Assessment of Liver Cancer Response to TACE Using MultiHance-Enhanced MRI.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment of Liver Cancer Response to TACE Using MultiHance-Enhanced MRI. (NCT00539253), a na na study. The primary outcome is Nodule Size.

2. Clinical Question

This is an imaging-assessment question, not a randomized test of TACE against another cancer treatment. The study record identifies hepatocellular carcinoma as the condition and gadobenate dimeglumine as the intervention. It does not specify a treatment-effect comparison between patients receiving different imaging agents or different TACE regimens. Consequently, the registry description can establish what the investigators set out to assess, but it cannot by itself establish how accurately MRI identified response or whether nodule size changed after treatment.

3. Trial Design

The registry describes a completed, single-group study sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Enrollment is listed as 45. The recorded start is 2007-09, and primary completion is recorded as 2013-03. The phase is listed as NA. Allocation is listed as NA, and masking is listed as NONE.

The intervention is gadobenate dimeglumine (MultiHance), a contrast agent used in the study’s functional triple-phase MRI assessment. The stated objective is to find out whether MultiHance can be used to show how a liver tumor responds to the chemotherapy given during TACE. The primary endpoint is maximal nodule size in centimeters at the 3 months timeframe.

A single-group design does not provide a concurrent randomized control group for separating the imaging assessment from other influences on observed measurements. The registry record does not describe a like-for-like control arm. It notes that a patient who did not participate by signing consent could receive any contrast used routinely at the facility, including the contrast used in the study. That description concerns care outside participation and does not define a study comparison.

The record does not report the protocol details needed to establish how imaging was scheduled, how measurements were made, or how readers handled possible differences in interpretation. It also does not report a statistical analysis plan or an endpoint analysis. The enrollment figure should not be treated as the number with endpoint data: the endpoint description says that the number analyzed reflects the number for whom data was available, but that analyzed number is 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: none observed

Overall Study

Analysis population for the primary outcome, as defined in the registry: The number of participants analyzed reflects the number of participants for whom data was available.

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 Nodule Size, measured over 3 months.

The primary endpoint is maximal nodule size measured in centimeters, with a timeframe of 3 months. It is a continuous measurement: it can take values across a range rather than representing a category such as response or no response. The registry identifies the planned summary as a mean with standard deviation.

Nodule size is relevant to the study’s stated imaging question because the research aims to assess how a liver tumor responds to chemotherapy given during TACE. Measuring the largest dimension offers a size-based description of a nodule at the recorded timeframe. A mean can describe the average measurement across the participants whose data are analyzed, while a standard deviation describes how dispersed those measurements are around the mean. These summaries do not, on their own, establish that an observed size reflects a treatment effect or how accurately the imaging method detects response.

The registry record does not report the mean, standard deviation, analyzed participant count, or any estimate of change from an earlier measurement. It also does not give a threshold for classifying a nodule as responding. Thus, the endpoint’s definition is available, but its observed value and its relationship to any other measurement are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous outcome: maximal nodule size in centimeters. For a continuous measurement, a mean provides a summary of the central level of the observed values. The standard deviation describes their variability around that mean. These summaries answer different questions. A mean alone does not show whether measurements were closely grouped or widely dispersed, while a standard deviation does not describe the direction or clinical meaning of a change.

The registry names the mean and standard deviation as the endpoint summary, but no values are reported. Without the mean, the standard deviation, and the number analyzed, a reader cannot assess the observed size distribution from the registry record. The record also does not report whether individual nodules or participants were the unit used in the analysis, beyond defining the endpoint as maximal nodule size and stating that the number analyzed reflects participants with available data. Further details about measurement and analysis are not reported in the registry record.

What would a confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimated quantity using a method with stated assumptions. For a mean, it can help distinguish the estimated average from the precision with which that average is known. It is not a range containing every individual measurement, and it does not remove potential bias from study design, missing observations, or measurement procedures. No confidence interval is reported for the primary endpoint in the registry record, so its precision cannot be assessed from the posted information.

What can a single-group design establish?

A single-group study can describe measurements collected within the group, if those results are reported. A comparison intended to estimate a difference between imaging approaches or treatment conditions requires relevant data from the groups being compared and an appropriate analysis. The registry classifies this study as single-group and does not describe a concurrent randomized comparison. The facility’s routine-use description for people who did not consent does not establish an analyzed control group. Therefore, no comparative treatment or imaging effect can be inferred from the design information alone.

