VAC071: A Study to Assess Efficacy of the ChAd63/MVA PvDBP Vaccines: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for VAC071: A Study to Assess Efficacy of the ChAd63/MVA PvDBP Vaccines (NCT04009096), a non-randomized phase 2 study. The primary outcome is Efficacy of the ChAd63 and MVA PvDBP Vaccines, Administered in a Heterologous Prime-boost Regimen, Assessed by a Reduced Parasite Multiplication Rate in Vaccinated Subjects.

2. Clinical Question

The central question concerns a laboratory-derived measure of parasite growth following deliberate malaria challenge, rather than malaria incidence during ordinary exposure. The primary endpoint is the quantitative PCR-derived parasite multiplication rate, expressed per 48hr. The planned primary analysis pools participants from Groups 1, 2 and 3 who underwent challenge and compares their endpoint with that of simultaneous malaria-naïve controls.

The registry record describes different vaccination histories across the groups. Group 1 was planned to receive a ChAd63 PvDBP dose followed by MVA PvDBP. Group 2 was planned to receive an initial ChAd63 PvDBP dose, a later second ChAd63 PvDBP dose and then MVA PvDBP. Group 3 was conditional on the number completing Group 2; its full regimen is not reported in the registry record. Consequently, the main question is not a randomized comparison of vaccine schedules. It is a comparison of pooled vaccinated participants with controls under the stated challenge conditions.

The numerical parasite multiplication rate results, the size and precision of any contrast, and the control-group results are not reported in the registry record. The clinical question can therefore be described from the registered design, but the registry information does not establish the direction or magnitude of the observed comparison.

3. Trial Design

VAC071 is registered as a Phase IIa, open-label, non-randomized, parallel study of ChAd63 PvDBP and MVA PvDBP. The condition is vivax malaria, and the stated study population is healthy adults living in the UK. The registry record lists 16 participants enrolled, a start date of 2019-07-18, primary completion on 2022-07-07, and a completed status. The sponsor is the University of Oxford.

The study used controlled human malaria infection. Participants were deliberately challenged with blood-stage malaria by intravenous injection, according to the brief description. The vaccination schedules varied: Group 1 was described as a heterologous prime-boost regimen, while Group 2 included an earlier ChAd63 PvDBP vaccination before the later prime-boost sequence. Group 3 could recruit additional volunteers if fewer than 6 volunteers completed the study in Group 2, with a stated aim of reaching 6 completers across those groups. The complete Group 3 schedule is not reported in the registry record.

The brief description places challenge approximately 4 weeks after the second vaccination. The group descriptions specify challenge 2-4 weeks after the relevant vaccination sequence for Groups 1 and 2. The primary endpoint timeframe is 3 months post CHMI. These descriptions identify the intended sequence and measurement period; they do not supply individual participant timelines or confirm the timing for every participant.

The primary efficacy population is described as per protocol: vaccinated volunteers across Groups 1, 2 and 3 who underwent challenge, with the group data pooled. The registry states that group-specific summary statistics were not reported because numbers in each group were too small for meaningful summaries. The comparison group consisted of malaria-naïve controls in simultaneous challenge under identical conditions. The study was not randomized, and the registry explicitly cautions that the arms are not a like-for-like control comparison. Detailed control recruitment, baseline characteristics, and allocation procedures 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:

Analysis population for the primary outcome, as defined in the registry: Primary efficacy analysis conducted as per protocol on pooled data from all volunteers across groups 1, 2 and 3 who underwent CHMI. Numbers in each group too small for meaningful summary statistics to be reported for each group 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.

6. Primary Endpoint

The registry lists the primary outcome as Efficacy of the ChAd63 and MVA PvDBP Vaccines, Administered in a Heterologous Prime-boost Regimen, Assessed by a Reduced Parasite Multiplication Rate in Vaccinated Subjects, measured over 3 months post CHMI.

