This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Assess the Safety and Immunogenicity of the Malaria Vaccine, R21, With Matrix-M1 Adjuvant (NCT02925403), a randomized phase 1, phase 2 study. The primary outcome is Safety and Tolerability of Administration of R21/Matrix-M1 Assessed by the Occurrence of Solicited Local and Systemic Adverse Events..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02925403 |
| Phase | Phase 1, Phase 2 |
| Condition | Malaria |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 13 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Oxford |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned healthy adult volunteers. Its official title describes West African adult volunteers, and the condition listed in the registry record is malaria. Enrollment was 13. The record does not provide further participant characteristics or eligibility details in the information reported for this analysis.
Intervention
The intervention of interest was R21 with Matrix-M1 adjuvant. The arm descriptions list 10μg R21/Matrix-M1 for Group 1 and 50μg R21/Matrix-M1 for Group 2, each on days 0, 28, and 56. The brief summary instead describes a low-dose vaccine group and a saline group, so the group assignments are not consistently described.
Comparator
Saline is listed as an intervention, and the brief summary describes saline injections on days 0, 28, and 56 as the control. However, the arm descriptions identify Group 2 as receiving R21/Matrix-M1 and list saline as Group 3. The posted primary outcome results include Group 1 and Group 2, not a clearly identified saline group.
Primary question
The primary outcome asks about the occurrence of solicited local and systemic adverse events in the first 7 days post vaccination. The reported event counts are 10 for Group 1 and 0 for Group 2. Because the record’s descriptions do not resolve the group assignments, these values do not establish a clear vaccine-versus-saline comparison. The record also does not report an inferential comparison for this outcome.
3. Trial Design
The registry record describes a randomized, controlled, single-blind, parallel study. Its official title calls it a Phase Ib study, while the phase listing includes Phase 1 and Phase 2. Enrollment was 13, and the status is completed. The listed start date is 2016-08-26 and the primary completion date is 2017-02-15. These record details describe the study’s registration, not a guarantee that every planned element is represented in the posted results.
The brief summary describes volunteers randomly allocated to a vaccine group or a saline group, with three vaccinations on days 0, 28, and 56. The arm descriptions, however, give Group 1 10μg R21/Matrix-M1 and Group 2 50μg R21/Matrix-M1 at those times, and list saline as Group 3. The posted primary results show Group 1 and Group 2 only. Thus, the arm labels and descriptions do not supply a consistent account of which results correspond to saline. The identity of the party blinded is not reported in the registry record.
The primary outcome is safety and tolerability, assessed through solicited local and systemic adverse events in the first 7 days post vaccination. The registry title also identifies immunogenicity as a study aim, but the details and results of immunogenicity measures are not reported in the registry record. The record lists four outcome measures, but no secondary outcome results are posted. The protocol’s planned allocation details, recruitment procedures, and study-specific statistical plan are not reported in the registry record.
The posted primary outcome gives Group 1 a sample size of 8.0 and an event count of 10. Group 2 has a sample size of 5.0 and an event count of 0. These are descriptive results. The registry record reports no analyses for the outcome and does not give a statistical comparison, confidence interval, or p-value. The enrollment figure and outcome-group counts should therefore be understood as record entries rather than as evidence of a particular analysis population.
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
| Stage | Group 1 | Group 2 |
|---|---|---|
| STARTED | 8 | 5 |
| COMPLETED | 8 | 4 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Group 1 | Group 2 |
|---|---|---|
| Lost to Follow-up | 0 | 1 |
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.
| Characteristic | Unit | Group 1 | Group 2 | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 5 | 13 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 | 5 | 13 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 3 | 5 | 8 |
| Sex: Female, Male: Male | Participants | 5 | 0 | 5 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Burkina Faso | participants | 8 | 5 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Safety and Tolerability of Administration of R21/Matrix-M1 Assessed by the Occurrence of Solicited Local and Systemic Adverse Events., measured over Assessment of solicited AEs in the first 7 days post vaccination..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Number of adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint counts solicited local and systemic adverse events. The local events listed are pain, redness, swelling, and pruritus at the injection site. The systemic events listed are temperature, feverishness, myalgia, arthralgia, malaise, headache, and nausea. The assessment timeframe is the first 7 days post vaccination, and the unit is number of adverse events.
