The SHUNT-V Study for Varices: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The SHUNT-V Study for Varices (NCT03583996), a na na study. The primary outcome is Disease Severity Index (DSI) Less Than/Equal to 18.3 to Rule Out Large Varices.

2. Clinical Question

This is a diagnostic-validation question, rather than a question about whether one treatment is better than another. The DSI threshold is intended to distinguish people whose test results suggest a lower likelihood of large esophageal varices. EGD results are described alongside the test results in the registry record, but the numerical diagnostic findings are not reported in the registry record.

The registry lists DSI and probability of large esophageal varices as secondary outcomes. It does not report the detailed definitions or results for those outcomes. The record therefore establishes the intended clinical question and the measurements used, but does not allow readers to assess the observed diagnostic performance from the registry information alone.

3. Trial Design

The SHUNT-V Study for Varices is recorded as a completed, single-group, open-label study sponsored by HepQuant, LLC. It has no applicable phase or allocation entry and no masking. The registry records an enrollment of 306 and lists chronic liver disease as the condition under study. The study start date was 2019-01-23, and primary completion was recorded as 2021-05-07.

All subjects in the open-label group received the HepQuant SHUNT Liver Diagnostic Test within 42 days of the scheduled EGD. The test description specifies 20mg of 13C Cholate mixed with Albumin via IV push and 40mg of d4 Cholate mixed with juice orally. Both doses were given simultaneously, one time. The record describes the test and EGD as the paired assessments relevant to the primary question.

The absence of a randomized comparison is important when interpreting the design. The study is not described as comparing assignment to different treatments or diagnostic strategies. Instead, it evaluates a test result in relation to the likelihood of large esophageal varices. Because masking is listed as none, the record does not describe a blinded assessment process.

The primary endpoint description focuses on subjects with DSI at or below 18.3 and identifies 275 people with both HepQuant SHUNT Test and EGD results among 280 who completed the test and EGD examination. The registry separately records enrollment as 306. These figures describe different stages or analysis details in the record; the registry does not explain all reasons for the differences between them. Further detail about recruitment, exclusions, protocol deviations, and the statistical analysis plan 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: A total of 306 subjects were enrolled in the study. For the analyses of all primary, secondary, and exploratory endpoints, only subjects who completed the HepQuant SHUNT Test and esophagogastroduodenoscopy (EGD) examination (N=280) were considered.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Of the 280 subjects who completed the HepQuant SHUNT Test and EGD examination, 275 had both HepQuant SHUNT Test and EGD results.

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 Disease Severity Index (DSI) Less Than/Equal to 18.3 to Rule Out Large Varices, measured over 1 day.

The primary endpoint is titled Disease Severity Index (DSI) at or below 18.3 to rule out large varices. Its unit is participants, and its measure is a count of participants. The description says the primary objective is to measure liver function using this threshold for subjects considered not likely to have large esophageal varices. Thus, the endpoint connects a numerical test threshold to the clinical aim of identifying people with a lower likelihood of large varices.

A threshold converts a continuous or graded test result into a classification for a particular question. In general, a rule-out threshold is intended to identify results that may help distinguish people unlikely to have the condition from those who may need further assessment. The usefulness of such a threshold depends on how test classifications correspond to the reference assessment and on the clinical context in which the test is used. These general principles do not establish the performance of this test in this study.

The registry record reports the endpoint definition and describes the relevant paired results, but does not report the observed number of participants meeting the threshold or the resulting diagnostic-performance estimates. Sensitivity, specificity, predictive values, and confidence intervals are not reported in the registry record. The endpoint’s stated purpose can therefore be described, but its observed accuracy or precision cannot be evaluated from the registry record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count convey?

The primary measure is a count of participants meeting the endpoint definition. A count is a direct description of how many people satisfy a specified criterion in the analysis population. Counts need a clearly defined denominator to be interpretable: the same count can represent different proportions in populations of different sizes. The registry describes 275 people with both test and EGD results within 280 who completed both examinations, but does not report the primary count. No proportion can therefore be described from the registry record.

For diagnostic questions, a count alone is usually not enough to establish how well a test performs. The count must be understood in relation to reference findings and the categories created by the test threshold. Diagnostic measures such as sensitivity and specificity use different parts of that comparison. Predictive values address another question: how likely a particular reference finding is among people with a given test classification. These are general statistical distinctions; the registry record does not report the numerical results needed to evaluate them for this study.

How should a threshold be understood?

The primary endpoint uses DSI at or below 18.3. A threshold separates test results into categories according to a chosen rule. This makes an interpretation easier to apply, but it also discards some detail: results on the same side of a threshold are grouped together even if their DSI values differ. A threshold can be useful only in relation to the purpose for which it was selected and the consequences of classification errors. The registry identifies the intended rule-out purpose, but does not report the evidence used to select the threshold or the diagnostic results at that threshold.

