Phase 1 Trial of a Malaria Vaccine in Young Kenyan Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1 Trial of a Malaria Vaccine in Young Kenyan Children (NCT00317473), a randomized phase 1 study. The primary outcome is Occurrence of Solicited Symptoms During a 8 Day Follow-up Period After Each Vaccination.

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel Phase 1 trial, recorded as completed. Its purpose, as described in the registry, was to assess the safety and reactogenicity of FMP1/AS02A in malaria-exposed children aged 12–47 months in western Kenya. The registry records enrollment of 135 participants. The study started in 2003-06, and primary completion was 2004-07.

The intervention was assigned at three dose levels. Children in the 10 ug group were vaccinated on days 0, 29, and 57; the 25 ug group received vaccinations on days 14, 42, and 70; and the 50 ug group received vaccinations on days 28, 56, and 84. The comparator was Imovax Rabies Vaccine, administered on corresponding FMP1/AS02A vaccination days. These schedules mean the dose groups also had different vaccination days. The registry does not report further details about how randomization or masking was implemented.

The primary outcome concerns solicited symptoms during an 8 day follow-up period after each vaccination, with a listed timeframe of 40 days. The secondary outcome listed is anti-FMP1 antibody titer responses. Although the registry identifies this endpoint and its general measurement, it does not report a primary-outcome result or a statistical analysis for it. The registry record also does not report the allocation ratio, detailed analysis populations, or a sample-size justification. The adverse-event summaries list 90 at risk in the FMP1/AS02A group and 45 at risk in the Imovax group, but these figures alone do not describe the allocation procedure or the numbers in each vaccine dose group.

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.

Population: one subject from FMP1/AS02A Cohort A withdrew after randomization and prior to baseline measurement

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Occurrence of Solicited Symptoms During a 8 Day Follow-up Period After Each Vaccination, measured over 40 days.

The primary endpoint is the occurrence of solicited symptoms during the 8 day follow-up period after each vaccination. The registry description includes any solicited symptoms, local symptoms, and general symptoms; it identifies the measure as a number of events. A timeframe of 40 days is listed. The record does not provide symptom-specific definitions, a complete list of solicited symptoms, or a breakdown of results by symptom category or vaccination.

Solicited symptoms are events actively sought according to a study’s monitoring approach, rather than events captured only when participants or caregivers report them spontaneously. In general, collecting these reports over a specified follow-up period can make short-term reactogenicity observable in a consistent way across groups. Local and general symptom categories can also describe different kinds of responses. These are general features of solicited symptom endpoints, not additional details about how this trial’s symptoms were elicited or classified.

The listed measure is a count of events, not a single reported participant-level comparison. The registry description says occurrence of any, local, or general symptoms, but does not give category-specific counts, a comparison estimate, or uncertainty intervals. It is therefore not possible to interpret the size or precision of a difference in the primary endpoint from the registry record. Anti-FMP1 antibody titer responses are listed separately as a secondary outcome; no result for that outcome is included in the registry record by the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry records a randomized, triple-masked, parallel design, but does not report the statistical analysis methods used for the primary endpoint. It lists no analyses. The following concepts are general explanations of how such data may be considered; they are not claims about analyses performed in this trial.

Why the endpoint’s form matters

The primary measure is described as a number of events, with symptoms grouped as any, local, or general and observed after vaccinations. A count can represent repeated events, while a participant-level outcome might record whether a person experienced at least one event. Those are different summaries: one can reflect the total burden of events, and the other the proportion of participants with any event. The registry does not specify which of these summaries was used for the primary analysis, nor does it provide symptom counts or participant counts by category.

Counts often have a distribution that differs from the familiar bell-shaped pattern assumed by some simple statistical methods. In general, a count analysis needs to account for the way event counts vary and for whether observations are independent. If repeated symptom observations from the same participant are included, they may be related rather than independent. How the trial handled repeated observations, if they were analyzed, is not reported in the registry record.

What over-dispersion means

In general, over-dispersion occurs when count data vary more than a chosen count model expects. If ignored, uncertainty estimates from that model can be too small, making results appear more precise than warranted. Analysts may consider methods that allow extra variation or account for clustering. This is a general statistical consideration for count outcomes; the registry record does not report whether over-dispersion was assessed or which model, if any, was used.

Why dose groups and timing matter

The study has three FMP1/AS02A dose groups and an Imovax comparator. The vaccine groups follow different schedules: the 10 ug group is vaccinated on days 0, 29, and 57; the 25 ug group on days 14, 42, and 70; and the 50 ug group on days 28, 56, and 84. The outcome description refers to follow-up after each vaccination. In general, a comparison could depend on whether symptoms are summarized by dose, by vaccination, by follow-up period, or across the full study. The registry does not report how these dimensions were handled in an analysis.