Solicited events are specified in advance for collection. In general, this approach can make safety monitoring more systematic by asking about particular symptoms over a defined period rather than relying only on unsolicited reports. The endpoint is intended to describe the short-term occurrence of those specified symptoms after vaccination. It is not, by itself, a complete account of every possible safety outcome, and it does not measure immune response.
The registry reports 10 events for Group 1 and 0 for Group 2. It does not explain whether the displayed count is a total across vaccination visits, how repeated symptoms in an individual were counted, or whether the counts refer to all events reported by participants. Those endpoint details are not reported in the registry record. The sample sizes are listed as 8.0 and 5.0, but the inconsistent arm descriptions also prevent a confident interpretation of the groups as vaccine and saline. No direct comparison of the endpoint is reported.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome values are 10 adverse events in Group 1 and 0 in Group 2. The recorded group sizes are 8.0 and 5.0, respectively. These figures describe the data entered for the outcome; they do not, on their own, quantify a treatment effect or establish a reliable difference between interventions. No inferential analysis, confidence interval, or p-value is reported in the registry record.
There is an important interpretive obstacle: the brief summary describes a vaccine group and a saline group, while the arm descriptions identify Group 1 and Group 2 as vaccine-dose groups and saline as Group 3. The primary outcome values are given for Group 1 and Group 2. The registry record does not reconcile these descriptions. Consequently, the event counts cannot be confidently assigned to a vaccine-versus-saline contrast from the posted information. The record also identifies Group 1 as the control in its outcome data, which does not resolve the conflict with the arm descriptions.
Counts are not the same as participant-level risks. The endpoint unit is number of adverse events, and the record does not clarify whether participants could contribute multiple events or how events across vaccination visits were handled. It would therefore be inappropriate to turn these counts into a proportion of participants or to describe them as the number of participants experiencing an event. No such calculation is needed to see that the registry gives a raw count, rather than a fully specified comparative estimate.
The safety listings add context but do not resolve the arm-label problem. For serious adverse events, the record lists 0 affected among 8 at risk in Group 1 and 0 among 5 at risk in Group 2; deaths are listed as 0 in each group. For other adverse events, it lists 8 affected among 8 at risk in Group 1 and 5 among 5 at risk in Group 2. These entries are limited to the groups as named in the record. They do not establish what occurred in an unreported saline group or give a complete account of event severity, timing, or causality.
The small group counts and lack of reported uncertainty estimates limit how precisely the results can be interpreted. A zero count in a group does not show that the underlying event possibility is absent. Conversely, the nonzero count in Group 1 cannot be attributed to a particular dose or comparator without consistent treatment assignments and a clear event-counting method. The registry record does not report an adjusted analysis or explain whether any analysis accounted for repeated events within participants.
The posted data therefore support a narrow descriptive statement: the primary outcome count is 10 in Group 1 and 0 in Group 2, and the serious adverse event and death counts are zero in the two listed groups. They do not support a clear estimate of the difference between R21/Matrix-M1 and saline, a claim about statistical significance, or a conclusion about immunogenicity. The registry record does not report the additional information needed for those interpretations.
9. Statistical Methods Explained
For the primary outcome, the registry reports an event count rather than a mean, a percentage, or a time-to-event measure. Counts record how many events were observed under the endpoint’s definition. Interpretation depends on what qualifies as an event, whether one participant can contribute more than one event, and the period over which events are accumulated. The endpoint description defines solicited symptoms and a first 7 days post vaccination assessment period, but how repeated events or repeated vaccination periods contribute to the posted count is not reported in the registry record.
What can a count comparison tell us?
