This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years (NCT01511250), a randomized phase 2 study. The primary outcome is Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01511250 |
| Phase | Phase 2 |
| Condition | Healthy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 360 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Takeda |
| Results posted | Yes |
2. Clinical Question
The trial asked whether the safety and antibody responses associated with Takeda’s tetravalent dengue vaccine could be assessed in healthy adults and children. The registry describes a randomized, placebo-controlled study with age-descending and expansion phases. Its stated purpose was to assess safety after subcutaneous vaccination and evaluate antibody responses to the four dengue virus serotypes.
Population
Healthy volunteers aged 1.5 to 45 years. The safety population included randomized participants who received at least one dose of vaccine or placebo.
Intervention
Tetravalent chimeric dengue vaccine, abbreviated TDV in the registry record. The described regimen was a 0.5 mL subcutaneous injection on Day 0 and Day 90.
Comparator
A placebo-matching 0.5 mL subcutaneous injection on Day 0 and Day 90.
Primary question
How many participants reported solicited injection-site adverse events, grouped by severity, within 14 days after either vaccination?
The primary outcome concerns local reactions recorded in participant diaries. The registry describes grading for pain, itching, redness, and swelling. It does not post the outcome counts by severity, so the record cannot establish how those counts compared between TDV and placebo. The broader question about antibody responses is represented by secondary outcomes covering seropositivity, seroconversion, neutralizing antibody titers, and fold rises for the four serotypes. Their results are not reported in the registry record.
3. Trial Design
This was a Phase 2, randomized, quadruple-masked, parallel-group, placebo-controlled study. Its official title describes an age-descending phase followed by an expansion phase. The trial enrolled 360 participants and is marked completed in the registry. The recorded study start was 2011-11-16, and primary completion was 2016-04-01.
Part I separated participants into age groups: 21 to 45 years, 12 to 20 years, 6 to 11 years, and 1.5 to 5 years. Each age group had a TDV arm and a placebo arm. Part II included participants aged 1.5 to 11 years and also had TDV and placebo arms. These groupings show that the study was organized to evaluate the vaccine across different ages, with a later expansion among younger participants. The record does not describe the rationale for the expansion or how enrollment decisions were made.
TDV and placebo were administered by subcutaneous injection, with doses scheduled on Day 0 and Day 90. In the vaccine arms, the stated vaccine volume was 0.5 mL. The registry describes TDV as containing four recombinant, live attenuated dengue virus strains. The placebo arms received a placebo-matching injection on the same schedule.
Randomization and quadruple masking are features of the design, but the registry record does not report how the random sequence was generated, how treatment assignments were concealed, or which groups of people were masked. It also does not report whether masking was assessed. These omissions do not change the recorded design classification, but they limit the detail available for evaluating how those features were implemented.
The listed enrollment is 360, while safety summaries are organized by the separate trial arms. The record does not explain all differences between planned enrollment and the arm-level safety counts. Detailed recruitment flow, withdrawals, and reasons for leaving the study 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.
Before assignment: Healthy participants were enrolled in the 2-part study to receive 0.5 mL tetravalent dengue vaccine (TDV) or placebo in 1 of 4 groups for Part I: 21-45 years, 12-20 years, 6-11 years, 1.5-5 years, and in 1 group for Part II: 1.5-11 years. Part II started after all subjects in Part 1 were enrolled.
Only the first 6 of 10 groups are shown.
Overall Study
| Stage | Part I: TDV 21 to 45 Years | Part I: Placebo 21 to 45 Years | Part I: TDV 12 to 20 Years | Part I: Placebo 12 to 20 Years | Part I: TDV 6 to 11 Years | Part I: Placebo 6 to 11 Years |
|---|---|---|---|---|---|---|
| STARTED | 24 | 14 | 22 | 14 | 21 | 17 |
| COMPLETED | 15 | 9 | 18 | 11 | 21 | 17 |
| NOT COMPLETED | 9 | 5 | 4 | 3 | 0 | 0 |
Reasons for not completing this period:
| Reason | Part I: TDV 21 to 45 Years | Part I: Placebo 21 to 45 Years | Part I: TDV 12 to 20 Years | Part I: Placebo 12 to 20 Years | Part I: TDV 6 to 11 Years | Part I: Placebo 6 to 11 Years |
|---|---|---|---|---|---|---|
| Withdrawal of Consent | 1 | 0 | 0 | 0 | 0 | 0 |
| Sponsor/Investigator Decision | 1 | 0 | 0 | 0 | 0 | 0 |
| Lost to Follow-up | 7 | 3 | 3 | 3 | 0 | 0 |
| Protocol Violation | 0 | 2 | 1 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The safety set included all randomized participants who received at least one dose of study vaccine (or placebo). Only categories for which there was at least 1 participant are reported.
