Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Healthy Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Healthy Infants (NCT01098474), a randomized phase 2 study. The primary outcome is Number of Subjects With Grade 3 Solicited Local Symptoms After Dose 1, Dose 2 and Across Doses.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 2 study sponsored by GlaxoSmithKline. It was open-label, meaning masking was not used. The registry lists an enrollment of 301 and describes the study population as healthy infants aged between and including 2 and 7 months who lived in a tuberculosis-endemic region. The study status is completed. Its start date was 2010-07-07, and its primary completion date was 2011-04-30.

The trial examined GSK Biologicals' candidate tuberculosis vaccine 692342 in relation to the primary Expanded Programme of Immunisation regimen. The arm descriptions include candidate-vaccine schedules after completion of the primary EPI regimen, as well as schedules in which candidate vaccine was administered concomitantly with EPI vaccines. Control regimens included Menjugate or the primary EPI regimen containing Tritanrix, Prevnar and Polio Sabin. These are different vaccination schedules, so the comparisons concern the regimens as assigned, not simply the presence or absence of the candidate vaccine in otherwise identical treatment.

Random allocation can reduce systematic differences between groups at assignment, but the registry record does not report the allocation procedure or whether allocation was concealed. With no masking, participants and study personnel could know which regimen was given. That matters particularly for outcomes that involve reporting or assessment of symptoms. The record does not report the detailed procedures used to collect or verify those symptom reports.

The record lists safety and immunogenicity as study aims and includes 61 outcome measures. Its primary outcome concerns severe solicited local symptoms; secondary outcome descriptions include M72-specific T-cell measures. The record does not report results for the primary outcome or statistical analyses. It therefore documents the design and intended measurements, but not an inferential comparison of the candidate-vaccine regimens.

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: One enrolled subject was not administered any vaccine and hence was not considered as having started the study.

Active Phase

Reasons for not completing this period:

Follow Up Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects for whom data were available. As the outcome was defined differently according to the doses received by the subjects in each group, it is presented separately.

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 Subjects With Grade 3 Solicited Local Symptoms After Dose 1, Dose 2 and Across Doses, measured over From Day 0 to Day 6.

The primary endpoint counts participants with grade 3 solicited local symptoms after dose 1, dose 2 and across doses. The symptoms assessed were pain, redness and swelling, with follow-up from Day 0 to Day 6. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness or swelling was defined as redness or swelling spreading beyond 20 millimeters of the injection site.

This endpoint is a measure of marked local reactions during the specified follow-up window. Reporting a participant count makes the outcome interpretable as the number of people meeting the endpoint definition, rather than the number of symptom episodes. The registry description says results are presented separately because the outcome was defined differently according to the doses received by participants in each group. That distinction is important: a count after a particular dose and a count across doses do not necessarily represent the same observation period or opportunity for a symptom to occur.

The endpoint is a safety measure, not a direct measure of immune response or tuberculosis prevention. The record lists immunogenicity as a study aim and describes immune-cell outcomes, but these are separate from the primary local-symptom endpoint. The primary endpoint counts and any statistical comparisons are not reported in the registry record, so the recorded definition alone cannot show how often the symptoms occurred or whether groups differed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is a way to allocate participants to study groups by chance. In general, it helps make groups comparable with respect to both measured and unmeasured characteristics at the time of assignment. It does not guarantee that groups will be identical, especially in a study with multiple regimens, and it does not address differences that arise after allocation. The registry record identifies the study as randomized but does not report the sequence-generation method, allocation concealment, or any stratification factors.

What does an open-label, parallel design imply?

In a parallel design, assigned groups receive their respective regimens rather than switching between them. An open-label design means masking was not used. General statistical consideration: knowledge of assignment can affect symptom reporting, clinical attention, or assessment, especially for outcomes that rely on participants' reports or observers' judgments. Randomization does not remove this potential measurement influence. The record does not describe additional steps to limit it.

How should participant counts be understood?

The primary endpoint is a count of participants meeting the grade 3 symptom definition. It is not described as a count of all symptom episodes. The record defines the Total Vaccinated cohort as vaccinated subjects for whom data were available, and says the primary outcome is presented separately because its definition depended on doses received in each group. In general, a participant count is most informative when read alongside its population, observation window and event definition. Here, the primary outcome counts are not reported, so neither event frequencies nor group contrasts can be interpreted.

