This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy and Safety of Primovist in Chinese Patients (NCT00526188), a non-randomized phase 3 study. The primary outcome is Difference in Sensitivity of Lesion Detection in MRI Images (Post-contrast MRI Minus Pre-contrast MRI) Measured as Percentage Points.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00526188 |
| Phase | Phase 3 |
| Condition | Known or Suspected Focal Liver Lesions |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 234 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bayer |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled Chinese patients with known or suspected focal liver lesions requiring further evaluation. The primary analysis population was narrower: participants in the per-protocol set whose pre- and post-contrast MRI image sets were evaluable for all blinded readers and who had at least 1 lesion in the Standard of Reference.
Intervention
Participants received Gadoxetic Acid Disodium, identified as Primovist or BAY86-4873, as an intravenous bolus during an MRI procedure. The recorded regimen was 0.025 mmol/kg body weight, or 0.1 ml/kg body weight, with one contrast-enhanced MRI procedure per patient.
Comparator
There was no separate control group. The primary comparison was between pre-contrast and post-contrast MRI images from the same study setting. The trial was non-randomized and single-group, so this is not a randomized, like-for-like comparison between treatment arms.
Primary question
The primary endpoint asked how much lesion-detection sensitivity differed between post-contrast and pre-contrast MRI image sets. The difference was expressed in percentage points and summarized as a mean with a 95% confidence interval. The numerical estimate and its confidence interval are not reported in the registry record.
In practical terms, the endpoint focuses on whether blinded readers detected a greater or smaller share of the lesions in the Standard of Reference when interpreting post-contrast images rather than pre-contrast images. The study also listed lesion-characterization precision and investigator-assessed lesion-detection sensitivity among its secondary outcomes. Their numerical results are not reported in the registry record.
3. Trial Design
This was a completed, multicenter, open-label Phase III study sponsored by Bayer. The registry record gives enrollment as 234 and describes the study as non-randomized, with no masking and a single-group model. These features matter when interpreting the findings: the study did not assign participants to randomized treatment and control arms, and it cannot provide a randomized between-group treatment comparison.
Participants with known or suspected focal liver lesions underwent MRI that included an initial scan without contrast and imaging after Primovist administration. The intervention description specifies one intravenous contrast injection and one contrast-enhanced MRI procedure per patient. The primary comparison used the pre-contrast and post-contrast image sets, so the contrast states are compared within the study rather than against an independently assigned control arm.
The primary endpoint was evaluated using blinded readers, even though the overall study is recorded as open-label and unmasked. The registry describes lesion detection by three blinded readers. It does not report the details of how reader blinding was maintained, how reader-level results were combined, or whether any additional reader training or adjudication procedures were used.
The primary assessment timeframe includes image assessments by investigators on the same day as treatment and assessments by blinded readers at the end of patient enrollment, from 29 September to 18 November 2008. The study start is recorded as 2007-08 and primary completion as 2008-08. The record does not give more detail about the operational sequence of all assessments.
The primary analysis population was defined by evaluability of both image sets for all blinded readers and the presence of at least 1 Standard of Reference lesion. Thus, enrollment and the primary endpoint population are not interchangeable. The number included in that endpoint population is not reported in the registry record. The record also does not report a separate comparator arm or a randomized allocation procedure.
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: 247 Chinese patients were recruited and screened. Among these, 13 patients were screening failures: withdrawal of consent (7 patients), non-fulfillment of the inclusion and exclusion criteria (3 patients), other reasons (3 patients). The remaining 234 patients received the study drug and were included in the safety analysis set.
