Low Dose ICG for Biliary Tract and Tumor Imaging: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Low Dose ICG for Biliary Tract and Tumor Imaging (NCT04942665), a randomized phase 2 study. The primary outcome is Quantitative Assessment - Bile Duct-to-liver Fluorescence Intensity Ratio.

2. Clinical Question

3. Trial Design

The registry classifies this as a randomized, double-masked, parallel phase 2 trial, marked completed. It lists enrollment of 60 and identifies the University of Florida as sponsor. The study dates run from 2021-09-15 to a primary completion date of 2022-09-15. These record details describe the registered study; they do not by themselves establish how many participants contributed usable data to every endpoint.

The arms differed in the stated intravenous indocyanine green dose before surgery: 0.05 mg in the low-dose arm and 2.5 mg in the standard-dose arm. The intervention record also names the PINPOINT Endoscopic Fluorescence device. The posted primary outcome summaries include 29 participants in the low-dose arm and 26 in the standard-dose arm. The reason these endpoint counts do not match the enrollment figure is not reported in the registry record. Neither enrollment nor endpoint counts should be interpreted as proof that every enrolled participant contributed to every analysis.

The primary endpoint was measured intraoperatively, over an average of 2 hours. The registry also lists three secondary outcomes concerning qualitative visualization and a bile duct-to-background fat fluorescence intensity ratio. The record contains a reported analysis for one secondary outcome, while analysis results for the other listed secondary outcomes are not reported in the registry record.

Randomization and masking are features of the registered design, but details such as the randomization method, allocation concealment, who was masked, and how masking was maintained are not reported in the registry record. The protocol, eligibility criteria, and analysis population are also not reported in the registry record. The design labels alone cannot answer those questions.

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: No enrolled patients were excluded from the study prior to group assignment.

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: 5 enrolled and randomized patients were excluded from analysis because their videos were either too dark or unusable due to technical issues with the scope, camera, or device tower.

6. Primary Endpoint

The registry lists the primary outcome as Quantitative Assessment - Bile Duct-to-liver Fluorescence Intensity Ratio, measured over intraoperative, average of 2 hours.

The primary endpoint is the bile duct-to-liver fluorescence intensity ratio. It is defined as the common bile duct fluorescence signal divided by the liver fluorescence signal, measured during surgery over an average of 2 hours. A ratio expresses the duct signal relative to the liver signal, rather than reporting either signal alone. This can be useful when the study question concerns how clearly biliary anatomy is distinguished against nearby liver tissue during imaging.

The registry specifies the median and inter-quartile range as the summary measures. The median describes the middle of the observed distribution, while the inter-quartile range describes the span from the lower to the upper quartile. These summaries are often useful when a distribution is skewed or includes influential extreme values, although the registry record does not explain why these measures were selected for this endpoint.

The posted median is 2.7 for the low-dose arm, with an inter-quartile range from 1.5 to 4.2. For the standard-dose arm, the median is 0.7, with an inter-quartile range from 0.6 to 0.8. These are descriptive summaries of the posted observations. The registry record does not report a confidence interval, p-value, or other inferential comparison for the primary endpoint. Therefore, the summaries do not quantify the precision of a difference between arms or establish whether the observed contrast is compatible with chance variation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary summary measure?

The primary endpoint is summarized with a median and inter-quartile range rather than a mean and standard deviation. The median identifies the center of the ordered observations. The inter-quartile range describes the middle portion of the distribution, running from the lower quartile to the upper quartile. These summaries are relatively resistant to extreme observations compared with the mean, which can be useful when data are skewed. That is a general statistical explanation; the registry record does not state the investigators’ reason for choosing these summaries.

The endpoint is a ratio of the common bile duct signal to the liver signal. A ratio can make a relative signal contrast easier to interpret than either signal on its own. However, the ratio does not reveal the separate values of its numerator and denominator, and the registry does not report those component measurements. The interpretation is therefore restricted to the reported relative measure.

What can be learned from the secondary comparison?

The reported secondary comparison uses a mean difference for the qualitative assessment of overall intraoperative visualization. A mean difference describes the subtraction of one arm’s average from the other arm’s average, as defined by the reported comparison. Its confidence interval expresses a range of values compatible with the data and statistical model at the stated confidence level. In general, a wider interval indicates less precision. The registry record’s interval spans zero, so values consistent with no mean difference are included, along with values on either side.

The reported p-value is unadjusted. In general, a p-value evaluates how unusual data at least as incompatible with a null hypothesis would be under the model and assumptions used, if that null hypothesis were true. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. Here, p = 0.335 applies to the reported secondary comparison, not to the primary ratio. The registry record does not report a multiplicity adjustment for this result.

