | Reported in the ClinicalTrials.gov record? | Interpretation |
|---|---|---|
| Primary endpoint | Yes | Disease Free Survival |
| Primary endpoint time frame | Yes | 84 months |
| Primary analysis method | Yes | Log-rank test |
| Analysis population | Yes | Registry-defined ITT |
| Hypothesis type | Yes | Superiority |
| Primary p-value | Yes | 0.3150 |
| Hazard ratio | No | Not reported in registry-reported statistical analysis |
| Confidence interval | No | Not reported in registry-reported statistical analysis |
| Median disease-free survival | No | Not reported in the ClinicalTrials.gov record |
| Event counts for primary endpoint | No | Not reported in the ClinicalTrials.gov record |
| Kaplan-Meier estimates | No | Not reported in the ClinicalTrials.gov record |
| Subgroup analyses | No | Not reported in the ClinicalTrials.gov record |
| Formal safety comparison | No | Serious adverse-event counts are reported without an inferential comparison |
| Stratification factors | No | Not reported in the ClinicalTrials.gov record |
| Interim analysis | No | Not reported in the ClinicalTrials.gov record |
| Multiplicity procedure | No | Not reported in the ClinicalTrials.gov record |
| Missing-data/imputation method | No | Not reported in the ClinicalTrials.gov record |
| Bayesian methods | No | Not reported in the ClinicalTrials.gov record |
12. Statistical Analysis in Context
The FACE analysis is a straightforward example of a randomized two-group time-to-event comparison. The statistical structure can be summarized as a sequence from randomization to an event-time endpoint and then to a formal survival comparison.
This structure is statistically useful because the analysis does not discard the timing of events. A participant with an event early in follow-up and a participant with an event much later do not provide identical time-to-event information, and participants without an observed event may contribute information up to their censoring time.
13. Planned Analysis vs Reported Analysis
For FACE, a formal statistical analysis is posted for the primary endpoint, so the appropriate distinction is between what the registry explicitly reports and what would normally accompany a complete time-to-event analysis.
| Component | FACE registry record | Statistical role |
|---|---|---|
| Endpoint | Disease Free Survival at 84 months | Primary time-to-event outcome |
| Population | Intent-to-treat (ITT), defined in the registry as randomized participants with no protocol deviations | Primary efficacy analysis population |
| Comparison | Letrozole vs Anastrozole | Randomized treatment comparison |
| Method | Log Rank | Comparison of time-to-event distributions |
| Hypothesis | Superiority | Tests whether survival experience differs between groups |
| Reported result | P = 0.3150 | Evidence measure under the specified test |
| Effect estimate | Not reported | Cannot quantify relative effect from the ClinicalTrials.gov record |
| Confidence interval | Not reported | Cannot quantify precision of an effect estimate from the ClinicalTrials.gov record |
A complete survival-results presentation would ordinarily be strengthened by treatment-specific Kaplan-Meier estimates, an effect estimate such as a hazard ratio when appropriate, and a confidence interval. Those values are not present in the registry-reported FACE statistical-analysis data and are therefore not added here.
14. Limitations
- Limited numerical reporting: the ClinicalTrials.gov record reports a p-value but does not provide a hazard ratio, confidence interval, median disease-free survival, or primary-endpoint event counts.
- No Kaplan-Meier curve: the ClinicalTrials.gov record does not include the event and censoring information needed to reproduce the survival curve.
- Interpretation of the p-value: a p-value does not measure treatment-effect magnitude or clinical importance.
- No reported stratification factors: the ClinicalTrials.gov record does not identify any stratification variables, so none are assumed.
- No reported multiplicity procedure: the ClinicalTrials.gov record does not describe alpha allocation, multiple-endpoint adjustment, or interim-analysis control.
- No reported proportional-hazards model: the registry-reported statistical method is a log-rank test. A Cox model or hazard ratio should not be inferred from the registry record.
- Safety inference: serious adverse-event counts are provided, but the ClinicalTrials.gov record does not report a formal statistical comparison of safety between treatment groups.
- Generalizability: the population represented by the trial is specifically described as postmenopausal women with hormone receptor and node positive breast cancer; the ClinicalTrials.gov record does not provide additional baseline or eligibility detail for broader generalization.
15. Why This Trial Matters Statistically
FACE is a useful teaching case because it demonstrates how a randomized clinical trial can be reduced to a clear statistical question: compare two treatment groups on a time-to-event endpoint using the treatment assignment created by randomization.
| Concept | How it appears in FACE |
|---|---|
| Randomization | The trial uses randomized allocation to two treatment groups. |
| Parallel-group design | The registry identifies the design model as parallel. |
| Superiority testing | The hypothesis type is reported as superiority. |
| Time-to-event endpoint | Disease Free Survival is the primary endpoint. |
| Intention-to-treat analysis | The primary analysis uses the registry-defined ITT population. |
| Log-rank test | The registered primary statistical method is Log Rank. |
| P-value interpretation | The primary analysis reports P = 0.3150. |
| Censoring | Time-to-event methodology must account for participants whose event time is not observed during follow-up. |
| Effect-size reporting | The ClinicalTrials.gov record does not report a hazard ratio or confidence interval, illustrating why a p-value should not be treated as a substitute for effect estimation. |
| Safety analysis | Serious adverse events are reported by arm as affected/at-risk counts. |
16. A Deeper Statistical Reading of the Primary Result
The primary result is P = 0.3150 from the reported log-rank comparison. That number describes the result of a hypothesis test; it does not provide the magnitude of the difference between letrozole and anastrozole.