Overall Study
| Stage | Gadoxetic Acid Disodium (Primovist, BAY86-4873) |
|---|---|
| STARTED | 234 |
| COMPLETED | 234 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants from the per protocol set with pre- and post-contrast MRI image sets evaluable for all blinded readers, with at least 1 lesion in the Standard of Reference (SOR)
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 | Gadoxetic Acid Disodium (Primovist, BAY86-4873) |
|---|---|---|
| Participants analysed | 234 | |
| Age, Continuous | years | 50.2 (SD 11.78) |
| Sex: Female, Male: Female | Participants | 79 |
| Sex: Female, Male: Male | Participants | 155 |
| Characterization of first liver lesion type of referral diagnosis: Hepatocellular carcinoma | participants | 47 |
| Characterization of first liver lesion type of referral diagnosis: Cholangiocarcinoma | participants | 1 |
| Characterization of first liver lesion type of referral diagnosis: Metastasis | participants | 58 |
| Characterization of first liver lesion type of referral diagnosis: Focal nodular hyperplasia | participants | 14 |
| Characterization of first liver lesion type of referral diagnosis: Hemangioma | participants | 42 |
| Characterization of first liver lesion type of referral diagnosis: Abscess | participants | 2 |
| Characterization of first liver lesion type of referral diagnosis: Focal fatty infiltration | participants | 1 |
| Characterization of first liver lesion type of referral diagnosis: Liver cyst | participants | 13 |
| Characterization of first liver lesion type of referral diagnosis: Inflammation | participants | 1 |
| Characterization of first liver lesion type of referral diagnosis: Harmatoma | participants | 1 |
| Characterization of second liver lesion type of referral diagnosis: No second liver lesion type | participants | 191 |
| Characterization of second liver lesion type of referral diagnosis: Hepatocellular carcinoma | participants | 3 |
| Characterization of second liver lesion type of referral diagnosis: Metastasis | participants | 5 |
| Characterization of second liver lesion type of referral diagnosis: Hemangioma | participants | 7 |
| Characterization of second liver lesion type of referral diagnosis: Hydatid cyst | participants | 1 |
| Characterization of second liver lesion type of referral diagnosis: Liver cyst | participants | 23 |
| Characterization of second liver lesion type of referral diagnosis: Calcification | participants | 1 |
| Characterization of second liver lesion type of referral diagnosis: Inflammatory pseudotumor | participants | 1 |
| Characterization of second liver lesion type of referral diagnosis: Not assessable | participants | 2 |
| Characterization of third liver lesion type of referral diagnosis: No third liver lesion type | participants | 231 |
| Characterization of third liver lesion type of referral diagnosis: Hemangioma | participants | 1 |
| Characterization of third liver lesion type of referral diagnosis: Liver cyst | participants | 1 |
| Characterization of third liver lesion type of referral diagnosis: Calcification | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Difference in Sensitivity of Lesion Detection in MRI Images (Post-contrast MRI Minus Pre-contrast MRI) Measured as Percentage Points, measured over Post administration assessment of study images (i.e. on the same day of treatment by the investigators and at the end of patient enrollment of the study from 29 September to 18 November 2008 by the Blinded Readers)..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage points |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the difference in sensitivity of lesion detection between post-contrast and pre-contrast MRI image sets, measured in percentage points. Sensitivity is defined in the registry as the number of lesions detected in a reader and image-set combination divided by the number of lesions in the Standard of Reference, multiplied by 100%. The endpoint then contrasts the sensitivity calculated from post-contrast images with that calculated from pre-contrast images.
This measure is used to describe detection relative to a reference set of lesions. It focuses on the proportion of reference lesions identified by readers, rather than simply reporting the number of image findings. Expressing the contrast as a difference in percentage points keeps the endpoint on the sensitivity scale and makes its direction interpretable: positive values would indicate greater sensitivity on post-contrast images, while negative values would indicate greater sensitivity on pre-contrast images. This is a general explanation of the scale, not a statement about the study's result.
The registry specifies a mean and a 95% confidence interval for the primary endpoint. However, neither the estimated mean difference nor the numerical interval is reported in the registry record. The endpoint population was the per-protocol set with evaluable pre- and post-contrast image sets for all blinded readers and at least 1 Standard of Reference lesion. The number of participants meeting those criteria is not reported in the registry record.
Assessing sensitivity can help describe lesion detection, but it does not by itself describe all aspects of diagnostic performance. The registry lists lesion-characterization precision as a secondary outcome, indicating that characterization was considered separately from detection. The results for that outcome are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical result needed to interpret this trial—the numerical mean difference in lesion-detection sensitivity and its 95% confidence interval—is not reported in the registry record. Consequently, the direction, magnitude, and precision of the primary endpoint cannot be judged from the recorded information. The endpoint definition explains what was intended to be measured, but it is not a substitute for the observed estimate.
The comparison is between pre-contrast and post-contrast image sets in a single-group study. This structure can describe differences in reader sensitivity across those image sets, but it is not a randomized comparison of Primovist against a separate control group. The absence of random allocation and a separate arm limits claims about causal attribution. In particular, no treatment-versus-control effect can be inferred from the design description alone.
Blinded readers performed lesion detection, which is relevant because reader awareness could influence image interpretation. The registry identifies three blinded readers, but does not report enough detail to assess the blinding procedures or how reader-specific estimates were combined. The primary endpoint is described as a mean, but the record does not provide the numerical result or details needed to reconstruct its uncertainty.
