This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Denosumab and MRI Breast Imaging (NCT02613416), a na phase 2 study. The primary outcome is Relative Change of ≥ 5% in Breast Density at 6 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02613416 |
| Phase | Phase 2 |
| Condition | Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 42 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Alison Stopeck |
| Results posted | Yes |
2. Clinical Question
The registry record describes a study of denosumab in pre- and post-menopausal women diagnosed with stage 0-III breast cancer who were not receiving anticancer treatment with hormonal therapies, chemotherapy, or radiation. The clinical question was whether breast density measured by MRI changed by at least 5% after 6 months on denosumab. The primary endpoint counted participants meeting that relative-change threshold.
Participants were to receive 6 monthly subcutaneous injections of denosumab, with breast density measured before treatment and after 6 months. The study was non-randomized and single-group; it did not include a placebo group or a separate control group. The registry summary states that the investigators intended to assess the extent of variability in breast density over time using before-and-after measurements.
This design can describe changes in the measured endpoint within the study group, but it cannot by itself distinguish a treatment-associated change from changes that might have occurred over time without treatment. In particular, there is no randomized comparison in the registry record that can support a like-for-like contrast between denosumab and a control intervention.
The registry lists enrollment as 42 and identifies the study as completed. However, it does not report the primary endpoint count or the proportion of participants who met the threshold. It therefore does not establish from the posted results how often the specified relative change was observed. The question can be stated from the endpoint definition, but the registry record does not provide the result needed to answer it.
3. Trial Design
This was a phase II, non-randomized, single-group study of denosumab. The registry lists allocation as not applicable and masking as none. The intervention is described as 6 monthly subcutaneous injections. The study summary specifies denosumab at 120 mg per injection and describes the population as pre- and post-menopausal women with stage 0-III breast cancer who were not receiving hormonal therapy, chemotherapy, or radiation.
Breast density was to be quantified by non-contrast MRI at baseline and after 6 months on denosumab. The stated primary endpoint concerns relative change in breast density at 6 months, with a threshold of at least 5%. The summary explains that no placebo treatment period or group would be used because the agent is injectable and that the investigators intended to characterize variability in breast density over time through before-and-after measurement.
The registry lists enrollment as 42, a start date of 2015-11, primary completion on 2021-08-20, and status as completed. The primary endpoint population description says that 5 subjects were excluded: ineligible (n=1), withdrew consent (n=1), implants both breasts (n=1), and image artifacts (n=2). These details identify stated reasons for exclusion, but the registry record does not explain the analysis population in enough detail to reconcile all listed participant counts.
The study was investigator initiated, with Alison Stopeck listed as sponsor; the summary says Amgen would provide denosumab. A detailed protocol, allocation procedure beyond the single-group designation, and statistical analysis plan are not reported in the registry record.
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.
Before assignment: 12 consented patients were determined to be eligible but withdrew consent before the start of the study intervention
Overall Study
| Stage | Denosumab 120 mg Subcutaneous |
|---|---|
| STARTED | 30 |
| COMPLETED | 30 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: 5 subjects were excluded (ineligible (n=1), withdrew consent (n=1), implants both breasts (n=1) and image artifacts (n=2).
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.
| Characteristic | Unit | Denosumab |
|---|---|---|
| Participants analysed | 30 | |
| Age, Continuous | years | 59.5 (SD 13) |
| Sex: Female, Male: Female | Participants | 30 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 28 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 29 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 30 |
| Percentage of Breast Density by Magnetic Resonance Imaging | percent | 19.74 (7.85 to 48.62) |
6. Primary Endpoint
The registry lists the primary outcome as Relative Change of ≥ 5% in Breast Density at 6 Months, measured over baseline, 6 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the count of participants with a relative change of at least 5% in breast density at 6 months. Breast density was to be measured using non-contrast MRI at baseline and after 6 months on denosumab. The endpoint turns a measured change into a binary outcome: a participant either meets the stated threshold or does not. The registry identifies the unit as participants and the measure as a count of participants.
A threshold-based endpoint can make a continuous measurement easier to summarize as the frequency of participants crossing a prespecified level of change. That is a general description of how such endpoints work; the registry record does not explain why this particular threshold was selected, whether it was prespecified in a protocol, or how the threshold relates to measurement variability or clinical importance.
