The Energy Dose Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Energy Dose Study (NCT01369147), a randomized phase 2 study. The primary outcome is Number of Participants With Hospital-acquired Infection.

2. Clinical Question

3. Trial Design

The Energy Dose Study (NCT01369147) is listed as a phase 2, randomized, triple-masked, parallel study sponsored by Emory University. The registry describes it as a single-center randomized clinical trial comparing energy doses in critically ill intensive care unit patients requiring parenteral nutrition because of intestinal failure or dysfunction. The listed start was 2011-07, the primary completion date was 2014-12-02, and the current status is terminated.

Three groups were assigned different parenteral-nutrition energy targets: 0.6 x measured REE, 1.0 x measured REE, and 1.3 x measured REE. The intended nutrition period was up to 28 days. The arm descriptions state that PN dosing took account of calories from propofol, clevidipine, dextrose-containing intravenous fluids exceeding 500 mL/day, and enteral feeding. The registry also lists these agents or feeding approaches among the interventions.

The brief summary says that the investigators intended to enroll 60 patients, with 20 per energy-dose group, to generate preliminary data for subsequent appropriately powered phase III multicenter trials. The recorded enrollment is 12. The registry record does not report why the study was terminated or explain the difference between intended and recorded enrollment. The primary endpoint result includes participants with complete data available; the posted arm counts for that result are 3, 4, and 4.

Other listed outcomes include participants with bloodstream infection, ventilator-free days, days in intensive care, and days in hospital. The record reports seven outcome measures, but detailed results for those outcomes are not included in the registry record for this analysis. The registry record does not report the allocation procedure in greater detail, the exact masking roles, or a full protocol description.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis includes participants with complete data available.

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: This analysis includes participants who have baseline data available; all data were unintentionally destroyed for one participant assigned to the 1.0 REE group.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Hospital-acquired Infection, measured over Up to Day 28.

The primary endpoint is the number of participants with a hospital-acquired infection during the study period, up to Day 28. It is a binary event outcome at the participant level: a participant either is or is not counted as having an infection for this endpoint. The registry describes the result as a count of participants and says that the analysis includes participants with complete data available.

In general, counting participants with an event provides an easily interpreted description of how many people experienced the outcome in each study group. Such a count does not, by itself, quantify the uncertainty around an arm-to-arm difference or establish whether differences might be due to chance. That requires an appropriate comparison and an uncertainty measure, such as a confidence interval. The registry record does not report those inferential results for this endpoint.

The posted counts are 1 participant in the 0.6 x measured REE arm, 0 in the 1.0 x measured REE arm, and 1 in the 1.3 x measured REE arm. They describe hospital-acquired infection counts in the complete-data population, not all participants originally intended for enrollment. The endpoint is distinct from the separately listed outcome of bloodstream infection. The registry record does not report the operational definition used to classify a hospital-acquired infection, how infection status was adjudicated, or how incomplete outcome data were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: it records whether a participant had a hospital-acquired infection during the stated period, up to Day 28. The result is posted as counts in three parallel randomized groups. In general, a binary outcome can be analyzed by comparing event proportions or by estimating a relative or absolute contrast between groups. Those comparisons also require an uncertainty measure. The registry record reports the arm counts but no two-arm estimates, confidence intervals, or p-values.

Why sparse events matter

General statistical explanation: when event counts are small, estimates of event frequencies and between-group contrasts can be unstable. A small change in the observed count can make a substantial difference to an estimate, and standard large-sample approximations may be unreliable. Methods intended for sparse binary data may use exact calculations or other approaches suited to small samples. The registry record does not report which method was prespecified or used. It explicitly notes that two-arm comparisons for this binary endpoint are missing or not estimable.

A confidence interval, in general, gives a range of values compatible with the data under a specified statistical model and method. Its width communicates precision: a wider interval indicates greater uncertainty. It is not a guarantee that the true value lies in the interval, and it does not replace attention to the study design or missing data. No confidence interval is reported for this endpoint in the registry record, so the precision of any arm-to-arm contrast cannot be read from the posted counts alone.

What the reported counts represent

The outcome description says the analysis includes participants with complete data available. Thus, the endpoint result pertains to that analysis population, rather than necessarily to everyone enrolled or randomized. The record reports 3 participants in the 0.6 x measured REE arm, 4 in the 1.0 x measured REE arm, and 4 in the 1.3 x measured REE arm for this endpoint. It reports event counts of 1, 0, and 1, respectively. The record does not explain how incomplete data were handled, whether participants were excluded from this endpoint analysis, or whether the complete-data population was defined before the results were examined.

