Study of ChimeriVax™ Tetravalent Dengue Vaccine in Healthy Peruvian Children Aged 2 to 11 Years: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of ChimeriVax™ Tetravalent Dengue Vaccine in Healthy Peruvian Children Aged 2 to 11 Years (NCT00788151), a randomized phase 2 study. The primary outcome is Percentage of Participants (Aged 2 to 11 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo.

2. Clinical Question

The trial also aimed to describe humoral immune responses before and after vaccination, assess safety in both age cohorts, and describe viremia after the first and second dengue vaccinations in a subgroup of 130 randomized participants. These aims put the primary safety question alongside immunogenicity and viremia questions; they do not establish that those other outcomes were analyzed or reported. The registry lists secondary outcomes concerning seropositivity for dengue virus serotypes, but does not give their results in the record.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group Phase 2 trial with a listed enrollment of 300. The study title and official title describe healthy children in Peru, aged 2 to 11 years, previously vaccinated against yellow fever. The summary separates participants into cohorts aged 2 to 5 years and 6 to 11 years. The registry record identifies Sanofi Pasteur, a Sanofi Company, as sponsor and records the study as completed.

Participants assigned to the CYD dengue vaccine group were scheduled to receive three injections at 0, 6, and 12 months. Participants assigned to the control group received placebo at 0 and 6 months, followed by pneumococcal polysaccharide vaccine at 12 months. The description states that both groups were followed for 6 months after the final vaccination, up to 18 months. These are the planned schedules described in the record; it does not give adherence or completion results for the schedules.

The dates recorded for study start and primary completion are 2008-09-26 and 2010-02-16. The primary outcome concerns the percentage of participants reporting solicited injection-site and systemic reactions after each injection. The outcome window runs from Day 0 after injection through Day 14 after injections 1, 2, and 3. Safety assessment used a safety analysis set comprising participants who received at least one dose of dengue or control vaccine. For a specified reaction category, the record defines the number analyzed as participants with available data for that category.

Random allocation is intended to reduce systematic differences between groups at assignment, while a parallel design assigns participants to one group rather than switching them between schedules. The registry identifies quadruple masking but does not report which participant, investigator, assessor, or other roles were masked. It also does not report the allocation method, concealment procedures, or the planned statistical analysis in enough detail to evaluate them.

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 300 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized in the study. Two participants were not vaccinated and were excluded from the Full analysis set and Safety analysis set.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on Safety analysis set which included all participants who received at least 1 dose of dengue or control vaccine. Here, 'number analyzed' = participants with available data for specified category.

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: Analysis was performed in Full analysis set which included all the participants present at vaccination 1 and received at least 1 dose of vaccine.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants (Aged 2 to 11 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo, measured over Day 0 (Post-Injection) up to Day 14 after injection 1, 2 and 3.

The primary endpoint is the percentage of participants aged 2 to 11 years who reported solicited injection-site or systemic reactions after each injection of CYD dengue vaccine or placebo. Injection-site reactions were pain, erythema, and swelling. Systemic reactions were fever, headache, malaise, myalgia, and asthenia. The assessment period began on Day 0 after an injection and continued through Day 14 after injections 1, 2, and 3.

The endpoint also defines severity thresholds for selected reactions. Grade 3 pain means incapacitating pain that prevents usual activities; Grade 3 erythema or swelling means a size >= 5 cm. Grade 3 fever is > 39.0°C. For headache, malaise, myalgia, and asthenia, Grade 3 means that the reaction prevents daily activities.

A percentage is useful for describing how commonly a specified event was reported within a group, provided its denominator is clear. In this record, the analysis population is the safety set, and the number analyzed for each category is the number with available data for that category. This endpoint can describe reported short-term reactions by injection and group. It is not, by itself, a measure of immune response, viremia, or dengue disease outcomes. Although the registry names the primary outcome, it does not report the percentages, group comparisons, or uncertainty estimates. The frequency and comparative precision of the reactions therefore cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A percentage endpoint begins with a binary classification for each participant and reaction category: the reaction was reported, or it was not reported. The percentage describes the share of participants with the event among those included in the relevant denominator. Here, the registry defines the primary safety analysis set as all participants who received at least one dose of dengue or control vaccine. It further states that the number analyzed for a specified category is the number with available data for that category. This category-specific denominator matters because not every participant necessarily has recorded data for every reaction or time point.

The primary endpoint is repeated across injection numbers and reaction categories. Each injection has its own post-injection observation window, and the listed reactions include both injection-site and systemic events. A reader should distinguish a result for one reaction after one injection from a result pooled across reactions or injections. The registry describes the outcome framework but does not report numerical results for these categories or explain whether any categories were combined in analysis.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimate under a stated statistical method. For a percentage, it reflects uncertainty about the event frequency in the population represented by the trial, given the observed participants and analysis assumptions. For a group contrast, an interval can indicate which differences remain compatible with the data and method. A narrow interval generally conveys greater precision than a wide interval, but an interval does not remedy biased measurement, missing data, or limitations in the study population. No confidence intervals for the primary endpoint are reported in the registry record.

