Prediction of Severity of Liver Disease by a 13C Octanoate Breath Test (OBT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prediction of Severity of Liver Disease by a 13C Octanoate Breath Test (OBT) (NCT01244503), a na phase 2 study. The primary outcome is The Peak Value of the PDR (Percentage Dose Recovery of 13C) of OBT (Octanoate Breath Test).

2. Clinical Question

The study asks whether the peak percentage dose recovery of ¹³C from the Octanoate Breath Test can help assess disease severity in people with suspected nonalcoholic fatty liver disease. Its intended reference for severity is the NAS scoring system based on liver biopsy histology. The registry description also frames the test as an aid, used alongside other clinical information and medical history, for evaluating severity and detecting NASH.

This is a question about measurement and classification, not a treatment comparison. The breath-test value is intended to characterize a metabolic process, while NAS is a histology-based score. The registry description states that a NAS score at least 5 indicates NASH. However, it does not report paired breath-test and NAS observations, a correlation, a classification accuracy measure, or any other estimate of how closely the test corresponds to histology. The intended clinical use is described, but the posted record does not establish how well that use was achieved.

3. Trial Design

This is a phase 2, single-group study sponsored by Virginia Commonwealth University. The registry lists an enrollment of 61 and describes the study population as people with metabolic syndrome and suspected nonalcoholic fatty liver disease, without another liver disease. Participants were to undergo the Sodium Octanoate Breath Test. The record does not describe a randomized allocation or a masking procedure; allocation is listed as NA and masking as none.

The study began in 2011-02, with primary completion recorded as 2012-05. Its status is terminated. The registry does not report why the study was terminated, whether the planned enrollment was reached, how many participants completed testing, or whether all enrolled participants contributed to the primary outcome. Those details should not be inferred from the enrollment field alone.

The primary outcome is the peak PDR value, expressed as percent per hour, over a timeframe of 1 hour. The described comparison is with NAS scoring from liver biopsy. A secondary outcome is listed as histology with NAS scoring. Although the registry lists 2 outcome measures, it does not provide numerical results for the primary or secondary outcome. It lists 0 analyses.

Because there is a single group and no like-for-like control arm, this design does not estimate a randomized contrast between treatments. Its central statistical task would instead be to evaluate how the breath-test measure relates to disease severity as represented by histology. The registry record does not give the detailed analysis methods used for that task.

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: Only subjects with metabolic syndrome and suspected non alcoholic fatty liver disease will undergo breath test. They must not have any other liver disease.

6. Primary Endpoint

The registry lists the primary outcome as The Peak Value of the PDR (Percentage Dose Recovery of 13C) of OBT (Octanoate Breath Test), measured over 1 hour.

The primary endpoint is the peak value of PDR, the percentage dose recovery of ¹³C, measured during the Octanoate Breath Test. It is reported in percent per hour, and the specified timeframe is 1 hour. In the registry description, PDR represents the rate of metabolism, and the peak is the highest rate reached by the liver during the test. The stated direction is that a higher peak corresponds to better liver health and function.

The endpoint is used because the study aims to assess whether a breath-test measure can indicate disease severity in people with suspected NAFLD. The intended benchmark is NAS, a histology score made up of steatosis, lobular inflammation, and hepatocellular ballooning. The registry describes the component scales as 0 to 3, 0 to 3, and 0 to 2, respectively, and states that a NAS score at least 5 indicates NASH. The total NAS range is 0 to 8.

These measures capture different kinds of information: PDR is a continuous metabolic measurement, whereas NAS is a score based on biopsy histology. Their relationship would need to be evaluated using participant-level or summary data. The record specifies the intended endpoint and comparison but does not report the PDR distribution, NAS results, or an estimate of their association. Thus, the endpoint definition alone does not show whether PDR tracked histologic severity in this study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical problem is to relate a continuous breath-test measurement to histologic severity. Peak PDR is recorded as a continuous value, while NAS is a score based on several histology features. The registry describes the NAS component scales and the criterion for NASH, but it does not report the analysis used to compare PDR with NAS. The general statistical considerations below explain what such analyses address; they do not describe methods confirmed to have been used in this study.

What does a mean and standard deviation describe?

A mean summarizes the central level of a continuous outcome, while a standard deviation describes how dispersed individual values are around that mean. The registry specifies these as the summary measures for the primary outcome, but does not post either value. A mean can be useful for describing a group, yet it does not show whether PDR differs across levels of histologic severity. It can also conceal skewness, outliers, or subgroups with different distributions. Reviewing the shape and spread of the measurements is generally important when interpreting a continuous endpoint.

A standard deviation is not the same as the uncertainty in the mean. General statistical inference typically uses a standard error or a confidence interval to express uncertainty about an estimated mean or relationship. The registry record does not report a confidence interval or standard error for this endpoint. No precision estimate for the study’s primary outcome can therefore be evaluated from the posted results.

How could the relationship with NAS be assessed?