The study’s stated purpose is to assess whether MultiHance-enhanced MRI can show how a liver tumor responds to TACE. To evaluate that broad question statistically, details about how response is defined and how imaging findings are related to response would be important. The registry record reports maximal nodule size as the primary endpoint, but it does not report a response definition, a reference standard, or an analysis of imaging accuracy. Those methods are not reported in the registry record.

How should planning calculations be read?

The registry describes planning assumptions for an illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes the target effect as a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s original design justification. The registry record does not report a sample-size justification for this single-group study, and no numerical planning outputs are stated in the record information available for interpretation.

Such calculations are hypothetical illustrations of the number of participants per arm that might be needed to detect a specified effect under selected assumptions. They are not observed power and do not change the study’s recorded single-group design. Because the record does not report an endpoint estimate, an observed effect cannot be reviewed alongside those assumptions. The planning illustration should not be read as evidence that the study was designed or powered to test a particular contrast.

In general, a normal approximation uses a simplified model for the sampling behavior of a statistic. Its relevance depends on the data structure and assumptions, including the outcome distribution and analysis design. Equal allocation between two arms describes a hypothetical comparison structure; it does not describe this registry’s single-group study. The registry does not report whether an alternative model or correction was considered.

Why do analysis details matter?

The mean and standard deviation are descriptive summaries, not a full analysis plan. Statistical interpretation may depend on how repeated measurements, multiple nodules, missing measurements, or departures from model assumptions were handled. The registry record does not report those procedures. General statistical practice would require methods to match the design and the level at which observations were collected; the available record is not detailed enough to assess that match.

Over-dispersion is a general concern when observed variability is greater than a model expects. If a model assumes less variability than the data contain, uncertainty can be understated. The registry record does not identify a model for the primary endpoint or report a dispersion assessment, so there is no basis to say whether over-dispersion was relevant or how it was handled. This is a general methodological point, not a finding about this study.

The record lists 0 analyses. It does not report a p-value, confidence interval, adjusted estimate, or statistical model for nodule size. Without results and analysis specifications, it is not possible to assess statistical significance, precision, adjustment for covariates, or sensitivity to alternative methods. The absence of these details in the registry record should be distinguished from a conclusion that no analysis was conducted outside the posted record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Multihance")
n   <- c(19)
m   <- c(6.4)
sp  <- c(4.5)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Multihance  19  6.400  4.500  4.231  8.569

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies 2 outcome measures, but the available endpoint details describe maximal nodule size as the primary outcome. The other outcome measure is not described in the record information. No multiplicity strategy is reported in the registry record. In general, when several outcomes or analyses are examined, multiplicity methods can address the increased chance of finding an apparently notable result by chance. Whether such adjustment was planned or used cannot be determined from the posted information.

The registry describes the endpoint analysis population as depending on the availability of data for participants. It does not report the analyzed participant count, how much endpoint data were missing, why data might be unavailable, or how missing measurements were handled. There is no reported method for imputation, exclusion, or sensitivity analysis. Consequently, the extent to which the analyzed participants represent those enrolled cannot be assessed from the registry record.

Enrollment is listed as 45, but that figure is not an endpoint denominator. The record’s wording explicitly distinguishes enrollment from the number analyzed, which reflects participants for whom data were available. Without the analyzed count and missing-data details, interpreting a mean as representative of all enrolled participants would require an unsupported assumption.

The registry lists 0 analyses and does not report an analysis population beyond the data-availability description. It does not state whether analyses were prespecified, whether any interim analyses occurred, or how any protocol deviations were handled. Those matters are not reported in the registry record. The result is limited transparency about multiplicity, missingness, and the population contributing to the primary endpoint.

12. 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.

For the Gadobenate Dimeglumine (Multi Hance) group, the registry lists 45 participants at risk for serious adverse events and 0 affected. It also lists 45 at risk for other adverse events and 0 affected. Deaths are listed as 0. No top serious adverse-event terms are listed in the registry record.

These figures describe what the registry reports for the group; they should not be interpreted as a comparison with another study arm, because no concurrent comparator is described. Nor do they establish how adverse events were defined, how actively they were collected, or what follow-up period was used. Those details are not reported in the registry record.

A recorded count of 0 means that the registry lists no affected participants for the specified category. It does not, without further information on ascertainment and follow-up, establish that no events occurred outside the data represented in the record. The figures are also distinct from the imaging endpoint: they do not provide evidence about nodule-size measurement, tumor response, or imaging performance.

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

The registry record documents a study intended to assess MultiHance-enhanced MRI for showing how liver tumors respond to chemotherapy given during TACE. It specifies maximal nodule size in centimeters at the 3 months timeframe as the primary endpoint and identifies the planned summary as a mean with standard deviation. These details clarify the research question and the type of measurement selected.

