Evaluation of Reproducibility of a Sporozoite Challenge Model for Plasmodium Vivax in Human Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Reproducibility of a Sporozoite Challenge Model for Plasmodium Vivax in Human Volunteers (NCT00367380), a randomized phase 2 study. The primary outcome is Infection for P. Vivax.

2. Clinical Question

The study addresses a model-validation question rather than a comparison of a vaccine or drug with a control treatment. The registry description says that volunteers would be exposed to infected mosquitoes and monitored until blood infection became patent. The stated purpose was to assess whether this challenge approach could be used to evaluate candidate P. vivax vaccines in later phase 2a trials.

The primary outcome is the prepatent period, expressed in days. The posted group means are 11.0 days for Group 1, 11.0 days for Group 2, and 9.0 days for Group 3. Their standard deviations are 2.0, 1.0, and 4.0 days, respectively. These summaries describe the recorded outcome in each group; they do not by themselves establish whether the model is reproducible or whether group differences are statistically distinguishable. The registry record does not report a statistical test or confidence interval for comparing the groups.

3. Trial Design

This was a randomized, open-label, parallel-group phase 2 trial. The registry record lists the study as completed and records enrollment of 18. Volunteers were allocated to three groups of 6, each associated with a different P. vivax parasite batch: 413ABM, 414WRR, and 418JAL. The record lists no masking.

The study description divides the work into two successive steps. In the first, infected blood from people with active P. vivax infection was to be collected, screened for infectious diseases, and used to feed colonized Anopheles albimanus mosquitoes through a membrane feeding assay. Sixteen days later, selected positive mosquito batches were to be used in the challenge step. These details describe the planned process in the registry summary; further operational details are not reported in the registry record.

In the challenge step, volunteers were to receive bites from 3±1 infected mosquitoes. Each group was exposed to a different isolated parasite. Volunteers were to be monitored after infection, with treatment once blood infection became patent as determined by microscopy of thick blood smears. The registry states that comparisons of the three groups would be used to assess reproducibility, but it does not report the statistical procedure planned for those comparisons.

Primary completion is listed as 2006-12, and the study start is listed as 2006-12. The primary endpoint was time to occurrence of P. vivax infection, described as the prepatent period, with a timeframe of twenty eight days. The registry reports group-level means and standard deviations for that endpoint. It does not report an inferential analysis, a detailed statistical analysis plan, or the reason for selecting the enrollment target.

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

Analysis population for the primary outcome, as defined in the registry: Values in the data table represent time to occurrence of P.Vivax infection (prepatent 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 Infection for P. Vivax, measured over Twenty eight days.

The primary endpoint is the time to occurrence of P. vivax infection, expressed as a prepatent period in days. It captures the interval from challenge to the first observed evidence of infection. In this study, blood smears were scheduled daily on days 7 to 23 and every other day until day 29. Any evidence of P. vivax infection was considered positive and was to be confirmed later by real-time polymerase chain reaction.

This endpoint is relevant to the stated model-reproducibility question because it describes when infection became detectable after exposure. Comparing its distribution across groups exposed to different parasite batches can help describe whether the challenge outcomes were similar. However, a mean alone does not show the timing pattern for each volunteer, the proportion with an observed infection, or the uncertainty around a group comparison.

The posted results give a mean and standard deviation for each group, with 6 volunteers listed in each. Group 1 has a mean of 11.0 days and standard deviation of 2.0; Group 2 has a mean of 11.0 days and standard deviation of 1.0; Group 3 has a mean of 9.0 days and standard deviation of 4.0. The registry record does not provide participant-level times, endpoint-specific missingness, or a confidence interval for any mean. The stated timeframe and assessment schedule therefore provide context for interpreting the summaries, but they do not supply the detail needed to reconstruct individual time-to-infection patterns.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted endpoint is continuous: time to infection is summarized in days. The registry identifies the reported measure as a mean with standard deviation. No analysis results beyond the group summaries are reported in the registry record. The explanations below distinguish what these summaries mean in general from what can be concluded for this trial.

What does the mean describe?

In general, a mean is the arithmetic average of the observed values in a group. It provides a compact description of the group’s center, but does not show every observation or the shape of the outcome distribution. In this trial, the reported means are 11.0 days for Group 1, 11.0 days for Group 2, and 9.0 days for Group 3. These values describe the group averages as posted; they do not establish how close individual participants’ times were to those averages.

What does the standard deviation describe?

In general, a standard deviation describes how spread out observations are around their mean, in the same units as the measure. It is not a confidence interval and does not directly quantify uncertainty in the mean. The posted standard deviations are 2.0 days for Group 1, 1.0 day for Group 2, and 4.0 days for Group 3. The larger value for Group 3 indicates greater observed dispersion around its mean in these summaries. The record does not provide the individual data needed to examine whether that dispersion is symmetric or influenced by an unusual observation.

How should uncertainty be assessed?

