Use of Omega-3 Fat Emulsion (Omegaven) in Infants With Parenteral Nutrition Associated Liver Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of Omega-3 Fat Emulsion (Omegaven) in Infants With Parenteral Nutrition Associated Liver Disease (NCT00862446), a na phase 4 study. The primary outcome is Number of Participants With Resolution of the Direct Hyperbilirubinemia.

2. Clinical Question

3. Trial Design

This is a completed Phase 4, single-group study sponsored by Vanderbilt University Medical Center. The registry record lists enrollment as 48 and identifies Omegaven as the intervention. Its treatment description says all infants receive Omegaven. Allocation is listed as not applicable, and masking is listed as none. The record therefore describes an unmasked study without a randomized or concurrent control group.

The study start is recorded as 2009-03, and primary completion as 2019-10. Those dates describe the registry record; they do not provide details about how long any individual participant received treatment or was followed. The primary endpoint timeframe is at discharge or up to 10 weeks.

The design can describe outcomes among the infants treated in the study, if those outcomes are reported. Without a control group, however, it cannot directly compare Omegaven with another treatment or with the course participants would have had without Omegaven. Changes over time could have multiple explanations, and the single-group design does not separate those explanations.

The registry record lists one primary outcome measure, but no analyses are listed. It does not report a statistical analysis plan, the method used to handle missing outcome information, or details of the analysis population. Enrollment is not itself an outcome denominator, and it should not be treated as evidence that every enrolled infant contributed to the primary endpoint analysis.

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 Number of Participants With Resolution of the Direct Hyperbilirubinemia, measured over At discharge or up to 10 weeks.

The primary endpoint counts participants whose direct hyperbilirubinemia resolves. Resolution is defined in the registry record as direct bilirubin <2.0 mg/dL, assessed at discharge or up to 10 weeks. This is a binary outcome: for each participant with an assessment, the outcome is either meeting the stated threshold or not meeting it. The registered measure is a count of participants, not a measure of the amount of change in bilirubin or the time taken to reach the threshold.

A threshold endpoint can make the clinical state of interest explicit and can support a clear count of participants meeting that definition. It also simplifies a continuous laboratory measurement into a yes-or-no outcome. That choice has limitations: participants with values close to the threshold may be classified differently despite having similar measurements, and the count does not show how far values were from the threshold.

The timeframe allows assessment at discharge or up to 10 weeks, but the record does not specify how assessments at different times were handled in the analysis. It also does not report the number meeting the endpoint, the number assessed, or an estimate of uncertainty. The endpoint definition is available; its observed result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who receive the intervention. It has no concurrent group to represent what might have happened under another treatment or without the intervention. The primary outcome is a participant count based on a threshold definition. If the count and analysis denominator were reported, they could describe the observed outcome in the analyzed group. They would not, on their own, estimate a treatment-versus-control difference.

The registry record identifies a single-group model and says all infants receive Omegaven. Allocation is not applicable, and masking is none. These details are important when interpreting any observed outcome: they describe the study structure, not proof of benefit or harm. The record does not report a statistical analysis plan or a method for adjusting for other factors.

How should a binary endpoint be analyzed?

In general, a binary endpoint classifies each assessed participant into one of two outcome categories. A count can be paired with an analysis denominator to estimate the frequency of the outcome. Uncertainty around that estimate can be expressed with a confidence interval. Those quantities answer different questions: the count describes observed events, an estimate describes their frequency in the analyzed group, and an interval describes the precision of that estimate under the statistical method.

The registered endpoint is the count of participants with resolution of direct hyperbilirubinemia, defined as direct bilirubin <2.0 mg/dL. No primary endpoint count, analysis denominator, estimate, or confidence interval is reported in the registry record. Therefore, the endpoint definition should not be mistaken for an endpoint result.

What does the planning calculation mean?

In general, sample-size planning asks how many participants would be needed under stated assumptions to detect an effect of a chosen size with a chosen statistical procedure. The planning illustration associated with this study is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is described as using a stated fraction of the observed effect. Those are planning assumptions, not evidence that the trial used a two-arm design.

The actual study is single-group, so the equal-allocation, two-arm planning setup does not describe its design. A planning illustration based on an observed effect is not an independent confirmation of that effect, and it is not observed power. Observed power is not a substitute for an estimate and its uncertainty; interpreting a planned sample size as proof of a result would be misleading. The registry record does not report the trial’s own sample-size justification or statistical plan.

