This page separates reported trial results from statistical interpretation. The numerical results presented here are restricted to the information contained in the ClinicalTrials.gov trial data posted on ClinicalTrials.gov for IBCSG 23-01 and its posted statistical analyses.
1. Trial at a Glance
IBCSG 23-01 was a randomized, parallel-group clinical trial evaluating axillary lymph node dissection versus no axillary lymph node dissection in women with node-negative breast cancer and sentinel lymph node micrometastases. The registered primary endpoint was 5-year disease-free survival, analyzed as a time-to-event outcome.
| Feature | IBCSG 23-01 |
|---|---|
| Trial name | IBCSG 23-01 |
| NCT ID | NCT00072293 |
| Condition | Breast Cancer |
| Population | Women with node-negative breast cancer and sentinel lymph node micrometastases |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 931 |
| Lead sponsor | ETOP IBCSG Partners Foundation |
| Status | Completed |
2. Clinical Question
The clinical question was whether women with node-negative breast cancer and sentinel lymph node micrometastases could undergo no axillary lymph node dissection rather than axillary lymph node dissection while maintaining disease-free outcomes according to the trial's prespecified time-to-event framework.
Population
Women with node-negative breast cancer and sentinel lymph node micrometastases.
Intervention
No axillary lymph node dissection.
Comparator
Axillary lymph node dissection.
Primary question
Does no axillary lymph node dissection preserve 5-year disease-free survival relative to axillary lymph node dissection under the registered non-inferiority framework?
3. Trial Design
Axillary lymph node dissection
- Axillary lymph node dissection procedure
- Comparator treatment in the randomized parallel-group design
No axillary lymph node dissection
- No axillary lymph node dissection procedure
- Intervention treatment in the randomized parallel-group design
The registry identifies the study as randomized, parallel, and unmasked. The ClinicalTrials.gov record does not provide a randomization ratio, detailed stratification factors, treatment schedules, or a treatment crossover description, so those design features are not added here.
4. Trial Timeline
Trial start
The registry lists December 2001 as the trial start.
Primary completion
The registry lists September 2012 as the primary completion date.
Results posted
ClinicalTrials.gov reports that results were posted, including three outcome measures and two statistical analyses.
5. Endpoints
| Endpoint | Registered definition | Time frame |
|---|---|---|
| 5-year Disease-Free Survival | Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to first evidence of invasive relapse at any site, second primary tumor (contralateral or non-breast) or death. | 5-year estimate reported after a median follow-up of 60 months |
| 5-year Overall Survival | Secondary time-to-event outcome reported in the posted statistical analysis. | 5-year estimate reported after a median follow-up of 60 months |
The registry identifies the primary endpoint as 5-year Disease-Free Survival and classifies it as a time-to-event endpoint. The ClinicalTrials.gov record also report 5-year Overall Survival as a secondary time-to-event endpoint.
6. Analysis Populations and Treatment Comparison
The posted primary and secondary statistical analyses both use the intention-to-treat population. This means the treatment comparison is anchored to the randomized assignment rather than redefining groups according to treatment received after randomization.
| Analysis | Population | Groups compared | Effect measure |
|---|---|---|---|
| 5-year Disease-Free Survival | Intention-to-treat | Axillary Dissection vs No Axillary Dissection | Hazard ratio |
| 5-year Overall Survival | Intention-to-treat | Axillary Dissection vs No Axillary Dissection | Hazard ratio |
7. Statistical Methodology
Primary analysis: one-sided non-inferiority test
The primary endpoint, 5-year disease-free survival, was analyzed using a 1-sided non-inferiority test in the intention-to-treat population. The posted effect measure was a hazard ratio, with an estimate of 0.78 and a two-sided 95% confidence interval of 0.55 to 1.11.
5-year Disease-Free Survival
95% CI: 0.55–1.11 · P = 0.004
Intention-to-treat analysis · 1-sided non-inferiority test
The registry analysis notes that the hazard ratio is calculated as no axillary dissection/axillary dissection. Thus, the point estimate of 0.78 corresponds to an estimated hazard approximately 22% lower in the no-dissection group under the fitted comparison.
The HR of 0.78 is a relative time-to-event measure. Because the ratio is below 1, the estimated instantaneous event hazard was lower for no axillary lymph node dissection than for axillary lymph node dissection under the reported analysis.