The registry’s note that the primary outcome has several categories or time points and is not reduced to one comparison is important for interpretation. It means the record does not offer one effect estimate that can serve as a common numerical summary of the primary endpoint. The record does not report a model, a contrast among dose groups, or a method for combining symptom categories. A single recalculated comparison or planning illustration cannot be derived from the listed outcome description alone.

Randomization, masking, and comparison

Randomization is a design approach intended, in general, to make assigned groups comparable with respect to measured and unmeasured characteristics. Masking can reduce the influence of expectations on reporting or assessment. The registry labels this study randomized and triple-masked, but does not describe the randomization sequence, concealment process, identities of the masked parties, or any assessment of masking. These design labels do not supply the missing outcome analysis.

A statistical comparison would ordinarily need a defined outcome summary, a comparison of interest, and an analysis method. Precision is often conveyed with a confidence interval; a p-value may also be reported under a specified test. Neither a primary-outcome estimate nor its uncertainty or test result appears in the registry record. General explanations of these methods cannot replace the trial’s missing numerical results.

Planning calculations and observed results

Sample-size planning is different from analyzing observed results. A planning calculation uses assumptions about an effect and variability to illustrate how many participants might be needed for a stated design and target power. Such a calculation does not describe the power actually achieved after a trial. The registry record does not report the trial’s own sample-size justification. It also does not provide a single observed primary effect to use as a common basis for recalculating a comparison, because the endpoint is not reduced to one comparison.

Any planning illustration should therefore be understood as conditional on its stated assumptions, rather than as evidence that the trial had a particular probability of detecting an effect. The record does not report a primary-outcome model, a planned contrast, or analysis results that would allow a direct comparison between a design calculation and the observed trial analysis.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome includes any, local, or general solicited symptoms, and the registry notes that it has several categories or time points rather than one comparison. Considering several symptoms, categories, doses, or follow-up periods can create multiplicity: in general, the more separate statistical tests or comparisons made, the greater the chance that at least one appears notable by chance. This is a general statistical concern, not evidence that a particular number of tests was performed in this trial.

The registry record does not report a multiplicity plan, a hierarchy among outcome categories, or a method for adjusting statistical tests. It also lists no analyses. Consequently, it is not possible to determine whether results were analyzed separately or combined, or how any multiple comparisons were handled. The record does not provide primary-outcome results or a single comparison that could be evaluated for multiplicity.

Missing-data handling is also not reported in the registry record. The record does not describe whether all randomized participants were included in each outcome analysis, how missed vaccinations or symptom follow-up were handled, or whether any participants were excluded from analyses. It does not identify analysis populations such as intention-to-treat or per-protocol groups. These details matter because the people with available follow-up may differ from those without it, and because different analysis populations can answer different questions.

The total enrollment and adverse-event denominators do not establish the analysis population for the primary endpoint. Without outcome-specific denominators and a description of missing-data methods, the completeness of symptom reporting cannot be assessed from the registry record.

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: convulsions (2.2%), bronchospasm (2.2%), intestinal obstruction (2.2%), anemia (1.1%), convulstions (1.1%).

The registry lists 90 at risk in the FMP1/AS02A Malaria Vaccine group and 45 at risk in the Imovax group. Serious adverse events affected 3 in the FMP1/AS02A group and 2 in the Imovax group; the record lists 1 death and 0 deaths, respectively. These figures are descriptive summaries, not adjusted estimates of treatment effect. The registry record does not report a statistical comparison or uncertainty interval for them.

The “other” adverse-event figures are 87 affected in the FMP1/AS02A group and 10 in the Imovax group. The record does not define the relationship between the serious and other categories or say whether the categories can overlap. They should not be added together or interpreted as mutually exclusive categories without that information. The record also does not report details that would clarify the circumstances, timing, or relatedness of the listed events.

The listed serious-event terms and percentages are Convulsions, 2.2%; Bronchospasm, 2.2%; Intestinal obstruction, 2.2%; Anemia, 1.1%; and Convulstions, 1.1%. The record does not give the denominators or event-level detail underlying these percentages. These summaries do not establish whether an event was caused by a vaccine. They describe what the registry lists, with important context and analysis details absent.

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

The registry record establishes that a Phase 1 randomized, triple-masked, parallel trial was conducted in children aged 12–47 months in western Kenya. It describes three FMP1/AS02A dose schedules, an Imovax Rabies Vaccine comparator, solicited symptoms as the primary outcome, and anti-FMP1 antibody titer responses as a secondary outcome. It also contains descriptive adverse-event summaries. These details identify the trial’s setting, interventions, and outcome questions.

