A Comparison of the Safety and Immunogenicity of Various Schedules of Dengue Vaccine in Healthy Adult Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Comparison of the Safety and Immunogenicity of Various Schedules of Dengue Vaccine in Healthy Adult Volunteers (NCT01542632), a randomized phase 1 study. The primary outcome is Number of Participants With Injection Site Reactions Following Either Vaccine Dose Worst Severity Reported.

2. Clinical Question

The trial’s stated purpose was to compare the safety, tolerability, and immunogenicity of different subcutaneous dose schedules in healthy adults. Immunogenicity concerns the immune response measured in the study; here, the record identifies dengue neutralizing antibodies in serum as an outcome. The central statistical question is therefore whether the recorded safety and immune-response measures differ across the assigned schedules, not whether a vaccine prevents dengue illness. The registry record does not report a disease-prevention outcome.

Six groups received distinct schedules. These included the original TDV, a new formulation, placebo injections, and the lower-dose schedule identified as 1/10 TDV. The schedules differed in injections on Day 0 and Day 90, with the Group 6 description specifying Days 1 and 90. Because several features vary across groups, a difference between groups would describe the assigned schedules as a whole; the record does not establish that any particular schedule feature was isolated as the only difference.

3. Trial Design

The registry classifies this as a randomized, Phase 1, parallel-group trial with triple masking. The official title describes it as a randomized Phase 1b study. Enrollment was 140, and the record lists the study status as completed. The sponsor was Takeda.

The six groups received different combinations of vaccine and placebo. Groups 1 through 3 received the original TDV on Day 0, with differences in whether doses on that day and Day 90 were vaccine or placebo. Groups 4 and 5 used the new formulation, with placebo or vaccine injections on Days 0 and 90. Group 6 is described as receiving 1/10 TDV on Days 1 and 90. The registry describes the injections as subcutaneous and lists 0.5 mL for the arm schedules. These are schedule descriptions, not evidence that the schedules produced equivalent exposure or response.

Random allocation means assignment to groups was determined through a random process, as stated in the registry. In general, random allocation is intended to reduce systematic differences between groups at baseline; it does not guarantee that groups will be identical, particularly in a study of this size. Triple masking indicates that the registry classifies the study as masked at three levels, but which individuals were masked and how masking was implemented are not reported in the registry record.

The record gives a study start of 2012-02-01 and primary completion of 2014-01-01. It states that each participant’s participation lasted approximately 5 months, including recruitment and data collection for primary outcomes through Day 120. Blood draws for safety laboratory measures and viremia, and serum collection for neutralizing antibody measures, were scheduled at specified study days. The record does not provide participant flow by group, protocol deviations, or a detailed account of follow-up completion.

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: Participants were enrolled in 1 of 6 treatment groups (GRP). GRP1: 1 dose TDV on Day 0 and 90, GRP2: 2 doses of TDV on Day 0, GRP3: 2 Doses of TDV on Day 0 and 1 dose of TDV on Day 90, GRP4: 1 Dose of TDV New Formula on Day 0 and 90, GRP5: 2 doses of TDV New Formula on Day 0 and 90 and GRP6: 1/10 dose of TDV on Day 0 and 90.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all enrolled participants who received at least one dose of study drug.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Injection Site Reactions Following Either Vaccine Dose Worst Severity Reported, measured over Day 0 to Day 104.

The primary endpoint counts participants with injection-site reactions following either vaccine dose, using the worst severity reported. It covers Day 0 to Day 104. The record names erythema, edema, pain, and itching. Erythema and edema were graded according to FDA guidance for preventive vaccine clinical trials in healthy adult and adolescent volunteers. Pain and itching were graded using CTCAE 4.03. The severity scales range from no symptom to severe or life-threatening, depending on the reaction type.

