Symbiofilm Trial in Allergic Kids (SYMBIOFILM-TAK): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Symbiofilm Trial in Allergic Kids (SYMBIOFILM-TAK) (NCT05034328), a registered phase not stated study. The primary outcome is AUC (Area Under Curve) of the Wisconsin Upper Respiratory Symptoms Survey for Kids (WURSS-K) During the 10-day Treatment Period.

2. Clinical Question

3. Trial Design

SYMBIOFILM-TAK (NCT05034328) is recorded as a completed, non-interventional post-market clinical investigation sponsored by Lallemand Pharma AG. The registry lists an enrollment of 186 and gives a start date of 2022-02-14 and a primary completion date of 2022-11-03. The stated aim was to assess Healsea® Children in a real-life setting among children with perennial allergy who are more prone to common cold.

The registry describes two treatment groups: children receiving Healsea® Children on top of conventional common-cold therapies as needed, and children receiving conventional therapies as needed, with nasal irrigation excluded. Because the investigation was non-interventional and allocation is not stated, these groups should not be treated as randomized arms. The registry explicitly cautions that they are not a like-for-like control comparison. Group differences could reflect factors other than the spray; the record does not provide enough information to identify or adjust for those factors.

The primary outcome was a continuous measure: cumulative WURSS-K AUC during the 10-day treatment period, summarized as a mean with standard deviation. The registry also lists secondary outcomes concerning days with specific symptoms, respiratory complications requiring antibiotic prescription after the treatment period, and use of concomitant treatments. The number of outcome measures and analyses is recorded as 9 for each. Numerical primary and secondary outcome results, and the statistical analysis details beyond the stated summary measure, are not reported in the registry record.

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: All included subjects who used the investigational medical device at least once and with non-missing value at Day1 and at least another non-missing time point between Day2 and Day10. Otherwise, the AUC was missing.

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 AUC (Area Under Curve) of the Wisconsin Upper Respiratory Symptoms Survey for Kids (WURSS-K) During the 10-day Treatment Period, measured over Cumulative AUC of the WURSS score assessed from Day 1 to Day 10.

The primary endpoint is the cumulative AUC of the WURSS-K from Day 1 to Day 10. The questionnaire was to be assessed once daily during that period. It was designed for children 4 to 10 years of age and includes symptom items, functional-impairment items, and a global-severity item. The registry describes symptom items covering runny nose, stuffy nose, sneezing, sore throat, cough, and feeling tired. Functional items concern activities such as sleeping, breathing, talking, walking or exercising, going to school, and playing with friends.

Items are scored from 0, meaning absent or no impairment, through 1, a little bad, 2, bad, and 3, very bad. The AUC combines the repeated daily scores across the treatment period, so it is intended to reflect the accumulated burden of symptoms and impairment over time rather than a score at just one assessment. The registry states that possible AUC values range from 0 WURSS-K score*day, for no impairment, to 420 WURSS-K score*day, for maximal impairment.

In general, a cumulative measure can represent both how severe symptoms are and how long they persist. The registry does not report the observed group means, standard deviations, or a between-group estimate for this endpoint, so the magnitude and precision of any observed difference cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary outcome as continuous and states that it is summarized by a mean and standard deviation. It does not report a specific inferential test, regression model, adjustment strategy, or confidence-interval method. These methods should not be inferred from the choice of summary statistics alone.

What does a mean describe?

In general, a mean is the arithmetic average of the observed values in the analysis group. For a cumulative WURSS-K AUC, it would describe the average accumulated score among the observations included in that group’s analysis. A mean is useful for comparing the central level of a continuous outcome, but by itself it does not show how values are distributed or how uncertain the estimated group difference is. The registry does not report the group means for this endpoint.

What does the standard deviation add?

In general, the standard deviation describes how dispersed individual observations are around their group mean. It is not the same as a standard error or a confidence interval: those address uncertainty in an estimate, whereas the standard deviation describes variability among observations. Interpreting dispersion also requires knowing the analysis sample and the shape of the outcome distribution. The standard deviations for the primary endpoint are not reported in the registry record.

Why use an AUC?

In general, an area-under-the-curve outcome condenses repeated measurements over time into a cumulative measure. This can reflect both the level of scores and how they persist across assessments. Here, the registry defines the time window as Day 1 to Day 10 and describes daily WURSS-K assessments. The AUC is expressed in WURSS-K score*day units, and the record gives its possible range as 0 to 420. The registry does not explain the numerical integration procedure used to obtain each participant’s AUC, so no specific calculation method should be assumed.

How should group comparisons be viewed?

