Lanreotide Autogel in the Symptomatic Treatment of Refractory Diarrhea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lanreotide Autogel in the Symptomatic Treatment of Refractory Diarrhea (NCT00891371), a na phase 2, phase 3 study. The primary outcome is Percentage of Patients Having Minimum Reduction of 50% or Normalization (≤3 Stools/24hours) in the Mean Number of Stools (Mean of Last 7 Days).

2. Clinical Question

The study asked whether lanreotide Autogel 120 mg was associated with a change in stool frequency among patients with refractory diarrhea. The primary endpoint was the percentage of patients meeting either of two criteria at Day 28: a reduction of at least 50% in the mean number of stools, or normalization to no more than 3 stools per 24 hours. The stool-frequency measure was based on the mean of the last 7 days.

The endpoint combines a relative reduction criterion with an absolute threshold. A patient could meet the endpoint by having a sufficiently large decrease from baseline, or by reaching the specified stool-frequency threshold. The registry record does not report how many patients met either criterion or the resulting percentage, so the magnitude and precision of the observed primary outcome cannot be assessed from this record.

The study also lists quality of life, stool consistency, percentage change in mean stool number, normalization frequency, and a related response criterion among its secondary outcomes. These measures address different aspects of symptoms and patient experience; they do not substitute for the unreported primary endpoint result.

3. Trial Design

The registry describes a Phase II–III, multicentre, prospective, exploratory, open-label study. It was completed and had an enrollment of 42. The listed condition is diarrhea, and the intervention is lanreotide Autogel 120 mg. The record gives a study start of 2009-07 and a primary completion date of 2012-08.

The design is single group, with no masking and allocation recorded as not applicable. No separate control arm is listed. Consequently, the study can describe outcomes among participants treated in the study, but its design does not provide a concurrent untreated or alternative-treatment group for a like-for-like comparison. Changes from baseline may be clinically descriptive, but they cannot by themselves distinguish a treatment-associated change from other influences over time.

The study is described as exploratory and open label. Open-label means that treatment assignment was not masked; in this single-group record there is no listed allocation to conceal. Awareness of treatment can affect reporting or assessment of subjective outcomes, including symptoms and quality of life. The registry record does not describe procedures used to limit such influences, so their handling is not reported in the registry record.

The enrollment figure is a study-level record and should not be assumed to be the denominator for every outcome. The primary population has an additional data-availability condition: treated subjects needed at least 3 days of primary efficacy variable data in both baseline and post-baseline periods. The record lists 36 people at risk for the adverse-event summaries, which is a different reported denominator. The registry does not explain the difference between these population counts.

The listed primary endpoint is assessed at Day 28 and uses stool frequency summarized as the mean of the last 7 days. The registry record does not report treatment duration beyond what is needed to identify that endpoint time point, details of visit schedules, eligibility criteria, dosing frequency, sample-size justification, or a statistical analysis plan. These details should not be inferred from the study title or its phase designation.

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.

Pre-assignment

Reasons for not completing this period:

Treatment

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to Treat (ITT) Population \[All treated subjects with at least 3 Days of available primary efficacy variable data for both Baseline and post Baseline periods\]

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: The Safety population was defined as all subjects who received at least one injection of the study medication.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients Having Minimum Reduction of 50% or Normalization (≤3 Stools/24hours) in the Mean Number of Stools (Mean of Last 7 Days), measured over Day 28.

The primary endpoint is a binary response measure: whether each patient met at least one of two stool-frequency criteria at Day 28. The criteria are a reduction of at least 50% in the mean number of stools, or normalization to no more than 3 stools per 24 hours. The frequency measure uses the mean of the last 7 days. The reported outcome is intended to be a percentage of patients meeting the combined criterion, rather than a mean change in stool count.

Using a combined response definition can capture more than one pattern of improvement. A patient whose stool frequency decreases substantially may qualify even if the normalization threshold is not reached; a patient who reaches the threshold may qualify without meeting the relative-reduction criterion. These are features of the endpoint definition, not evidence that either outcome occurred.

In general, a binary endpoint is straightforward to interpret as the proportion meeting a prespecified condition, but it discards detail about the size of changes among people who do not meet the response threshold. Results can also depend on the precise definition of response, the measurement window, and the availability of baseline and follow-up data. The registry record does not report the observed percentage, its uncertainty interval, or details of how missing measurements were handled beyond the stated population requirement. Therefore, the primary response rate and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint count?

The primary endpoint is a percentage: the proportion of eligible participants who met a response condition at Day 28. The condition is met by a reduction of at least 50% in mean stool number, or by normalization to no more than 3 stools per 24 hours. The frequency summary uses the mean of the last 7 days. Since the record does not give the observed percentage, there is no estimate to interpret for this endpoint.

In general, a binary response endpoint turns an underlying measurement into a yes-or-no classification. This can make the clinical meaning of a result accessible, but it also means that people just on opposite sides of a threshold are classified differently even if their measurements are similar. It also hides variation among responders and among nonresponders. Those are general properties of threshold-based outcomes, not evidence about the participants in this study.

