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 Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast MRI (NCT01067976), a non-randomized phase 3 study. The primary outcome is Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01067976 |
| Phase | Phase 3 |
| Condition | Breast Cancer, Diagnostic Imaging |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 446 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bayer |
| Results posted | Yes |
2. Clinical Question
Population
People with newly diagnosed breast cancer referred for contrast-enhanced breast MRI were studied. The primary analysis included 388 participants in the Full Analysis Set who had regions of malignant disease verified by the Standard of Truth. The study description refers to women with a recent breast cancer diagnosis.
Intervention
Participants received gadobutrol by intravenous injection at 0.1 mmol/kg body weight. Each participant had an unenhanced MRM followed by a gadobutrol-enhanced MRM. The study evaluated images from both modalities.
Comparator
The main imaging comparison was contrast-enhanced MRM (CMRM) versus unenhanced MRM (UMRM). This is a within-participant comparison of imaging modalities, not a comparison between separately assigned treatment groups. Additional listed comparisons involved XRM and combinations of imaging modalities.
Primary question
For each reader, how sensitive was CMRM compared with UMRM for detecting the full extent of malignant breast disease? Sensitivity was based on the proportion of malignant breast regions identified as malignant, with the mean calculated across participants. The registry record describes the endpoint and analysis population, but numeric sensitivity estimates and confidence intervals are not reported in the registry record.
3. Trial Design
This was a phase 3, open-label, multicenter study with a single-group design and non-randomized allocation. The study enrolled 446 participants and is recorded as completed. Its stated purpose was to assess the efficacy and safety of gadobutrol for imaging both breasts in people with newly diagnosed breast cancer. The study began in 2010-02, and primary completion was recorded as 2011-07.
Each participant first underwent unenhanced MRM and then gadobutrol-enhanced MRM. The gadobutrol dose was 0.1 mmol/kg body weight, administered intravenously at a rate of 2 ml/sec. Because the same participants received both imaging assessments, the central comparison concerns images obtained before and after contrast administration, rather than outcomes in randomized intervention and control groups.
The study was open label, but the official title specifies corresponding blinded image reading. The image sets were evaluated in randomized fashion. This refers to the order in which image sets were evaluated; it does not change the non-randomized allocation or make the study a randomized trial. The record does not report further details of the reader-blinding procedures.
The primary endpoint was sensitivity for detecting the full extent of malignant breast disease using CMRM versus UMRM, evaluated per reader. The primary analysis population comprised 388 participants in the Full Analysis Set with malignant regions verified by the Standard of Truth. Listed secondary outcomes included breast-level specificity and percentage differences in participant-level detection for index and additional cancers across imaging comparisons. Numeric results for these outcomes 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.
Overall Study
| Stage | Gadobutrol (Gadavist, BAY86-4875) |
|---|---|
| STARTED | 446 |
| Received Treatment | 426 |
| Fulfilled Requirements of FAS Population | 390 |
| COMPLETED | 424 |
| NOT COMPLETED | 22 |
Reasons for not completing this period:
| Reason | Gadobutrol (Gadavist, BAY86-4875) |
|---|---|
| Study drug never administered | 20 |
| Study prematurely discontinued | 2 |
Analysis population for the primary outcome, as defined in the registry: The analyses were based on 388 participants in the Full Analysis Set (FAS) who had regions with malignant disease verified by Standard of Truth (SOT).
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 | Gadobutrol (Gadavist, BAY86-4875) |
|---|---|---|
| Participants analysed | 426 | |
| Age, Continuous | years | 55.5 (SD 10.4) |
| Sex: Female, Male: Female | Participants | 426 |
| Sex: Female, Male: Male | Participants | 0 |
| Race/Ethnicity, Customized: White | participants | 320 |
| Race/Ethnicity, Customized: Asian | participants | 103 |
| Race/Ethnicity, Customized: Black | participants | 2 |
| Race/Ethnicity, Customized: Native Hawaiian/other Pacific Islander | participants | 1 |
| Country: Colombia | participants | 19 |
| Country: Finland | participants | 53 |
| Country: Germany | participants | 172 |
| Country: Italy | participants | 25 |
| Country: Korea (South) | participants | 102 |
| Country: Switzerland | participants | 4 |
| Country: United States | participants | 51 |
6. Primary Endpoint
The registry lists the primary outcome as Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader, measured over Immediately before injection and after injection.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | sensitivity % |
| Endpoint classification | Continuous Endpoint |
The primary endpoint concerns sensitivity for detecting the full extent of malignant breast disease on CMRM compared with UMRM, reported per reader. For an individual participant, sensitivity was defined as the proportion of malignant breast regions that the clinical investigators and the blinded readers recognized as malignant using the relevant imaging modality. The endpoint was then expressed as a mean across participants.
