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 SonoVue®-Enhanced Ultrasound (US) Versus Unenhanced US for Focal Liver Lesion Characterization (NCT00829413), a na phase 3 study. The primary outcome is Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00829413 |
| Phase | Phase 3 |
| Condition | Liver Neoplasms |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 353 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bracco Diagnostics, Inc |
| Results posted | Yes |
2. Clinical Question
Population
Patients with at least one target focal liver lesion requiring work-up for characterization. The primary endpoint description identifies an Intent-to-diagnose population of 259 subjects; 119 had lesions classified as malignant by the truth standard and were included in the sensitivity assessment.
Intervention
SonoVue-enhanced ultrasound (SonoVue CE-US), used to characterize focal liver lesions as benign or malignant. The registry describes patients receiving SonoVue and undergoing ultrasound investigations of the target lesion.
Comparator
Unenhanced ultrasound (UE-US) of the same target lesion. The study is described as an intrapatient comparison, rather than a comparison between separately randomized groups.
Primary question
For lesions malignant according to the truth standard, how often did each ultrasound approach correctly characterize the lesion as malignant? The record defines sensitivity as the percentage of true positive lesions among all malignant lesions per truth standard, with diagnoses from three off-site assessors.
The study addresses diagnostic classification, not a treatment effect. Its stated purpose was to compare the sensitivity and specificity of SonoVue-enhanced and unenhanced ultrasound for distinguishing benign from malignant focal liver lesions. The primary endpoint listed in the record is sensitivity; specificity is part of the study purpose, but its numerical result is not reported in the registry record.
The reference diagnosis could be based on contrast-enhanced CT and/or MRI, tissue pathology or histology, or six-month follow-up. This is a composite truth standard, rather than one uniform verification method for every lesion. The endpoint timeframe is 24 hours to 6 months. The record says that each subject had a single lesion to characterize, so the lesion was equivalent to the subject for this analysis.
3. Trial Design
This was a Phase III, completed study of SonoVue-enhanced ultrasound compared with unenhanced ultrasound for focal liver lesion characterization. It enrolled 353 participants and is described as a single-group, intrapatient comparative study. In an intrapatient comparison, both imaging approaches are considered for a participant's target lesion; the comparison is therefore within participants rather than between independent treatment arms. The registry lists allocation as not applicable and masking as none. It should not be interpreted as a randomized, masked trial.
The study record describes patients with at least one target lesion requiring diagnostic work-up. The intervention listing names SonoVue, and the arm description says patients underwent unenhanced ultrasound of the target lesion. The primary endpoint is described for an Intent-to-diagnose population of 259 subjects. Of these, 119 had a lesion considered malignant under the truth standard and contributed to the sensitivity assessment. Reasons that the enrollment count and the endpoint population differ are not reported in the registry record.
Three off-site assessors posted the diagnoses used for the primary endpoint, and the record states that these assessors were blinded to patient data. It does not specify in the information available whether the assessors were blinded to the imaging method, how the imaging examinations were presented to them, or how disagreements were resolved.
The truth standard could use contrast-enhanced CT and/or MRI, tissue pathology or histology from surgery or biopsy, or six-month follow-up. The study therefore combines different sources of diagnostic verification. The registry does not report how the choice of truth-standard component was made, whether the same verification process was used for all participants, or how cases without an available truth-standard diagnosis were handled. The protocol details and statistical plan are 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.
Before assignment: A total of 67 patients received SonoVue in the training phase and were included only in safety population. A total of 259 patients received SonoVue in the efficacy phase. The 67 patients, included within the "Not Completed" category below, are the training patients.
Overall Study
| Stage | Safety Population |
|---|---|
| STARTED | 353 |
| COMPLETED | 259 |
| NOT COMPLETED | 94 |
Reasons for not completing this period:
| Reason | Safety Population |
|---|---|
| No study drug admimnistered | 13 |
| Training Patients | 67 |
| No truth standard procedure available | 9 |
| Technically inadequate truth standard | 2 |
| Indeterminate diagnosis from truth stand | 3 |
Analysis population for the primary outcome, as defined in the registry: Among 259 ITD subjects, 119 were malignant by truth standard and were included for sensitivity.
