Low Dose Fat for the Prevention of Liver Disease in Babies With Gastrointestinal Disorders: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Low Dose Fat for the Prevention of Liver Disease in Babies With Gastrointestinal Disorders (NCT01373918), a randomized phase 4 study. The primary outcome is Presence of Cholestasis.

2. Clinical Question

3. Trial Design

This was a Phase 4, randomized, parallel-group trial with no masking. The two arms compared low-dose and standard-dose intravenous fat emulsion. The registry identifies the emulsion in both arms as Intralipid, a soybean oil emulsion, and describes the doses as approximately 1 g/kg/d and approximately 3 g/kg/d, respectively. The lack of masking means that the registry does not describe a blinded comparison; it does not, by itself, establish whether outcome assessment was influenced by knowledge of treatment assignment.

The participants were neonates with congenital or acquired gastrointestinal disorders receiving parenteral nutrition. Treatment was described as continuing through the course of parenteral nutrition or until hospital discharge, death, or 100 days of life, whichever came first. The primary outcome timeframe is likewise described as ending at 100 days of life, hospital discharge, or death, whichever came first. The record does not provide further detail about follow-up after these stopping points.

Enrollment was 41. The trial started in 2010-12 and had a primary completion date of 2014-07. Its current registry status is terminated. The reason for termination, timing of the decision, and whether termination affected planned enrollment or follow-up are not reported in the registry record. It would therefore be inappropriate to infer why the trial ended or whether it ended early relative to a target.

The registry lists mortality rate and anthropometric measurements among secondary outcomes. It does not report analyses for those outcomes. No reason for choosing the treatment doses, allocation procedures beyond randomization, or details about stratification are reported in the registry record. Randomization is intended in general to balance prognostic factors across groups, but with a small enrolled trial, chance imbalances can remain. The registry information does not permit an assessment of the balance of participant characteristics between arms.

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: 41 subjects were enrolled in the study. Only subjects who required \> 14 days of parenteral nutrition and who had an abdominal surgery were included in the final analysis.

Overall Study

Reasons for not completing this period:

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 Presence of Cholestasis, measured over prior to 100 days of life, hospital discharge, or death whichever comes first.

The primary endpoint was the presence of cholestasis, recorded as a participant count. The registry defines cholestasis by a direct bilirubin > 2 mg/dL. The outcome timeframe ends before 100 days of life, at hospital discharge, or at death, whichever comes first. The endpoint is binary in concept: a participant either meets the stated definition during the specified period or does not. The record does not provide details about the timing or frequency of bilirubin measurement, how borderline or repeated measurements were handled, or how outcome status was determined when measurements were unavailable.

In general, a clinical endpoint should represent an outcome relevant to the condition under study and should be defined consistently for participants in each group. A laboratory threshold can make an outcome operationally measurable, but its interpretation depends on how measurements are collected and how the definition is applied. Here, the threshold provides the stated rule for identifying cholestasis; the registry record does not provide further measurement procedures.

The registry does not present the primary endpoint as one extractable comparison. It indicates that the primary outcome has several categories or time points and is not reduced to one comparison. Consequently, the record does not give a single participant count by arm for the primary endpoint, nor a comparative estimate or confidence interval. The endpoint definition alone cannot show whether the groups differed. It also cannot establish how precisely any potential difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization and unblinded allocation describe different parts of a trial. Randomization assigns participants to treatment groups using a chance-based process, with the aim of reducing systematic differences in baseline characteristics. Masking concerns whether participants, clinicians, or outcome assessors know the assigned treatment. The registry identifies this trial as randomized and with no masking. It does not report further details of the randomization procedure or identify which people, if any, assessed outcomes without knowledge of assignment.

What does a binary endpoint comparison involve?

In general, a binary endpoint classifies each participant into one of two outcome states, such as meeting or not meeting a defined condition during follow-up. A comparison can describe the event count and the number assessed in each group, then estimate how the groups differ. Common effect measures include a difference in event proportions, a relative measure, or an odds-based measure. Each answers a related but distinct question, and each needs a clearly defined analysis population and outcome window. The registry gives a binary endpoint definition but does not report counts or a selected effect measure for the primary comparison.

For this endpoint, cholestasis was defined by direct bilirubin > 2 mg/dL. In general, consistent outcome assessment matters because different measurement schedules or rules for repeated tests can change which participants are classified as having an event. The registry record does not describe measurement frequency, adjudication, or how missing laboratory data were handled. These omissions prevent assessment of whether the stated definition was applied comparably in both arms.

How should uncertainty be interpreted?

