Study Investigating a Delayed-Release Pancrelipase in Patients With Pancreatic Exocrine Insufficiency (PEI) Due to Cystic Fibrosis (CF): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Investigating a Delayed-Release Pancrelipase in Patients With Pancreatic Exocrine Insufficiency (PEI) Due to Cystic Fibrosis (CF) (NCT00690820), a randomized phase 3 study. The primary outcome is Coefficient of Fat Absorption (%).

2. Clinical Question

The clinical question focuses on a measurable aspect of nutrient absorption in children with cystic-fibrosis-related pancreatic exocrine insufficiency. The registry record describes the study objective as assessing the effect of pancrelipase on fat and nitrogen absorption. The primary endpoint is the coefficient of fat absorption, expressed as a percentage, rather than a clinical event or a long-term health outcome.

The posted results compare mean endpoint values for pancrelipase and placebo. They report a higher mean coefficient of fat absorption for pancrelipase. The results also include measures of nitrogen absorption, fat excretion, stool weight, stool frequency, and symptom-related days. These secondary measures provide related information about absorption and gastrointestinal outcomes, but they do not replace the prespecified primary endpoint.

The registry record reports enrollment of 17 and an analysis population defined by randomization and at least one post-baseline efficacy measurement. The endpoint summaries list 16 observations for each treatment. The record does not explain why the endpoint counts differ from the enrollment count or how participants' crossover sequences were handled in the reported estimates.

3. Trial Design

This was a Phase 3, randomized, double-blind, multi-center, placebo-controlled crossover study. It evaluated pancrelipase delayed-release 12,000 unit capsules in subjects aged 7–11 with pancreatic exocrine insufficiency due to cystic fibrosis. The registry record names Solvay Pharmaceuticals as the sponsor and marks the study as completed. It lists the start as 2008-06 and primary completion as 2008-12.

A crossover design compares treatments across treatment periods within the study framework. In general, such designs can make within-participant comparisons possible, but interpretation depends on details such as treatment sequence, period effects, and possible carryover. The specific sequence, period structure, washout arrangements, and analysis treatment of these features are not reported in the registry record. Those details should not be inferred from the crossover label alone.

The primary endpoint was assessed over a 5-day timeframe. The description says stools were collected on 3 days during the 5 days treatment period. The analysis population was the Full Analysis Sample, defined in the record as randomized subjects with at least one post-baseline efficacy measurement. The primary endpoint summaries list 16 observations for placebo and 16 for pancrelipase. The registry enrollment is 17; the record does not explain the difference between enrollment and endpoint analysis counts.

The sponsor's posted primary analysis is an ANOVA comparison, with p < 0.001. The model terms, assumptions, handling of crossover structure, and any covariate adjustments are not reported in the registry record. The record also does not report the original sample-size justification, planned interim analyses, or a detailed statistical analysis plan. Thus the posted design features establish the broad trial structure but do not fully specify how the sponsor's statistical model represented the repeated treatment periods.

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: Twenty three subjects had given their consent and 17 subjects were randomly allocated to pancrelipase/placebo or placebo/pancrelipase. One subject did not complete the first period of the treatment (consent withdrawal).

Period 1

Reasons for not completing this period:

Period 2

Analysis population for the primary outcome, as defined in the registry: The analysis was done on the Full Analysis Sample defined as the randomized subjects with at least one post-baseline efficacy measurement.

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 Coefficient of Fat Absorption (%), measured over 5 days.

The primary endpoint is the coefficient of fat absorption, reported as a percentage and summarized as a mean with standard deviation. The registry record defines it using fat intake and fat excretion: 100*[fat intake-fat excretion]/fat intake. Stools were collected on 3 days during the 5 days treatment period. The record states that higher values indicate a better response.

