Special Investigation (All Cases) of LipaCreon in Patients With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Special Investigation (All Cases) of LipaCreon in Patients With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis (NCT01427712), a registered phase not stated study. The primary outcome is Number of Patients With Adverse Drug Reaction.

2. Clinical Question

This is a descriptive safety and effectiveness investigation, rather than a controlled estimate of treatment effect. The central statistical question is how many patients in the analyzed group experienced the specified outcomes, and how much uncertainty surrounds those counts. Because the registry does not report a control arm, outcomes cannot be compared with what would have happened to similar patients without LipaCreon or under another treatment. The study also records nutritional measures and symptoms related to pancreatic exocrine insufficiency as secondary outcomes, but the registry record does not report numerical results for those measures.

3. Trial Design

The registry identifies this as a completed special investigation of LipaCreon in patients with pancreatic exocrine insufficiency due to cystic fibrosis. It reports total enrollment of 24 and an intervention of pancrelipase. The study start is recorded as 2011-08, and primary completion as 2018-03. The record describes an observational period of approximately 7 years in study completers, measured from the start of dosing to the end of observation or discontinuation.

The regimen description says that pancrelipase 600 mg/dose was generally taken orally immediately after a meal, 3 times a day. It also says that dosage was adjusted appropriately according to the patient's condition. The record does not provide further details about the dose-adjustment criteria or how treatment adherence was assessed.

Survey forms were collected for 21 patients. The record states that none of these patients was excluded from either the safety or efficacy analysis, so both analysis sets included 21 patients. The relationship between the total enrollment of 24 and the 21 collected forms is not explained in the registry record. Reasons that forms were not collected for other enrolled patients are not reported in the registry record.

The allocation method is not stated, and the study is not a randomized comparison. No separate control group is described. As a result, the observed outcomes are within-group descriptions and cannot establish a comparative treatment effect. The registry lists 15 outcome measures, including nutritional endpoints such as BMI, serum total protein, albumin, total cholesterol, triglycerides, and haemoglobin, as well as steatorrhoea and frequency of bowel movements. Numerical results for these secondary outcomes are not reported in the registry record.

The registry record does not report a sample-size justification, a detailed statistical analysis plan, or the criteria used to define the observation period for each participant. It also does not report interim analyses. These omissions limit what can be inferred about the study's planned precision and its analytic procedures.

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: Among the 21 patients from whom the survey forms were collected, no patient was excluded from the safety analysis or efficacy analysis, and both the safety analysis set and the efficacy analysis set included 21 patients.

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: 21 are effective number for safety analysis.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Adverse Drug Reaction, measured over From the start of Lipacreon treatment to the end of the observation period or discontinuation. Approximately 7 years in the study completers (From date of dosage start, up to 7 years)..

The primary endpoint is the number of patients with an adverse drug reaction. The registry defines an adverse event broadly: an unfavourable or unintended disease, symptom, sign, or abnormal laboratory finding in a patient who received LipaCreon, whether or not the event was considered related to the medicinal product. An event was treated as an adverse drug reaction if its relationship with LipaCreon could not be ruled out.

The registry describes two considerations for judging a relationship: timing between use of the medicinal product and onset of the event, including relapse after readministration, and the presence of other potential factors. This is an attribution judgment, not simply a count of every adverse event. Consequently, an adverse event and an adverse drug reaction are not interchangeable concepts in the endpoint definition.

A count of affected patients is useful for describing how often the defined event occurred in the safety population. It is particularly direct for a small, non-randomized investigation, where a complex comparative estimate is not available. However, a count alone does not communicate the full range of possible event risk in a wider population, nor does it establish that treatment caused an event. Interpretation also depends on the duration and completeness of observation, the consistency of event ascertainment, and the criteria used to judge relatedness. The registry describes observation through the end of the period or discontinuation, with approximately 7 years in study completers.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The principal statistical task for a count endpoint is to identify how many analyzed participants experienced the event and how many were considered at risk of experiencing it. A participant-level count is different from an episode count: one person may have more than one episode, but a binary summary ordinarily records whether each person had at least one qualifying event. The registry describes the outcomes as participants with an event, in counts. The posted adverse-event figures therefore need to be read according to their stated affected-participant and at-risk categories, not as a measure of event duration or episode burden.

