Study of a Tetravalent Dengue Vaccine in Healthy Adult Subjects Aged 18 to 45 Years in India: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of a Tetravalent Dengue Vaccine in Healthy Adult Subjects Aged 18 to 45 Years in India (NCT01550289), a randomized phase 2 study. The primary outcome is Percentage of Participants With Antibody Titer ≥ 10 1/Dil Against Each Dengue Virus Serotype Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo.

2. Clinical Question

The study’s stated primary objectives were to describe neutralizing antibody responses before vaccination and after each dose, and to describe safety after each dose. Its secondary objective was to detect symptomatic dengue cases during the trial. These aims distinguish an immunogenicity assessment—measurement of an immune response—from a clinical disease assessment. A detectable antibody response is not itself a count of symptomatic dengue cases, and the record does not report such case results.

The comparison is therefore framed around antibody status for each serotype and its change over the scheduled vaccination period. The registry lists several antibody outcomes, including results by flavivirus immune status and geometric mean titers, but it does not provide outcome values or analyses for those outcomes. The clinical question is clear; the numerical evidence needed to estimate the size and precision of any between-group difference is not reported in the registry record.

3. Trial Design

The registry describes a completed phase 2 trial with randomized allocation, single masking, and a parallel-group model. The study evaluated immunogenicity and safety of a tetravalent dengue vaccine in healthy adults aged 18 to 45 years in India. Enrollment was 189. The registry lists CYD dengue vaccine and placebo as the two interventions; the placebo is described as NaCl 0.9% solution.

The vaccine group was scheduled to receive a dose at 0, 6, and 12 months. The placebo group was scheduled on the same timetable. Matching follow-up schedules can support comparisons of measurements taken at similar points in time, though the registry record does not explain allocation procedures, concealment, or how adherence to the schedule was assessed. It identifies masking as single, but who was masked is not reported in the registry record.

The primary antibody endpoint was measured before injection 1 and 28 days after each injection, through 13 months after injection 1. Dengue neutralizing antibody levels were measured using a dengue plaque reduction neutralization test. The analysis population is described as the Full Analysis Set with available data for each time point. The record does not report the number contributing data at each assessment or whether participants were excluded from particular analyses.

The registry also lists safety assessments and a secondary objective of detecting symptomatic dengue cases during the trial. It does not report the detailed visit schedule for symptom surveillance, the operational definition of a symptomatic case, or the duration and completeness of surveillance. The primary completion date is 2013-12, the start date is 2012-03, and the study status is completed. These administrative details describe the record, not the timing or completeness of individual participants’ follow-up.

The sample-size justification, allocation ratio, and detailed statistical analysis plan are not reported in the registry record. The posted sample-size assumptions describe planning illustrations based on an observed effect and specified assumptions; they are not the trial’s own design justification and do not represent observed power. No numerical outcome analyses are listed in the registry record, so the design alone cannot establish the size or precision of an antibody difference.

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 189 participants who met all inclusion and no exclusion criteria were randomized and vaccinated in this trial; 187 were included in the Full Analysis Set.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Dengue neutralizing antibody titers were assessed in the Full Analysis Set with available data for each time point.

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 Percentage of Participants With Antibody Titer ≥ 10 1/Dil Against Each Dengue Virus Serotype Before and After Each Vaccination With Either Tetravalent Dengue Vaccine or a Placebo, measured over Pre-injection 1 and 28 days post each injection (up to 13 months post-injection 1).

The primary endpoint is the percentage of participants whose dengue neutralizing antibody titer meets the stated threshold of 10 1/Dil against each dengue virus serotype. The registry specifies assessment before the first injection and 28 days after each injection, through 13 months after injection 1. Antibody levels were measured by dengue plaque reduction neutralization test. The analysis population was the Full Analysis Set with available data at each time point.