In general, a comparison of group means estimates how far apart the observed group averages are. A confidence interval around that comparison can show its precision, and a statistical test can assess compatibility with a specified null hypothesis. These inferential tools depend on assumptions and a clearly defined analysis. The registry record does not report a group contrast, confidence interval, p-value, or detailed inferential method for the primary endpoint.

Even a precise observational association is not automatically a causal effect. In general, confounding occurs when factors related to both treatment-group membership and outcome contribute to the observed comparison. Random allocation is one way trials can reduce that concern, but allocation is not stated; the registry describes the investigation as non-interventional and says the arms are not a like-for-like control comparison. Whether any adjustment was performed is not reported in the registry record.

What do the planning assumptions mean?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning illustrations, not evidence of the study’s original design or observed power. In general, a sample-size calculation estimates the number of participants needed under its assumptions to detect a specified effect with a chosen operating characteristic. It does not show the probability that a completed study’s findings are true, and a planning target is not an observed result. The numerical planning outputs and the observed effect used as their basis are not reported in the registry record.

The record does not give enough information to verify distributional assumptions, assess model diagnostics, or determine whether the analysis accounted for repeated measurement beyond constructing the AUC. Such details matter because an analysis method should suit the outcome and design. Without the reported estimates and full analysis specification, readers can explain the intended endpoint and summary measure, but cannot independently evaluate the primary statistical result.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Healsea® Children: Isotonic Seawater Based Nasal S", "Conventional Therapies")
n   <- c(101, 85)
m   <- c(36.56, 55.54)
sp  <- c(21.14, 27.86)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Healsea® Children: Isotonic Seawater Based Nasal S  101  36.560  21.140  32.387  40.733
CARM  Conventional Therapies  85  55.540  27.860  49.531  61.549

11. Multiplicity, Missing Data and Analysis Populations

The registry records 9 outcome measures and 9 analyses. The primary outcome is cumulative WURSS-K AUC during the 10-day treatment period. Listed secondary outcomes include days with runny nose, stuffy nose, sneezing, sore throat, cough, and feeling tired; respiratory complications requiring antibiotic prescription after the treatment period; and use of concomitant treatments.

When several outcomes are analyzed, the chance of obtaining at least one apparently noteworthy result can increase if each is tested separately. In general, multiplicity procedures can control that concern, but they may affect interpretation and precision. Whether the analyses used any multiplicity adjustment, which outcomes were treated as confirmatory, and whether analyses were prespecified are not reported in the registry record. The listing of outcomes and analyses alone does not establish how their results should be ranked or interpreted.

The primary analysis population is defined as included subjects who used the investigational medical device at least once and had a non-missing value at Day 1 plus at least another non-missing time point between Day 2 and Day 10. Otherwise, the AUC was missing. This definition clarifies the minimum assessment information required, but the number of participants in that analysis population is not reported in the registry record.

In general, missing outcome data can affect estimates if the observations that are missing differ systematically from those that are available. The registry does not report the amount or pattern of missing primary endpoint data, any imputation procedure, or sensitivity analyses addressing missingness. It also does not describe whether the secondary outcome analyses used the same analysis population. These omissions limit assessment of how representative the analyzed observations were and how robust the findings would be to alternative missing-data assumptions.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for the Healsea® Children group as affecting 0 participants among 101 at risk, and for the conventional-therapies group as affecting 0 participants among 85 at risk. Deaths are recorded as 0 in each group. The record also lists other adverse events affecting 17 participants among 101 at risk in the Healsea® Children group and 23 participants among 85 at risk in the conventional-therapies group.

These are counts as recorded, not percentages or estimates of comparative risk. No rates or contrasts are calculated. The record’s serious-event count does not establish that no events occurred outside the recorded observation or reporting process. The criteria and follow-up procedures used for event collection are not reported in the registry record. The record does not state whether the other adverse events were considered related to either treatment, nor does it provide event-level descriptions in the listed serious-event terms. The top serious terms list is empty.

In general, safety counts need context about the population monitored, the period of observation, event definitions, and completeness of reporting. The at-risk counts are the group-specific denominators recorded for these safety summaries; they should not be substituted for the primary endpoint analysis population. These figures describe what the registry records and do not establish a causal comparison between the groups.

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

The registry establishes that SYMBIOFILM-TAK was a completed, non-interventional post-market investigation addressing Healsea® Children used alongside conventional therapies for common cold in children with perennial allergy and symptoms of acute infectious rhinitis. It specifies a cumulative WURSS-K AUC as the primary endpoint, assessed from Day 1 to Day 10, and describes the questionnaire’s symptom, functional-impairment, and global-severity content.