Counting participants with an event is a binary-outcome approach: each participant is classified according to whether the event occurred, rather than how many times it occurred. Using the worst reported severity retains the highest recorded grade for a participant over the stated period. In general, this can make a safety summary easier to interpret when symptoms are recorded repeatedly or at different grades. It also means that the summary does not show the timing, duration, or sequence of reactions.

The registry says that only score categories with at least one participant are reported. That reporting rule means an unlisted severity category cannot be treated as a separately reported zero without additional information. Although the endpoint definition is present, the record does not provide an analyzed result for this primary outcome. It also does not report a statistical comparison for injection-site reactions, so the endpoint definition alone cannot establish whether the groups differed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, triple-masked, parallel-group study. In general, randomization supports comparisons by assigning participants to groups through chance rather than investigator choice. It helps address confounding by measured and unmeasured baseline factors on average, although chance imbalances can remain. A parallel design means participants are assigned to a group and followed under that group’s schedule, rather than crossing through multiple schedules. The registry does not report the randomization sequence, allocation concealment procedures, or the identities of the people masked.

What does the primary endpoint count?

The primary endpoint is a participant count: participants who experienced injection-site reactions following either vaccine dose, classified by the worst severity reported. This is a binary outcome at the participant level, because the relevant distinction is whether a participant had an event. The grading criteria differ by symptom type: erythema and edema use FDA guidance, while pain and itching use CTCAE 4.03. As a general statistical matter, binary outcomes can be described with counts and proportions, and groups can be compared with an appropriate model or test. The registry does not report a model, test, effect estimate, or confidence interval for this endpoint.

Worst severity is a summary across observations: it retains the highest grade recorded for a participant during the stated period. In general, that approach can represent the most severe recorded experience, but it discards information about how long a reaction lasted, how often it occurred, and whether severity changed. The record says only categories with at least one participant are reported. The observed categories and their group-specific values are not available in the record’s primary-outcome result, so no severity distribution can be reconstructed from the endpoint definition.

How should the group schedules be understood?

The six groups are schedule groups, not repeated observations of the same participants under different schedules. Comparisons among them could address the overall assigned schedules, but the vaccine formulations, numbers of injections, and placebo use vary. In general, interpreting a difference between groups requires attention to these design differences and to the particular contrast being estimated. The registry record does not state a prespecified hierarchy of comparisons or identify one primary pairwise contrast.

The trial is classified as Phase 1, and its stated focus is safety, tolerability, and immunogenicity. In general, early-phase studies often describe safety and biological response, but that general context does not establish the statistical plan or objectives beyond what the registry states. The record does not report a sample-size justification, power calculation for the trial, or assumptions used to choose the enrollment target.

What is missing from the analysis report?

The registry lists six outcome measures and zero analyses. It does not report an analysis population for the primary endpoint beyond the definition of the safety population: enrolled participants who received at least one dose of study drug. It does not describe whether results were analyzed according to randomized assignment, how missing observations were handled, or whether any participants were excluded from specific analyses. It also does not provide a statistical model, adjustment variables, testing procedure, or confidence intervals.

In general, a confidence interval communicates uncertainty in an estimated effect and depends on the data and analysis method. A p-value, when reported, measures compatibility of data with a specified null model under its assumptions; it does not measure clinical importance. Neither a p-value nor a confidence interval for the primary endpoint is reported in the registry record. Thus there is no basis to label a difference statistically significant or to quantify its precision.

Multiplicity arises when several outcomes, time points, groups, or comparisons are tested. In general, conducting many tests without an appropriate strategy can increase the chance of at least one false-positive finding. This study description includes multiple groups and secondary outcomes, but the record does not report a multiplicity procedure or the testing plan. The absence of a stated procedure should not be interpreted as evidence that no such procedure existed outside the registry record.