As a general statistical point, comparing counts requires attention to the observation process as well as the numerical totals. If participants can contribute multiple events, the count may reflect several events in some people and none in others. A simple total does not show that distribution. A count may also be influenced by differences in how long or how often people were observed. The record gives the assessment timeframe but does not report a detailed event-counting rule or an analysis that accounts for these features.
Count outcomes can show more variability than a simple model assumes. In general, over-dispersion means that the observed spread in counts exceeds the spread expected under a chosen count model. If present, it can make standard errors too small under an unsuitable model, so uncertainty may be understated. The registry record does not report a count model, a dispersion estimate, or a model-based analysis. Over-dispersion is a general consideration, not a finding about this study.
What is reported for inference?
The registry lists no analyses for the primary outcome. It reports no confidence interval, p-value, adjusted estimate, or model specification. A confidence interval is a general way to express uncertainty around an estimated quantity; it does not appear in the posted primary outcome results. A p-value, when used, addresses how compatible data are with a specified null model and depends on the test and assumptions. No p-value or test is reported, so there is no basis to characterize the outcome as statistically significant or not statistically significant.
The absence of a comparative analysis matters especially because the group assignments are inconsistent across the record. Randomization is a design feature intended, in general, to help balance participant characteristics across assigned groups. It does not resolve uncertainty about which intervention each posted result represents. Since the arm descriptions and the brief summary conflict, a statistical contrast between the reported groups would not be interpretable as a vaccine-versus-saline estimate without clarification.
How should planning calculations be read?
The posted planning illustration is based on the observed effect, uses a two-sided significance level of 0.05, equal allocation, and a normal approximation. It considers the effect to detect as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power, and do not show what the trial was designed to detect unless the design assumptions match the study’s actual plan. The trial’s own sample-size justification is not reported in the registry record. Because the primary outcome lacks a reported two-arm comparison, any illustration based on an observed effect should not be treated as a validated treatment-effect estimate.
In general, a sample-size calculation depends on an assumed effect, variability, significance threshold, allocation, and analysis method. Changing those assumptions changes the planning result. The registry’s stated assumptions describe the illustration, not necessarily the study protocol. The record does not report whether an interim analysis was planned or conducted. No interim analysis should be inferred from the posted information.
What does the design contribute?
The record describes random allocation, a controlled design, single masking, and a parallel model. In general, a parallel design assigns participants to groups that remain distinct during the study, while masking is intended to limit the influence of knowledge about assignment. The identity of the masked party is not reported in the registry record. These design labels alone do not show whether masking was maintained or how allocation was implemented.
The posted results include group sizes and counts, but no analysis population definition is reported. There is no stated method for handling withdrawals, missing endpoint observations, or participants who did not complete all vaccinations. The record does not report an adjustment for baseline characteristics, repeated observations, or multiple outcomes. Those omissions mean the results should be read as the registry’s descriptive entries, without assuming a particular analysis method.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures, but no secondary outcome results are posted. It does not report a plan for controlling multiplicity, such as how interpretation would account for testing several outcomes or comparisons. The statistical plan and any pre-specified hierarchy among outcomes are not reported in the registry record. Without those details, it is not possible to determine whether a multiplicity adjustment was planned or used.
The primary outcome has a stated timeframe and symptom list, but the record does not explain how missing symptom reports were handled or how incomplete follow-up affected the count. The number of participants included in each analysis population, and the definitions of those populations, are not reported in the registry record. The group sample sizes are listed, but they do not by themselves establish which participants contributed complete endpoint data or whether all randomized participants were analyzed.
The record does not report withdrawals, exclusions, protocol deviations, or imputation methods. It also does not state whether analysis followed randomized assignment or another population definition. These are distinct questions: a trial may enroll participants, assign them to groups, and have fewer participants contribute to a particular outcome. The posted information does not describe those steps in enough detail to assess them.
