Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody (NCT00606632), a na phase 3 study. The primary outcome is Sensitivity and Specificity of 124I-cG250 PET/CT Versus Diagnostic CT..

2. Clinical Question

3. Trial Design

This completed multicenter Phase III study, NCT00606632, evaluated pre-surgical imaging in patients with operable renal masses. The record lists an enrollment of 226 and identifies Heidelberg Pharma AG as the sponsor. The study started in 2008-03, with primary completion in 2009-11. Its stated purpose was to demonstrate the diagnostic utility of 124I-cG250 PET/CT in this setting.

The study is described as single group, with no random allocation. Participants received 124-Iodine-cG250 (124I-cG250) and underwent both PET/CT and diagnostic CT. The scans were performed days (+/-2days) after receipt of the investigational product. This arrangement supports a diagnostic comparison of two imaging modalities in the same study participants; it is not a parallel treatment comparison with a separate control arm. No masking is recorded for the trial as a whole, while the primary endpoint description specifies that three central readers were independent and blinded.

Histopathology served as the reference standard for determining whether ccRCC was present. The primary outcome was sensitivity and specificity, expressed as proportions of participants and described as an average estimate across the three readers for each imaging modality. The endpoint population excluded cases without the specified histopathology result or images evaluated as readable by the blinded readers. The number meeting that definition is not reported in the registry record.

Secondary outcomes listed include accuracy, positive predictive value, and negative predictive value for PET/CT versus CT. The record lists four outcome measures and two analyses, but the numerical outcome results and details of the analyses are not reported in the registry record. No protocol-level details about the statistical plan, sample-size justification, or interim analyses are 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITD (Intend-to-Diagnose) observed case: All subjects who were enrolled and infused with the investigational product and who had a "standard-of-truth" (histopathology) result and images evaluated as readable by the blinded readers

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 Sensitivity and Specificity of 124I-cG250 PET/CT Versus Diagnostic CT., measured over 6 months.

The primary endpoint measures sensitivity and specificity for identifying ccRCC from imaging, using histopathology as the standard of truth. Sensitivity describes the proportion of participants with ccRCC who are correctly identified by an imaging assessment. Specificity describes the proportion without ccRCC who are correctly identified as not having it. These measures address different kinds of diagnostic classification and should be interpreted separately rather than collapsed into one judgment.

The registry record describes the endpoint as the average estimate from three independent, blinded central readers for each imaging modality. It also specifies a 95% confidence interval for the estimates and a 6 months timeframe. However, numerical estimates and confidence intervals are not reported in the registry record. The record therefore defines what was intended to be measured but does not allow readers to assess the observed sensitivity, specificity, or their precision.

Using histopathology as the reference standard gives the imaging assessments a defined basis for classifying disease status. The endpoint population was restricted to enrolled and infused participants with a histopathology result and images deemed readable by the blinded readers. The number excluded by these requirements is not reported in the registry record. The secondary diagnostic outcomes listed are accuracy, positive predictive value, and negative predictive value; their numerical results are also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a diagnostic accuracy endpoint. It asks how well each imaging assessment classifies participants against histopathology, the designated standard of truth. The record describes sensitivity and specificity as proportions of participants and says the reported estimate is averaged across three independent, blinded central readers for each modality. Numerical estimates and confidence intervals are not reported in the registry record, so only the meaning of these measures—not their observed performance—can be explained.

What do sensitivity and specificity describe?

In general, sensitivity is the fraction of people who truly have a condition who are classified as positive by a test. Specificity is the fraction of people who do not have the condition who are classified as negative. They focus on different parts of the diagnostic classification: sensitivity concerns missed cases, while specificity concerns false alarms. These general definitions do not imply anything about the results of this study. For NCT00606632, the record says histopathology determined disease status and that the endpoint concerned correct identification of ccRCC or its absence.

Why use a reference standard?

General explanation: diagnostic accuracy needs a basis for deciding whether a test classification is correct. A reference standard supplies that classification for the purpose of evaluation. Here, the registry record identifies histopathology as the standard of truth because it is the definitive method for accurately identifying ccRCC. The quality and completeness of the comparison depend on participants having both an interpretable imaging assessment and a reference-standard result. The endpoint population explicitly required histopathology and readable images, but the number meeting these requirements is not reported in the registry record.

What does the reader average mean?

The endpoint description states that three independent, blinded central readers assessed each imaging modality and that the measure was an average estimate across readers. In general, using multiple readers can capture variation in image interpretation, while blinding can reduce the influence of knowledge that might affect a reading. The record does not report reader-specific estimates, a measure of reader agreement, or the precise method used to combine reader estimates. It is therefore not possible to assess how much readings differed or how the averaging affected uncertainty.