In general, randomized trials may estimate treatment-group effects according to the group assigned, regardless of adherence, or may use other analysis populations. Those choices answer different questions and can affect interpretation. The registry record does not report an intention-to-treat analysis or another named analysis population beyond its statement that the primary analysis includes participants with complete data available. It does not report whether randomization was stratified, how allocation was generated, or how deviations from assigned nutrition targets were handled.

Multiplicity and multiple outcomes

Multiplicity arises when a study evaluates several outcomes, comparisons, or time points: repeated testing can increase the chance of at least one apparently unusual result. General approaches include identifying one primary test in advance, adjusting for multiple tests, or treating secondary results as exploratory. The registry lists one primary outcome and four secondary outcome titles, and reports seven outcome measures overall. It does not report a multiplicity strategy, a hierarchy among secondary outcomes, or the number of planned comparisons. The registry record lists zero analyses, so no adjustment method or formal test results are available to assess.

Sample-size illustrations

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are described as detecting a stated fraction of the observed effect. For outcomes other than time-to-event outcomes, their units are participants per arm; time-to-event calculations instead use total events. These are planning illustrations, not observed power and not evidence that the trial had a particular probability of finding an effect. The registry record does not report the trial's own sample-size justification. No numerical illustration results are included in the registry record for this analysis.

In general, over-dispersion refers to variability greater than a statistical model expects. It matters when selecting a model for outcomes such as counts, because ignoring extra variability can make uncertainty appear too small. The primary endpoint is reported as a binary participant count, and the registry record does not report an over-dispersion analysis. The record also does not report a model specification, covariate adjustment, interim analysis, or stopping rule. Those details should not be inferred from the outcome format or the trial's terminated status.

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("Parenteral Nutrition Energy Dose at 0.6 x Measured", "Parenteral Nutrition Energy Dose at 1.0 x Measured", "Parenteral Nutrition Energy Dose at 1.3 x Measured")
n      <- c(3, 4, 4)
events <- c(1, 0, 1)
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  Parenteral Nutrition Energy Dose at 0.6 x Measured  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6
ARM  Parenteral Nutrition Energy Dose at 1.0 x Measured  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Parenteral Nutrition Energy Dose at 1.3 x Measured  4  1  25.0  0.6  80.6  4.6  69.9  5.3  71.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of hospital-acquired infection and four secondary outcome titles: participants with bloodstream infection, ventilator-free days, days in intensive care, and days in hospital. It reports seven outcome measures in total. Evaluating multiple outcomes or comparisons can create multiplicity concerns in general, because the probability of a chance finding may rise as the number of tests increases. The registry record does not report a plan for controlling multiplicity, a hierarchy for secondary outcomes, or which secondary outcomes were intended to support confirmatory conclusions.

The primary outcome description states that the analysis includes participants with complete data available. The reported endpoint analysis counts are 3, 4, and 4 across the three energy-dose groups. The registry record does not report the number or characteristics of participants with missing primary endpoint data, the reason for missingness, or an imputation or sensitivity-analysis method. It also does not report whether all randomized participants were included in an intention-to-treat analysis.

The registry record lists no analyses and says two-arm binary comparisons are missing or not estimable. It therefore does not provide a statistical analysis plan, an adjusted or unadjusted inferential result, or a documented approach to missing data and multiplicity. In general, these choices affect how a result should be interpreted; their absence means the posted event counts should be treated descriptively rather than as a completed confirmatory comparison.

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.

The adverse-event figures list zero serious adverse events in each of the three energy-dose groups. They also list zero other adverse events and zero deaths in each group. The corresponding numbers at risk are 3 in the 0.6 x measured REE group and 4 in each of the 1.0 x and 1.3 x measured REE groups. These figures describe the entries in the registry record; they do not establish that no adverse events occurred outside the recorded categories or reporting period.

In general, a zero count in a small group does not prove that the underlying event risk is zero. It indicates only that no events of that category were recorded among the listed participants at risk. Safety interpretation depends on the event definitions, observation period, completeness of reporting, and the amount of follow-up. The registry record does not report detailed event definitions, exposure time, or additional follow-up information for these figures. No serious adverse-event terms are listed. The figures should therefore be read as reported counts, not as a precise comparative safety estimate or a guarantee of absence of risk.

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

The posted primary result describes hospital-acquired infection counts by randomized energy-dose group through Day 28: 1 in the 0.6 x measured REE group, 0 in the 1.0 x measured REE group, and 1 in the 1.3 x measured REE group. The analysis includes participants with complete data available, with reported arm counts of 3, 4, and 4. These are observations from a small, terminated phase 2 study, whose recorded enrollment was 12.

