Phase 3 Trial of Serbian Seasonal Influenza Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 3 Trial of Serbian Seasonal Influenza Vaccine (NCT02935192), a randomized phase 3 study. The primary outcome is Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity).

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, triple-masked, parallel-group, placebo-controlled study of a seasonal trivalent split, inactivated influenza vaccine produced by Institute Torlak. It was conducted in volunteers aged 18-65 in Serbia. The vaccine arm received the seasonal trivalent split, inactivated vaccine; the placebo arm received phosphate buffered saline. The sponsor was Institute of Virology, Vaccines and Sera, Torlak.

The registry record lists enrollment of 480. The study started on 2016-11-28, had primary completion on 2017-01-08, and is marked completed. Those dates describe the record’s study timeline; they do not establish the timing or duration of every outcome assessment.

The primary outcome is a participant count for solicited adverse events described as local and systemic reactogenicity, with a 30-minute post-vaccination timeframe. The analysis population is described as subjects who were randomized and received a study vaccination. The record’s endpoint description names local events, including redness or erythema, swelling or induration, and pain, while the endpoint title also refers to systemic reactogenicity. It does not explain that difference or give a detailed outcome definition for systemic events.

The registry lists nine outcome measures and zero analyses. No allocation ratio, randomization procedure, masking roles, protocol details, statistical analysis plan, or sample-size justification is reported in the registry record. The listed group counts for adverse-event summaries are not a substitute for the primary endpoint results or a complete accounting of participants across all analyses.

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: Twenty-three (23) subjects failed screening and were not assigned to a treatment group. An additional 8 subjects withdrew consent prior to receiving any study product.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was conducted for subjects who were randomized and received a study vaccination

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.

Population: Participants enrolled and vaccinated without major protocol deviations

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity), measured over 30-minute post-vaccination period.

The primary endpoint is the number of participants experiencing one or more solicited adverse events associated with local and systemic reactogenicity. The specified timeframe is the 30-minute post-vaccination period. The description lists local reactions: redness or erythema, swelling or induration, and pain. Because the title includes both local and systemic events but the detailed description lists local events, it is not clear from the registry record exactly which systemic events were included in the primary endpoint.

A participant count is a binary-outcome summary at the individual level: each participant either meets the endpoint definition or does not. Counting participants with one or more events differs from counting every event, because a person with multiple listed reactions may still contribute only once to a participant-level count. Whether and how that rule was applied to this endpoint is not reported in the registry record.

Solicited events are events actively sought using specified questions or observations, rather than events that depend solely on spontaneous reporting. In general, such endpoints can describe short-term reactogenicity within a defined observation window. The registry does not report the endpoint results, the precise ascertainment procedure, or a between-arm estimate. Therefore, the endpoint’s stated purpose and definition can be described, but its observed frequency and comparative result cannot.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint, each participant is classified according to whether the specified outcome occurred. A participant count can be presented alone, or alongside the number evaluated, an arm-to-arm contrast, and an uncertainty interval. The registry record defines the primary outcome as a participant count and identifies an analysis population of randomized subjects who received a study vaccination. It does not report the primary counts, arm-specific denominators for that endpoint, a contrast, or an uncertainty interval.

What does a participant count represent?

A count of participants with one or more events is not the same as a count of all event episodes. If the outcome rule is participant-level, several qualifying symptoms in one person may still be represented as one affected participant. This distinction matters when interpreting adverse-event summaries. The primary outcome description uses a participant count, but the record does not give enough detail to determine how multiple symptoms or repeated reports were handled.

The endpoint description lists redness or erythema, swelling or induration, and pain, and the endpoint title includes local and systemic reactogenicity. The distinction between these descriptions should be retained rather than resolved by assumption. The record does not state which systemic symptoms were solicited, how symptoms were graded, or how they were combined into the primary endpoint. Such definitions are important because the classification rule determines who is counted as having the outcome.

Why does the observation window matter?

The stated timeframe is the 30-minute post-vaccination period. In general, an endpoint’s observation window defines which events are eligible to count for that analysis. It does not describe events outside the window, and it should not be treated as a measure of all adverse events throughout the study. The registry record does not report the details of event collection or whether separate windows were used for other outcomes.

Solicited outcomes are generally collected through active questioning or structured observation. This approach can make the endpoint more systematic than relying only on spontaneous reports, but interpretation still depends on the exact questions, assessment schedule, and scoring rules. Those details are not reported in the registry record. The word “solicited” alone does not establish how consistently assessments were completed or how missing assessments were handled.

How should arm comparisons be interpreted?

