Clinical Trial of Anaferon for Children Efficacy in Prevention of Influenza and Other ARVI: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial of Anaferon for Children Efficacy in Prevention of Influenza and Other ARVI (NCT03301155), a randomized phase 4 study. The primary outcome is Time From Taking the First Dose of the Study Drug to the Onset of Influenza/ARVI Symptoms..

2. Clinical Question

The clinical question focuses on the timing of symptom onset rather than only on whether a child became ill. For this endpoint, a longer recorded time corresponds to symptoms arising later among the children represented in the analysis. The registry also lists secondary questions concerning children who did not fall ill, symptoms requiring antibacterial therapy, hospitalization, and adverse events. Those outcomes address different aspects of the trial and should not be treated as interchangeable with the primary time-based measure.

The record does not report enough detail to establish how symptom-free children at the end of follow-up were handled in the mean calculation, or how the primary endpoint was operationalized beyond its description as time from the first dose to symptom onset. Those details matter when interpreting a time-to-event outcome, so the posted group means and the separately reported Cox regression should be read as distinct summaries rather than assumed to be the same analysis.

3. Trial Design

The registry describes NCT03301155 as a completed phase 4 randomized, quadruple-masked, parallel-group clinical trial sponsored by Materia Medica Holding. Its official title describes an international multicenter, placebo-controlled study of prevention during seasonal peaks. Enrollment is listed as 1036. The recorded start date is 2017-10-03, and primary completion is listed as 2019-05-20.

The two interventions were Anaferon for Children and placebo. The arm description specifies an oral tablet taken once daily, approximately at the same time. It also describes taking the product away from meals and allowing the tablet to dissolve in the mouth. The placebo is described as following the Anaferon for Children scheme. Some details of the Anaferon arm description are truncated in the registry record, so no further administration details can be established from that description.

The primary endpoint is time from the first dose to onset of influenza or acute respiratory viral infection symptoms, measured in days during 12 weeks of treatment and based on medical records. It is designated as a mean for the intention-to-treat population, with 95% confidence intervals. The primary group summaries list 520 for Anaferon for Children and 501 for placebo. The record does not explain how these endpoint denominators relate to the enrollment figure or why the denominators differ across the primary and safety reporting.

The registry lists 5 outcome measures and 8 analyses, with 4 secondary outcomes posted. It identifies analyses using logistic regression and Cox regression for the primary comparison. A detailed protocol, full statistical analysis plan, eligibility criteria, and sample-size justification are not reported in the registry record. The sample-size illustrations associated with the observed secondary result are planning calculations, not a description of how the trial was originally designed.

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: Intention-to-treat (ITT)

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 Time From Taking the First Dose of the Study Drug to the Onset of Influenza/ARVI Symptoms., measured over in 12 weeks of the treatment.

The primary endpoint measures the time from the first dose of study drug to the onset of influenza or acute respiratory viral infection symptoms. The registry specifies days as the unit, a 12-week treatment timeframe, medical records as the source, and the intention-to-treat population as the analysis population. It reports a mean and 95% confidence interval for each arm.

A time-to-symptom endpoint carries information about when illness begins, not just whether an event is recorded. In general, time-to-event methods can use information about both the occurrence and timing of an event. They can also account for observations that end before an event is recorded, but the registry record does not describe the handling of children who had no recorded symptoms during follow-up or other censoring details. It is therefore important not to assume how such observations entered the reported means or regression analyses.

The posted arm means are 428.8 days for Anaferon for Children, with a 95% confidence interval of 351.0 to 523.8, and 275.8 days for placebo, with a 95% confidence interval of 232.7 to 326.9. These are the registry’s reported summaries; no unadjusted two-arm recalculation is available for this continuous endpoint. The record also reports a Cox regression result, which summarizes the comparison differently from the group means. Because details of endpoint construction are not reported, the numerical summaries should be interpreted as the results recorded by the sponsor rather than as a fully documented account of every analysis choice.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous time measure, reported as a mean in days for each arm. A mean condenses the observations into a single group summary, while a confidence interval conveys uncertainty around that summary under the method used to construct it. These summaries do not show the distribution of individual times or how heavily the mean may be influenced by unusually long observations. The registry does not report additional distributional summaries for this endpoint.

What does the Cox regression estimate?