The denominator for the sensitivity calculation is based on lesions in the Standard of Reference. The record does not report the number of lesions used, the reference-standard procedures, or how uncertainty arising from multiple lesions within a participant was handled. These omissions make it difficult to assess the statistical precision beyond what would be conveyed by the stated confidence interval, which itself is not numerically reported.
The registry lists secondary outcomes concerning lesion-detection sensitivity assessed by investigators and precision of lesion characterization. It does not provide their results in the information recorded. No conclusion about those outcomes can therefore be drawn. The record also does not report whether the primary analysis was adjusted for covariates, whether there were interim analyses, or whether a prespecified statistical analysis plan governed the reader-level calculations.
Safety information is reported separately from the imaging endpoint. The registry lists 0 participants with serious adverse events among 234 at risk and 20 with other adverse events among 234 at risk. The deaths field is not reported in the registry record, and no serious adverse-event terms are listed. These entries should be read as recorded safety counts, not as a full characterization of event severity, timing, or causal relationship.
Overall, the available registry information describes the study question, endpoint construction, and design, but does not provide the efficacy estimates required to judge the observed imaging difference. The posted data therefore support a description of what was measured and some recorded safety counts, not a conclusion about the size or certainty of a change in sensitivity.
9. Statistical Methods Explained
The primary endpoint is a continuous measure: a difference in sensitivity expressed in percentage points. The registry specifies the mean as the parameter of interest and a 95% confidence interval as its dispersion summary. The numerical mean and interval are not reported in the registry record, so the endpoint can be explained but not quantitatively interpreted.
What does sensitivity represent?
The registry defines sensitivity for each reader and image-set combination using the lesions in the Standard of Reference. The numerator is the number of those lesions detected by the reader in that image set, and the denominator is the number of lesions in the reference. The calculation is expressed as a percentage. In general, sensitivity describes how many reference-positive findings a method identifies; it does not by itself describe false-positive findings or every aspect of diagnostic accuracy.
For the primary endpoint, the post-contrast sensitivity is compared with the pre-contrast sensitivity. A difference in percentage points is an absolute contrast between two percentage-scale values. This is distinct from a relative percentage change. The endpoint is based on within-study image sets rather than on randomized treatment groups. That distinction is important: the statistical contrast describes the image-reading results under the study's assessment conditions, while the design does not establish a randomized between-arm contrast.
Why report a mean and confidence interval?
A mean summarizes the average endpoint value across the analysis units used by the study. A confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. In general, a narrower interval indicates greater precision than a wider interval; an interval that includes values on both sides of no difference can leave the direction uncertain. These are general statistical interpretations. Because the numerical estimate and interval are not reported in the registry record, neither the precision nor the range of values compatible with the primary result can be assessed.
The registry says that lesion-detection sensitivity was calculated for each blinded reader and image-set combination, and that the post-minus-pre difference was calculated for each blinded reader. It does not report how these reader-level differences were combined for the stated mean, how their dependence was handled, or whether participant-level clustering was included. These are relevant methodological details because image readings and lesions from the same participant may not be statistically independent. The record does not describe the model or variance method used.
What role does the Standard of Reference play?
The Standard of Reference supplies the lesion count used as the sensitivity denominator. The primary population also required at least 1 lesion in this reference and evaluable images for all blinded readers. Such requirements define which participants can contribute to the endpoint, but the registry does not report the reference-standard method, its assessment procedures, or the number of qualifying participants and lesions. Those details would help readers understand how the endpoint population was formed and how the sensitivity estimate was supported.
What do the planning illustrations mean?
The registry describes sample-size planning illustrations computed from the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a stated fraction of the observed effect. The record explicitly distinguishes these illustrations from the trial's own design. They are planning calculations, not observed power, and they do not establish that the trial was designed or analyzed as a two-arm randomized study. The numerical planning outputs and observed effect used for those calculations are not reported in the registry record.
General sample-size planning asks how many participants would be needed under stated assumptions to detect an effect of a chosen size with a chosen probability of statistical significance. Such calculations depend on the assumed effect and variability. If the observed effect used in a planning illustration is itself uncertain, the resulting planning figures inherit that uncertainty. The registry record does not report the assumptions beyond those stated, nor a sample-size justification for the actual single-group study.
Why can over-dispersion or clustering matter?