Why are uncertainty and assumptions important?

Every statistical estimate depends on data quality, the analysis population, and assumptions of the chosen method. In general, a confidence interval communicates sampling uncertainty, but it does not account automatically for bias from missing data, outcome measurement, or lack of a control group. The endpoint is a count, but the registry record does not state how incomplete measurements or assessments at different times were handled. It also does not report an analysis population or a primary outcome analysis.

Over-dispersion is a general concern when observed variation is greater than a model assumes. It can make uncertainty estimates too small if a model does not accommodate that extra variation. For a simple binary outcome, the appropriate model and its assumptions depend on the analysis question and data structure. There is no basis in the registry record for saying that an over-dispersion adjustment was required or used in this study. More broadly, no specific primary-outcome model or inferential method is reported.

The endpoint timeframe is at discharge or up to 10 weeks. When participants have measurements at different times, an analysis must define which measurement determines endpoint status and how participants without an assessment are treated. Those rules can affect the analyzed count and interpretation. They are not reported in the registry record, so the results cannot be reconstructed or checked from the endpoint description alone.

Finally, statistical significance and clinical meaning are not interchangeable. In general, a p-value evaluates compatibility of data with a specified null model under stated assumptions; it does not measure the size or importance of an effect. A confidence interval can help show the range of effects compatible with data, but neither measure resolves the lack of a control group. The registry record reports no primary outcome p-value or interval. No inferential conclusion about the endpoint can be drawn from a planning illustration or from the endpoint definition alone.

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("Omegaven Treatment")
n      <- c(48)
events <- c(29)
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  Omegaven Treatment  48  29  60.4  45.3  74.2  46.3  73.0  46.2  73.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure: the count of participants with resolution of direct hyperbilirubinemia. It does not list any analyses. A single registered primary outcome reduces the apparent scope for multiple primary-endpoint tests in the record, but the record does not report a statistical analysis plan or explain how secondary outcomes, subgroup analyses, or repeated assessments were handled. It is therefore not possible to assess the full multiplicity strategy.

Missing outcome information is also consequential for a count-based endpoint. The record does not report how many participants had an assessment at discharge or within the stated timeframe, how an unobserved endpoint was classified, or whether any imputation or sensitivity analysis was used. The enrollment figure of 48 is not an analysis denominator, and the record does not establish that all enrolled participants contributed endpoint data.

The analysis population is not reported in the registry record. It does not say whether the primary analysis included all enrolled participants, only participants with an observed endpoint, or another defined group. Nor does it report participant flow or reasons for unavailable assessments. These omissions prevent assessment of whether missingness could have affected the endpoint count or its interpretation.

In general, missing-data methods rely on assumptions about why values are missing; different assumptions can lead to different conclusions. That is a general statistical issue, not a claim about what happened in this study. Because the registry record does not describe missingness or analysis methods, the impact of missing data cannot be evaluated from the posted information.

12. 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

Serious events with the highest arm-level rate: hypertriglyceridemia (10.4%), coagulopathy (2.1%).

The registry record lists an Omegaven Treatment group with 48 at risk for serious adverse events and 5 affected. It also lists 48 at risk and 0 affected in the other-adverse-event fields. These are descriptive figures; the record does not provide the event-level detail needed to interpret timing, duration, severity beyond the recorded classification, or relationships among events and participants.

The listed serious adverse event terms include hypertriglyceridemia at 10.4% and coagulopathy at 2.1%. The registry record also lists 6 deaths. It does not describe their causes, timing, or whether they were considered related to treatment. The figures therefore should not be read as evidence that Omegaven caused these events, nor do they establish that it did not.

At-risk counts are denominators for the recorded safety fields, not a substitute for the primary endpoint analysis population. Safety figures should be interpreted separately from the unreported resolution outcome. The registry record does not give enough detail to reconstruct event counts from the listed percentages or to determine whether participants experienced more than one event.

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

The registry record establishes that a completed, unmasked, single-group Phase 4 study evaluated Omegaven in infants with parenteral nutrition associated liver disease. Its primary question concerns resolution of direct hyperbilirubinemia, defined as direct bilirubin <2.0 mg/dL at discharge or up to 10 weeks. But the record does not report the number of participants meeting that endpoint or an analysis of it.