The result does not establish that the energy targets differ, that they are equivalent, or that any one target changes infection risk. The registry record provides no inferential analysis, confidence interval, or p-value for the primary endpoint, and the binary two-arm comparisons are listed as missing or not estimable. Without a reported contrast and its uncertainty, the raw counts cannot indicate the precision of a treatment-effect estimate.

The registry's brief summary describes the study as generating preliminary data for future appropriately powered phase III multicenter trials. That framing is consistent with treating the reported counts as preliminary rather than definitive. The registry record reports a planned enrollment of 60, with 20 per energy-dose group, but recorded enrollment is 12. It does not report why the study was terminated or the reason enrollment was below the planned total.

In general, a trial's result is interpreted in light of its design, outcome definition, analysis population, missing data, and statistical uncertainty. Several of these details are not reported in the registry record. The counts can be stated accurately, but they should not be used alone to make a causal or clinical claim. The record also lists separate secondary outcomes, but their detailed results are not reported in the registry record for this analysis.

14. Why This Trial Matters Statistically

Statistically, this trial illustrates the difference between posting outcome counts and estimating a comparative effect. The primary endpoint is reported in a direct form: the number of participants with a hospital-acquired infection in each randomized arm. Such counts are useful for describing what was observed, but they do not provide a measure of how uncertain a difference between arms would be. The registry record reports no confidence intervals, p-values, or estimable two-arm binary comparisons.

The study also highlights the interpretive limits of small event counts. With only a few participants represented in the primary analysis in each group, the observed counts cannot support a precise comparison. This is a general statistical limitation of sparse data, not evidence for or against a particular energy target. The record's intended enrollment of 60 and recorded enrollment of 12 make the gap between planned scale and recorded enrollment important context, while the reason for termination is not reported in the registry record.

Another important issue is the analysis population. The endpoint description specifies complete-data participants, but the record does not explain missingness or report an analysis of all randomized participants. That information matters because a complete-data result may not represent all participants enrolled. Likewise, the registry lists several secondary outcomes but does not report a multiplicity strategy or detailed secondary results.

The trial therefore offers a clear example of why statistical interpretation depends on more than the direction of raw counts. Design information, prespecified methods, missing-data handling, and uncertainty estimates are needed to judge what the data can support. The registry record provides some design and outcome details, but not the inferential information needed for a comparative conclusion.

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 trial-specific limitations affect interpretation. Recorded enrollment is 12, while the brief summary describes an intended enrollment of 60, with 20 participants per energy-dose group. The registry status is terminated, but the reason for termination is not reported in the registry record. The posted primary endpoint analysis includes complete-data participants, with group counts of 3, 4, and 4. The record does not explain missing data or show whether all randomized participants were included in an analysis.

The primary outcome is reported as participant counts through Day 28, without an inferential comparison, confidence interval, or p-value. The registry marks binary two-arm comparisons as missing or not estimable. It does not report the operational definition or adjudication method for hospital-acquired infection, nor a statistical analysis plan, adjustment approach, or multiplicity strategy. The fact that four secondary outcomes are listed does not supply their results; detailed findings for those outcomes are not reported in the registry record.

The registry describes the study as single-center and phase 2, with a stated purpose of generating preliminary data for later multicenter trials. Its findings therefore need to be read within that context. The record does not report details of the randomization procedure, masking roles, adherence to assigned energy targets, protocol deviations, or an interim analysis. These details should not be assumed. The posted information supports a description of the reported counts, but not a precise estimate of comparative effects or a definitive conclusion about the three energy-dose targets.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Energy Dose Study — NCT01369147.
• Registry record last updated 2022-06-10; status last verified 2022-05.
• Results first posted 2022-06-10.
• 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

NCT01369147, The Energy Dose Study, is listed as a randomized, triple-masked, parallel phase 2 trial sponsored by Emory University. It compared parenteral-nutrition energy targets of 0.6 x, 1.0 x, and 1.3 x measured REE in critically ill patients requiring PN. The registry describes a planned enrollment of 60 and records enrollment of 12; the study status is terminated.

The primary outcome was the number of participants with hospital-acquired infection up to Day 28 among those with complete data available. The posted counts were 1, 0, and 1 across the three arms, with analysis counts of 3, 4, and 4. The registry lists no analyses and reports no estimable two-arm binary comparison. Four secondary outcomes are listed, but detailed results are not reported in the registry record. The reason for termination, missing-data handling, and the trial's statistical analysis plan are not reported in the registry record.