Magnetic Resonance Imaging of the Liver in Children 0-2 Months of Age With an Intravenous Injection of Eovist/Primovist Which is a Contrast Agent: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Magnetic Resonance Imaging of the Liver in Children 0-2 Months of Age With an Intravenous Injection of Eovist/Primovist Which is a Contrast Agent (NCT02084628), a na phase 3 study. The primary outcome is Number of Subjects With Additional Diagnostic Information From Combined (Pre-contrast And Post-contrast) Images Compared With Pre-contrast Images.

2. Clinical Question

The study asked whether adding post-injection images contributed diagnostic information beyond the images obtained before injection. The endpoint description includes examples of such information: clearer delineation of a lesion border, better definition of internal morphology or location, improved characterization, or better assessment of a lesion’s communication with the biliary system. The endpoint was a participant count, not a direct measure of how often any one type of additional information occurred.

This was not a randomized comparison of the contrast agent against another intervention or against no contrast. Instead, the planned comparison used two image sets from the same diagnostic episode: pre-contrast images and combined pre-contrast and post-contrast images. The record says images were taken before injection and after injection within about 15 minutes. The registry record does not report how many participants had additional diagnostic information, so the primary question cannot be answered from the posted outcome data.

3. Trial Design

The registry describes an open-label, multi-center, single-group phase 3 study of gadoxetate disodium for enhanced liver MRI in children aged 0–2 months. Allocation is listed as not applicable and masking as none. The study is therefore not a randomized, blinded comparison between treatment groups. The registry reports enrollment of 1 participant and a status of terminated. The recorded start was 2015-02, and primary completion was 2015-08.

The intervention was a single manual intravenous injection of Eovist/Primovist at 0.1 mL/kg body weight, corresponding in the record to 0.025 mmol/kg body weight, followed by a manual saline flush of at least 5 mL of 0.9% sodium chloride solution. The intended imaging assessment compared pre-contrast images with combined pre-contrast and post-contrast images. The timeframe for the primary endpoint describes the images as taken before injection and after injection within about 15 minutes.

The study summary also describes blood tests before and after imaging and 3 blood samples collected up to 8 hours after injection to measure the amount of contrast agent in the blood. Several radiologists were to evaluate the images. The summary describes contacting the family doctor about diagnosis and treatment after MRI results were known, and contacting a parent or legal guardian six months after the study to ask about problems, especially involving skin, joints, and eyes.

Those descriptions establish the intended study procedures, but the registry record does not report the number of participants who completed each procedure or the number of evaluable scans. It also does not report why the study was terminated, the protocol’s sample-size justification, or a statistical analysis plan. With a single-group design and no like-for-like control arm, any interpretation must focus on the recorded imaging comparison and the limits of the available participant-level data.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: One participant was enrolled in the study.

Overall Study

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 Number of Subjects With Additional Diagnostic Information From Combined (Pre-contrast And Post-contrast) Images Compared With Pre-contrast Images, measured over Images were taken pre-injection and post-injection (within about 15 minutes).

The primary endpoint was the number of participants with additional diagnostic information from combined pre-contrast and post-contrast images compared with pre-contrast images. The registry gives examples of what could count as additional information: better delineation of a lesion border, better definition of internal morphology or location, better characterization of a lesion, or better assessment of communication with the biliary system. The outcome is expressed as a count of participants, rather than as a continuous score or a count of each imaging feature.

This endpoint addresses whether the image set that includes post-injection images adds information beyond the pre-contrast image set. The within-participant image comparison is suited to that question because the two sets are assessed in relation to the same participant. It is not, however, a randomized treatment comparison and does not by itself establish how the findings would compare with another imaging strategy or in a broader population.

The endpoint description says that the number of participants with additional information was recorded and analyzed. The registry record does not report the observed count, an estimate of uncertainty, or the criteria used to determine whether information was meaningfully additional. As a result, the stated measurement can be described, but its observed value and precision cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that were actually used for the primary endpoint are not reported in the registry record. The record reports 0 analyses, and it does not include an analysis plan, an endpoint estimate, or a measure of uncertainty. The explanations below are general statistical context for understanding the kind of outcome described; they do not imply that any particular method was used in this study.

What kind of outcome is the primary endpoint?

General: A participant count records how many people meet a stated outcome definition. For this trial, the outcome was whether a participant had additional diagnostic information from combined images compared with pre-contrast images. A count is different from a continuous measurement, such as a numerical score, and different from a count of separate imaging features. The registry’s definition frames the endpoint at the participant level, even though the examples refer to several kinds of possible image information.

To interpret a participant count, readers normally need both the number meeting the outcome and the number assessed. The registry record reports enrollment of 1 participant but does not report the primary outcome count or the analysis denominator. Enrollment does not, by itself, establish that the participant completed imaging, had evaluable images, or was included in a particular analysis. Those details are not reported in the registry record.

What does the image comparison tell us?

