Proton Pump Inhibitors (PPI) and Fat Absorption in Cystic Fibrosis (CF) and Exocrine Pancreatic Insufficiency (EPI): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Proton Pump Inhibitors (PPI) and Fat Absorption in Cystic Fibrosis (CF) and Exocrine Pancreatic Insufficiency (EPI) (NCT03551691), a randomized phase 2 study. The primary outcome is Coefficient of Fat Absorption.

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, quadruple-masked crossover trial sponsored by Children's Hospital of Philadelphia. The registry reports enrollment of 19 and a completed status. Its brief description says participants were randomized to receive omeprazole or placebo for 28 days, then crossed over to receive the other treatment for another 28 days. Fat absorption markers were measured after each course. The intervention descriptions specify omeprazole 20mg daily and a daily placebo capsule.

In a crossover design, each participant receives both treatments in sequence. This can make within-participant comparisons useful because each person can serve as their own reference. The validity of that comparison depends on the design and analysis addressing issues such as treatment order, time or period effects, and any residual effects from an earlier course. The registry record does not report a washout period or describe how these issues were handled statistically. It also does not give the randomization method or explain the masking procedures behind the quadruple-masked designation.

The primary outcome timeframe was after 28 days of treatment or placebo. The record also lists duodenal pH and fat absorption via malabsorption blood test as secondary outcomes. It does not report the trial's sample-size justification or detailed statistical analysis plan. Although the record is marked completed, completion status alone does not supply results for every planned outcome or identify which participants were included in each 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.

Before assignment: 19 subjects were randomized. There were 13 evaluable subjects who completed data collection at the end of the treatment period and 6 subjects did not complete data collection.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary outcome measurement (CFA) was not available for 2 participants who got study drug first and 2 participants who got placebo first.

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 randomized, crossover study includes baseline characteristics for 13 participants who both or either active and/or placebo treatment. Only data for 11 participants were available for analysis.

6. Primary Endpoint

The registry lists the primary outcome as Coefficient of Fat Absorption, measured over After 28 days of treatment or placebo.

The primary endpoint was coefficient of fat absorption (CFA), expressed as % fat absorption. The registry describes it as a gold standard measurement of fat malabsorption and specifies that the outcome was measured after 28 days of treatment or placebo. It reports the mean and standard deviation for the treatment summaries.

In general, a continuous measure such as CFA retains information about the magnitude of a measurement rather than sorting participants into categories. A mean describes the central value in a group of observations. A standard deviation describes how dispersed the observations are around that mean; it is not a measure of uncertainty in the mean. Those summaries can characterize the posted measurements, but they do not by themselves quantify the uncertainty around a treatment comparison.

The registry's reported mean was 80.0 with a standard deviation of 20.0 for omeprazole, and 77.0 with a standard deviation of 16.0 for placebo. The record does not provide confidence intervals for these summaries or a paired estimate comparing treatment courses. It also states that the primary outcome measurement was unavailable for 2 participants who received study drug first and 2 participants who received placebo first. Consequently, the reported endpoint summaries should be read alongside this missing-outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the mean and standard deviation describe?

The registry characterizes CFA as a continuous outcome and reports a mean and standard deviation for each treatment summary. In general, the mean is the arithmetic average of the measured values in the summarized observations. The standard deviation describes the spread of those observations around their mean. A larger spread means the measured values are more dispersed; it does not mean that the estimated mean is necessarily less precise by the same amount, because precision also depends on the amount and structure of the data.

For this record, the reported summaries are a mean of 80.0 and standard deviation of 20.0 for omeprazole, and a mean of 77.0 and standard deviation of 16.0 for placebo. These figures describe the posted observations but do not supply a confidence interval for the treatment contrast. A confidence interval, in general, gives a range of values compatible with the data and analysis under the method's assumptions. No such interval for the primary treatment comparison is reported in the registry record.

Why does the crossover structure matter?

In general, a crossover trial assigns a sequence of treatments and measures participants under more than one treatment condition. Since the same participant contributes measurements under both conditions, those measurements are correlated. A statistical comparison should generally account for this within-participant relationship rather than treating every measurement as if it came from an unrelated person. Ignoring that structure can give an inappropriate estimate of uncertainty.

Crossover analyses may also need to consider treatment sequence and period. A period effect is a change associated with when a measurement is taken rather than with the treatment itself. Carryover refers to a residual influence of an earlier treatment period on a later one. These are general methodological considerations, not evidence that either issue occurred in this trial. The registry record does not report a washout period, the statistical model, or how period, sequence, or carryover were evaluated.