In general, rule-out approaches emphasize whether people with a negative classification are unlikely to have the condition, while also requiring attention to people who may be missed. A threshold’s performance cannot be established by its label or stated purpose. It depends on observed comparisons with the reference assessment, the participants studied, and the analysis methods. Those numerical comparisons are not reported in the registry record.

What does the design imply for statistical comparisons?

A single-group study can describe test results and their relationship to a reference assessment, but it does not provide a randomized group comparison. Allocation is listed as not applicable and masking as none. Accordingly, the study should not be read as a randomized treatment trial or as a direct comparison between assigned interventions. The record does not report whether test interpretation and EGD assessment were blinded to one another.

In general, uncertainty around an estimate is often conveyed with a confidence interval. A confidence interval communicates the range of values compatible with the data under the method used; it is not a guarantee that the true value lies within the interval. The registry record does not report confidence intervals for the primary endpoint or diagnostic measures. It also does not report a p-value for the primary endpoint. Without estimates and uncertainty intervals, readers cannot assess how precise the findings are.

What can the planning assumptions establish?

The record includes a sample-size planning illustration based on an observed effect. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. The record says that this is a planning illustration, not the trial’s own design. It should not be interpreted as observed power, nor as evidence that the actual single-group study used two-arm allocation. The planning illustration does not replace the trial’s observed results or a description of its own analysis plan.

In general, planning calculations depend on assumptions about the effect of interest, variability, error tolerance, and design. If the assumed effect changes, the planning requirement can change too. An illustration based on a previously observed effect is conditional on that effect being relevant to a future study. The registry record does not report a sample-size justification for the SHUNT-V study itself, or enough information to evaluate its design assumptions.

What details are needed to assess the analysis?

Readers would need to know how the primary outcome was calculated, how the 18.3 threshold was applied, which reference definition of large varices was used, and how missing or incomplete paired observations were handled. They would also need estimates with uncertainty and an explanation of any adjustment or subgroup analyses. These details are not reported in the registry record. The record lists six analyses and two outcome measures, but does not explain the relationship among those analyses, identify their full statistical methods, or describe a strategy for handling multiple analyses.

In general, a statistical method is most interpretable when its outcome definition, population, assumptions, and uncertainty are clear. The registry’s endpoint description provides part of that framework, particularly the threshold and the paired-results population description. It does not provide the numerical primary findings or sufficient analysis detail to independently assess the diagnostic conclusion.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and six analyses. It identifies the DSI threshold as the primary endpoint and lists DSI and probability of large esophageal varices among secondary outcomes. It does not describe how the six analyses relate to the outcomes, whether they include subgroup or sensitivity analyses, or which analysis is considered primary within each outcome.

When several outcomes or analyses are examined, the chance of at least one apparently notable result can increase if each is assessed independently. In general, multiplicity procedures can control or contextualize that issue, but the appropriate approach depends on the planned questions and analysis structure. A multiplicity plan, including any adjustment or prioritization strategy, is not reported in the registry record. The absence of that information does not establish that no plan existed; it means the record does not document one.

The endpoint description identifies 275 people with both test and EGD results among 280 who completed the test and EGD examination. The record also states an enrollment of 306. It does not provide a complete participant-flow account or explain all differences between these figures. The handling of missing DSI or EGD results, withdrawals, protocol deviations, or incomplete assessments is not reported in the registry record.

The analysis population is therefore only partly described. The primary endpoint description indicates a paired-results group, but the record does not fully specify inclusion criteria for each analysis or whether any other analysis populations were used. It also does not report an approach to imputation, exclusions, or sensitivity analyses for missing data. These gaps limit the ability to assess whether the analyzed participants represent the enrolled group and how missing observations might affect the findings.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: coronary artery disease (0.3%), pleural effusion (0.3%), peritonitis bacterial (0.3%), septic shock (0.3%), hyperosmolar state (0.3%).

For the open-label group, the registry reports serious adverse events for 5 of 297 at risk, other adverse events for 40 of 297 at risk, and 1 death. The listed at-risk denominator is 297; it is not the same figure as the study’s recorded enrollment or the paired-results population described for the primary endpoint. The registry does not explain the reason for this safety denominator.

The serious adverse-event terms listed among the most frequent are Coronary Artery Disease, Pleural Effusion, Peritonitis Bacterial, Septic Shock, Hyperosmolar State, and Metabolic Encephalopathy. Each is reported as 0.3%. These entries describe reported terms and their registry percentages; they do not establish that the test caused the events. The registry record does not provide event narratives or an assessment of causal relationship in the information.

Safety counts require context, including the population monitored, the definitions used, the observation period, and how events were collected. Those details are not reported in the registry record. The event figures should therefore be read as descriptive reports from the open-label group, not as a comparison with another group or as a complete estimate of risk attributable to the test.