What does a count describe?

A count is a direct description of the analyzed group. To generalize beyond that group, readers also need to consider the uncertainty inherent in observing only a limited number of patients. In general, a confidence interval expresses uncertainty about a population quantity under specified statistical assumptions. It does not show that every value in the interval is equally plausible, and it does not account automatically for biases such as incomplete follow-up or inaccurate event classification. The registry record does not report a confidence interval for the primary endpoint.

For this investigation, the denominator matters. The safety and efficacy analysis sets each included 21 patients, while total enrollment was 24. A count without its denominator is difficult to interpret; even with a denominator, it describes this analysis set rather than necessarily describing every enrolled patient or the broader population. The reason for the difference between enrollment and the analyzed sets is not reported in the registry record.

Why does the comparison design matter?

Random assignment, when used, can help balance measured and unmeasured participant characteristics between groups. No randomized allocation is reported for this investigation, and no control group is described. The registry therefore supports a within-group description, not a randomized comparison. A count observed during LipaCreon treatment cannot on its own distinguish treatment-related events from events arising from cystic fibrosis, other health conditions, other care, or background occurrence.

In general, confounding is a concern when factors related to both treatment and outcome can influence the observed association. In an uncontrolled investigation, there is no concurrent comparison group to help account for such factors. Statistical adjustment can sometimes address measured characteristics, but the registry record reports 0 analyses and does not describe an adjusted analysis. It would be inappropriate to infer an adjustment method or a causal estimate from the available record.

How should event attribution be understood?

The primary endpoint is not every adverse event; it is the number of patients with an adverse drug reaction under the registry's definition. The record says that an adverse event was considered an adverse drug reaction when a relationship with LipaCreon could not be ruled out. It also describes temporal association and other potential factors as considerations. This classification involves a judgment about relatedness. A reported adverse drug reaction count would therefore depend both on which events were observed and on how their relationships to treatment were assessed.

The serious adverse event terms are a separate descriptive safety summary. Seriousness and relatedness are distinct concepts: an event can be serious without being judged treatment-related, and a related event need not be serious. The record does not give event-level judgments connecting each listed serious term to LipaCreon. As a result, the serious-event listings should not be treated as the primary adverse drug reaction outcome.

What do the planning illustrations mean?

In general, sample-size planning asks how many participants a future study might need to detect a chosen effect under specified assumptions. The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such calculations are conditional on assumptions about the target effect, variability, allocation, and analysis. They are not measurements of the completed study's power and should not be read as observed results.

The record's planning illustrations use fractions of the observed effect, and distinguish calculations for participants per arm from total-event calculations in time-to-event settings. These are design scenarios, not a retrospective statement of what the study was powered to detect. The investigation itself is not reported as a randomized two-arm study. A sample-size justification for the actual study is not reported in the registry record.

What can be concluded from unreported analyses?

The registry lists 15 outcome measures and 0 analyses. The absence of reported analyses means that no inferential results for those outcomes can be described from the record. This does not establish that no analyses were undertaken outside the registry; it means their methods and results are not reported in the registry record. There are no posted primary endpoint confidence intervals or p-values to interpret. General statistical methods cannot replace those missing results, and the counts should remain descriptive.

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("LipaCreon")
n      <- c(21)
events <- c(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  LipaCreon  21  1  4.8  0.1  23.8  0.8  22.7  1.1  22.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary adverse drug reaction endpoint and secondary measures of nutrition and symptoms. When a study evaluates multiple outcomes, the chance of at least one apparently notable result can rise if each is tested independently without accounting for multiplicity. In general, multiplicity procedures may adjust significance thresholds or otherwise control the interpretation of a family of tests. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which outcomes would be treated as confirmatory.