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 | ITD Population |
|---|---|---|
| Participants analysed | 259 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 185 |
| Age, Categorical: >=65 years | Participants | 74 |
| Age, Continuous | years | 56.9 (SD 13.4) |
| Sex: Female, Male: Female | Participants | 123 |
| Sex: Female, Male: Male | Participants | 136 |
| Race/Ethnicity, Customized: White | participants | 206 |
| Race/Ethnicity, Customized: Black | participants | 22 |
| Race/Ethnicity, Customized: Asian | participants | 12 |
| Race/Ethnicity, Customized: Other | participants | 19 |
| Region of Enrollment: United States | participants | 132 |
| Region of Enrollment: Europe | participants | 93 |
| Region of Enrollment: Canada | participants | 34 |
6. Primary Endpoint
The registry lists the primary outcome as Sensitivity: Percentage of True Positive Lesions Among All Malignant Lesions Per Truth Standard, measured over 24 hours to 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of true positive lesions |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is sensitivity: the percentage of lesions classified as true positive among lesions judged malignant by the truth standard. In this study, a true positive is defined as a target lesion characterized as malignant by both ultrasonography and the truth standard. Sensitivity focuses on the ability of an imaging assessment to identify lesions that are malignant according to the reference diagnosis; it does not, by itself, describe performance for lesions classified as benign.
The endpoint is clinically relevant to diagnostic evaluation because the stated task is to distinguish benign from malignant focal liver lesions. A sensitivity estimate describes the proportion of reference-standard malignant lesions that receive a malignant classification from the ultrasound assessment. Its meaning depends on how the truth standard is established and on which lesions enter the denominator.
The record reports that the sensitivity population included 119 malignant lesions among 259 Intent-to-diagnose subjects. It also says that diagnoses were provided by each of three off-site assessors and that the unit of analysis was the lesion, equivalent to the subject because each subject had a single lesion to characterize. The endpoint timeframe is 24 hours to 6 months, reflecting the stated period associated with diagnostic assessment and truth-standard ascertainment.
The record gives the endpoint definition and a 95% confidence interval as its dispersion measure, but numerical sensitivity estimates and confidence limits are not reported in the registry record. Consequently, the size and precision of the sensitivity estimates, and any numerical difference between imaging approaches, cannot be described from the registry information available.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the diagnostic question and the planned comparison structure, but it does not report numerical results for the primary sensitivity endpoint. It therefore does not establish from the posted results whether either imaging approach had higher sensitivity, or how large or precise any difference was. Although the study purpose mentions both sensitivity and specificity, numerical results for those measures are not reported in the registry record.
The primary endpoint is defined among lesions considered malignant by the truth standard. Its denominator is not the full enrollment count: the record states that 119 malignant lesions among the 259 Intent-to-diagnose subjects were included for sensitivity. The record does not give the sensitivity numerators, estimates, or confidence limits. Without these, readers cannot assess the observed rate of correct malignant classification or its uncertainty.
The intrapatient structure is important for understanding the intended comparison. Both imaging approaches concern the same participant's target lesion, so the comparison is not equivalent to a trial in which one group receives one approach and a separate group receives the other. Paired diagnostic data can account for the fact that the two assessments concern the same lesion. However, the registry information does not report the analysis procedure used to account for pairing, nor does it report a statistical test or a confidence interval for a between-method contrast.
The reference diagnosis could come from imaging, pathology or histology, or follow-up. These methods do not constitute one identical verification procedure across all cases. The registry does not explain how verification sources were selected or how uncertainty in the truth standard was addressed. This matters because sensitivity is defined relative to the reference classification: a lesion's designation as malignant under the truth standard determines whether it contributes to the sensitivity denominator.
The record identifies three off-site assessors and says they were blinded to patient data. It does not state whether assessments were blinded to the ultrasound method or whether assessor-specific results differed. Inter-reader agreement is listed as a secondary outcome, but its numerical findings are not reported in the registry record. The number of analyses is recorded as 15, while the detailed analysis procedures and any adjustment for multiple outcomes or analyses are not reported.
These limitations in the registry record do not show that the study lacked a prespecified plan or that its conduct was flawed. They mean that the posted information is insufficient to reconstruct the primary comparison or judge its statistical precision. Interpretation should remain descriptive: the record documents an intrapatient diagnostic study and defines its endpoint and reference standard, but does not provide the numerical evidence needed to compare diagnostic performance.