Why does the denominator matter?

A percentage depends on both the number meeting the response rule and the number included in the analysis. The primary population is described as treated subjects with at least 3 days of available primary efficacy variable data for both baseline and post-baseline periods. This condition defines who can contribute under that population description; it does not provide the actual endpoint denominator or explain how participants without adequate data were otherwise handled.

The registry separately reports 36 people at risk for the adverse-event summaries, while the study enrollment is 42. These counts relate to different measures and cannot be substituted for the primary endpoint denominator. The reason for the difference is not reported in the registry record.

What can an uncontrolled design establish?

This study is single group, with allocation not applicable and no separate comparator listed. A single-group design can describe outcomes over time within the treated group. In general, however, an observed before-and-after change does not isolate the effect of treatment, because there is no concurrent group to represent what might have happened without the intervention or under another intervention. That limitation applies even when the change is measured carefully.

The record describes the study as open label. In general, knowledge of treatment can affect symptom reporting, attention to symptoms, or assessment. The extent of any such influence cannot be determined from this record, which does not report methods for masking outcome assessment or otherwise addressing potential measurement effects.

How should uncertainty be understood?

For a percentage, uncertainty reflects how much the estimate might vary because it is based on a limited set of observations. A confidence interval is a statistical range associated with an estimate under a specified method and assumptions. It helps readers distinguish a precise estimate from one compatible with a broad range of possible values. The registry record does not report a confidence interval for the primary endpoint, so precision cannot be judged.

A significance test, when used, evaluates data against a specified statistical hypothesis under a model. A p-value does not measure the probability that a treatment works, nor does it describe the size or clinical importance of an effect. No primary p-value or testing procedure is reported in the registry record. It would therefore be inappropriate to infer statistical significance from the study title, design, or endpoint definition.

What do the planning assumptions mean?

The record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial itself used that design. The actual trial is recorded as single group, so an equal-allocation two-arm scenario is not a description of its design.

In general, sample-size planning asks how many participants would be needed under assumed conditions to have a chosen probability of detecting an effect if that effect were present. Such an illustration is sensitive to the assumed effect, variability, analysis method, and design. It is not observed power, and it does not establish the probability that a result is true. The registry record does not report a sample-size justification for the trial’s own design. The primary result itself is not reported in the registry record, so no trial-specific interpretation of the observed endpoint estimate can be made from the record.

Why might count data need special care?

Stool frequency is a count measure. In general, count outcomes can have a variance that differs from the mean, and observations may vary more than a simple model assumes. Over-dispersion refers to variability greater than expected under a basic count model; if present and ignored, uncertainty estimates can be too small. Whether over-dispersion occurred in this study, and whether any model for count data was used, are not reported in the registry record. The stated primary endpoint is a binary response percentage, so any analysis of the underlying counts would be a distinct analytic question.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary stool-frequency response and secondary measures involving quality of life, stool consistency, stool counts, normalization, and a related response criterion. Considering multiple outcomes can create a multiplicity issue: in general, the more statistical tests conducted, the greater the chance of at least one apparently notable result arising by chance if no adjustment or prespecified hierarchy is used. Whether any multiplicity adjustment, outcome hierarchy, or selective reporting strategy was planned is not reported in the registry record.

The record lists zero analyses. It does not provide analysis-specific estimates, uncertainty intervals, p-values, or a statistical plan. Therefore, it is not possible to determine which outcomes were formally tested, whether analyses were prespecified, or whether any adjustment for multiple comparisons was used. The fact that several outcomes are listed does not establish that they were all analyzed or that any particular statistical procedure was applied.

The primary population definition requires treated subjects to have at least 3 days of available primary efficacy variable data for both baseline and post-baseline periods. This is the reported availability condition. The registry record does not explain how missing measurements were handled, whether additional imputation or sensitivity analyses were used, or how participants who did not meet the data requirement were represented in analyses. A minimum-data rule alone does not describe the full missing-data strategy.

In general, missingness can affect an estimate if the people with available measurements differ systematically from those without them. The direction and size of any effect depend on the missingness pattern and the analysis assumptions. There is not enough information in the registry record to assess those issues for this trial.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pancytopenia (2.8%), steatorrhoea (2.8%), bronchopneumonia (2.8%), pneumonia (2.8%), hypovolaemia (2.8%).

The registry lists adverse-event summaries for the Lanreotide Autogel 120 mg group, with 36 people at risk in each of the reported serious and other adverse-event summaries. Five were reported as affected by serious adverse events, and 30 were reported as affected by other adverse events. These are separate categories in the record; they should not be added together or interpreted as necessarily involving different people.

The record lists pancytopenia, steatorrhoea, bronchopneumonia, pneumonia, hypovolaemia, and syncope among the most frequent serious-event terms, each reported as 2.8%. These terms describe reported events, not proof that the intervention caused them. The registry record does not provide further detail about event timing, severity beyond the serious classification, relationship assessment, or patient-level overlap among terms.