What it does not establish from the information recorded is the numerical result for that endpoint. Group means, standard deviations, a between-group estimate, confidence intervals, and p-values are not reported in the registry record. The listed secondary outcomes likewise have no numerical findings in the record. It is therefore not possible to characterize the size, direction, or precision of an outcome difference from the registry information.

Even if a group difference is reported elsewhere, the design cautions against interpreting it automatically as an effect caused by the spray. The study is non-interventional, allocation is not stated, and the registry says the arms are not a like-for-like control comparison. In general, observed differences in such groups may reflect treatment selection or other group differences as well as the intervention. The record does not report whether such factors were measured or adjusted for.

The safety counts show what was recorded for serious events, other events, and deaths in the two groups. They do not establish that all events were captured or that any group difference was caused by treatment. The registry does not provide event definitions or a detailed account of the safety-monitoring process.

Accordingly, this record is useful for understanding the study question, design, endpoint, and reported safety counts, but it does not contain the outcome estimates needed to determine how the primary endpoint differed between groups or how precisely any difference was estimated. It should not be read as demonstrating either benefit or lack of benefit.

14. Why This Trial Matters Statistically

This investigation is statistically notable because it combines a repeated symptom-and-function measure with a real-life, non-interventional comparison. The WURSS-K AUC is intended to capture cumulative burden across daily assessments, rather than relying on one symptom score at one time. That choice makes the endpoint relevant to the duration and severity of a respiratory episode as represented by the questionnaire, while also requiring a clearly defined analysis population and careful handling of incomplete assessments.

The registry gives a specific eligibility rule for calculating the primary AUC: device use at least once, a Day 1 value, and another non-missing time point between Day 2 and Day 10. This makes the intended minimum data requirement explicit. However, without the number of observations that met it or a missing-data analysis, readers cannot assess how that rule affected the analyzed population.

The comparison also illustrates the difference between describing outcomes in observed groups and making a causal claim. The record identifies a non-interventional design, does not state allocation, and warns that the arms are not a like-for-like control comparison. In general, such design features mean that estimates need cautious interpretation because group differences may be entangled with other differences between participants or care pathways.

Finally, the registry record demonstrates why endpoint definitions and numerical results must be read together. It describes the measure and its scale in detail, yet does not report the outcome estimates needed to quantify an observed comparison. The record can therefore support discussion of measurement and design, but not a statistical conclusion about the magnitude or precision of the primary outcome difference.

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 registry identifies the investigation as non-interventional, and allocation is not stated. It explicitly warns that the arms are not a like-for-like control comparison. This limits causal interpretation: in general, differences in participant characteristics, clinical circumstances, or care choices can influence an observational group comparison. The registry does not report whether such factors were measured, balanced, or adjusted for.

The comparator is described as conventional therapies for common cold as needed, with nasal irrigation excluded, while the spray was used on top of conventional therapies as needed. The record does not give further detail about which conventional therapies were used, how their use varied, or how treatment exposure was recorded. This makes the care contrast less precisely characterized in the registry record.

The primary outcome analysis required a particular pattern of non-missing WURSS-K observations and at least one use of the device. The analysis-population size, missing-data pattern, imputation methods, and sensitivity analyses are not reported in the registry record. The numerical primary and secondary results and detailed inferential methods are also not reported, preventing assessment of effect magnitude and precision.

The WURSS-K description notes that the questionnaire was designed for children 4 to 10 years of age, but the enrolled children’s ages are not reported in the registry record. The registry’s product description says Healsea® Children is indicated for children above 6 years; this does not establish the ages of participants in this investigation. Follow-up and adverse-event collection details, along with criteria used to define serious and other events, are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Symbiofilm Trial in Allergic Kids (SYMBIOFILM-TAK) — NCT05034328.
• Registry record last updated 2025-01-20; status last verified 2023-03.
• Results first posted 2025-01-20.
• 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

SYMBIOFILM-TAK (NCT05034328) is listed as a completed, non-interventional post-market clinical investigation sponsored by Lallemand Pharma AG, with enrollment of 186. It assessed Healsea® Children added as needed to conventional common-cold therapies among children with perennial allergy presenting with symptoms of acute infectious rhinitis. The comparator group received conventional therapies as needed, with nasal irrigation excluded.

The primary endpoint was cumulative WURSS-K AUC from Day 1 to Day 10, summarized as a mean and standard deviation. The record describes 9 outcome measures and 9 analyses, but numerical efficacy results and detailed inferential methods are not reported in the registry record. It also cautions that allocation is not stated and the groups are not a like-for-like control comparison. Safety listings record zero serious adverse events and zero deaths in both groups, alongside counts for other adverse events. These registry entries describe the study’s design and recorded outcomes but do not establish a causal treatment effect.