This endpoint expresses the proportion of assessed participants who meet a defined antibody criterion. A proportion can be useful for describing how common a response threshold is within a group, and it can be compared across groups or assessment times when the relevant estimates are reported. The serotype-specific framing matters because the vaccine includes four dengue serotypes, and an overall summary could obscure different response patterns across them.

As a general statistical point, a threshold-based endpoint simplifies a continuous or dilution-based measurement into a responder classification. That can make the result easier to communicate, but it also discards information about how far titers lie above or below the threshold. The registry separately lists geometric mean titer outcomes, which retain information about the scale of measured titers, but does not report their numerical results either.

The registry record does not report the percentages at any time point, confidence intervals, or a comparison between vaccine and placebo. It therefore supports description of the intended endpoint and measurement approach, but not an estimate of response frequency or comparative precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a percentage of participants who meet a titer threshold, assessed separately for each dengue serotype and at multiple time points. This is a binary outcome at the participant level: a measured titer is classified as meeting or not meeting the criterion. The group percentage describes the frequency of participants meeting that criterion among those with available data for the relevant assessment.

What does a percentage measure?

As a general statistical explanation, a percentage is a proportion expressed on a scale from none to all of the assessed participants. It is intuitive, but its interpretation depends on the denominator. If some participants have no measurement at a visit, the denominator may differ across time points or groups. The registry states that the Full Analysis Set with available data was used for each time point, but does not report the actual denominators or the missing-data handling rules. The total enrollment of 189 is not necessarily the denominator for every reported endpoint.

The antibody cutoff defines a responder classification. For an individual, the outcome is whether the titer reaches at least 10 1/Dil. The endpoint then summarizes how many assessed participants meet that criterion. As a general point, classification at a cutoff can make interpretation straightforward, but participants with measurements close to either side of the threshold may be classified differently despite similar underlying values. It also gives less detail than reporting the distribution of titers. The registry lists geometric mean titers and geometric mean titer ratios as additional outcomes, but their numerical results are not reported in the registry record.

Why are the serotypes and visits distinct?

The endpoint is specified for each dengue virus serotype rather than as a single undifferentiated antibody result. That permits a reader to consider whether measured responses differ across serotypes. The planned assessments also span the period before vaccination and after successive injections. Repeated measurements can describe the pattern over time, but comparisons across visits require attention to the fact that the same participants may contribute more than one observation. The statistical method used to account for repeated measurements is not reported in the registry record.

General statistical interpretation also depends on distinguishing within-group change from a randomized comparison between groups. A rise in a group’s antibody measure over time, by itself, does not quantify how that group differs from placebo. A comparative estimate should identify the groups, time point, outcome scale, and analysis population. The registry record does not report a primary between-group estimate or the model used to obtain one.

What does uncertainty add?

As a general explanation, a confidence interval describes uncertainty around an estimated quantity under the method’s assumptions. A narrow interval indicates greater precision than a wide interval, while an interval that spans a broad range leaves more possible values compatible with the data. The registry record does not report confidence intervals for the primary endpoint, so its precision cannot be assessed. A p-value, if reported, would address a different question and would not replace an estimate and its interval; no primary p-value is reported.

The trial’s outcomes encompass multiple serotypes, time points, and additional antibody summaries. General statistical practice recognizes that examining many outcomes can increase the chance of at least one apparently unusual finding when each is considered separately. Adjustment methods, outcome prioritization beyond the stated primary objective, and any multiplicity strategy are not reported in the registry record. Without those details and numerical results, the evidence cannot be interpreted as a set of confirmatory hypothesis tests.

How should the planning illustrations be read?

The stated planning assumptions describe illustrations using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not a record of the trial’s original sample-size justification. Any sample-size figures generated under such assumptions are planning illustrations, not observed power and not evidence that the trial achieved a particular level of power. The sample-size justification used to design the trial is not reported in the registry record.

As a general point, planning calculations depend on assumptions about the target effect, variability or event frequency, allocation, and analysis method. If assumptions differ from what is observed, the resulting illustration may not describe the trial’s actual operating characteristics. Here, the registry record does not provide the primary outcome estimates needed to evaluate how closely any planning assumption corresponds to the trial observations, nor does it report a detailed statistical analysis plan.