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

The registry record establishes that SHUNT-V was designed to evaluate a liver-function diagnostic test in relation to the likelihood of large esophageal varices. It identifies a primary DSI threshold at or below 18.3 and describes paired test and EGD results for part of the study population. It also records secondary outcomes concerning DSI and probability of large esophageal varices. These registry entries clarify the study’s intended question and general structure.

The registry record does not report the numerical primary endpoint result or the diagnostic-performance estimates needed to judge how well the threshold classified participants. As a result, it does not establish from the posted information whether the DSI threshold can rule out large varices, how often classifications agreed with EGD, or how precise any observed performance estimate was. The endpoint wording expresses the study objective; it should not be mistaken for a reported finding.

The study is single-group and open label, not a randomized comparison of diagnostic strategies or treatments. The record therefore cannot support a treatment-effect comparison. Nor can the safety counts alone establish that the test caused the reported adverse events. They are descriptive safety figures for the group and denominator recorded in the registry.

In general, a diagnostic test’s clinical meaning depends on the population in which it is evaluated, the reference assessment, the chosen threshold, the consequences of false classifications, and the precision of the estimates. The registry gives some design and endpoint information, but does not report many details needed to judge those considerations. It also does not document the analysis plan for missing data or multiplicity. Consequently, the study’s intended diagnostic question is clear, while the strength and precision of the answer cannot be assessed from the registry record alone.

13. Why This Trial Matters Statistically

This study is statistically relevant because it frames a diagnostic question around a prespecified-looking threshold and a clinical reference examination. For diagnostic research, the central issue is not simply whether a test produces a measurement, but whether that measurement meaningfully classifies people in relation to the condition of interest. Defining a threshold makes the proposed classification rule explicit and gives readers a concrete question to evaluate.

The record also illustrates why analysis populations matter. Enrollment is recorded as 306, while the primary endpoint description refers to 280 people who completed the test and EGD and 275 with both results. A diagnostic comparison depends on paired information: without both a test result and reference assessment, a participant cannot contribute to the same kind of paired evaluation. The record identifies a paired-results population but does not fully explain participant flow or missing-data handling.

A second statistical lesson is the distinction between an objective and an observed result. The registry states that the study aimed to assess DSI at or below 18.3 for ruling out large varices, but does not report the numerical primary finding or its uncertainty. An intended use is not evidence of performance. Diagnostic claims require estimates that can be assessed for both magnitude and precision.

Finally, the single-group, open-label design and absence of a randomized comparator shape the interpretation. This design is directed at test evaluation rather than a randomized treatment comparison. Clarity about the reference assessment, blinding, outcome definitions, and statistical methods would help readers assess possible sources of bias. Several of these details are not reported in the registry record, making transparent reporting of the full results especially important for statistical appraisal.

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 study from the registry record is that the primary numerical result is not reported. The endpoint is defined as a participant count using DSI at or below 18.3, but the record gives no count, proportion, diagnostic-performance estimate, or confidence interval. The intended purpose of the threshold therefore cannot be checked against the observed findings.

The record describes 275 people with both HepQuant SHUNT Test and EGD results among 280 who completed both examinations, and separately records enrollment of 306. It does not provide a complete account of participant flow or explain why the figures differ. The criteria governing the paired-results population, and the treatment of missing or incomplete results, are not reported. That limits assessment of how the analysis population was formed.

The study is recorded as single-group and open label, with no applicable allocation. The registry does not state whether EGD assessment was blinded to test results or whether test interpretation was blinded to EGD findings. It also does not provide a detailed definition of large varices, a full analysis plan, or the methods used to estimate diagnostic performance. Those omissions prevent assessment of possible measurement or analysis biases.

The registry lists two outcome measures and six analyses, but does not describe the multiplicity strategy or explain the analyses in detail. The sample-size assumptions are described as a planning illustration rather than the study’s own design, and the record does not report a study-specific sample-size justification. Finally, safety figures are reported without the event narratives, collection details, or causal assessments needed to interpret them fully. These limitations concern what can be evaluated from the registry record and do not, by themselves, establish that the study procedures were inadequate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The SHUNT-V Study for Varices — NCT03583996.
• Registry record last updated 2025-04-11; status last verified 2025-03.
• Results first posted 2025-04-11.
• 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 SHUNT-V Study for Varices is recorded as completed and sponsored by HepQuant, LLC. It was a single-group, open-label study in chronic liver disease, with enrollment of 306. The study began on 2019-01-23, and primary completion was recorded as 2021-05-07.

Participants received the HepQuant SHUNT Liver Diagnostic Test in relation to a scheduled EGD. The primary endpoint concerned DSI at or below 18.3 as a threshold intended to rule out large esophageal varices. The endpoint description identifies 275 people with both test and EGD results among 280 who completed both examinations.

The registry record does not report the numerical primary outcome or diagnostic-performance estimates. Safety entries include serious adverse events for 5 of 297 at risk, other adverse events for 40 of 297 at risk, and 1 death. The record lists two outcome measures and six analyses, but does not fully describe their methods or multiplicity handling.