Experience of Mutaflor Suspension Use in Preterm Infants for Immunity Improvement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Experience of Mutaflor Suspension Use in Preterm Infants for Immunity Improvement (NCT01540162), a registered phase not stated study. The primary outcome is The Number (Rate) of Patients With Acute Respiratory Infections.

2. Clinical Question

3. Trial Design

The registry describes an open-labelled, controlled, parallel-group study of Mutaflor in preterm infants. Its official title specifies treatment for 3 Weeks and a 1 Year Follow-up Period. The listed enrollment is 62, and the study status is COMPLETED. The sponsor is Odessa National Medical University. The recorded start is 2011-03 and primary completion is 2012-07.

Group I received Mutaflor suspension at 1 ml once a day during the first week of life and three times per week during the second and third week. Group II remained unexposed to Mutaflor. The groups therefore differ in exposure as described in the record. However, allocation is not stated, and the record explicitly cautions that the arms are not a like-for-like control comparison. The label “controlled” does not establish that assignment was randomized or that the groups were otherwise comparable.

The primary endpoint concerns acute respiratory infections in the first 28 days of life, while the title also identifies a longer follow-up period. The registry does not report the schedule or completeness of follow-up assessments, nor does it explain how the longer follow-up relates to each outcome. It lists three outcome measures and one analysis, but the listed secondary outcome titles repeat the acute respiratory infection outcome. Further outcome definitions and analysis details are not reported in the registry record.

The design information establishes the treatment schedule and the intended comparison, but it is not enough to assess whether group differences can be attributed to treatment. Without stated allocation procedures and reported baseline or adjusted analyses, differences between groups could reflect factors other than Mutaflor exposure. The registry record does not report a protocol-level account of those issues.

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

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 The Number (Rate) of Patients With Acute Respiratory Infections, measured over first 28 days of life.

The primary endpoint is the number of participants with acute respiratory infections during the first 28 days of life. The registry definition includes Acute Rhinitis, Acute Rhinopharyngitis, Acute Bronchitis, Acute Bronchiolitis and Pneumonia. It is a binary participant-level outcome in the sense that a participant is counted according to whether the defined event occurred; the registry describes its meaning as participants with an event.

In general, an endpoint of this kind can provide a clinically interpretable count of participants experiencing an event over a stated period. It does not, by itself, describe the timing, duration, severity or recurrence of infections. Those features would require additional definitions and results. The registry record does not report such details for this endpoint.

The outcome is relevant to the stated aim of observing immunity improvement, but the endpoint definition alone cannot establish improvement. Interpretation requires the group-specific results and a clearly described comparison, including how participants were assigned and analyzed. The primary-outcome counts, an effect estimate and its precision are not reported in the registry record. Consequently, the endpoint’s intended role can be described, but its observed result cannot be interpreted from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary outcome as a number of participants with an event. For statistical interpretation, this is a binary outcome at the participant level: each participant is classified according to whether the specified acute respiratory infection outcome occurred within the stated timeframe. The record’s definition names Acute Rhinitis, Acute Rhinopharyngitis, Acute Bronchitis, Acute Bronchiolitis and Pneumonia. The result would ordinarily be presented as group-specific event counts and a comparison between groups, but the primary-outcome results and comparative estimate are not reported in the registry record.

What does a confidence interval convey?

In general, a confidence interval expresses uncertainty around an estimated effect under the assumptions of the statistical method. A narrower interval indicates greater precision for that estimate; a wider interval indicates less precision. The interval is not a guarantee that the true effect lies within its limits, and it does not correct for bias from non-random allocation, incomplete follow-up or outcome measurement. No confidence interval for the primary endpoint is reported in the registry record.

What would a p-value answer?

In general, a p-value measures how compatible the observed data are with a specified null model, assuming the model and its assumptions apply. It does not quantify the probability that the null hypothesis is true, nor does it tell readers whether an effect is important. It also cannot compensate for a weak comparison design. The registry record does not report a p-value for the primary endpoint or describe a primary-outcome test.

Why does allocation matter?

In general, random allocation is intended to make treatment groups comparable with respect to both measured and unmeasured characteristics, on average. A controlled comparison without stated allocation procedures has a different interpretive status. Differences in prognosis, clinical care, or other characteristics may contribute to an observed group difference. Here, the registry says allocation is not stated and cautions that the arms are not a like-for-like control comparison. The record does not report enough detail to assess or adjust for potential confounding.

How should sample-size illustrations be understood?