Finally, the listed safety counts are descriptive. Statistical methods for comparing serious or other adverse events, adjustment for exposure or follow-up, and formal safety analyses are not reported in the registry record. The counts can be stated as recorded, but they should not be treated as a modeled comparative effect or as a complete account of all safety outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several antibody outcomes: serotype-specific threshold percentages, results distinguished by flavivirus immune status, and geometric mean titers and ratios. The primary endpoint itself is assessed across multiple serotypes and time points. These related outcomes create multiple opportunities for comparisons, but the statistical plan for managing multiplicity is not reported in the registry record. It does not specify whether particular comparisons were prioritized, whether adjustment was intended, or how the many measures were to be interpreted together.

The record lists zero analyses, and no numerical estimates for the primary endpoint are reported. Thus, there are no posted primary results from which to judge the size, direction, or precision of an effect, and no reported analysis details to assess whether multiple testing was addressed. The absence of reported analyses should not be interpreted as evidence of no difference or no response.

The primary endpoint population is the Full Analysis Set with available data for each time point. The record does not provide the number of participants with available measurements at each visit or by group. It also does not describe reasons for missing measurements, imputation, sensitivity analyses, exclusions, or the handling of participants without a complete sequence of measurements. Those details are important because a percentage based on observed data can be affected if availability differs across groups or relates to antibody status.

The registry does not report a full statistical analysis plan or the sample-size justification. The stated planning assumptions are not a substitute for those details. Without the analysis rules and contributing denominators, readers cannot fully assess how outcome selection, missing data, or repeated measurements influenced the intended analysis.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5.00% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: viral upper respiratory tract infection (1.6%), anaemia megaloblastic (0.8%), pyrexia (0.8%).

The registry reports serious adverse events for the CYD dengue vaccine and placebo groups. The number at risk was 127 in the vaccine group and 61 in the placebo group; serious adverse events affected 1 participant in each group. The record also lists other adverse events affecting 14 participants in the vaccine group and 3 in the placebo group. These are counts as recorded, not adjusted comparisons.

Among the serious adverse-event terms listed, viral upper respiratory tract infection is reported as 1.6%, while anaemia megaloblastic and pyrexia are each reported as 0.8%. These entries identify terms and percentages; they do not provide a full account of event timing, recurrence, severity grading, relatedness assessment, or duration. The registry record does not report deaths.

As a general statistical point, adverse-event counts depend on how events are defined, how long participants are observed, and whether participants have comparable opportunities for events to be detected. A count alone does not show whether an event was caused by an intervention. A comparative safety interpretation also requires context such as follow-up, event ascertainment, and the analysis approach. Those details are not reported in the registry record, so the counts should be read descriptively rather than as proof of a causal difference.

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

The registry record establishes that a randomized, single-masked, parallel phase 2 study was conducted in healthy adults aged 18 to 45 years in India. It describes a vaccine and placebo schedule, an antibody assay, a serotype-specific threshold endpoint, and selected safety counts. It does not report numerical results for the primary antibody endpoint, confidence intervals, or a statistical comparison of vaccine with placebo.

Accordingly, the record does not establish the size or precision of any difference in the percentage of participants meeting the antibody criterion. It also does not show whether responses varied by serotype, changed after successive vaccinations, or differed by flavivirus immune status. Although the registry lists related antibody outcomes, their results are not reported. The secondary objective was to detect symptomatic dengue cases, but case results are not reported either.

These absences do not mean that no antibody responses or symptomatic cases occurred. They mean that the registry record does not provide the numerical evidence needed to characterize those outcomes. Likewise, the serious adverse-event counts do not, by themselves, establish a cause or a comparative safety effect. The record gives descriptive counts but not the fuller context needed for a causal interpretation.