The primary endpoint is the quantitative PCR-derived parasite multiplication rate (PMR), reported as a rate per 48hr. In general, a multiplication rate describes how the measured parasite quantity changes over a defined interval. Quantitative PCR provides a laboratory measure of parasite material; it is not itself a direct measure of symptoms or clinical disease. In this study, the registry identifies PMR as the efficacy endpoint after controlled human malaria infection.

The endpoint is intended to capture parasite growth after challenge. Comparing PMR between vaccinated participants and malaria-naïve controls under simultaneous, identical challenge conditions provides a way to assess whether the measured growth pattern differs between those groups. The registry specifies a median and full range as the summary format, and identifies the assessment timeframe as 3 months post CHMI.

A median describes the middle of an ordered set of measurements, while the full range describes its lowest and highest observed values. In general, these summaries can convey the center and spread of a small or variable dataset without requiring a normal distribution assumption for the measurements themselves. They do not, on their own, quantify the precision of a between-group contrast.

The registry describes pooling data from challenged participants in Groups 1, 2 and 3 for the primary efficacy analysis. It does not provide the numerical PMR values, group medians, full range, estimated contrast, or uncertainty interval. The endpoint definition therefore explains what was intended to be measured, but the registry record does not allow a reader to assess the observed result or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary endpoint is parasite multiplication rate derived from quantitative PCR. The planned summary is the median with the full range, at 3 months post CHMI. The primary analysis is described as a comparison between pooled data from challenged volunteers in Groups 1, 2 and 3 and malaria-naïve controls taking part in simultaneous challenge under identical conditions. The registry does not name a statistical test or give a numerical effect estimate.

What does the endpoint summary describe?

In general, the median is the middle observation when measurements are ordered. It is less influenced by unusually high or low values than the mean. The full range gives the minimum and maximum observations, so it conveys the total span of the observed values but not the shape of the distribution between those extremes. For a small sample, the range can be especially sensitive to individual observations. Neither the median nor the range provides a direct estimate of uncertainty in the comparison between groups.

The registry gives no PMR values or summary statistics. It also does not report a confidence interval, standard error, or p-value for the primary comparison. A confidence interval, as a general statistical concept, expresses the uncertainty around an estimate under the assumptions of the chosen method. A p-value, in general, measures how incompatible the observed data are with a specified null model; it is not a measure of effect size or clinical importance. No such inferential result for PMR is reported in the registry record.

Why does pooling matter?

The primary population is described as a per-protocol pool of volunteers from Groups 1, 2 and 3 who underwent CHMI. Pooling can produce an overall summary for the combined participants, but it can conceal differences among the component groups. This matters because the registered schedules were not identical: Group 1 had a prime-boost sequence, while Group 2 included an earlier ChAd63 PvDBP dose before its later sequence. Group 3 was conditional, and its full regimen is not reported in the registry record. The registry states that the numbers in each group were too small for meaningful group-specific summary statistics.

A per-protocol analysis generally focuses on participants who meet specified study requirements, but the registry does not provide the detailed inclusion rules, participant flow, or reasons for any exclusions. The exact number of participants in the primary analysis is not reported in the registry record. As a result, the stated enrollment of 16 should not be treated as the size of the efficacy analysis population.

How should the comparator be understood?

The planned comparator was malaria-naïve controls undergoing simultaneous challenge under identical conditions. The trial allocation is non-randomized, and the registry cautions that its arms are not a like-for-like control comparison. In general, random allocation supports comparability by reducing systematic differences at baseline. Without randomization, observed differences may reflect both the intervention and differences between participants or their selection into groups. The registry record does not describe a statistical adjustment strategy, baseline balance assessment, or a method for addressing possible confounding.

Simultaneous challenge and identical stated conditions provide context for the comparison, but they do not remove all possible sources of difference. Control-group size, characteristics, and outcome summaries are not reported in the registry record. The size of any observed PMR contrast and its precision therefore cannot be evaluated from the registered information.

What do the planning assumptions mean?