How should a confidence interval be understood?

General explanation: a confidence interval expresses the statistical uncertainty around an estimate. A narrower interval indicates greater precision under the method used, while a wider interval indicates less precision. The endpoint specifies a 95% confidence interval, but the bounds are not reported in the registry record. Without the estimate and its interval, readers cannot judge either the level of observed sensitivity or specificity or the precision of those estimates. A confidence interval also does not, by itself, resolve questions about study design, missing observations, or whether the analysis matches the intended clinical question.

What is special about comparing both scans in the same participants?

In general, when two diagnostic procedures are performed in the same participants, their results are related rather than independent. A comparison can use the paired nature of the observations, because each participant contributes information about both modalities. This design differs from comparing two independent groups. The record confirms that every patient underwent PET/CT and CT, but it does not report the specific statistical test or model used to compare the modalities. No particular paired-data method should therefore be attributed to the investigators.

The primary endpoint focuses on sensitivity and specificity. The registry also lists accuracy, positive predictive value, and negative predictive value as secondary outcomes. In general, accuracy summarizes correct classifications across disease-positive and disease-negative participants; predictive values describe the chance that a positive or negative result corresponds to the reference-standard status. Predictive values can depend on how common the condition is in the population being assessed. These general properties do not reveal this study's values: the secondary outcome results are not reported in the registry record.

The registry record lists a 6 months timeframe for the primary endpoint, but does not provide further details about the timing of endpoint assessment. It does not report the analysis code, statistical model, hypothesis tests, significance threshold for the primary comparison, or any adjustment method. These details should not be inferred from the endpoint labels. Nor does the record report interim analyses or a sample-size justification. Enrollment of 226 describes the study overall; it is not, by itself, the number analyzed for every outcome or evidence about statistical precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists sensitivity and specificity as the primary endpoint and identifies accuracy, positive predictive value, and negative predictive value as secondary outcomes. It also lists four outcome measures and two analyses. The numerical findings for these measures, the full analysis details, and any hierarchy among outcomes are not reported in the registry record. It is consequently unclear how the investigators treated the multiple diagnostic measures or whether any adjustment or prespecified prioritization was used. No multiplicity procedure should be assumed.

The endpoint analysis population was defined as enrolled participants who received the investigational product, had a histopathology result, and had images judged readable by the blinded readers. This is an observed-case definition with requirements for available reference-standard and imaging data. The number of participants meeting it, and the number not meeting it, are not reported in the registry record. Reasons for missing histopathology, unreadable images, or other exclusions are also not reported in the registry record.

These omissions limit interpretation of analysis completeness. If participants without evaluable data differ from those included, diagnostic estimates may not represent the full enrolled population; this is a general concern, not a claim that such differences occurred in this study. The registry record does not describe imputation, sensitivity analyses for missing data, or a flow of participants through the endpoint analysis. Details of the statistical analysis population beyond the stated endpoint definition are not reported in the registry record.

The record does not report a statistical analysis plan, interim analyses, or a sample-size justification. Enrollment of 226 should not be mistaken for the endpoint-specific sample size or proof of adequate precision. With no numerical outcome estimates or confidence intervals, multiplicity and missing-data considerations cannot be connected to the magnitude or stability of the observed diagnostic findings.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary anastomotic leak (1.3%), pleural effusion (1.3%), pulmonary embolism (1.3%), haematoma (1.3%), abdominal pain (0.9%).

The adverse-event record lists 226 participants at risk for serious adverse events and 33 affected. For other adverse events, it lists 226 at risk and 191 affected. These are registry counts; they do not describe the number of events per participant, the severity distribution beyond the serious-event classification, or whether individuals were counted in both categories. No deaths are listed in the record.

The serious adverse-event terms listed with percentages are urinary anastomotic leak, pleural effusion, pulmonary embolism, and haematoma, each at 1.3%; abdominal pain and dyspnoea are each at 0.9%. These terms and percentages describe entries in the safety record, not evidence that the imaging procedure caused them. The record does not provide a causal assessment or further event-level context in the information.

These figures should be interpreted separately from the diagnostic endpoint. They are safety observations in the study population and do not indicate whether PET/CT classified ccRCC accurately. The record does not report additional detail about timing, duration, outcome, or attribution for each event term. The counts also should not be converted into comparative risks: this was a single-group imaging study, not a randomized safety comparison between treatment groups.

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

This registry record identifies a focused diagnostic question: how 124I-cG250 PET/CT compares with diagnostic CT for detecting ccRCC in pre-surgical patients with renal masses, using histopathology as the reference standard. It describes a completed multicenter Phase III study with enrollment of 226 and an endpoint based on the average estimates of three independent, blinded central readers. Those design details clarify what the study set out to evaluate.