What can be inferred from the posted outcome summaries?

The record provides arm-level means, standard deviations, and counts, but it does not provide the participant-level paired measurements or a crossover treatment estimate. It also indicates that values were missing or not estimable for a two-arm comparison of the continuous endpoint. Accordingly, a simple recalculation from the posted summaries is not a substitute for the trial's paired analysis. No recalculated treatment effect, confidence interval, or p-value is presented.

In general, a p-value addresses how compatible data are with a specified null model and its assumptions; it is not a measure of the magnitude or clinical importance of an effect. A confidence interval is usually more informative about precision because it describes the range of effects compatible with the data under the analysis. Neither is reported for this primary comparison. The absence of those quantities in the registry record does not itself show that an effect is present or absent.

How should planning illustrations be read?

In general, a sample-size planning illustration translates an assumed effect and statistical design into a hypothetical number of participants needed for a chosen power target. The registry's described illustrations use the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. They are planning scenarios, not a report of the trial's design rationale and not observed power.

Because the trial is a crossover study, planning assumptions should match the intended analysis and its within-participant structure to be applicable. The registry does not report that the illustrations were used to plan this trial. They therefore should not be interpreted as evidence that the trial was adequately or inadequately sized, or as a substitute for a reported analysis of the observed data.

What statistical plan is reported?

The registry record does not report a detailed statistical analysis plan, model specification, method for constructing uncertainty intervals, or approach to missing outcome data. It lists no posted analyses for the outcomes. These absences limit assessment of how the sponsor intended to estimate the treatment contrast and how the reported descriptive values relate to that intended analysis. General methodological descriptions explain why those details matter; they do not fill in what is not reported.

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("Omeprazole", "Placebo")
n   <- c(7, 4)
m   <- c(80, 77)
sp  <- c(20, 16)
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  Omeprazole  7  80.000  20.000  61.503  98.497
CARM  Placebo  4  77.000  16.000  51.540  102.460

11. Multiplicity, Missing Data and Analysis Populations

The registry lists CFA as the primary outcome and lists duodenal pH and fat absorption via malabsorption blood test as secondary outcomes. It reports two secondary outcomes and three outcome measures. The numerical secondary-outcome results and their analysis details are not reported in the registry record. The record also lists no posted analyses.

When a study assesses multiple outcomes or makes multiple statistical comparisons, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures may be used to control that risk, or investigators may define a limited set of primary comparisons in advance. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how results across outcomes were handled together. This does not imply that a particular adjustment was or was not used outside the information in the record.

The record states that the primary CFA measurement was unavailable for 2 participants who received study drug first and 2 participants who received placebo first. It does not explain why these measurements were unavailable, whether missingness was related to observed participant characteristics, or whether any values were imputed. In general, missing outcomes can affect both the estimate and its precision, particularly if the probability of missingness is related to the outcome. The registry does not report sensitivity analyses addressing that possibility.

The analysis population is also not specified. The record does not say whether the analysis included participants according to randomized sequence, included only those with measurements in both periods, or used another population definition. These details are especially relevant for a crossover comparison. Enrollment and the available endpoint counts should therefore not be treated as interchangeable descriptions of the analysis population.

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 registry reports serious adverse event figures separately for omeprazole and placebo. For each treatment group, 11 participants were listed as at risk and 0 serious adverse events were reported. The record also lists 0 other adverse events and 0 deaths for each group. No serious adverse event terms are listed.

These are counts as recorded, not evidence that the underlying risk is zero. A count of zero means no events were reported in the registry's group summary; it does not establish that an event could not occur or that the treatments have identical safety profiles. Counts also do not show the timing, duration, severity beyond the serious-event classification, or relationship of an event to treatment.

Because this was a crossover trial, participants received both treatments in sequence. The at-risk count for each treatment should not be read as a count of different people across the whole study. The registry does not provide participant-level safety data, exposure-adjusted rates, or details of adverse-event collection and attribution. These figures are therefore a limited summary of the events recorded for each treatment group, rather than a complete comparison of safety.

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

The posted record documents a randomized, quadruple-masked crossover trial that compared omeprazole with placebo in participants with cystic fibrosis and exocrine pancreatic insufficiency. It reports CFA means and standard deviations after treatment or placebo and gives counts for those summaries. It also reports that some primary measurements were unavailable in both treatment sequences. These are descriptive details about the registry entry.