The registry reports 0 analyses. It therefore does not provide statistical results for the listed secondary outcomes, and it does not report p-values or confidence intervals for the primary endpoint. The statistical analysis plan, including any approach to multiplicity, is not reported in the registry record. There is no basis to infer whether analyses were adjusted, exploratory, or omitted from registry reporting.

Missing-data handling is also not described. The registry states that 21 patients with collected survey forms were included in both the safety and efficacy analysis sets, with no exclusions from those sets. It does not explain the relationship between those 21 patients and total enrollment of 24, describe missing measurements within the included patients, or report imputation or sensitivity analyses. Missing outcomes can affect estimates if the likelihood of missingness is related to participant condition or outcome; this is a general statistical concern, not a claim about what occurred in this study.

The record also does not report whether all participants completed the intended observation period, apart from describing approximately 7 years in study completers and observation through discontinuation or the end of observation. The completeness and timing of individual follow-up are not reported in the registry record. Those gaps limit assessment of how much opportunity each participant had for outcome ascertainment.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pharyngitis (4.8%), pneumonia (4.8%), enteritis infectious (4.8%), dehydration (4.8%), hyperkalaemia (4.8%).

The safety summary records 21 patients at risk for serious events and 4 in the serious-event affected count. It also records 21 at risk and 4 in the other-event affected count. These are participant counts in the posted summary, not a comparison between treatment groups. The registry lists Pharyngitis, Pneumonia, Enteritis infectious, Dehydration, Hyperkalaemia, and Haematochezia among the serious adverse event terms, with 4.8% reported for each term.

Each term's reported percentage is a descriptive registry figure. The record does not explain whether a participant could contribute to more than one term, the number of episodes for each term, or the event-level timing. The listed terms should not be added together or interpreted as a count of unique patients. The registry also records 3 deaths, but does not report causes or treatment relationships. The serious-event counts and terms do not establish that LipaCreon caused any event, and they are not interchangeable with the primary endpoint, which concerns adverse drug reactions under a separate relatedness definition.

The record does not give a concurrent comparator or a confidence interval for these safety counts. Consequently, the figures describe what was recorded in the analyzed group but do not provide a comparative estimate of risk or a precise estimate for a wider population.

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

The posted record documents a completed special investigation with 24 enrolled patients and 21 patients included in each of the safety and efficacy analysis sets. It describes LipaCreon use and reports adverse-event summary counts, serious-event terms, and deaths. These details are useful for understanding what the investigation collected and what safety events were recorded in the analyzed group.

The record does not report a numerical result for the primary endpoint, the number of patients with an adverse drug reaction. It also does not report numerical results for the listed nutritional and symptom outcomes. Therefore, no primary endpoint frequency or secondary-outcome change can be stated from the registry record. The serious adverse event count and terms are separate safety information and should not be substituted for the primary endpoint.

The investigation does not describe a randomized comparison or a control group. Its observations cannot establish whether the treatment changed event risk, nutrition, symptoms, or other outcomes relative to another treatment or no treatment. They also cannot establish that a particular adverse event was caused by LipaCreon. Relatedness is part of the primary endpoint definition, but the registry does not provide the primary result or event-level attribution details.

In general, observed data from a small group can be informative about events that occurred during the study, while still leaving considerable uncertainty about how often those events would occur in a broader population. Interpretation depends on complete follow-up, outcome definitions, ascertainment, and analysis methods. Several of these details are not reported in the registry record. The most defensible reading is thus descriptive: the registry records the study population and selected safety information, but does not provide enough reported outcome analysis for a comparative or causal conclusion.

