Post Marketing Surveillance Study for Evaluation of Efficacy and Safety of Dotarem in Magnetic Resonance Mammography: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Post Marketing Surveillance Study for Evaluation of Efficacy and Safety of Dotarem in Magnetic Resonance Mammography (NCT03041298), a registered phase not stated study. The primary outcome is Image Quality.

2. Clinical Question

The study asked whether MR mammography performed with Dotarem could be characterized in terms of diagnostic efficacy, reliability and safety in a post-marketing setting. Its primary outcome was image quality during the MRI procedure, rated on a 5-point scale. The record also includes counts for serious and other adverse events.

3. Trial Design

This was a non-interventional post-marketing surveillance study sponsored by Guerbet. The registry describes the intervention as MR mammography with Dotarem and states that all included patients underwent that procedure. The study was marked completed. The recorded start date is 2011-09 and the primary completion date is 2013-10; the study summary describes the surveillance period as running from September 2011 to December 2013.

The stated purpose was to generate additional information about Dotarem’s diagnostic efficacy, reliability and safety in MR mammography. The summary says the study was conducted in accordance with section 67, paragraph 6 of the German drug regulation, Arzneimittelgesetz. These descriptions establish the post-marketing context, but do not by themselves specify how participants were recruited, how image ratings were assigned, or how adverse events were collected.

Enrollment was 1537. This is the enrollment figure in the registry record; it should not automatically be treated as the number contributing data to every outcome. The primary outcome description says image quality was missing for 16 patients. The record does not give category counts for the ratings, nor does it state how the missing ratings were handled.

The record does not describe a randomized allocation or a control group. Its skip information explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The intervention description instead says all included patients underwent the procedure. No protocol details beyond the recorded descriptions, such as site procedures or assessor training, are 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

Analysis population for the primary outcome, as defined in the registry: Image quality was missing for 16 patients.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Image Quality, measured over During MRI procedure.

The primary endpoint is image quality during the MRI procedure. The registry describes a 5-point rating scale with the categories “excellent,” “good,” “moderate,” “poor” and “very poor.” The endpoint is expressed in participants, and its stated parameter is a count of participants. The record notes that image quality was missing for 16 patients.

In general, image-quality ratings can describe how clearly an examination depicts the features that clinicians need to assess. An ordinal scale such as this orders ratings from more favorable to less favorable, but the steps between adjacent categories are not necessarily equal. A category count therefore describes the distribution of ratings without assuming that the difference between “excellent” and “good” is quantitatively identical to the difference between “moderate” and “poor.”

The registry record does not report how many participants received each rating. It also does not report a summary estimate, confidence interval or statistical test for this endpoint. The stated objective of generating diagnostic-efficacy and reliability information should not be mistaken for a reported endpoint result: without the rating distribution or analysis, the outcome’s observed pattern cannot be characterized from the recorded information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by distinguishing a descriptive surveillance study from a comparative experiment. This study is described as non-interventional and post-marketing. All included patients underwent MR mammography with Dotarem, while the registry does not describe a control group. A count or rating distribution from such a setting can describe observations among included patients, but it does not, by itself, isolate the effect of the contrast agent from other factors that could influence imaging or event reporting.

What does the image-quality scale represent?

The primary endpoint is categorical and ordered: “excellent,” “good,” “moderate,” “poor” and “very poor.” In general, ordered categories preserve rank information, but do not imply equal spacing between categories. A simple category count can show how ratings are distributed; an average score would require an explicit numeric coding and an assumption about what that coding means. The registry record does not report a numeric coding, category frequencies, or an analysis method for these ratings. It is therefore not possible to reconstruct a summary statistic from the recorded endpoint description.

The endpoint is described as a count of participants, so the natural descriptive information would include the number rated in each category and the number with no recorded rating. The record states that image quality was missing for 16 patients, but does not report the category counts. Missing ratings can affect the interpretation of a distribution if the patients without ratings differ from those with ratings. In general, missing-data handling should be stated because excluding missing observations, imputing values, or using another approach can lead to different interpretations. The registry record does not report which approach, if any, was used.

What can safety counts establish?

The safety entries are counts of participants with events, with the corresponding numbers at risk recorded for the group. Such counts describe the events captured in the registry record. They are not automatically estimates of comparative risk: that requires an appropriate comparison and an analysis that accounts for the study design. Here, the record provides no like-for-like control group. It also does not report event definitions, follow-up duration for each participant, adjudication procedures, or the completeness of event collection in the information available for this analysis.