9. Statistical Methods Explained
The endpoint and design can be understood using general diagnostic-statistics concepts. The registry defines sensitivity as the percentage of reference-standard malignant lesions that are classified as malignant by ultrasound. The primary endpoint description includes results from three off-site assessors, but numerical assessor-specific estimates are not reported in the registry record.
What sensitivity measures
In general, sensitivity is a conditional proportion: it describes test classifications among cases known, according to a reference standard, to have the condition of interest. Here the condition is a malignant focal liver lesion, and the reference classification is based on contrast-enhanced CT and/or MRI, tissue pathology or histology, or six-month follow-up. A true positive requires agreement that the lesion is malignant between ultrasonography and the truth standard. Sensitivity does not describe how often benign lesions are correctly classified; that is the role of specificity.
The listed sensitivity population is 119 malignant lesions within the Intent-to-diagnose population of 259 subjects. The record says each subject had one lesion to characterize, making the lesion the unit of analysis and equivalent to the subject for this endpoint. This unit-of-analysis statement is useful: multiple lesions from one participant would raise questions about dependence among observations, but the record says there was a single target lesion per subject for characterization.
Why the paired structure matters
In general, an intrapatient comparison assesses both approaches in the same participant. The resulting observations are paired because they refer to one lesion and one participant, rather than to independent groups. A statistical comparison should account for this pairing. For diagnostic classifications, the pattern of agreement and disagreement between the two methods can be important; knowing only the separate sensitivity estimates would not fully describe the paired contrast. The registry record does not report the specific statistical test or model used for the comparison.
Allocation is listed as not applicable, and the design is described as single-group and intrapatient. These descriptions do not support interpreting the study as a randomized comparison between treatment arms. Masking is listed as none. Separately, the primary endpoint description says the three off-site assessors were blinded to patient data. The record does not specify the full masking arrangements for image acquisition, interpretation, or adjudication.
How to read the confidence interval
In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater statistical precision than a wider interval, while an interval's location indicates which values are compatible with the estimate and its uncertainty under that method. The primary endpoint lists a 95% confidence interval as its dispersion measure, but the numerical estimate and limits are not reported in the registry record. No conclusion about the endpoint's precision can therefore be drawn from the record.
Reference-standard considerations
A diagnostic test's sensitivity is always relative to the reference classification used to identify cases. Here, the truth standard could involve contrast-enhanced imaging, pathology or histology, or follow-up. In general, using more than one verification route can make a study feasible across different clinical circumstances, but it can also mean that not every participant's status is established in the same way. The record does not explain how verification routes were selected, whether the truth standard was applied uniformly, or how indeterminate or unavailable reference assessments were handled. These are relevant details because the reference classification defines which lesions count as malignant for the endpoint.
Multiple outcomes and analyses
The record lists eight outcome measures and 15 analyses. In general, assessing multiple endpoints, assessors, or comparisons can increase the chance that at least one finding appears notable by chance if no plan addresses multiplicity. Adjustment methods and the prespecified hierarchy, if any, are not reported in the registry record. It is therefore not possible to determine how the study handled multiplicity or which analyses were considered primary beyond the endpoint designation recorded for sensitivity.
Specificity, accuracy, predictive values, specific diagnoses of malignant and benign lesions, and inter-reader agreement are listed as secondary outcomes. The registry does not report their numerical results in the information available. Predictive values in general depend on the distribution of disease in the population being assessed, while sensitivity and specificity are defined relative to the reference classification. These concepts should not be treated as interchangeable measures.
Planning illustrations are not trial results
In general, sample-size calculations based on an observed effect are planning illustrations rather than evidence that a study had a particular probability of detecting an effect. The record describes planning assumptions of a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as a stated fraction of the observed effect. Those assumptions do not describe the actual intrapatient study design, which is listed as a single-group comparison. The record does not report its own sample-size justification, and planning illustrations should not be interpreted as observed power or as evidence about the endpoint result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures and 15 analyses. Besides sensitivity, the listed outcomes include accuracy, positive and negative predictive values, specific diagnoses of malignant and benign focal liver lesions, and inter-reader agreement. The study purpose also refers to specificity. The numerical findings for these outcomes and analyses are not reported in the registry record.