The registry reports a Cox regression hazard ratio of 0.645, with a 95% confidence interval of 0.496 to 0.839 and p = 0.022. In general, a Cox model compares event rates over time while accounting for the ordering of event times. A hazard ratio is a relative measure, not a difference in days, and it is not the same quantity as a ratio of group means. Its interpretation depends on the event definition, which group is the reference, and how the model was specified. Those details are not reported in the registry record. The Cox result therefore should be quoted as recorded, without converting it into an absolute change in time or assigning an unreported interpretation to its coding.

What does the logistic regression result add?

The registry lists logistic regression for the primary two-arm comparison and reports p = 0.001. In general, logistic regression models the odds of a binary outcome. A p-value summarizes how compatible the observed data are with a specified null model under the analysis assumptions; it does not quantify the size of an effect. No logistic-regression effect estimate or confidence interval is reported, and the registry does not describe the binary outcome used in that model. The result can therefore be reported as a posted p-value, but it cannot be used to recover an absolute event difference or an odds ratio.

How should the confidence intervals be read?

In general, a confidence interval reflects the sampling uncertainty of an estimate under its statistical procedure. A narrower interval indicates greater precision under that procedure, while a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its endpoints, and it does not account automatically for biases, model misspecification, missing-data problems, or measurement limitations. Here, the registry provides 95% intervals for each mean and for the Cox hazard ratio. No interval is reported for the logistic result.

The mean and Cox summaries address time to symptom onset in different ways. They should not be combined as though they were duplicate estimates from one common scale. The record does not explain how children without a recorded event during follow-up contributed to the mean, or whether and how censoring was represented in the analyses. In general, time-to-event analyses require attention to censoring and to the assumptions used to compare event timing. The relevant assumptions and diagnostics are not reported in the registry record.

What do the secondary calculations represent?

For the secondary outcome concerning symptoms requiring antibacterial therapy, the posted count summaries are 3 participants in the Anaferon for Children arm and 8 in the placebo arm. The reported sponsor analysis is Fisher exact, with p = 0.137. An unadjusted recalculation from the posted counts gives a risk difference of -0.010, with a 95% confidence interval of -0.023 to 0.003 and p = 0.115. These are different analyses and need not produce identical p-values. The recalculated risk difference is an absolute comparison of the observed proportions, while relative measures such as a risk ratio or odds ratio express the comparison on different scales.

General statistical note: when binary outcomes are uncommon, the number of observed events can be small, and estimates may be imprecise. Exact methods such as Fisher’s exact test are one approach to testing an association in a two-group setting. An unadjusted calculation from summary counts does not reproduce any covariate adjustment or other model choices that may have been used in a sponsor analysis. No additional modeling details for the reported Fisher test are given.

The planning illustrations use the observed secondary effect as a starting point and display assumptions for detecting fractions of that effect. They assume a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrations specify participants per arm for 80% power and participants per arm for 90% power. They are not observed power, do not describe the original design justification, and should not be read as a guarantee that a future study of the displayed size would achieve those operating characteristics. In general, planning estimates depend on assumptions about the underlying effect, event rates, allocation, analysis method, and follow-up; departures from those assumptions can change the needed sample size.

The record also includes secondary analyses, but a complete statistical analysis plan is not reported. The number and type of posted analyses do not establish whether outcomes were prespecified, whether analyses were adjusted, or whether all planned analyses are represented. Those uncertainties limit any attempt to reconstruct the full inferential strategy from the registry record alone.

10. Analyses Reported by the Sponsor

The registry’s primary results are sponsor-reported regression analyses: logistic regression with p = 0.001 and Cox regression with a hazard ratio of 0.645, a 95% confidence interval of 0.496 to 0.839, and p = 0.022. The record does not provide a logistic-regression effect estimate or its confidence interval. The primary group means are also posted, but a recalculated two-arm comparison is not available for this continuous endpoint.

For the secondary outcome concerning symptoms requiring antibacterial therapy, an unadjusted recalculation from the posted counts gives a risk difference of -0.010, with a 95% confidence interval of -0.023 to 0.003 and p = 0.115. The sponsor’s reported Fisher exact analysis has p = 0.137. These p-values arise from different analysis procedures and are not expected to match exactly. Neither should be treated as a replacement for the other: the recalculation is a simple unadjusted analysis of posted summary counts, while the registry result is the sponsor’s stated analysis.

