Contrast Sonography for Evaluation of Liver Tumors Prior to Radiofrequency Ablation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Contrast Sonography for Evaluation of Liver Tumors Prior to Radiofrequency Ablation (NCT00584402), a na na study. The primary outcome is Percent of Tumors With Increased Echogenicity (Brightness) Following Contrast-enhanced Sonography.

2. Clinical Question

The clinical question is about whether small intrahepatic tumors become more conspicuous on ultrasound images after contrast administration. Increased brightness is the registered imaging outcome; it is not itself a measure of tumor treatment response or patient outcome. The secondary objective was to estimate how tumor type, size, location, and depth might relate to conspicuity. The registry lists a secondary outcome concerning increased echogenicity by those tumor characteristics, but does not report subgroup results.

The study is registered as a single-group evaluation, with no randomized comparator. Its design therefore addresses an imaging change observed around contrast administration, rather than a difference in outcomes between independently assigned groups. The registry record does not report the numerical result needed to quantify the observed change.

3. Trial Design

This completed study is registered as NCT00584402, with the title “Contrast Sonography for Evaluation of Liver Tumors Prior to Radiofrequency Ablation.” The registry lists University of California, Davis as the sponsor, the condition as liver neoplasms, and the phase as NA. The recorded study start is 2007-04, and the primary completion is 2009-03. Enrollment is listed as 8.

The design metadata identify the study as single-group, with allocation recorded as NA and masking as NONE. The intervention is perflutren lipid microspheres, and the arm is described as contrast sonography. The study summary describes systemic intravenous administration of ultrasound contrast followed by real-time ultrasound evaluation. Images before and after contrast were visually compared, and the primary outcome description states that one tumor per participant was analyzed.

The primary objective was to estimate the increase in conspicuity of small intrahepatic tumors with contrast-enhanced sonography. The secondary objectives concerned possible effects of tumor type, size, location, and depth on conspicuity. The registry lists a primary endpoint for the percent of tumors with increased echogenicity and a secondary outcome concerning the number of participants with increased echogenicity by tumor characteristics.

These design features define a descriptive imaging assessment, not a controlled efficacy comparison. There is no separate untreated or alternative-imaging arm in the registry record, and no randomization is described. The record does not report a protocol-level explanation for the choice of design, a sample-size justification, or how the enrollment target was determined. It also does not describe assessor training, image-reading procedures beyond visual comparison, or whether image evaluation was repeated or independently reviewed.

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: Closed to enrollment

Overall Study

Analysis population for the primary outcome, as defined in the registry: Tumors were evaluated prior and post contrast injection, 1 tumor per participant

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 Percent of Tumors With Increased Echogenicity (Brightness) Following Contrast-enhanced Sonography, measured over 15 min.

The primary endpoint is the percent of tumors with increased echogenicity, meaning increased brightness, following contrast-enhanced sonography. Echogenicity is an imaging characteristic: the endpoint asks whether the tumor appears brighter after contrast than before it. The registry describes visual evaluation of real-time ultrasound images and comparison of pre-contrast with post-contrast images. Its stated timeframe is 15 min.

This endpoint is used to address the study’s central imaging question: whether contrast-enhanced sonography increases the conspicuity of small intrahepatic tumors. A more conspicuous image could make a lesion easier to identify in the imaging assessment, but the endpoint does not directly measure diagnostic accuracy, a change in clinical management, or a patient outcome. Those are different questions and are not reported as the primary endpoint.

The outcome description states that one tumor per participant was analyzed. However, the registry record does not report the numerical percentage, the number of tumors with increased echogenicity, or an uncertainty interval for the endpoint. It also does not explain the operational threshold used to classify a tumor as having increased echogenicity, or report whether the visual classification was made by a single reader or resolved among readers. Consequently, the endpoint’s intended meaning is clear, but its observed magnitude and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as single-group and lists no analyses. Understanding what that does—and does not—mean is important when reading the endpoint description. The statistical ideas below are general explanations; the registry record does not report that these methods were used.

What does a single-group imaging assessment estimate?

A single-group study can describe what was observed in the evaluated group. Here, the primary endpoint is framed as the percent of tumors with increased echogenicity after contrast. The image comparison is within the imaging evaluation: pre-contrast and post-contrast images are visually compared. This can produce a descriptive count or proportion if classifications and a denominator are available.

A single-group result is not the same as a comparison between independently assigned groups. In a randomized comparison, assignment helps create groups that can be compared under a defined design. In a before-and-after image assessment, each observation is tied to the same evaluation context. This can be useful for describing image appearance, but it does not supply a separate control condition. The registry does not report a formal comparison or an inferential estimate.

What does a percent endpoint convey?

A percentage expresses the share of evaluated units meeting a defined condition. For this endpoint, the condition is increased echogenicity after contrast, and the unit is a tumor. The study description states that one tumor per participant was analyzed. For a percentage to be reproducible, readers also need the count of tumors meeting the condition, the denominator used, and the decision rule for classifying increased brightness. The registry record does not report the endpoint’s numerator, numerical percentage, or classification threshold.

