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 Observational Post-marketing Study on the Safety and Efficacy of Dotarem® (SECURE Study) (NCT01523873), a registered phase not stated study. The primary outcome is Frequency of Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01523873 |
| Phase | Phase not stated |
| Condition | General Safety Profile of DOTAREM |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 35921 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Guerbet |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled 35921 participants. Its safety-population entries list 35474 participants at risk for serious and other adverse events. The registry record does not report further population characteristics or a detailed eligibility description, so the findings cannot be placed in context by age, clinical condition, or other participant features from this record alone.
Intervention
The study concerns Dotarem®, a contrast agent administered for magnetic resonance examination. It is described as an observational post-marketing study intended to assess the product’s general safety profile prospectively. The registry record does not describe a treatment assignment process, dose, or administration protocol in the details available for this analysis.
Comparator
No like-for-like control comparison is established in the registry record. The study is not reported as a randomized comparison, and allocation is not stated. Accordingly, any groups or arms associated with the record should not be read as randomized treatment and control groups or as a basis for estimating a causal contrast.
Primary question
The primary outcome is the frequency of adverse events during usual follow-up after Dotarem administration. The stated observation window ranges from <30 min to 1 hour after magnetic resonance examination. The registry says that adverse events were notified and described. The practical question is therefore what adverse-event experience was recorded during this follow-up, not whether Dotarem caused a particular event or performed better than another treatment. The record also names nephrogenic systemic fibrosis incidence, image quality, and diagnostic quality as secondary outcomes.
3. Trial Design
SECURE is identified as an observational post-marketing study sponsored by Guerbet. The stated purpose is to assess the general safety profile of Dotarem, and the brief description says this assessment was prospective. The registry lists the study as completed, with a start date of 2008-11 and primary completion in 2013-07. Enrollment is 35921.
An observational design records events in the context of care rather than assigning participants to study treatments through randomization. That distinction matters when interpreting event counts: these data can describe what was recorded in the study population, but a comparison between groups would need a valid, clearly described comparator and a suitable analysis. The registry record does not state allocation, and it does not establish a randomized comparison. Its groups are not a like-for-like control comparison.
The safety results identify a safety population of 35474 at risk for serious and other adverse events. Enrollment and the safety-population count are distinct figures in the record; the reasons for the difference are not reported in the registry record. The record does not report a detailed account of participant flow, exclusions, or the criteria used to define the safety population.
The primary outcome is frequency of adverse events. The stated follow-up is usual follow-up after Dotarem administration, from <30 min to 1 hour after magnetic resonance examination. The listed secondary outcomes are nephrogenic systemic fibrosis incidence, image quality, and diagnostic quality. The registry lists four outcome measures overall, but the details available do not provide a complete account of how each was assessed.
No detailed protocol, randomization method, allocation process, or comparison plan is reported in the registry record. The observational design and the absence of a defined control comparison limit conclusions to description of the posted observations.
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 | All Included Patients |
|---|---|
| STARTED | 35921 |
| Administered With Dotarem | 35474 |
| COMPLETED | 35499 |
| NOT COMPLETED | 422 |
Reasons for not completing this period:
| Reason | All Included Patients |
|---|---|
| Protocol Violation | 422 |
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 | All Included Patients |
|---|---|---|
| Participants analysed | 35499 | |
| Age, Continuous | years | 49.5 (SD 17.9) |
| Age, Customized: <18 years | participants | 1631 |
| Age, Customized: from 18 to 64 years | participants | 26058 |
| Age, Customized: ≥65 years | participants | 7735 |
| Gender: Female | Participants | 18838 |
| Gender: Male | Participants | 16620 |
| Region of Enrollment: France | participants | 7692 |
| Region of Enrollment: Argentina | participants | 43 |
| Region of Enrollment: Austria | participants | 703 |
| Region of Enrollment: China | participants | 7064 |
| Region of Enrollment: Germany | participants | 9988 |
| Region of Enrollment: India | participants | 6803 |
| Region of Enrollment: Italy | participants | 328 |
| Region of Enrollment: Saudi Arabia | participants | 372 |
| Region of Enrollment: Spain | participants | 1039 |
| Region of Enrollment: United Kingdom | participants | 1467 |
6. Primary Endpoint
The registry lists the primary outcome as Frequency of Adverse Events, measured over During the time of usual follow-up post Dotarem administration (from less than 30 min to 1 hour after magnetic resonance examination)..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Adverse Events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled Frequency of Adverse Events, with the unit described as adverse events and the parameter described as a number. The registry states that adverse events were notified and described. Its timeframe is usual follow-up after Dotarem administration, from <30 min to 1 hour after magnetic resonance examination. This defines the period during which the reported events were considered for the endpoint; it does not establish longer-term surveillance.
