Clinical Study of Efficacy and Safety of Raphamin in the Treatment of ARVI in Children 12-18 Years Old: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Study of Efficacy and Safety of Raphamin in the Treatment of ARVI in Children 12-18 Years Old (NCT04918771), a randomized phase 3 study. The primary outcome is Time to Resolution of Acute Respiratory Viral Infection (ARVI) Symptoms (ARVI, Confirmed by Polymerase Chain Reaction (PCR))..

2. Clinical Question

3. Trial Design

The registry record identifies this as a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Masking is recorded as quadruple. The record does not specify which particular groups of people were masked, so that detail is not reported in the registry record. The sponsor is Materia Medica Holding.

The study concerns Raphamin for treatment of ARVI in children aged 12–18. Both Raphamin and placebo are described as tablets for oral use. The registry record does not report the dose, treatment duration, or detailed treatment schedule in the intervention descriptions. It records an enrollment of 435 and a completed study, with a start date of 2021-04-29 and primary completion date of 2023-07-21.

Randomization and a placebo comparator establish a design intended to compare outcomes between assigned groups. The parallel-group structure means the groups are followed as separate groups rather than participants crossing between treatments. The registry record does not report the randomization method, allocation ratio, concealment procedures, site locations, eligibility criteria beyond the age and condition reflected in the title and record, or the study's original sample-size justification.

The primary endpoint was mean time to resolution of PCR-confirmed ARVI symptoms during 14 days of observation. The endpoint description defines resolution using both temperature and symptom-score criteria. The listed analysis groups contain 122 participants assigned to Raphamin and 107 assigned to placebo for this endpoint. Those figures describe the posted endpoint analysis, not the total enrollment. The registry record does not report why the analyzed groups are smaller than the enrollment figure.

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.

Before assignment: A total of 435 patients signed informed consent, of which 10 patients did not pass screening (not meet inclusion criteria or non-inclusion criteria). 5 patients had significant deviations from the procedure for signing informed consent. However, they were randomized and received study therapy. But these patients are not counted as randomized.

Overall Study

Reasons for not completing this period:

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 to Resolution of Acute Respiratory Viral Infection (ARVI) Symptoms (ARVI, Confirmed by Polymerase Chain Reaction (PCR))., measured over 14 days of observation.

The primary endpoint measures the number of days until resolution of PCR-confirmed ARVI symptoms. Resolution required an axillary temperature of ≤37.3°C and a total symptom score of ≤2. PCR confirmation means the endpoint was evaluated in the context of virus detection, as described in the registry record. The observation timeframe was 14 days.

The symptom score combined six flu-like nonspecific symptoms—headache, chills, sweating, weakness, muscle pain, and drowsiness—with seven nasal, throat, or chest symptoms. Each symptom was rated on a four-point scale from no symptom to severe symptom. Temperature was converted to points using the temperature categories in the endpoint definition, and the resulting TSS ranged from 0 to 42; higher scores indicated a worse outcome. The resolution rule therefore uses both a temperature threshold and a low overall symptom score rather than relying on one symptom alone.

Time to resolution is a continuous measure expressed in days, and the posted arm summaries report means and standard deviations. Comparing group means offers a direct description of average time to meet the stated resolution criteria. It does not, by itself, describe every participant’s course or the shape of the time-to-resolution distribution. The registry record does not report additional details about how participants without documented resolution by the end of observation were handled.

7. Results Posted in the Registry

• Raphamin: mean 3.30 versus 4.40 on control; difference -1.10 (95% CI -1.68 to -0.52), standardized effect d = -0.51; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Time to Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed).

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Raphamin: mean 3.40 versus 3.90 on control; difference -0.50 (95% CI -0.91 to -0.09), standardized effect d = -0.24; z-test p = 0.018.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Raphamin than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Patients Reporting Worsening of Illness.

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Raphamin: 0.5% (1/199) versus 0.0% (0/205) on control; risk difference 0.5 percentage points (95% CI -0.5 to 1.5); unadjusted two-proportion z-test p = 0.310.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Raphamin and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Patients With Clinically Relevant Abnormal Laboratory Findings.

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Raphamin: 0.5% (1/206) versus 0.0% (0/214) on control; risk difference 0.5 percentage points (95% CI -0.5 to 1.4); unadjusted two-proportion z-test p = 0.308.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Raphamin and the control. The interval gives the range of effects that remain compatible with the data.