A percentage alone would describe the observed frequency in the analyzed set, not necessarily the frequency in all patients or all liver tumors. Generalizing beyond the evaluated participants requires attention to how participants and tumors were selected, the clinical setting, and the consistency of image reading. Those details are not reported in the registry record.

Why does uncertainty matter?

A point estimate, such as a proportion, does not show how much it might vary under repeated sampling. A confidence interval is a general statistical way to express uncertainty around an estimate. It gives a range of values compatible with the data and the method used, rather than making the point estimate appear exact. The registry record does not report a confidence interval or another measure of uncertainty for the primary endpoint.

Uncertainty is especially relevant when a study has limited enrollment. Estimates based on a limited set of observations can vary substantially, even if the observed proportion appears high or low. This is a general statistical consideration, not a calculation of the precision in this study. The registry record does not provide enough endpoint data to calculate or assess that precision.

What can statistical significance testing add?

A hypothesis test evaluates whether data are inconsistent with a specified null model under stated assumptions. A p-value, when reported, is not the probability that the null hypothesis is true and does not measure the size or practical importance of an effect. Testing also depends on a prespecified question, an analysis method, and appropriate data. The registry record lists no analyses and reports no p-value, test statistic, or inferential comparison. No conclusion about statistical significance can be drawn from the endpoint description alone.

How should subgroup questions be treated?

The secondary objectives name tumor type, size, location, and depth as factors that might relate to conspicuity. Subgroup analysis divides observations according to characteristics and examines whether results vary across those groups. Such analyses can be informative, but they usually involve fewer observations within each subgroup than in the overall assessment. Their estimates may therefore be less precise. The registry record does not report subgroup counts, subgroup estimates, uncertainty intervals, or a statistical method for comparing subgroups.

Subgroup results also need careful interpretation when many potential patterns are examined. A pattern can appear by chance, especially when many outcomes or subgroup contrasts are considered. A prespecified analysis plan and a clear approach to multiplicity help readers distinguish planned questions from exploratory findings. Neither is described in the registry record.

What does a planning calculation represent?

Sample-size planning uses assumptions about the effect worth detecting, outcome variability, significance level, power, and study design. A planning illustration based on an observed effect is hypothetical: it asks what a future study might require under specified assumptions. It does not represent the power achieved by the completed study, and it does not demonstrate that the observed effect is reliable. The registry record does not report its own sample-size justification. Because the primary endpoint result is not reported, the observed effect cannot be evaluated from this record.

In general, analysis choices should match the unit of observation and the outcome structure. If observations are clustered, related, or over-dispersed, a method that assumes independent observations or simple binomial variation may understate uncertainty. Over-dispersion means that outcomes vary more than a simple model expects; suitable methods can account for that extra variation. The registry description says one tumor per participant was analyzed, but it does not report a statistical model, assessment of dependence, or method for handling variation across participants. These are general considerations, not claims about an analysis actually performed in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and a secondary outcome. The primary endpoint concerns the percent of tumors with increased echogenicity after contrast. The secondary outcome concerns participants with increased echogenicity according to tumor type, size, location, and depth. Although the objectives are described, the registry record does not report an analysis plan specifying which comparisons would be confirmatory, how subgroup results would be tested, or whether any multiplicity adjustment was planned.

Multiplicity is the issue that arises when several statistical questions are examined. Considering many outcomes or subgroup patterns can increase the chance of finding an apparently notable result by chance. This is a general statistical concern. Without a documented testing strategy or reported analyses, the record does not allow readers to assess how multiplicity was handled or whether any particular subgroup result was prespecified.

The registry reports no analyses. It does not report how missing or unevaluable images were handled, whether any participants or tumors were excluded from the endpoint analysis, or the analysis population used. The description states that one tumor per participant was analyzed, but it does not establish that every enrolled participant contributed an evaluable tumor. Those details are not reported in the registry record.

The record also does not describe an intention-to-treat or other named analysis population, imputation of missing observations, or sensitivity analyses. These omissions do not show that missing data occurred; they mean that the registry record does not describe the relevant handling or analysis. As a result, the available description is insufficient to determine whether the endpoint summary, if calculated, would include all enrolled participants or a subset with usable images.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The registry’s serious-adverse-event listing records 8 at risk and 0 affected for the Contrast Sonography group. The death count is 0. The record lists no serious adverse event terms. These are the safety counts recorded in the registry; they do not replace a detailed description of how adverse events were monitored or classified.

A count of zero affected means that no serious adverse events are recorded in this entry for the group. It does not establish that the risk of a serious adverse event is absent. Safety counts from a small study can provide limited information about uncommon events, and the registry record does not report an uncertainty estimate for these counts. The listing also does not describe the observation period used for safety follow-up or provide details about event ascertainment.

The registry separately contains zero entries for other adverse events at risk and affected. These fields should not be read as evidence that all possible adverse effects were assessed and ruled out; the record does not explain those entries. The listed counts describe what was entered in the registry, not a comprehensive safety analysis.