The serious adverse event information gives participants at risk and participants affected for each group. Those are descriptive counts. General statistical consideration: a count alone does not express uncertainty, and comparisons between counts require attention to the group denominators, the outcome definition and the analysis method. The registry record does not report inferential comparisons or confidence intervals for these figures. No rate or contrast should be inferred from the counts alone.

What can confidence intervals and p-values tell a reader?

General explanation: a confidence interval describes the statistical uncertainty around an estimate under a specified method and assumptions. A narrower interval indicates greater precision than a wider interval, but does not itself determine clinical importance. A p-value describes how compatible observed data are with a specified null model, given the analysis assumptions; it is not the probability that a treatment works or that a finding is due to chance. Neither confidence intervals nor p-values for the primary endpoint are reported in the registry record. The statistical plan for the trial is also not reported in the registry record.

What do the sample-size assumptions mean?

The record 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. It says the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not a report of the trial's original design justification and not observed power. The record does not report the original sample-size justification, and the planning assumptions alone cannot establish that the trial was adequately powered for its primary endpoint. For time-to-event tables the described convention is total events; for other outcomes it is participants per arm. No new sample-size estimate or power conclusion follows from these assumptions.

The registry record lists 61 outcome measures and no analysis records. It does not describe whether a particular model, covariate adjustment, missing-data method or interim analysis was used. These methods cannot be inferred from the fact that the study was randomized or from the endpoint definitions.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 61 outcome measures, including repeated descriptions of M72-specific T-cell outcomes, and identifies several dose-related categories for the primary local-symptom outcome. Assessing multiple outcomes or time points creates a multiplicity issue: in general, the more comparisons considered, the greater the chance that at least one result may appear noteworthy by chance if no adjustment or prespecified interpretation strategy is used. The record does not report a multiplicity adjustment, a hierarchy of outcomes, or a statistical plan for controlling interpretation across the listed outcomes.

The primary outcome is presented separately because its definition varies according to doses received. The record does not report a single combined comparison across the dose categories. It also does not report how comparisons between regimens were specified or whether any results were selected for emphasis after data review. These details are not reported in the registry record.

The primary analysis population is described as the Total Vaccinated cohort, including vaccinated subjects for whom data were available. This identifies the general population used for the endpoint, but does not explain how participants with missing data were handled or whether the availability of data differed across groups. No imputation method, missingness analysis, or sensitivity analysis is reported in the registry record.

The study is randomized, but the record does not identify an intention-to-treat analysis population or explain whether participants were analyzed according to assignment, vaccination received, or another rule for outcomes beyond the stated Total Vaccinated cohort. It does not report an analysis population for each secondary outcome. Because no analysis records are listed, readers cannot determine how incomplete observations, multiple outcomes or dose-specific assessments were incorporated in formal statistical inference.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchopneumonia (4.0%), sepsis (2.0%), gastroenteritis (2.0%), thermal burn (2.0%), pyrexia (2.0%).

The serious adverse event summaries report, for each group, the number of participants at risk and the number affected. In the SB692342 2 Dose Group, 2 were affected among 50 at risk; in the SB692342 1 Dose Group, 3 were affected among 50 at risk. The Control Menjugate Group had 3 affected among 50 at risk. The SB692392 2 Dose + Tritanrix + Prevnar + Polio Sabin Group had 1 affected among 49 at risk; the corresponding 1 Dose group had 1 affected among 52 at risk. The Control Tritanrix + Prevnar + Polio Sabin Group had 1 affected among 49 at risk.

These are descriptive participant counts. They do not show whether events were judged related to vaccination, and the record does not report a comparative statistical analysis. The listed serious-event terms are bronchopneumonia (4.0%), sepsis (2.0%), gastroenteritis (2.0%), thermal burn (2.0%), pyrexia (2.0%) and rash (2.0%). The record does not clarify the denominator for those percentages in the available information, so they should not be treated as group-specific rates.

One death is recorded in the Control Menjugate Group, with none recorded in the other listed groups. The record does not establish a causal relationship between the death and a study vaccine. These figures describe what is recorded; they are not, on their own, a comparative safety conclusion.

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

The study record establishes that a randomized, open-label phase 2 trial assessed a candidate tuberculosis vaccine in healthy infants in a tuberculosis-endemic region. Its design considered vaccine administration after completion of the primary EPI regimen and administration alongside EPI vaccines. It also identifies a primary endpoint focused on grade 3 solicited local symptoms over a defined short follow-up window, and describes immune-response outcomes as secondary measures.