In general, a randomized comparison estimates how outcomes differed between assigned groups under the study’s analysis approach. An absolute difference would describe the gap between the groups’ event frequencies; a relative measure would express one frequency in relation to the other. Neither measure can be calculated from the available primary endpoint information because the endpoint counts and denominators are not reported. No adjusted estimate or unadjusted estimate is reported in the registry record.

A confidence interval would communicate uncertainty around an estimated comparison. Its width depends on the amount of information and the variability in the observed outcomes, among other features of the analysis. A narrow interval indicates greater precision than a wide interval, but either must be interpreted in relation to the question being studied. No interval is reported for the primary endpoint. A p-value, if reported, would address compatibility with a specified null model; it would not by itself describe the size or practical importance of an effect. No primary endpoint p-value is reported.

What can the serious-event summaries establish?

The serious-event summary gives counts of affected participants and participants at risk for each arm. These counts describe the entries in that safety summary. They do not by themselves establish causation, comparative risk, or statistical significance. General assessment of a safety comparison also depends on definitions, follow-up, completeness of collection, and the analysis population. The registry record does not report those details for the serious-event summary.

Over-dispersion is a general statistical concern when the variability in count data is greater than a chosen model expects. It can make model-based uncertainty estimates too small if the model does not allow for the extra variability. This issue cannot be evaluated from the primary endpoint record because no primary results or model-based analysis are reported. Moreover, the listed primary outcome is a participant-level binary count, not a reported count model with a dispersion estimate.

How do planning illustrations differ from trial results?

A sample-size calculation is a planning exercise about how much information might be needed under stated assumptions. It is not an observed result and does not show that a trial had a particular probability of detecting an effect after the data were collected. The planning assumptions listed for illustrations are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the target effect defined as a fraction of the observed effect. The illustrations are explicitly based on the observed effect and are not the trial’s own design justification. The registry record does not report the trial’s sample-size justification. No planning count is stated in the information for this analysis, and any such illustration should not be described as observed power.

Overall, the available record permits description of the design, endpoint definition, and some adverse-event counts. It does not permit reconstruction of the primary statistical analysis. That requires outcome values, denominators, analysis choices, and uncertainty estimates that are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists nine outcome measures and zero analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or an adjustment for testing multiple outcomes. Multiplicity is a general concern when many hypotheses are tested: the chance of at least one apparently unusual result can increase as more tests are considered. Whether that concern applied to formal testing in this study cannot be determined from the record. The number of listed outcomes alone does not show that each outcome was tested or that any particular adjustment was required.

Missing-data handling is not reported in the registry record. The primary endpoint analysis population is described as subjects who were randomized and received a study vaccination, but the record does not state how many participants were randomized, vaccinated, assessed, or included in the endpoint analysis. It also does not describe exclusions, incomplete assessments, or any method for addressing missing endpoint observations. Without those details, the completeness of the primary endpoint data cannot be evaluated.

The same limitation applies to analysis populations beyond the stated primary endpoint population. The record does not describe an intention-to-treat analysis, a per-protocol analysis, or other analysis sets. It does not report whether the outcome results were analyzed according to randomized assignment or actual vaccination receipt. These methods can answer different questions in general, so the population definition and handling of participants after randomization are important for interpretation.

No interim analyses, stopping rules, or prespecified subgroup analyses are reported in the registry record. Their absence from the record should not be interpreted as proof that none occurred; it means these details are not reported. With no primary analysis results or analysis plan, the robustness of any treatment comparison cannot be assessed.

11. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute lymphocytic leukemia (0.3%), varicocele (0.3%).

The safety summary lists serious adverse events for participants at risk in the Vaccine and Placebo groups. It reports 2 affected participants among 312 at risk in the Vaccine group and 0 among 156 at risk in the Placebo group. Other adverse events are listed for 13 of 312 at risk in the Vaccine group and 8 of 156 at risk in the Placebo group. Deaths are listed as 0 in both groups.

These figures are descriptive summaries, not a statistical test or causal assessment. The record does not give confidence intervals, a comparison estimate, event timing, or information about whether the events were judged related to the study intervention. The top serious-event terms are Acute Lymphocytic Leukemia and Varicocele, each listed as 0.3%. The record does not explain the denominator or arm assignment for those percentages in the summary, so they should not be used to infer a group-specific rate.

Serious and other adverse-event categories should not be treated as interchangeable with the primary solicited endpoint. The primary endpoint has a stated 30-minute post-vaccination timeframe and a description focused on reactogenicity; the safety summary does not report that same endpoint. The registry record does not provide enough detail to determine whether participants could be counted in more than one safety category or how the summaries relate to the primary analysis population.

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

This record establishes the design and stated purpose of a Phase 3 randomized, triple-masked, placebo-controlled study of a seasonal trivalent split, inactivated influenza vaccine produced by Institute Torlak in volunteers aged 18-65 in Serbia. It identifies solicited adverse events as the primary outcome and specifies a 30-minute post-vaccination period. It also reports selected serious and other adverse-event counts and lists deaths as 0 in both groups.

