Biliary Excretion of Conjugated Bile Acids in Humans Measured by 11C-cholylsarcosine PET/CT: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Biliary Excretion of Conjugated Bile Acids in Humans Measured by 11C-cholylsarcosine PET/CT (NCT01879735), a non-randomized phase 1 study. The primary outcome is Percentage of Participants in Whom we Could Quantify Hepatic Transport of 11C-CSar.

2. Clinical Question

3. Trial Design

This is a phase 1, non-randomized, unmasked, parallel study sponsored by the University of Aarhus. The registry record lists enrollment of 22 and a completed status. The recorded study period runs from 2013-06 to primary completion in 2014-09. The study concerns PET/CT measurement of hepatic transport using the bile acid tracer 11C-CSar, with ICG also listed as an intervention.

The brief description frames the work as protocol development, involving PET/CT examinations of healthy people and patients with cholestatic disorders. The listed conditions are cholestasis, primary sclerosing cholangitis, and primary biliary cirrhosis. The registry describes two methodological aims: examine ICG’s effect on 11C-CSar transport kinetics, and assess whether bolus or constant infusion is preferable for the PET/CT scanning method. The infusion experiments may use ICG if it does not affect 11C-CSar kinetics, according to the arm description.

These aims should not be read as randomized comparisons of treatments. Non-randomized allocation means the record does not establish that the groups are comparable in the way random assignment is intended to achieve. The registry record does not report the detailed allocation process, participant flow, group characteristics, or the number of participants completing each measurement. It also does not report a statistical analysis plan, sample-size justification, or numerical outcome results. The primary outcome timeframe states that all measurements are performed in one day; further timing details 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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants in Whom we Could Quantify Hepatic Transport of 11C-CSar, measured over All measurements are performed in one day..

The primary endpoint is the percentage of participants in whom investigators could quantify hepatic transport of 11C-CSar. It is a measure of whether the imaging and measurement approach produced a quantifiable transport assessment, rather than a reported measure of clinical benefit. The registry names the outcome as a percentage of participants and gives the timeframe as one day for all measurements.

In general, a proportion endpoint can communicate the frequency of a defined event—in this case, successful quantification—within the participants assessed. It is useful for a protocol-development study because it focuses on whether the intended measurement can be obtained. Interpretation depends on knowing how success was defined, which participants were included in the denominator, and whether missing or unusable measurements were counted as failures or handled another way. Those operational details are not reported in the registry record.

The record lists the outcome measure but does not provide its numerical result, a denominator for the analysis, or an uncertainty estimate. Consequently, the proportion itself and the precision of any estimate cannot be assessed from the registry record. The endpoint also does not, by itself, establish that the measured quantity reflects a patient-important outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a percentage endpoint: the share of participants in whom hepatic transport of 11C-CSar could be quantified. It gives no numerical endpoint result, no analysis population definition, and no reported statistical analysis. The explanations below are general statistical context, not a description of analyses documented for this study.

What does a percentage endpoint represent?

In general, a percentage is a proportion expressed on a percentage scale. Its interpretation depends on a clear event definition and denominator. Here, the named event is the ability to quantify hepatic transport. For a complete interpretation, readers would need to know the operational criterion for “could quantify,” which participants were eligible for the calculation, and how unsuccessful, incomplete, or missing measurements were classified. These details are not reported in the registry record. The absence of them limits reproducibility and makes it difficult to compare the endpoint across studies.

A percentage is descriptive unless an analysis adds a comparison or an uncertainty estimate. Even when an observed percentage is available, it should be read in light of how many observations contributed to it and how participants were selected. The registry record does not give an analyzed denominator or a confidence interval. It is therefore not possible to characterize the precision of this endpoint from the posted results.

How would a confidence interval help?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical model and its assumptions. It conveys uncertainty in a way that a single percentage cannot. A narrow interval generally indicates greater precision than a wide interval, although precision does not establish that a measurement is clinically important or free of bias. No confidence interval for the primary endpoint is reported in the registry record.

For a comparison between conditions, an interval around a difference can help show both the direction and uncertainty of that contrast. Such an interpretation also relies on the study design and analysis being appropriate. This record describes non-randomized methodological contrasts, but does not report estimates, intervals, or an analysis method for them. There is consequently no reported contrast to interpret statistically.

Why does the non-randomized design matter?