Counting adverse events is a way to describe the safety experience recorded during a specified period. For a count to be interpretable, readers need to know what qualifies as an event, how events are collected, whether the count refers to events or participants affected, and how much follow-up participants contribute. Those details are not reported in the registry record beyond the brief description of notification and the stated follow-up window.
The record classifies this as a count outcome rather than reducing it to one comparison. The posted safety entries give counts for serious and other adverse events in the safety population, but the primary outcome description does not report a single inferential estimate, confidence interval, or statistical test. The secondary outcomes include nephrogenic systemic fibrosis incidence, image quality, and diagnostic quality. Their presence indicates additional study interests, but their measurement definitions and results are not reported in the registry record details.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry’s safety-population entries list 9 affected under serious adverse events and 35 affected under other adverse events, each among 35474 at risk. These are descriptive counts. They show that the record contains entries in both categories; they do not by themselves identify the causes of events, establish the likelihood of an event for an individual, or demonstrate a causal relationship with Dotarem.
The primary outcome is described as a frequency, but the posted primary result does not include a reported statistical analysis. The record lists zero analyses. It therefore does not provide an adjusted estimate, a confidence interval, or a test of a specific hypothesis for the primary endpoint. The separate safety counts should not be mistaken for a complete statistical evaluation of the endpoint.
The serious-event term list displays 0.0% beside Adverse event, Death, Multi-organ failure, Renal failure, Haemorrhagic diathesis, and Cardiac failure. A displayed percentage of 0.0% is not sufficient to conclude that no event occurred, particularly when the safety-population entry separately records 9 affected under serious adverse events. The registry record does not report the precision or rounding convention for those term percentages, nor does it explain how the listed terms relate to the aggregate serious-event count. The two forms of reporting therefore cannot be reconciled from the record alone.
The study’s observational design is also important. There is no randomized treatment assignment or like-for-like control comparison reported. Counts observed after administration can describe the recorded experience, but without an appropriate comparator they cannot isolate the effect of Dotarem from other explanations. The registry record also does not report participant characteristics, event ascertainment procedures in detail, or follow-up beyond the stated usual follow-up window.
In general, confidence intervals communicate the uncertainty around an estimate, while a statistical test evaluates data against a specified null hypothesis. Neither is reported for the primary result in this registry record. The posted counts should therefore be read as a limited descriptive account, not as a precise comparative or causal estimate.
9. Statistical Methods Explained
What does a count outcome describe?
The primary endpoint is a count-type outcome: the registry describes the frequency of adverse events and specifies the unit as adverse events. In general, a count records how many events are observed under a defined set of observation conditions. It is not automatically the same as the number of participants who experience an event. One participant might have more than one event, and the registry record would need to clarify whether its count refers to events, affected participants, or both. The primary outcome description says events were notified and described, but it does not report these counting details.
Counts are also interpreted in light of the time during which events could be recorded and the population under observation. The stated follow-up runs from <30 min to 1 hour after magnetic resonance examination. The safety entries use 35474 participants at risk. The record does not give individual follow-up durations or additional details about how that population was assembled. Consequently, the posted information does not support a more detailed time-based estimate.
Why is the design relevant to statistical interpretation?
In general, random assignment helps make groups comparable with respect to measured and unmeasured characteristics, on average. This record is observational, does not state allocation, and does not establish a like-for-like control comparison. The reported event counts therefore describe observations in the safety population rather than an experimental contrast. Statistical adjustment can sometimes address measured differences, but it cannot be assumed to have been performed; no analysis is reported in the registry record.
For a causal interpretation, analysts would need a clearly defined comparison, information about the people included, and a plan for handling factors that may influence both treatment exposure and outcomes. Such a plan is not reported in the registry record. No causal effect should be inferred simply from the timing of an event after administration.
What do uncertainty measures add?
In general, a confidence interval gives a range of estimates compatible with the observed data under the assumptions of the method. Its width reflects precision: narrower intervals indicate greater precision, while wider intervals indicate greater uncertainty. A p-value, when used with a prespecified hypothesis and model, describes how unusual the observed data would be under a null hypothesis. Neither measure replaces consideration of design, bias, or clinical meaning.
The registry record does not report a confidence interval, p-value, model-based estimate, or test for the primary endpoint. It lists zero analyses. This means the safety counts can be stated descriptively, but the record does not provide inferential uncertainty around them. General methods for counts might use rates, count models, or exact methods depending on the data structure and assumptions; none can be attributed to this study from the information reported.
How should planning illustrations be understood?
Any sample-size values associated with planning illustrations are not observed study outcomes and are not the study’s own design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event illustrations, the calculation concerns the total number of events using the Schoenfeld method; other illustrations are expressed as participants per arm.