Those details do not provide the primary endpoint result. The registry record does not report how many participants in each arm experienced one or more of the specified solicited events, or the statistical comparison between arms. It therefore does not establish the magnitude or precision of a primary endpoint difference. The posted serious-event counts likewise do not establish whether a difference between groups is attributable to the vaccine, nor do they supply a formal comparison.

The study’s title refers to safety and immunogenicity, but immunogenicity measurements and results are not reported in the information for this analysis. There are also no reported efficacy outcomes from which to draw a conclusion about protection against influenza. A study’s phase, design, and intended question are not themselves evidence of an outcome.

In general, a trial result is interpreted by considering the endpoint definition, analysis population, comparison estimate, uncertainty, and missing data, as well as the study design. Several of these elements are not reported in the registry record. The result should therefore be described narrowly: the record identifies the trial and its planned primary safety question, and it posts selected safety counts, but it does not report the primary endpoint analysis needed to quantify that question.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why study design and reported results must be distinguished. The record describes randomized allocation, triple masking, a parallel design, a placebo comparator, and a defined primary safety question. Those features identify the intended structure of the comparison. They do not, without outcome counts and an analysis, establish what the comparison found.

The endpoint also illustrates why precise definitions matter. Its title refers to local and systemic reactogenicity, while its description names local events, including redness or erythema, swelling or induration, and pain. The timeframe is specified as 30 minutes after vaccination. A reader can identify the intended observation window, but cannot fully determine the outcome rule because systemic event details and assessment procedures are not reported in the registry record.

The safety summary provides participant counts that can be read descriptively, but no uncertainty estimates or statistical comparison. This distinction is central to biostatistical interpretation: counts show what the record lists, while inferential analyses are needed to quantify uncertainty around a group contrast. Even an analysis would depend on the endpoint definition, population, and data completeness.

The record lists nine outcome measures but zero analyses. Without a reported analysis plan, it is not possible to assess how outcomes were prioritized, whether multiplicity was addressed, or how missing data were handled. The trial is therefore a useful reminder that registry design information and posted results serve different purposes. Transparent outcome reporting, denominators, analysis methods, and uncertainty estimates are necessary for a reader to evaluate the statistical evidence.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation is that the registry record does not report results for the listed primary endpoint. It names a participant-level outcome and a 30-minute post-vaccination timeframe, but gives no arm-specific primary endpoint counts, analysis denominators, effect estimate, confidence interval, or test result. The stated primary question therefore cannot be quantified from the posted record.

The primary endpoint description is also incomplete or internally broader in its title than in its detail: the title includes local and systemic reactogenicity, while the description lists local events only. The registry record does not clarify which systemic events were assessed or how the listed events were combined. Symptom grading, ascertainment procedures, and handling of repeated or multiple symptoms are not reported.

The enrollment figure is 480, while the safety summaries list 312 participants at risk in the Vaccine group and 156 in the Placebo group. The registry record does not explain the relationship between these figures, and the safety denominators should not be taken as the primary endpoint analysis denominators. No participant flow or primary endpoint analysis population size is reported.

Other trial-specific limitations include the absence of a reported statistical analysis plan, sample-size justification, missing-data approach, multiplicity strategy, interim analysis information, and detailed masking roles. The record lists nine outcome measures and zero analyses. It also does not report immunogenicity results despite the study’s stated aim of examining immunogenicity. These reporting gaps limit assessment of the intended questions and the precision and robustness of any comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 3 Trial of Serbian Seasonal Influenza Vaccine — NCT02935192.
• Registry record last updated 2019-04-19; status last verified 2019-01.
• Results first posted 2019-04-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02935192 is a completed Phase 3 randomized, triple-masked, parallel-group, placebo-controlled study of a seasonal trivalent split, inactivated influenza vaccine produced by Institute Torlak in volunteers aged 18-65 in Serbia. The sponsor was Institute of Virology, Vaccines and Sera, Torlak. The study started on 2016-11-28 and reached primary completion on 2017-01-08. Listed enrollment was 480.

The primary outcome is the number of participants with solicited adverse events related to local and systemic reactogenicity during the 30-minute post-vaccination period. Its description names local redness or erythema, swelling or induration, and pain. The registry record lists nine outcome measures and zero analyses, but does not report the primary endpoint results or immunogenicity results.

Safety summaries list serious adverse events in 2 of 312 participants at risk in the Vaccine group and 0 of 156 in the Placebo group; deaths are listed as 0 in both groups. These summaries are descriptive and do not provide an inferential comparison.