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: The full analysis set (FAS) included all randomized participants who received at least one dose of study vaccine or placebo and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received.
Only the first 6 of 11 groups are shown.
| Characteristic | Unit | Part I: TDV 21 to 45 Years | Part I: Placebo 21 to 45 Years | Part I: TDV 12 to 20 Years | Part I: Placebo 12 to 20 Years | Part I: TDV 6 to 11 Years | Part I: Placebo 6 to 11 Years |
|---|---|---|---|---|---|---|---|
| Participants analysed | 24 | 14 | 22 | 14 | 21 | 17 | |
| Age, Continuous | years | 29.2 (21.0 to 45.0) | 30.1 (21.0 to 40.0) | 15.5 (12.0 to 19.0) | 16.8 (12.0 to 20.0) | 8.4 (6.0 to 11.0) | 7.8 (6.0 to 11.0) |
| Sex: Female, Male: Female | Participants | 10 | 8 | 12 | 7 | 6 | 8 |
| Sex: Female, Male: Male | Participants | 14 | 6 | 10 | 7 | 15 | 9 |
| Race: Asian | participants | 3 | 3 | 16 | 8 | 16 | 12 |
| Race: Hispanic or Latino | participants | 20 | 10 | 6 | 6 | 4 | 5 |
| Race: White | participants | 1 | 1 | 0 | 0 | 1 | 0 |
| Race: Black or African American | participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Seropositive to any Serotype at Day 0: Seropositive to any Serotype=No | participants | 5 | 2 | 7 | 1 | 12 | 14 |
| Seropositive to any Serotype at Day 0: Seropositive to any Serotype=Yes | participants | 19 | 12 | 15 | 13 | 9 | 3 |
| Height | meters (m) | 1.68 (1.57 to 1.82) | 1.65 (1.53 to 1.87) | 1.58 (1.38 to 1.72) | 1.60 (1.41 to 1.73) | 1.29 (1.08 to 1.52) | 1.27 (1.13 to 1.42) |
| Weight | kilograms (kg) | 81.6 (41.4 to 115.1) | 80.2 (56.3 to 120.4) | 57.0 (28.6 to 93.4) | 59.5 (48.6 to 89.9) | 31.2 (18.5 to 51.2) | 27.0 (20.3 to 37.5) |
| Body Mass Index (BMI) | kg/m^2 | 28.81 (14.70 to 41.30) | 29.05 (21.30 to 38.70) | 22.60 (15.00 to 33.60) | 23.09 (18.60 to 31.50) | 18.38 (12.90 to 28.80) | 16.56 (14.20 to 20.60) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity, measured over Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with solicited local injection-site adverse events recorded in diaries after either vaccination dose. The registry’s timeframe is within 14 days after the Day 0 or Day 90 vaccination. It describes four reaction types: pain, itching (pruritus), redness (erythema), and swelling (edema or induration). Counts are classified by severity rather than expressed as a single continuous measurement.
The grading approach combines symptom grades with size-based grades. Pain and itching use the Common Terminology Criteria for Adverse Events, Version 4.03. Redness and swelling grades are derived from the recorded length of the longest diameter, using FDA guidance for preventive vaccine clinical trials. The registry describes Grade 0 as no pain or itching, and provides size thresholds for redness and swelling, including Grade 4 for potentially life-threatening skin findings. In the record’s size definitions, Grade 0 is <2.5 cm, Grade 1 is 2.5-5 cm, Grade 2 is 5.1-10 cm, and Grade 3 is >10 cm.
Counting participants with reactions by severity is useful for describing the frequency and range of reported local events. Severity categories preserve information that would be lost in a single total count. They also mean the outcome comprises multiple categories and vaccination timepoints. The registry reports that only categories with at least one participant are included. The actual primary outcome counts by category are not reported in the registry record, so the size and precision of any treatment comparison cannot be assessed from that record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record supports a description of the study’s design, intended outcomes, and some safety summaries. It does not provide a statistical analysis of the primary endpoint. In particular, there are no posted counts for solicited local injection-site adverse events by severity, no treatment contrast for that endpoint, and no confidence interval or p-value. Accordingly, the registry record does not establish the magnitude or precision of a difference between TDV and placebo for the primary outcome.