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is stated as a fraction of the observed effect. Such illustrations are not observed power and do not establish how the original trial was designed. No numerical planning results are included in the record analyzed here, and the original protocol’s sample-size justification is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and zero analyses. It identifies the primary injection-site-reaction outcome and two secondary outcome topics: serotype-specific TDV viral RNA detection after vaccinations, and geometric mean neutralizing antibody titers for all four dengue serotypes. The registry record does not report a multiplicity strategy for outcomes, time points, or comparisons among the six groups.

In general, multiplicity matters when several hypotheses are assessed. If many tests are performed, the chance of at least one apparently unusual result can increase unless the testing strategy accounts for the number and structure of comparisons. Possible approaches depend on the study objectives and analysis plan. No particular approach can be attributed to this trial from the registry record.

The record gives the safety-population definition: enrolled participants who received at least one dose of study drug. It does not report a separate analysis population for immunogenicity, a population defined by protocol adherence, or whether results were analyzed according to randomized assignment. The record also does not explain how missing endpoint observations, missed visits, withdrawals, or incomplete blood samples were handled. These details are not reported in the registry record.

The primary outcome description specifies Day 0 to Day 104, while the study description says primary-outcome data collection continued through Day 120. The registry does not explain this distinction further. It also does not provide a participant flow diagram or group-specific completion counts. Without these details, the extent and handling of missing data cannot be assessed from the registry entry.

These omissions do not show that the original investigators lacked an analysis plan or did not address missingness or multiple testing. They mean only that such methods are not reported in the registry record. Since no analyses are listed, there are no reported adjusted comparisons or uncertainty estimates to evaluate.

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% reporting threshold.

Most frequent non-serious adverse event terms

The serious-adverse-event summary lists zero affected participants in each of the six groups. The numbers at risk are 25 in Group 1, 25 in Group 2, 24 in Group 3, 21 in Group 4, 21 in Group 5, and 24 in Group 6. These are descriptive counts from the registry record; no formal comparison or uncertainty estimate is reported.

In general, an observed count of zero is not proof that an event cannot occur. It describes what was recorded in the participants represented in that group, while the underlying event risk remains uncertain. The record does not provide event-specific definitions or further details for the serious-adverse-event summary, and it does not list serious-event terms.

The record separately lists participants with other adverse events: 24 in Group 1, 18 in Group 2, 20 in Group 3, 16 in Group 4, 17 in Group 5, and 18 in Group 6. These are not serious-event counts and should not be conflated with the zero serious-event entries. The registry summary does not supply details on event types, severity, or timing. The counts alone do not establish comparative safety or explain why counts differ among groups.

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

The registry record establishes that a randomized, triple-masked, parallel-group Phase 1 study compared six dengue vaccine schedules in healthy adult volunteers. It defines a primary safety outcome based on injection-site reactions and identifies viral RNA detection and neutralizing antibody titers as secondary outcomes. It also provides descriptive counts for serious and other adverse events by group.

What the record does not establish is the size or precision of a difference in the primary endpoint. No primary-outcome analysis is listed, and the record explicitly says the outcome has several categories or time points and was not reduced to one comparison. No confidence interval, p-value, or model-based estimate is reported. The secondary outcome topics are named, but their results and analyses are not reported.

The serious-event listing contains zero affected participants for each group, while the other-adverse-event counts vary across groups. These figures are descriptive, and the record provides no statistical comparison that would indicate whether differences are more than expected from sampling variation. The counts should not be used to infer that one schedule is safer, nor should zero recorded serious events be interpreted as evidence of zero underlying risk.

In general, study findings must be interpreted in light of the population, treatment schedules, outcome definitions, follow-up, and analysis methods. This trial involved healthy adults and was designed around safety and immunogenicity measures; the registry does not report a clinical dengue-prevention outcome. Therefore, the posted information cannot establish vaccine effectiveness against dengue disease. It also does not support conclusions about populations outside the stated healthy-adult context or about schedules not studied.

