Eovist vs. Dotarem Healthy Volunteer MRI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Eovist vs. Dotarem Healthy Volunteer MRI (NCT02431598), a randomized phase 4 study. The primary outcome is Subject Breath Hold Capacity, as Measured by Number of Seconds a Subject Can Hold His/Her Breath.

2. Clinical Question

The central statistical feature is the crossover arrangement: each participant experienced all three conditions. This makes the outcomes repeated observations within participants rather than results from three independent parallel groups. Comparisons should therefore account for the fact that measurements from the same person may be related. The registry record does not report the method used to analyze that within-participant structure.

3. Trial Design

The registry describes a randomized, single-masked, placebo-controlled crossover study, listed as Phase 4 and completed. Its title identifies Eovist and Dotarem in healthy volunteers undergoing MRI. The brief description says volunteers received three blinded, randomized injections while having a liver MRI and holding their breath. The study arms likewise state that each participant received a clinical dose of Eovist, Dotarem, and normal saline in random order, without being told which agent was administered on a given occasion.

Enrollment was 44. Because the same participants received all three agents, the three arm-specific results represent repeated treatment conditions, not three separate parallel groups. The arm-level records each list 44, consistent with the registry description that all participants received all three drugs. These arm counts should not be added to infer a number of unique participants.

During scanning, oxygen saturation and heart rate were monitored. Following the scan, participants completed a questionnaire about the breath hold. The primary endpoint was breath-hold capacity in seconds following administration, up to 5 minutes. Secondary outcomes included oxygen saturation and heart rate over the same stated timeframe, the percentage with transient severe motion based on arterial-phase imaging artifacts, and artifact severity on a 1-5 scale.

The record lists Duke University as sponsor and identifies three study sites in the brief description. It gives a start date of 2015-06 and primary completion date of 2015-09. Further details about sequence-generation procedures, concealment of treatment order, the identity of the masked party beyond the participants, and handling of period or order effects are not reported in the registry record. The planned statistical model and any sample-size justification are also 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

Analysis population for the primary outcome, as defined in the registry: All participants received all three drugs.

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 Subject Breath Hold Capacity, as Measured by Number of Seconds a Subject Can Hold His/Her Breath, measured over following contrast administration, up to 5 minutes.

The primary endpoint was subject breath-hold capacity, measured as the number of seconds a participant could hold their breath following contrast administration, up to 5 minutes. Breath-hold duration was relevant to the study’s stated concern about transient dyspnea and motion during arterial-phase MRI. A shorter or interrupted breath hold could be associated with motion artifact during image acquisition, while the endpoint directly records how long the volunteer could sustain the instructed breath hold.

The registry reports the endpoint as a median with a full range for each treatment condition. The median describes the middle of the observed durations after ordering them; the full range gives the smallest and largest reported values. These summaries convey the center and spread of the recorded values, but they do not describe how each individual’s duration changed between treatments. In a crossover study, within-participant changes are particularly informative because each person contributes observations under every condition.

The posted medians were 28.0 seconds for Eovist, 38.0 seconds for Dotarem, and 35.0 seconds for saline. The corresponding full ranges were 8.0 to 117.0, 23.0 to 125.0, and 20.0 to 108.0 seconds. Those summaries describe the observed treatment-condition distributions. The registry record does not post a primary-endpoint comparison, confidence interval, or inferential analysis, so the medians alone do not establish whether the differences are larger than would be expected from sampling variation.

Breath-hold duration is one component of the clinical question, not a complete measure of breathing symptoms or image quality. The record does not report a primary endpoint result for transient dyspnea itself. Motion-related outcomes appear among the secondary measures.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the primary summaries tell us?

The primary outcome is reported as a median and full range, rather than a mean and standard deviation. A median identifies the central observation in an ordered set of measurements. It is less influenced by unusually high or low values than a mean. The full range reports the observed endpoints of the data, but does not indicate how values are distributed between those endpoints. With ranges extending from 8.0 to 117.0 seconds, 23.0 to 125.0 seconds, and 20.0 to 108.0 seconds, the record indicates considerable variation in breath-hold duration within each condition.

A group-level median does not reveal the pattern of paired changes. For example, it does not show whether the same participants tended to have shorter breath holds under one agent, whether changes varied in direction, or how large within-person changes were. Those questions require participant-level paired data or reported paired analyses. Neither a primary comparison nor its uncertainty is reported in the registry record.

Why does the crossover structure matter?

In a crossover trial, a participant receives more than one treatment condition. Measurements from the same person are generally related because personal characteristics and measurement tendencies persist across conditions. A suitable comparison can use each participant as their own control, accounting for this within-person association. A parallel-group method that assumes independent observations does not use that design information and may calculate uncertainty incorrectly.

Randomized treatment order helps avoid systematically assigning one treatment to an earlier or later position, but it does not by itself address every possible period, sequence, or carryover effect. The registry record does not report the specific analysis method, whether treatment order was modeled, or how these potential design features were handled. No conclusions about their handling can be drawn from the arm summaries alone.