Deaths are not reported in the registry record. That should not be read as confirmation that no deaths occurred. The record also does not provide a comparator group for interpreting these adverse-event counts. In general, adverse-event counts describe events observed and recorded in a study; causal attribution requires careful assessment and cannot be established from a count alone.

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

The record describes a prospective, open-label, single-group study of lanreotide Autogel 120 mg in patients with refractory diarrhea. It specifies a primary endpoint based on stool-frequency response at Day 28, defined by at least a 50% reduction in mean stool number or normalization to no more than 3 stools per 24 hours. It also lists several secondary outcomes and adverse-event summaries.

However, the registry record does not report the observed primary endpoint percentage or its uncertainty. Without those results, the size and precision of the primary response estimate cannot be assessed. The record also does not report numerical results for the listed secondary outcomes or describe formal analyses. The endpoint definition identifies what was intended to be measured; it is not itself a result.

The single-group design also limits what any within-group outcome could establish. In general, change from baseline does not provide a controlled estimate of what would have happened without the intervention or with another intervention. The open-label design is relevant to interpretation of symptom and quality-of-life measures, since treatment awareness can influence reporting or assessment. The record does not describe methods to address those issues.

The adverse-event figures describe events recorded in the study group, with the denominators and affected counts stated in the registry. They do not by themselves establish that the intervention caused an event, and the absence of a reported death count cannot be interpreted as evidence that there were no deaths. The record does not provide a comparator-based safety assessment.

Overall, the registry record supplies design and endpoint definitions, but it does not supply the numerical primary efficacy result or a reported statistical analysis of it. It therefore cannot support a conclusion about the magnitude, precision, or comparative effect of treatment in this trial. These limitations concern what can be concluded from this registry record, not what might be available from other sources.

13. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported result are both necessary for statistical interpretation. The registry specifies a patient-level response rule for stool frequency at Day 28, including the measurement window and the two ways a participant could qualify. That definition makes the intended outcome understandable, but without the observed percentage and its uncertainty, readers cannot evaluate how often the response occurred or how precisely it was estimated.

It also illustrates the distinction between describing change and estimating a comparative effect. A single-group study can record outcomes among treated participants, but it has no listed concurrent control group to provide a direct comparison. In general, the absence of such a comparator makes causal interpretation more limited, even when a before-and-after measure is available.

The population definition and adverse-event denominators show why analysis populations should be read carefully. The study enrollment, the primary endpoint population rule, and the adverse-event risk set are different record elements. They should not be treated as though they necessarily describe the same participants or denominator. The registry does not explain how these populations relate to each other.

Finally, the record lists multiple outcomes but does not report analyses or a statistical plan. This prevents assessment of how the outcomes were prioritized, how missing data were handled, or whether multiplicity was considered. These are not minor technical details: they affect how confidently readers can interpret reported findings. In this case, because the primary numerical result is not reported in the registry record, the most important statistical lesson is the boundary between a well-described measurement and evidence about its observed value.

14. 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 registry record leaves important trial-specific details unreported. It does not give the observed primary endpoint percentage, an uncertainty interval, a test result, or the denominator used for that endpoint. It also does not report numerical results for the listed secondary outcomes. As a result, the efficacy outcome cannot be quantitatively interpreted from this record.

The single-group, open-label design has no listed concurrent comparator and does not mask treatment. These features limit comparative and causal interpretation. The record does not report whether outcome assessment was independent or whether procedures were used to reduce possible effects of treatment awareness on symptom reporting.

The primary population definition requires a minimum availability of primary efficacy data in both baseline and post-baseline periods, but the registry does not describe the broader missing-data strategy. It does not state how participants failing that data requirement were handled, whether imputation was used, or whether sensitivity analyses were conducted. The relationship between the enrollment of 42, the primary analysis population, and the adverse-event risk set of 36 is also not explained.

The record lists multiple outcomes but does not report a statistical analysis plan, an outcome hierarchy, or a multiplicity approach. It also does not report the trial’s sample-size justification. The planning assumptions described in the record do not substitute for a documented justification for this single-group study design.

Finally, safety information is limited to the reported counts and event terms. The registry record does not provide the detail needed to assess event timing, individual overlap, attribution, or comparative risk. Deaths are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Lanreotide Autogel in the Symptomatic Treatment of Refractory Diarrhea — NCT00891371.
• Registry record last updated 2019-01-15; status last verified 2019-01.
• Results first posted 2015-09-29.
• 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.

18. Record Summary

NCT00891371 is a completed Phase II–III, multicentre, prospective, exploratory, open-label, single-group study of lanreotide Autogel 120 mg for refractory diarrhea. The registry lists an enrollment of 42 and identifies stool-frequency response at Day 28 as the primary endpoint. Response was defined as at least a 50% reduction in mean stool number or normalization to no more than 3 stools per 24 hours, using the mean of the last 7 days.

The registry record does not report the observed primary endpoint result, its precision, or numerical results for the listed secondary outcomes. It lists adverse-event counts for a risk set of 36, including five affected by serious adverse events and 30 affected by other adverse events. The record has no separate comparator group, and deaths are not reported in the registry record.