B. Lactis HN019 for Functional Constipation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for B. Lactis HN019 for Functional Constipation (NCT01463293), a randomized phase 3 study. The primary outcome is Whole Gut Transit Time.

2. Clinical Question

The study also listed gastrointestinal symptoms and other aspects of bowel function as secondary outcomes. These included patient-reported constipation symptoms and quality of life, bowel function, relief, movement frequency, stool consistency, product satisfaction and adverse events. The registry record lists nine outcome measures, but reports zero analyses. It therefore does not provide comparative results for these secondary outcomes either.

The clinical question is framed around a measurable transit endpoint and a dose-ranging comparison. The registry record does not establish whether either dose changed transit time, whether the doses differed from one another, or how any observed changes related to symptoms. Those questions require analysed outcome data, which are not reported in the registry record.

3. Trial Design

The registry describes a completed, randomized, parallel-group, phase 3 trial sponsored by Fonterra Research Centre. Enrollment was 224. The study record lists three arms: high-dose B. lactis HN019, low-dose B. lactis HN019 and placebo. The high-dose capsule contained 10 billion cfu and the low-dose capsule contained 1 billion cfu; the comparator was a placebo capsule.

The official title describes a double-blind, randomized, placebo-controlled dose-ranging trial. The registry’s masking field records quadruple masking. These labels describe masking in the record; further details about which people or roles were masked, and how masking was maintained, are not reported in the registry record. Random allocation and a parallel-group model are recorded, but the method used to generate the allocation sequence, allocation concealment procedures and any stratification are not reported.

The planned study period was four weeks. The primary endpoint description says whole gut transit time would be assessed using abdominal x-rays on days 0 and 28. The record gives a start of 2012-03 and a primary completion of 2013-03, and lists the study status as completed.

The primary-endpoint population note materially limits interpretation: only 39 out of the 224 enrolled subjects consumed the radio-opaque markers in line with the protocol. The record attributes the absence of further analyses to substantial protocol deviations and a lack of sufficient evaluable subjects. It does not report how participants were assigned among the arms for the primary analysis, how many were evaluable in each arm, or whether any other analysis populations were considered.

Other design details—including the planned statistical model, the intended treatment contrasts, the sample-size justification and any planned interim analyses—are not reported in the registry record. The record therefore supports a description of the design and the reason no further analyses were performed, but not a reconstruction of the intended analysis plan.

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: Only 39 out of the 224 enrolled subjects consumed the radio-opaque markers in line with the protocol. Because of the substantial number of protocol deviations and the lack of sufficient evaluable subjects, no further analyses of the study data were performed. The study appears not to have yielded evaluable data.

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 Whole Gut Transit Time, measured over 4 weeks.

Whole gut transit time is the primary endpoint. In general, transit time describes how long material takes to pass through the gastrointestinal tract. The registry says the endpoint was to be assessed using abdominal x-rays on days 0 and 28. Its population note refers to radio-opaque markers, which are visible on x-ray; in general, such markers can provide information about transit as they move through the gut.

A transit measure can serve as a physiological endpoint: it focuses on movement through the digestive tract rather than relying only on a participant’s report of symptoms. The trial also listed patient-reported and bowel-function outcomes, which address related but distinct aspects of constipation. A change in a physiological measure and a change in symptoms are not interchangeable; each requires its own analysis and interpretation.

The registry record does not specify the endpoint’s unit, the summary parameter, its dispersion measure, or the detailed rule for deriving a participant’s transit-time value from the x-rays. Those measurement and analysis details are not reported in the registry record. Although the planned assessment days are identified, the record does not provide analysed values at either time point or a comparison of change between groups.

Most importantly, the record says only 39 participants followed the marker procedure in line with the protocol and that there were not enough evaluable subjects for further analyses. No estimated treatment effect, uncertainty interval or statistical test for whole gut transit time is reported. The endpoint’s clinical and statistical role can be described, but its observed result cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

General explanation: randomization assigns participants to study groups using a chance-based process. When implemented as planned, it can reduce systematic differences between groups at the start of a trial, supporting a fair comparison. Randomization does not prevent later non-adherence, missing outcome data or protocol deviations, and it cannot make an outcome analysable when too few participants have usable measurements.

The registry records a randomized, parallel-group design with high-dose probiotic, low-dose probiotic and placebo arms. It does not report the sequence-generation method, allocation concealment, stratification factors or the planned statistical contrast. Those details are not reported in the registry record, so the exact allocation and analysis procedures cannot be reconstructed.

What does masking mean?

General explanation: masking aims to limit the influence of expectations or knowledge of treatment assignment on participant experience, clinical care, outcome assessment or analysis. The official title calls the trial double-blind, while the registry masking field records quadruple masking. The record does not explain which roles were masked or how the masking arrangements worked. Masking is a design feature; it does not substitute for complete outcome measurement or statistical analysis.

Why does evaluability matter?