14. Why This Trial Matters Statistically

This investigation is statistically relevant because it illustrates the difference between collecting safety information and reporting an estimable treatment effect. The registry describes a long observation period in study completers, an adverse drug reaction endpoint, and a set of nutritional and symptom outcomes. It also reports 21 patients in the safety and efficacy analysis sets. These features establish the broad scope of the data collection, while the lack of a comparator constrains the questions the data can answer.

For biostatistical interpretation, a count should be connected to its endpoint definition, denominator, and observation period. Here, the primary outcome is based on adverse-event relatedness, while the serious adverse event terms are a separate safety summary. Keeping these concepts distinct prevents a serious event from being assumed to be treatment-related and prevents all adverse events from being treated as adverse drug reactions.

The record also makes visible how incomplete reporting can limit interpretation. Although 15 outcome measures are listed, 0 analyses are reported. The primary endpoint's numerical result, uncertainty interval, and inferential analysis are not reported in the registry record. Nor are the sample-size justification, missing-data methods, or multiplicity procedures. In general, these details help readers assess precision, selection, and the risk of overinterpreting selected findings.

Planning illustrations can be useful for thinking about a future comparison, but their assumptions do not turn an uncontrolled investigation into a comparative trial. The stated two-sided significance level of 0.05, equal allocation, and normal approximation are planning conditions, not evidence that the completed study had a particular observed power. The main statistical lesson is that design and reporting define the limits of inference: descriptive safety counts can be reported as such, while comparative and causal questions require information the registry does not provide.

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 central limitation is the absence of a reported control group and the lack of randomized allocation. The registry explicitly describes a non-randomized comparison, with allocation not stated. Accordingly, observed outcomes cannot be interpreted as differences caused by LipaCreon. Patient characteristics, the underlying condition, other care, and changes over time may all be relevant to observed outcomes, but the registry does not provide information that permits their effects to be separated.

The total enrollment was 24, while the safety and efficacy analysis sets each included 21 patients. The registry does not explain why survey forms were not collected for all enrolled patients. It does not report individual follow-up completeness, reasons for discontinuation, or missing outcome measurements among those analyzed. These omissions limit assessment of potential selection and missing-data effects.

The primary endpoint is defined through an assessment of whether a relationship to LipaCreon could be ruled out. The record describes general criteria involving timing and other possible factors, but does not report detailed adjudication procedures, assessor blinding, or event-level relatedness judgments. The numerical primary endpoint result is also not reported in the registry record. The serious-event terms and death count are reported without causes, timing, or treatment-relatedness details.

Although 15 outcome measures are listed, the registry reports 0 analyses and does not include numerical results for the secondary outcomes. A statistical analysis plan, sample-size justification, multiplicity approach, interim analyses, and missing-data methods are not reported in the registry record. These gaps make it difficult to evaluate the intended inferential framework, the precision of estimates, and whether outcome reporting followed prespecified priorities.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Special Investigation (All Cases) of LipaCreon in Patients With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis — NCT01427712.
• Registry record last updated 2022-06-10; status last verified 2022-03.
• 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

The registry describes a completed special investigation of LipaCreon in patients with pancreatic exocrine insufficiency due to cystic fibrosis. Total enrollment was 24, and 21 patients were included in both the safety and efficacy analysis sets. The intervention was pancrelipase, generally administered orally after meals, with dose adjustments according to patient condition.

The primary endpoint was the number of patients with an adverse drug reaction during treatment and observation or until discontinuation. The registry lists 15 outcome measures but reports 0 analyses. The primary endpoint result and numerical results for the secondary outcomes are not reported in the registry record.

The adverse-event summary records 4 in the serious-event affected count and 4 in the other-event affected count, with 21 at risk for each. Six serious adverse event terms are listed at 4.8% each, and 3 deaths are recorded. The study has no reported control group or randomized allocation, so the safety information is descriptive rather than a comparative treatment estimate. Important details about missing data, multiplicity, and the statistical analysis plan are not reported in the registry record.