The record does not report the observed endpoint mean, standard deviation, analyzed participant count, or inferential analysis. As a result, it does not show whether nodule size changed, how large any change may have been, or how precisely a result was estimated. It also does not report a comparison of MultiHance with another contrast agent or an analysis of imaging accuracy. No conclusion about the imaging method’s ability to identify response can be drawn from the endpoint definition alone.

The single-group design is important to the scope of interpretation. A group’s measurement can describe the people with available data, but without a relevant comparison and a suitable analysis it cannot isolate the effect of the imaging agent or establish what would have occurred under another approach. The registry’s note about routine contrast use for people who did not consent does not constitute a study control group.

The safety entries list 0 serious adverse events, 0 other adverse events, and 0 deaths, with 45 listed at risk in each adverse-event category. These are registry-reported figures, not a detailed safety analysis. Event definitions and ascertainment procedures are not reported in the registry record.

Accordingly, the record supports a description of the study’s purpose, design classification, and planned primary measurement, but not a judgment about the observed tumor-size results or the effectiveness of the imaging assessment. Such judgments would require outcome estimates, analysis details, and information about data availability that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a clinically motivated question and the evidence needed to answer it statistically. The motivating question is whether MultiHance-enhanced MRI can show how a liver tumor responds to TACE. The primary endpoint translates part of that question into a measurable quantity: maximal nodule size in centimeters at the 3 months timeframe. Defining the measurement is necessary, but it is not a substitute for reporting the observed values and their uncertainty.

The single-group classification also matters. A description of size in a group can be informative, but a comparison of imaging approaches or a claim about response requires an analysis designed to address that question. Without a concurrent comparator or a reported accuracy analysis, it is important not to treat the study’s purpose as a demonstrated finding.

The registry record also highlights why enrollment and analysis denominators should be distinguished. Enrollment is 45, while the endpoint description says that the analyzed count reflects participants with data available. Since that analyzed count is not reported, the reader cannot evaluate how much information contributed to the primary outcome or whether unavailable data could affect interpretation.

Finally, design information and results serve different roles. The record identifies the endpoint and summary approach but lists 0 analyses and does not report endpoint estimates. This is a useful reminder that statistical conclusions depend not only on the question and measurement, but also on transparent outcome reporting, analysis methods, and missing-data information. Those elements are not reported in the registry record.

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.

The registry record provides limited information for evaluating this study beyond its stated objective, design classification, enrollment, intervention, endpoint, and adverse-event counts. It does not report the primary endpoint results or an analysis. The absence of a mean, standard deviation, analyzed count, or inferential estimate prevents assessment of the observed nodule-size measurements and their precision.

The study is classified as single-group, with allocation listed as NA and masking as NONE. No like-for-like control comparison is described. The record’s statement about routine contrast use for people who did not participate does not provide comparative study data. This limits what can be concluded about differences between contrast agents or the independent contribution of MultiHance.

Further endpoint details are not reported in the registry record. These include how the maximal dimension was measured, whether readings were independently assessed, how the 3 months timeframe was operationalized, and how a tumor response was defined. The record does not report an imaging accuracy analysis or a reference standard for response assessment.

Although enrollment is listed as 45, the analyzed number is not reported; the registry notes that it depends on data availability. The amount and handling of missing endpoint data are not reported. The record also does not report a statistical analysis plan, multiplicity handling, interim analyses, or sample-size justification. The planning assumptions described for an illustration do not establish the trial’s original design rationale or observed power.

These limitations concern what can be assessed from the registry record. They do not establish that the unreported procedures or analyses were absent from other study materials; those details are simply not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessment of Liver Cancer Response to TACE Using MultiHance-Enhanced MRI. — NCT00539253.
• Registry record last updated 2017-09-26; status last verified 2017-08.
• Results first posted 2017-09-26.
• 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 a completed single-group study of gadobenate dimeglumine (MultiHance) for functional triple-phase MRI assessment of liver cancer response to TACE. Hepatocellular carcinoma is the listed condition, and enrollment is 45. The recorded study start is 2007-09, with primary completion at 2013-03. Phase is listed as NA, allocation as NA, and masking as NONE.

The primary endpoint is maximal nodule size in centimeters at the 3 months timeframe, summarized as a mean with standard deviation. The record says the number analyzed reflects participants with available data, but does not report that analyzed count or endpoint results. It lists 0 analyses. Safety entries list 0 serious adverse events, 0 other adverse events, and 0 deaths. The registry record does not report a concurrent comparison group, endpoint estimates, or detailed analysis methods.