For a binary outcome, an uncertainty interval can communicate how precisely an observed proportion is estimated under a specified statistical model. In general, an interval is not a guarantee that the true value lies within its limits; it expresses uncertainty under the method’s assumptions. The registry record does not report confidence intervals for the safety counts or the primary outcome. The listed percentages for serious-event terms are registry entries and should be quoted as reported rather than treated as newly calculated rates.

What does the record say about analysis?

The registry reports 5 outcome measures and 0 analyses. It does not report inferential tests, adjusted estimates, or a statistical analysis plan in the information. The absence of a recorded analysis means that no p-value or model-based conclusion should be inferred from the endpoint labels or safety counts. It also means there is no basis for claiming that covariates, clustering, or potential confounding were addressed in a statistical model.

Multiplicity concerns arise when multiple outcomes or multiple statistical tests are considered. In general, testing many hypotheses can increase the chance of obtaining a nominally notable result by chance. A prespecified hierarchy, adjustment method, or clear distinction between primary and exploratory analyses can help readers interpret multiple results. The registry lists multiple outcome measures, but the record does not describe a multiplicity procedure. Because no analyses are recorded, it is not possible to assess how multiplicity was handled in practice.

How should the planning illustrations be understood?

The planning assumptions associated with the sample-size illustrations describe a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. They state that the effect to detect is a specified fraction of the observed effect; for time-to-event tables, the illustration uses a total event count based on the Schoenfeld approach, while other illustrations are expressed as participants per arm. These are planning assumptions, not evidence that the surveillance study itself used two randomized arms. The study description says all included patients underwent the procedure, and the registry cautions that it is not a randomized comparison.

In general, a planning calculation asks how much information a future design might need under chosen assumptions. It is not an observed result and should not be described as observed power. The registry record does not report a sample-size justification for the study’s own design. Any planning illustration based on an observed effect also depends on the stability and relevance of that effect; it does not repair the absence of a comparator or supply the missing image-quality results.

Over-dispersion is a general issue when variability in observed counts exceeds what a simple statistical model assumes. It can make standard errors too small if ignored. The registry record does not report a model for count variability or indicate that over-dispersion was assessed. This general consideration should not be mistaken for a claim that over-dispersion occurred in this study.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 5 outcome measures and 0 analyses. It identifies image quality as the primary endpoint, but does not report how the other outcomes were ranked or whether any multiplicity strategy was specified. In general, testing several endpoints can make isolated nominal findings harder to interpret. A prespecified analysis plan can clarify which results are confirmatory and how any adjustment is handled. Such a plan or adjustment method is not reported in the registry record.

For the primary endpoint, image quality was missing for 16 patients. The record does not say why ratings were missing, whether missingness differed across clinical or procedural circumstances, or how missing observations were handled. It also does not report the number of participants contributing ratings in each category. These omissions prevent assessment of whether the reported distribution, if analyzed, might be sensitive to missing data.

The enrollment figure is 1537, but enrollment alone does not establish the analysis population for each outcome. The record does not specify an analysis set, exclusions, or denominators for the image-quality categories. No imputation method, sensitivity analysis, or missing-data assumption is reported. As a result, readers cannot determine from the registry record whether all enrolled participants were included in every analysis or how absent observations influenced conclusions.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: rash (0.1%), urticaria (0.1%), tachycardia (0.1%), dysphagia (0.1%).

Among the all-included-patients group, the registry reports 1537 participants at risk for serious adverse events and 1 participant with a serious adverse event. For other adverse events, it reports 1537 at risk and 4 participants affected. The recorded number of deaths is 0. The leading serious adverse-event terms listed are Rash, Urticaria, Tachycardia and Dysphagia, each reported as 0.1%.

These are descriptive counts from the registry record. They do not establish whether an event was caused by Dotarem, and no comparison group is reported for estimating a relative difference. The record does not provide confidence intervals or details about event ascertainment, follow-up, or adjudication. The term-level percentages should be read as recorded, not recalculated or interpreted as comparative estimates. Counts across event categories should not be added to infer a total, since the record does not establish whether participants could appear in more than one category.

