Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants (NCT00342628), a randomized phase 2 study. The primary outcome is Number of Infants With Adverse Reactions After Vaccination.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 2 study with no masking. The registry lists 301 participants as enrolled and the study status as completed. The start is recorded as 2006-07 and primary completion as 2008-04. The sponsor was the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The three groups differed in the vaccine schedule. Infants in the Vi-rEPA group received Vi-rEPA and DTP at 2, 4, and 6 months, then Vi-rEPA at 12 months. Infants in the Hib-TT group received Hib-TT and DTP at 2, 4, and 6 months, then Hib-TT at 12 months. The DTP group received DTP at 2, 4, and 6 months. The brief summary describes Hib-TT as not yet used in Vietnam at the time of the study.

The registry describes observation of reactions at 6, 24, and 48 hours after each injection. It also describes maternal and cord blood collection and infant blood sampling at 7 and 12 months, with an additional sample at 13 months for infants given Vi-rEPA or Hib-TT at 12 months. The listed antibody measures include responses to Vi, Hib, diphtheria, tetanus, and pertussis antigens.

The brief summary says the infant IgG anti-Vi response was to be compared with responses in 2 to 5 year-olds in an efficacy trial in Dong Thap Province, Vietnam. The registry record does not report a result for that comparison. It also does not report the randomization method, allocation concealment, detailed eligibility criteria, or a statistical analysis plan.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The number of infants injected in each group for each injection was used to determine the rate of adverse reactions.

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 Infants With Adverse Reactions After Vaccination, measured over at 2, 4, 6 and 12 months.

The primary endpoint is the number of infants with specified adverse reactions after vaccination. The registry lists fever of at least 38.0 C; induration of at least 2.5cm at the DTP site or the Vi-rEPA/Hib-TT site; erythema of at least 2.5cm at either site; and inconsolable crying lasting less than 4hr or at least 4hr. The outcome timeframe is 2, 4, 6, and 12 months.

The registry says the number of infants injected in each group for each injection was used to determine the rate of adverse reactions. That denominator is relevant because the number of infants receiving an injection can vary across visits. The endpoint concerns the occurrence of reactions; it does not, by itself, describe their severity beyond the listed definitions, duration beyond the crying categories, or relationship to vaccination.

Monitoring reactions is one way to describe the safety experience of a vaccine schedule in a study population. The endpoint’s multiple reaction categories and assessment times also mean that a single count cannot fully represent the safety profile. The registry record does not report results for each reaction category and time point, nor does it report a single combined primary-outcome estimate or a comparative analysis. Thus the endpoint is defined, but its primary analysis and findings are not available in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is described as randomized, parallel, and unmasked. In a parallel-group trial, participants are assigned to one group and followed under that group’s schedule. Randomization is intended, in general, to reduce systematic differences between groups at the time of assignment. Whether it achieved that balance in this study cannot be assessed from the registry record because allocation details and baseline characteristics are not reported. The record also does not say whether allocation was concealed before assignment.

What does the primary outcome count?

The primary outcome is a count of infants with specified reactions after vaccination, rather than a continuous measurement such as an antibody concentration. The listed reaction definitions include fever at or above 38.0 C, induration and erythema at or above 2.5cm at named injection sites, and two duration categories for inconsolable crying. Results would need to preserve the distinction among those outcomes and the scheduled assessments at 2, 4, 6, and 12 months. Combining categories or visits could obscure differences in what was measured. The registry’s record of zero analyses means that such outcome-specific results are not reported there.

How should counts and rates be understood?

A count records how many participants experienced an event; a rate or proportion relates that count to a defined number at risk. The registry says the number of infants injected in each group for each injection was used to determine adverse-reaction rates. This matters when the number receiving an injection differs across visits. In general, a count without its denominator can be difficult to interpret, while a rate without a clear definition of the observation period can also be misleading. The posted serious and other adverse-event summaries include numbers at risk, but do not provide the primary reaction outcomes by category and visit.