It does not mean that 22% of patients avoided an event, that 22% more patients were disease-free at 5 years, or that every patient experienced a 22% reduction in risk. A hazard ratio is a model-based relative measure of event rates over follow-up.
The 95% confidence interval of 0.55–1.11 describes statistical uncertainty around the estimated hazard ratio. It is not an interval containing the outcomes that individual patients can experience.
The P = 0.004 value is evidence against the null hypothesis specified for the reported one-sided non-inferiority test. A p-value does not measure the magnitude of the treatment effect and should not be read as the probability that the treatment effect is real.
Non-inferiority requires comparison with a prespecified non-inferiority margin. The registry text identifies the analysis as a non-inferiority test and reports that the original design targeted a one-sided statistical significance level of 10%, but the exact margin is not contained in the ClinicalTrials.gov record. Therefore, the margin itself should not be reconstructed from the observed HR or confidence interval.
Secondary analysis: 5-year Overall Survival
The secondary 5-year Overall Survival analysis used the log-rank test in the intention-to-treat population. The effect measure was again a hazard ratio, with the same stated direction of no axillary dissection relative to axillary dissection.
5-year Overall Survival
90% CI: 0.52–1.54 · P = 0.73
Intention-to-treat analysis · Log-rank test · Superiority hypothesis
The HR of 0.89 means that the estimated hazard of death was lower in the no-dissection group than in the dissection group under the reported hazard-ratio comparison, with the estimated relative hazard approximately 89% of the comparator hazard.
This does not mean that mortality was 11% lower in an absolute sense, nor does it mean that 11% of patients survived because of the intervention. The hazard ratio is not an absolute survival difference.
The 90% confidence interval of 0.52–1.54 is relatively broad and includes 1.00, indicating substantial statistical uncertainty around the estimated relative hazard. The interval describes uncertainty around the estimated treatment comparison, not individual patient outcomes.
The reported P = 0.73 does not provide evidence of a statistically significant superiority difference under the posted analysis. Importantly, a non-significant p-value is not proof that the two treatments have exactly identical effects; it indicates that the observed data did not provide evidence for the superiority hypothesis under the stated analysis.
8. Results Summary
| Endpoint | Analysis | Effect estimate | Confidence interval | P-value |
|---|---|---|---|---|
| 5-year Disease-Free Survival | 1-sided non-inferiority test | HR 0.78 | 95% CI 0.55–1.11 | 0.004 |
| 5-year Overall Survival | Log-rank; superiority hypothesis | HR 0.89 | 90% CI 0.52–1.54 | 0.73 |
The two analyses answer different statistical questions. The primary disease-free survival analysis was framed as non-inferiority, whereas the secondary overall survival analysis was framed as superiority. Their p-values therefore cannot be interpreted as though they arose from the same hypothesis.
9. Statistical Methods Explained
Why was an intention-to-treat analysis used?
In a randomized trial, the intention-to-treat principle preserves the comparison created by randomization. Participants remain associated with the group to which they were randomized when efficacy outcomes are analyzed. This helps maintain the causal interpretation supported by random allocation and avoids redefining the comparison according to later treatment behavior.
What does an HR of 0.78 mean?
For the primary endpoint, the registry defines the HR as no axillary dissection divided by axillary dissection. An HR of 0.78 therefore indicates a lower estimated instantaneous disease-free-survival event hazard in the no-dissection group under the fitted time-to-event comparison. A useful derived interpretation is that 0.78 is 22% below 1.00, but this should not be converted into a statement that 22% of patients benefited.
Why is non-inferiority different from superiority?
A superiority trial asks whether one treatment provides evidence of a better outcome than another. A non-inferiority trial asks whether the new or alternative strategy is not unacceptably worse than the comparator according to a prespecified margin. The distinction is important because a hazard ratio below 1 alone does not establish non-inferiority, and a conventional two-sided confidence interval should not be interpreted without reference to the prespecified non-inferiority framework.
Why does the primary confidence interval extend above 1?
The reported two-sided 95% CI for the primary HR is 0.55–1.11. Because this interval includes 1, it should not be interpreted using the simple rule that a two-sided 95% CI excluding 1 is required for every non-inferiority conclusion. Non-inferiority is evaluated against the prespecified margin using the appropriate one-sided hypothesis framework. The exact margin is not contained in the ClinicalTrials.gov record, so it cannot be inferred here.
