PEP uP Protocol in Surgical Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PEP uP Protocol in Surgical Patients (NCT02459275), a randomized phase 4 study. The primary outcome is Total Amount of Protein Received.

2. Clinical Question

The study’s stated objective was to assess the safety, feasibility and effectiveness of an aggressive feeding protocol in increasing protein and energy delivery to critically ill surgical patients. The registered primary endpoint addresses protein received relative to protein prescribed. It does not directly report the broader energy-delivery objective in its primary-endpoint definition.

The registry record does not report an estimate comparing the groups for this endpoint, nor does it report uncertainty around such an estimate. It therefore cannot establish from the posted results whether protein delivery differed between the PEP uP Protocol and Standard of Care groups. The registered objective and hypothesis describe what the investigators intended to evaluate, not a finding. Details of eligibility, baseline nutritional status, and the specific population included in the primary endpoint analysis are not reported in the registry record.

3. Trial Design

The registry record describes PEP uP Protocol in Surgical Patients as a phase 4 randomized trial with a parallel model and no masking. The sponsor is Clinical Evaluation Research Unit at Kingston General Hospital. The study began in 2015-07, had a primary completion date of 2017-09, and is listed as terminated. Enrollment is recorded as 36. The reason for termination is not reported in the registry record.

The intervention arm is described as receiving the PEP uP protocol with a pro motility agent. The intervention was to continue until tube feeds stopped or the patient was fed meals orally, with follow-up until hospital discharge or 60 days, whichever occurred first. Metoclopramide is also listed as an intervention. The comparator description starts with standard formula polymeric tube feeds at 20 ml/hour and gastric residual volume checks every 4 hours; the remainder of that description is not reported in the registry record.

There is an important design ambiguity in the registry information. The design fields describe a randomized parallel trial, while an analysis note identifies the design as cluster-randomized and cautions that simple individual-level re-analysis would be misleading. The record does not explain this difference or identify the unit of randomization in enough detail to resolve it. Because observations from participants in the same cluster may be correlated, treating all participants as independent could give misleading uncertainty estimates. The sponsor’s own analysis takes precedence over a simple individual-level re-analysis when interpreting a cluster design.

The primary endpoint is total protein received, expressed as a percentage of the amount prescribed at baseline, over 12 days. Secondary outcomes listed are time to initiation of enteral nutrition, ICU length of stay, mortality, and hospital length of stay. The registry record does not provide a statistical analysis plan, group-specific primary outcome results, or an explanation of the termination.

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 Total Amount of Protein Received, measured over 12 days.

The primary endpoint is the total amount of protein received from enteral nutrition or parenteral nutrition, including protein counted from propofol, divided by the amount prescribed according to the baseline assessment. It is expressed as a percentage of the prescribed amount and assessed over 12 days. The registry identifies the measure as a mean with standard deviation as its dispersion.

Expressing received protein relative to the prescribed amount gives the endpoint a reference point: it describes delivery in relation to what was prescribed rather than reporting only an amount in isolation. The mean can summarize the average value in a group, while the standard deviation describes how spread out individual values are around that mean. These are descriptive statistics; neither one alone quantifies the precision of a between-group comparison.

This endpoint is relevant to the registered objective of assessing whether the feeding protocol increases protein delivery. It remains a measure of nutritional delivery, not a direct measure of clinical recovery. The record lists other clinical outcomes separately, including mortality and lengths of stay. No group means, standard deviations, between-group estimate, confidence interval, or test result for the primary endpoint is reported in the registry record. The endpoint’s actual observed value and comparative result therefore cannot be interpreted from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

General: For a continuous outcome, a group mean gives the average observed value, and a standard deviation describes the variability of individual observations around that average. The standard deviation is not the same as the standard error: the former describes variation among observations, while the latter describes uncertainty in an estimate such as a mean. A standard deviation by itself does not show whether a difference between groups is precise or compatible with no difference.

For this trial, the registry identifies total protein received as a mean with standard deviation. It does not post either group’s mean or standard deviation. It also does not report a between-group estimate, so the actual size and direction of any primary outcome difference are not available for interpretation.

What would a confidence interval add?

General: A confidence interval expresses the uncertainty around an estimate using a range of values compatible with the data and the method used to construct the interval. Its width reflects precision: a wider interval indicates less precision than a narrower one. An interval should be interpreted in relation to the outcome scale and the question being asked, not as a guarantee that the true value lies within its endpoints.

No confidence interval for the primary endpoint is reported in the registry record. Consequently, it is not possible to judge how precisely the trial estimated a group difference, or which magnitudes of difference remain compatible with the posted evidence. A p-value, if reported, would not replace an estimate and its confidence interval: it would not describe the size of a difference or its practical importance.

Why does the randomization unit matter?