This measure expresses the share of fat intake not accounted for by measured fat excretion. It is used as a direct, quantitative measure of fat absorption in this study population, where pancreatic exocrine insufficiency is the condition under study. The endpoint is therefore closely connected to the stated objective of assessing fat absorption, rather than being a general measure of health or a long-term clinical outcome.

The endpoint is a continuous measure. A mean summarizes the central value across observations, while a standard deviation describes variation among the observations. These summaries do not show every individual value or the distribution's shape. The collection schedule and calculation make the measure specific to the stated treatment period; they do not establish what occurred outside that timeframe.

The primary results show a mean of 47.41 for placebo and 82.81 for pancrelipase. The reported mean difference is 35.4, with a 95% confidence interval from 26.2 to 44.6. These figures describe the posted short-term endpoint comparison. They do not by themselves establish durability, broader effects on cystic fibrosis, or effects on outcomes not measured in the study.

7. Results Posted in the Registry

• Pancrelipase: mean 82.81 versus 47.41 on control; difference 35.40 (95% CI 26.20 to 44.60), standardized effect d = 2.67; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Coefficient of Nitrogen Absorption (%)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Pancrelipase: mean 80.33 versus 44.98 on control; difference 35.35 (95% CI 24.60 to 46.10), standardized effect d = 2.28; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Pancrelipase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Total Fat Excretion (Grams)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Pancrelipase: mean 58.10 versus 182.90 on control; difference -124.80 (95% CI -160.74 to -88.86), standardized effect d = -2.41; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Pancrelipase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Total Stool Weight (Grams)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Pancrelipase: mean 161.40 versus 436.50 on control; difference -275.10 (95% CI -357.67 to -192.53), standardized effect d = -2.31; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Pancrelipase than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary endpoints form a coherent broad pattern around nutrient absorption and stool output. The posted continuous analyses report higher mean nitrogen absorption and lower mean total fat excretion and total stool weight in the pancrelipase condition than in the placebo condition. These directions align with the primary finding of a higher mean coefficient of fat absorption. Taken together, the endpoints provide related short-term measures rather than independent confirmation of a long-term clinical benefit.

The registry lists other secondary outcomes, including stool frequency and day-based measures of flatulence, formed or normal stools, and abdominal pain. Results for every listed secondary outcome are not reproduced in the posted continuous analyses summarized in the record. Their exact estimates or findings should not be inferred from the other measures. The listed number of outcome measures and analyses does not itself establish which outcomes were prespecified, how their analyses were conducted, or whether every planned analysis was reported.

Secondary results generally carry less weight than the primary endpoint for several reasons. They are additional outcomes beyond the main question, and testing multiple outcomes raises the chance of finding a nominally notable result by chance. Whether that risk was controlled depends on a prespecified multiplicity strategy, which is not reported in the registry record. The record also does not provide enough information to assess whether the outcomes were ranked or whether any adjustment was applied.

The secondary measures are not substitutes for the primary endpoint and should be interpreted in context with the small study, short measurement period, and crossover-analysis details that are not reported. Their overall direction is broadly consistent with the primary result, but consistency across related measures does not remove uncertainty about missing data, analysis choices, multiplicity, or generalizability.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Coefficient of Nitrogen Absorption (%)
• Total Fat Excretion (Grams)
• Total Stool Weight (Grams)
• Stool Frequency
• Percentage of Days With no Flatulence.
• Percentage of Days With Formed/Normal Stools.
• Percentage of Days With no Abdominal Pain.

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a continuous primary endpoint summarized by its mean and standard deviation. A mean is the arithmetic average of observed measurements. A standard deviation describes how dispersed observations are around that average. These quantities describe the observed endpoint summaries; neither alone describes the precision of the treatment contrast.

What does the mean difference represent?

The mean difference compares the reported average coefficient of fat absorption under pancrelipase with the average under placebo. The posted estimate is 35.4, with the contrast expressed as pancrelipase relative to placebo. A positive estimate means the pancrelipase mean is higher for this endpoint. The arm means are 82.81 and 47.41, respectively. No additional calculation is needed to interpret the reported contrast.