What does the 5-year time frame add?
The registered endpoint is a time-to-event outcome summarized at 5 years. This is different from a simple proportion observed at a single visit because disease-free survival accounts for the timing of events and censoring during follow-up. The registry defines the endpoint from randomization to the first qualifying invasive relapse, second primary tumor, or death.
Why use a log-rank test for overall survival?
The log-rank test is designed to compare time-to-event distributions between groups while accounting for the timing of events and censoring. It is therefore a natural method for an overall-survival endpoint. In the posted secondary analysis, the log-rank method was used together with the hazard-ratio effect measure.
Why should the p-value not be treated as an effect size?
A p-value summarizes how compatible the observed data are with a specified null hypothesis under the statistical model. It depends on the effect, variability, information, and sample size. The hazard ratio and its confidence interval provide information about the magnitude and precision of the estimated treatment comparison; the p-value does not replace them.
10. Understanding the Primary Non-Inferiority Analysis
The primary statistical feature of IBCSG 23-01 is the non-inferiority framework. This is important because the clinical interpretation of an alternative treatment strategy can depend on whether it preserves an acceptable amount of the comparator's efficacy rather than whether it demonstrates a statistically significant advantage.
The exact numerical margin is not reported in the ClinicalTrials.gov record. It should therefore not be reverse-engineered from the observed hazard ratio, confidence interval, or p-value.
The registry-reported analysis also states that, as originally designed, the target accrual was 1960 patients with analysis planned after 558 events, based on 90% power and a one-sided statistical significance level of 10%. These were design targets rather than the observed enrollment and event results reported in the primary analysis reported here.
11. Hazard Ratios and Confidence Intervals
Both posted analyses use a hazard ratio, but the uncertainty intervals have different confidence levels. The primary disease-free survival analysis reports a 95% two-sided CI, while the secondary overall survival analysis reports a 90% two-sided CI.
| Endpoint | HR | CI level | CI | Direction |
|---|---|---|---|---|
| 5-year Disease-Free Survival | 0.78 | 95% | 0.55–1.11 | No dissection / dissection |
| 5-year Overall Survival | 0.89 | 90% | 0.52–1.54 | No dissection / dissection |
The primary estimate is 0.78, but the plausible values represented by its reported 95% interval extend from 0.55 to 1.11. The secondary estimate is 0.89, with a reported 90% interval from 0.52 to 1.54. These intervals show that point estimates should not be interpreted without considering their precision.
A confidence interval crossing 1 does not by itself answer a non-inferiority question. Conversely, a confidence interval excluding 1 in a superiority analysis would not automatically answer a non-inferiority question. The hypothesis framework and prespecified margin determine the relevant decision rule.
12. Safety Results
The ClinicalTrials.gov record reports serious adverse events by randomized arm as affected participants divided by those at risk. The reported figures are:
| Arm | Serious adverse events | Affected / at risk |
|---|---|---|
| Axillary Dissection | Serious adverse events | 1 / 447 |
| No Axillary Dissection | Serious adverse events | 0 / 453 |
The ClinicalTrials.gov record reports one affected participant among 447 at risk in the axillary-dissection group and zero among 453 at risk in the no-dissection group. These are the reported serious-adverse-event counts and denominators; they should not be expanded into a broader safety profile that is not contained in the ClinicalTrials.gov record.
The safety denominators also should not be confused with the overall trial enrollment of 931. The registry provides 447 and 453 as the affected/at-risk figures for this specific serious-adverse-event measure.
13. Multiplicity and Hypothesis Testing
The ClinicalTrials.gov record identifies two posted statistical analyses: one primary and one secondary. The primary hypothesis type is non-inferiority or equivalence, while the secondary hypothesis type is superiority.
| Analysis | Role | Hypothesis type | Method |
|---|---|---|---|
| 5-year Disease-Free Survival | Primary | Non-inferiority or equivalence | 1-sided non-inferiority test |
| 5-year Overall Survival | Secondary | Superiority | Log-rank test |
The ClinicalTrials.gov record does not describe an alpha-allocation procedure between the primary and secondary endpoints, a multiplicity-adjustment strategy, or an interim-analysis plan. Those features therefore cannot be reconstructed from the registry information provided.