Sensitivity is a measure of how often a method identifies disease that is present according to a reference standard. It is relevant to this study because the question concerns whether each imaging approach identifies malignant regions verified by the Standard of Truth. The study also listed breast-level specificity as a secondary outcome; specificity addresses the identification of regions without the target condition, but it is not the primary endpoint described in the record.
The endpoint is not a direct measure of whether imaging changes clinical decisions or improves health outcomes. It assesses image-based identification of malignant regions under the study’s definitions. The primary analysis was based on 388 participants in the Full Analysis Set who had Standard-of-Truth-verified malignant regions. The registry record does not report the numeric mean sensitivity estimates or their 95% confidence intervals, so the size and precision of the comparison cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study’s structure supports a comparison of two imaging approaches within participants: unenhanced MRM and gadobutrol-enhanced MRM. That is distinct from comparing outcomes across independently assigned groups. The endpoint focuses on readers’ sensitivity for detecting the full extent of malignant breast disease, using malignant regions verified by the Standard of Truth as the basis for assessment.
The registry record gives the endpoint definition and identifies 388 participants in the primary Full Analysis Set. It does not report the sensitivity estimates, the 95% confidence intervals, or a numerical contrast between CMRM and UMRM. Accordingly, the direction, magnitude, and precision of the primary comparison are not reported in the registry record. There is no basis in this record for stating that one imaging modality had higher sensitivity than the other.
The design also determines how the comparison should be understood. Participants underwent the unenhanced examination before the enhanced examination, and images were read in randomized fashion. The randomized image-reading order does not mean that participants were randomized to different treatment groups. Since the intervention sequence was not randomized, differences between the two image assessments cannot be interpreted as a randomized between-group treatment effect.
The record lists additional outcomes, including breast-level specificity and percentage differences in participant-level detection of index and additional cancers across CMRM, UMRM, XRM, and combined imaging comparisons. It does not provide numeric results for these outcomes. It therefore does not establish the size or precision of any secondary comparison, either.
The registry records 446 participants enrolled and 388 participants in the described primary analysis population. It does not explain the difference between those counts or report how participants without qualifying verified malignant regions were handled. Those figures refer to different populations and should not be treated as interchangeable.
In statistical terms, an estimate alone would describe the observed performance in the analyzed population, while a confidence interval would convey uncertainty around that estimate. General explanation: a confidence interval is a range of values compatible with the data and the method used to construct it; it does not show the probability that a particular effect is true. Here, the endpoint specifies 95% confidence intervals, but their limits are not reported in the registry record. There are also no reported p-values or inferential test results to interpret.
The record describes a diagnostic imaging comparison, not a comparison of clinical outcomes such as survival or treatment decisions. Its stated endpoint can inform how malignant regions were detected by the imaging approaches under the study’s definitions, but the registry record does not provide the numeric results needed to quantify that performance.
9. Statistical Methods Explained
The registry describes a continuous primary measure: mean sensitivity, expressed as a percentage, with 95% confidence intervals. The endpoint is defined from participant-level proportions of malignant breast regions recognized as malignant, followed by averaging those sensitivities across participants. This definition makes the unit of analysis and the aggregation step important: the endpoint is not described as a single pooled count of every region across all participants.
What does sensitivity measure?
Sensitivity describes the fraction of target-positive cases identified by a method, according to a specified reference standard. In this study, the relevant targets were malignant breast regions verified by the Standard of Truth. A reader’s assessment counted a region as recognized when it was identified as malignant using the imaging modality under evaluation. The registry’s definition includes evaluations by clinical investigators and three blinded readers, and says sensitivity was calculated as a mean across participants.
General explanation: sensitivity is informative about detection among cases known to have the target condition. It does not, by itself, describe how often a method correctly classifies regions without the target condition. That separate aspect of diagnostic performance is commonly assessed with specificity, which the registry lists as a secondary outcome. Neither measure alone describes every feature of an imaging test or its consequences in clinical practice.
Why compare imaging within participants?
The design included an unenhanced MRM followed by a gadobutrol-enhanced MRM for participants. A within-participant comparison examines both imaging approaches in the same person, rather than assigning different people to separate imaging groups. General explanation: when measurements from the same participant are related, an analysis should account for that pairing because observations from one person are not necessarily independent. The specific statistical procedure used to account for the paired imaging assessments is not reported in the registry record.
The imaging sequence was unenhanced first and enhanced afterward. The record says image sets were evaluated in randomized fashion and identifies blinded image reading. These details concern reading procedures; they do not establish random assignment of participants to intervention groups. Allocation is recorded as non-randomized, masking as none, and the study model as single group.
How should a confidence interval be read?
The primary measure was to be accompanied by a 95% confidence interval. General explanation: a confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis procedure. A narrower interval indicates greater precision than a wider interval, while the interval’s position describes which values are compatible with the data and method. A confidence interval is not a guarantee that the true value lies within its particular limits, and it does not by itself determine whether a difference is practically important.