In general, an analysis could examine whether PDR changes systematically with NAS, or whether PDR distinguishes participants who meet the stated NASH criterion from those who do not. The appropriate approach depends on the question, the observed distributions, and the intended use of the test. A relationship with the ordered or component-level histology information is not identical to classification at a threshold. Correlation alone, for example, would not establish how accurately a test classifies individuals.

For classification, general evaluation may consider sensitivity, specificity, and measures of overall discrimination, along with uncertainty and the consequences of the selected threshold. A classification rule would need to be specified and assessed; it cannot be reconstructed from the endpoint description. The registry record does not report such a rule or any classification statistics. It also does not report whether analyses used the total NAS score, its components, the stated NASH threshold, or another representation of histology.

Why does over-dispersion matter?

Over-dispersion means that the observed variability is greater than a statistical model assumes. In general, ignoring it can make standard errors too small and confidence intervals too narrow, giving an overly precise impression. Whether this issue is relevant depends on the outcome and model. Peak PDR is described as continuous, but the record provides no distributional summaries or model details from which to judge its variability. There is therefore no basis for claiming that over-dispersion was present or that a particular correction was needed.

The same caution applies to unusual values and incomplete observations. Extreme measurements can influence means and fitted relationships, while missing paired test and biopsy values can change the analysis population. A sound analysis would make clear how these issues were examined and handled. Their handling is not reported in the registry record.

What do the planning illustrations mean?

Sample-size planning illustrations are based on the observed effect and use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They represent hypothetical planning scenarios for detecting a stated fraction of an observed effect; they are not the study’s own design or an estimate of observed power. In general, a planning calculation describes the sample size an assumed future design would require under its assumptions. It does not demonstrate that a completed study had adequate power, and it cannot replace an estimate with a confidence interval.

The actual record describes a single-group study rather than equal allocation between two arms. The two-arm planning assumptions therefore do not mirror the registered design. The registry does not report a sample-size justification for the single-group evaluation, the effect used in the planning illustrations, or an analysis showing how the enrolled group size related to a prespecified target. Those details are not reported in the registry record.

What can be concluded from the posted methods information?

The registry defines the primary measure, its units, its timeframe, and the histology context. It does not report the estimator or model used to evaluate the relationship, how uncertainty was quantified, how missing values were handled, or whether any analysis adjusted for other clinical information. The description that OBT may be used with clinical information and medical history is an intended context, not evidence that an adjusted model was fitted. With no posted outcome values or analyses, statistical interpretation must remain at the level of the proposed question and endpoint.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Sodium Octanoate Breath Test")
n   <- c(61)
m   <- c(23.27)
sp  <- c(4.93)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Sodium Octanoate Breath Test  61  23.270  4.930  22.007  24.533

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures, including peak PDR as the primary outcome and histology with NAS scoring as a secondary outcome. It does not report the results for either measure, the number of statistical tests performed, or a plan for controlling multiplicity. Multiplicity arises when several outcomes, comparisons, or analyses are examined: the more opportunities there are to find a nominally noteworthy result, the more important it becomes to explain which analyses were planned and how the findings were interpreted. No multiplicity strategy is reported in the registry record.

The record lists 0 analyses. This means the posted registry entry does not present an analysis result for the stated endpoints; it does not establish what analyses may have been conducted outside the registry. Statistical methods, analysis populations, and any prespecified hierarchy among outcomes are not reported in the registry record.

Missing-data handling is also not described. The enrollment field records 61, but that does not specify how many participants had both an interpretable breath test and the histology information needed for the primary question. The registry does not report outcome-specific denominators, exclusions, reasons for missing measurements, or methods used to address missingness. Without these details, it is not possible to judge whether the analyzed observations represented the intended study population.

Nor does the record define an analysis population, such as all enrolled participants or only those with complete endpoint measurements. These are material reporting gaps because the number and characteristics of analyzed participants can affect estimates and their precision. No assumptions about missingness or multiplicity should be inferred from the single-group design or the endpoint descriptions.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry separates serious adverse events from other adverse events for the Sodium Octanoate Breath Test group. It records 61 at risk for serious events and 0 affected. For other adverse events, it records 61 at risk and 4 affected. Deaths are listed as null, and the record contains no top serious-event terms. The null entry for deaths does not provide a reported death count; deaths are not reported in the registry record.

These figures are event summaries, not a comparison between groups. The study has no separate control arm, so they cannot establish whether an event rate was higher or lower than under another intervention. The registry does not provide event descriptions for the other adverse events, individual-level timing, severity, or a causal assessment. The serious-event count and the other-event count should be read as separate categories, not added together. The posted information describes recorded safety counts only and does not, by itself, establish a causal relationship with the test.

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

The study was designed to examine whether the peak PDR from an Octanoate Breath Test could help assess liver disease severity in people with suspected NAFLD, using NAS histology scoring as the reference. The registry gives a rationale for the measure: PDR represents the rate of metabolism, and a higher peak is described as indicating better liver health and function. It also specifies the NAS components and the criterion that a score at least 5 indicates NASH.