Interim analyses and stopping rules are not reported in the registry record. Their absence from the available record should not be interpreted as evidence that they were or were not part of the protocol. Likewise, no assumptions about missingness or sensitivity analyses can be made from the posted results. These reporting gaps limit assessment of the analysis process, independently of the ambiguity in the treatment-group descriptions.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Group 1 | 0 | 8 | 0.0% |
| Group 2 | 0 | 5 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1 | 0 of 8 |
| Group 2 | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group 1 | 8 of 8 |
| Group 2 | 5 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1 | Group 2 |
|---|---|---|---|
| Neutropaenia | Blood and lymphatic system disorders | 6 of 8 | 2 of 5 |
| Neutropaenia | Blood and lymphatic system disorders | 5 of 8 | 2 of 5 |
| Neutropaenia | Blood and lymphatic system disorders | 3 of 8 | 3 of 5 |
| Epigastralgia | Gastrointestinal disorders | 1 of 8 | 2 of 5 |
| Rhinitis | Respiratory, thoracic and mediastinal disorders | 2 of 8 | 0 of 5 |
| Bronchitis | Respiratory, thoracic and mediastinal disorders | 2 of 8 | 0 of 5 |
| Anaemia | Blood and lymphatic system disorders | 1 of 8 | 1 of 5 |
| Anaemia | Blood and lymphatic system disorders | 1 of 8 | 1 of 5 |
| Elevated Creatinine | Renal and urinary disorders | 1 of 8 | 1 of 5 |
| Swelling | Skin and subcutaneous tissue disorders | 2 of 8 | 0 of 5 |
The serious adverse event listings report 0 affected among 8 at risk in Group 1 and 0 among 5 at risk in Group 2. Deaths are listed as 0 for each group. These are the registry’s group-level figures; they do not establish that serious events were impossible or that the groups were equivalent. With limited group sizes, a zero observed count remains a descriptive result rather than proof that an event cannot occur.
For other adverse events, the record lists 8 affected among 8 at risk in Group 1 and 5 among 5 at risk in Group 2. These entries should not be confused with the primary endpoint’s count of 10 and 0. The primary endpoint counts solicited events, whereas the safety listing gives affected counts for its other-adverse-event category. The registry does not explain the relationship between these summaries or provide enough detail to reconcile them.
The group labels remain important: the record does not consistently identify Group 2 as saline, and its arm descriptions list a further saline group without corresponding posted primary outcome values. The safety figures therefore describe the reported groups only. They do not provide a reliable treatment-specific comparison, establish causality, or describe the full range of possible safety outcomes.
12. What the Result Does, and Does Not, Mean
The registry record offers a limited description of short-term solicited adverse events in a small randomized study. It reports 10 events for Group 1 and 0 for Group 2 during the first 7 days post vaccination. It also reports zero serious adverse events and zero deaths in each listed group, alongside other-adverse-event affected counts of 8 among 8 at risk and 5 among 5 at risk. These are the posted data, not estimates of the underlying event rates.
The main interpretive limit is that the group descriptions conflict. The brief summary describes vaccine and saline groups, while the arm descriptions identify two R21/Matrix-M1 dose groups and a separate saline group. The outcome results include only Group 1 and Group 2. The record does not clarify which posted group, if any, represents saline. Consequently, the data do not establish a clear comparison of vaccine with saline or a dose comparison that can be interpreted with confidence.
The counts do not show how events were distributed across participants, whether events recurred, or how events across vaccinations were combined. The record does not report a statistical test, confidence interval, or adjusted analysis. It is therefore not possible to judge the precision of a comparative effect from the posted primary outcome, or to describe it as statistically significant or not statistically significant.
These results also do not answer the immunogenicity question named in the study title. No immunogenicity result is included in the posted information used for this analysis. Nor do the safety summaries establish causation: a registry entry records events and affected counts, but the registry entries do not state that an event was caused by an intervention.