General explanation: an outcome can be analysed only when there are usable observations and a defined method for comparing groups. Here, the primary endpoint depended on the marker procedure and x-ray assessment. The record says only 39 participants consumed the radio-opaque markers in line with the protocol and says the evaluable sample was insufficient for further analyses. It does not report an analysed primary-endpoint dataset or group-specific evaluability counts.

When measurements are unavailable or protocol procedures are not followed, the analysis can lose information and may no longer represent the randomized comparison as intended. If missingness or deviations differ between groups, the resulting comparison may also be biased. General statistical practice would examine the pattern, reasons and group distribution of missing or invalid measurements. The registry does not report those details, so it is not possible to assess whether such differences occurred or how they might affect an estimate.

How should estimates and uncertainty be read?

General explanation: an effect estimate expresses the size and direction of a comparison on the scale of the endpoint. A confidence interval gives a range of values compatible with the data and analysis assumptions, and helps communicate precision. A wide interval generally signals less precision than a narrow one, although interpretation depends on the endpoint and context. A p-value summarizes how unusual data at least as incompatible with a null hypothesis would be under that hypothesis and the test assumptions; it is not the probability that a treatment works or that the null hypothesis is true.

No primary-endpoint effect estimate, confidence interval or p-value is reported in the registry. Consequently, there is no basis for judging the size, direction, precision or statistical significance of a group contrast. The absence of a reported test is not a non-significant test result.

What is multiplicity?

General explanation: multiplicity arises when several hypotheses or outcomes are examined. With multiple tests, the chance of at least one apparently unusual result can increase if each test is treated as though it were the only test. Prespecified testing sequences, adjustment methods or a clear distinction between primary and exploratory outcomes can help readers interpret a collection of results. The registry lists a primary outcome and several secondary outcomes, but the multiplicity strategy is not reported in the registry record. Since no analyses are reported, there are no posted tests to evaluate for multiplicity.

What do planning calculations mean?

General explanation: sample-size planning uses assumptions about an effect and variability to describe the amount of information a future study might need for a chosen design. A planning illustration is not an observed treatment effect, and it does not measure the power achieved by a completed trial. The registry’s planning assumptions describe illustrations based on fractions of an observed effect, but an analysed primary effect is not reported. Any planning output should therefore be read as a hypothetical design calculation, not as evidence about what this trial demonstrated.

The record does not report the trial’s own sample-size justification, its assumed effect size, or its intended analysis model. Those aspects of the statistical plan are not reported in the registry record. The information available supports a description of the analysis shortfall, but not a full account of the methods that would have been applied had sufficient evaluable data been available.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies whole gut transit time as the primary endpoint and lists secondary outcomes covering symptoms, quality of life, bowel function, relief, movement frequency, stool consistency, product satisfaction and adverse-event frequency. It reports nine outcome measures and zero analyses. The multiplicity strategy—such as whether outcomes were tested in a hierarchy, whether any adjustment was planned, or which analyses were considered primary—is not reported in the registry record.

General explanation: multiplicity is relevant when several outcomes or comparisons are tested, because interpreting each test in isolation can overstate the strength of evidence across the whole set. A prespecified strategy helps clarify whether results are confirmatory or exploratory. In this case there are no reported outcome tests or effect estimates to interpret, so the multiplicity approach cannot be evaluated from posted results.

For the primary endpoint, the record says only 39 out of the 224 enrolled subjects consumed the radio-opaque markers in line with the protocol. It attributes the decision not to conduct further analyses to substantial protocol deviations and insufficient evaluable subjects. The number of missing or unusable outcomes by group, reasons for deviation, and any imputation or sensitivity analyses are not reported in the registry record.

The analysis population is also not defined beyond the primary-endpoint note. The record does not say whether an intention-to-treat, per-protocol or other population was used for any analysis. Since it reports that no further analyses were performed, there is no basis for assessing whether an analysis preserved randomized assignment or how missing outcomes were handled. These omissions prevent evaluation of both the statistical plan and the robustness of any comparative finding.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events affecting 0 participants in the high-dose probiotic group among 74 at risk, 0 in the low-dose probiotic group among 79 at risk, and 0 in the placebo group among 71 at risk. These are the serious-event figures recorded for the groups; they do not establish that no adverse event of any kind occurred.

For other adverse events, the record reports 17 affected participants among 74 at risk in the high-dose group, 16 among 79 at risk in the low-dose group, and 20 among 71 at risk in the placebo group. These are descriptive counts. The registry does not provide a comparative statistical analysis, so the counts should not be treated as evidence of a tested difference between groups.

Deaths are not reported in the registry record. The record also does not give further detail about the nature, timing, severity or relatedness of the other adverse events, nor does it describe how adverse events were collected or analysed. The serious-event counts and other-event counts address different categories and should not be combined. They also cannot resolve the limitations affecting the primary efficacy analysis.

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

The registry record establishes that a randomized, placebo-controlled dose-ranging study was conducted and completed, and that its planned primary endpoint was whole gut transit time. It also documents a major obstacle to analysing that endpoint: only 39 out of the 224 enrolled subjects consumed the radio-opaque markers in line with the protocol. The record says substantial protocol deviations and an insufficient number of evaluable subjects led to no further analyses.