The record does not report the primary endpoint results or statistical analyses. It therefore cannot show from the posted information how often grade 3 local symptoms occurred in each group, how precisely any group difference was estimated, or whether an observed difference would be compatible with chance under a specified statistical model. The serious adverse event counts and listed terms offer descriptive safety information, but they do not establish causation or comparative risk.

The study's focus on safety and immunogenicity should not be confused with a demonstration of prevention of tuberculosis. The record describes immune-cell outcomes, but does not report the results of those outcomes in the information. It also does not report a clinical tuberculosis-prevention endpoint. Consequently, the documented design and outcome definitions do not establish vaccine efficacy.

More generally, randomized allocation can support fair comparisons when outcomes are collected and analyzed appropriately, but open-label assessment and incomplete reporting can limit interpretation. The record does not provide enough information to assess the statistical precision, missing-data handling, multiplicity strategy or causal attribution for safety events. The defensible conclusion is limited to the study population, regimens and measures recorded, with no claim about whether a treatment works or does not work.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a randomized comparison among different vaccination schedules in a defined infant population. The candidate vaccine was considered both after completion of the primary EPI regimen and concomitantly with EPI vaccines. Those distinct schedules raise a design question about how to interpret the regimen as a whole: a group contrast may reflect differences in timing and co-administration as well as the candidate vaccine itself.

The primary endpoint also illustrates why operational definitions matter. “Grade 3” was tied to specified effects on normal activity or to redness or swelling extending beyond 20 millimeters from the injection site. A clear definition makes an endpoint more reproducible, but interpretation still depends on how symptoms were elicited and assessed. Because the study was open-label, awareness of the assigned regimen could be relevant to reporting or assessment of symptoms.

At the same time, the registry record shows the limits of interpreting a trial from design information alone. Enrollment and a detailed endpoint definition do not substitute for outcome counts, uncertainty estimates or a prespecified analysis plan. With no primary endpoint results or analysis records reported, readers cannot assess the precision of comparisons or judge whether differences between groups are statistically distinguishable.

The record therefore offers a useful illustration of the separation between trial design, outcome measurement and statistical evidence. It describes what the study set out to examine and gives some serious-event summaries, but leaves the central primary-outcome comparison unreported. That gap limits the conclusions that can be drawn from the registry record.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for statistical interpretation is that the registry record does not report the primary outcome counts or analyses. It defines grade 3 solicited local symptoms and their follow-up window, but without group results there is no basis for assessing event frequency, comparative effects or precision. The record also does not report confidence intervals or p-values for the listed serious adverse event summaries.

The open-label design may be relevant to symptom reporting and assessment. The registry record does not describe methods used to reduce or evaluate any effect of knowing the assigned regimen. It also does not report allocation concealment, the randomization procedure, or baseline comparisons that could help readers understand the groups at entry.

The endpoint is separated by dose-related categories because the outcome definition varied with doses received. The record does not explain how those categories were combined or compared in an inferential analysis. Although it lists 61 outcome measures, it does not report a multiplicity strategy, an analysis hierarchy, or a statistical plan. Missing-data procedures beyond the definition of the Total Vaccinated cohort are not reported in the registry record.

The serious adverse event summaries are descriptive, and the relationship of events to vaccination is not reported. The record lists percentages for serious-event terms but does not explain their denominator in the information available for interpretation. One death is recorded in the Control Menjugate Group, but the circumstances and causal assessment are not reported. Finally, the registry record describes safety and immunogenicity outcomes, but does not report a clinical tuberculosis-prevention outcome. These limitations preclude conclusions about efficacy and constrain comparative safety interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity Study of a Candidate Tuberculosis Vaccine in Healthy Infants — NCT01098474.
• Registry record last updated 2019-06-27; status last verified 2019-06.
• Results first posted 2018-11-27.
• 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

This completed, randomized, open-label phase 2 study was sponsored by GlaxoSmithKline and enrolled 301 healthy infants aged between and including 2 and 7 months in a tuberculosis-endemic region. It assessed GSK Biologicals' candidate tuberculosis vaccine 692342 in schedules after or alongside the primary EPI regimen.

The primary outcome counted participants with grade 3 solicited local symptoms after dose 1, dose 2 and across doses, from Day 0 to Day 6. The registry record defines the symptoms and grade criteria, and identifies the Total Vaccinated cohort as the population for the analysis. It also lists serious adverse event summaries and secondary immune-response measures.

Primary outcome results and statistical analyses are not reported in the registry record. The serious-event figures are descriptive and do not establish causality or a comparative safety conclusion.