The secondary findings show a mixed level of detail and precision. The posted clinically diagnosed and/or PCR-confirmed time-to-resolution result is directionally similar to the primary time-to-resolution comparison, while the binary results for worsening illness and clinically relevant abnormal laboratory findings are based on sparse event counts. These secondary outcomes address related but distinct questions and should not be treated as interchangeable measures of the primary endpoint.

The registry lists 11 secondary outcomes, including symptom severity and resolution, antipyretic use, worsening illness, adverse events, and vital signs. Results for the other listed secondary outcomes are not reported in the registry record. The available secondary results therefore do not provide a complete account of every registered outcome.

Secondary results generally carry less evidential weight than a prespecified primary result, particularly when many outcomes are examined. Each additional test creates another opportunity to observe a low p-value by chance. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes. The posted secondary p-values are unadjusted, so they should be read as exploratory or supportive rather than as independent confirmation of the primary finding. This is a general interpretation principle; the registry does not describe the sponsor’s intended role for each secondary analysis.

The sparse binary event counts also limit how much can be inferred about uncommon outcomes. A small number of observations can leave substantial uncertainty even when the displayed group counts differ. Conversely, a non-small p-value is not proof that groups are identical. The secondary results contribute context, but they do not replace the primary endpoint or resolve questions about unreported outcomes and analysis procedures.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Severity of ARVI (Clinically Diagnosed and/or PCR-confirmed).
• Percentage of Patients With Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed).
• Time to Resolution of ARVI Symptoms (Clinically Diagnosed and/or PCR-confirmed).
• Percentage of Patients With Resolution of ARVI Symptoms (PCR-confirmed).
• Dosing Frequency of Antipyretics.
• Percentage of Patients Reporting Worsening of Illness.
• Occurrence and Type of Adverse Events (AE) During the Treatment. AE Severity.
• Changes in Vital Signs: Pulse Rate/Heart Rate in Beats Per Minute (Bpm).

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean difference express?

A mean difference subtracts one group’s average from the other’s. The recalculation uses Raphamin minus placebo, so a negative value means the Raphamin group’s posted mean was lower. The registry’s reported analysis gives a positive difference, which reflects the reverse group order. A sign change from reversing subtraction does not change the size of the contrast. For time to resolution, the comparison concerns average days to meet the recorded resolution criteria, not a claim that every participant had the same experience.

The primary outcome is continuous: it is measured in days and summarized with a mean and standard deviation. A t-test is a commonly used method for comparing two group means. The registry reports a two-sided t-test of final values. A two-sided test considers evidence for a difference in either direction, rather than testing only for a difference favoring one specified group. The registry also classifies the analysis as superiority. The record does not provide further detail on the test assumptions or any adjustments beyond the stated analysis.

What does the p-value tell the reader?

A p-value measures how compatible the observed data are with a specified null model of no group difference, under the assumptions of the analysis. A small p-value indicates that the data would be relatively unusual under that null model. It is not the probability that the null hypothesis is true, and it does not quantify the chance that the result is due to bias or confounding. Nor does it measure the size or practical importance of a difference. The primary registry analysis reports p< 0.001, while the recalculation reports p < 0.001; both are small values in their respective reported analyses.

The posted secondary tests include a t-test for the continuous time-to-resolution measure and Fisher exact tests for binary outcomes. Fisher’s exact test evaluates the association between group assignment and a binary outcome using the observed counts. It is often used when counts are sparse. For the secondary outcomes, the registry reports p=0.007 for clinically diagnosed and/or PCR-confirmed time to resolution, p=0.493 for worsening illness, and p=0.49 for clinically relevant abnormal laboratory findings. These are unadjusted results in the posted record.

Why can over-dispersion matter?

Over-dispersion is a general statistical concern when the variability in data is greater than a model assumes. If a model understates variability, standard errors can be too small and uncertainty can appear narrower than it is. This concept is most relevant to outcomes analyzed with count or rate models, rather than a simple comparison of means by t-test. The registry’s primary analysis is described as a t-test; the record does not report an over-dispersion assessment or a model-based analysis for the primary endpoint. The registry’s symptom-score construction includes multiple symptoms and temperature points, but that does not establish that the primary time measure was over-dispersed.