The record describes planning illustrations computed from the observed effect, rather than from the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm for a specified power level. Such calculations are planning scenarios; they are not observed power and do not show that the study was adequately designed or that its result is precise. The registry record does not report a sample-size justification used to plan this trial, and no illustration values are stated in the information available for interpretation.

What can the event counts establish?

Counts describe how many participants were recorded as experiencing an event, within the listed at-risk groups. They are useful for understanding the scale of the reported observations, but counts alone do not provide an adjusted effect estimate or uncertainty interval. In general, sparse or unevenly distributed events can make estimates less precise. The registry does not report a primary-outcome estimate, its precision, or the method used for an inferential comparison. It also does not report whether an analysis adjusted for other factors.

Over-dispersion is a concern for some count outcomes when variability exceeds what a chosen count model expects. In general, it matters because a model that understates variability can produce overly narrow uncertainty intervals and misleading tests. The named endpoint is reported as participants with an event, rather than a recurrent-event count, and the registry record does not report a model or dispersion assessment. There is therefore no basis in the record for saying that an over-dispersion method was used or needed.

Finally, a statistical method is interpretable only alongside its population, endpoint definition, missing-data handling and analysis plan. Those details are not fully reported in the registry record. A numerical result, even if available, would need to be read in light of these design and reporting limitations rather than as an isolated measure of treatment effect.

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("Group I", "Group II")
n      <- c(30, 32)
events <- c(3, 14)
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  Group I  30  3  10.0  2.1  26.5  3.5  25.6  3.6  25.8
ARM  Group II  32  14  43.8  26.4  62.3  28.2  60.7  28.1  60.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and one analysis. The secondary outcome list repeats the title for acute respiratory infections. The additional outcome details and the relationship between the listed outcomes are not reported in the registry record. It does not state whether the repeated listing represents separate timepoints, duplicate entries or distinct analyses.

Multiplicity arises in general when several outcomes, timepoints or comparisons are tested. The more tests undertaken, the greater the chance that at least one result appears statistically notable by chance if no adjustment or prespecified hierarchy is used. A statistical plan may address this with a hierarchy, adjusted thresholds or other procedures, but the registry record does not report a multiplicity strategy. It also does not report whether the primary endpoint and analysis were prespecified in a protocol.

The record does not describe missing outcome data, exclusions, withdrawals, or the population included in the primary analysis. It therefore does not report whether all enrolled participants were analyzed, how missing outcomes were handled, or whether any sensitivity analyses were conducted. In general, missingness can affect interpretation when the likelihood of an outcome being observed is related to participant characteristics or outcome status. Without a description of the missing-data process and analysis population, the potential impact cannot be assessed.

The study title specifies a 1 Year Follow-up Period, but the registry information does not describe completeness of follow-up or how missing follow-up observations were handled. These omissions limit assessment of both the primary endpoint and any longer-term outcomes. They should be distinguished from evidence that a particular method was or was not used: the relevant procedures are simply not reported in the registry record.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute respiratory and gastrointestinal infections (62.5%).

The registry lists serious adverse events for Group I as 11 participants affected among 30 at risk, and for Group II as 20 participants affected among 32 at risk. For other adverse events, it lists 15 participants affected among 30 at risk in Group I and 22 among 32 at risk in Group II. These are descriptive entries; the record does not report a comparative safety estimate, confidence interval or statistical test.

The registry also lists Acute Respiratory and Gastrointestinal Infections as a top serious term, with 62.5%. The denominator and counting basis for this percentage are not reported in the registry record, so it cannot be connected confidently to the group-specific entries. The record does not report deaths in the provided serious-event entries.

In general, adverse-event counts should be read with their definitions, observation period, ascertainment method and analysis population. The registry record does not give enough detail to determine whether events were counted once per participant or by episode, how seriousness was defined, or whether follow-up exposure differed. The figures do not establish that an event was caused by treatment, nor do they provide a complete comparative safety assessment.

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

The registry record documents a study intended to observe Mutaflor use for immunity improvement in preterm newborn infants. It describes an exposed group and a group that remained unexposed, names acute respiratory infections during the first 28 days of life as the primary endpoint, and reports several adverse-event entries. The study status is COMPLETED. These registry entries characterize the study and its recorded outcomes, but they do not supply the primary comparison result.

The primary endpoint’s group-specific results, an effect estimate and its precision are not reported in the registry record. It is therefore not possible to determine from the record whether the number of participants with acute respiratory infections differed between groups, or how precisely any such difference was estimated. The adverse-event counts are descriptive and do not answer the primary efficacy question.

