A Trial of a Walter Reed Army Institute of Research (WRAIR) Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial of a Walter Reed Army Institute of Research (WRAIR) Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults (NCT00239577), a randomized phase 2 study. The primary outcome is Number of Subjects With Any and Grade 3 Solicited Local Symptoms.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, observer-blind, single-center, controlled Phase 2 study. Its official title describes two doses of various formulations of the WRAIR live attenuated tetravalent dengue vaccine compared with a placebo control, administered on a 0-6-month schedule, to healthy adults. The registry describes the study as evaluating safety and immunogenicity.

The registry summary says that 5 different formulations were evaluated. The arm descriptions identify Dengue Formulation 17a, Dengue Formulation 17b, Dengue Formulation 19 and placebo. Formulation 17a and placebo are described as two-dose schedules at Months 0 and 6. The descriptions for Formulations 17b and 19 mention two primary doses and a booster, but the timing text is incomplete in the registry record. It therefore does not fully describe the schedules or reconcile the stated number of formulations with the arm descriptions.

The trial record reports enrollment of 86 and status as completed. Its recorded start date is 2006-04-05, and primary completion is recorded as 2007-06-19. The registry identifies GlaxoSmithKline as sponsor. These details describe the recorded design and conduct; they do not establish how many participants contributed data to each outcome or analysis.

For the primary safety outcome, the analysis population was the Primary Total Vaccinated Cohort, defined as vaccinated subjects with at least one vaccine administration documented and data available. The registry does not report the randomization method, allocation concealment, masking procedures beyond the observer-blind label, or whether the analysis population was defined before enrollment began. Further details of the protocol and statistical plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Primary Phase

Reasons for not completing this period:

Booster Phase

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Primary Total Vaccinated Cohort, which included all vaccinated subjects (with at least one vaccine administration documented) for whom data were available.

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 Number of Subjects With Any and Grade 3 Solicited Local Symptoms, measured over During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine.

The primary endpoint counts participants with any and Grade 3 solicited local symptoms during the 21-day (Days 0-20) follow-up after Dose 1. The assessed local symptoms were pain, redness and swelling. “Any” includes an occurrence regardless of intensity grade. Grade 3 pain was defined as pain that prevented normal activity; Grade 3 redness or swelling was defined as redness or swelling spreading beyond 20 millimeters (mm) of the injection site.

Participant counts are a direct way to describe how many people experienced an event during a specified observation period. Reporting both any-grade and Grade 3 symptoms distinguishes the occurrence of symptoms at any intensity from events meeting the registry’s more severe definitions. The endpoint is descriptive as recorded: without arm-level counts, denominators for this specific outcome, or a stated comparison estimate, it cannot establish the size or precision of a difference between groups.

The primary analysis was performed in the Primary Total Vaccinated Cohort, which included vaccinated subjects with at least one documented vaccine administration and available data. The registry does not report the primary endpoint counts by arm, confidence intervals, or a test of a treatment contrast. The primary endpoint’s results and inferential uncertainty are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count describe?

A participant count records how many people in a defined group experienced an event. It differs from a count of event episodes: one participant may experience more than one event, while a participant-level measure usually counts that person once for the specified outcome. The primary endpoint is explicitly framed as the number of subjects with symptoms. For the serious adverse-event summaries, the registry reports participants with serious adverse events and the numbers at risk in each arm.

Counts need a denominator and a clear observation period to be interpretable. The serious adverse-event figures have group-specific numbers at risk, while the primary endpoint specifies follow-up during the 21-day (Days 0-20) period after Dose 1. The primary outcome’s arm-specific denominators are not reported in the registry record, so its counts and rates cannot be reconstructed from the information recorded. Counts from different follow-up periods or populations should not be treated as directly comparable.

Why distinguish any symptoms from Grade 3 symptoms?

The primary outcome uses two definitions: any occurrence, regardless of intensity, and a more severe category defined by activity interference for pain or spread beyond 20 millimeters (mm) for redness or swelling. Separate reporting can describe both the breadth of symptom occurrence and the subset meeting the stated Grade 3 threshold. These categories are not interchangeable. A count for any symptom does not reveal how many met the Grade 3 definition, and the Grade 3 definition should not be replaced with an unstated clinical interpretation.

What would an inferential comparison add?

In general, an estimate of a difference between groups summarizes the direction and size of the observed contrast. A confidence interval describes the range of values compatible with the data and the statistical method, under its assumptions. It communicates precision as well as the estimate: a wider interval indicates less precision than a narrower interval. A p-value, when reported, assesses how compatible the observed data are with a specified null hypothesis under the chosen model. It is not the probability that the null hypothesis is true, and it does not describe the size or clinical importance of an effect.