The most defensible reading is limited: the registry describes the trial and records adverse-event counts, but does not provide the analyses needed to quantify comparative primary or secondary outcomes. The absence of an analysis in the registry record is not evidence that an analysis was never performed elsewhere.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of a multi-group early-phase design in which schedules, formulations, and placebo use vary. Such a structure creates several possible contrasts, and the interpretation depends on which comparison was planned and how it relates to the study question. The registry record does not identify a single primary pairwise contrast or provide an analysis plan, making clear why design details and analysis reporting are essential for understanding comparative results.

The primary endpoint also illustrates a common safety-summary choice: counting participants according to whether they experienced a reaction and retaining the worst recorded severity. In general, this makes participant-level event summaries possible, but it reduces repeated symptom observations to a single classification. Reporting the definition is useful, yet counts by severity and group are needed to interpret the outcome, and those primary endpoint results are not reported in the registry record.

The study includes multiple secondary outcomes, repeated collection days, and six schedule groups. In general, those features raise questions about multiple comparisons, time-point selection, missing observations, and the target analysis population. The registry record does not describe how those issues were handled. This does not prove that the underlying study lacked methods for them; it highlights the limits of the registry entry as an analysis report.

Finally, the distinction between a schedule study and a disease-prevention trial matters. The stated outcomes concern safety, viral RNA, and neutralizing antibody measures. These can characterize observed responses in the study, but the registry record does not report a dengue illness-prevention endpoint. Statistical interpretation must stay within the outcomes and population documented rather than extending the findings to an unreported question.

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 main limitation for interpreting results is that the registry lists zero analyses. Although the primary endpoint and secondary outcome topics are described, their group-specific results are not reported as analyses. No effect estimates, confidence intervals, or hypothesis tests are available for the primary endpoint. The registry’s note that the primary outcome was not reduced to one comparison further limits direct comparative interpretation.

The sample-size justification for the original trial is not reported in the registry record. The record describes a planning illustration based on an observed effect, but such an illustration is not the original trial’s design rationale and is not observed power. Without the protocol’s assumptions or a reported analysis, the enrollment of 140 cannot be evaluated as adequate for any particular contrast from this record alone.

The study has six groups with differences in formulation, dose schedule, and placebo administration. This complicates attributing any hypothetical group difference to a single feature. The record does not report a prespecified comparison hierarchy, multiplicity adjustment, or detailed statistical model. Participant flow, group-specific follow-up completion, and the handling of missing safety or immune-response measurements are also not reported in the registry record.

The serious-adverse-event summary reports zero affected participants in each group, but no confidence limits or event-term details are provided. Other adverse-event counts are also listed without event descriptions or inferential comparisons. These summaries do not convey the full timing, severity, duration, or clinical context of events.

Finally, the study concerns healthy adults and reports safety and immunogenicity objectives. The registry does not report a clinical dengue-prevention outcome. Any interpretation beyond the documented study population, schedules, and recorded outcomes would exceed what this registry record supports.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Comparison of the Safety and Immunogenicity of Various Schedules of Dengue Vaccine in Healthy Adult Volunteers — NCT01542632.
• Registry record last updated 2019-07-18; status last verified 2019-07.
• Results first posted 2015-01-09.
• 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

NCT01542632 is a completed randomized, triple-masked, parallel-group Phase 1 study sponsored by Takeda. It enrolled 140 healthy adult volunteers and compared six schedules involving TDV, a new formulation, placebo, or the 1/10 TDV schedule. The official title specifies ages 18–45 years.

The primary endpoint was the number of participants with injection-site reactions after either vaccine dose, using the worst reported severity from Day 0 to Day 104. Secondary outcomes concerned serotype-specific viral RNA detection and geometric mean neutralizing antibody titers. The record lists six outcome measures and zero analyses, and does not report comparative results for the primary endpoint or secondary outcomes.

The serious-adverse-event summary lists zero affected participants in each group. Other adverse-event counts are also reported descriptively. Analysis methods, missing-data handling, multiplicity procedures, and the original sample-size justification are not reported in the registry record.