The record does not report the numerical sensitivity or specificity estimates, their 95% confidence intervals, or the numerical results for the listed secondary diagnostic outcomes. It therefore cannot establish how often either modality correctly classified participants, how precise the estimates were, or whether one modality performed better than the other. It also cannot support a conclusion about equivalence, superiority, or clinical utility. The absence of posted numerical findings is not evidence that the modalities performed the same way or that the study found no difference.

The endpoint's relevance is diagnostic classification, not a treatment effect or a patient outcome. Accuracy against histopathology does not, on its own, show whether using imaging changes subsequent decisions or outcomes. The record does not report those questions. Similarly, the adverse-event counts are safety observations and do not resolve the comparative diagnostic question or establish that an event was caused by the imaging procedure.

The stated analysis population required infusion, histopathology, and readable images. Because the number of participants who met that definition and the handling of missing or unreadable information are not reported in the registry record, the scope and completeness of any endpoint analysis cannot be judged. The available information supports understanding the intended design and endpoint, but not drawing a quantitative conclusion about diagnostic performance.

13. Why This Trial Matters Statistically

This trial is statistically notable for its within-participant diagnostic comparison. Each patient underwent PET/CT and CT, so the question concerns two imaging assessments made in the same study population rather than outcomes in separate randomized groups. In general, paired diagnostic information can be useful because comparisons can account for the fact that both assessments come from the same individuals. The registry record does not report the statistical method used to analyze that pairing, so no particular approach can be attributed to the investigators.

The study also specifies histopathology as its reference standard and defines sensitivity and specificity separately. This emphasizes that diagnostic performance is not a single attribute: correctly identifying disease and correctly identifying its absence are distinct tasks. The three-reader average and blinded central reading process are also relevant design features, although the reader-specific estimates and agreement are not reported in the registry record.

At the same time, statistical interpretation depends on the results and their uncertainty, not only on a well-defined question. Numerical endpoint estimates, confidence intervals, the endpoint-specific sample size, and the analysis details are not reported in the registry record. Consequently, the design can be described, but its measured diagnostic performance cannot be quantified from the record. This distinction is important when reading registry information: a complete description of an endpoint does not substitute for posted outcome estimates.

The study further illustrates why analysis-population definitions matter. The primary endpoint applied to participants with an infusion, histopathology, and readable images. Without counts for exclusions or missing information, the representativeness of that population cannot be assessed. These limitations are central to evaluating how far diagnostic estimates could generalize beyond the participants who were evaluable.

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 main limitation for interpreting the diagnostic question is that the registry record does not report numerical results for the primary endpoint. Sensitivity, specificity, their 95% confidence intervals, and the values for the listed secondary diagnostic outcomes are absent. Diagnostic performance and precision therefore cannot be evaluated from the registry record.

The endpoint population was restricted to participants who were enrolled and infused, had histopathology, and had readable images. The record does not report how many participants met these criteria, how many were excluded, or why data were unavailable or unreadable. This prevents assessment of the endpoint analysis's completeness and of how its population relates to the overall enrollment of 226.

The record states that estimates were averaged across three independent, blinded central readers, but reader-specific results and agreement measures are not reported. The precise approach used to combine reader assessments, and the statistical method used to compare imaging modalities, are not reported in the registry record. The timing is listed as 6 months, without further endpoint-assessment detail.

The study was single group, with each patient receiving both imaging procedures; it was not a randomized comparison. The record does not report a sample-size justification, interim analyses, a full statistical plan, or details on handling missing data and multiple outcomes. These omissions make it difficult to assess design assumptions, analysis choices, and the robustness of any intended comparison. They do not establish that the study was conducted improperly; they mark limits of what can be evaluated from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody — NCT00606632.
• Registry record last updated 2018-10-02; status last verified 2018-09.
• Results first posted 2014-04-14.
• 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

NCT00606632 was a completed multicenter Phase III single-group study of pre-surgical imaging in patients with operable renal masses. Enrollment was 226. The study compared 124I-cG250 PET/CT with diagnostic CT, with both scans performed after receipt of the investigational product. Histopathology was the reference standard for ccRCC status.

The primary endpoint was sensitivity and specificity, described as average estimates across three independent, blinded central readers, with a 95% confidence interval and a 6 months timeframe. Accuracy, positive predictive value, and negative predictive value were listed as secondary outcomes. Numerical results for these outcomes, the endpoint analysis sample size, and further statistical analysis details are not reported in the registry record. The record therefore defines the diagnostic question but does not permit quantitative assessment of the findings.