14. Crossover, Stratification, and Missing Data
Crossover
The ClinicalTrials.gov record does not report treatment crossover. No crossover effect on the overall-survival comparison is inferred.
Stratification
The ClinicalTrials.gov record does not identify randomization or analysis stratification factors. No stratified Cox or stratified log-rank procedure is assumed.
Missing data
The ClinicalTrials.gov record does not specify a missing-data or imputation method for the time-to-event analyses.
Bayesian methods
No Bayesian method is reported in the ClinicalTrials.gov record.
This distinction is important for an independent statistical review. Time-to-event analyses naturally incorporate censoring, but the ClinicalTrials.gov record does not provide enough information to describe the exact censoring rules, missing-data handling, or imputation procedures used in the underlying statistical analysis.
15. Statistical Assumptions Behind the Hazard Ratio
A hazard ratio is most naturally interpreted through a proportional-hazards framework when the relative hazard is reasonably stable over time. The ClinicalTrials.gov record reports hazard ratios but do not provide diagnostic information about the proportional-hazards assumption.
For IBCSG 23-01, the posted analysis defines the numerator as no axillary lymph node dissection and the denominator as axillary lymph node dissection.
This formula helps explain the direction of the reported estimates. An HR below 1 indicates a lower estimated event hazard for the numerator group; an HR above 1 would indicate a higher estimated event hazard. It does not directly provide a difference in 5-year percentages or a difference in median survival.
16. Limitations
- Registry-level detail: the analysis is restricted to the ClinicalTrials.gov record. The registry information does not provide the full statistical analysis plan.
- Non-inferiority margin: the registry-reported analysis describes a non-inferiority design and provides original design targets, but the exact numerical non-inferiority margin is not included in the ClinicalTrials.gov record.
- Confidence-interval interpretation: the primary 95% CI extends from 0.55 to 1.11. Non-inferiority cannot be assessed by simply applying a conventional superiority rule based on whether this interval crosses 1.
- Secondary endpoint precision: the overall-survival estimate of 0.89 has a 90% CI from 0.52 to 1.54, indicating substantial uncertainty around the point estimate.
- Endpoint information: the ClinicalTrials.gov record does not include median disease-free survival, median overall survival, Kaplan-Meier curves, or time-specific survival percentages beyond the registered 5-year endpoint descriptions.
- Event information: the ClinicalTrials.gov record does not report the number of disease-free-survival or overall-survival events used in the posted analyses.
- Stratification: no stratification factors are reported, so stratified analyses should not be assumed.
- Crossover: crossover is not described in the ClinicalTrials.gov record, so its potential effect on interpretation cannot be quantified here.
- Missing data: no imputation or missing-data strategy is reported in the ClinicalTrials.gov record.
- Safety scope: the ClinicalTrials.gov record consists specifically of serious adverse events by arm and does not provide a comprehensive adverse-event profile.
- Hazard-ratio assumptions: the registry reports HR estimates but does not provide sufficient information to assess proportional hazards directly.
17. Why This Trial Matters Statistically
IBCSG 23-01 is a useful statistical teaching example because the primary question is framed around non-inferiority rather than superiority. That changes how the hazard ratio, confidence interval, and p-value must be interpreted.
| Concept | How it appears in IBCSG 23-01 |
|---|---|
| Randomization | Randomized parallel-group comparison of two surgical strategies |
| Intention-to-treat analysis | Both posted efficacy analyses use the ITT population |
| Time-to-event endpoint | 5-year disease-free survival is the registered primary endpoint |
| Hazard ratio | Reported for both disease-free survival and overall survival |
| Confidence interval | 95% CI for the primary HR and 90% CI for the secondary HR |
| Non-inferiority | Primary disease-free survival analysis uses a 1-sided non-inferiority test |
| Log-rank test | Reported method for the secondary overall-survival analysis |
| Hypothesis testing | Primary and secondary analyses use different hypothesis types |
| Design targets | Original design description includes target accrual, event target, power, and one-sided significance level |
| Safety denominators | Serious adverse events are reported as affected participants among those at risk by arm |
The trial therefore illustrates why a statistical result should always be read in the context of the estimand, endpoint, analysis population, hypothesis, confidence interval, and decision rule. A hazard ratio of 0.78 means something different when evaluated in a non-inferiority framework than it would in a conventional superiority analysis.