In general, random allocation is used to reduce systematic differences between comparison groups. In a non-randomized study, groups or conditions can differ for reasons other than the measurement approach being examined. Statistical adjustment can sometimes address measured differences, but cannot guarantee that unmeasured differences are removed. The registry record does not report group characteristics, an adjustment model, or a detailed allocation procedure. It is not possible to determine from the record whether comparisons accounted for participant differences.

The unmasked design is also a feature to consider. In general, knowledge of an assigned condition can affect aspects of measurement or assessment when judgment is involved. The registry record does not describe masking of outcome assessment or provide information that would show whether this was a practical concern for the PET/CT measurements.

What can be inferred from the listed study aims?

The stated aims concern whether ICG affects 11C-CSar transport kinetics and whether bolus or constant infusion is the preferred scanning method. In general, a study can address such questions with prespecified outcome definitions and comparisons, but the registry record does not report a statistical plan, estimates, or results for these aims. Its descriptions of intended experiments cannot substitute for observed data.

The record also includes a planning-illustration assumption: two-sided significance level 0.05, equal allocation, and a normal approximation, with an effect defined as a stated fraction of an observed effect. These are described as planning assumptions, not as the trial’s own design justification. No observed effect or numerical illustration is reported in the registry record. Such planning quantities, when available, are projections under assumptions, not observed power or evidence that a study detected an effect.

Finally, the registry record lists no analysis results. Without outcome estimates, uncertainty measures, analysis definitions, and participant-level disposition, the statistical interpretation remains descriptive of the study’s purpose and reporting status rather than its empirical findings.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("ICG Infusion", "Infusion Method")
n      <- c(6, 16)
events <- c(6, 16)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  ICG Infusion  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Infusion Method  16  16  100.0  79.4  100.0  80.6  100.0  80.5  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no analysis results. It does not report a prespecified statistical analysis plan, a hierarchy of outcomes, or a procedure for handling multiple comparisons. The study descriptions include more than one methodological question—ICG’s effect on tracer kinetics and bolus versus constant infusion—but the record does not explain whether these were treated as separate formal hypotheses or how any multiplicity was addressed.

In general, testing several hypotheses can increase the chance of obtaining an apparently notable result by chance if the analyses are interpreted without accounting for the number of comparisons. A prespecified plan can clarify which outcome is primary and how secondary or exploratory analyses should be interpreted. No such details are reported in the registry record, so it is not possible to assess multiplicity handling.

The record does not report missing-data methods, the number of participants with evaluable measurements, or how unsuccessful or incomplete quantification was treated. This is especially relevant for a primary endpoint defined by whether transport could be quantified: missing data and failed quantification may have different meanings, but the registry does not state how they were distinguished. The analysis population and any exclusions are also not reported.

These omissions do not establish that the study lacked procedures for analysis or data handling; they mean those procedures are not reported in the registry record. Without them, readers cannot determine which participants contributed to each result or how robust the endpoint would be to alternative handling of missing measurements.

12. 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 0% reporting threshold.

The registry record reports zero serious adverse events among 6 participants at risk in the group titled “ICG's Effect on 11C-CSar Transport,” and zero among 16 participants at risk in the group titled “Bolus vs. Constant Infusion.” It also reports zero other adverse events in each of those groups. These are group-specific counts; the record does not establish whether the groups are mutually exclusive, so they should not be added to form a total.

These counts describe what is recorded for the listed groups. They do not establish that no adverse events occurred outside the categories shown or that every participant had complete safety follow-up. The registry record does not provide adverse-event definitions, collection procedures, follow-up duration, or a list of non-serious event terms. Deaths are not reported in the record; they should not be interpreted as zero.

In general, an adverse-event count is descriptive and should be read alongside the number at risk, how events were defined and collected, and the duration of observation. The primary outcome timeframe states that measurements were performed in one day, but that does not specify the safety follow-up period. The recorded zero counts alone do not support broader conclusions about safety.

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

This study’s stated purpose is methodological: to develop a PET/CT examination protocol using 11C-CSar in healthy people and patients with cholestatic disorders. Its primary outcome concerns whether hepatic transport could be quantified. The registry record also describes experiments to examine ICG’s effect on tracer kinetics and to compare bolus and constant infusion approaches.

The record does not report a numerical primary outcome result or analysis results for the methodological comparisons. Thus, it cannot establish how often transport was quantified, how the approaches compared, or how precisely any observed result was estimated. A description of intended work is not a substitute for reported findings.