General: Randomization determines how treatment assignments are allocated. In an individually randomized trial, participants are assigned separately. In a cluster-randomized trial, groups of participants are assigned together. Participants in the same cluster can have more similar outcomes than participants in different clusters. This within-cluster similarity is called intracluster correlation. If an analysis treats clustered participants as independent, it can underestimate uncertainty and make confidence intervals too narrow or tests too optimistic.

The registry’s design fields describe a randomized parallel trial, while an analysis note calls it cluster-randomized and cautions against a simple individual-level re-analysis. The record does not resolve the discrepancy or report the sponsor’s primary outcome analysis. For a cluster design, an appropriate analysis generally accounts for clustering, but the particular method used in this trial is not reported in the registry record. No cluster-adjusted result can be reconstructed from the posted primary outcome information.

What is over-dispersion, and why can it matter?

General: Over-dispersion occurs when observed variation is greater than a statistical model expects. It can arise when observations are more alike within groups, when the model does not capture important sources of variability, or when the outcome distribution differs from the assumed distribution. If over-dispersion is ignored, standard errors may be too small and uncertainty may be understated. For a continuous endpoint summarized by a mean and standard deviation, the observed spread is directly relevant to describing variability; model-based comparisons may also need to account for the study structure.

The registry record does not report a model, a dispersion assessment, or any diagnostic checks for the primary endpoint. Over-dispersion is therefore a general consideration rather than a finding about this trial.

What can the sample-size illustration establish?

General: A sample-size calculation describes how many observations a planned study might require under chosen assumptions about the target effect, significance level, allocation, and analysis. It is a planning illustration, not an observed result and not a measure of the probability that a completed trial’s finding is correct. A calculation based on an effect seen in the same trial is especially dependent on that observed estimate and should not be mistaken for an independent confirmation.

The registry record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It specifies that the target effect is a stated fraction of the observed effect. However, the primary endpoint effect is not reported in the registry record, and the available record does not report a primary endpoint analysis. No planning count can therefore be interpreted as evidence about the trial’s observed effect or as observed power. For a time-to-event outcome, the record’s stated approach concerns total events; for other outcomes, the illustration concerns participants per arm.

In this trial, the absence of posted primary endpoint estimates prevents assessment of the observed mean difference, its uncertainty, or its relation to any planning target. The statistical plan, including the chosen model, any covariate adjustment, and any procedures for cluster correlation, is not reported in the registry record.

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("PEP uP Protocol", "Standard of Care")
n   <- c(19, 17)
m   <- c(55.1, 52.9)
sp  <- c(24.4, 23.2)
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  PEP uP Protocol  19  55.100  24.400  43.340  66.860
CARM  Standard of Care  17  52.900  23.200  40.972  64.828

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes: time to initiation of enteral nutrition, ICU length of stay, mortality, and hospital length of stay. It also records six outcome measures. When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase if each is tested separately without an adjustment or a prespecified hierarchy. General approaches include defining one primary comparison, setting an order for testing, or adjusting inference across a family of tests. The strategy selected for this trial is not reported in the registry record.

Missing outcome data can also affect interpretation. If participants lack measurements, a complete-case analysis may describe a selected subset rather than all randomized participants, especially when missingness is related to health status or treatment. Analytic approaches depend on why data are missing and on assumptions about the missing values. The registry record does not report how missing primary endpoint measurements were handled, how many participants contributed endpoint data, or whether sensitivity analyses were conducted.

The record does not report the analysis population, such as whether the primary analysis included all randomized participants or a narrower group. It also does not describe adherence handling, protocol deviations, or the statistical approach to the noted cluster-randomized design. These omissions mean that readers cannot determine which participants informed any primary estimate or whether the analysis accounted for the study structure. Since no primary outcome analysis is reported in the registry record, neither the impact of missing data nor the handling of multiple outcomes can be evaluated from the posted results.

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: temporary qtc prolongation (5.3%).

The registry reports serious adverse event counts separately by group. In the PEP uP Protocol group, 19 were recorded as at risk and 1 as having a serious adverse event. In the Standard of Care group, 17 were recorded as at risk and 0 as having a serious adverse event. The top serious term listed is temporary QTC prolongation, at 5.3%. The registry also records deaths as 1 in the PEP uP Protocol group and 2 in the Standard of Care group.

These are descriptive counts. They do not establish that the intervention caused or prevented an event, and the listed counts should not be treated as a precise comparison of risk. With few events, estimates can be highly uncertain. The record does not report a comparative safety estimate, confidence interval, statistical test, or details on event timing and relatedness. It also does not clarify in the posted results how the listed serious term relates to the overall serious adverse event counts.

The recorded deaths are presented separately from the serious adverse event counts and should not be assumed to be caused by the intervention. The safety figures can describe what the registry reports, but they cannot alone establish a causal safety difference between groups.