When a study evaluates multiple outcomes, assessors, or related comparisons, general statistical practice distinguishes prespecified primary analyses from additional analyses. If many tests are conducted, the chance of at least one apparently notable result can increase. A multiplicity strategy may use an ordered testing plan, an adjustment to significance thresholds, or another prespecified approach. The registry does not report whether any such strategy was used, how analyses were prioritized, or how the 15 analyses relate to the listed outcomes.
The record identifies an Intent-to-diagnose population of 259 subjects and says 119 malignant lesions contributed to sensitivity. Enrollment was 353. Reasons for the difference between enrollment and the endpoint population, and participant flow through the analyses, are not reported in the registry record. The registry also does not describe missing or indeterminate imaging results, missing truth-standard assessments, exclusions, or how missing data were handled.
The record does not report the statistical analysis plan, interim analyses, or any prespecified rules for handling discordant assessments. These omissions do not establish that such procedures were absent; they limit what can be verified from the registry record. The available information supports identifying the endpoint and its analysis population, but not reconstructing the full analysis strategy.
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 | 4 | 340 | 1.2% |
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 | 45 of 340 |
Most frequent serious adverse event terms
| Event term | Organ system | Safety Population |
|---|---|---|
| Dehydration | Metabolism and nutrition disorders | 1 of 340 |
| Colon cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 340 |
| Hepatic hemorrhage | Hepatobiliary disorders | 1 of 340 |
| Rectal haemorrhage | Gastrointestinal disorders | 1 of 340 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Safety Population |
|---|---|---|
| Nausea | Gastrointestinal disorders | 6 of 340 |
| Headache | Nervous system disorders | 6 of 340 |
| Diarrhea | Gastrointestinal disorders | 4 of 340 |
| Flatulence | Gastrointestinal disorders | 3 of 340 |
| Dizziness | Nervous system disorders | 3 of 340 |
| Dyspepsia | Gastrointestinal disorders | 2 of 340 |
| Fatigue | General disorders | 2 of 340 |
| Injection site pain | General disorders | 2 of 340 |
| Muscle spasms | Musculoskeletal and connective tissue disorders | 2 of 340 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 340 |
Serious events with the highest arm-level rate: dehydration (0.3%), colon cancer metastatic (0.3%), hepatic hemorrhage (0.3%), rectal haemorrhage (0.3%).
The safety population is listed as 340 participants at risk. The registry record lists 4 under serious adverse events and 45 under other adverse events in this population. These are the recorded figures; the registry information does not provide event-level detail for all adverse events or clarify in the displayed details whether multiple events could have been reported for one participant.
Four serious adverse-event terms are listed, each with a frequency of 0.3%: dehydration, colon cancer metastatic, hepatic hemorrhage, and rectal haemorrhage. The registry record does not provide additional detail about timing, relatedness to SonoVue, severity criteria, or the clinical circumstances of these events. The death count is not reported in the registry record.
Safety counts should be read separately from the diagnostic-performance endpoint. They describe adverse-event reporting in the safety population and do not establish that an event was caused by the intervention. The registry information also does not support comparing safety between imaging approaches, since the study is described as a single-group intrapatient study rather than a randomized comparison of separate safety groups.
12. What the Result Does, and Does Not, Mean
The record describes a Phase III, completed intrapatient study comparing SonoVue-enhanced with unenhanced ultrasound for characterizing focal liver lesions. It defines sensitivity relative to a truth standard that could include contrast-enhanced CT and/or MRI, tissue pathology or histology, or six-month follow-up. It also identifies the endpoint population and the number of malignant lesions included in the sensitivity assessment.
Those details establish what the primary diagnostic question was, but they do not provide the numerical answer. Sensitivity estimates, confidence limits, and a numerical comparison between imaging approaches are not reported in the registry record. The record therefore does not support a conclusion about which approach had greater sensitivity, the magnitude of any difference, or how precisely either estimate was measured. Specificity is part of the stated study purpose, but its numerical results are also not reported.
Even when numerical diagnostic estimates are available, they describe performance relative to the reference standard and population used in a study. They do not automatically establish performance in every clinical setting. In general, the composition of the population and the way reference diagnoses are obtained can affect how estimates apply elsewhere. Here, the truth standard used more than one possible verification route, and details about how those routes were selected are not reported.