The registry record does not report the sensitivity estimates or confidence-interval limits. Consequently, it is not possible to describe the observed level of sensitivity, the difference between CMRM and UMRM, or the precision of that difference from the record. No p-values or hypothesis-test results are reported in the information available for this study.
What does the analysis population mean?
The primary analysis population was the Full Analysis Set of 388 participants who had regions with malignant disease verified by the Standard of Truth. This definition restricts the stated analysis to participants with verified malignant regions. The registry separately records 446 participants enrolled. Reasons that the analysis population is smaller than the enrollment count, and the handling of participants not included in that population, are not reported in the registry record.
General explanation: defining an analysis population clarifies which participants contribute to a particular estimate. It does not, on its own, establish that missing information or exclusions cannot influence the result. To assess that possibility, readers would need information about missing measurements, exclusions, and sensitivity analyses; those details are not reported in the registry record.
What can be inferred from the listed secondary measures?
The listed secondary outcomes cover breast-level specificity and percentage differences in participant-level detection of index and additional cancers for several imaging comparisons. These outcomes indicate that the study considered diagnostic performance beyond the primary sensitivity measure. The registry lists 25 outcome measures and records zero analyses. Numeric secondary results, methods for comparing modalities, and any adjustment for multiple statistical comparisons are not reported in the registry record.
General explanation: when many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is assessed separately. Multiplicity procedures may address that issue, but whether and how they are used depends on the analysis plan. No such procedure is described in the registry record, so no claim about adjustment can be made.
The study’s analysis plan, sample-size justification, interim analyses, and specific statistical tests are not reported in the registry record. Without the numerical endpoint results and those methodological details, interpretation should remain limited to the stated design, outcome definition, and analysis population.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 25 outcome measures, including the primary sensitivity endpoint and secondary outcomes for specificity and detection comparisons. It records zero analyses. Numeric results for the primary and secondary outcomes are not reported in the registry record. The record also does not describe whether the study used a prespecified hierarchy, adjusted significance thresholds, or another procedure to address multiple outcomes or comparisons. The implications of multiplicity therefore cannot be assessed.
The primary analysis population is described as 388 participants in the Full Analysis Set who had regions of malignant disease verified by the Standard of Truth. The record separately gives an enrollment of 446. It does not report the reasons participants were not included in the stated analysis population, how missing imaging or reference-standard information was handled, or whether any missing-data sensitivity analyses were performed.
General explanation: missing data can affect an estimate when the availability of measurements is related to participant characteristics or outcomes. An analysis population definition identifies who contributed to the stated endpoint, but it does not explain the consequences of missing or unavailable measurements. The record does not provide enough information to evaluate those consequences.
The exact statistical analysis plan, sample-size justification, interim analyses, and specific inferential procedures are not reported in the registry record. These omissions limit assessment of whether the analyses followed prespecified methods and how uncertainty or multiple comparisons were handled.
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 |
|---|---|---|---|
| Gadobutrol (Gadavist, BAY 86-4875) | 0 | 426 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Gadobutrol (Gadavist, BAY 86-4875) | 10 of 426 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Gadobutrol (Gadavist, BAY 86-4875) |
|---|---|---|
| Headache | Nervous system disorders | 7 of 426 |
| Dizziness | Nervous system disorders | 6 of 426 |
The safety record lists 426 participants at risk in the gadobutrol group. It records 0 participants with serious adverse events and 10 participants with other adverse events. No serious adverse event terms are listed. Deaths are not reported in the registry record.
These figures are counts of participants, not a description of the number, nature, timing, or duration of individual events. The registry entry does not provide event-level details or explain the distinction used for the “other” adverse-event category. It also does not provide a comparison group for interpreting these counts. The study had a single-group design, and the listed safety group is the gadobutrol group.
General explanation: safety counts are best read alongside information about how events were defined, collected, and followed, as well as the number of participants observed. The registry record reports the count of participants at risk and the counts affected, but does not report additional follow-up or ascertainment details. These figures describe the recorded safety information and should not be taken as a complete account of all possible events.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 3, open-label, multicenter, single-group study evaluated gadobutrol-enhanced breast MRI in people with newly diagnosed breast cancer. Participants underwent unenhanced and gadobutrol-enhanced MRM, with image sets evaluated in randomized fashion. The primary endpoint was defined as mean sensitivity for detecting the full extent of malignant breast disease, per reader, using Standard-of-Truth-verified malignant regions.
The record does not report the primary sensitivity estimates, their 95% confidence intervals, or a numerical comparison between CMRM and UMRM. It therefore does not show how large the observed sensitivity was, how the two imaging approaches compared, or how precisely any difference was estimated. Secondary outcome results are also not reported in the registry record. No conclusion about the direction or size of the findings can be drawn from the endpoint definitions alone.