The record also lists a secondary outcome concerning absolute change greater than 1% in breast density. Absolute and relative change describe different ways to express change, so the stated thresholds should not be treated as interchangeable. The registry record does not provide the numerical primary endpoint result, nor does it provide enough detail to assess the MRI measurement procedure, repeatability, or handling of measurements that could not be evaluated.
Because the primary outcome is not reported in the registry record, its count, uncertainty, and distribution cannot be interpreted from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the trial’s design and the definition of its primary endpoint, but it does not give the primary endpoint result. In particular, no count is reported for participants with a relative change of at least 5% in breast density at 6 months, and no estimate of the frequency or its precision is available in the record. Consequently, the endpoint cannot be interpreted as showing how often the threshold was met.
This absence also prevents a meaningful assessment of the observed magnitude of change. The endpoint is defined by crossing a threshold, but the record does not report the number meeting it, the number not meeting it, or a continuous summary of the measured changes. A threshold count alone would not describe every aspect of the distribution; in this case, even that count is not reported.
The design further limits what any before-and-after finding could establish. As a general statistical point, observing change over time within a single group does not isolate the effect of an intervention from time-related changes, measurement variability, or other influences. The registry summary explicitly states that no placebo treatment period or group would be used, and the study is listed as non-randomized and single-group. There is therefore no randomized control comparison to interpret.
The enrollment listing is 42, while the endpoint population description reports 5 exclusions with stated reasons. The serious adverse event figures list 30 at risk in the denosumab group. These figures refer to different registry entries and should not be combined or treated as if they necessarily describe the same analysis set. The record does not explain their relationship or provide a full accounting of participants included in each analysis.
The posted safety figures report 0 serious events affecting participants among 30 at risk in the denosumab group, and 0 deaths. These are the figures reported for the listed serious adverse event information; they do not supply the missing primary efficacy result or establish that no other types of adverse events occurred.
Any planning illustration based on a fraction of an observed effect depends on an observed effect being available. Since the primary outcome result is not reported in the registry record, such planning values cannot be grounded in a reported primary effect. Planning sample sizes are hypothetical design calculations in any case, not measures of power achieved by the completed trial. No sponsor analysis or recalculated endpoint estimate is reported for comparison.
9. Statistical Methods Explained
How should the endpoint be read?
The primary outcome is a binary participant-level measure: whether a participant had a relative change in breast density of at least 5% at 6 months. The registry specifies a count as the measure and participants as the unit. In general, a binary endpoint reduces a measured quantity to categories determined by a threshold. This can be useful when the research question concerns the proportion meeting a defined criterion, but it also discards information about the size and direction of changes within each category.
The registry describes MRI measurements at baseline and after 6 months on denosumab. It does not report the underlying measurements, an average change, a distribution of changes, or the count meeting the threshold. Thus, the endpoint definition is available, but its outcome value is not. No interval estimate can be assessed without a reported estimate and analysis.
What does a confidence interval convey?
In general, a confidence interval describes statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while neither width nor location establishes that an observed association is causal. The registry record does not report a confidence interval for the primary endpoint. Without the endpoint result and its uncertainty, the precision of the primary finding cannot be evaluated.
What does the single-group design permit?
As a general statistical principle, a before-and-after comparison in a single group describes within-group change over time. Without a concurrent control group, it cannot separate a treatment-related change from other changes occurring during the same period. Randomization is a way to support comparable groups for a treatment contrast; this record lists the study as non-randomized, with allocation not applicable and masking none. The summary states that a placebo group or period would not be used. Accordingly, the design does not provide a randomized between-group estimate of the effect of denosumab.
What do the planning assumptions mean?
The registry’s planning description identifies a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. For time-to-event planning, it describes a total number of events using the Schoenfeld approach; for other outcomes, it describes participants per arm. These are planning conventions, not descriptions of the actual single-group trial allocation.
In general, a sample-size calculation estimates how many observations a proposed design would need under specified assumptions. It does not show that a completed study had a particular probability of detecting an effect, and a planning figure is not observed power. The registry labels these calculations as planning illustrations rather than the trial’s own design. The primary observed effect is not reported in the registry record, so the stated fraction-of-observed-effect basis cannot be evaluated from the posted outcome information. No planning sample-size values are included in the registry record for this analysis.