The record does not flag a discrepancy between the sponsor analysis and the recalculation. The recalculation is useful as a transparent check based on the posted counts, but it does not establish the sponsor’s full analysis choices or address any adjustment that may have been used. The primary sponsor analyses remain the only reported model-based primary comparisons in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, 4 posted secondary outcomes, and 8 analyses. It reports more than one analysis for the primary comparison and includes several secondary questions. When multiple outcomes or analyses are examined, the chance of obtaining at least one small p-value by chance can increase. Statistical approaches to multiplicity can define how the overall false-positive risk is controlled, but the registry record does not report whether any such approach was prespecified or applied. The reported p-values should therefore be understood as results of their individual analyses, not assumed to have a multiplicity adjustment.

The record identifies the primary endpoint population as intention-to-treat. In general, an intention-to-treat analysis aims to analyze participants according to their assigned group, but the label alone does not specify how missing measurements, incomplete follow-up, protocol deviations, or participants without a recorded event were handled. The registry does not report those procedures for the primary endpoint. It also does not describe imputation, sensitivity analyses, or the assumptions used for incomplete outcome data.

For the primary time-to-symptom endpoint, handling of participants without symptoms by the end of follow-up and any censoring rules are not reported in the registry record. Such details are important because the analysis of time depends on how follow-up ends and how event status is determined. The record says the outcome was based on medical records, but does not describe adjudication, completeness of records, or procedures for resolving uncertain onset dates.

The registry does not report an interim-analysis plan, stopping rules, a full statistical analysis plan, or a sample-size justification. Their absence from the record does not establish that these procedures were absent from the conduct of the trial; it means they cannot be assessed from the registry information. Likewise, the available record does not establish which analyses were prespecified and which may have been exploratory. These reporting gaps affect how confidently the statistical evidence can be evaluated, particularly when considering several outcomes alongside the primary endpoint.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: partial cramps (0.2%).

The safety record reports serious adverse events for 528 participants at risk in the Anaferon for Children group and 508 in the placebo group. It records 1 serious adverse event in the Anaferon for Children group and 0 in the placebo group. Deaths are recorded as 0 in both groups. The registry lists “Partial cramps” at 0.2% among the top serious adverse event terms; the record does not provide enough context in this listing to assign that term to a particular arm.

These are event counts within the safety denominators recorded by the registry. They should not be read as a complete description of every aspect of safety, and the small number of serious events means the record gives limited information about uncommon outcomes. A count of zero in an arm does not establish that an event cannot occur; it indicates that none was recorded in that group in the posted results.

The registry also reports other adverse events in 49 participants at risk in the Anaferon for Children group and 44 in the placebo group. The record does not describe severity classifications, follow-up after treatment, relatedness assessments, or the full coding and aggregation rules for these events. Those limitations should be kept distinct from the serious-event figures. The posted safety counts are descriptive registry results, not a basis for individualized medical decisions.

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

The posted results describe a randomized, masked comparison of Anaferon for Children and placebo, with time to influenza or acute respiratory viral infection symptoms designated as the primary endpoint. The registry reports separate arm means and confidence intervals and two regression-analysis p-values, including a Cox hazard ratio with a confidence interval. These statistics describe the trial’s recorded observations under the analyses listed in the registry.

They do not, by themselves, show how well the results generalize to children outside the enrolled study population or to settings with different seasonal patterns, follow-up, or outcome recording. The registry provides limited information about participant eligibility, baseline characteristics, endpoint construction, missing data, and model specification. Without those details, readers cannot fully assess possible sources of bias or reproduce the sponsor’s analyses.

A p-value does not measure the size or clinical importance of an effect, and a confidence interval does not remove uncertainty about design and reporting limitations. The logistic regression p-value is not accompanied by an effect estimate or interval, while the Cox estimate depends on model and reference-group details that are not reported. The mean summaries and the Cox result use different statistical descriptions of the endpoint and should not be collapsed into a single number.

The secondary results offer additional observations but have less inferential weight when multiplicity procedures and full outcome details are unavailable. The safety figures report few serious events, but sparse counts cannot establish the absence of uncommon harms. The trial record can support careful description of the posted results; it cannot answer every question about the magnitude, precision, robustness, or broader relevance of the findings.