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

The study asks a focused imaging question: whether small intrahepatic tumors appear brighter after contrast-enhanced sonography. The registry describes visual comparison of images before and after the systemic intravenous contrast injection, with increased echogenicity as the primary endpoint. It also identifies tumor type, size, location, and depth as factors of interest.

What the record does not provide is the numerical primary outcome. There is no reported percentage of tumors with increased echogenicity, count meeting that endpoint, confidence interval, or statistical analysis. Therefore, the record cannot show how often the intended imaging change was observed or how precisely it was estimated. The missing numerical result is not evidence of either a positive or a negative finding.

The single-group design also limits the type of conclusion that could be drawn, even if a descriptive result were available. Pre-contrast and post-contrast image comparison can characterize the imaging appearance in the evaluated setting. Without a separate control group, it does not provide a randomized estimate of a difference between contrast sonography and another approach. It also does not answer whether imaging findings changed clinical decisions or improved patient outcomes; those questions are not reported as outcomes in the registry record.

The secondary objective suggests interest in whether conspicuity varies by tumor characteristics, but the registry does not report those results. It is not possible to assess subgroup patterns or their precision. Nor does the record provide enough information to judge how images were classified, whether readers agreed, or how any unevaluable images were handled.

The appropriate interpretation is consequently narrow: the registry records a completed imaging study, its endpoint definition, and safety counts, but it does not report the quantitative primary result or an analysis. No conclusion about the magnitude, certainty, or clinical consequences of an imaging effect can be drawn from the registry record alone.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its primary question is framed around an imaging feature rather than a patient-level clinical event. The endpoint is the percent of tumors with increased echogenicity after contrast, and the description specifies visual comparison of pre-contrast and post-contrast images. Correct interpretation therefore depends on the unit of analysis, the image-classification rule, and how uncertainty is reported.

The registry states that one tumor per participant was analyzed. That detail helps identify the intended observational unit, but it does not supply the endpoint result or establish how many observations were evaluable. Clear reporting of the numerator, denominator, and classification process would be needed to understand the observed percentage and reproduce its interpretation. The registry record does not report those numerical details.

The design also illustrates the distinction between a descriptive within-evaluation comparison and a controlled group comparison. A before-and-after image assessment can address whether brightness changed in the observed setting. It does not have the same interpretation as a randomized comparison between alternative approaches. Recognizing that distinction prevents a descriptive imaging outcome from being read as a comparative treatment effect.

Finally, the registry identifies potential subgroup factors but reports no analyses. This makes the study a useful example of why secondary questions need prespecified methods and cautious interpretation. Subgroup estimates can be imprecise, and examining multiple characteristics creates multiplicity concerns. With no reported endpoint result, uncertainty estimate, or analysis, the record demonstrates the importance of complete statistical reporting as much as it documents the intended study question.

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 primary limitation for interpreting the registry record is that it does not report the numerical result for the primary endpoint. No estimate of the percent of tumors with increased echogenicity, endpoint count, confidence interval, or statistical test is reported. The study’s central quantitative finding therefore cannot be assessed from the registry record.

The study is registered as a single-group assessment with no separate control arm. The pre-contrast and post-contrast image comparison can describe an observed imaging change, but the design does not provide a randomized between-group comparison. The registry record does not explain whether other factors affecting image appearance were considered.

The endpoint description relies on visual comparison, but the record does not specify a threshold for increased echogenicity, reader qualifications, blinding of image readers, independent review, or how reader disagreement was handled. It also does not report image quality criteria or procedures for images that could not be evaluated. These omissions limit assessment of measurement consistency.

The registry names tumor type, size, location, and depth as secondary factors, but reports no subgroup findings or subgroup counts. It does not describe a multiplicity strategy, missing-data approach, analysis population, or statistical model. No sample-size justification is reported. These details are not reported in the registry record, so their absence should not be taken as proof that the procedures were not used outside the record.

Finally, the safety entry reports zero serious adverse events among 8 at risk, but does not provide a detailed account of monitoring, follow-up duration, or event ascertainment. The counts are limited evidence about safety and do not establish the absence of risk.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Contrast Sonography for Evaluation of Liver Tumors Prior to Radiofrequency Ablation — NCT00584402.
• Registry record last updated 2017-07-11; status last verified 2017-07.
• Results first posted 2017-07-11.
• 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

NCT00584402 is a completed, single-group study sponsored by University of California, Davis, evaluating contrast-enhanced sonography for small liver tumors before radiofrequency ablation. Enrollment is listed as 8; the study start is 2007-04 and primary completion is 2009-03. The intervention was perflutren lipid microspheres, identified in the study summary as Definity.

The primary endpoint was the percent of tumors with increased echogenicity after contrast, assessed by visual comparison of pre-contrast and post-contrast images within 15 min. The description states that one tumor per participant was analyzed. The numerical endpoint result and statistical analyses are not reported in the registry record. Secondary questions concerned tumor type, size, location, and depth.

The serious-adverse-event listing records 8 at risk, 0 affected, and 0 deaths. The registry record does not report a sample-size justification, a detailed statistical plan, or procedures for multiplicity and missing data.