The record does not report a numerical result for the primary symptom endpoint, a statistical comparison between groups, or a precision estimate. It therefore does not show the magnitude or uncertainty of any difference in solicited symptoms. Although antibody titer responses are listed as a secondary outcome, no result for that outcome is reported in the registry record described by the registry record. The record does not support a conclusion about the direction or size of an effect on either endpoint.

In general, the absence of a reported estimate is different from an estimate showing no difference. Without a reported primary-outcome comparison, the data available in the registry record do not establish whether symptom occurrence differed between the groups. Likewise, the descriptive serious adverse-event counts are not, by themselves, evidence that an intervention caused or prevented events. The registry record does not report an adjusted safety analysis, a causal assessment, or uncertainty intervals for those figures.

The record also does not report the analysis populations, handling of missing observations, or a sample-size justification. Those omissions limit assessment of how complete the outcome data were and how the study’s size related to the precision of its intended comparisons. The study’s Phase 1 designation and stated safety and immunogenicity focus are relevant context, but do not supply the missing outcome results.

Accordingly, the registry information describes the design and some safety summaries, while leaving the central numerical evidence for the primary and secondary outcomes unreported. It should not be read as a definitive statistical comparison of the vaccine dose groups with the comparator.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is described as several symptom categories or time points rather than as one comparison. That distinction matters: a study can define an outcome of interest without the registry presenting a single estimate that answers the central comparison in a readily interpretable way. Here, the primary endpoint is described as the occurrence of any, local, or general solicited symptoms during an 8 day follow-up period after each vaccination, with a 40 days timeframe. No primary result or analysis is listed.

The study also includes three vaccine doses with different vaccination schedules, alongside a comparator administered on corresponding vaccination days. In general, dose, timing, symptom category, and repeated follow-up can all shape how results are summarized. A clear analysis would need to state which comparisons were planned and how observations across categories and visits were treated. These statistical details are not reported in the registry record.

The registry’s adverse-event figures illustrate another important distinction: descriptive counts are not the same as a statistical comparison. Counts can provide a concise record of events, but a comparative interpretation also depends on definitions, denominators, follow-up completeness, analysis methods, and uncertainty. Those details are not available for the listed safety summaries.

Finally, the record identifies anti-FMP1 antibody titer responses as a secondary outcome but does not include results for it. Separating a stated outcome from its reported evidence is central to statistical reading. The trial description communicates what investigators set out to assess; the registry record, as described, does not communicate numerical results sufficient to quantify the primary or secondary outcome comparisons.

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 contains no primary-outcome results, despite describing the symptom endpoint and its follow-up period. It does not provide counts by symptom category, dose group, vaccination, or follow-up period, nor a single comparison estimate. This prevents assessment of the magnitude and precision of the primary outcome. The listed secondary antibody outcome also has no reported result in the record.

Statistical methods are not described. The record lists no analyses and does not report a model, test, confidence interval, or approach to multiple comparisons. It does not explain how repeated symptom observations were handled or whether event counts and participant-level outcomes were distinguished. These omissions prevent evaluation of the appropriateness of an analysis for the endpoint’s structure.

Further limitations are that the registry does not report the allocation ratio, randomization procedure, or detailed masking procedures. It does not describe missing-data handling, outcome-specific denominators, or analysis populations. A sample-size justification for the trial is not reported in the registry record. The adverse-event summaries lack event-level context and an explained relationship between the serious and other categories; the denominators for the listed serious-event percentages are also not reported.

The record describes dose groups with different vaccination schedules, but does not explain how dose and timing were represented in the outcome analysis. These are limitations of the information reported in the registry, rather than proof that the trial itself did not collect or analyze such information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 1 Trial of a Malaria Vaccine in Young Kenyan Children — NCT00317473.
• Registry record last updated 2017-10-02; status last verified 2017-05.
• Results first posted 2017-10-02.
• 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

NCT00317473 is a completed, randomized, triple-masked, parallel Phase 1 trial with 135 participants. It enrolled children aged 12–47 months in western Kenya and compared three FMP1/AS02A dose schedules with Imovax Rabies Vaccine on corresponding vaccination days. The registry lists solicited symptoms during follow-up after vaccination as the primary outcome and anti-FMP1 antibody titer responses as a secondary outcome.

The record lists 90 at risk in the FMP1/AS02A group and 45 in the Imovax group for the adverse-event summaries. It reports serious adverse events affecting 3 and 2, other adverse events affecting 87 and 10, and deaths of 1 and 0, respectively. It lists no statistical analyses and does not report a primary-outcome comparison, an antibody result, or a trial sample-size justification. The study started in 2003-06, with primary completion in 2004-07.