Extension Study of H01_04TP to Evaluate the Booster Response Induced by Vi-CRM197 in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Extension Study of H01_04TP to Evaluate the Booster Response Induced by Vi-CRM197 in Adults (NCT01438996), a non-randomized phase 2 study. The primary outcome is Anti-Vi ELISA Geometric Mean Concentration (GMC).

2. Clinical Question

3. Trial Design

This completed study was a Phase 2, open-label, single-center extension of H01 04TP (NCT01193907). Its stated purpose was to assess immunogenicity and the kinetics of the anti-Vi antibody response after NVGH Vi-CRM197 vaccination in adults who had previously received either NVGH Vi-CRM197 or Vi-polysaccharide (Typherix), and in naïve healthy adults. The registry lists the study condition as typhoid fever.

The study used a nonrandomized, parallel-group design with no masking. The groups were defined by prior vaccination history: NVGH Vi-CRM/NVGH Vi-CRM, Vi-PS/NVGH Vi-CRM, and NVGH Vi-CRM in naïve adults. Each listed regimen included one 0.5 mL dose of NVGH Vi-CRM197 5.0 mcg. Because group membership reflected prior vaccination rather than random assignment, the groups are not like-for-like randomized comparators. Differences in their outcomes could reflect differences in previous vaccination or other group characteristics, as well as the response to the study dose.

The registry lists enrollment as 51. The study began in 2011-10, reached primary completion in 2011-12, and is marked completed. The primary endpoint was anti-Vi ELISA geometric mean concentration at 3 days after vaccination. The registry also lists secondary outcomes concerning post-vaccination reactions, adverse events, and serious adverse events, and 9 outcome measures in total. It records 0 analyses. A detailed statistical analysis plan, participant flow by endpoint, and explanation of the analysis populations 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.

Overall Study

Reasons for not completing this period:

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 Anti-Vi ELISA Geometric Mean Concentration (GMC), measured over At 3 days after vaccination.

The primary endpoint was anti-Vi ELISA geometric mean concentration (GMC), expressed in ELISA Units/mL, at 3 days after vaccination. ELISA is an assay used to measure antibodies that bind to a target; in this study the target was Vi. The endpoint therefore describes the concentration of measured anti-Vi antibodies at the specified time point, rather than a clinical illness outcome.

A geometric mean is often used for antibody measurements because such values can be unevenly distributed, with some measurements much larger than others. On a logarithmic scale, the geometric mean corresponds to averaging transformed measurements and converting the result back to the original scale. General concept: this can provide a representative summary when measurements are right-skewed, but it does not show the range of individual responses or how many participants had low or high values.

The endpoint description specifies a 95% confidence interval as the dispersion measure. General concept: a confidence interval conveys uncertainty around an estimated population value, conditional on the analysis method and assumptions. Its width is informative about precision; it is not a range that contains every participant's measurement. The registry record identifies the measure and time point but does not report the GMC estimate or confidence interval limits. Thus, the primary endpoint's observed magnitude and precision are not available in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a Phase 2, open-label, single-center, nonrandomized, parallel-group extension study. These features affect how results should be read. The methods below explain the statistical meaning of the listed measures and design; they do not supply analysis procedures absent from the registry record.

What does the geometric mean describe?

The primary endpoint was anti-Vi ELISA geometric mean concentration in ELISA Units/mL at 3 days after vaccination. General concept: laboratory measurements such as antibody concentrations can be skewed, so an arithmetic average may be strongly influenced by unusually large observations. A geometric mean is based on the average of logarithmically transformed values, then expressed on the original measurement scale. It can serve as a group-level summary when values vary multiplicatively. It does not describe every participant's result, the spread of individual measurements, or the proportion meeting any threshold. The registry does not report the GMC estimate, individual-level distribution, or threshold-based outcome.

How should the confidence interval be understood?

The endpoint specifies a 95% confidence interval. General concept: a confidence interval expresses uncertainty about an estimated quantity under the statistical method and assumptions used. Greater width generally indicates less precision, while narrower width indicates greater precision, but interpretation also depends on the scale and analysis. A confidence interval is not a guarantee about the range of participant values and does not by itself establish clinical importance. Since neither the estimated GMC nor the confidence interval limits are reported, precision cannot be evaluated from the registry record.

What does the group structure permit?

The parallel groups were defined by prior vaccination history, and allocation was nonrandomized. General concept: random assignment can balance measured and unmeasured baseline characteristics on average, whereas nonrandom assignment may leave groups differing in ways that affect outcomes. Here, prior vaccination is an explicit group distinction, and other group characteristics are not described in the record. As a result, group-specific summaries can describe observed responses in each history group, but a contrast between groups is not automatically a causal estimate. The study is open-label, and the registry records masking as none. The laboratory assay is identified as ELISA, but blinding of laboratory personnel is not reported in the registry record.