How should the secondary comparisons be read?

The oxygen saturation and heart-rate comparisons are unadjusted recalculations from the posted means, standard deviations, and arm counts. They are not analyses reported by the sponsor. For each listed treatment contrast, the calculated mean difference is 0.0 and the corresponding interval includes zero, the value representing no difference. A confidence interval describes a range of estimates compatible with the data and the method used; it communicates precision as well as direction. An interval that includes zero does not establish equivalence. A formal equivalence conclusion would require prespecified margins and an analysis designed for that question, neither of which is reported in the registry record.

The motion outcome is binary: a participant either had the specified transient severe motion outcome or did not. A risk difference expresses the difference between the proportions in two conditions. Its confidence interval indicates uncertainty around that difference. The recalculated comparisons are unadjusted and their intervals include no difference. The p-values, 0.306 and 0.078, also come from these unadjusted recalculations, not from reported sponsor analyses. A p-value is a measure of how incompatible the observed data are with a specified null model under the analysis assumptions; it is not the probability that the null hypothesis is true, nor does it measure clinical importance.

Motion events were uncommon in the posted counts: the recalculated contrasts use 3 versus 1 events for Eovist versus Dotarem and 3 versus 0 for Eovist versus saline, with 44 listed in each condition. Sparse counts limit precision. When event numbers are small, adding or removing a single event can materially affect a proportion or relative effect estimate. This is one reason to attend to confidence intervals and underlying counts rather than interpreting a p-value in isolation.

What do the planning illustrations mean?

The planning values use the observed Eovist-Dotarem motion effect as a reference and show illustrations for detecting 100% of that observed effect, 75% of the observed effect, and 50% of the observed effect. Under the stated planning assumptions—two-sided significance level 0.05, equal allocation, and a normal approximation—the illustrations report 329 participants per arm for 80% power and 440 participants per arm for 90% power when planning for 100% of the observed effect. For 75% of the observed effect, they report 655 participants per arm for 80% power and 876 for 90% power. For 50% of the observed effect, they report 1,628 participants per arm for 80% power and 2,179 for 90% power.

These are planning illustrations based on the observed effect, not the study’s original design calculation and not observed power. Smaller effects require larger planned sample sizes under the same assumptions. The values should not be read as a retrospective claim about the probability that this trial detected an effect. The registry record does not report the original sample-size justification, and a planning calculation based on sparse observed events is sensitive to the effect estimate used.

All recalculated comparisons are unadjusted. The record does not report a multiplicity strategy or a model for repeated observations. Therefore, the comparisons are useful as descriptive statistical context, but they do not replace a prespecified analysis that accounts for the crossover structure and the set of outcomes considered.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity adjustment or testing hierarchy for the primary and secondary outcomes. The study assessed breath-hold capacity, oxygen saturation, heart rate, transient severe motion, and motion-artifact severity, and the record includes multiple treatment conditions. When multiple outcomes or contrasts are examined, unadjusted tests do not control the overall chance of at least one false-positive result across the full set of tests. Consequently, an unadjusted p-value should be interpreted as a result for its particular contrast, not as a confirmatory finding across the study.

The record lists no reported analyses for the primary endpoint or the secondary outcomes. It does not describe a prespecified statistical analysis plan, how the crossover and repeated measurements were modeled, whether order or period effects were examined, or how missing observations were handled. These details are not reported in the registry record. Their absence from the record should not be taken to mean that no analysis or planning occurred outside the registry; it means the posted record does not document those methods.

Analysis populations are also not described beyond the primary endpoint population statement that all participants received all three drugs. The registry does not report whether all enrolled participants contributed data to every outcome, whether any observations were excluded, or how incomplete participant records were treated. Missing-data counts and reasons are not reported in the registry record. Without those details, it is not possible to assess whether missingness could have affected the summaries or comparisons.

The posted arm summaries list 44 observations for each treatment condition. Because the design is crossover, these are repeated condition-specific records from participants who received all three agents, not separate independent cohorts. The record does not report how many paired observations were available for each comparison or how the analysis handled any incomplete pairs.

11. Safety Results

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

Other (non-serious) adverse events

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

The registry lists 44 participants at risk in each treatment condition for serious adverse events and other adverse events, with zero affected participants in each category for Eovist, Dotarem, and saline. These are the recorded event counts for the listed groups. The adverse-event record does not list any serious adverse-event terms.

Zero recorded events does not prove that an event cannot occur or that the agents have identical safety profiles. Rare events may not appear in a study of this size, and the registry summary does not provide a precision estimate for the event rates. The crossover design also means each participant received each condition; the group records should not be interpreted as independent parallel groups or summed to describe unique participants.

Death counts are not reported in the registry record. The posted safety figures are limited to the categories and groups recorded there, and should not be extended to outcomes that are not reported.