For a continuous endpoint, differences retain the endpoint's scale. Here the measure is expressed as a percentage, so the contrast concerns the coefficient on that scale. It is not a risk ratio, an odds ratio, or the percentage of participants who responded. The registry record does not define a threshold for an individual response, and the mean difference should not be interpreted as the change experienced by every participant.

What does the p-value tell the reader?

The sponsor reports an ANOVA analysis with p < 0.001. A p-value is a measure of how incompatible the observed data are with a specified null model, under the assumptions of the statistical analysis. A small p-value is not the probability that the null hypothesis is true, nor does it describe the size or clinical importance of an effect. It also does not address biases or design limitations not represented in the model.

The posted unadjusted re-calculation from summary statistics also reports p < 0.001. This calculation is distinct from the sponsor's ANOVA, which is the registry's own reported analysis. The registry record does not report the ANOVA model terms, exact test statistic, treatment of crossover periods, or whether the test accounted for within-participant correlation. Therefore, the two p-values' numerical agreement does not establish that the calculations make identical assumptions.

Why does the crossover design matter?

General statistical explanation: in a crossover design, a participant may contribute measurements under more than one treatment condition. Those observations can be related because they come from the same participant. Methods that account for this relationship can differ from methods that treat all observations as independent. Period effects and carryover from an earlier treatment can also matter in some crossover settings. The registry identifies the model as crossover, but the sequence, periods, washout, carryover assessment, and model handling are not reported in the registry record. It is therefore not possible to assess those features from the posted summaries alone.

The endpoint summaries list 16 observations for each treatment, while enrollment is reported as 17. This should not be read as evidence of the number of unique people contributing across conditions, nor does the record explain why the counts differ. The stated Full Analysis Sample definition requires randomization and at least one post-baseline efficacy measurement. Details of any missing observations, exclusion decisions, and imputation methods are not reported in the registry record.

How should dispersion be distinguished from precision?

General statistical explanation: standard deviation describes variability among observations, whereas a confidence interval for a mean difference describes uncertainty in the estimated contrast. The primary arm standard deviations are 16.84 and 8.29. The reported 95% confidence interval for the difference is 26.2 to 44.6. The first pair characterizes arm-level spread; the interval characterizes precision of the estimated comparison under its analysis assumptions. A confidence interval is not a prediction interval for an individual measurement.

Over-dispersion is general statistical language for variability greater than a model expects. If it occurs, standard errors based on an overly restrictive variance model can be too small, making intervals too narrow and tests too optimistic. The registry record does not report an over-dispersion assessment for this endpoint, and the continuous outcome summaries do not establish that over-dispersion was present. The broader point is that uncertainty estimates depend on assumptions about the data and design.

What do the secondary analyses add?

The registry lists seven secondary outcomes, including nitrogen absorption, fat excretion, stool weight, stool frequency, and day-based symptom measures. Posted analyses include continuous results for nitrogen absorption, total fat excretion, and total stool weight. These offer related measures of absorption and stool output. They are secondary to the primary endpoint and involve multiple outcomes. Unless multiplicity is addressed, repeated testing can increase the chance of at least one apparently notable result under a collection of null hypotheses. The multiplicity strategy is not reported in the registry record.

The interpretation of all these analyses also depends on the analysis populations, missing data, and crossover structure. The primary population definition is reported, but the record does not provide a detailed missing-data account or a complete statistical analysis plan. The posted estimates are informative summaries, while the limits of reporting constrain independent reconstruction of the sponsor's full analysis.

11. Confidence Intervals and Precision

The primary estimated mean difference is 35.4, and its 95% confidence interval runs from 26.2 to 44.6. The interval lies above zero and is relatively informative about the direction of the posted comparison: under the interval's assumptions, the data are compatible with a positive difference in the coefficient of fat absorption. The sponsor's reported p-value, p < 0.001, is consistent with that interval-based reading.