For binary outcomes such as whether an infant had a specified reaction, a group comparison can be expressed in several ways, including a difference in proportions or a relative measure. These answer different questions and should be accompanied by uncertainty estimates. A confidence interval, in general, describes a range of values compatible with the observed data under the statistical model and its assumptions; it is not a guarantee that the true value lies within that particular interval. The registry does not report comparative estimates or confidence intervals for the primary endpoint, so no measure of precision for those comparisons can be interpreted.

What does the registry say about the analysis?

The record lists no analyses. It does not identify a statistical test, regression model, adjustment variables, handling of repeated assessments, or method for combining reactions across visits. Because infants could be assessed at more than one scheduled time, a full analysis might need to account for repeated observations if it estimates an overall pattern across visits. This is a general methodological consideration, not a claim about the analysis used in the trial. The registry record does not report whether repeated observations were analyzed together or separately.

The record also does not report a sample-size justification, target power, interim analyses, stopping rules, or a prespecified hierarchy for the primary and secondary outcomes. The enrollment number alone does not reveal how the study’s design was chosen or how precise its comparisons were expected to be. No sample-size conclusion can be drawn from enrollment alone.

Why do multiple outcomes matter?

The primary endpoint includes several kinds of reaction and multiple scheduled assessment times. Secondary outcomes include IgG anti-Vi levels and antibody responses to tetanus toxoid, diphtheria toxoid, pertussis toxin, and Hib capsular polysaccharide. When many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures can control or describe that issue, but the appropriate approach depends on the planned questions and analysis. No multiplicity strategy is reported in the registry record, and no outcome analyses are posted.

The record therefore supports a description of the intended methods and outcome definitions, but not an evaluation of statistical significance, effect magnitude, or precision. Those interpretations require outcome-specific results and a clear account of the analysis population and methods.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint contains multiple reaction categories and is assessed at 2, 4, 6, and 12 months. The registry also lists several secondary antibody outcomes. This creates multiple possible comparisons across groups, outcomes, and assessment times. In general, examining many comparisons can increase the chance of observing an apparently notable result by chance. A prespecified hierarchy or multiplicity adjustment can address some of this concern, but the registry record does not report whether either was planned or used.

The record lists zero analyses. It does not give outcome-specific denominators by visit, participant flow, withdrawals, or the number of infants included in each analysis. It also does not report how missing measurements, missed visits, or incomplete antibody samples were handled. No imputation method, sensitivity analysis, or missing-data assumption is reported in the registry record.

The analysis population is also not specified. The record does not say whether results were intended to include all randomized infants, only those who received a vaccine, or participants with measurements available at each visit. These choices can affect the interpretation of estimates, particularly when follow-up or data availability differs between groups. The registry’s safety counts should not be treated as a substitute for a clearly defined analysis population or a complete account of missing data.

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 serious adverse event terms

Serious events with the highest arm-level rate: death (1.0%).

The registry lists serious adverse events separately from other adverse events. For serious events, it records 1 affected participant among 100 at risk in the Vi-rEPA Plus DTP group, 1 among 101 in the Hib-TT Plus DTP group, and 0 among 100 in the DTP Vaccines group. For other adverse events, it records 0 affected participants in each group. These are descriptive counts; the registry record does not provide comparative statistical analyses or uncertainty estimates for them.

The serious-event summary also lists “Death” as a top serious term at 1.0%, while the group-level death counts are recorded as missing. The record does not explain this discrepancy or provide enough detail to determine how the term listing relates to the group counts. The death entry should therefore not be interpreted as a complete account of deaths by group. The registry record does not report event timing, participant-level descriptions, causality assessments, or outcomes for the serious events.

These entries do not establish whether an event was caused by a vaccine, and they do not capture the primary endpoint’s individual reaction categories. Their interpretation is limited to what the registry records, with the missing details and the death-count inconsistency kept in view.

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

The registered study is a randomized evaluation of Vi-rEPA and Hib-TT schedules given alongside DTP in infants in Vietnam. Its stated aims included safety, immunogenicity, and compatibility with DTP. The record defines a primary safety endpoint and lists secondary antibody outcomes. It also records limited group-level adverse-event counts.