In general, a confidence interval describes a range of estimates compatible with the observed data under the assumptions of the statistical method. A narrow interval indicates greater precision than a wide interval, while an interval that includes values representing no group difference may be compatible with both little difference and potentially meaningful differences. A p-value, in general, measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions were true. It does not measure the probability that a treatment works, and it does not convey the size or clinical importance of an effect.

No confidence interval or p-value for the primary comparison is reported in the registry record. The result cannot therefore be described as statistically significant, statistically non-significant, precise, or imprecise on the basis of the primary outcome. A missing estimate is not equivalent to an estimate of zero, and a missing p-value is not evidence for or against a difference.

What can the sample-size illustration establish?

In general, a sample-size calculation is a planning exercise that asks how many participants may be required to detect a specified effect under stated assumptions. The registry's planning description refers to a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect stated as a fraction of an observed effect. These are planning assumptions, not evidence that the trial used the same assumptions in its design. The registry record does not report the trial's own statistical plan or sample-size justification.

Planning calculations do not establish the power achieved by a completed trial. In particular, a calculation based on an observed effect is a retrospective planning illustration; it should not be called observed power. Its interpretation depends on the selected effect size and assumptions, and it cannot replace an effect estimate with an uncertainty interval. No numerical planning results are reported in the registry record. In addition, the registry does not provide a single primary comparison from which an observed effect can be interpreted.

Why do analysis details matter?

General statistical interpretation depends on knowing which participants were included, how outcomes were handled, which comparison was prespecified, and what method was used. An analysis of all randomized participants can preserve the advantages of random assignment, while analyses restricted to participants with complete data can be affected if missingness is related to treatment or outcome. The registry record does not report the analysis population, missing-data methods, or an analysis method for the primary outcome.

The trial's primary endpoint timeframe includes several possible stopping events: 100 days of life, hospital discharge, or death, whichever came first. In general, differing follow-up durations can affect the opportunity to observe an event. The record does not describe an adjustment for time at risk or a time-to-event analysis. It would be inappropriate to assume that such an analysis was used. The registry explicitly does not reduce the primary outcome to one comparison because it has several categories or time points. That limits the conclusions available from the posted result record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary outcomes that include mortality rate and anthropometric measurements. It does not report analyses for these outcomes. A multiplicity plan describing how the risk of false-positive findings across several outcomes or comparisons would be controlled is not reported in the registry record. Without such a plan, readers cannot determine whether any outcome comparisons were designated as confirmatory or how multiple tests would have been interpreted.

The primary outcome is described as having several categories or time points and is not reduced to one comparison. The record therefore does not provide a single primary effect estimate or a set of clearly reported primary comparisons to interpret. It also does not state whether any interim analyses were planned or conducted; that information is not reported in the registry record.

Missing-data methods and analysis populations are not reported in the registry record. The enrollment number does not indicate how many participants had primary endpoint measurements, how many were included in an analysis, or how missing outcomes were classified. In general, missing data can affect a comparison when the likelihood of missingness differs between groups or is related to the outcome. The registry information is insufficient to assess whether that concern arose or how it was addressed.

These reporting gaps do not prove that the trial team lacked plans or analyses. They mean that the registry record does not make those methods available for statistical appraisal. No inference about the effects of multiplicity, missingness, or analysis-population choices can be made without further reporting.

11. 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.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: hyperglycemia (10.0%), hypertriglyceridemia (6.2%).

The registry lists serious adverse events affecting 2 of 20 participants at risk in the low-dose intravenous fat emulsion group and 1 of 16 participants at risk in the standard-dose group. It lists 0 other adverse events affecting participants in each group. These are the counts recorded for the respective safety categories; they should not be substituted for the primary cholestasis outcome.

The registry also lists hyperglycemia at 10.0% and hypertriglyceridemia at 6.2% among the top serious terms. The record does not make clear in this information how those terms map to the treatment groups, so they should not be assigned to a particular arm. Death counts are not reported in the safety entries.

In general, safety counts require context: definitions of seriousness, observation periods, completeness of event collection, and the number of participants assessed all affect their interpretation. The figures do not include a comparative statistical analysis or an uncertainty interval. They therefore describe recorded events but do not establish whether the treatments differ in safety. The record also does not provide enough detail to assess the clinical course or severity of the individual events.

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

The record establishes that a randomized, parallel-group trial compared a low dose with a standard dose of intravenous soybean oil emulsion among neonates with congenital or acquired gastrointestinal disorders. It specifies the dose descriptions, the absence of masking, and a primary endpoint defined by direct bilirubin > 2 mg/dL. It also documents that enrollment was 41 and that the trial status is terminated.