A confidence interval is not a statement that 95% of individual participants' values fall between its limits. It expresses uncertainty about an estimated population contrast under a specified analysis and its assumptions. The interval also does not include uncertainty about every possible source of bias, model misspecification, missing data, or limitations in the registry reporting. Its precision should therefore be judged together with the design and analysis information available.

The arm-level standard deviations are 16.84 for placebo and 8.29 for pancrelipase. These show that observed values varied within each treatment summary; they are not confidence limits. The primary endpoint summaries list 16 observations in each arm. Because the study is a crossover trial, the participant-level dependence and exact analysis structure matter for the uncertainty calculation. Those details are not reported in the registry record, so the posted interval cannot be independently reconstructed as a crossover-model interval from the information in the record.

The interval pertains to the short-term coefficient measured during the 5-day treatment period. It does not indicate precision for longer-term outcomes, for subgroups, or for any endpoint that was not measured or posted. The sample size and the unreported design and model details place important boundaries on how broadly the confidence interval can be generalized.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts. The calculations are illustrations based on the observed effect, not the trial's original design; the original design assumptions are not reported in the registry record.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is a stated fraction of the observed effect. The rows describe planning for 100%, 75%, and 50% of the observed effect. The 80% power column indicates the illustrated participants per arm for a design with an 80% chance of rejecting the null under the planning assumptions if the target effect were true. The 90% power column gives the corresponding illustration for a 90% chance.

These percentages describe a design property under specified assumptions, not the probability that the trial's conclusion is correct. The figures are not evidence about the probability that a treatment effect exists, and they do not represent the achieved power of the completed trial. This is not observed power.

The illustrations use the observed effect as their starting point. Because an observed estimate can be imprecise and may not represent the effect expected in a future study, the scenarios should be treated as planning aids rather than definitive sample-size recommendations. Smaller target effects require more participants under otherwise comparable assumptions. The registry record does not report that these illustrations were used to plan the trial, and they do not reconstruct its original sample-size justification.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 35.400; pooled standard deviation σ = 13.272.
2. n = 2 × (1.96 + 0.842)² × 13.272² / 35.400² = 2.2, rounded up to 3 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 35.4                      # observed difference in means
sigma <- 13.2723340072498                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(690820)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 3 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 4 (80% power), 6 (90% power)
 50% of observed effect: n per arm = 9 (80% power), 12 (90% power)
power.t.test: 3.5 
Simulated power at n = 3 per arm: 0.694 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor's own primary analysis is reported as an ANOVA comparing placebo and pancrelipase, with p < 0.001. The registry does not provide an ANOVA estimate or confidence interval, and it does not report the model terms or details of how the crossover design was represented. The reported sponsor result is therefore the trial's formal posted analysis, while the estimate and interval discussed in the re-calculation are simple unadjusted calculations from the posted summary statistics.

The unadjusted re-calculation gives a mean difference of 35.4, with a 95% confidence interval from 26.2 to 44.6 and p < 0.001. The sponsor's analysis and the re-calculation agree on the reported direction and the p-value threshold. The record marks no discrepancy between them. This agreement is reassuring as a consistency check, but it does not make their methods interchangeable: the sponsor reports an ANOVA, whereas the re-calculation uses the published group summaries and does not reproduce unreported model features.

For interpretation of the trial's own statistical analysis, the sponsor's reported analysis takes precedence. The re-calculation is useful for expressing the contrast and its approximate precision from the posted summaries, but it cannot replace a fully specified analysis of crossover data. The registry record does not report enough detail to verify how the sponsor handled sequence, period, or within-participant structure.