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

The registry record identifies a clinically relevant question: whether a feeding protocol intended to increase protein and energy delivery changes protein received relative to the amount prescribed for critically ill surgical patients. It also gives the primary endpoint’s definition, the study’s design fields, enrollment, and selected safety counts. These details help readers understand what the investigators intended to measure and what information is posted.

However, the primary endpoint results are not reported in the registry record. There are no group means, standard deviations, comparative estimate, confidence interval, or p-value for total protein received. It is therefore not possible to determine from the posted results whether the groups differed, how large any difference was, or how precisely it was estimated. The study hypothesis is not an observed result, and the stated objective should not be presented as a finding.

The record’s termination status and enrollment figure do not explain why the trial ended or whether the intended analysis was completed. The reason for termination and the primary endpoint analysis population are not reported in the registry record. In addition, the design fields and analysis note differ on whether randomization was parallel at the individual level or clustered. That issue matters because the appropriate uncertainty estimate depends on the unit of randomization.

The serious adverse event and death counts provide limited descriptive safety information, but they do not establish causation or comparative safety. The registry does not report a precision estimate for those comparisons. Taken together, the posted information describes the trial and its planned question but does not provide enough outcome evidence to support a conclusion about the primary endpoint or a causal claim about safety.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint is not enough to interpret a clinical study. The registry specifies a continuous primary outcome, its measurement period, the components included in the received-protein measure, and its expression relative to the baseline prescription. Those details make the intended quantity understandable. Yet without the group summaries and comparative estimate, readers cannot assess the observed effect or its precision.

The design ambiguity is also statistically important. The registry describes a randomized parallel model, but an analysis note identifies cluster randomization and warns that a simple individual-level re-analysis would be misleading. The unit of randomization determines how the analysis should account for dependence among observations. Failing to account for clustering can make uncertainty appear smaller than it is. The record does not resolve the ambiguity or report a primary endpoint analysis that would clarify how the issue was handled.

The terminated status, enrollment information, and sparse serious event counts further illustrate the difference between descriptive registry information and an interpretable comparative result. Enrollment does not establish the number analyzed, and event counts without uncertainty estimates do not establish a reliable group difference. The registry record does not provide the termination reason, missing-data approach, analysis population, or multiplicity strategy.

For clinical researchers and biostatisticians, the central lesson is to distinguish the registered question from the evidence needed to answer it. A protocol objective, endpoint definition, and safety count may describe what was studied, but conclusions require analyzed outcome data and a method consistent with the trial design.

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 most important limitation for interpreting this trial is that the registry record does not report the primary endpoint results. Without group-level summaries or a comparative estimate, the principal question about protein delivery cannot be evaluated. The record also does not report confidence intervals or a test result for the primary endpoint, so neither the magnitude nor the precision of a comparison is available.

The listed status is terminated, but the reason for termination is not reported in the registry record. The record does not say whether termination related to feasibility, recruitment, safety, administrative decisions, or another cause; no explanation should be inferred. Enrollment is recorded as 36, but the number included in the primary outcome analysis and the amount of missing outcome data are not reported.

The design description is internally ambiguous: the design fields describe a randomized parallel trial, while an analysis note identifies cluster randomization. The registry record does not clarify the randomization unit, the number or nature of clusters, or the method used to account for clustering. It does not provide a primary endpoint analysis that could be checked against the design.

Other details needed to judge the evidence are also not reported in the registry record, including baseline group characteristics, eligibility criteria, the statistical analysis plan, the analysis population, multiplicity handling, and missing-data procedures. The Standard of Care description is incomplete. The posted serious adverse event counts are sparse, and no comparative safety estimate or uncertainty interval is given. These limitations restrict interpretation to a description of the registered design and posted counts rather than conclusions about efficacy or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PEP uP Protocol in Surgical Patients — NCT02459275.
• Registry record last updated 2020-10-27; status last verified 2020-10.
• Results first posted 2020-10-27.
• 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

PEP uP Protocol in Surgical Patients is listed as a phase 4 randomized trial with a parallel model and no masking. It is sponsored by Clinical Evaluation Research Unit at Kingston General Hospital, has enrollment recorded as 36, and is listed as terminated. The study began in 2015-07, with primary completion in 2017-09.

The primary endpoint is total protein received from enteral nutrition or parenteral nutrition, including propofol, divided by the amount prescribed at baseline and expressed as a percentage over 12 days. The registry record does not report the primary endpoint results or a comparative analysis. It lists time to initiation of enteral nutrition, ICU length of stay, mortality, and hospital length of stay as secondary outcomes.

The record describes the PEP uP protocol with a pro motility agent and lists metoclopramide as an intervention. It reports serious adverse event counts and deaths by group, but no comparative safety analysis. A design note identifies cluster randomization, in contrast with the randomized parallel design fields; the record does not resolve that discrepancy.