In general, evidence that a measurement can be obtained is distinct from evidence that it is accurate, reproducible, or useful for a clinical decision. Those properties require relevant definitions and results. The registry record does not report validation findings, repeatability estimates, diagnostic performance, or clinical outcomes. It also does not report a statistical analysis plan that would clarify how the stated aims were evaluated.

The study’s non-randomized design should also limit causal interpretations of differences between conditions. The record does not provide group-level characteristics, numerical contrasts, or adjustment methods. It would therefore be inappropriate to interpret the design descriptions alone as establishing that ICG changes tracer kinetics or that one infusion method performs better.

The appropriate reading is narrow: the registry documents a phase 1 protocol-development study, its broad measurement aims, and a primary endpoint based on quantifiability. It does not provide the posted numerical evidence needed to judge the observed measurement success or compare methods. These reporting gaps leave the empirical result unresolved in the registry record.

14. Why This Trial Matters Statistically

The study raises a statistical issue that is central to measurement research: an intended measurement method must be evaluated in terms of whether it produces an interpretable result. The primary outcome is framed around quantifying hepatic transport of 11C-CSar, making the feasibility of measurement the stated focus rather than a clinical treatment outcome.

For that kind of endpoint, clear operational definitions are important. Readers need to know what qualified as successful quantification, which attempts entered the denominator, and how incomplete or unusable scans were handled. The registry record does not report these details or a numerical result. Consequently, the central measurement question remains difficult to assess from the posted record alone.

The study also illustrates why a methodological contrast should not automatically be treated as a randomized comparison. The record is explicitly non-randomized and describes distinct experimental aims involving ICG and infusion method. In general, differences between conditions can reflect group composition or other factors as well as the method under evaluation. Without reported allocation details, participant characteristics, estimates, and an analysis approach, those influences cannot be assessed.

Reporting uncertainty is equally important. A percentage without a denominator or interval would provide limited information about precision; here, even the numerical percentage is not reported. The record therefore describes a question that matters for interpreting a novel imaging measurement, but does not provide the statistical results needed to quantify what was learned.

For researchers, the distinction between protocol development, measurement performance, and clinical usefulness is important. Each is a different question and requires its own outcome definitions and evidence. The registry record identifies the first as the broad purpose, but does not report enough numerical results to evaluate performance or clinical implications.

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 principal limitation for interpretation is that the registry record lists the primary outcome but does not report its numerical result. It also lists no analysis results. Readers cannot assess the proportion of participants with quantifiable hepatic transport, the uncertainty around that proportion, or the findings for the stated methodological comparisons.

The outcome definition is brief. The record does not describe the criterion for successful quantification, the analysis denominator, how failed or missing measurements were handled, or the population included in each analysis. It also does not report participant characteristics by condition or experimental group. These omissions make it difficult to assess selection, comparability, and generalizability.

The design is non-randomized and unmasked. The record does not detail how participants were assigned to the described experiments, whether outcome assessment was masked, or whether any statistical adjustment was used. As a result, the potential influence of group differences or assessment procedures cannot be evaluated from the registry record.

The record does not report a sample-size justification, statistical analysis plan, multiplicity procedure, or missing-data strategy. It also does not give numerical results for the ICG and infusion-method aims. The safety information is limited to group-level adverse-event counts; definitions, collection methods, follow-up duration, and death counts are not reported. These limitations describe gaps in registry reporting and do not establish what may have been documented elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Biliary Excretion of Conjugated Bile Acids in Humans Measured by 11C-cholylsarcosine PET/CT — NCT01879735.
• Registry record last updated 2015-02-23; status last verified 2014-07.
• Results first posted 2015-02-23.
• 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

NCT01879735 is a completed phase 1, non-randomized, unmasked, parallel study sponsored by the University of Aarhus, with enrollment of 22. The study concerns development of a PET/CT protocol using 11C-CSar in healthy people and patients with cholestatic disorders. Its stated methodological aims involve examining ICG’s effect on tracer kinetics and comparing bolus with constant infusion.

The primary outcome is the percentage of participants in whom hepatic transport of 11C-CSar could be quantified, with measurements described as occurring in one day. The registry record does not report a numerical primary outcome result, analysis results, or a statistical analysis plan. It reports zero serious and zero other adverse events in each of two listed groups, while deaths are not reported.