A Study of a Vaccine for Pneumonia in Adults and Toddlers in Kenya: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of a Vaccine for Pneumonia in Adults and Toddlers in Kenya (NCT02543892), a randomized phase 1, phase 2 study. The primary outcome is Highest Grade of Reactogenicity Events in the Adult Cohort: Vaccination 1.

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase 1-2 study sponsored by PATH. Its title describes a safety and immunogenicity study of PATH-wSP in Kenyan adults and toddlers. The registry record lists enrollment of 248 and a completed status. The study began on 2016-08-10, with primary completion on 2018-01-04.

The intervention groups received two PATH-wSP injections, either 0.6 mg or 1 mg, with a 28 day interval. Placebo groups received two normal saline injections on the same interval. The study summary describes a staged sequence: adults first received the lower dose or placebo; a higher dose was then tested after the lower dose was considered safe. After safety was established in adults, the lower and higher doses were tested in toddlers, beginning with the lower dose. Further details of the dose-escalation decision process are not reported in the registry record.

The adverse-event record lists separate adult vaccine groups at 0.6 mg and 1.0 mg, an adult placebo group, toddler vaccine groups at both doses, and a toddler placebo group. Its adult placebo results are not separated by dose stage. Although randomization and quadruple masking are recorded, the method of sequence generation, allocation concealment, and identities of the masked parties are not reported in the registry record. The record also does not describe the exact analysis populations or the statistical comparison planned for the primary outcome.

Immunogenicity outcomes include IgG antibody geometric mean concentration, geometric mean fold change, and the number of participants with an IgG seroresponse against pneumococcal proteins. The registry lists eight outcome measures, but does not report their numerical findings. The study's stated focus is safety and immune response, not clinical prevention of pneumonia.

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.

Only the first 6 of 8 groups are shown.

Received Vaccination 1

Received Vaccination 2

Reasons for not completing this period:

Had Immunology Data

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.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Highest Grade of Reactogenicity Events in the Adult Cohort: Vaccination 1, measured over 7 days after the first dose (Day 7).

The primary endpoint is the highest grade of reactogenicity events in the adult cohort after vaccination 1. The assessment timeframe is 7 days after the first dose, on Day 7, and the outcome unit is participants. Reactogenicity events are solicited adverse events assessed after vaccination. Local events included injection-site symptoms; systemic events included rash, headache, axillary fever or temperature, fatigue or malaise, and arthralgia or myalgia. The registry describes assessments during the 60 minutes after vaccination, daily during the first week, and at a clinic visit one week after vaccination, with daily home visits during that week.

The grade describes interference with activity: grade 0 means no event, grade 1 means no interference, grade 2 means some interference, and grade 3 means the event prevents daily activity. A highest-grade summary can represent the most severe event observed for a participant over the defined assessment period, rather than treating each symptom or observation as a separate participant-level result. This can make event severity easier to summarize, while losing detail about the specific symptom and when it occurred.

The registry record does not report the primary endpoint counts by grade, a treatment contrast, or an uncertainty interval. It notes that the outcome has several categories or time points and is not reduced to one comparison. Consequently, the endpoint definition is available, but its observed distribution and comparative interpretation are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a randomized parallel design mean?

In general, random assignment allocates participants to study groups by chance. This is intended to make the groups comparable at the outset, although chance imbalances can still occur. A parallel design means participants remain in an assigned group rather than crossing over between treatments. The registry record describes this study as randomized and parallel, but does not report the randomization method, allocation concealment, or group characteristics at baseline. Those details are needed to assess how assignment was implemented and how comparable the groups were in practice.

What does quadruple masking mean?

Masking generally means that some people involved in a trial do not know which treatment a participant received. It can reduce the influence of expectations on participant reports, clinical assessments, and decisions. The registry labels the study quadruple-masked, but does not identify which roles were masked or describe how masking was maintained. The label alone does not show whether masking remained intact throughout the study.

How should a count outcome be understood?

The primary outcome is expressed as a count of participants, with categories based on the highest reactogenicity grade. A participant-level count differs from counting every symptom occurrence: one person can report more than one event, while a highest-grade summary records the most severe grade within the defined assessment. In general, categorical results are best interpreted with the number of participants in each category and a clearly defined comparison group. The registry record does not report the primary category counts or a contrast, so no comparative estimate can be interpreted.

Why does the outcome structure matter?

A categorical outcome with multiple grades preserves information about severity, but it does not automatically yield one summary comparison. A statistical plan might compare the full distribution, select a particular grade threshold, or use another prespecified summary. These choices answer different questions. The registry record says the primary outcome has several categories or time points and is not reduced to one comparison. The specific method used to analyze those categories is not reported in the registry record, and no outcome analyses are listed.