In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. When a study has multiple observations for a participant or multiple readings of the same images, results may be correlated. Treating correlated observations as independent can make uncertainty appear too small. This is a general methodological consideration for lesion- and reader-based endpoints, not a claim that over-dispersion occurred in this study. The registry record does not report whether the analysis assessed over-dispersion or accounted for correlation among lesions, readers, and participants.
The trial record names three outcome measures and three analyses, but does not give a complete statistical analysis plan. It does not report the exact analysis models, how missing image readings were treated, or how the primary endpoint's confidence interval was calculated. Without those details and the numerical result, a recalculation from posted summary statistics is not possible.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures and three analyses. It identifies the primary endpoint as the difference in lesion-detection sensitivity for post-contrast minus pre-contrast MRI images, and lists secondary outcomes for investigator-assessed lesion-detection sensitivity and lesion-characterization precision. The record does not report whether the analyses were ordered in a testing hierarchy, whether adjustments were made for multiple comparisons, or how any multiplicity was handled. It also does not report interim analyses or a full statistical analysis plan.
Multiplicity is a general concern when several outcomes or analyses are considered: conducting multiple significance tests can increase the chance of at least one apparently notable result by chance. Whether an adjustment is appropriate depends on the questions and analysis plan. In this study, the registry's listing of outcomes alone does not establish which analyses were confirmatory or whether any formal adjustment was used.
The primary endpoint population is defined by per-protocol status, evaluability of both image sets for all blinded readers, and at least 1 lesion in the Standard of Reference. The size of that analysis population is not reported in the registry record. The record does not describe the extent or reasons for missing images or readings, the handling of participants who did not meet the evaluability criteria, or any imputation procedures.
These omissions matter because excluding participants with incomplete images can affect both the precision and the generalizability of an estimate. That is a general statistical concern, not evidence that missingness biased this study. The record also does not report results for a broader analysis population that could be compared with the per-protocol endpoint population.
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 |
|---|---|---|---|
| Gadoxetic Acid Disodium (Primovist, BAY86-4873) | 0 | 234 | 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 |
|---|---|
| Gadoxetic Acid Disodium (Primovist, BAY86-4873) | 20 of 234 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Gadoxetic Acid Disodium (Primovist, BAY86-4873) |
|---|---|---|
| Hypertension | Vascular disorders | 4 of 234 |
| Blood lactate dehydrogenase increased | Investigations | 3 of 234 |
| Blood bilirubin increased | Investigations | 3 of 234 |
| Hypotension | Vascular disorders | 2 of 234 |
| Blood glucose increased | Investigations | 2 of 234 |
| Nausea | Gastrointestinal disorders | 2 of 234 |
| White blood cell count decreased | Investigations | 2 of 234 |
| Blood pressure systolic increased | Investigations | 1 of 234 |
| Blood pressure diastolic increased | Investigations | 1 of 234 |
| Injection site pain | General disorders | 1 of 234 |
The registry records 0 participants with serious adverse events among 234 at risk for the Primovist group. It records 20 participants with other adverse events among 234 at risk. No serious adverse-event terms are listed. The deaths field is not reported in the registry record, so it should not be interpreted as a recorded zero.
These counts describe the safety entries recorded for the study. The registry information does not provide event-level detail, timing, duration, severity within the other-adverse-event category, or an assessment of whether events were considered related to Primovist. The category labeled other adverse events should not be treated as equivalent to serious events; the record reports the categories separately.
In general, adverse-event counts depend on how events are defined, collected, and coded. A count alone does not describe the type of event or establish its cause. The study is single-group and does not supply a randomized safety comparison against a control arm. The recorded counts therefore describe what the registry lists for this group, without establishing comparative risk.
12. What the Result Does, and Does Not, Mean
The study addresses an imaging question: how lesion-detection sensitivity differed between pre-contrast and post-contrast MRI images in patients with known or suspected focal liver lesions. It uses a mean difference in percentage points and specifies a 95% confidence interval. The numerical primary result is not reported in the registry record, so the amount and direction of the observed difference, and its statistical precision, cannot be stated.
The design was non-randomized and single-group, with no masked allocation and no separate control arm. The image-set comparison can describe reader performance across pre-contrast and post-contrast images under the study's conditions. It cannot be interpreted as a randomized comparison between Primovist and an alternative treatment. General causal interpretation requires considering the study design and potential sources of bias, not just the endpoint definition.