These assumptions are generic planning conventions, not evidence that this observational study used two randomized arms or was designed around a particular effect. In particular, the record does not establish a like-for-like comparison or report the study’s own sample-size justification. A planning calculation based on an observed effect is not observed power and does not establish that the study could reliably detect a specified effect. The registry record does not report an interim-analysis plan or a detailed statistical analysis plan.
What can be concluded from the posted methods?
The record supports a descriptive reading of the event counts and the stated observation window. It does not support reconstructing a statistical model or verifying how events were classified, counted, or analyzed. General statistical methods can clarify what additional information would be useful, but they cannot fill in methods that are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry names a primary outcome and lists secondary outcomes of nephrogenic systemic fibrosis incidence, image quality, and diagnostic quality. It also reports four outcome measures overall. When a study examines multiple outcomes, multiplicity can affect how readers interpret evidence from statistical tests: repeated testing can increase the chance of at least one apparently notable finding. In general, a study may address this through a prespecified hierarchy, adjustment, or a clearly exploratory interpretation.
The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or an analysis plan for the four outcome measures. It does not report an interim-analysis plan. No hypothesis tests are reported for the primary endpoint, and the record lists zero analyses. It is therefore not possible to assess how multiple outcomes were handled or whether any formal adjustment was intended.
Missing-data methods are also not reported in the registry record. The enrollment is 35921, while the safety population at risk is 35474. The record does not explain the difference or describe missing outcome observations, withdrawals, exclusions, or imputation. A reader cannot determine from these details whether all enrolled participants contributed to the safety counts, why some were not included in the stated safety population, or how any incomplete follow-up was treated.
The record does not provide a detailed definition of the analysis populations beyond naming the safety population, nor does it specify whether the primary endpoint used another population. These omissions constrain reproducibility and make it difficult to assess the possibility of selection bias. They also limit conclusions about how representative the posted safety counts are of all enrolled participants.
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 |
|---|---|---|---|
| Safety Population | 9 | 35474 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Safety Population | 35 of 35474 |
Most frequent serious adverse event terms
| Event term | Organ system | Safety Population |
|---|---|---|
| Adverse event | General disorders | 2 of 35474 |
| Death | General disorders | 2 of 35474 |
| Multi-organ failure | General disorders | 2 of 35474 |
| Renal failure | Renal and urinary disorders | 2 of 35474 |
| Haemorrhagic diathesis | Blood and lymphatic system disorders | 1 of 35474 |
| Cardiac failure | Cardiac disorders | 1 of 35474 |
| Cardio-respiratory arrest | Cardiac disorders | 1 of 35474 |
| Cardiovascular insufficiency | Cardiac disorders | 1 of 35474 |
| Mitral valve incompetence | Cardiac disorders | 1 of 35474 |
| Intra-abdominal haemorrhage | Gastrointestinal disorders | 1 of 35474 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Safety Population |
|---|---|---|
| Urticaria | Skin and subcutaneous tissue disorders | 9 of 35474 |
| Nausea | Gastrointestinal disorders | 7 of 35474 |
| Vomiting | Gastrointestinal disorders | 4 of 35474 |
| Pruritus | Skin and subcutaneous tissue disorders | 2 of 35474 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 35474 |
| Crohn's disease | Gastrointestinal disorders | 1 of 35474 |
| Chills | General disorders | 1 of 35474 |
| Extravasation | General disorders | 1 of 35474 |
| Feeling hot | General disorders | 1 of 35474 |
| Injection site erythema | General disorders | 1 of 35474 |
Serious events with the highest arm-level rate: adverse event (0.0%), death (0.0%), multi-organ failure (0.0%), renal failure (0.0%), haemorrhagic diathesis (0.0%).
The safety-population entries state that 9 participants were affected under serious adverse events and 35 under other adverse events, each among 35474 at risk. These are the counts recorded in the registry, not a comparison between treatment groups. The available record does not provide detailed criteria for seriousness, event adjudication, or the relationship of each event to Dotarem.
The listed serious-event terms each carry a displayed value of 0.0%: Adverse event, Death, Multi-organ failure, Renal failure, Haemorrhagic diathesis, and Cardiac failure. Those displayed values should not be interpreted as proof that the corresponding terms never occurred. The aggregate serious-event entry lists 9 affected, while the registry record does not explain the term-level percentages, their rounding, or the relationship between those terms and the aggregate count.
In general, safety counts are easier to interpret when definitions, observation periods, denominators, and event-level detail are reported consistently. Here, the stated window is usual follow-up from <30 min to 1 hour after magnetic resonance examination. The record does not provide enough detail to evaluate longer-term safety or to attribute an event to the product. The counts are descriptive observations, not evidence of causation.
12. What the Result Does, and Does Not, Mean
The results establish that the registry contains a completed observational post-marketing study of Dotarem and reports safety-population counts for serious and other adverse events. The recorded counts are 9 affected under serious adverse events and 35 under other adverse events, each among 35474 at risk. These figures describe the entries in the record during the stated usual follow-up period.