Why do denominators and group sizes matter?

Percentages depend on the number of participants counted as having the event and the number of participants assessed. If denominators vary across reactions or injection visits, the percentages may describe different sets of participants. That is why an event percentage should be read together with its denominator and the definition of the analysis population. The record gives the general definition of the safety set and category-level availability, but not the primary outcome denominators or event counts. The listed group sizes for serious and other adverse events should not be assumed to be the denominators for every primary reaction category.

How should group comparisons be interpreted?

In general, a randomized comparison estimates how outcomes differed between assigned groups, subject to the conduct of the trial, outcome ascertainment, missingness, and the analysis method. A difference in observed percentages is an estimate, not a guarantee that the same difference would occur in another population. Its uncertainty and clinical interpretation depend on the event counts, denominators, and analysis. The registry record does not report the primary endpoint group estimates, a contrast, a confidence interval, or a p-value, so there is no primary endpoint comparison to interpret statistically.

What is over-dispersion, and does it apply?

As a general concept, over-dispersion occurs when the variability in data is greater than a chosen statistical model expects. It is relevant when a model’s assumptions about variation are too restrictive, because uncertainty estimates may then be misleading. The primary outcome is described as a percentage, but the registry does not identify a model for its analysis or report evidence of over-dispersion. It would therefore be inappropriate to claim that over-dispersion was present or that a particular adjustment was used.

What do planning calculations mean?

In general, sample-size planning calculations illustrate how many participants might be needed under stated assumptions about an effect, allocation, significance level, and statistical approximation. They are conditional planning exercises, not counts of observed participants and not evidence that a trial had a particular probability of finding a result. The stated planning assumptions for this record refer to two-sided significance level 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of an observed effect. The record does not report the trial’s own sample-size justification. These planning calculations should not be described as observed power.

The registry lists enrollment of 300, but does not report the rationale for that target, the assumptions used by the investigators, or whether the enrollment was intended to support the safety, immunogenicity, or viremia objectives. The planning assumptions do not establish the original design rationale. Nor can they replace the unreported primary outcome estimates. Any statistical interpretation should separate design features and planning illustrations from the results actually recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures and several secondary outcomes, including seropositivity assessments across age groups, serotypes, and vaccination time points. When many outcomes, categories, or time points are considered, the chance of at least one apparently notable result can increase if each is tested separately without an appropriate analysis plan. In general, multiplicity methods may control that risk or distinguish confirmatory from exploratory analyses. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical analysis plan that explains how multiple comparisons were handled. It is not possible to determine from the record whether adjustment was planned or used.

The registry identifies the safety analysis set as participants who received at least one dose. For a specified category, the number analyzed is defined as participants with available data. This makes the intended population description clearer, but the record does not provide primary endpoint denominators by reaction category and injection, missing-data counts, reasons for missingness, or methods for handling missing observations. It also does not report whether participants with incomplete follow-up were included in every analysis.

The trial summary describes a viremia subgroup of 130 randomized participants, with 100 in the dengue vaccine group and 30 in the control group. The record does not report the subgroup’s results or explain the analysis population used for those results. The number of analyses is listed as 0, and numerical primary outcome analyses are not reported. Consequently, the record does not establish which planned outcomes were analyzed, how missing results were treated, or whether all analyses were prespecified. These gaps limit assessment of selective reporting and the robustness of any outcome interpretation.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: food poisoning (1.0%), inguinal hernia (1.0%), gastrointestinal infection (1.0%), pneumonia (1.0%), vascular purpura (0.5%).

The registry reports serious adverse event counts of 2 among 199 participants in the CYD dengue vaccine group and 4 among 99 participants in the control group. For the other-adverse-event count, it reports 71 among 199 in the CYD dengue vaccine group and 29 among 99 in the control group. No deaths are listed for either group. These are descriptive counts with the group denominators recorded for these safety entries. They are not the same as the unreported percentages for the solicited primary endpoint.

The record lists food poisoning, inguinal hernia, gastrointestinal infection, and pneumonia at 1.0% each, and vascular purpura and epiphyseal disorder at 0.5% each, among the top serious adverse event terms. These entries identify reported terms and percentages; they do not establish that the events were caused by the assigned intervention. The record does not give event narratives, timing in relation to injections, severity details beyond the serious-event classification, or a causal assessment. Nor does it report a statistical comparison of serious adverse events between groups.

In general, safety counts are interpreted in light of the population observed, duration of follow-up, ascertainment, and event definitions. The trial schedule describes follow-up up to 18 months, but the registry does not provide a complete account of event-specific observation time or missing safety information. The counts should therefore be read as the record’s reported summaries, not as a complete assessment of comparative risk.

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

This record describes a randomized, quadruple-masked, parallel-group Phase 2 study in healthy Peruvian children aged 2 to 11 years who had previously received yellow fever vaccine. It gives the two vaccination schedules, the planned follow-up, the solicited reactions used for the primary safety outcome, and some aggregate adverse event counts. Those details help readers understand the intended comparison and the type of safety information collected.