Those descriptions explain what the investigators intended to evaluate. They do not show the observed relationship between PDR and histology. The registry record does not report the primary outcome mean or standard deviation, a comparison across NAS levels, a classification result, or uncertainty estimates. It therefore cannot establish from its posted results whether PDR tracked severity or identified participants meeting the stated NASH criterion.

The single-group design is relevant to the scope of any potential finding. The question concerns the performance or association of a measurement within a selected population, not a randomized comparison of treatments. Even if an association were reported, it would not by itself show that using the test changes clinical decisions or outcomes. The record describes the test as an aid alongside other clinical information and medical history; it does not report an evaluation of a decision process or patient outcomes.

The enrolled population is limited in the registry description to people with metabolic syndrome and suspected NAFLD who have no other liver disease. The results, if available, would need to be interpreted in that context. The record does not report whether the findings generalize to other populations, and it does not provide results from which transportability could be assessed.

The appropriate conclusion from the available registry information is therefore about the study question and reporting status: the intended measure and histology reference are specified, but outcome findings and analysis details are not reported in the registry record. Neither efficacy nor lack of efficacy can be concluded from that absence.

14. Why This Trial Matters Statistically

This study raises a useful statistical question about how a physiological measurement can be evaluated against a histology-based assessment. Peak PDR is continuous, while NAS summarizes features observed in liver biopsy. Comparing measures that have different scales and represent different aspects of disease requires a clearly defined estimand: for example, whether the interest is in association with severity, discrimination at a classification threshold, or some other form of agreement. These questions are related but not interchangeable.

The registry makes the intended comparison visible by naming NAS as the reference and giving the threshold used to indicate NASH. That specificity helps distinguish the proposed measurement question from a treatment-effect question. Yet a clear question must be accompanied by results and uncertainty estimates to support interpretation. The registry record lists the primary outcome but does not report its values or the analysis connecting it to NAS.

The trial also illustrates why design and planning assumptions must be kept separate. The registered study is single-group, whereas the sample-size planning assumptions describe equal allocation between two arms. Planning scenarios can help readers understand assumptions about future comparisons, but they do not describe the design actually used and are not observed power. The registry record does not report a sample-size justification for the single-group analysis.

Finally, the terminated status and absence of posted analyses make transparent outcome reporting particularly important. The status alone does not explain what happened, and missing results do not establish the direction of any finding. For biostatisticians and clinical researchers, the key lesson is to separate the biological rationale, measurement definition, analysis plan, and empirical results. Here, the rationale and endpoint definition are recorded; the evidence needed to assess the endpoint’s observed performance is not reported in the registry record.

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 registry record does not provide numerical results for the primary peak PDR endpoint or the secondary NAS outcome. It also does not report confidence intervals, p-values, an association estimate, classification performance, or an analysis population. This prevents assessment of both the size and precision of the relationship the study was intended to evaluate.

The study is single-group, with no randomized control comparison. That design is consistent with assessing a measurement against histology, but it cannot support a randomized treatment contrast. The registry does not report the methods used to compare the breath-test measure with NAS, whether the relationship was adjusted for other clinical information, or how any threshold was selected and evaluated.

Although the enrollment field records 61, the number with complete paired breath-test and biopsy data is not reported in the registry record. Nor are missingness, exclusions, measurement failures, or analysis-population rules described. The absence of these details limits evaluation of potential selection effects and statistical precision.

The record lists the study as terminated but does not report the reason. It does not state whether the planned objectives were completed or explain the relationship between the enrollment entry and the analyses. The sample-size planning assumptions describe an equal-allocation, two-arm scenario, unlike the registered single-group design; the registry does not report the rationale for this difference or a design-specific sample-size justification.

Finally, the registry’s population description is specific to metabolic syndrome and suspected NAFLD, excluding other liver disease. No posted results allow assessment of how findings might apply beyond that group. These are limitations of the information reported and of the design’s scope; they do not establish what the unreported results would have shown.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Prediction of Severity of Liver Disease by a 13C Octanoate Breath Test (OBT) — NCT01244503.
• Registry record last updated 2015-07-28; status last verified 2015-07.
• Results first posted 2015-07-28.
• 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

NCT01244503 is a phase 2, single-group study sponsored by Virginia Commonwealth University. It evaluates the Sodium Octanoate Breath Test in people with metabolic syndrome and suspected nonalcoholic fatty liver disease, with no other liver disease. The registry lists an enrollment of 61, a start in 2011-02, primary completion in 2012-05, and a status of terminated.

The primary endpoint is peak PDR, measured in percent per hour over 1 hour, with NAS histology scoring as the stated reference for disease severity. The record also lists histology with NAS scoring as a secondary outcome. It reports 0 analyses and does not post numerical outcome results, statistical estimates, or uncertainty measures. The reason for termination and the handling of missing measurements are not reported in the registry record.