The registry record does not report a primary-endpoint contrast, confidence interval, or p-value. No inferential conclusion about differences in local symptoms can be drawn from the endpoint definition alone. The absence of an estimate is not a zero estimate, and it does not establish that the groups had the same outcome.

How should planning calculations be understood?

In general, sample-size planning uses assumptions about the effect to detect, the significance level, allocation, and statistical method to estimate a design requirement. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. Such calculations are planning illustrations, not observed outcomes and not evidence of the probability that the completed study detected an effect. They are not “observed power.” The record does not report that these assumptions were the trial’s own design basis or provide a trial sample-size justification.

For an outcome based on participant counts, methods may compare event proportions or model the counts, depending on the endpoint definition and analysis plan. The appropriate approach depends on details such as the planned contrast, denominators, follow-up, and handling of missing observations. Those details, along with the model and any adjustment variables used for the primary endpoint, are not reported in the registry record. No statistical procedure should be imputed from the randomized design alone.

What can the safety counts establish?

Group-level serious adverse-event counts describe what was recorded in each arm. They do not, by themselves, estimate a causal effect or account for uncertainty. General statistical reasoning cautions that event counts can be imprecise, especially when events are sparse; formal comparison would require a prespecified estimand and method, along with clear definitions and follow-up. The registry does not report those comparative methods or an uncertainty interval for the serious-event figures. It also does not report a causal attribution for the listed events.

Over-dispersion is a general concern when variation in count outcomes exceeds what a simple model assumes. It can make standard errors too small if the model fails to account for extra variability. This trial’s primary endpoint is reported as participant counts rather than a model specification, and the record does not report a fitted count model or a dispersion assessment. It would be inappropriate to claim that over-dispersion was present or that a particular adjustment was used.

The registry reports 30 outcome measures and 0 analyses. It does not report the statistical analysis plan, a multiplicity procedure, or how the many outcome measures were prioritized beyond the designation of a primary outcome. Accordingly, the record does not establish whether reported tests, if any, were adjusted for multiple comparisons. There is no reported primary inferential result to interpret or to assess for multiplicity.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures, including safety outcomes covering solicited symptoms, unsolicited adverse events, serious adverse events, laboratory findings and physical examination findings. It reports 0 analyses. The primary outcome is identified, but the registry record does not report a statistical analysis plan, a hierarchy for interpreting secondary outcomes, or any adjustment for multiple testing. Whether multiplicity was addressed in the study’s analyses is not reported in the registry record.

The primary analysis population is defined as the Primary Total Vaccinated Cohort: all vaccinated subjects with at least one documented vaccine administration and available data. The record does not specify how many participants had available data for the primary outcome by arm, how missing symptom observations were handled, or whether any imputation or sensitivity analyses were performed. The available-data criterion alone does not describe the missing-data mechanism or show whether missing observations could affect interpretation.

The registry’s primary endpoint contains both any and Grade 3 symptom categories, assessed for pain, redness and swelling. The record does not report whether each category was tested separately, whether a combined rule was used, or how analyses across symptoms and categories were controlled. It also does not report a prespecified primary contrast or a procedure for repeated or multiple assessments.

These gaps limit interpretation of both positive and null findings; in this record, the primary outcome counts and inferential results are not reported. Without an analysis plan and outcome-level data, it is not possible to determine how missingness or multiplicity influenced the reported evidence.

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: procedural hypertention (11.1%), hodgkin's disease (11.1%), demyelinating polyneuropathy (4.8%), physical assault (4.8%).

The serious adverse-event figures are reported as participants affected and participants at risk in each group: Dengue Formulation 17a, 0 of 22; Dengue Formulation 17b, 1 of 22; Dengue Formulation 19, 1 of 21; and placebo, 1 of 21. The registry also reports zero deaths in each group. These counts describe the registry record; they do not establish whether an event was caused by the vaccine or placebo.

The record lists serious-event terms with percentages: “Procedural hypertention,” 11.1%; “Hodgkin's disease,” 11.1%; “Demyelinating polyneuropathy,” 4.8%; and “Physical assault,” 4.8%. The listed information does not assign these terms to particular groups or state whether they were considered related to an intervention. It also does not provide enough detail to interpret the percentages as group-specific comparative risks.

Small descriptive event counts do not by themselves establish a difference between groups. The registry does not report a statistical comparison or uncertainty interval for serious adverse events. The separate “other” adverse-event category should not be confused with serious adverse events, and its detailed definition is not reported in the registry record.