What is the role of recalculation?

The recalculated primary comparison is an unadjusted calculation from posted arm-level summary statistics. It is useful as a check on the direction and approximate magnitude of the contrast, but it is not a replacement for the registry’s own analysis. The registry analysis uses final values and reports its own estimate, confidence interval, and test. No discrepancy is flagged in the record. The recalculation and the registry analysis have opposite signs because their group subtraction directions differ, and their absolute differences are close.

The recalculated estimates for the secondary continuous and binary outcomes likewise use the posted arm summaries and are unadjusted. A recalculated result may not reproduce every detail of the original analysis, particularly where the registry does not report the analysis population, missing-data handling, or model specifications. For that reason, the sponsor’s reported analysis remains the primary reference for its stated test, while recalculation is an interpretive aid.

What does the planning illustration represent?

The planning figures use the observed effect as a starting point and show hypothetical participant requirements under stated assumptions. They are not the trial’s original sample-size calculation, which is not reported in the registry record. They also do not show the power achieved by the completed trial. The assumptions and the distinction between planning and observed results are important when interpreting those figures.

11. Confidence Intervals and Precision

A confidence interval gives a range of values that are reasonably compatible with the data and the statistical method used to construct it. In repeated use of the same method under its assumptions, intervals at a stated confidence level would contain the target value at that rate. A 95% confidence interval is not a guarantee that the true value lies in that particular interval, and it does not include uncertainty from biases or limitations that the analysis does not account for.

For the primary endpoint, the registry reports a mean difference of 1.09 days with a 95% confidence interval from 0.51 to 1.67. The reported direction follows the registry analysis’s group order; the recalculation expresses the contrast as Raphamin minus placebo and is negative. Read with that direction in mind, the interval indicates that the reported difference is estimated with greater precision than a very wide interval would imply. The registry’s own estimate and interval should be read together with its reported test, rather than interpreting the sign without checking which group is subtracted from which.

The arm standard deviations are 1.7 days for Raphamin and 2.6 days for placebo. These describe participant-to-participant variation around each group mean; they are not confidence intervals for the means. A standard deviation and a confidence interval answer different questions: the former describes spread among observations, while the latter describes uncertainty in an estimated group contrast.

Precision is specific to the analyzed data and endpoint. The primary endpoint counts are 122 and 107, whereas the registry enrollment is 435. The registry record does not report how the analysis counts arose or how missing data were handled, so the posted interval does not resolve those questions. The interval also does not address possible multiplicity from the many registered outcomes. It quantifies uncertainty under the reported analysis, not every source of uncertainty relevant to interpreting the study.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not a record of the trial’s original design calculation. The assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original sample-size assumptions and justification are not reported in the registry record.

For this continuous primary endpoint, the planning figures are participants per arm. The rows plan for 100%, 75%, and 50% of the observed effect. At 100% of the observed effect, the illustration gives 61 participants per arm for 80% power and 82 participants per arm for 90% power. At 75% of the observed effect, it gives 109 participants per arm for 80% power and 146 participants per arm for 90% power. At 50% of the observed effect, it gives 244 participants per arm for 80% power and 327 participants per arm for 90% power.

In plain terms, 80% power is the planned probability of detecting an effect of the specified size under the stated assumptions if that effect is present; 90% power sets a higher detection probability and therefore requires a larger planned sample in these illustrations. Smaller effects are harder to distinguish from random variation, so planning to detect a smaller fraction of the observed effect requires more participants. The record’s general note says time-to-event illustrations, if present, give total events, while other illustrations give participants per arm; the primary endpoint figures are participants per arm. These figures are not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.100; pooled standard deviation σ = 2.167.
2. n = 2 × (1.96 + 0.842)² × 2.167² / -1.100² = 60.9, rounded up to 61 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.1                      # observed difference in means
sigma <- 2.16728783595457                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4918771)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 61 (80% power), 82 (90% power)
 75% of observed effect: n per arm = 109 (80% power), 146 (90% power)
 50% of observed effect: n per arm = 244 (80% power), 327 (90% power)
power.t.test: 61.9 
Simulated power at n = 61 per arm: 0.795 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s primary analysis is a two-sided t-test of final values. It reports a mean difference of 1.09, a 95% confidence interval from 0.51 to 1.67, and p< 0.001, and labels the analysis as superiority. The posted group means are 3.3 days for Raphamin and 4.4 days for placebo. The registry’s positive estimate is consistent with subtracting the Raphamin mean from the placebo mean; the recalculation instead defines the difference as Raphamin minus placebo and therefore has a negative sign.