15. Multiplicity, Missing Data and Analysis Populations

The registry record reports the primary endpoint and multiple secondary outcomes, but a multiplicity strategy is not reported in the registry record. When several outcomes or statistical tests are examined, the chance of at least one small p-value under a collection of null hypotheses can increase. Statistical approaches can control that risk, but the record does not state whether any adjustment was planned or applied. The secondary p-values should therefore be read as reported, without assuming family-wise error control or another correction.

The primary analysis population is defined as randomized subjects with at least one post-baseline efficacy measurement. The record does not report how many randomized participants lacked a post-baseline efficacy measurement, the reasons for any missing measurements, or whether missing data were imputed. It also does not describe sensitivity analyses for missingness. Enrollment is 17, whereas the primary endpoint summaries list 16 observations for each treatment; the reason for that difference is not reported in the registry record.

The crossover design makes the analysis population and data structure particularly relevant. The record does not report the treatment sequence, period-specific counts, whether all participants contributed observations under both conditions, or how incomplete treatment sequences were handled. It also does not report how within-participant correlation, period effects, or carryover were addressed. These omissions limit independent evaluation of the sponsor's model and the precision estimates.

The record identifies the sponsor's primary method as ANOVA but does not provide a detailed statistical analysis plan, model terms, or interim-analysis information. The original sample-size justification is not reported in the registry record. These omissions do not negate the posted result, but they prevent a full assessment of prespecification, missing-data handling, and the statistical procedures used across the outcome family.

16. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse event figures show zero serious adverse events among 16 participants at risk in the placebo group and zero among 17 participants at risk in the pancrelipase group. The registry lists other adverse events affecting 9 of 16 participants at risk in the placebo group and 5 of 17 in the pancrelipase group. These are counts in the record, not estimates of comparative safety from a powered safety analysis.

The record does not list serious adverse event terms, and the death counts are not reported in the registry record. A zero count of serious adverse events in the posted groups does not establish that the risk is absent; uncommon events can be difficult to characterize in a small trial. The adverse-event figures should be read as descriptive reports for this study, not as proof that one treatment is safer than the other.

The registry record does not provide detailed event definitions, severity, timing, attribution, or exposure-adjusted rates in the summarized safety information. The crossover design and differing at-risk counts also mean that the figures should not be interpreted as if they were necessarily independent parallel groups. The safety information is limited to what is posted and does not cover risks beyond the recorded study period.

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

The posted primary result shows a higher mean coefficient of fat absorption for pancrelipase than for placebo during the stated 5-day treatment period. The mean difference is 35.4, with a 95% confidence interval from 26.2 to 44.6; the sponsor reports p < 0.001. This describes a short-term comparison on the study's primary absorption measure among the analyzed observations.

The result does not show that every participant had a higher value under pancrelipase, because group means do not describe each individual's response. It does not establish a lasting effect beyond the measurement period, and it does not show effects on outcomes that were not reported. Nor does a statistically small p-value establish the clinical importance of the observed difference. The record does not provide a threshold for a clinically meaningful change in this endpoint.

The result applies most directly to children aged 7–11 with pancreatic exocrine insufficiency due to cystic fibrosis who were represented in this study. It should not automatically be generalized to other ages, causes of pancreatic insufficiency, or populations with different characteristics. The registry record does not report subgroup analyses that would establish whether the result differs across participant groups.

The study's crossover structure can support comparisons across treatment conditions, but the registry does not report enough detail to evaluate sequence, period, washout, carryover, or the sponsor model's handling of correlated observations. The unadjusted re-calculation from summary data is not a replacement for the sponsor's reported ANOVA. These reporting limits affect how fully the analysis can be independently assessed.

The secondary endpoints generally show directions consistent with the primary absorption result, but they are additional outcomes and multiplicity handling is not reported. Safety counts are descriptive and arise from a small study. The record therefore supports a focused conclusion about the posted short-term primary endpoint, while leaving broader clinical interpretation, longer-term outcomes, and uncommon safety events uncertain.