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

The record does show that a post-marketing surveillance study was conducted to gather information on MR mammography with Dotarem, with image quality designated as its primary outcome and safety events also recorded. It gives an enrollment figure and reports selected serious and other adverse-event counts, along with the number of deaths recorded. These details describe the study’s scope and the data entered in the registry.

It does not show the image-quality distribution. Although the 5-point scale is specified, category counts and an analysis are not reported in the registry record. The stated aims of evaluating diagnostic efficacy and reliability are not themselves evidence of a particular finding. Without the primary endpoint results, the recorded information cannot establish how image quality was rated or how precisely any rating pattern was estimated.

The safety counts also have limited interpretive reach. They are not a comparison against an untreated group or another contrast agent, and they do not by themselves establish that Dotarem caused or did not cause an event. The absence of reported uncertainty estimates means the precision of these counts cannot be judged from the registry record. Nor does the listed absence of deaths establish that no deaths occurred outside the recorded study data.

Because the study is non-interventional and no like-for-like comparator is described, its data should not be interpreted as a randomized estimate of a treatment effect. The posted information is best read as a record of study purpose, outcome definitions and selected event counts. It does not support claims about comparative efficacy, comparative safety, or the certainty of an image-quality effect.

13. Why This Trial Matters Statistically

This study illustrates a central statistical distinction: recording an outcome and reporting its result are different things. The registry identifies image quality as the primary endpoint and defines its ordered categories, but does not report the category counts or an analysis. A clearly named outcome helps readers understand what investigators intended to assess; without results, however, the outcome cannot answer the clinical question.

The post-marketing, non-interventional setting is also statistically important. Surveillance can describe observations in routine use, while a comparison designed to estimate differences requires a suitable comparator and methods that address sources of bias. The registry describes all included patients as having undergone MR mammography with Dotarem and cautions that the study is not a randomized comparison. Accordingly, the safety counts are informative as recorded observations, not as estimates of relative risk.

The missing image-quality ratings matter for transparency. The record notes that ratings were missing for 16 patients, but does not explain the missingness or its handling. Reporting the outcome distribution, analysis population and missing-data approach would help readers understand how much evidence supports any interpretation. The same principle applies to safety: counts are easier to interpret when event definitions, follow-up and uncertainty are reported.

Finally, the registry’s analysis entries are absent even though multiple outcomes are listed. This makes it impossible to assess the statistical methods or multiplicity handling. The case demonstrates why endpoint definitions, complete results and analysis details are all needed for a reader to evaluate precision and limitations, rather than relying on study aims alone.

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 primary limitation for interpreting efficacy and reliability is that the registry record does not report the image-quality category counts or an analysis. The outcome is defined, but its observed distribution is unavailable. Although the record notes missing image-quality data for 16 patients, it does not describe the reasons for missingness, the handling of those observations, or the analysis population.

The study has no like-for-like control comparison described in the record. All included patients underwent MR mammography with Dotarem, and the record cautions that the study is not randomized. The safety counts therefore cannot be interpreted as comparative estimates or as proof of a causal relationship. The registry does not report confidence intervals, adjusted analyses or a statistical analysis plan.

Further limitations include the absence of reported participant characteristics, eligibility details, event-collection procedures and outcome-assessment procedures in the information available for this analysis. The record also does not report how the listed 5 outcome measures were prioritized beyond identifying image quality as primary, or how multiplicity was addressed. These gaps limit assessment of selection, measurement, precision and the generalizability of observations. The limitations identify what is not reported; they do not establish that a particular bias or problem occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Post Marketing Surveillance Study for Evaluation of Efficacy and Safety of Dotarem in Magnetic Resonance Mammography — NCT03041298.
• Registry record last updated 2017-05-02; status last verified 2017-03.
• Results first posted 2017-05-02.
• 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.

18. Record Summary

The registry record describes a completed, non-interventional post-marketing surveillance study sponsored by Guerbet. All included patients underwent MR mammography with Dotarem. Enrollment was 1537; the recorded start date was 2011-09 and primary completion date was 2013-10.

Image quality during the MRI procedure was the primary endpoint, measured on a 5-point scale. The record notes missing image-quality data for 16 patients but does not report the category results or an analysis. Safety entries report 1 serious adverse event and 4 other adverse events among 1537 at risk, with 0 deaths. The record lists 5 outcome measures and 0 analyses. No randomized comparator or like-for-like control comparison is described.