The recalculated unadjusted mean difference is -1.1 days, with p < 0.001. Its magnitude is close to the sponsor’s reported 1.09-day difference, with the apparent direction reversed by group ordering and the small magnitude difference consistent with the posted values being rounded. The record does not flag a discrepancy. The sponsor’s own analysis is the relevant reference for its stated test and analysis method; the recalculation is a simple check based on arm-level summaries and is not an alternative adjusted analysis.

The registry analysis and recalculation both indicate a difference in the posted primary group means. That agreement should not be stretched into conclusions about unreported analysis choices. The registry record does not report the analysis population details, missing-data method, or any additional adjustments, and the recalculation cannot recover those features from the summary statistics.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, comparisons, or analyses are tested. The more tests that are conducted, the greater the chance that at least one result may appear notable by chance, even when no corresponding effect exists. Methods such as adjusted significance thresholds or a prespecified testing hierarchy can address this issue, but the registry record does not report a multiplicity strategy. The secondary p-values are therefore best read as unadjusted results, not as a family-wise confirmatory set.

The record lists 12 outcome measures and 25 analyses, but does not describe how those analyses were organized, whether all were prespecified, or which were included in a formal testing sequence. It also does not report whether interim analyses were conducted. No interim-analysis plan should be inferred from the reported results.

Missing-data methods and analysis populations are also not reported in the registry record. The total enrollment is 435, while the primary endpoint summaries include 122 participants in the Raphamin group and 107 in the placebo group. Other posted outcomes use different group counts. Those differences indicate that outcome-specific counts vary, but the record does not explain why, identify exclusions, or describe the handling of participants without an observed endpoint. It would be inappropriate to assume a particular intention-to-treat, per-protocol, or other analysis population.

For a time-to-resolution outcome, handling participants whose resolution is not observed by the end of follow-up can affect the analysis. The endpoint timeframe is 14 days, but the record does not report whether such observations were censored, excluded, imputed, or handled by another method. Likewise, no details are reported about missing symptom measurements, withdrawals, or sensitivity analyses. These omissions do not negate the posted estimates, but they constrain assessment of how robust they are to incomplete outcome data.

16. 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: worsening flu (0.5%).

The posted serious adverse event counts are 1 among 206 participants at risk in the Raphamin group and 0 among 214 at risk in the placebo group. The record identifies worsening flu as a top serious adverse event term and reports it as 0.5%. There were 0 deaths in each group. The registry also reports 6 other adverse events in the Raphamin group and 5 in the placebo group, using the same respective at-risk counts.

These figures are counts recorded during the study, not precise estimates of the full range of possible safety outcomes. With few events, differences between groups are difficult to characterize precisely, and zero recorded events in a group does not establish that an event cannot occur. The record does not provide a detailed account of event timing, severity beyond the recorded serious category, or the basis for judging relatedness to treatment. The serious-event figures should therefore be read as descriptive registry results, not as a complete safety assessment or a basis for medical decisions.

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

The posted data show lower mean time to resolution in the Raphamin arm than in the placebo arm for the primary PCR-confirmed endpoint: 3.3 days compared with 4.4 days. The recalculated contrast is -1.1 days when expressed as Raphamin minus placebo. The registry’s own analysis reports a 1.09-day difference in the opposite subtraction direction, with a 95% confidence interval from 0.51 to 1.67 and p< 0.001. These statistics describe the observed comparison and its uncertainty under the reported analysis.

The findings do not establish that every participant experienced a shorter illness, or that the difference applies to children outside the studied population and endpoint definition. The primary endpoint was based on PCR-confirmed ARVI and a particular combination of temperature and symptom-score thresholds over 14 days. Results for a different case definition, outcome, population, or follow-up period are not established by this comparison.