No confidence interval is included in the ClinicalTrials.gov record. Therefore, the uncertainty around an effect-size estimate cannot be quantified from the posted information provided for this page.
No treatment-specific disease-free survival probability, median disease-free survival, or event count is reported. Consequently, the absolute clinical separation between the two randomized groups cannot be calculated from the provided record.
The analysis concerns the timing of disease-free survival events rather than a simple binary endpoint. That distinction is why a survival-analysis method such as the log-rank test is used.
17. Trial Timeline
Trial start
The FACE trial began in December 2005 according to the ClinicalTrials.gov record.
Randomized comparison
The trial is a phase 3 randomized, parallel-group comparison of letrozole and anastrozole.
Primary endpoint time frame
Disease Free Survival is registered with an 84-month time frame.
Primary completion
The registry lists September 2014 as the primary completion date.
Trial status
The registry profile identifies the study status as completed.
18. Serious Adverse Events by Treatment Arm
The registry provides serious-adverse-event counts using an affected/at-risk format. These data are useful descriptively but should not be mistaken for a formal inferential comparison.
Letrozole
486/2049 participants are reported as affected/at risk for serious adverse events.
Anastrozole
520/2062 participants are reported as affected/at risk for serious adverse events.
The denominators in this safety field are distinct from the overall enrollment figure of 4172. Without additional registry information explaining the safety population construction, the page does not infer why those denominators differ from total enrollment.
19. Clinical Interpretation vs Statistical Interpretation
Statistical interpretation
The primary disease-free survival comparison used a log-rank test in the registry-defined ITT population and produced a p-value of 0.3150 under a superiority hypothesis.
Clinical interpretation
The ClinicalTrials.gov record does not contain enough effect-size information to quantify the absolute or relative difference in disease-free survival between letrozole and anastrozole.
This distinction is important. A statistical test can answer a prespecified hypothesis-testing question, while a clinically informative treatment comparison also benefits from estimates of effect, their uncertainty, and absolute outcome measures. Those additional numerical results are not included in the registry-reported FACE statistical-analysis record.
20. Important Interpretation Issues
- P-value versus effect size: the reported 0.3150 p-value should not be treated as an effect-size measure.
- Confidence intervals: no confidence interval is posted on ClinicalTrials.gov for the primary analysis, so precision of a treatment-effect estimate cannot be evaluated from the available record.
- Event timing: disease-free survival depends on the timing of qualifying events and therefore requires time-to-event methods.
- Censoring: survival analyses require appropriate handling of participants whose event status is not observed through the end of follow-up.
- Analysis population: the registry's specific ITT definition should be retained rather than substituted with assumptions about other analysis populations.
- No proportional-hazards claim: the ClinicalTrials.gov record reports a log-rank test but no Cox model or hazard ratio, so proportional-hazards modeling should not be attributed to this analysis.
- No multiplicity conclusion: the ClinicalTrials.gov record does not describe multiple-endpoint adjustment or alpha spending.
- No subgroup conclusion: subgroup analyses are not included in the ClinicalTrials.gov record and therefore are not interpreted here.
21. Related Tutorials
Learn more about the methods used in this trial:
22. Related Calculators
23. Sources
- ClinicalTrials.gov: FACE — NCT00248170.
Continue through Clinical Biostats
Explore related biostatistics tutorials, statistical calculators, and clinical trial analyses.
24. Record Summary
FACE is a randomized phase 3, parallel-group trial comparing letrozole with anastrozole in the adjuvant treatment of postmenopausal women with hormone receptor and node positive breast cancer. Its registered primary endpoint is Disease Free Survival over 84 months, defined from randomization to the first qualifying recurrence, new invasive contralateral breast cancer, or death from any cause.
The registry reports a formal log-rank test in its defined intention-to-treat population, with a superiority hypothesis and a reported p-value of 0.3150. The ClinicalTrials.gov record does not report a hazard ratio, confidence interval, median disease-free survival, Kaplan-Meier estimates, or primary-endpoint event counts. Those quantities therefore cannot be responsibly reconstructed or inferred from the available data.
The trial also reports serious adverse events by arm as 486/2049 for letrozole and 520/2062 for anastrozole. Because no formal inferential safety comparison is reported, these values are presented descriptively rather than converted into an additional statistical conclusion.