The outcome is not a single binary event summarized at one timepoint. It includes several types of local reactions, multiple severity categories, and observations after either vaccination dose. The record explicitly indicates that this primary outcome was not reduced to one comparison because it has several categories or timepoints. That is important when interpreting any attempt to describe the endpoint as though it were a single overall event rate: a single figure would not reflect the full structure specified in the outcome definition.
Arm-level safety summaries list participants at risk and participants affected by serious adverse events and other adverse events. These counts describe events in each listed arm, but the registry does not provide an adjusted comparison, confidence interval, or statistical test for them. The listed denominators also differ across age groups and parts of the study. Without an analysis plan and a clear account of how the separate groups are intended to be compared, those counts should be read descriptively rather than as a single treatment-effect estimate.
The record lists selected serious adverse event terms with percentages, including dengue fever and influenza at 7.7%, abscess limb and cellulitis at 5.9%, and urinary tract infection and viral infection at 4.8%. It does not state the denominator or provide enough context to interpret these percentages as rates for a particular treatment arm or as comparisons with placebo. The event terms and percentages therefore cannot, by themselves, determine whether risks differ between groups.
Secondary outcomes address vaccine viremia and antibody responses to the four dengue serotypes, as well as confirmed dengue fever. The registry lists these outcome types but does not report their analyses. No conclusion about the antibody response or confirmed dengue fever can be drawn from an outcome list alone.
Overall, the record is informative about the trial’s intended design and measurement framework, but its posted results do not permit a quantitative interpretation of the primary endpoint. The relevant point is not that a result is favorable or unfavorable; it is that estimates and uncertainty for the primary comparison are not reported in the registry record.
9. Statistical Methods Explained
What does a participant count represent?
The primary endpoint is a count of participants who experienced a specified event, separated by event type and severity. In general, a participant count is a direct description of how many people in an analysis group met an outcome definition. It is not the same as the number of individual episodes: a participant with more than one reaction could still be counted as a participant with an event, depending on the outcome’s exact rules. The registry record does not report detailed rules for handling repeated reactions or assigning a participant to a severity category.
Counts are easiest to interpret alongside the number of participants assessed in each arm and a clearly defined observation period. Here, the endpoint specifies diary-recorded local reactions within 14 days after either vaccination. The registry also says the safety set comprises randomized participants who received at least one dose of study vaccine or placebo. The primary endpoint’s arm-specific counts and denominators are not reported in the registry record, so event frequencies and treatment contrasts cannot be reconstructed.
Why keep severity categories separate?
In general, severity categories distinguish events with different levels of intensity or clinical grading. Combining them can simplify a summary, but it can also conceal whether the underlying events were mostly mild or included more severe grades. Reporting categories separately can make the pattern more visible. At the same time, multiple categories create a more complex result than a single yes-or-no endpoint. Interpretation requires knowing how categories were defined, whether they overlap for a participant, and which comparisons were planned. The registry describes grading criteria but does not report the full analysis rules or the category-specific results.
What can a confidence interval tell a reader?
General explanation: a confidence interval gives a range of values compatible with an estimate under the statistical method used. A narrow interval indicates greater precision than a wide interval, while an interval spanning values on both sides of no difference may leave the direction or size of a treatment contrast uncertain. A confidence interval does not correct for bias, incomplete outcome collection, or inappropriate analysis choices. No confidence intervals for the primary outcome are reported in the registry record, so its precision cannot be judged from this source.
Why might over-dispersion matter?
General explanation: over-dispersion arises when event-count variability is greater than a chosen statistical model expects. If it is ignored, standard errors can be too small and confidence intervals too narrow. The primary endpoint is described as participants with events in severity categories, rather than as a repeated event count with a stated distributional model. The registry record does not report a model or an over-dispersion assessment, so there is no basis to say whether either was used or needed.
What do the planning illustrations mean?
The registry describes planning illustrations based on the 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 expressed as a stated fraction of the observed effect. Those calculations are planning illustrations, not evidence that the trial had a particular probability of detecting an effect. They are not observed power. The trial’s own sample-size justification, design assumptions, and any formal power calculation are not reported in the registry record. The illustration’s numerical sample-size values are not reported in the registry record.
How should multiplicity affect interpretation?