18. What the Primary Result Does — and Does Not — Establish
The reported primary HR of 0.78 indicates a lower estimated disease-free-survival event hazard for no axillary lymph node dissection relative to axillary lymph node dissection under the posted analysis.
It does not directly report a 5-year absolute difference, a median disease-free-survival difference, the fraction of patients who benefit, or the probability that an individual patient will remain disease-free.
The reported P = 0.004 belongs to the one-sided non-inferiority test. It is evidence against the null hypothesis defined by that testing framework; it is not a measure of the size of the treatment effect.
The exact non-inferiority margin is essential for independently reconstructing the numerical decision rule. Because that margin is not contained in the ClinicalTrials.gov record, this page does not manufacture or infer it.
19. Overall Survival in Context
The secondary overall-survival analysis reports an HR of 0.89, with a two-sided 90% CI of 0.52–1.54 and P = 0.73. The wide interval shows that the point estimate alone is not a complete description of the uncertainty in the comparison.
The overall-survival analysis also uses a different hypothesis type from the primary analysis. It is labeled as a superiority analysis and uses the log-rank test. Therefore, its p-value should be interpreted as a test of superiority rather than as a second test of the primary non-inferiority question.
20. Serious Adverse Events: Statistical Perspective
The serious-adverse-event data are sparse: one affected participant is reported among 447 at risk in the axillary-dissection group, compared with zero among 453 at risk in the no-dissection group.
| Measure | Axillary Dissection | No Axillary Dissection |
|---|---|---|
| Affected participants | 1 | 0 |
| At risk | 447 | 453 |
| Reported format | 1/447 | 0/453 |
With such small counts, the absence of a reported serious adverse event in one group should not be interpreted as proof that the true event rate is zero. The ClinicalTrials.gov record does not provide a confidence interval or a formal between-group statistical test for this safety measure, so no such inferential comparison is added.
21. A Practical Reading of the IBCSG 23-01 Results
A disciplined reading of the posted results can follow five steps.
- Start with the endpoint. The primary endpoint is 5-year disease-free survival, defined as time from randomization to invasive relapse, second primary tumor, or death.
- Identify the analysis population. The primary analysis uses intention-to-treat.
- Identify the hypothesis. The primary comparison is a one-sided non-inferiority test rather than a superiority test.
- Read the effect estimate with its interval. The HR is 0.78 with a 95% CI of 0.55–1.11.
- Interpret the p-value within its testing framework. The reported P = 0.004 belongs to the one-sided non-inferiority analysis and should not be interpreted as an effect-size measure.
The same process can then be applied to the secondary overall-survival result, while recognizing that its hypothesis type, confidence level, and statistical method differ from those of the primary endpoint.
22. Related Tutorials
Learn more about the methods used in this trial:
23. Related Calculators
24. Sources
- ClinicalTrials.gov: IBCSG 23-01 — NCT00072293.
- PubMed: PMID 30196031.
- PubMed: PMID 23491275.
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25. Record Summary
IBCSG 23-01 is a randomized parallel-group trial in women with node-negative breast cancer and sentinel lymph node micrometastases, comparing axillary lymph node dissection with no axillary lymph node dissection. Its registered primary endpoint is 5-year disease-free survival, defined as time from randomization to invasive relapse at any site, second primary tumor, or death. The posted primary analysis uses an intention-to-treat population and a one-sided non-inferiority test, reporting an HR of 0.78, a two-sided 95% CI of 0.55–1.11, and P = 0.004. The secondary overall-survival analysis reports an HR of 0.89, a two-sided 90% CI of 0.52–1.54, and P = 0.73 using a log-rank method and a superiority hypothesis.
The central statistical lesson is that these numbers cannot be interpreted independently of their hypothesis frameworks. The primary result is a non-inferiority analysis, so its decision rule depends on a prespecified margin that is not contained in the ClinicalTrials.gov record. The secondary overall-survival result is a superiority analysis and therefore answers a different question. Together, the results illustrate how hazard ratios, confidence intervals, p-values, intention-to-treat analysis, and non-inferiority logic fit together in a randomized time-to-event trial.