In general, a small study can contribute descriptive safety information while remaining unable to characterize uncommon outcomes precisely. A zero count is compatible with uncertainty about the underlying possibility of an event. That general principle is relevant to the serious-event figures, but it is not a numerical estimate for this study. The findings should be read as a narrow record of the listed outcomes and groups, with substantial limits on comparative interpretation.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it illustrates the difference between a randomized design and an interpretable comparison. Randomization can support a fair comparison when group assignment and outcome reporting are clear. Here, the record describes randomization, but its summary and arm descriptions do not agree about which groups received vaccine or saline. The outcome values alone cannot repair that ambiguity.
It also demonstrates why endpoint definitions matter. The primary outcome is a count of solicited symptoms over a stated assessment period, while the safety listing includes affected counts for serious and other adverse events. These are related safety descriptions but not interchangeable measures. Without clear rules for repeated events and links between summaries, readers should not treat the event count as a participant count or assume that all reported safety quantities have the same denominator.
The record is also a reminder that descriptive counts and inferential estimates serve different purposes. Counts state what was entered for the groups. An uncertainty estimate or model would be needed to express the precision of a comparison, and no such analysis is reported. General planning calculations cannot substitute for an analysis of the observed data, particularly when the treatment mapping is unclear.
Finally, reporting completeness is part of statistical interpretability. Information about analysis populations, missing data, multiplicity, and the statistical plan is not reported in the registry record. Those omissions do not determine the direction of any treatment effect, but they limit assessment of how the posted results were produced and what conclusions they can support. The case therefore highlights the value of aligned arm descriptions, transparent endpoint methods, and clearly reported analyses.
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 most direct limitation is inconsistency in treatment-group descriptions. The brief summary presents a vaccine group and a saline group, whereas the arm descriptions list Group 1 and Group 2 as receiving different R21/Matrix-M1 doses and identify saline as Group 3. The primary outcome results include only Group 1 and Group 2. This leaves the treatment represented by each result uncertain and prevents a clear interpretation as a vaccine-versus-saline comparison.
The primary outcome is reported as a total number of adverse events, but the record does not state whether multiple events from the same participant were counted separately or how observations from the vaccination schedule were combined. The displayed counts therefore cannot be safely read as numbers of participants with an event. The relationship between the primary endpoint counts and the separate other-adverse-event affected counts is also not reported.
The listed group sizes are limited, and the record contains no confidence interval or inferential analysis to describe uncertainty. The registry does not report an analysis population, handling of missing observations, withdrawals, or exclusions. It also does not provide the study’s statistical plan, sample-size justification, interim-analysis details, or a clear account of masking procedures. These details are not reported in the registry record and should not be inferred.
Although the study title includes immunogenicity, no immunogenicity results are available in the registry record described by the posted outcome information. The record lists four outcome measures, but no secondary results are posted. The safety entries also concern only the listed categories and groups; they cannot be assumed to represent every safety outcome collected during the study. These limitations apply to interpretation of the registry record and do not establish what may have been assessed outside the posted results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess the Safety and Immunogenicity of the Malaria Vaccine, R21, With Matrix-M1 Adjuvant — NCT02925403.
- Registry record last updated 2019-11-06; status last verified 2017-06.
- Results first posted 2019-11-06.
- 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.
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18. Record Summary
The registry record describes a completed randomized, controlled, single-blind, parallel Phase Ib study, with Phase 1 and Phase 2 also listed. Enrollment was 13. The study concerns R21 with Matrix-M1 and saline in healthy adult volunteers; its official title identifies West African adult volunteers. The primary outcome measures the number of solicited local and systemic adverse events during the first 7 days post vaccination.
The posted primary outcome values are 10 events for Group 1 and 0 for Group 2, with listed group sizes of 8.0 and 5.0. Serious adverse events and deaths are reported as 0 in both groups. Other adverse events are listed as affecting 8 of 8 at risk in Group 1 and 5 of 5 at risk in Group 2. No analysis is reported for the primary outcome.
The brief summary and arm descriptions conflict about which group received saline, and the posted primary results do not include a clearly identified saline group. The registry record does not report a comparative estimate, confidence interval, p-value, analysis population, or immunogenicity results. The figures therefore support descriptive reading only, with treatment-specific interpretation limited by the unclear arm mapping.