In general, a confidence interval gives a range of values compatible with a statistical procedure and the observed data, under the assumptions of that procedure. It can help distinguish a precise estimate from one with substantial uncertainty. The registry record does not report confidence intervals for the group means or for comparisons among groups. The standard deviations should not be read as substitutes for those intervals. With 6 volunteers listed in each group, the group summaries alone provide limited information about the precision of a mean or a comparison.

What does randomization contribute?

In general, random allocation can reduce systematic differences between groups at assignment, on average, when implemented as planned. It does not guarantee that small groups will have identical characteristics, nor does it remove uncertainty from outcome estimates. The registry describes random assignment to three groups and a parallel design. It does not report the randomization procedure, allocation concealment, baseline characteristics, or any analysis adjusting for participant characteristics. These details are not reported in the registry record, so the influence of those design features cannot be assessed from the posted summaries.

Why is the outcome schedule relevant?

In general, an outcome measured at scheduled visits may be observed with less temporal precision than an event monitored continuously. The registry reports that thick blood smears were performed daily on days 7 to 23 and every other day until day 29, and that any evidence of infection was considered positive and confirmed later by real-time polymerase chain reaction. This schedule gives context for how the prepatent period was assessed. The analysis method for timing between observations, confirmation, or any event not observed within the assessment period is not reported in the registry record.

Why is over-dispersion sometimes important?

In general, over-dispersion refers to variability greater than a statistical model assumes. If a model underestimates variability, its standard errors can be too small and its confidence intervals or tests can be misleading. The posted endpoint is summarized as a continuous measure using means and standard deviations, but no model-based analysis is reported. It is therefore not possible to determine whether over-dispersion was assessed or whether a model requiring such an assessment was used. The variation in the group summaries alone does not establish a particular distributional problem.

What can be said about hypothesis testing?

A test of group differences would require a defined comparison and a method that accounts for the design and the outcome. The registry record does not report a p-value, test statistic, or inferential comparison among the three groups. No recalculated comparison is presented, and there is no sponsor analysis in the record to take precedence over a recalculation. The posted descriptive summaries should consequently be interpreted without a claim of statistical significance, equivalence, or non-inferiority.

What about planning calculations?

In general, sample-size planning uses assumptions about an outcome difference, variability, significance level, allocation, and desired power. Planning illustrations based on an observed effect are not observed power and are not evidence that a completed study was adequately powered. Numerical planning estimates and the trial’s own sample-size justification are not reported in the registry record. The record does mention a planning framework based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. Those assumptions do not supply an inferential result for this three-group challenge study.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Group 1", "Group 2", "Group 3")
n   <- c(6, 6, 6)
m   <- c(11, 11, 9)
sp  <- c(2, 1, 4)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Group 1  6  11.000  2.000  8.901  13.099
CARM  Group 2  6  11.000  1.000  9.951  12.049
CARM  Group 3  6  9.000  4.000  4.802  13.198

11. Multiplicity, Missing Data and Analysis Populations

The study has three groups and a primary endpoint, but the registry record does not report a statistical analysis plan describing which group comparisons were intended. It also does not report whether any adjustment for multiple comparisons was planned or performed. In general, making multiple statistical comparisons can increase the chance of at least one false-positive result if each comparison is interpreted independently. Whether that issue applies to a particular conclusion depends on the planned hypotheses and analysis; these are not reported in the registry record.

The posted outcome information consists of a mean and standard deviation for each group. The record does not state whether the analysis included all randomized volunteers, only volunteers with an observed infection, or another analysis population. The number of endpoint observations contributing to each summary is not separately described beyond the group sizes listed. Missing endpoint values, exclusions, protocol deviations, and their handling are not reported in the registry record.

These omissions matter because a group summary may be influenced by which participants contribute data and how incomplete observations are handled. In general, an analysis that excludes participants with missing outcomes can differ from one that uses all randomized participants under stated assumptions. Without information on completeness and analysis populations, it is not possible to assess whether the posted summaries represent all assigned volunteers or to evaluate potential bias from missing data.

The record does not report interim analyses, stopping rules, or a prespecified primary analysis method. Such details should not be inferred from the completed status or from the descriptive results. The supported interpretation is limited to the posted group-level summaries and the methods expressly described in the registry record.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events affecting participants in Group 1, Group 2, and Group 3. It also lists other adverse events affecting 1 participant in Group 1, 4 participants in Group 2, and 1 participant in Group 3. These are participant counts as recorded; the registry does not provide the event terms or further descriptions for these other adverse events.

The serious-event figures are not evidence that no adverse events of any kind occurred. Serious adverse events and other adverse events are separate categories in the registry record. In general, a count of participants affected does not convey event severity beyond the category definition, timing, duration, or relationship to study procedures. Those details are not reported in the registry record.

Deaths are not reported in the registry record. The adverse-event information does not include an event-level account or a narrative explaining the group counts. These figures should therefore be read as the posted safety summaries, not as a complete description of all events or as a basis for comparing safety between groups.