As a result, the posted results do not quantify a difference between either probiotic dose and placebo, or between the two doses. There is no reported effect estimate, confidence interval or p-value for transit time. The listed secondary outcomes likewise have no comparative analyses in the registry. The available information therefore cannot establish the direction, size or precision of a treatment effect on the primary or secondary outcomes.

This absence of an analysed result should not be translated into a finding of no effect, equivalence or lack of statistical significance. Such conclusions require an analysis and an appropriate interpretation of its estimate and uncertainty. Nor does the record justify a claim that supplementation changed transit time or symptoms. It leaves those comparative questions unresolved.

The adverse-event information is descriptive and limited to group counts. The record reports no participants affected by serious adverse events in the listed groups, and reports other adverse-event counts, but it supplies no comparative safety analysis or details about event types, timing or relatedness. These data should be interpreted separately from efficacy and with those reporting limits in mind.

In general, a completed randomized trial can still produce an inconclusive record when the planned outcome cannot be measured or analysed adequately. The design describes how a comparison was intended to be made; it is not itself evidence of the comparison’s result. Here, the registry documents the study design and analysis failure, but does not provide a statistical estimate capable of answering the primary clinical question.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a study being completed and a primary outcome being successfully analysed. The registry records a randomized, parallel-group, placebo-controlled dose-ranging design, yet also says that substantial protocol deviations and too few evaluable participants prevented further analyses. A design can support a comparison only if the required outcome data are available in a form suitable for that comparison.

The marker procedure was central to assessing whole gut transit time. The registry’s note that only 39 participants followed that procedure in line with protocol shows why outcome-specific adherence matters: enrollment alone does not guarantee that the primary endpoint can be estimated. The record does not report the reasons for deviations, their distribution by treatment group, or whether they were associated with participant characteristics. Without these details, the potential impact on selection and bias cannot be determined.

The study also shows why a list of planned outcomes is not equivalent to a set of findings. Symptoms, quality of life and bowel-function measures may address different dimensions of constipation, but the registry reports zero analyses. No result for those outcomes can be inferred from their inclusion in the study record.

From a statistical perspective, the key limitation is not merely a missing p-value. There is no reported primary-endpoint estimate or uncertainty interval, so readers cannot assess effect size or precision. A result cannot be treated as null, negative or equivalent when no analysis is reported. The distinction is important for evidence synthesis: an unavailable comparative estimate cannot be combined or weighed in the same way as a completed analysis, though the underlying study and its limitations remain relevant to the record of research.

The case underscores the need to preserve clear outcome procedures and report the disposition of participants and measurements. Such reporting helps readers judge whether missing data could affect the randomized comparison and whether any analysis answers the intended question. The registry provides a reason for the lack of further analysis, but not enough detail to assess the consequences of the deviations.

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 most direct limitation is that the primary endpoint has no reported analysis. The registry states that only 39 out of the 224 enrolled subjects consumed the radio-opaque markers in line with the protocol and that the number of evaluable subjects was insufficient for further analyses. No group-specific evaluability information is reported, which prevents assessment of whether the problem was distributed evenly across the randomized arms.

The record does not explain the nature or timing of the protocol deviations, why participants did not consume the markers as directed, or whether these deviations were related to treatment assignment or outcome. It also does not describe the number of participants with missing x-rays, the rules for deriving transit time, or any attempt to address missing or invalid data. These details are not reported in the registry record.

Measurement and analysis specifications are sparse. The primary endpoint description gives the assessment method and timing, but the unit, parameter, dispersion measure and statistical model are not reported. The planned treatment contrasts and the trial’s own sample-size justification are also not reported. The registry’s masking field and the wording in the official title use different masking labels, while the operational details are not reported.

Finally, the registry lists secondary outcomes but provides no analyses for them. The multiplicity plan, analysis populations and handling of missing secondary data are not reported. Safety reporting is also limited: deaths are not reported in the registry record, and details such as adverse-event terms, timing and relatedness are absent. These limitations mean the available record supports a description of the study and its analysis shortfall, but not a comparative estimate of efficacy or a complete assessment of safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: B. Lactis HN019 for Functional Constipation — NCT01463293.
• Registry record last updated 2014-07-24; status last verified 2014-06.
• Results first posted 2014-07-24.
• 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

NCT01463293 is a completed, randomized, parallel-group, phase 3 dose-ranging trial sponsored by Fonterra Research Centre. It enrolled 224 adults with constipation and compared high-dose B. lactis HN019, low-dose B. lactis HN019 and placebo over four weeks. The primary endpoint was whole gut transit time, assessed using abdominal x-rays on days 0 and 28.

The registry reports that only 39 participants consumed the radio-opaque markers in line with the protocol. Due to substantial protocol deviations and insufficient evaluable subjects, no further analyses were performed. The record lists nine outcome measures and zero analyses; it reports no comparative estimate for the primary endpoint or secondary outcomes. Serious adverse-event figures are recorded by group, while deaths and further details of adverse events are not reported in the registry record.