General: Comparing two assessments from the same participant can focus attention on what is added by the second assessment. Here, the stated comparison is pre-contrast images versus combined pre-contrast and post-contrast images. This differs from comparing outcomes in two independent groups. Because the endpoint asks whether combined images provide additional information, interpretation depends on how readers define and record that information and how they handle assessments that are uncertain or disagree.

The registry describes several radiologists evaluating images, but it does not report the number of readers, their individual assessments, a consensus procedure, or a method for measuring agreement. Reader agreement matters because image interpretation can involve judgment. A statistical analysis may describe agreement or combine ratings according to a prespecified rule, but no such approach is reported in the registry record. No assumption should be made about how the study handled multiple readers.

What would an uncertainty estimate contribute?

General: A confidence interval gives a range of values compatible with an estimate under the assumptions of the statistical method. It helps readers distinguish a precisely estimated result from one with substantial uncertainty. For a participant-level count or proportion, an interval can be useful when the sample is small, because a single observed participant can have a large influence on the estimate. The registry does not report a primary endpoint estimate or confidence interval, so there is no study-specific precision interval to interpret.

A p-value, when used, addresses how compatible data are with a specified statistical null model. It is not a measure of clinical importance, and it does not replace an estimate or its uncertainty. No primary endpoint p-value is reported in the registry record. The record also does not specify a null hypothesis or significance threshold for the primary analysis. It would therefore be inappropriate to infer a hypothesis test from the endpoint description alone.

What can the planning assumptions establish?

General: Sample-size planning asks how many observations might be needed to estimate an effect or detect a chosen effect under stated assumptions. Planning calculations are not trial outcomes, and they are not observed power. The planning assumptions associated with this record describe a hypothetical two-arm calculation with equal allocation, while the registered study design is single-group. This distinction is important: such a planning illustration should not be mistaken for the actual design, the number enrolled, or evidence about the primary endpoint.

The registry record does not report the protocol’s own sample-size justification or a planned effect used by the investigators. It also does not report an observed primary endpoint value from which a reader could assess an effect-based planning illustration. Therefore, no study-specific conclusion about the adequacy of the planned sample size or the power of the trial can be drawn from the posted information. In general, power calculations are prospective design tools; they do not establish the probability that a particular result is true.

Why might count data need careful modeling?

General: Statistical models for counts depend on how the outcome is defined and on assumptions about the process generating the observations. A participant-level yes-or-no outcome is not analyzed in the same way as a count of multiple lesions or imaging findings. For repeated observations or multiple readers, the observations may be related rather than independent. Over-dispersion is a general concern when count data vary more than a model expects, but it is not a reported feature of this endpoint or an analysis documented for this study. The registry does not state that a count model, a binary-outcome model, or any other particular model was used.

The record lists secondary outcomes that include lesion counts, yes-or-no assessments of contrast enhancement and visualization, changes in diagnosis, and diagnostic confidence. These outcomes do not all have the same statistical form. Their definitions and analysis methods would matter when interpreting their results, but the registry does not report outcome-level analyses. Statistical explanations of possible methods must therefore remain general rather than being presented as a description of the trial’s actual analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Gadoxetate Disodium (Eovist/Primovist, BAY86-4873)")
n      <- c(1)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Gadoxetate Disodium (Eovist/Primovist, BAY86-4873)  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures overall, including a primary outcome and secondary outcomes addressing lesion detection, contrast enhancement, biliary-system visualization, diagnostic changes, and diagnostic confidence. It reports 0 analyses. The statistical analysis plan, including any prespecified hierarchy among outcomes or adjustment for multiple testing, is not reported in the registry record.

General: When a study tests or estimates many outcomes, the chance of obtaining apparently notable findings can increase if each is considered separately. Multiplicity methods can address that issue, or a protocol can identify a primary outcome and define secondary outcomes as supportive or exploratory. The record identifies a primary endpoint, but it does not describe how multiplicity was handled. No claim about adjustment, prioritization beyond the registry labels, or confirmatory status of secondary findings can be made.

Missing-data handling is also not reported in the registry record. The record does not say whether the enrolled participant completed imaging, whether all images were evaluable, or how an unavailable or indeterminate assessment would have been treated. It does not report an analysis population, such as which participants were included in the primary endpoint analysis. Enrollment and analysis denominators should not be treated as interchangeable when completion and evaluability are unknown.

General: Missing observations can affect interpretation when the likelihood of missingness is related to participant characteristics, procedures, or outcomes. Statistical approaches depend on the reason and pattern of missingness, as well as the outcome definition. Because the registry does not describe missing observations or analytic handling, it is not possible to assess whether missingness affected the reported results. In this study, the absence of reported outcome analyses means that no result can be evaluated for multiplicity or missing-data sensitivity.

12. 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 adverse-event summary lists 1 participant at risk for serious adverse events and 0 participants affected by serious adverse events. It also lists 1 participant at risk for other adverse events and 0 participants affected by other adverse events. These are the figures recorded for the gadoxetate disodium study group. The record lists no serious adverse-event terms.

These counts should be read in the context of enrollment of 1 participant. They describe the registry’s recorded counts, not a precise estimate of the frequency of adverse events in a wider population. With such limited enrollment, the absence of a recorded event in the summary cannot establish that an event would not occur in other participants or under other circumstances.