The endpoint also has a specific scope. It measures detection relative to lesions in the Standard of Reference. It does not, by itself, establish how well findings were characterized, nor does it summarize every possible clinical consequence of an imaging result. The registry lists characterization precision as a secondary outcome, but its numerical result is not reported in the registry record.
The primary analysis required evaluable images for all blinded readers and at least 1 reference lesion. The record does not state how many participants met those criteria, or describe missing-image handling. This makes the relationship between the enrollment figure and the endpoint analysis population unclear from the recorded information.
Accordingly, the registry entry documents a relevant imaging endpoint, a single-group design, and selected safety counts, but does not provide the numerical efficacy result needed to assess the observed effect. It does not support a conclusion about whether sensitivity increased or decreased, how large any difference was, or how precisely it was estimated. Those questions remain unresolved by the information reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between the clinical imaging question and the design used to address it. The endpoint compares readings of pre-contrast and post-contrast images, while the study is recorded as a non-randomized, single-group trial. Understanding that within-study contrast prevents it from being mistaken for a randomized comparison between treatment arms.
The outcome is defined against a Standard of Reference and is calculated at the reader and image-set level. That structure raises general analytical considerations about repeated readings and potentially clustered lesions. The registry explains the sensitivity calculation and the primary population criteria, but does not report the model used to combine reader-level results or account for dependence. This illustrates why a clear endpoint formula is useful, while also showing that a formula alone does not fully specify the statistical analysis.
The record also makes the boundary between planning and observed evidence important. It describes planning illustrations based on the observed effect, but explicitly says those illustrations are not the trial's own design. Planning outputs cannot replace a reported treatment estimate, and they are not observed power. The numerical primary result and planning figures are not reported in the registry record.
Finally, the entry lists outcomes and safety counts without a complete account of multiplicity, missing-data handling, or analysis populations. These details are needed to assess how robustly the results were analyzed. Since numerical efficacy findings are not reported, the most defensible statistical reading is a careful description of the intended measurement, the single-group design, and the limits of what the registry record establishes.
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 numerical estimate for the primary endpoint and its 95% confidence interval are not reported in the registry record. This is the most important limitation for interpreting efficacy: without them, the direction, magnitude, and precision of the observed difference cannot be assessed. Numerical results for the listed secondary outcomes are also not reported.
The study is described as non-randomized and single-group, without masking. There is no separate randomized control arm, so the pre-contrast and post-contrast image comparison should not be read as a randomized treatment contrast. Although the endpoint includes blinded readers, the registry does not describe the blinding procedures in enough detail to assess their implementation.
The primary analysis population is restricted to per-protocol participants with both image sets evaluable for all blinded readers and at least 1 Standard of Reference lesion. The number in that population, the number of lesions, the number of missing or unevaluable readings, and the reasons for missingness are not reported in the registry record. The record does not describe imputation, sensitivity analyses, or results for alternative analysis populations.
Other details needed for a fuller statistical appraisal are not reported in the registry record, including the method used to combine reader-level results, handling of within-participant or within-reader correlation, the construction of the confidence interval, and any multiplicity adjustment. The registry also does not report reference-standard procedures or a complete statistical analysis plan. These gaps limit evaluation of the precision and potential sources of bias in the endpoint.
The safety entry provides serious and other adverse-event counts, but not event-level descriptions or causal assessments. The deaths field is not reported in the registry record. These limitations mean the available safety information cannot characterize the nature or timing of events or support a comparative safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of Primovist in Chinese Patients — NCT00526188.
- Registry record last updated 2015-05-01; status last verified 2015-04.
- Results first posted 2009-12-30.
- 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.
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18. Record Summary
The registry describes a completed, multicenter, open-label Phase III study of Primovist in Chinese patients with known or suspected focal liver lesions. It records a non-randomized, single-group design and enrollment of 234. Participants received an intravenous bolus of Gadoxetic Acid Disodium during an MRI procedure.
The primary endpoint was the mean difference in lesion-detection sensitivity between post-contrast and pre-contrast MRI images, expressed in percentage points and specified with a 95% confidence interval. The primary population was defined by per-protocol status, evaluable pre- and post-contrast images for all blinded readers, and at least 1 Standard of Reference lesion. The numerical primary estimate, confidence interval, and analysis-population size are not reported in the registry record.
The registry lists 0 participants with serious adverse events and 20 with other adverse events among 234 at risk. It does not report deaths in the deaths field. Results for the listed secondary outcomes and details of missing-data handling, multiplicity, and the statistical analysis plan are not reported in the registry record.