The study’s non-randomized, single-group design is relevant to interpretation. It compares two imaging assessments within participants, but it is not a randomized comparison of separate groups. The recorded randomization applies to the order of image-set evaluation, not to participant allocation. These design features describe what was compared; they do not substitute for the missing outcome estimates.
General explanation: diagnostic sensitivity is one aspect of test performance. It does not alone establish effects on treatment decisions, health outcomes, or the overall balance of benefits and harms. The registry’s listed endpoints focus on detection measures, and the numeric results needed to characterize those measures are absent.
The record reports 0 participants with serious adverse events and 10 with other adverse events among 426 at risk in the gadobutrol group. Those counts are limited safety information and do not supply event descriptions or a control-group comparison. In sum, the record explains the study question and the intended measurements, but does not report numerical efficacy results sufficient to judge the observed diagnostic performance.
13. Why This Trial Matters Statistically
This study is statistically notable for its within-participant imaging comparison. Each participant underwent unenhanced MRM and then gadobutrol-enhanced MRM, allowing the study to define a comparison of image-based detection approaches within the same participants. That design differs from a randomized trial in which participants are allocated to distinct intervention groups. Recognizing the distinction is important when interpreting what the comparison can establish.
The primary endpoint also has a specific diagnostic focus: sensitivity for identifying the full extent of malignant breast disease, assessed per reader and averaged across participants. The endpoint definition identifies how regions and participant-level sensitivities contributed to the measure. The analysis population is also explicitly described as 388 participants with malignant regions verified by the Standard of Truth, while the overall enrollment is 446.
Several readers were involved, and the official title describes blinded image reading. The record also states that image sets were evaluated in randomized fashion. Together, these details make clear that reader assessment and reading order were part of the study’s design. They should not be confused with randomized participant allocation, which the record identifies as non-randomized.
The record’s main statistical limitation is that it does not report the numeric primary endpoint results or their confidence intervals. Although the endpoint is defined and its intended precision measure is specified, the actual sensitivity estimates and uncertainty cannot be evaluated. Secondary outcomes are listed, but their results and methods for handling multiple comparisons are not reported in the registry record.
This study therefore illustrates why a clearly defined diagnostic endpoint and design description are not enough to assess the findings. Interpretation also requires the observed estimates, their uncertainty, and details of analysis and missing-data handling. Those results and methodological details are not reported in the registry record.
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 registry record does not report numeric results for the primary sensitivity endpoint, including the 95% confidence intervals specified for that measure. It also does not report numeric results for the listed secondary outcomes. The magnitude, direction, and precision of the imaging comparisons therefore cannot be assessed from the record.
The study was open label, non-randomized, and single group. Participants received unenhanced MRM followed by gadobutrol-enhanced MRM. The registry notes randomized evaluation of image sets and blinded image reading in the official title, but does not give further details of the blinding procedures or reader-level analysis. The reading order should not be mistaken for randomized allocation of participants.
The primary analysis population included 388 participants with Standard-of-Truth-verified malignant regions, while 446 participants were enrolled. The record does not explain this difference, report the number or nature of missing measurements, or describe how participants outside the primary analysis population were handled. It also does not describe missing-data sensitivity analyses.
The registry lists 25 outcome measures and records zero analyses. It does not report whether multiplicity adjustments were applied, which statistical tests were used, or whether the analysis plan included interim analyses. A sample-size justification is not reported in the registry record. These omissions prevent evaluation of several aspects of the planned and completed statistical analysis.
The listed safety counts are limited to 426 participants at risk, with 0 affected by serious adverse events and 10 affected by other adverse events. Event descriptions and deaths are not reported in the registry record. The absence of these details constrains interpretation of the safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast MRI — NCT01067976.
- Registry record last updated 2014-11-11; status last verified 2014-11.
- Results first posted 2014-11-11.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01067976 is a completed phase 3, open-label, multicenter, single-group study sponsored by Bayer. It enrolled 446 participants with newly diagnosed breast cancer and evaluated gadobutrol-enhanced breast MRM against unenhanced MRM. Gadobutrol was administered intravenously at 0.1 mmol/kg body weight at 2 ml/sec. The study began in 2010-02, with primary completion recorded as 2011-07.
The primary endpoint was mean sensitivity for detecting the full extent of malignant breast disease, per reader. The stated Full Analysis Set comprised 388 participants with malignant regions verified by the Standard of Truth. The registry lists 25 outcome measures and zero analyses. Numeric results for the primary and secondary outcomes, confidence-interval limits, and detailed statistical methods are not reported in the registry record.
For safety, 426 participants were listed at risk; 0 had serious adverse events and 10 had other adverse events. Deaths are not reported in the registry record.