General explanation: multiplicity occurs when several hypotheses, outcomes, groups, or timepoints are examined. If many tests are considered, the chance of at least one apparently unusual result can increase unless the analysis accounts for that structure. This trial lists local events by reaction and severity, antibody outcomes for four dengue serotypes, and additional safety and viremia outcomes. The registry record does not report a prespecified testing hierarchy, a multiplicity adjustment, or a detailed statistical analysis plan. It is therefore not possible to determine how multiple comparisons were handled.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists outcomes covering several domains: local and systemic safety, vaccine viremia, seropositivity, seroconversion, neutralizing antibody titers, fold rises, and confirmed dengue fever. Several antibody outcomes are defined for each of the four dengue serotypes. The primary safety endpoint itself includes different local reactions and severity categories after either vaccination. This creates multiple outcome dimensions and timepoints that can matter when interpreting a collection of statistical tests.
In general, multiplicity can make apparently notable findings more likely when many comparisons are tested. A prespecified hierarchy or adjustment can help control interpretation, but the registry record does not report whether such procedures were planned or used. A detailed statistical analysis plan, including rules for selecting the primary comparison and handling secondary outcomes, is not reported in the registry record. The registry lists 14 outcome measures and no analyses; that absence means there are no posted analysis results from which to assess multiplicity handling.
The recorded safety population includes all randomized participants who received at least one dose of vaccine or placebo. This defines who was eligible for the safety summaries, but it does not describe how missing diary entries, missed visits, or incomplete antibody measurements were treated. Methods for missing data, imputation, censoring, and sensitivity analyses are not reported in the registry record. Nor does the record provide a detailed participant flow account for each outcome.
Analysis populations for immunogenicity outcomes are not reported in the registry record. The difference between a treated safety population and an analysis population for antibody measurements may be consequential, but the record does not describe those rules. These omissions limit assessment of selection, missingness, and reproducibility; they do not establish that the study analyses were inappropriate.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Part I: TDV 21 to 45 Years | 4 | 24 | 16.7% |
| Part I: Placebo 21 to 45 Years | 0 | 14 | 0.0% |
| Part I: TDV 12 to 20 Years | 1 | 22 | 4.5% |
| Part I: Placebo 12 to 20 Years | 0 | 14 | 0.0% |
| Part I: TDV 6 to 11 Years | 4 | 21 | 19.0% |
| Part I: Placebo 6 to 11 Years | 1 | 17 | 5.9% |
| Part I: TDV 1.5 to 5 Years | 1 | 23 | 4.3% |
| Part I: Placebo 1.5 to 5 Years | 2 | 13 | 15.4% |
| Part II: TDV 1.5 to 11 Years | 14 | 159 | 8.8% |
| Part II: Placebo 1.5 to 11 Years | 2 | 53 | 3.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Part I: TDV 21 to 45 Years | 11 of 24 |
| Part I: Placebo 21 to 45 Years | 7 of 14 |
| Part I: TDV 12 to 20 Years | 13 of 22 |
| Part I: Placebo 12 to 20 Years | 8 of 14 |
| Part I: TDV 6 to 11 Years | 9 of 21 |
| Part I: Placebo 6 to 11 Years | 11 of 17 |
Most frequent serious adverse event terms
| Event term | Organ system | Part I: TDV 21 to 45 Years | Part I: Placebo 21 to 45 Years | Part I: TDV 12 to 20 Years | Part I: Placebo 12 to 20 Years | Part I: TDV 6 to 11 Years | Part I: Placebo 6 to 11 Years |
|---|---|---|---|---|---|---|---|
| Cholecystitis | Hepatobiliary disorders | 1 of 24 | 0 of 14 | 0 of 22 | 0 of 14 | 0 of 21 | 0 of 17 |
| Cholecystitis acute | Hepatobiliary disorders | 1 of 24 | 0 of 14 | 0 of 22 | 0 of 14 | 0 of 21 | 0 of 17 |
| Incision site haematoma | Injury, poisoning and procedural complications | 1 of 24 | 0 of 14 | 0 of 22 | 0 of 14 | 0 of 21 | 0 of 17 |
| Incision site haemorrhage | Injury, poisoning and procedural complications | 1 of 24 | 0 of 14 | 0 of 22 | 0 of 14 | 0 of 21 | 0 of 17 |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | 1 of 24 | 0 of 14 | 0 of 22 | 0 of 14 | 0 of 21 | 0 of 17 |