The death field is null, not a reported count of zero. Deaths are therefore not reported in the registry record. The adverse-event summary also does not provide additional detail about event definitions, observation duration for these counts, or event-level assessments. The study summary describes planned follow-up contact six months after the study, but it does not report the outcome of that contact. These data support only a narrow description of what the registry lists; they do not support a broader safety conclusion.

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

The registry documents a study designed to assess liver MRI with gadoxetate disodium in infants aged 0–2 months and to evaluate whether combined pre-contrast and post-contrast images provide additional diagnostic information compared with pre-contrast images. It also describes planned safety monitoring and measurement of plasma gadolinium concentrations. Those aims and procedures explain the questions the study was intended to address.

The posted record does not report the primary endpoint result, secondary outcome results, or statistical analyses. Consequently, it does not provide an observed estimate of how many participants had additional diagnostic information, how precisely that outcome was estimated, or whether the listed secondary imaging outcomes occurred. The registry record does not establish a direction or magnitude of an imaging effect. No conclusion about benefit or lack of benefit follows from an outcome value that is not reported.

The design was single-group, open-label, and not randomized. Its primary comparison was between image sets from before and after injection, rather than between independent intervention groups. Even with outcome results, that design would need to be interpreted according to its scope and limitations. The enrollment of 1 participant further restricts the extent to which observations could represent other infants.

The adverse-event summary records 0 participants affected by serious events and 0 affected by other events among 1 participant at risk in each category, while deaths are not reported in the registry record. These counts are descriptive and do not establish the safety profile in a broader population. Overall, the registry record describes the study question and procedures but leaves the principal efficacy-related outcome and the statistical analyses unreported.

14. Why This Trial Matters Statistically

This study is statistically instructive because it separates a clearly stated measurement question from the evidence needed to answer it. The primary endpoint asks whether combined images provide additional diagnostic information beyond pre-contrast images. Defining that comparison is useful, but a question alone is not an estimate: the registry must also report the observed outcome and the number of participants assessed for readers to judge what the data show.

The record also illustrates why design labels and analysis details matter. A single-group study with no masking is different from a randomized comparison, and a within-participant image comparison should not be described as a treatment-versus-control result. Readers need the endpoint definition, the comparison being made, the analysis population, and an account of uncertainty to understand the evidential scope.

Enrollment of 1 participant underscores the distinction between feasibility or procedural information and stable estimates about outcomes. A small enrollment can make an estimate highly dependent on individual observations. In this record, the primary outcome value is not reported, so there is no estimate to interpret or precision to assess. The listed planning assumptions concern a hypothetical two-arm calculation, not the actual single-group design, and should not be taken as trial results or observed power.

Finally, the record shows why missing analysis information is substantive rather than cosmetic. It does not report how image-reader assessments were combined, how missing or indeterminate observations were handled, or whether multiplicity was addressed. These details shape the meaning of results when available. Here, the central statistical lesson is that a registered endpoint and a detailed procedure description do not substitute for posted outcome data and a transparent account of analysis.

15. 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 are specific to the information recorded for this study. Enrollment was 1 participant, and the study is listed as terminated. The registry record does not report why termination occurred or whether the participant completed all planned procedures. It also does not report the number of evaluable images or the number included in the primary endpoint assessment.

The primary endpoint is described as a participant count, but its result is not reported. The record does not give reader-level judgments, a procedure for resolving disagreements, or a threshold for determining when information was sufficiently additional to meet the endpoint. Although several radiologists were to evaluate images, the registry does not explain how their assessments contributed to the recorded outcome.

The registry does not report the statistical analysis plan, sample-size justification, analysis populations, or methods for missing data and multiplicity. The planning assumptions describe a two-arm illustration, while the registered study is single-group; those assumptions do not establish the study’s actual design rationale. There are also no reported estimates or uncertainty intervals for the primary or secondary outcomes.

These limitations concern what can be assessed from the registry record and should not be read as evidence that a particular procedure was or was not performed. The record describes the intended imaging, blood sampling, and follow-up, but it does not report completion or findings for those procedures. This leaves both the imaging outcome and the scope of the safety follow-up uncertain.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Magnetic Resonance Imaging of the Liver in Children 0-2 Months of Age With an Intravenous Injection of Eovist/Primovist Which is a Contrast Agent — NCT02084628.
• Registry record last updated 2016-09-23; status last verified 2016-08.
• Results first posted 2016-09-23.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes an open-label, multi-center, single-group phase 3 study of gadoxetate disodium for enhanced liver MRI in children aged 0–2 months. It reports enrollment of 1 participant and a terminated status. The intervention was a single intravenous dose of 0.1 mL/kg body weight, followed by a saline flush.

The primary endpoint was the number of participants with additional diagnostic information from combined pre-contrast and post-contrast images compared with pre-contrast images. The registry record does not report the primary endpoint result or statistical analyses. The adverse-event summary lists 0 affected participants for serious and other adverse events among 1 participant at risk in each category; deaths are not reported in the registry record.