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

The posted results describe breath-hold duration and several secondary outcomes among healthy volunteers receiving Eovist, Dotarem, and saline during MRI. The primary medians differ across conditions, while the full ranges are broad. The registry record does not report a formal primary comparison or its uncertainty. Therefore, these descriptive values do not establish whether the observed differences represent a reproducible treatment effect, nor do they establish that the conditions are equivalent.

The record is specific to the study population and setting: healthy volunteers undergoing liver MRI, with measurements following administration up to 5 minutes. It is not a report of clinical outcomes in patients undergoing diagnostic imaging. The findings should not be generalized beyond that context without evidence from relevant populations and settings. The registry record does not report detailed participant characteristics that would support more specific judgments about generalizability.

The secondary findings likewise have limits. Group means for oxygen saturation and heart rate are the same across conditions, and the motion outcome is uncommon in the posted counts. The recalculated unadjusted comparisons are not sponsor-reported analyses and do not model the crossover structure. Their uncertainty and the absence of a reported multiplicity plan mean that they should not be treated as definitive tests.

The safety summary reports no serious or other adverse events in the listed groups, but this does not rule out uncommon events. The record also does not report deaths. Overall, the data are best read as descriptive registry results from a small crossover study with repeated measurements. The record does not provide enough statistical detail to determine the precision of the primary treatment contrasts or to draw a confirmatory conclusion about differences among agents.

13. Why This Trial Matters Statistically

This trial raises a useful statistical issue: the same volunteers received all three conditions, so the comparison is inherently within-person. That design can reduce the influence of stable differences between participants when the analysis uses the paired structure appropriately. It also means that marginal summaries for each condition are not enough to reconstruct the treatment comparison. The participant-level association across conditions is essential for estimating the uncertainty of a paired contrast.

The primary endpoint illustrates why reporting both descriptive summaries and an analysis matters. Medians and ranges show the spread of observed breath-hold durations, but they do not say how each participant’s duration changed across conditions. A design-matched estimate and confidence interval would make the treatment contrast and its precision clearer. Such a primary comparison is not reported in the registry record.

The secondary motion outcome also illustrates the challenges of sparse data. Few events can produce imprecise estimates, and a single event may have a substantial influence on the observed proportion. Planning values based on the observed effect can help illustrate the scale of a future study under stated assumptions, but they are not evidence that the present study had a particular observed power. They are especially sensitive to the effect estimate when events are few.

Finally, the record offers an opportunity to distinguish absence of a reported result from evidence of no effect. Similar posted means or zero recorded adverse events do not prove equivalence or rule out uncommon outcomes. Clear reporting of the crossover analysis, paired estimates, confidence intervals, missing data, and multiplicity handling would help readers judge what the data support and how precisely.

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.

Several limitations follow from the information recorded for this specific study. The population comprised healthy volunteers undergoing liver MRI, so the results do not directly describe patients with illness or other clinical circumstances. The registry identifies three study sites but does not report participant characteristics or further eligibility details, limiting assessment of how closely the volunteers represent other populations.

The central reporting limitation is the absence of a posted primary-endpoint comparison. The median and full range are available for each condition, but no paired estimate, confidence interval, or reported inferential method is given. Because participants received every condition, independent-group comparisons would not fully reflect the design; the registry record does not say how repeated measurements were analyzed.

The record also does not report how randomization was implemented, how treatment sequence was handled analytically, whether period or carryover effects were considered, or how missing observations were treated. It does not provide participant-level paired data. This prevents reconstruction of the within-person contrasts from the displayed marginal summaries.

Secondary motion events are sparse, which limits precision and makes estimates sensitive to individual events. The associated recalculations are unadjusted and do not account for multiple outcomes or the crossover structure. The registry does not report a multiplicity plan, a sponsor analysis for these comparisons, or a sample-size justification for the original study. The planning illustrations instead use an observed effect and stated assumptions.

Finally, the registry’s safety counts are limited to the adverse-event categories recorded, and death counts are not reported in the registry record. Zero recorded events should not be interpreted as proof that uncommon events cannot occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Eovist vs. Dotarem Healthy Volunteer MRI — NCT02431598.
• Registry record last updated 2017-04-14; status last verified 2017-03.
• Results first posted 2017-04-14.
• 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

NCT02431598 is a completed randomized, single-masked, placebo-controlled crossover study sponsored by Duke University and listed as Phase 4. It enrolled 44 healthy volunteers and compared Eovist, Dotarem, and saline; each participant received all three in randomized order while undergoing liver MRI.

The primary endpoint was breath-hold capacity in seconds following administration, up to 5 minutes. The registry reports medians and full ranges but no primary inferential comparison. Secondary outcomes covered oxygen saturation, heart rate, transient severe motion, and motion-artifact severity. The record lists zero serious and zero other adverse events in each treatment group; death counts are not reported in the registry record.

The available results are descriptive. The registry record does not report the statistical analysis plan, paired treatment comparisons for the primary endpoint, missing-data handling, or multiplicity procedures.