What can the time point say about kinetics?

The primary endpoint is measured at 3 days after vaccination. The study objective refers to antibody-response kinetics, which concerns how measurements change over time. General concept: describing a trajectory requires measurements at stated time points and a method for comparing or modeling those repeated observations. A single primary time point alone cannot characterize a full trajectory. The registry record does not give the other time points, the longitudinal analysis method, or the corresponding results, so the kinetics cannot be reconstructed from the primary endpoint description.

How should planning calculations be read?

Any sample-size illustration based on the observed effect is a planning calculation, not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. General concept: such calculations show how a hypothetical design might perform under specified assumptions. They do not demonstrate that the completed study had a particular probability of finding a result, and they are not a substitute for interpreting the observed estimate and its uncertainty. The registry record does not report the trial's own sample-size justification. The study's nonrandomized groups also make a simple two-arm planning illustration an imperfect representation of the actual design.

What analysis details remain uncertain?

The registry lists 0 analyses, and it does not report a statistical analysis plan, model for the endpoint, approach to missing measurements, or analysis population definition. General concept: these choices can affect the estimate, its uncertainty, and the participants represented by a result. Without these details and the endpoint numbers, the analysis cannot be independently appraised from the registry record. The posted endpoint definition should therefore be distinguished from a complete statistical methods description.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including the primary anti-Vi ELISA GMC endpoint and secondary outcomes concerning post-vaccination reactions, adverse events, and serious adverse events. It records 0 analyses. The record does not report a multiplicity strategy, such as whether outcomes were tested within a hierarchy, whether any adjustment was planned, or how multiple time points or group contrasts were handled. The number of outcome measures alone does not establish how many formal statistical tests were conducted.

General concept: when several outcomes, time points, or comparisons are examined, the chance of at least one apparently notable result can increase if each is assessed independently. Methods for controlling or describing that issue depend on the intended estimands and analysis plan. In the absence of a reported plan or results, it is not possible to determine whether multiplicity was addressed or to interpret any nominal significance level for this study. No p-values or tested contrasts are reported in the registry record.

Missing-data methods and endpoint-specific analysis populations are also not reported in the registry record. The overall enrollment is 51, but the registry does not state how many participants contributed to the primary GMC estimate, whether all scheduled measurements were available, or how missing measurements were handled. The listed safety risk counts are not a substitute for the primary endpoint denominator. It is therefore not possible to assess whether exclusions or missing observations could have affected the antibody summary.

The record does not report whether interim analyses were planned or conducted, nor does it give a sample-size justification for the trial. These omissions should be treated as unreported information, not as evidence that a particular procedure was or was not used. Any planning illustration based on an observed effect should be read as a design scenario, not as observed power or confirmation of the trial's statistical plan.

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 registry safety summary lists serious adverse events for three groups. In the NVGH Vi-CRM/NVGH Vi-CRM group, 0 serious events are recorded among 14 participants at risk. In the Vi-PS/NVGH Vi-CRM group, 0 are recorded among 12 at risk. In the NVGH Vi-CRM group, 0 are recorded among 20 at risk. The registry lists no serious-event terms in its serious-event term field. These are the posted group counts, not estimates of risk beyond the participants included in the respective safety records.

The same summary records other events affecting 14 of 14 participants in NVGH Vi-CRM/NVGH Vi-CRM, 12 of 12 in Vi-PS/NVGH Vi-CRM, and 20 of 20 in NVGH Vi-CRM. The registry also lists secondary outcomes for any post-vaccination reaction, adverse events, and serious adverse events, but does not provide definitions or detailed event descriptions alongside these figures. The category labels should therefore be interpreted as registry safety fields rather than as a detailed account of event severity, duration, or causality.

Death counts are not reported in the registry record. Zero serious events in these groups does not establish that serious events are impossible or that the study can rule out uncommon events. The record does not report a longer-term safety analysis or detailed follow-up information.

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

This study addresses an immunogenicity question: how anti-Vi antibody concentration was to be assessed after NVGH Vi-CRM197 vaccination in adults with different prior vaccination histories. Its primary endpoint, ELISA GMC at 3 days after vaccination, is a laboratory measure. It does not directly measure prevention of typhoid fever, symptom burden, or another clinical benefit.