| Abscess limb | Infections and infestations | 0 of 24 | 0 of 14 | 0 of 22 | 0 of 14 | 0 of 21 | 1 of 17 |
| Cellulitis | Infections and infestations | 0 of 24 | 0 of 14 | 0 of 22 | 0 of 14 | 0 of 21 | 1 of 17 |
| Dengue fever | Infections and infestations | 0 of 24 | 0 of 14 | 0 of 22 | 0 of 14 | 1 of 21 | 0 of 17 |
| Hand-foot-and-mouth disease | Infections and infestations | 0 of 24 | 0 of 14 | 1 of 22 | 0 of 14 | 0 of 21 | 0 of 17 |
| Urinary tract infection | Infections and infestations | 0 of 24 | 0 of 14 | 0 of 22 | 0 of 14 | 1 of 21 | 0 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part I: TDV 21 to 45 Years | Part I: Placebo 21 to 45 Years | Part I: TDV 12 to 20 Years | Part I: Placebo 12 to 20 Years | Part I: TDV 6 to 11 Years | Part I: Placebo 6 to 11 Years |
|---|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 4 of 24 | 3 of 14 | 7 of 22 | 1 of 14 | 4 of 21 | 3 of 17 |
| Upper respiratory tract infection | Infections and infestations | 0 of 24 | 1 of 14 | 0 of 22 | 1 of 14 | 3 of 21 | 2 of 17 |
| Myalgia | Musculoskeletal and connective tissue disorders | 0 of 24 | 1 of 14 | 2 of 22 | 4 of 14 | 0 of 21 | 0 of 17 |
| Fatigue | General disorders | 0 of 24 | 2 of 14 | 2 of 22 | 2 of 14 | 0 of 21 | 1 of 17 |
| Pharyngitis | Infections and infestations | 2 of 24 | 1 of 14 | 1 of 22 | 1 of 14 | 0 of 21 | 0 of 17 |
| Pyrexia | General disorders | 0 of 24 | 1 of 14 | 2 of 22 | 1 of 14 | 1 of 21 | 0 of 17 |
| Nasopharyngitis | Infections and infestations | 0 of 24 | 0 of 14 | 3 of 22 | 0 of 14 | 1 of 21 | 0 of 17 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 0 of 24 | 0 of 14 | 2 of 22 | 1 of 14 | 1 of 21 | 0 of 17 |
| Injection site pain | General disorders | 2 of 24 | 0 of 14 | 2 of 22 | 0 of 14 | 0 of 21 | 0 of 17 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 1 of 24 | 1 of 14 | 0 of 22 | 0 of 14 | 0 of 21 | 2 of 17 |
Serious events with the highest arm-level rate: dengue fever (7.7%), influenza (7.7%), abscess limb (5.9%), cellulitis (5.9%), urinary tract infection (4.8%).
The safety summaries list, for each arm, the number of participants at risk and the number affected by serious adverse events and other adverse events. For example, the Part I TDV group aged 21 to 45 years lists 24 participants at risk, with 4 affected by serious adverse events and 11 affected by other adverse events. The corresponding placebo group lists 14 at risk, with 0 affected by serious adverse events and 7 affected by other adverse events. The remaining arm-level values are recorded by age group and study part.
These are descriptive counts. The registry record does not provide an adjusted comparison or uncertainty interval for the serious adverse event counts. Groups have different denominators, and the trial includes multiple age bands and a separate expansion part, so the counts should not be combined into a treatment contrast without a specified analysis. Death counts are not reported in the registry record.
The record separately lists selected serious adverse event terms and percentages: dengue fever and influenza at 7.7%, abscess limb and cellulitis at 5.9%, and urinary tract infection and viral infection at 4.8%. The denominator and the assignment of those percentages to arms or populations are not reported in the registry record. They should not be read as arm-specific incidence estimates or as evidence of a treatment difference.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this was a randomized, placebo-controlled Phase 2 study of TDV in healthy volunteers aged 1.5 to 45 years, with safety and antibody response among its stated aims. It describes the vaccine schedule, placebo schedule, age-based groups, and the way the primary local-reaction outcome was graded. It also posts arm-level counts for serious and other adverse events and selected serious-event terms.
Those details do not amount to a complete statistical evaluation of the primary question. The registry does not report the primary endpoint’s category-specific results, a treatment-effect estimate, a confidence interval, or a p-value. It also does not report analyses of the antibody outcomes, vaccine viremia, or confirmed dengue fever. The record therefore cannot quantify the size or precision of the primary comparison or support a conclusion about the secondary outcomes.