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

The results describe the prepatent-period summaries observed in the three challenge groups: means of 11.0, 11.0, and 9.0 days, with standard deviations of 2.0, 1.0, and 4.0 days. Each group has 6 volunteers listed. These observations provide a descriptive view of timing and dispersion following exposure to the different parasite batches.

The study’s stated aim was to evaluate reproducibility of a P. vivax sporozoite challenge model. The posted summaries alone do not establish that aim. The registry does not report a reproducibility definition, a statistical comparison, confidence intervals, or a decision threshold. Similar group averages do not establish statistical equivalence, while a difference between averages does not establish that batches behave differently beyond the observed sample.

The results also do not establish the efficacy of a candidate vaccine or drug. The registry describes a challenge-model evaluation in volunteers, not a posted comparison of candidate treatment with a control treatment. The stated reason for evaluating the model was to support future evaluation of candidate P. vivax vaccines in phase 2a trials; that future use is a rationale, not a result demonstrated by the present summaries.

More broadly, results from these groups cannot on their own establish how outcomes would generalize to other volunteers, parasite batches, mosquito exposures, or study settings. The registry record does not report participant-level data, uncertainty estimates, or a detailed analysis plan that would support broader conclusions. The defensible reading is therefore narrow: the record reports group-level means and standard deviations for time to infection, with the stated design and assessment schedule, but no inferential conclusion about reproducibility.

14. Why This Trial Matters Statistically

This trial is statistically notable because its central question concerns reproducibility across challenge batches rather than a conventional comparison of an active treatment with a control. For this question, the definition of reproducibility is important: investigators need to specify what degree of similarity in outcomes would count as acceptable, and which outcome features matter. The registry record states the objective of evaluating reproducibility but does not report a quantitative criterion or statistical method for reaching that determination.

The three group summaries illustrate why both central tendency and spread matter. The means for Groups 1 and 2 are each 11.0 days, while Group 3’s mean is 9.0 days. The standard deviations are not the same across groups, with 4.0 days reported for Group 3 compared with 2.0 and 1.0 days for the other groups. A focus on means alone would not capture this difference in observed dispersion. Conversely, these summaries do not reveal individual values or provide uncertainty around the group estimates.

Small groups make uncertainty especially relevant. A concise descriptive summary can be useful, but it cannot replace a planned inferential analysis when the research question is whether outcomes are sufficiently consistent across batches. A well-defined comparison would need to account for the three-group structure and clarify the relevant margin or criterion for reproducibility. Those elements are not reported in the registry record.

The case also demonstrates the distinction between a model-validation rationale and evidence that a model is validated. The posted results describe an endpoint and its group-level summaries. Whether those results meet a reproducibility standard cannot be determined from the registry information reported.

15. 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 interpreting the result is that the registry reports descriptive group summaries but no statistical comparison, confidence intervals, or formal reproducibility criterion. It is therefore not possible to quantify uncertainty around group differences or decide whether any observed variation meets a prespecified standard.

Each group has 6 volunteers listed, and the registry does not provide participant-level endpoint values. This limits evaluation of the distributions, possible outliers, and the contribution of individual observations to the means and standard deviations. The record also does not report endpoint-specific completeness, missing-data handling, or the analysis population.

Although randomization and a parallel design are reported, the randomization procedure and baseline characteristics are not reported in the registry record. Masking is listed as none. Further details about the challenge procedures, actual mosquito exposure received by each participant, and implementation of follow-up are not reported beyond the registry description.

The primary endpoint was assessed on a scheduled smear timetable, with later confirmation by real-time polymerase chain reaction. The record does not explain how event timing between visits, unconfirmed results, or outcomes not detected during the assessment period were handled analytically. It also does not report a detailed statistical plan, multiplicity procedures, interim analyses, or the study’s sample-size justification.

Safety information is limited to aggregate participant counts for serious and other adverse events. Event descriptions, timing, and deaths are not reported in the registry record. These reporting gaps restrict interpretation of both the endpoint and safety findings, and make broad conclusions about reproducibility or generalizability unwarranted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Reproducibility of a Sporozoite Challenge Model for Plasmodium Vivax in Human Volunteers — NCT00367380.
• Registry record last updated 2021-03-22; status last verified 2021-02.
• Results first posted 2014-06-03.
• 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.

19. Record Summary

The registry record describes a completed, randomized, open-label, parallel phase 2 study evaluating reproducibility of a Plasmodium vivax sporozoite challenge model in healthy volunteers. Enrollment is listed as 18, assigned across three groups of 6, with each group associated with a different parasite batch.

The primary endpoint is time to occurrence of P. vivax infection, or prepatent period, measured in days. The reported means are 11.0 days for Group 1, 11.0 days for Group 2, and 9.0 days for Group 3; the corresponding standard deviations are 2.0, 1.0, and 4.0 days. The registry does not report an inferential comparison or confidence intervals.

Serious adverse events are listed as affecting zero participants in each group. Other adverse events are listed as affecting 1, 4, and 1 participants in Groups 1, 2, and 3, respectively. Event details, analysis populations, missing-data handling, and a formal reproducibility criterion are not reported in the registry record.