Accordingly, the statistical interpretation should stay close to the reported endpoint, analysis population, and model outputs. It should not turn a registry result into a universal conclusion about prevention or safety. Important details not reported in the registry record remain necessary for a fuller assessment.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary endpoint is framed as time to symptom onset, while the registry reports both group means and a Cox regression analysis. These summaries answer related but nonidentical statistical questions. Understanding that distinction helps prevent a hazard ratio from being interpreted as a change in days or a mean from being treated as a complete description of event timing.

The record also illustrates why estimates and uncertainty matter alongside p-values. The Cox result has a reported effect estimate and confidence interval, whereas the logistic regression result is reported only as a p-value. Without the effect size and uncertainty for the latter, its magnitude is not available from the registry. Similarly, the primary endpoint’s group means are presented without a recalculated two-arm estimate, so the sponsor’s model output is the only reported inferential comparison for that endpoint.

The secondary outcome with an unadjusted recalculation shows how analysis choices can affect a reported p-value. The recalculation is based on posted counts and is not a substitute for the sponsor’s test. The difference reinforces that a statistical result depends on the procedure used, not only on the observed event counts. Planning illustrations based on an observed secondary effect also show why planning assumptions should be distinguished from observed trial results and from the original design rationale.

Finally, the registry leaves important methods unreported, including multiplicity handling, missing-data procedures, and details needed to interpret the time-to-event analysis. These gaps do not negate the posted results, but they constrain their precision and reproducibility. The trial is therefore a useful case for reading registry evidence as a combination of observed summaries, model-based inference, and methodological information that may remain unavailable.

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 limitations specific to this trial arise from the level of detail in the registry record. The primary endpoint is described as time from first dose to symptom onset, but the record does not explain how symptom onset was defined, how it was verified from medical records, or how participants without recorded symptoms by the end of follow-up were handled. These omissions make it difficult to assess exactly what the reported means represent or to evaluate the Cox analysis assumptions.

The primary population is identified as intention-to-treat, but the registry does not describe missing-data handling, protocol deviations, adherence, or the exact analysis denominator rules. The posted primary arm denominators are not the same as the safety denominators, and the reason for that difference is not reported. The record also does not provide baseline characteristics or detailed eligibility criteria, limiting assessment of the population represented and its comparability with other settings.

Although the record lists logistic and Cox regression, it does not report the full model specifications, covariates, coding, diagnostics, or reference-group details. The logistic analysis lacks a reported effect estimate and confidence interval. The primary continuous endpoint has no recalculated two-arm estimate from the posted summary statistics. These features restrict independent verification and make it important to keep the sponsor’s model results distinct from simple summaries.

For the secondary outcomes, the registry does not document a multiplicity strategy or a complete statistical analysis plan. The available reporting does not establish which analyses were prespecified, and not every listed secondary question has a complete set of estimates and uncertainty measures in the record. The sample-size illustrations are based on an observed secondary effect and are not the trial’s own design justification.

Safety reporting is also limited to the posted counts and selected event terminology. Further information on severity, attribution, duration, and ascertainment is not reported in the registry record. These reporting limitations do not establish that the trial was conducted improperly; they identify information needed for a more complete statistical assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Trial of Anaferon for Children Efficacy in Prevention of Influenza and Other ARVI — NCT03301155.
• Registry record last updated 2020-05-06; status last verified 2019-05.
• Results first posted 2020-05-06.
• 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

NCT03301155 is a completed phase 4 randomized, quadruple-masked, parallel-group trial sponsored by Materia Medica Holding. The registry lists enrollment of 1036 and describes an international multicenter comparison of Anaferon for Children with placebo during seasonal peaks of influenza and other acute respiratory viral infections.

The primary endpoint is time from the first dose to symptom onset during 12 weeks of treatment, based on medical records and designated for the intention-to-treat population. The registry reports arm means with 95% confidence intervals, a Cox regression hazard ratio of 0.645 with a 95% confidence interval of 0.496 to 0.839 and p = 0.022, and a logistic regression p-value of 0.001. The logistic analysis has no posted effect estimate or confidence interval.

The record also lists secondary outcomes and adverse-event counts. Important details about missing data, multiplicity, endpoint handling, and model specification are not reported in the registry record, limiting independent reconstruction and interpretation of the analyses.