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

This study record describes a randomized, placebo-controlled Phase 2 evaluation of live attenuated tetravalent dengue vaccine formulations in healthy US adults. It identifies a primary safety endpoint based on solicited local symptoms after Dose 1 and gives definitions for any and Grade 3 symptoms. It also reports selected adverse-event counts by group. Those details clarify what was intended to be measured and offer limited descriptive safety information.

The record does not report the primary endpoint counts by arm, a treatment contrast, confidence intervals, or a p-value. It therefore does not establish whether local symptoms were more or less common in any vaccine formulation group than in placebo, nor how precisely any such difference could be estimated. Likewise, the serious adverse-event counts do not demonstrate a causal relationship, a comparative safety effect, or equivalence. No deaths were recorded in the listed groups, but that fact alone does not characterize every safety outcome or exclude other risks.

The registry summary describes evaluation of safety and immunogenicity, but the results available in the record do not include an immunogenicity endpoint result. The posted information therefore cannot support conclusions about immune response. It also cannot establish protection against dengue or a clinical benefit.

Missing outcome details and absent inferential methods should be treated as limits on interpretation, not as findings that there was no effect. The counts are descriptive observations in a particular trial record, with a defined adult population and study setting. They do not by themselves answer questions about other populations, formulations, schedules, or outcomes. The record’s statements should be kept distinct from any broader claim about vaccine effectiveness or safety.

13. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and a reported result are both necessary for statistical interpretation. The registry defines local symptoms, the observation period and the vaccinated analysis population. Those details establish what the primary measure was meant to capture. But without arm-level counts or an estimated contrast, readers cannot quantify the observed primary result or assess its precision.

The record also distinguishes several formulations and includes a placebo group. That structure makes clarity about the planned comparison especially important. A statement that a study is randomized does not by itself tell the reader which contrasts were primary, how results across formulations were handled, or whether multiplicity was controlled. Those analysis details are not reported in the registry record.

Safety reporting shows another basic statistical distinction: counts of participants with events describe observations, while comparisons and uncertainty estimates address how strongly those observations support a difference. The serious adverse-event counts are available, but no comparative analysis is reported. Descriptive figures can be useful without answering a causal question.

Finally, registry records can expose gaps between a high-level study summary and the detail available for interpretation. The summary describes 5 formulations, whereas the arm descriptions identify three vaccine formulations and placebo; some booster timing text is incomplete. Recognizing such limits is part of careful evidence reading. It prevents the study design, outcome definitions, and available results from being treated as more complete than the record supports.

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 primary outcome’s arm-level counts, denominators, and inferential estimates are not reported in the registry record. The principal safety question therefore cannot be quantitatively assessed from the available primary endpoint information. The registry reports 0 analyses, and does not provide the statistical analysis plan, model, prespecified contrasts, confidence intervals, or p-values.

The trial summary describes 5 vaccine formulations, while the arm descriptions identify Formulations 17a, 17b and 19, as well as placebo. The descriptions for Formulations 17b and 19 are truncated and do not fully report booster timing. The registry record does not reconcile these differences or provide the complete formulation and schedule details. This limits the ability to identify precisely which regimens are represented by the described arms.

The primary analysis population includes vaccinated subjects with available data, but arm-specific primary outcome denominators and missing-data handling are not reported. The record also does not explain whether the listed serious adverse-event terms were considered related to study intervention or assign those terms to specific groups. The other adverse-event category’s detailed definition is not reported.

The registry does not report a sample-size justification, multiplicity approach, or full protocol and statistical methods. These omissions limit assessment of precision, analysis choices and the strength of any comparative interpretation. The study is recorded as single-center and conducted in healthy adults, so its description does not itself establish applicability to other settings or populations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Trial of a Walter Reed Army Institute of Research (WRAIR) Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults — NCT00239577.
• Registry record last updated 2019-02-19; status last verified 2019-02.
• Results first posted 2019-02-19.
• 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

The registry record describes a completed, randomized, parallel-group, observer-blind, single-center, controlled Phase 2 study of WRAIR live attenuated tetravalent dengue vaccine formulations and placebo in healthy US adults. Enrollment is recorded as 86. The primary endpoint was participants with any and Grade 3 solicited local symptoms during the 21-day (Days 0-20) follow-up after Dose 1.

The primary endpoint counts and comparative analyses are not reported in the registry record. Serious adverse-event counts are listed by group, with one or fewer participants affected in each arm; zero deaths are recorded in each group. The record does not report a statistical analysis plan, multiplicity handling, or primary-outcome missing-data procedures. It describes 5 formulations in the summary, while arm descriptions identify Formulations 17a, 17b and 19 and placebo.