18. Why This Trial Matters Statistically

This trial illustrates why the design and the endpoint need to be read together. The primary measure is a continuous coefficient of fat absorption, calculated from intake and excretion, and the study uses a crossover design. The reported mean contrast is readily interpretable on the endpoint's scale, but a crossover analysis also depends on how repeated observations within participants and treatment periods are modeled. Those details are not reported in the registry record.

The distinction between statistical evidence and precision is also important. The sponsor reports p < 0.001, while the posted estimate is accompanied by a 95% confidence interval from 26.2 to 44.6. The p-value addresses compatibility with a null model under analysis assumptions; the interval conveys uncertainty about the magnitude and direction of the estimated contrast. Neither resolves missing design details or establishes clinical importance.

The trial is small, with enrollment of 17 and primary endpoint summaries listing 16 observations for each treatment. Such counts make transparent reporting of analysis populations and missing data especially useful. The registry defines the primary analysis population, but does not explain the count difference or detail missing-data handling.

Finally, related secondary outcomes can strengthen the coherence of an interpretation without replacing the primary outcome or eliminating multiplicity concerns. Here, posted measures of nitrogen absorption and stool output generally align with the primary endpoint's direction, while the multiplicity strategy is not reported. The record is a useful example of how a clear statistical signal can coexist with limits on independent reconstruction, broader generalization, and interpretation of secondary evidence.

19. 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 limitations in the registry record concern design and analysis detail. Although the study is identified as a crossover trial, the treatment sequence, period structure, washout, and handling of carryover are not reported in the registry record. The sponsor's ANOVA is named, but its model terms and treatment of within-participant correlation are not described. This limits independent appraisal of whether the posted uncertainty estimates fully reflect the crossover structure.

The registry reports enrollment of 17 and endpoint summaries with 16 observations for each treatment, but does not explain the counts or provide a participant flow account. The primary analysis population definition is stated, yet reasons for missing measurements, handling of incomplete crossover data, imputation, and sensitivity analyses are not reported. The record also does not provide individual-level data for reanalysis.

The primary measurement covers a 5-day treatment period, with stools collected on 3 days. The registry does not report longer-term efficacy outcomes in the posted results. The small study and short timeframe limit conclusions about durability and less common safety events. The age range and condition specified for the trial also limit direct generalization beyond the studied population.

Multiplicity handling for the secondary outcomes is not reported in the registry record. The original sample-size justification, interim analyses, and detailed statistical analysis plan are also not reported. Finally, while the primary endpoint has a clear statistical result, the record does not provide a clinically meaningful threshold for interpreting the size of the difference. These limitations qualify interpretation without changing the values posted for the primary comparison.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study Investigating a Delayed-Release Pancrelipase in Patients With Pancreatic Exocrine Insufficiency (PEI) Due to Cystic Fibrosis (CF) — NCT00690820.
• Registry record last updated 2010-06-02; status last verified 2010-02.
• Results first posted 2010-03-10.
• 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.

23. Record Summary

This completed Phase 3 study was randomized, double-blind, multi-center, placebo-controlled, and crossover. It evaluated pancrelipase delayed-release 12,000 unit capsules in children aged 7–11 with pancreatic exocrine insufficiency due to cystic fibrosis. The registry lists Solvay Pharmaceuticals as sponsor, enrollment of 17, a start of 2008-06, and primary completion of 2008-12.

The primary outcome was the coefficient of fat absorption over 5 days. Mean values were 47.41 for placebo and 82.81 for pancrelipase; the reported mean difference was 35.4, with a 95% confidence interval from 26.2 to 44.6. The sponsor's ANOVA result was p < 0.001. Secondary results cover nitrogen absorption and stool measures, with safety counts also posted.

The primary analysis population is defined, but crossover model details, missing-data handling, multiplicity procedures, and the original sample-size justification are not reported in the registry record. The results describe a short-term endpoint comparison and should be interpreted within those reporting limits.