What the record does not establish is whether the groups differed in the primary outcome. No single primary comparison, effect estimate, confidence interval, or p-value is reported. The registry's endpoint description is not itself evidence of an outcome difference. Nor does the absence of a reported comparison show that there was no difference. The direction and size of any comparative effect, and the precision with which it might be estimated, remain unknown from the registry record.

The safety counts provide limited descriptive information about serious and other adverse events, but they do not provide a comparative analysis. The listed serious-event counts are small, and the record does not report the broader context needed to interpret event patterns, including detailed observation and analysis methods. No conclusion about comparative safety should be drawn from the counts alone.

These results cannot be generalized to populations beyond the enrolled neonatal population without evidence about eligibility, participant characteristics, and clinical settings. The registry does not report those details in a way that allows such an assessment. It also does not report why the trial was terminated or how termination affected follow-up and analysis. Thus, the supported interpretation is limited to the trial's recorded design and available descriptive information; the primary comparative finding is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between registering a clinical question and reporting an interpretable statistical result. The registry identifies a target population, randomized treatment groups, dose descriptions, an endpoint definition, and a follow-up window. Those details help readers understand what was intended to be compared. But a treatment comparison requires outcome data and an analysis that quantify the contrast and its uncertainty. Those primary comparison details are not reported in the registry record.

The issue is particularly relevant for a binary endpoint defined by a laboratory threshold. The threshold makes the outcome concrete, but interpretation still depends on how often measurements were taken, how outcome status was established, and how unavailable measurements were handled. Those operational details are not reported. A defined endpoint therefore does not by itself guarantee that readers can evaluate consistency of measurement or reproduce the analysis.

The trial also shows why a record's enrollment figure cannot substitute for an analysis population. Enrollment was 41, but the registry does not report the number assessed for the primary endpoint or the number included in an analysis. These quantities answer different questions. Without endpoint counts by group and an analysis method, neither the direction nor the precision of a treatment contrast can be assessed.

Finally, status and design alone do not explain the evidence. The record identifies the trial as terminated but does not report the reason. It would be unsound to infer the termination circumstances or their relationship to results. For statistical interpretation, complete reporting of outcomes, methods, missing data, and analysis populations is necessary to distinguish a genuinely small or uncertain effect from a result that is simply unavailable in the registry.

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 trial-specific limitation in interpreting this record is the absence of a single primary outcome comparison. Although the endpoint is named and defined, the registry does not report the outcome counts by arm, a comparative estimate, a confidence interval, or a p-value. The primary finding therefore cannot be quantified or assessed for precision.

The registry says the primary outcome has several categories or time points and is not reduced to one comparison. It does not explain those categories or time points further in the information. The endpoint timeframe ends at 100 days of life, hospital discharge, or death, whichever comes first, but the record does not detail follow-up duration by participant or how these different endpoints to observation were handled analytically.

Enrollment was 41, but the number contributing primary endpoint data and the analysis population are not reported. Missing-data handling is also not reported. Consequently, it is not possible to assess whether outcome availability differed by arm or whether the analysis preserved the randomized comparison. The registry does not provide baseline characteristics that would allow evaluation of chance imbalances between groups.

The trial is listed as terminated, but the reason and timing of the termination decision are not reported. The registry does not provide the statistical plan, sample-size justification, analysis methods, or information about interim analyses. These omissions preclude assessment of whether the reported outcomes and methods followed a prespecified plan. They do not demonstrate that such plans or analyses were absent; they limit what can be verified from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Low Dose Fat for the Prevention of Liver Disease in Babies With Gastrointestinal Disorders — NCT01373918.
• Registry record last updated 2016-06-16; status last verified 2016-05.
• Results first posted 2016-06-16.
• 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 describes a Phase 4, randomized, unblinded, parallel-group trial in neonates with congenital or acquired gastrointestinal disorders. It compared low-dose intravenous soybean oil emulsion, approximately 1 g/kg/d, with standard-dose emulsion, approximately 3 g/kg/d. Enrollment was 41; the trial started in 2010-12, had a primary completion date of 2014-07, and is listed as terminated.

The primary outcome was presence of cholestasis, defined by direct bilirubin > 2 mg/dL, with follow-up ending at 100 days of life, hospital discharge, or death, whichever came first. The registry does not report a single primary comparison, effect estimate, confidence interval, or p-value. Safety entries include serious events affecting 2 of 20 participants at risk in the low-dose group and 1 of 16 in the standard-dose group; no primary efficacy conclusion can be drawn from these entries.