They do not establish that Dotarem caused the reported events, nor do they quantify a causal effect relative to another product or to no exposure. The study is not reported as randomized, allocation is not stated, and no like-for-like control comparison is established. Without a suitable comparison and a reported analysis, differences attributable to treatment cannot be separated from other factors.
The counts also do not give a complete picture of safety over time. The reported follow-up ranges from <30 min to 1 hour after magnetic resonance examination. The registry record does not report longer-term follow-up, detailed event definitions, ascertainment procedures, or a full account of participant flow. The listed adverse-event terms with displayed percentages of 0.0% do not resolve the meaning of the aggregate serious-event count because the registry does not explain their relationship.
The record names nephrogenic systemic fibrosis incidence, image quality, and diagnostic quality as secondary outcomes, but the details do not include their results or measurement methods. The primary endpoint likewise has no reported inferential analysis, confidence interval, or hypothesis test. Thus the result is best read as a limited descriptive safety record, rather than a comparative estimate or a definitive assessment of benefit, harm, or causation.
13. Why This Trial Matters Statistically
Post-marketing observational studies can document events in routine-use settings and contribute descriptive information about a product’s safety experience. This study is relevant statistically because it illustrates the distinction between a large enrollment count and a complete, interpretable analysis. Enrollment is 35921, while the stated safety population is 35474 at risk. The record does not explain that difference, so the denominator and population definition require careful attention.
It also illustrates why event counts need context. The primary outcome is a frequency, but a useful interpretation depends on event definitions, ascertainment, follow-up, and whether the count represents events or participants. The record gives a follow-up window and states that events were notified and described, but it does not report further detail about these procedures. Counts alone do not provide a measure of statistical precision or a basis for causal attribution.
The study is observational and does not establish a like-for-like comparator. That design can describe recorded experience, but it does not provide the same basis for a causal contrast as a randomized comparison. The registry lists zero analyses and does not report confidence intervals, hypothesis tests, missing-data methods, or a multiplicity plan. This makes transparent reporting of the underlying methods especially important.
Finally, the serious-event summary and the term-level display need to be read together with caution: the safety entry lists 9 affected, while the listed terms display 0.0%. The registry does not explain how those values correspond. This is a practical reminder that rounded displays and aggregate counts may not answer the same question, and that definitions and reporting conventions are necessary for a clear statistical account.
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.
Important details needed to assess the study’s representativeness and event ascertainment are not reported in the registry record. The participant characteristics and eligibility criteria are not described in the available details. Enrollment is 35921, but the safety population is 35474 at risk, and the reasons for the difference are not reported. Participant flow, exclusions, withdrawals, and incomplete follow-up are also not described.
The outcome definition is brief: adverse events were notified and described, during usual follow-up from <30 min to 1 hour after magnetic resonance examination. The registry does not report detailed event definitions, how events were collected or verified, or whether the count refers to events or affected participants for the primary endpoint. The safety entries are reported as affected counts, but the record does not provide event-level detail or attribution assessments.
No randomized comparator is established, and allocation is not stated. The registry does not report adjustment for potential confounding or an analysis plan. It also does not report an inferential analysis of the primary outcome, uncertainty estimates, missing-data methods, multiplicity handling, or interim analyses. The study’s sample-size justification is not reported in the registry record.
The record lists serious-event terms with displayed percentages of 0.0% while the safety entry records 9 affected under serious adverse events. It does not explain the percentages’ precision or their relationship to the aggregate count. The secondary outcomes are named, but detailed methods and results are not reported in the information available. These limitations restrict interpretation to the descriptive information recorded and prevent a fuller assessment of precision, completeness, and causality.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Observational Post-marketing Study on the Safety and Efficacy of Dotarem® (SECURE Study) — NCT01523873.
- Registry record last updated 2017-02-24; status last verified 2017-01.
- Results first posted 2016-01-22.
- 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
The registry identifies SECURE as a completed observational post-marketing study sponsored by Guerbet. The study began in 2008-11, reached primary completion in 2013-07, and enrolled 35921 participants. Its stated purpose was prospective assessment of the general safety profile of Dotarem.
The primary outcome was frequency of adverse events during usual follow-up after magnetic resonance examination, from <30 min to 1 hour. The safety population lists 35474 at risk, with 9 affected under serious adverse events and 35 under other adverse events. Secondary outcomes include nephrogenic systemic fibrosis incidence, image quality, and diagnostic quality.
The registry does not establish a randomized or like-for-like control comparison and lists zero analyses. It does not report a statistical analysis of the primary outcome, detailed event methods, or explanations for the difference between enrollment and the safety population. The posted counts are descriptive and do not establish causation.