As a general statistical principle, evidence about an estimate’s precision requires both the estimate and an uncertainty measure, interpreted with the analysis population and assumptions. Those primary endpoint results are absent from the registry record. The study’s design and objectives can be described, but the record does not support a conclusion about the magnitude of an antibody response or a treatment effect. It should not be read as evidence that the vaccine works or does not work.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a registry can describe a complex immunogenicity question while leaving the numerical answer unavailable. The primary endpoint is not a single measurement at a single visit: it concerns a threshold-based percentage for each dengue serotype, measured before vaccination and after successive doses. The registry also lists results by flavivirus immune status and geometric mean titer outcomes. Each kind of measure answers a different descriptive question.

The distinction between the design and the results is important. Randomization, a parallel-group structure, and a placebo comparator define a framework for comparison. They do not themselves provide the observed difference or its uncertainty. Likewise, describing a plaque reduction neutralization test identifies how antibody levels were measured, but does not reveal the distribution of the measurements or the percentage meeting the threshold.

The record also illustrates why denominators and missingness matter. Enrollment was 189, while the primary endpoint population is defined by available data at each time point. Without time-specific denominators, readers cannot determine how many observations contributed to a given percentage or whether availability changed over follow-up. Multiple serotypes and time points further make a transparent analysis plan important for interpreting a collection of findings.

Finally, safety counts are most useful when accompanied by context about event ascertainment, follow-up, and comparative methods. The record lists serious and other event counts, but does not report those additional details. Statistical interpretation therefore depends not only on the trial’s design, but also on complete outcome reporting and clear analysis descriptions. In this record, those details are limited, so the strongest conclusions concern what was planned and recorded rather than comparative efficacy or precision.

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 principal limitation for interpreting the primary objective is that numerical antibody results are not reported in the registry record. No percentages, group contrasts, confidence intervals, or primary p-values are available. This prevents assessment of the response pattern by serotype or time point and prevents evaluation of the precision of a comparative estimate.

The registry defines the analysis population as the Full Analysis Set with available data at each time point, but does not report the number assessed at each visit. Missing-data reasons and handling methods are not reported. Because the endpoint is a percentage, changes in the set of participants with available measurements could affect interpretation across visits; the record does not allow that possibility to be evaluated.

The registry also does not report the allocation ratio, who was masked, baseline characteristics, or a detailed statistical analysis plan. Multiplicity procedures for the range of serotype-specific, time-specific, and immune-status outcomes are not reported. The sample-size justification is not reported in the registry record, and the stated planning assumptions are not evidence of observed power.

Safety interpretation is constrained by the selected counts and terms in the record. Detailed definitions, event timing, exposure duration, relatedness assessments, and the method for comparing groups are not reported. Deaths are not reported in the registry record. Symptomatic dengue case results, despite being a secondary objective, are also not reported. These limitations mean that the record supports a description of the trial framework and selected observations, but not a complete assessment of its outcome evidence.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of a Tetravalent Dengue Vaccine in Healthy Adult Subjects Aged 18 to 45 Years in India — NCT01550289.
• Registry record last updated 2022-04-05; status last verified 2022-03.
• Results first posted 2016-11-03.
• 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

NCT01550289 is a completed phase 2 randomized, single-masked, parallel study of a tetravalent dengue vaccine in healthy adults aged 18 to 45 years in India. Enrollment was 189. The vaccine and placebo groups were scheduled for doses at 0, 6, and 12 months.

The primary endpoint was the percentage meeting a dengue neutralizing antibody threshold for each serotype, assessed before injection 1 and 28 days after each injection through 13 months after injection 1. The assay was a dengue plaque reduction neutralization test, and the endpoint population was the Full Analysis Set with available data at each time point.

Numerical primary outcome results and statistical analyses are not reported in the registry record. Safety entries include serious adverse events affecting 1 participant in each group and other adverse events affecting 14 participants in the vaccine group and 3 in the placebo group. The record also lists serious-event terms and percentages, but does not report deaths or symptomatic dengue case results.