Accordingly, the record does not quantify the observed frequency of resolution, the uncertainty around that frequency, or a comparison with another treatment. The absence of a reported primary result should not be interpreted as a finding of no resolution. It means the primary outcome result is not reported in the registry record.

Even if a single-group outcome count were available, it would describe what happened among the analyzed participants, not establish what Omegaven caused. Without a concurrent comparator, differences from an earlier state or expectations could reflect factors other than the intervention. The design is not a randomized comparison, and causal claims are not supported by a treated-group count alone.

The safety information is also descriptive. The listed serious adverse event figures and deaths do not identify causation, and the record does not give the timing or other context needed to assess attribution. They should not be combined with the primary endpoint as though they answer the same question.

The appropriate interpretation is therefore limited: the registry describes a relevant clinical question, an intervention, a threshold-based endpoint, and selected safety figures, but does not provide the primary outcome analysis. The information cannot establish whether the endpoint was commonly or rarely met, how precisely it was estimated, or whether outcomes differed because of Omegaven.

14. Why This Trial Matters Statistically

This study is statistically important because it illustrates the difference between a clearly registered outcome and a reported outcome result. The primary endpoint has a specified threshold and timeframe, but the registry record does not give the endpoint count, analysis denominator, or uncertainty. Without those elements, readers cannot evaluate the observed outcome quantitatively.

It also highlights the interpretive limits of a single-group design. A treated-group outcome can describe participants’ experience, but a comparison is needed to distinguish the intervention’s effect from other explanations. The record explicitly describes all infants as receiving Omegaven and does not provide a like-for-like control group. Statistical methods cannot recover the missing counterfactual comparison from a single group alone.

The planning assumptions further show why sample-size calculations should be read in their design context. The described planning illustration uses equal allocation between two arms, whereas the study is single-group. Such planning material does not establish that this study was designed or analyzed as a two-arm comparison, and it is not observed power.

Finally, the record separates a clinical endpoint from safety reporting. A resolution count and adverse-event figures answer different questions, and neither should be interpreted as a causal result without appropriate design and analysis. Clear outcome reporting, denominators, uncertainty measures, and analysis-population definitions would be needed to support a fuller statistical interpretation.

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.

Several limitations specific to this record constrain interpretation. The primary outcome result and analysis are not reported, despite a defined threshold and timeframe. The registry record therefore does not show the endpoint count, analysis denominator, estimate, or uncertainty. It also does not report the analysis population or participant flow, so the relationship between listed enrollment and endpoint assessment is unclear.

The single-group design has no concurrent comparator. Outcomes among participants receiving Omegaven cannot by themselves establish what would have occurred with another intervention or without Omegaven. The absence of masking is recorded, but the registry record does not describe outcome-assessment procedures or whether laboratory measurements were handled in a blinded manner.

Important operational details are not reported in the registry record, including dose, treatment schedule, and the handling of assessments made at different points within the stated timeframe. The record does not describe missing-data methods, a statistical analysis plan, or the trial’s sample-size justification. These gaps limit evaluation of how the primary endpoint would have been analyzed.

Safety interpretation is also limited by the absence of event timing, causal assessments, and further event-level detail. The listed deaths and adverse-event figures should not be attributed to treatment on the basis of the registry information alone. The record offers descriptive information but not enough context for a complete benefit-risk assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Use of Omega-3 Fat Emulsion (Omegaven) in Infants With Parenteral Nutrition Associated Liver Disease — NCT00862446.
• Registry record last updated 2021-01-05; status last verified 2020-12.
• Results first posted 2020-12-14.
• 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

The registry record describes NCT00862446, a completed Phase 4, single-group study sponsored by Vanderbilt University Medical Center. Enrollment is listed as 48. The study start is 2009-03, and primary completion is 2019-10. All infants in the treatment group receive Omegaven; allocation is not applicable and masking is none.

The primary outcome is the number of participants with resolution of direct hyperbilirubinemia, defined as direct bilirubin <2.0 mg/dL at discharge or up to 10 weeks. The registry record does not report a primary outcome count or analysis. It lists serious adverse event figures, other adverse-event fields, and 6 deaths, without enough detail to establish causation.

The study addresses outcomes in a treated group, not a randomized treatment comparison. Its primary result, analysis denominator, missing-data approach, and statistical plan are not reported in the registry record.