The secondary outcome uses means and standard deviations, whereas the primary outcome uses medians and inter-quartile ranges. A standard deviation describes spread around the mean under its usual interpretation; it is not the same as a confidence interval for the mean. For a mean difference, uncertainty depends on both the spread of observations and the amount of information in each arm. The registry record reports an unadjusted interval and p-value for the secondary endpoint, but does not report a corresponding inferential analysis for the primary endpoint.

Why does uncertainty matter?

Observed summaries are estimates based on the analyzed observations. A confidence interval gives information about their uncertainty under the method used. Without an interval or another inferential measure for the primary endpoint, the posted medians alone cannot establish how precisely the underlying group contrast is estimated. In general, an observed difference can be compatible with a broad range of population differences, especially when the available information is limited or the data are variable.

Over-dispersion is a general concern when variability exceeds what a statistical model assumes. If a model understates variability, its standard errors may be too small and its intervals may be too narrow. The registry record does not report a model-based primary analysis or enough distributional detail to assess over-dispersion for the primary endpoint. This is therefore a general statistical consideration, not a finding about this trial.

How should planning illustrations be read?

The registry includes a planning illustration based on the observed effect for the secondary mean difference, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Its rows describe planning for 100%, 75%, and 50% of the observed effect. For planning for 100% of the observed effect, it gives 239 participants per arm for 80% power and 319 participants per arm for 90% power. For planning for 75% of the observed effect, the corresponding figures are 424 and 567 participants per arm. For planning for 50% of the observed effect, they are 953 and 1,275 participants per arm.

These are sample-size planning illustrations, not observed power and not the trial’s own design justification. The record explicitly describes them as computed from the observed effect rather than from the trial’s design. They depend on the stated assumptions and on the observed secondary effect, so they should not be read as confirming that the trial was designed to detect the primary endpoint difference. The trial’s sample-size justification is not reported in the registry record.

More generally, power is a design concept: it describes the probability that a specified analysis will detect an effect of a specified size under its assumptions. It cannot be inferred simply by plugging the observed result into a post hoc calculation. The planning illustrations are useful only as conditional scenarios for future planning under the assumptions stated in the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled. This matters because the record lists several outcomes, and testing multiple outcomes can increase the chance of obtaining at least one apparently unusual result by chance. An adjustment plan, a hierarchy for interpreting outcomes, or a distinction between confirmatory and exploratory analyses is not reported in the registry record. The unadjusted secondary p-value should therefore be read as the result of that comparison, not as evidence that the study-wide chance of a false-positive result has been controlled.

Missing-data handling is also not reported in the registry record. The primary endpoint summaries include 29 participants in the low-dose arm and 26 in the standard-dose arm, while the registered enrollment is 60. The reason for the difference between enrollment and endpoint analysis counts is not reported in the registry record. The record does not state whether observations were unavailable, excluded, or otherwise not included, nor does it describe any imputation or sensitivity analysis. No explanation for the missingness pattern can be inferred from the counts alone.

The analysis populations are not reported in the registry record. It is therefore unclear whether the posted summaries follow an intention-to-treat population, a per-protocol population, or another definition. The record also does not describe participant flow, exclusions after randomization, or the handling of protocol deviations. These details affect how closely an analysis preserves the benefits of randomization and how broadly its results can be interpreted.

Other elements of the statistical plan, including interim analyses and the sample-size justification, are not reported in the registry record. The planning illustration based on an observed secondary effect is not evidence of the trial’s original design assumptions. Taken together, the missing information limits assessment of selection, missingness, and selective testing. These are reporting limitations; the registry record does not establish that any particular bias occurred.

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 records zero serious adverse events among 29 participants at risk in the low-dose arm and zero among 26 participants at risk in the standard-dose arm. It also records zero other adverse events in each arm and zero deaths in each arm. No top serious adverse event terms are listed.

These figures describe what the registry records for the stated at-risk groups. They do not show that the risk of an adverse event is zero, or that the two doses have identical safety. With no recorded events, the data provide limited information about the range of possible event rates, especially for uncommon harms. The registry record does not report additional detail about event definitions, collection procedures, follow-up duration, or how adverse events were assessed. The figures should be read as recorded counts within this study, not as a general safety guarantee.

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

The primary endpoint summaries show a higher posted median bile duct-to-liver fluorescence intensity ratio in the low-dose arm than in the standard-dose arm. The reported inter-quartile ranges describe the spread of the middle portion of each arm’s observations. This is a descriptive contrast in the registry data. The record does not provide a primary-endpoint confidence interval, p-value, or adjusted comparison, so it does not quantify the uncertainty of the contrast or establish whether it is statistically distinguishable from chance variation.

The secondary qualitative visualization comparison has a reported mean difference and unadjusted p-value, but it is a separate endpoint. Its result cannot be substituted for a primary analysis of the ratio. The other listed secondary outcomes have no results reported in the registry record. Thus, the posted evidence does not provide a complete inferential account across the registered outcomes.