The study's intrapatient structure means the two ultrasound approaches were compared for the same target lesion, rather than in independent randomized groups. That design is suited to a paired diagnostic comparison, but the registry does not report the analysis method or numerical paired results. The record also does not give the detailed statistical plan, handling of missing data, or multiplicity strategy.
Accordingly, the registry record supports a description of the trial's diagnostic objective, design, endpoint definition, population, and listed safety figures. It does not support claims that either ultrasound approach is superior, that one approach has a particular accuracy, or that the study establishes a clinical benefit. Those conclusions require results and methodological detail not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable because it frames diagnostic performance as an intrapatient comparison. Comparing two imaging approaches on the same target lesion differs from comparing separate groups: observations are paired, and the methods' differing classifications are central to the comparison. Clear reporting of the paired analysis is important for interpreting the precision and direction of any difference.
The endpoint also highlights the role of a reference standard in diagnostic research. Sensitivity is not an independent label attached to an imaging approach; it is calculated relative to which lesions the truth standard classifies as malignant. This record allows several verification sources, including contrast-enhanced imaging, tissue pathology or histology, and follow-up. The chosen reference process and its consistency across participants can therefore shape the meaning of the endpoint.
The registry identifies three off-site assessors, an Intent-to-diagnose population, and the number of malignant lesions included for sensitivity. Those details help define the planned estimand and analysis population. At the same time, the numerical sensitivity results, confidence limits, paired comparison method, and assessor-specific findings are not reported in the registry record. The contrast between a clearly defined diagnostic question and missing numerical results illustrates why endpoint definitions alone are not enough to assess findings.
Finally, the record lists multiple outcomes and analyses, making transparent reporting of analysis priorities and multiplicity relevant. Such details help readers distinguish confirmatory comparisons from additional assessments. The registry record does not report that statistical strategy, so interpretation must remain limited to the study's design and stated objectives rather than inferred performance conclusions.
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 most direct limitation for interpreting this trial is that numerical results for the primary sensitivity endpoint are not reported in the registry record. The estimate, its 95% confidence interval, and the numerical comparison between SonoVue-enhanced and unenhanced ultrasound are unavailable. Specificity and the listed secondary outcomes also lack numerical findings in the record.
The endpoint description identifies an Intent-to-diagnose population of 259 subjects and 119 malignant lesions, while the study enrollment is 353. The reasons for this difference are not reported. Participant flow, exclusions, missing or indeterminate assessments, and the handling of unavailable truth-standard information are also not reported. This limits assessment of how the analyzed population relates to the enrolled population.
The truth standard could be based on contrast-enhanced CT and/or MRI, tissue pathology or histology, or six-month follow-up. The record does not specify how these sources were selected, whether all participants underwent verification in the same way, or how conflicting results were managed. Because the truth standard determines the endpoint denominator, these details would be relevant to interpreting sensitivity.
The record says three off-site assessors were blinded to patient data, but does not provide full information about masking of image interpretation, the assessment workflow, or resolution of disagreements. Inter-reader agreement is listed as an outcome, but findings are not reported. The registry also does not describe the paired statistical method, multiplicity plan, missing-data approach, interim analyses, or sample-size justification.
These are limitations of the information reported in the registry record, not evidence that the study necessarily lacked procedures for addressing them. They prevent a full evaluation of the analysis and its precision from the record alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: SonoVue®-Enhanced Ultrasound (US) Versus Unenhanced US for Focal Liver Lesion Characterization — NCT00829413.
- Registry record last updated 2018-08-03; status last verified 2017-11.
- Results first posted 2018-08-03.
- 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 Phase III, single-group intrapatient study of SonoVue-enhanced versus unenhanced ultrasound for focal liver lesion characterization. Enrollment was 353; the primary sensitivity description concerns 259 Intent-to-diagnose subjects, including 119 malignant lesions by the truth standard.
The primary endpoint is sensitivity, defined as the percentage of true positive lesions among lesions considered malignant by the truth standard. Three off-site assessors contributed diagnoses. The truth standard could include contrast-enhanced CT and/or MRI, pathology or histology, or six-month follow-up.
Numerical primary and secondary outcome results, the detailed statistical plan, and explanations of participant flow are not reported in the registry record. The safety population is listed as 340, with 4 recorded under serious adverse events and 45 under other adverse events. The record lists four serious adverse-event terms, each at 0.3%.