What would uncertainty measures add?

In general, a confidence interval describes a range of estimates compatible with the observed data under a statistical model and procedure. It communicates precision as well as the direction and scale of an estimate. A p-value, in general, describes how unusual the data would be under a specified null model; it does not measure the probability that a treatment works or establish clinical importance. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. Without an estimate and its uncertainty, the primary result cannot be assessed for precision.

Why can adverse-event counts not answer every safety question?

Counts of participants with events are useful descriptive information, but interpretation depends on definitions, follow-up, and the analysis population. Serious events and other events are distinct registry categories. A count does not by itself establish whether an event was caused by a study intervention, whether the same participant experienced more than one event, or whether follow-up was complete. General comparisons also need to account for the different group sizes and the amount of observation. The record does not provide event-level timing, attribution, or a comparative statistical analysis.

What can planning calculations say?

In general, a sample-size calculation is a planning tool based on assumptions about the outcome, target effect, significance level, allocation, and statistical method. It is not a measure of the probability that a completed study detected an effect. The registry's planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it defines the target effect as a stated fraction of the observed effect. These are planning assumptions, not a report of observed power. The actual planning values and their application to a particular comparison are not reported in the registry record.

Over-dispersion is a general concern when observed variation in count data is greater than a model assumes; ignoring it can make uncertainty estimates too small. It is not clear from the registry record that an over-dispersed count model was relevant or used for this categorical participant outcome. No statistical model, adjustment strategy, or variance method is reported. The registry record therefore supports a description of the design and endpoint, but not a reconstruction of the primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcome domains: the primary reactogenicity measure and secondary immune-response outcomes covering IgG geometric mean concentration, geometric mean fold change, and seroresponse. It reports eight outcome measures, but does not provide numerical findings for them. When a study evaluates multiple outcomes, grades, time points, or treatment contrasts, multiplicity can arise because there are several opportunities to observe apparently notable results. Statistical approaches may address this by prioritizing outcomes, adjusting inference, or clearly distinguishing confirmatory from exploratory analyses. The multiplicity approach for this study is not reported in the registry record.

The record does not list statistical analyses, and it does not report p-values, confidence intervals, or adjusted comparisons for the outcomes described. The primary outcome itself is noted to have several categories or time points and is not reduced to one comparison. The prespecified method for handling those categories, and whether any particular contrast was primary, are not reported in the registry record.

Missing-data procedures are also not reported in the registry record. It does not describe how incomplete assessments, missed visits, withdrawals, or unavailable outcome measurements were handled. The analysis populations are not named, and the record does not clarify whether analyses included all randomized participants, only participants who received vaccination, or another defined group. These omissions limit assessment of potential bias from missing observations or differences between the groups included in an analysis.

It is not possible to infer a missing-data or multiplicity strategy from the study's phase, design, or completed status. Those methods, along with outcome-specific analysis populations, would be needed to interpret any comparative result more fully.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.0%), bronchial hyperreactivity (2.0%), gastroenteritis (2.0%), malaria (2.0%), febrile convulsion (2.0%).

The registry lists serious adverse events, other adverse events, and deaths separately for the adult and toddler groups. Serious-event counts were 0 in each of the adult PATH-wSP groups and the adult placebo group; the toddler 0.6 mg PATH-wSP group had 2 affected participants, the toddler 1.0 mg PATH-wSP group had 1, and the toddler placebo group had 5. The corresponding groups at risk are listed as 12, 12, 24, 50, 50, and 100, respectively. Deaths are listed as 0 in every group.

For other adverse events, the registry lists 9 affected participants in each adult PATH-wSP group and 20 in the adult placebo group; the toddler groups list 45, 44, and 87 affected participants, respectively. These are descriptive counts, not adjusted comparisons. The registry also lists serious-event terms with percentages, including Pneumonia at 2.0%, Bronchial hyperreactivity at 2.0%, Gastroenteritis at 2.0%, Malaria at 2.0%, Febrile convulsion at 2.0%, and Pneumococcal bacteremia at 1.0%.

The record does not report event attribution, timing, recurrence, or a statistical comparison. Counts alone do not establish that an event was caused by a vaccine or placebo, and they do not capture the full clinical context of an event.

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

The registry record establishes that PATH-wSP was studied against placebo in adults and toddlers in a randomized, quadruple-masked, parallel-group phase 1-2 trial. It also specifies the primary safety question, the reactogenicity grading approach, and descriptive adverse-event counts. Those details describe the design and some posted safety information; they are not a complete report of the trial's outcomes.

