An Evaluation of Tilmanocept by IV Injection Using SPECT/CT vs PET Imaging in Subjects With Liver Metastases.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Evaluation of Tilmanocept by IV Injection Using SPECT/CT vs PET Imaging in Subjects With Liver Metastases. (NCT03029988), a non-randomized phase 1 study. The primary outcome is Visualization of Lesions by FDG PET/CT Imaging and by Tc 99m Tilmanocept SPECT/CT Imaging..

2. Clinical Question

The study’s clinical question concerns imaging agreement, not whether one imaging method improves patient outcomes. Concordance asks whether two methods produce corresponding findings in the same subjects. It is distinct from asking whether either method is correct against an independent reference standard. The registry record names the imaging methods and the disease setting, but does not report an independent reference standard or a detailed definition of concordance.

The study planned to examine subjects with colorectal carcinoma and liver metastases. Its brief summary describes estimating concordance of Tc 99m localization in liver metastases using SPECT/CT and abdominal FDG PET/CT per subject. The primary outcome entry instead describes lesion visualization by both imaging methods, with a timeframe within 7 days after tilmanocept administration. How the per-subject concordance objective and lesion-count endpoint were to be combined or interpreted is not reported in the registry record.

Because allocation was non-randomized and the design was sequential, the cohorts should not be read as randomized comparator groups. The registry record does not establish that their participants were intended to provide a direct comparative estimate of dose effects.

3. Trial Design

The registry record identifies this as a Phase 1, non-randomized, unmasked, sequential study. Enrollment is listed as 3. The study began on 2017-07-26, and its primary completion date is 2018-09-24. Its status is TERMINATED. The record does not state why it was terminated, and no reason should be inferred from the status alone.

Two cohorts are described. Cohort 1 was to receive a single intravenous injection of 50 µg tilmanocept radiolabeled with 2.0 mCi Tc99m. Cohort 2 was to receive a single intravenous injection of 200 µg tilmanocept radiolabeled with 2.0 mCi Tc99m. The Cohort 2 description also begins a statement about whether additional enrollment might provide meaningful data, but the available description is incomplete. Further details of that decision process are not reported in the registry record.

Sequential describes the registered model; it does not, by itself, establish a formal interim analysis, stopping boundary, or prespecified rule for moving between cohorts. Those protocol details are not reported in the registry record. Allocation is listed as non-randomized and masking as none. Accordingly, the cohort structure does not support interpreting the study as a randomized comparison, and differences between cohorts would not automatically isolate dose as the cause.

The interventions include tilmanocept as a drug and SPECT/CT imaging as a procedure. The outcome timeframe is within 7 days after tilmanocept administration. Although FDG PET/CT is part of the stated imaging question, the record does not give additional procedural timing details for that scan.

The registry lists one outcome measure and zero analyses. The enrollment figure is 3, while the safety entry lists 3 participants at risk in Cohort 1. The record does not give a complete accounting of participant disposition by cohort or explain how enrollment was distributed between the two cohorts. A sample-size justification, target enrollment rationale, and detailed statistical analysis 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.

Overall Study

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.

Population: No subjects enrolled in Cohort 2

6. Primary Endpoint

The registry lists the primary outcome as Visualization of Lesions by FDG PET/CT Imaging and by Tc 99m Tilmanocept SPECT/CT Imaging., measured over Within 7 days after Tc 99m tilmanocept administration.

The primary outcome is titled “Visualization of Lesions by FDG PET/CT Imaging and by Tc 99m Tilmanocept SPECT/CT Imaging.” Its unit is lesions, and the registry describes the parameter as a number. The timeframe is within 7 days after Tc 99m tilmanocept administration. The primary objectives also include estimating per-subject concordance between tilmanocept localization on SPECT/CT and abdominal FDG PET/CT in liver metastases from colorectal carcinoma.

A lesion count records how many lesions are visualized by an imaging method. Comparing counts or lesion-level findings can describe whether the methods identify corresponding findings, but agreement in counts alone does not necessarily mean the same individual lesions were identified. A per-subject concordance assessment can address whether findings correspond within each subject, though the registry record does not specify the exact concordance definition, unit of analysis, or scoring procedure.