Why can over-dispersion matter?
General explanation: over-dispersion occurs when outcome variability is greater than assumed by a statistical model. If ignored, model-based uncertainty can be understated and statistical conclusions can appear more precise than warranted. This issue is relevant to some count outcomes, but the registry record does not report an over-dispersion assessment, model, or dispersion estimate for this study. The primary endpoint is described as a participant count meeting a binary criterion; no detailed model for its analysis is reported.
Can a recalculated result be compared with the sponsor’s analysis?
A recalculated result based on posted summary statistics can sometimes provide a simple, unadjusted check of a reported analysis. It does not replace an analysis that accounts for the trial design or prespecified methods. The registry record does not report a primary endpoint summary statistic or sponsor analysis from which to make such a recalculation. There is therefore no recalculated primary estimate to compare with a sponsor result, and no discrepancy between the two is reported.
The statistical analysis plan, model specification, confidence interval method, covariate adjustment, and any approach to repeated measurements are not reported in the registry record. These methods should not be inferred from the endpoint definition or the planning assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint concerning relative change of at least 5% in breast density at 6 months and a secondary outcome concerning absolute change greater than 1%. It also reports two outcome measures and one analysis. The record does not state whether the outcomes were tested as a family, whether any multiplicity adjustment was planned, or how conclusions across outcomes were to be prioritized. The approach to multiplicity is not reported in the registry record.
The record’s description of exclusions identifies 5 subjects and gives reasons: ineligible (n=1), withdrew consent (n=1), implants both breasts (n=1), and image artifacts (n=2). These entries do not fully specify whether exclusions occurred before or after enrollment, which analyses they affect, or how missing MRI measurements were handled. The registry record does not report an imputation method, a missing-data sensitivity analysis, or assumptions about why measurements or outcomes might be missing.
Analysis populations are also not described in enough detail to identify whether the primary endpoint used all enrolled participants, only participants with evaluable MRI measurements, or another defined group. The listed enrollment is 42, while the primary endpoint description and serious adverse event figures give other participant counts. The record does not reconcile these counts, so they should not be combined to create an assumed analysis denominator.
These gaps matter because exclusions and unavailable measurements can affect the interpretation of an endpoint, especially when the outcome depends on paired baseline and follow-up measurements. That is a general statistical consideration, not a claim about the direction or size of any bias in this trial. The registry record does not provide enough information to evaluate the effects of missing data or the population included in the primary analysis.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Denosumab | 0 | 30 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Denosumab | 0 of 30 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Denosumab | 0 of 30 |
The registry lists the denosumab group with 30 participants at risk for serious adverse events and 0 participants affected. It also lists 30 at risk for other adverse events and 0 affected, and reports 0 deaths. No serious adverse event terms are listed. These are the posted safety figures for the registry entry.
The at-risk counts are the denominators associated with these safety fields. They should not be assumed to match the enrollment listing or the population used for the primary endpoint. The registry record does not explain how the safety population relates to the listed enrollment of 42 or to the 5 exclusions described in the endpoint population information.
In general, a zero count in a registry summary means that no events are recorded in that category for the stated group and denominator. It does not establish that the treatment has no safety risks. Interpretation also depends on event definitions, observation time, reporting completeness, and whether events were collected consistently. Details about these matters are not reported in the registry record. The posted figures also do not describe non-serious event types, their severity, or their timing beyond the listed categories.
The safety counts should therefore be read narrowly: the registry reports no serious events, other events, or deaths in the listed denosumab safety figures. They do not resolve the missing primary endpoint result or provide a comparison with a control group.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed phase II study intended to examine breast-density measurements before and after 6 months of denosumab. Its primary endpoint is clearly described as a participant count meeting a relative-change threshold of at least 5%. The record also identifies the study as non-randomized and single-group, and gives a rationale for not including a placebo period or group.
What the posted results do not provide is the primary endpoint count. Without that count, readers cannot tell how many participants met the threshold, estimate the frequency of that outcome, or judge its precision. The registry also does not report a numerical result for the secondary outcome. A defined endpoint is not itself evidence of an observed result.
Even if a before-and-after change were reported, a single-group design would describe change over time rather than establish that denosumab caused it. This is a general limitation of uncontrolled before-and-after comparisons. The registry record has no randomized control comparison, and it does not provide a placebo group. It therefore cannot support a like-for-like estimate contrasting denosumab with a control intervention.