The trial’s randomized design is relevant to comparing groups, but interpretation also depends on how randomization was implemented, which participants were analyzed, missing-data handling, and adherence to the planned analyses. Those details are not reported in the registry record. The difference between enrollment and the primary endpoint analysis counts is not explained there. These gaps limit assessment of both the estimate and the population to which it may apply.

The data do not establish that either dose improves surgical outcomes, changes patient health outcomes, or is preferable in practice. The registry describes an imaging-focused study, and the posted primary measure is a fluorescence ratio. The record does not report outcome evidence that would justify conclusions beyond those imaging summaries. Nor do zero recorded adverse events establish an absence of risk.

The appropriately bounded conclusion is that the registry posts different descriptive primary medians between the dose arms, while omitting the inferential analysis needed to characterize the precision of that difference. The result is informative as a record of observed imaging measurements, but it does not by itself establish a causal effect, clinical benefit, equivalence, or safety advantage.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it puts a quantitative imaging measure at the center of a comparison between two dose strategies. The ratio is defined using the common bile duct signal relative to the liver signal, so it captures a contrast between anatomical signals rather than an isolated fluorescence measurement. The registry’s use of medians and inter-quartile ranges also highlights that a distributional summary can be more informative than reporting only an average when the shape of the data may matter.

The record also illustrates why descriptive separation and inferential evidence are not the same. The posted primary medians differ, but the registry gives no confidence interval or p-value for that endpoint. Without an uncertainty estimate, a reader cannot judge the precision of the observed contrast from the registry results. The secondary comparison includes inferential statistics, but it answers a related, not identical, question. Keeping those outcomes distinct is essential to avoid treating one result as confirmation of another.

The planning illustration is another useful statistical distinction. It translates an observed secondary effect into conditional sample-size scenarios under stated assumptions. Such planning figures can help frame future study design, but they do not indicate the power of this completed study and are not evidence of the original sample-size rationale. The registry record does not report that rationale.

Finally, the record underscores the importance of transparent analysis populations, missing-data methods, and multiplicity plans. Their absence does not prove that the analyses were flawed, but it makes independent assessment harder. For biostatisticians and clinical researchers, the main lesson is to separate the registered design, observed summaries, reported inferential analysis, and unreported methods rather than treating them as a single complete evidence package.

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 central limitation is that the registry posts primary endpoint summaries without a primary inferential comparison. The medians and inter-quartile ranges describe the analyzed observations, but the record does not provide an interval or test for the between-arm contrast. Precision and statistical compatibility with alternative values therefore cannot be assessed from the primary results as posted.

The primary endpoint analysis counts are 29 for the low-dose arm and 26 for the standard-dose arm, while enrollment is listed as 60. The registry record does not explain the relationship between those figures. It also does not report participant flow, analysis-population definitions, or missing-data methods. This prevents assessment of whether the analyzed participants represent all randomized participants or whether missingness could have influenced the summaries.

The record lists three secondary outcomes, but reports results for only one. The available secondary analysis is unadjusted, and multiplicity handling is not reported. It is therefore difficult to determine how the secondary result fits into the overall prespecified testing strategy. The other secondary outcomes cannot be used to corroborate or challenge the primary result because their results are not reported in the registry record.

Additional trial-specific details are absent, including the randomization procedure, masking implementation, eligibility criteria, and the reasons for the selected primary summary measures. The registry record also does not provide detailed definitions or collection procedures for adverse events. These omissions limit assessment of internal validity and interpretability, but they do not establish that a particular design or analysis problem occurred.

Finally, the primary measure is an intraoperative fluorescence ratio. The registry record does not provide evidence linking this measure to patient-centered outcomes. Conclusions should remain limited to the recorded imaging endpoints and should not be extended to clinical effectiveness or broader safety claims.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Low Dose ICG for Biliary Tract and Tumor Imaging — NCT04942665.
• Registry record last updated 2023-08-30; status last verified 2023-08.
• Results first posted 2023-08-30.
• 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

The registry identifies NCT04942665 as “Low Dose ICG for Biliary Tract and Tumor Imaging,” a completed, randomized, double-masked, parallel phase 2 trial sponsored by the University of Florida. The registered enrollment is 60, with study dates from 2021-09-15 to primary completion on 2022-09-15.

The comparison is between indocyanine green at 0.05 mg intravenously before surgery and a standard dose of 2.5 mg intravenously before surgery. The primary endpoint is the intraoperative bile duct-to-liver fluorescence intensity ratio, summarized by median and inter-quartile range. The posted medians are 2.7 for low dose and 0.7 for standard dose. No inferential comparison for this primary endpoint is reported in the registry record.

The record includes one reported secondary analysis, other listed secondary outcomes without posted results, and zero recorded serious adverse events, other adverse events, and deaths in both arms. Analysis populations, missing-data procedures, multiplicity handling, and the sample-size justification are not reported in the registry record.