The sample-size planning illustrations are described as calculations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The planning target is expressed as a stated fraction of the observed effect. These are planning illustrations, not the trial’s own design justification and not observed power. General sample-size calculations estimate how many participants might be needed under specified assumptions; they do not establish that a completed study has adequate precision or that an effect is present.

The registry does not report its own sample-size justification. It also does not report an observed numerical effect to which a reader could relate the planning illustrations. No conclusion about the adequacy of the actual analysis size can be drawn from those assumptions alone. Any planning quantity should be interpreted as conditional on its assumptions, rather than as a finding about the participants enrolled in VAC071.

More broadly, over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. If a model understates variability, its uncertainty estimates may be too narrow. The registry does not state whether over-dispersion was assessed or what model was used for PMR. No model diagnostics, distributional assumptions, or sensitivity analyses are reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists one primary efficacy endpoint and four secondary outcome areas: safety, humoral immunogenicity, cellular immunogenicity, and immunological readouts for association with reduced parasite multiplication rate. Multiple outcomes can create a multiplicity issue because examining several hypotheses can increase the chance of at least one apparently notable result by chance. In general, a prespecified testing hierarchy or adjustment method can address that concern. Whether such a strategy was planned or used is not reported in the registry record.

The registry describes the primary efficacy analysis population as per protocol and pooled across Groups 1, 2 and 3 among volunteers who underwent CHMI. The detailed definition of per-protocol eligibility, handling of protocol deviations, and analysis population counts are not reported in the registry record. The number of participants with an available primary endpoint is also not reported.

Missing-data methods are not reported in the registry record. There is no description of how missing PMR measurements were handled, whether any imputation was used, or whether analyses examined sensitivity to missing observations. Participant flow and reasons for non-completion or exclusion are likewise not reported. These omissions limit assessment of whether the analyzed participants represent all enrolled or challenged participants.

The registry does not report an analysis plan, interim analyses, or a multiplicity adjustment. These items should not be inferred from the endpoint list or the completed status. The posted information is sufficient to identify the broad efficacy question and stated analysis population, but not to reconstruct the full statistical plan or determine how missing data and multiple outcomes were handled.

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 non-serious adverse event terms

The registry lists no serious adverse events and no deaths in the reported vaccination categories. Following ChAd63 PvDBP vaccination, 16 participants were at risk for serious events and 0 had a reported serious event; 16 were at risk for other adverse events and 2 had a reported event in that category. Following MVA PvDBP vaccination, 8 participants were at risk for serious events and 0 had a reported serious event; 8 were at risk for other adverse events and 2 had a reported event in that category. Deaths are listed as 0 in both categories.

These counts describe the registry’s reported safety categories; they do not establish that no serious event could occur. The number at risk differs between the vaccination categories, and the record does not provide the adverse-event terms, follow-up duration for these summaries, or details about severity and relatedness for the other events. The term list for serious events is empty. The safety counts should therefore be read as reported observations within the listed groups, not as a precise estimate of uncommon-event risk or a comparison of vaccine regimens.

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

The registered design asks whether parasite multiplication rate after controlled challenge differed between pooled vaccinated participants and malaria-naïve controls. It is a focused, laboratory-based efficacy question in healthy adults, with a defined endpoint and a stated comparison under simultaneous challenge conditions. The record also makes clear that vaccine schedules varied and that the primary efficacy analysis pooled the vaccinated groups.

The registry does not report the numerical PMR results, a group contrast, or a measure of statistical uncertainty. It therefore cannot establish the direction, magnitude, or precision of the observed efficacy comparison. Completion status and enrollment do not substitute for those results. Nor can the recorded absence of serious adverse events in the listed categories establish that serious events are impossible; those observations need to be interpreted in light of the limited reported counts and missing event details.

The study’s non-randomized design limits causal interpretation of a difference between vaccinated participants and controls. In general, without randomization, differences in participant characteristics or selection can contribute to an observed group contrast. Pooling distinct schedules further means that a combined result, if reported elsewhere, would not by itself identify the result of each separate vaccination schedule.