The safety entry reports 0 serious events affecting participants among 30 at risk, 0 other events affecting participants among 30 at risk, and 0 deaths. Those figures describe the listed safety data only. They are not a substitute for complete safety reporting, and the registry record does not include details needed to assess event definitions, observation time, or completeness.
The record does not report the analysis plan, missing-data methods, confidence intervals, or a reconciliation of the participant counts across endpoint and safety information. These omissions constrain assessment of both the results and their precision. Overall, the registry supports a description of the study question and design, but not a conclusion about the primary outcome or a causal treatment effect.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary question is framed around change in an imaging biomarker measured within one group over time. The design highlights an important distinction: a study can measure before-and-after change, but that change is not automatically a treatment effect. Without a concurrent comparison group, other influences and measurement variability cannot be separated from a change associated with the intervention. The registry summary itself describes the intent to assess variability over time and explains that a placebo period or group would not be used.
The endpoint also illustrates the trade-off involved in using a threshold. Counting participants who cross a relative-change criterion produces an interpretable event count, but it does not convey the full distribution of measured changes. The registry additionally lists an absolute-change endpoint, which represents a different measurement scale. The reasons for selecting either threshold and their clinical interpretation are not reported in the registry record.
Equally important is the distinction between a registered endpoint and a posted result. The endpoint is specified, but the count and uncertainty needed to interpret it are absent. Readers should not treat the presence of a complete endpoint definition as evidence that the result is available or that an effect was observed.
Finally, the participant counts in the enrollment, endpoint-exclusion, and safety entries are not reconciled. Clear analysis-population reporting is important for understanding the denominator behind an estimate and judging how exclusions or missing measurements may affect interpretation. The registry record does not provide that reconciliation. These features make the record useful for understanding the planned measurement question while leaving the outcome and its precision unresolved.
14. 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 principal trial-specific limitation is the absence of the primary endpoint result in the registry record. Although the endpoint is defined, the count of participants meeting the threshold is not reported. The record also does not give the numerical secondary outcome result, continuous MRI changes, or uncertainty estimates. This prevents interpretation of the magnitude and precision of the breast-density findings.
The single-group, non-randomized design has no control comparison. The registry states that there would be no placebo group or treatment period. Accordingly, within-group changes cannot be separated from time-related change, measurement variability, or other influences. Masking is listed as none, and the record does not explain any steps taken to limit measurement or assessment bias.
The participant accounting is incomplete. Enrollment is listed as 42; the endpoint population description reports 5 exclusions with stated reasons; and the serious adverse event information lists 30 at risk. The record does not explain how these entries relate or identify the analysis population for each outcome. It also does not describe the handling of missing MRI data or the timing and stage of the stated exclusions.
Further methodological details—including a statistical analysis plan, outcome model, confidence interval method, multiplicity approach, and missing-data sensitivity analyses—are not reported in the registry record. The imaging description identifies non-contrast MRI at baseline and after 6 months, but does not provide details about measurement reproducibility or assessment procedures. These limitations restrict what can be concluded from the record; they do not establish the direction of any bias or the value of an unreported result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Denosumab and MRI Breast Imaging — NCT02613416.
- Registry record last updated 2024-08-23; status last verified 2024-08.
- Results first posted 2024-08-23.
- 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.
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18. Record Summary
The registry identifies NCT02613416, Denosumab and MRI Breast Imaging, as a completed phase II study. It lists enrollment as 42, with a start date of 2015-11 and primary completion on 2021-08-20. The study was non-randomized and single-group, with no masking listed.
Participants were described as pre- and post-menopausal women with stage 0-III breast cancer who were not receiving hormonal therapy, chemotherapy, or radiation. The intervention was 6 monthly subcutaneous injections of denosumab. Breast density was to be assessed by non-contrast MRI at baseline and after 6 months.
The primary endpoint counted participants with a relative change of at least 5% in breast density. The registry record does not report the primary endpoint result. The endpoint population description lists 5 exclusions, and the safety entry lists 0 serious events among 30 at risk and 0 deaths. Analysis methods, missing-data handling, and the relationship among participant counts are not reported in the registry record.