The registry record does not report the numerical GMC estimates or their 95% confidence intervals. It therefore does not establish from the posted primary endpoint information how large the measured response was, how precise the estimate was, or how group summaries compared. The stated objective includes antibody kinetics, but the registry record does not provide the time-course measurements needed to describe that pattern. No analysis results are listed.

The design also limits what any group contrast could mean. Participants were not randomized, and group membership reflected prior vaccination history. Differences between the groups could be associated with that history or with other differences not reported in the record. A descriptive comparison would not by itself isolate the causal effect of a booster or establish that prior vaccination produced a particular response.

The safety summary records 0 serious adverse events in each listed group, alongside other-event counts and at-risk denominators. These observations describe the participants represented in the safety summary; they do not establish the absence of risk beyond those observations. Death counts are not reported in the registry record.

Planning sample-size illustrations are distinct from study findings. They describe hypothetical design requirements under stated assumptions and are not observed power or evidence that an effect occurred. Overall, the registry record documents the question, design, endpoint, and selected safety counts, while leaving the primary numerical findings and important analysis details unreported. It cannot support a conclusion about clinical effectiveness.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clear endpoint definition and a reportable result. The registry identifies an antibody measure, its assay scale, a summary statistic, a confidence interval format, and a time point. Those details define what the investigators intended to measure. Without the GMC estimate and interval limits, however, readers cannot assess the observed magnitude or precision.

The group structure also matters. The study compares descriptions across prior vaccination histories, but it is nonrandomized and open-label. A group contrast in this setting is not automatically an unbiased estimate of the effect of a booster or of prior priming. Statistical adjustment, if any, would need to be specified and its assumptions assessed; the registry record does not report an analysis model or adjusted results.

The study objective mentions antibody kinetics, while the primary endpoint names a specific post-vaccination time point. That distinction illustrates why a longitudinal claim requires measurements and analysis details beyond a single endpoint definition. The registry record does not provide enough timing and result information to reconstruct a trajectory.

Finally, the record shows why enrollment, safety counts, and planning calculations answer different questions. The listed enrollment describes the study overall; safety denominators describe the groups represented in those safety fields; planning calculations are hypothetical design illustrations. None can replace an endpoint-specific estimate with uncertainty. Reading each quantity according to its role avoids treating design information as a result or descriptive counts as a complete analysis.

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 registry record does not report the primary endpoint GMC estimates, the 95% confidence interval limits, or the number of participants contributing to that endpoint. This prevents assessment of the antibody response's magnitude and precision. Although the study objective refers to kinetics, the record does not give the full set of measurement times or their results.

The nonrandomized design is a trial-specific limitation for interpreting differences among the prior-history groups. The registry identifies the groups by previous vaccination, but does not report baseline characteristics or adjustment methods that could help assess comparability. With no masking, expectations or procedures could potentially influence outcomes, although the registry does not describe whether or how this was evaluated. Laboratory blinding is not reported in the registry record.

The record lists 9 outcome measures but provides limited detail beyond the primary endpoint and broad safety outcomes. It does not report a statistical analysis plan, handling of missing data, analysis populations, multiplicity methods, interim analyses, or the trial's sample-size justification. It also records 0 analyses. These omissions prevent appraisal of the endpoint analysis and the relationship between planned and reported analyses.

The safety summary gives group-specific at-risk counts and event counts, but detailed event descriptions and death counts are not reported in the registry record. The overall enrollment of 51 and the safety denominators are different registry entries; the record does not explain participant accounting across these fields. The study is listed as single-center, and the record does not give information to assess how well its participants represent other populations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Extension Study of H01_04TP to Evaluate the Booster Response Induced by Vi-CRM197 in Adults — NCT01438996.
• Registry record last updated 2014-03-24; status last verified 2014-02.
• Results first posted 2014-03-24.
• 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

NCT01438996 is a completed Phase 2, open-label, single-center extension study with nonrandomized parallel groups and no masking. It evaluated NVGH Vi-CRM197 vaccination in adults previously given NVGH Vi-CRM197, adults previously given Vi-polysaccharide (Typherix), and naïve adults. Each listed regimen included one 0.5 mL dose of NVGH Vi-CRM197 5.0 mcg. Enrollment was 51; the study began in 2011-10 and primary completion was in 2011-12.

The primary endpoint was anti-Vi ELISA GMC in ELISA Units/mL at 3 days after vaccination, with a 95% confidence interval specified. Numerical GMC results and interval limits are not reported in the registry record, which lists 0 analyses. Safety fields record 0 serious adverse events among 14, 12, and 20 participants at risk in the respective groups. Death counts and detailed primary endpoint analysis information are not reported in the registry record.