The record does not report the primary outcome percentages or their group comparison. It therefore does not establish how frequently participants reported the solicited reactions after either schedule, how the groups differed, or how precise such a difference might be. The serious adverse event counts and other adverse event counts are available as descriptive summaries, but they do not answer the primary endpoint question and do not establish causation.

The trial also aimed to describe immune responses and viremia, and the registry lists secondary seropositivity outcomes. Numerical results for these outcomes are not reported in the registry record. Their presence as objectives or outcome titles should not be mistaken for evidence of a particular immune response or virologic result.

In general, a randomized design can support a comparison between assigned groups when the relevant outcome data, analysis, and uncertainty are reported. Design labels alone do not reveal the results or demonstrate that all sources of bias were avoided. A study’s findings also apply most directly to the population and setting studied; this record concerns healthy children in Peru with prior yellow fever vaccination and does not describe other populations. The available information supports a description of the trial’s design and recorded safety summaries, but not a conclusion about the primary endpoint’s comparative result.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between a clearly specified outcome and a reported result. The registry defines solicited local and systemic reactions, their assessment window after each injection, and severity criteria for selected events. Those details make the intended measurement more concrete. Yet the primary outcome percentages and statistical comparisons are not reported in the registry record. An outcome definition alone cannot show the frequency of events, the difference between groups, or the precision of an estimate.

The study also illustrates why analysis populations and denominators are central to percentage outcomes. The registry states that the safety set includes participants who received at least one dose and that the number analyzed for a category is based on data availability. In principle, that information helps readers understand who contributes to an estimate. Without category-specific denominators and results, readers cannot assess whether denominators varied across reactions or injections, or how missing observations may have affected the summaries.

There is also a distinction between the trial’s multiple scientific aims and the evidence visible in its record. Safety, immune response, and viremia are separate outcome domains, and secondary seropositivity outcomes are listed. The record does not include their numerical results or a reported multiplicity strategy. This makes it important to avoid treating a list of planned measures as a list of findings.

Finally, the aggregate serious adverse event counts demonstrate the value and limits of descriptive safety summaries. Counts can communicate what was recorded in each group, but they do not establish causation or provide a complete comparative analysis. Statistical interpretation depends on definitions, denominators, follow-up, and uncertainty, as well as the outcome estimates themselves.

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.

A central limitation of the available record is that it names the primary safety endpoint but does not report its numerical results. There are no reaction percentages, event counts, group contrasts, confidence intervals, or p-values for the primary outcome in the registry record. The listed enrollment of 300 does not show how many participants contributed data to each reaction category or injection visit.

The registry records 19 outcome measures but does not give numerical results for the listed seropositivity outcomes or for the viremia objective. It also does not report a detailed statistical analysis plan, sample-size justification, multiplicity approach, or methods for handling missing observations. Without those details, it is not possible to evaluate how analyses were selected, whether all planned outcomes were reported, or how robust the results would be to different reasonable analytical choices.

The serious and other adverse event summaries are limited to aggregate counts and selected serious event terms. The record does not supply individual event narratives, timing, duration, severity details beyond the serious classification, or a causal assessment. It does not report a comparative statistical analysis of these events. The counts therefore should not be interpreted as proof that any event was caused by an assigned schedule.

The registry identifies quadruple masking but does not specify the masked roles or explain how masking was maintained. It does not report allocation concealment or participant flow details. The trial’s population is described as healthy Peruvian children aged 2 to 11 years previously vaccinated against yellow fever; the record does not establish how applicable its results would be to other populations. These limitations concern the information recorded and do not imply that unreported procedures or analyses were absent from the full study documentation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of ChimeriVax™ Tetravalent Dengue Vaccine in Healthy Peruvian Children Aged 2 to 11 Years — NCT00788151.
• Registry record last updated 2022-04-05; status last verified 2022-03.
• Results first posted 2019-07-29.
• 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

The registry record describes a completed randomized, quadruple-masked, parallel-group Phase 2 trial sponsored by Sanofi Pasteur, a Sanofi Company. It lists enrollment of 300 healthy Peruvian children aged 2 to 11 years who had previously received yellow fever vaccine. The CYD dengue vaccine schedule comprised injections at 0, 6, and 12 months; the control schedule comprised placebo at 0 and 6 months and pneumococcal polysaccharide vaccine at 12 months. Both groups were described as having follow-up up to 18 months.

The primary outcome was the percentage reporting solicited injection-site or systemic reactions through Day 14 after each injection. The registry record does not report numerical results for that endpoint. It reports serious adverse event counts of 2 among 199 in the CYD dengue vaccine group and 4 among 99 in the control group, other adverse event counts of 71 among 199 and 29 among 99, respectively, and no deaths in either group. Numerical results for the listed immunogenicity and viremia outcomes are not reported in the registry record.