The posted findings also do not establish the size or direction of effects for all registered secondary outcomes. Results for several listed secondary measures are not reported in the registry record, and the available secondary analyses are unadjusted. Sparse adverse-event counts cannot rule out uncommon harms or characterize their likelihood precisely. The registry record does not describe missing-data handling or analysis populations in enough detail to assess those issues fully.

Statistical evidence of a group difference is not the same as proof of a specific mechanism, a guarantee of an individual outcome, or a complete benefit-risk assessment. The results are best understood as estimates from the recorded trial comparison, with their interpretation bounded by the endpoint, analysis, and reporting details available in the registry record.

18. Why This Trial Matters Statistically

This trial is statistically informative because it records a randomized, placebo-controlled comparison for a defined continuous endpoint and reports both arm summaries and a sponsor analysis. The primary outcome has an interpretable unit—days to symptom resolution—and a stated criterion combining temperature and symptom burden. That makes the estimate more concrete than a result reported only as a test statistic.

The example also illustrates why the order of subtraction matters. The recalculated contrast is Raphamin minus placebo, while the registry’s reported estimate is positive and follows the opposite direction. Without attending to group order, a reader could misread the sign. Comparing the absolute magnitude and the stated group means helps clarify the direction while retaining the sponsor’s own analysis as the main reported test.

The record also shows why a statistically notable primary result is only part of a trial’s evidence. The endpoint analysis counts differ from total enrollment, and the reason is not reported. Multiple secondary outcomes are listed, but the registry does not report a multiplicity approach, missing-data method, or detailed analysis-population definitions. Safety counts are sparse, which limits precision for rare events. These features matter when distinguishing an estimate from the broader conclusions a reader might wish to draw.

Finally, the planning illustration makes the relationship between assumed effect size and required sample size visible. It is not the trial’s original design justification and does not describe power observed after completion. Keeping that distinction clear prevents a planning calculation from being mistaken for a property of the trial results.

19. 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 design and analysis details unreported. It does not give the original sample-size justification, detailed randomization procedures, allocation concealment, the specific parties included in quadruple masking, or the planned interim-analysis strategy. The intervention descriptions identify oral tablets but do not state the dose or schedule.

The primary endpoint summaries include 122 participants assigned to Raphamin and 107 assigned to placebo, while total enrollment is 435. The registry record does not explain the difference or define the analysis population. It also does not report missing-data handling, reasons for absent endpoint observations, or sensitivity analyses. These omissions make it difficult to judge how participant inclusion or incomplete follow-up may have affected the estimates.

The primary measure is restricted to PCR-confirmed ARVI and uses a specified symptom-and-temperature resolution rule over 14 days. The result should not be assumed to describe other definitions of illness or outcomes. The available posted secondary results cover only some of the 11 listed secondary outcomes. A multiplicity strategy is not reported, so unadjusted secondary p-values warrant caution.

The safety results include few serious events, and the record does not provide a detailed account of event relatedness or timing. Sparse counts cannot precisely characterize uncommon events. More generally, registry summaries do not supply all the information needed to assess protocol deviations, site variation, or the conduct of each analysis. These are limitations of what is reported in the registry record; they do not by themselves show that a particular bias occurred.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Clinical Study of Efficacy and Safety of Raphamin in the Treatment of ARVI in Children 12-18 Years Old — NCT04918771.
• Registry record last updated 2024-10-15; status last verified 2023-08.
• Results first posted 2024-10-15.
• 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.

23. Record Summary

The registry record describes a completed phase 3, multicenter, randomized, quadruple-masked, parallel-group placebo-controlled study of Raphamin for ARVI in children aged 12–18. Enrollment was 435. The study started on 2021-04-29 and reached primary completion on 2023-07-21.

The primary endpoint was mean time to resolution of PCR-confirmed ARVI symptoms during 14 days of observation. The posted means were 3.3 days for Raphamin and 4.4 days for placebo. The registry reports a two-sided t-test with a mean difference of 1.09, a 95% confidence interval from 0.51 to 1.67, and p< 0.001; the recalculated Raphamin-minus-placebo difference is -1.1 days.

The record lists 11 secondary outcomes and includes results for three in the registry record. It reports sparse adverse-event counts, including 1 serious adverse event in the Raphamin group and 0 in the placebo group, with 0 deaths in either group. Multiplicity handling, missing-data methods, detailed analysis populations, and the original sample-size justification are not reported in the registry record.