What the record does not provide is equally important: it reports no primary-outcome analyses, no reaction results by type and assessment time, and no numerical antibody findings. There are no comparative effect estimates, confidence intervals, or p-values for those outcomes. The serious-event counts are descriptive and are accompanied by incomplete detail, including missing group-level death counts despite a serious-term listing for Death.

In general, a randomized design can support comparisons between groups, but interpretation depends on complete outcome reporting, clear denominators, analysis methods, and information about missing observations. Here, the registry record does not report those elements in enough detail to evaluate comparative effects or their precision. The enrollment figure and the description of scheduled assessments do not fill that gap.

Therefore, the posted information documents what investigators intended to study and gives some safety entries, but it does not establish how the groups compared on the defined primary endpoint or antibody outcomes. The absence of reported analyses is not evidence that the groups were the same, nor is it evidence of a difference. It means that the comparative questions cannot be answered from the registry results reported.

13. Why This Trial Matters Statistically

This trial is statistically notable for the way its primary endpoint combines several clinically distinct reaction definitions with repeated assessment times. Fever, injection-site findings, and crying are not interchangeable outcomes, and their patterns may differ across visits. Clear reporting by category and time point is important for readers to understand what was counted and how the groups were compared.

The study also illustrates why outcome definitions are only one part of a statistical report. The registry describes the reaction thresholds and says the number of infants injected at each visit was used to determine rates. But without reported outcome counts by category and visit, analysis methods, and uncertainty estimates, readers cannot quantify the differences or assess their precision.

Another statistical issue is the breadth of the intended assessment: a primary safety outcome, several antibody outcomes, and comparisons across three schedules. Multiplicity and analysis-population choices can influence how results are interpreted. The registry record does not report a strategy for these issues, and it lists no analyses.

Finally, the serious-event entries show why data completeness and internal consistency matter. The group counts, risk denominators, serious-term listing, and missing death counts need to be interpreted together rather than reduced to a simple conclusion. In this record, the design and outcome definitions are documented more fully than the numerical analysis results. That distinction is central to sound statistical interpretation.

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 most important limitation for interpreting the registry record is the absence of reported primary-outcome analyses. Although the endpoint specifies reaction types and assessment times, no corresponding results are given by category or visit. The antibody outcomes are also listed without numerical findings. This prevents assessment of comparative effect magnitude and precision.

The record does not report participant flow, group baseline characteristics, adherence to the schedules, withdrawals, or visit-specific denominators for the primary reactions. It therefore does not show how many participants contributed data at each assessment or whether data availability differed between groups. Missing-data methods and analysis populations are not reported.

There is also limited detail on adverse events. The registry provides group-level serious and other event counts, but does not describe event timing, clinical features, relatedness, or outcomes. The “Death” serious-term entry is accompanied by missing group-level death counts, and the record does not explain the relationship between them.

Other design details are not reported, including the randomization procedure, allocation concealment, blinding of outcome assessment, sample-size justification, interim analyses, and statistical analysis plan. The record states that the study was unmasked, but does not explain whether reaction assessment was independently blinded. These omissions limit assessment of possible bias and of the planned statistical interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Immunogenicity and Compatibility With DTP of a Typhoid Fever Vaccine in Infants — NCT00342628.
• Registry record last updated 2012-06-27; status last verified 2012-05.
• Results first posted 2012-06-27.
• 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.

18. Record Summary

NCT00342628 is a completed randomized, parallel-group phase 2 study sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The record lists enrollment of 301 and evaluates Vi-rEPA with DTP, Hib-TT with DTP, and DTP alone in infants in Vietnam.

The primary outcome is the number of infants with specified adverse reactions after vaccination at 2, 4, 6, and 12 months. Secondary outcomes include antibody responses to Vi, Hib, diphtheria, tetanus, and pertussis antigens. The registry describes the schedules and sample collection but lists zero analyses. It does not report primary-outcome results, comparative estimates, uncertainty intervals, or antibody findings. Serious and other adverse-event counts are recorded, with limited event detail and missing group-level death counts.