The record does not report an analyzed treatment contrast for the primary endpoint. In particular, it does not give a paired estimate, confidence interval, or p-value. Without those results and details of the analysis population and missing-data handling, the magnitude and precision of a treatment effect cannot be determined from the posted information. The arm-level means should not be treated as a complete crossover comparison.

The record also does not report numerical findings for the secondary outcomes. The adverse-event summaries list no events in the categories reported, but those counts do not establish absence of risk or provide a detailed safety comparison. These limits concern what is available in the registry record; they do not establish what may have been reported elsewhere.

In general, a trial result is best interpreted by considering the effect estimate, its uncertainty, the analysis plan, and the population represented by the data. Here, the posted information allows a reader to understand the trial question and the reported descriptive endpoint values, but not to determine whether the primary treatment contrast was meaningfully different, how precisely it was estimated, or how the missing measurements influenced the analysis. No treatment recommendation follows from these registry summaries.

14. Why This Trial Matters Statistically

This trial is statistically notable because its crossover design creates a within-participant comparison. In general, that design can account for stable differences between participants, but it requires analysis that respects the relationship between measurements from the same person. Arm-level means and standard deviations alone do not reveal the paired pattern of outcomes or the uncertainty of a paired contrast.

The record also illustrates why outcome-specific counts matter. Enrollment is reported as 19, while the CFA summaries have counts of 7 for omeprazole and 4 for placebo, and unavailable measurements are noted in both treatment sequences. Readers need to distinguish the overall enrollment figure from the observations contributing to a particular summary. The record does not explain the relationship between these counts and the analysis population.

A further statistical issue is the gap between descriptive results and inferential results. Means characterize the observed data, while an estimate of the treatment contrast and its uncertainty would address the comparative question. Those inferential quantities are not reported for CFA in the registry record. Nor are the methods needed to assess treatment sequence, period effects, or missing outcomes.

The trial therefore provides a useful example of how registry summaries can identify a focused clinical question and design while leaving important analytical details unresolved. Planning illustrations based on an observed effect can help frame hypothetical future-study requirements, but they are not observed power and do not replace a reported primary analysis. The distinction between study design, descriptive summaries, and inferential evidence is central to reading the record accurately.

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 principal limitation of the posted results is the absence of a reported treatment comparison for the primary continuous outcome. The record gives means, standard deviations, and counts but no paired estimate, confidence interval, or p-value. The details needed to judge the crossover analysis, including treatment sequence and period handling, are not reported in the registry record.

The record states that CFA measurements were unavailable for 2 participants who received study drug first and 2 who received placebo first. It does not give reasons for missingness or describe the method used to handle it. The analysis population is not specified, so it is unclear from the registry whether the summaries represent participants with measurements in both periods or another analysis set.

Additional limitations of the available record include the absence of numerical secondary-outcome results, a detailed statistical plan, and information on multiplicity handling. The registry does not report a washout period or how any potential carryover was considered. These omissions prevent a full appraisal of how the trial's crossover design and outcomes were analyzed.

The adverse-event information is limited to group-level counts, without participant-level details or further information about exposure, timing, or attribution. The registry reports completed status, but this does not resolve the missing analytical and outcome details. These limitations describe the information in the registry record and should not be taken as proof that unreported analyses or information do not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Proton Pump Inhibitors (PPI) and Fat Absorption in Cystic Fibrosis (CF) and Exocrine Pancreatic Insufficiency (EPI) — NCT03551691.
• Registry record last updated 2024-04-30; status last verified 2024-04.
• Results first posted 2024-04-30.
• 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 a completed phase 2, randomized, quadruple-masked crossover trial sponsored by Children's Hospital of Philadelphia. Enrollment was 19. Participants were assigned to treatment order and received omeprazole 20mg daily and placebo in separate 28-day courses, with fat absorption assessments after each course.

The primary outcome was CFA, reported as a mean with standard deviation after 28 days of treatment or placebo. The record gives means of 80.0 for omeprazole and 77.0 for placebo, with standard deviations of 20.0 and 16.0, respectively. CFA measurements were unavailable for 2 participants in each treatment sequence. The registry does not report a primary treatment comparison or numerical secondary-outcome results.

Serious adverse event counts, other adverse event counts, and deaths were reported as 0 for each treatment group. The registry does not report a detailed statistical plan, analysis population, missing-data method, or multiplicity approach.