As a general statistical point, an imaging comparison is informative only when its endpoint is defined clearly enough to establish what counts as a match and how uncertain or indeterminate findings are handled. Such details are not reported in the registry record. Nor does the record report numerical endpoint findings, an estimate of concordance, or an uncertainty interval. The stated endpoint therefore identifies the intended measurement but does not establish the observed imaging agreement.

The objective also includes safety monitoring through adverse events and changes over time in laboratory tests, vital signs, and physical examination findings. Specific results for those laboratory, vital-sign, and examination measures are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does concordance mean?

As a general statistical concept, concordance describes the degree to which two measurement methods give corresponding findings. For imaging, the meaning depends on how the findings are paired and scored. If the goal is to compare lesion localization, the method must define what qualifies as the same lesion across scans, how uncertain findings are handled, and whether agreement is assessed per lesion or per subject. The registry record states that concordance was to be estimated per subject, but does not report the precise definition or calculation method.

Agreement is not identical to accuracy. Two imaging methods can agree with one another without either being compared against an independent standard that establishes which finding is correct. The registry record describes FDG PET/CT as the comparator imaging method, but does not report an independent reference standard. It also does not report a diagnostic accuracy endpoint such as sensitivity or specificity.

What does a lesion count capture?

The primary outcome is described as the number of lesions visualized by FDG PET/CT and by Tc 99m tilmanocept SPECT/CT. Counts can summarize the number of findings detected by each method. However, the same count from two methods does not necessarily mean the methods detected the same lesions. Conversely, different counts alone do not describe which findings differed. For that reason, the registry’s stated per-subject concordance objective is conceptually distinct from the count endpoint.

The record does not provide a scoring manual, lesion-matching rules, adjudication process, or a detailed definition of the analysis unit. It also does not report whether readers were blinded to findings from the other modality. Masking is listed as none, but the record does not clarify how that designation applied to image interpretation. These omissions matter because assessment and reader knowledge can influence how imaging findings are recorded.

How should uncertainty be assessed?

As a general statistical concept, an estimate describes the observed result in a sample, while a confidence interval communicates how uncertain that estimate is under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, but neither the estimate nor an interval is reported for the primary endpoint in the registry record. Without them, the amount of uncertainty around imaging concordance cannot be evaluated.

The listed enrollment is 3, so any interpretation would also need to account for the limited number of enrolled subjects. The registry does not report how many participants had evaluable results for both imaging methods. Where outcomes are assessed per subject, the number of subjects is especially relevant; where lesions are counted, multiple lesions within one subject may not be statistically independent. The record does not describe whether or how within-subject clustering would be addressed.

What can the sample-size assumptions tell us?

The registry information describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also says the effect to detect is a stated fraction of the observed effect. These are assumptions for an illustration, not the study’s reported design rationale or a record of achieved power. No sample-size illustration values are included in the registry record for this analysis, and the registry record does not report a prospective sample-size justification.

As a general principle, a sample-size calculation depends on the outcome scale, expected effect, variability, significance threshold, allocation assumptions, and desired power. An illustration that uses an observed effect is especially dependent on that estimate, which can be unstable in a small study. Such a calculation is for planning, not “observed power” and not evidence that the enrolled sample was adequate. Also, an assumption of equal allocation in a planning exercise does not demonstrate that participants in this sequential, non-randomized study were allocated equally.

The stated illustration convention distinguishes total event counts for time-to-event outcomes from participants per arm for other outcomes. The primary endpoint is a lesion count, but the record does not supply a corresponding sample-size result or explain how the illustration maps to the registered imaging objective. It should not be treated as the study’s own sample-size plan.

What does the design imply for comparisons?

Randomization, in general, is used to reduce systematic differences between comparison groups. This study is registered as non-randomized, so the two cohorts cannot be presumed comparable in all respects. Its sequential model also means the cohorts were not registered as concurrently randomized groups. The record does not report adjustment methods or a prespecified causal comparison of dose groups.

The imaging methods are to be compared within the clinical question, but the exact paired analysis is not reported. A paired design generally uses observations from the same subjects to compare methods, which can account for shared subject characteristics. The registry describes concordance per subject, yet does not report whether all participants received both scans, whether each scan was evaluable, or the statistical method for paired observations.