Even a reported difference would require cautious interpretation. Allocation is not stated, and the record warns that the groups are not a like-for-like control comparison. The registry does not report enough information about baseline characteristics, outcome ascertainment, missing data or adjusted analyses to establish that any group contrast would be attributable to Mutaflor rather than other differences.

In general, absence of a reported statistically significant result is not evidence that groups are equivalent; equivalence requires an appropriate design, a defined margin and an analysis that addresses that question. Conversely, a statistically notable result would not by itself establish clinical importance or overcome bias. No equivalence analysis, non-inferiority framework or primary-outcome inferential result is reported in the registry record.

The appropriate reading is therefore limited: the registry describes the intervention schedule, comparator exposure status, primary endpoint definition and recorded safety entries. It does not provide the information needed to conclude that Mutaflor improved immunity, changed infection occurrence, or had a particular comparative safety effect.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a stated research question and a reported estimate. The registry identifies a population, an intervention schedule, an unexposed comparison group and a primary endpoint with a defined observation period. Those details help readers understand what the study intended to examine.

At the same time, a treatment comparison depends on more than naming two groups. Allocation procedures are central to assessing whether groups can be compared fairly. Here, allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. That warning changes how any group difference should be interpreted, even if outcome counts are available elsewhere.

The record also illustrates why outcome definitions and outcome results must be distinguished. The primary endpoint is clearly named as participants with acute respiratory infections during the first 28 days of life, and the infection types are listed. Yet the primary results and their statistical uncertainty are not reported in the registry record. A precise definition cannot substitute for a numerical estimate, and a count without a suitable comparison cannot establish a treatment effect.

The safety entries reinforce a separate lesson: raw event counts are descriptive. Understanding their comparative meaning requires context about ascertainment, timing, event definitions and analysis. The record lists counts by group but does not report a comparative safety analysis or uncertainty estimates.

Finally, sample-size planning illustrations based on an observed effect are not evidence of observed power and do not replace a prospective design rationale. The registry record does not report the trial’s own sample-size justification or a full statistical analysis plan. Taken together, the study highlights the value of reporting allocation, analysis populations, missing-data handling, effect estimates and precision alongside endpoint definitions.

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.

Several trial-specific limitations affect interpretation. The registry describes the study as open-labelled, and allocation is not stated. It expressly warns that the arms are not a like-for-like control comparison. The record does not provide enough information about group comparability or adjustment for differences between groups. These points limit causal interpretation of any contrast.

The primary endpoint is defined, but its group results and inferential analysis are not reported in the registry record. The record also does not provide a confidence interval, p-value or effect estimate for the primary comparison. The listed adverse-event counts do not resolve the absence of an efficacy result.

Further details are not reported about eligibility criteria, baseline characteristics, outcome ascertainment, follow-up completeness, missing data, analysis populations, withdrawals, protocol deviations or sensitivity analyses. The title identifies a 1 Year Follow-up Period, but the registry information does not explain which outcomes were assessed across that period or how those assessments were handled analytically.

The record lists three outcome measures and one analysis, while the secondary outcome titles repeat the acute respiratory infection outcome. It does not explain the listing or report a multiplicity strategy. The statistical analysis plan and the trial’s own sample-size justification are not reported in the registry record. These omissions make it difficult to assess whether analyses followed prespecified methods or how much uncertainty surrounds the study’s findings.

These are reporting limitations in the registry record; they do not establish that a procedure was absent from the conduct of the study. They do mean that the available record cannot support a complete appraisal of the trial’s comparative results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Experience of Mutaflor Suspension Use in Preterm Infants for Immunity Improvement — NCT01540162.
• Registry record last updated 2015-09-10; status last verified 2015-08.
• Results first posted 2015-09-10.
• 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

NCT01540162 is a completed, open-labelled, controlled, parallel-group study sponsored by Odessa National Medical University. The record lists enrollment of 62, a start date of 2011-03 and primary completion in 2012-07. Its title describes Mutaflor treatment for 3 Weeks and a 1 Year Follow-up Period in preterm infants.

Group I received Mutaflor at 1 ml once a day during the first week of life and three times per week during the second and third week. Group II remained unexposed. Acute respiratory infections during the first 28 days of life are named as the primary endpoint. The registry defines the infections included in that outcome, but does not report its group results or a comparative statistical analysis. Allocation is not stated, and the record cautions that the groups are not a like-for-like control comparison.

Serious and other adverse-event counts are recorded by group, but a comparative safety analysis is not reported. Details on missing data, analysis populations, multiplicity and the statistical analysis plan are not reported in the registry record.