The primary endpoint results are not reported in the registry record. Without grade-specific participant counts, a treatment contrast, or uncertainty estimates, the frequency and comparative distribution of reactogenicity grades cannot be determined from this record. The listed adverse-event counts provide descriptive information but do not establish a causal relationship or a difference between treatments. They should not be treated as substitutes for a complete analysis of the primary endpoint.

The secondary outcomes concern immune responses to pneumococcal proteins. Their names indicate that the study planned to assess antibody concentration, fold change, and seroresponse, but the record does not report their findings. Therefore, the available record does not establish the magnitude or precision of any immune-response comparison.

The trial is described as a safety and immunogenicity study, not as a test of clinical pneumonia prevention. Although pneumonia is the condition named in the record, no result on prevention of pneumonia is reported. A completed study status means the registry lists the study as completed; it does not supply missing outcome results or show that a particular clinical effect was demonstrated.

In general, judging a treatment comparison requires outcome estimates, their uncertainty, and enough information about analysis methods and participants to evaluate possible bias. The registry record does not report the primary analysis, analysis populations, or missing-data approach. Any interpretation should therefore remain limited to the trial design, stated outcome definitions, and descriptive safety counts that are recorded.

13. Why This Trial Matters Statistically

This trial raises statistical questions that are common in early-stage studies involving more than one age group and dose. The registry describes an adult dose sequence followed by testing both doses in toddlers after safety was established in adults. This staged structure makes it important to know how safety decisions were defined and how results from each age and dose group were to be summarized. The decision criteria and statistical methods for those stages are not reported in the registry record.

The primary endpoint is a graded participant-level safety outcome, rather than a single continuous measurement. Such outcomes can retain severity information, but the analysis depends on how grades and assessment times are combined and which comparison is chosen. The record notes multiple categories or time points without reducing them to one comparison, and it does not report the analysis method or result. This leaves the central statistical question unresolved in the available record.

Safety and immunogenicity also represent different kinds of evidence. Descriptive event counts address observed safety reports, while antibody outcomes require summaries and comparisons of immune measurements. Listing both outcome domains does not make one a substitute for the other. Their numerical results and uncertainty are not reported in the registry record.

Finally, a sample-size planning illustration is not observed power. Planning calculations depend on assumptions about the target effect and analysis; they do not show what the completed study established. The registry's planning description gives assumptions, but the available record does not give the primary outcome estimate needed to evaluate a completed comparison. This illustrates why clear outcome reporting, analysis details, and uncertainty measures are essential to interpreting a trial.

14. Limitations

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

The main limitation for interpretation is that the registry record does not report the primary reactogenicity results or the secondary immunogenicity findings. It gives the primary outcome definition but no grade-specific counts, treatment contrast, or uncertainty estimate. Its note that the primary outcome has several categories or time points further means that the intended summary cannot be recovered from the endpoint title alone.

Some safety data are available, but their interpretation is limited. The record does not describe event attribution, timing, recurrence, or how the listed categories relate to the solicited reactogenicity assessments. It also does not provide a comparative statistical analysis. The adult placebo adverse-event group is not split by dose stage in the listed results, limiting direct dose-stage interpretation from those counts.

Other trial details needed to assess bias and applicability are not reported in the registry record. These include eligibility criteria, baseline characteristics, the randomization and allocation-concealment methods, the roles masked, adherence, withdrawals, missing-data handling, analysis populations, and outcome-specific statistical methods. The record also does not report the rationale for the planned enrollment or the decision rules used in the staged testing.

The registry describes a study of safety and immunogenicity, so the listed outcomes do not establish an effect on clinical pneumonia. The record's completed status does not resolve the absent results. These limitations are specific to the information recorded and do not establish what may be reported elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of a Vaccine for Pneumonia in Adults and Toddlers in Kenya — NCT02543892.
• Registry record last updated 2018-11-28; status last verified 2018-11.
• Results first posted 2018-11-28.
• 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

NCT02543892 is a completed randomized, quadruple-masked, parallel-group phase 1-2 study sponsored by PATH. It enrolled 248 and studied PATH-wSP at 0.6 mg and 1 mg against normal saline placebo in Kenyan adults and toddlers. The study summary describes a staged dose sequence, with adult testing before toddler testing.

The primary outcome is the highest grade of adult reactogenicity events after vaccination 1, assessed 7 days after the first dose. The registry describes local and systemic events and grades from 0 to 3. Secondary outcomes concern IgG antibody concentration, fold change, and seroresponse against pneumococcal proteins.

Descriptive adverse-event counts are listed, but primary endpoint and immunogenicity results, statistical analyses, analysis populations, missing-data methods, and multiplicity procedures are not reported in the registry record. The available record therefore describes the trial design and selected safety counts without a complete comparative outcome analysis.