As a general point, over-dispersion arises when observed variability in count data exceeds what a simple count model assumes. It can make standard errors too small if a model fails to account for the extra variation. The registry record does not report a count-data model, a dispersion assessment, or any model-based analysis. It is therefore not possible to say whether over-dispersion was assessed or relevant in the analysis actually used.

Finally, the record’s zero reported analyses should be read as an absence of registry-reported analysis results, not as evidence for a particular statistical method or as proof that no analysis occurred elsewhere. The detailed analysis plan, handling of missing scans, and any sensitivity analyses are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and zero analyses. It does not report a multiplicity strategy, such as a prespecified hierarchy of outcomes or an adjustment for testing multiple outcomes. The primary objectives include imaging concordance and safety monitoring, and the registered endpoint refers to visualization by two imaging methods. The record does not explain how these objectives relate statistically or whether additional exploratory comparisons were planned.

As a general statistical concept, multiplicity can arise when several hypotheses or outcomes are examined. Without a stated plan, the chance of false-positive findings across multiple tests cannot be evaluated from a collection of nominal test results alone. In this case, no primary endpoint test results are reported, so there is no reported multiplicity-adjusted or unadjusted inference to interpret.

Missing-data handling is not reported in the registry record. The entry does not say how missing scans, unevaluable images, incomplete lesion assessments, or missing safety measurements would be treated. It also does not report the number of participants with complete data for each endpoint or the reasons for any missing observations.

The registry record does not define analysis populations, such as an intention-to-treat or per-protocol population, and does not report which participants were included in any analysis. The listed enrollment is 3, and Cohort 1 has 3 participants at risk in the safety entry, but these figures do not establish the number with evaluable paired imaging or the endpoint-specific analysis population. No missing-data assumptions or sensitivity analyses are reported. Consequently, the completeness and representativeness of the endpoint data cannot be assessed from the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety entry lists Cohort 1 with 3 participants at risk. It records 0 participants with serious adverse events, 2 with other adverse events, and 0 deaths. These are participant counts, not event rates, and no percentages are stated. The record lists no serious adverse event terms.

The zero serious-event count means that no serious adverse events are recorded for those at risk in this entry. It does not establish that serious events are impossible, nor does it by itself characterize safety across a larger population. The count is based on a small recorded group, and the registry does not report the observation duration for safety outcomes separately from the study timeframe.

The “other” adverse-event count is a separate category from serious adverse events in the registry entry. The event terms, severity details, timing, and relationship to tilmanocept are not reported in the available record. The count therefore indicates that other adverse events were recorded for 2 participants, but does not describe their nature or attribution.

The safety objective also mentions monitoring changes over time in laboratory tests, vital signs, and physical examination findings. Results for those assessments are not reported in the registry record. The cohort-specific counts should not be generalized to Cohort 2 or treated as a complete safety summary for every participant, because a corresponding safety entry for that cohort is not included in the record.

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

The registry record establishes that investigators planned an exploratory assessment of technetium Tc 99m tilmanocept localization by SPECT/CT in subjects with liver metastases from colorectal carcinoma, with abdominal FDG PET/CT as the imaging comparator. It also identifies the intended primary timeframe as within 7 days after tilmanocept administration and states that concordance was to be estimated per subject.

It does not establish how many lesions either method visualized, whether findings matched, or how precise an estimate of concordance might have been. No endpoint estimate, confidence interval, or analysis result is reported. The study objective must not be mistaken for a result: the planned comparison alone cannot show agreement, superiority, diagnostic accuracy, or a clinical effect.

The record also does not establish a causal dose comparison between cohorts. The study was non-randomized and sequential, and the registry does not report a comparative analysis controlling for potential differences. The cohort descriptions specify different tilmanocept amounts, but the design details do not support attributing any hypothetical difference in findings to dose.

The reported safety counts are limited to the Cohort 1 entry: 0 serious adverse events and 2 participants with other adverse events among 3 at risk, with 0 deaths. Those counts provide descriptive information, not a broad or definitive safety conclusion. Terms and detailed outcomes for the other adverse events, as well as laboratory and vital-sign results, are not reported in the registry record.