General explanation: a non-significant test, if one were reported, would not by itself prove that two groups are equivalent. Likewise, a difference in raw counts would not by itself establish a reliable treatment effect, particularly when group sizes and outcome definitions differ. Here, the registry does not post a primary endpoint test or estimate at all. The appropriate interpretation is that the comparison is not quantitatively reported in this record, not that the groups were the same or different.
The planning illustrations described in the registry are not trial results and are not observed power. They do not substitute for an outcome estimate or its uncertainty. Similarly, the listed serious adverse event counts and percentages should remain descriptive in the absence of the analysis details needed to interpret them as comparative risks.
These limitations concern what can be concluded from the registry record. They do not establish what analyses may have appeared elsewhere or whether additional data exist outside the record. For the posted information alone, the most defensible reading is a description of design, outcome definitions, and selected safety counts, with the primary statistical comparison and secondary outcome analyses not reported.
13. Why This Trial Matters Statistically
This trial raises several useful statistical issues for clinical researchers. Its population spans healthy volunteers from early childhood through adulthood, and its design separates age groups into an initial part and a younger expansion part. That structure makes clear why age-specific reporting matters: a combined summary can obscure how many participants contributed to each group and whether results were consistent across ages. The registry record lists the groups but does not provide inferential analyses by age.
The primary outcome also illustrates the difference between a clearly described measurement and a statistically interpretable result. The registry specifies diary collection, grading systems, reaction types, and a post-vaccination observation window. Those definitions help readers understand what was intended to be counted. Yet without the category-level counts, denominators, and treatment estimates, neither the size nor precision of the comparison can be assessed.
The safety summaries show why event counts should be interpreted in their group context. The trial has multiple age-specific and expansion groups, with different numbers of participants at risk. Reporting counts without an accompanying comparative analysis leaves open how differences in group size, age composition, and study part should be handled. Selected serious-event percentages also need a clear denominator before they can be understood as risks.
Finally, the secondary outcomes span four serotypes and several kinds of antibody response, alongside viremia and confirmed dengue fever. This breadth makes prespecification and multiplicity procedures important statistical topics. The registry record does not report the plan for those analyses. The case therefore illustrates that detailed endpoint definitions and a randomized design are valuable, but interpretation also depends on posted estimates, uncertainty, analysis populations, missing-data rules, and the statistical plan.
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 this trial from the registry record is the absence of posted analyses for the primary endpoint. Although the endpoint and grading criteria are described, counts by severity and reaction type are not reported. No treatment-effect estimate, confidence interval, or p-value is available for that endpoint. The registry also lists no analyses, so the record cannot support a quantitative account of the primary comparison.
The population and study structure add interpretive complexity. Participants were grouped by age in Part I, while Part II covered ages 1.5 to 11 years. The record does not explain how results from the expansion part were intended to be integrated with Part I, or whether the groups were intended for direct comparison. It does not report participant flow, withdrawals, or reasons for discontinuation by arm.
Other important analysis details are not reported in the registry record: the sample-size justification, statistical analysis plan, randomization procedures, allocation concealment, handling of missing data, analysis populations for antibody outcomes, and multiplicity procedures. The planning assumptions that are described do not provide a substitute for the trial’s own design justification or for results.
For serious adverse events, arm-level counts are available, but comparative estimates and uncertainty are not. Selected event-term percentages are listed without a reported denominator or arm attribution. Death counts are not reported in the registry record. These limitations restrict interpretation of the posted safety summaries and should not be treated as evidence for or against a treatment effect.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years — NCT01511250.
- Registry record last updated 2023-04-12; status last verified 2023-04.
- Results first posted 2018-03-27.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01511250 is a completed, randomized, quadruple-masked, parallel-group Phase 2 study of tetravalent chimeric dengue vaccine in healthy volunteers aged 1.5 to 45 years. The registry describes placebo control, age-based groups, and vaccination on Day 0 and Day 90. Enrollment is listed as 360.
The primary outcome counts diary-recorded local injection-site adverse events by severity within 14 days after either dose. The registry describes safety and antibody-response objectives and lists additional outcomes for viremia, serotype-specific antibody measures, and confirmed dengue fever. It posts some arm-level serious and other adverse event counts, but does not report primary endpoint analyses or secondary outcome analyses.
As a result, the record describes the design and measurement framework but does not provide a quantitative estimate or precision for the primary treatment comparison. Detailed analysis methods, missing-data handling, and multiplicity procedures are not reported in the registry record.