The study addresses response to deliberate blood-stage challenge in healthy adults living in the UK. The registry does not report evidence about outcomes during natural exposure, other populations, or clinical settings beyond the described challenge study. Any extension beyond the registered population, regimen, challenge conditions, and endpoint would require evidence not reported in the registry record. The statistical description defines what the study set out to compare; the registry record does not provide enough outcome information to determine what the comparison found.

13. Why This Trial Matters Statistically

VAC071 is statistically notable for using a controlled human malaria infection design to study a quantitative measure of parasite growth after challenge. The primary endpoint is explicitly defined as quantitative PCR-derived parasite multiplication rate per 48hr, and the registry specifies a median and full range. Clear endpoint definition is important because it identifies the measured quantity and the time context for interpreting it.

The record also exposes a design feature that matters for inference: allocation was non-randomized, and the registry cautions that the arms are not a like-for-like control comparison. That distinction is central when interpreting any between-group result. A numerical difference could be described as an observed contrast, but causal interpretation would depend on comparability and analysis details that are not reported in the registry record.

Pooling participants across groups is another important statistical choice. The group schedules differed, but group numbers were considered too small for meaningful separate summaries. Pooling can support a broader combined estimate while limiting conclusions about regimen-specific outcomes. The statistical question is therefore tied to the pooled vaccinated population rather than to a clean head-to-head comparison of schedules.

Finally, the registry’s missing numerical efficacy results illustrate why design information and outcome reporting serve different purposes. The design identifies what the investigators planned to measure and compare; it does not tell readers the observed size or precision of the effect. The listed safety counts also require context about follow-up and event details. Together, these features make the record useful for understanding the study question and its inferential limits, while leaving its numerical efficacy findings unavailable in 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 numerical efficacy results are not reported in the registry record. PMR values, summary statistics, the vaccinated-control contrast, uncertainty estimates, and inferential results are absent. Without them, the magnitude and precision of the primary comparison cannot be assessed.

The efficacy analysis was planned as a pool across Groups 1, 2 and 3, although vaccination schedules varied. The registry says that group-specific summaries were not meaningful because the numbers were too small. The full Group 3 regimen is not reported in the registry record, and the number analyzed in each group is not stated. This limits interpretation of any pooled estimate as a result attributable to a particular schedule.

The non-randomized allocation is an additional limitation. The record does not describe baseline characteristics, control-group size, adjustment for differences between groups, or methods for addressing confounding. The stated simultaneous challenge conditions do not resolve those unreported design and analysis details.

Other relevant information is also absent: participant flow, detailed per-protocol criteria, missing endpoint handling, multiplicity procedures, the statistical model or test, and the registry’s own sample-size justification. Safety reporting lists event counts but does not provide event descriptions or the follow-up details needed to interpret the other adverse events fully. These limitations do not alter the registered study question, but they constrain what can be concluded from the registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: VAC071: A Study to Assess Efficacy of the ChAd63/MVA PvDBP Vaccines — NCT04009096.
• Registry record last updated 2024-04-12; status last verified 2022-09.
• Results first posted 2024-04-12.
• 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

VAC071 (NCT04009096) is a completed, open-label, non-randomized Phase IIa study sponsored by the University of Oxford. It enrolled 16 healthy adults living in the UK and evaluated ChAd63 PvDBP and MVA PvDBP in a controlled human malaria infection study. The registered primary endpoint was quantitative PCR-derived parasite multiplication rate per 48hr, summarized by median and full range at 3 months post CHMI.

The primary efficacy comparison was planned between pooled challenged participants from Groups 1, 2 and 3 and malaria-naïve controls undergoing simultaneous challenge under identical conditions. The registry states that group-specific summaries were not meaningful because group numbers were small. Numerical efficacy results, control-group details, and key statistical analysis details are not reported in the registry record. Safety listings record 0 serious adverse events in the reported vaccination categories, alongside 2 other adverse events in each category.