In practical statistical terms, the registry record is informative about the study’s question and structure, but not about the primary imaging result. Any stronger interpretation would require reported imaging findings, a defined analysis, and information about which participants and images contributed to that analysis.

13. Why This Trial Matters Statistically

This study raises a useful statistical distinction between comparing imaging methods and comparing treatments. Its central question is whether two modalities localize liver metastases in a concordant way within subjects. That is a measurement-agreement problem, not a randomized efficacy comparison. Keeping that distinction clear prevents the dose cohorts from being treated as a control comparison and prevents an imaging objective from being interpreted as an outcome benefit.

The registry also illustrates why endpoint definitions matter. Counting lesions visualized by each modality and assessing whether the modalities identify corresponding lesions are related but not interchangeable tasks. The former summarizes counts; the latter requires a rule for matching findings and defining agreement. The record states both a lesion-visualization endpoint and a per-subject concordance objective, while leaving the calculation details unreported.

Small exploratory studies can be useful for developing and evaluating measurement questions, but their interpretation depends on transparent reporting of participant flow, evaluable scans, endpoint definitions, and uncertainty. Here, enrollment is listed as 3, yet primary endpoint results and analysis methods are not reported. That makes the limits of inference as important as the intended question.

The entry further shows why design labels must be read carefully. Sequential, non-randomized cohorts with different doses do not create a randomized dose comparison. Likewise, a sample-size illustration based on an observed effect is not a prospective justification or evidence of achieved power. Clear separation of design, planning assumptions, and observed data is necessary for sound interpretation.

Finally, registry status and outcome reporting are distinct. The study is marked TERMINATED, but the reason is not stated. Without reported primary results or a termination explanation, neither can be inferred from the other.

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 registry record does not report numerical primary endpoint findings, including lesion counts or a concordance estimate. It therefore offers no basis for assessing the direction, magnitude, or precision of the imaging comparison. The record also does not report confidence intervals or hypothesis-test results.

Enrollment is listed as 3, and the safety entry covers 3 participants in Cohort 1. A complete cohort-by-cohort enrollment and disposition account is not reported. Nor is the number of subjects with evaluable results from both imaging methods stated. This prevents assessment of whether all enrolled participants contributed to the primary endpoint.

The study is non-randomized and sequential, with no masking. The registry does not describe a direct randomized comparison, adjustment for cohort differences, or specific safeguards against interpretive bias. The Cohort 2 description is incomplete in the record, and details of any rule for additional enrollment are not fully reported.

The operational definition of concordance, lesion matching, image reading procedures, and handling of indeterminate or missing scans are not reported in the registry record. These details affect how a comparison of imaging findings should be interpreted. The record also does not report an independent reference standard, so the stated comparison should not be read as establishing diagnostic accuracy.

A sample-size justification, detailed statistical analysis plan, multiplicity approach, analysis populations, and missing-data methods are not reported. Although the registry includes planning-illustration assumptions, those assumptions are not the study’s documented design justification. The reason for TERMINATED status is also not reported. These limitations are specific to the information available in the registry record; they do not establish what may have been documented elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Evaluation of Tilmanocept by IV Injection Using SPECT/CT vs PET Imaging in Subjects With Liver Metastases. — NCT03029988.
• Registry record last updated 2020-09-10; status last verified 2020-09.
• Results first posted 2019-11-18.
• 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

NCT03029988 is a Phase 1, non-randomized, unmasked, sequential study of intravenous technetium Tc 99m tilmanocept imaging in subjects with liver metastases from colorectal carcinoma. Enrollment is listed as 3; the study began on 2017-07-26, had a primary completion date of 2018-09-24, and is marked TERMINATED. The registry record does not state why it was terminated.

The primary question concerns concordance between tilmanocept SPECT/CT and abdominal FDG PET/CT, with lesion visualization specified within 7 days after administration. Cohort 1 is described as receiving 50 µg tilmanocept with 2.0 mCi Tc99m; Cohort 2 is described as receiving 200 µg with 2.0 mCi. No primary analysis results are reported.

The safety entry for Cohort 1 records 0 serious adverse events, 2 participants with other adverse events, and 0 deaths among 3 at risk. The record does not report the event terms or full results of the other stated safety assessments.