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 of MVA85A in Healthy Infants (NCT00953927), a randomized phase 2 study. The primary outcome is To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00953927 |
| Phase | Phase 2 |
| Condition | Tuberculosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 2797 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Aeras |
| Results posted | Yes |
2. Clinical Question
Population
BCG-vaccinated, HIV-negative infants without tuberculosis were eligible. The study description identifies infants aged 126 to 182 days, recruited at a single site in South Africa. The primary safety outcome is described for all subjects vaccinated.
Intervention
The investigational vaccine was MVA85A/AERAS-485. The study evaluated its safety, immunogenicity, and prevention of tuberculosis. Some participants were placed in cohorts for different safety and immunogenicity tests.
Comparator
The control was Candida Skin Test Antigen. The registry describes control-group cohorts for different safety and immunogenicity tests as well.
Primary question
The primary outcome assessed the safety profile of MVA85A/AERAS-485, expressed as a percentage of subjects vaccinated. Adverse events were collected for 28 days after vaccination; serious adverse events were collected from vaccine dosing throughout the study.
3. Trial Design
This was a Phase II, randomized, double-blinded, parallel-group controlled trial. The registry records quadruple masking. Participants were assigned to MVA85A/AERAS-485 or Candida Skin Test Antigen control. The study focused on BCG-vaccinated, HIV-negative infants without tuberculosis.
The study description says that infants aged 126 to 182 days were to be followed for 15 to 36 months, at a single site in South Africa. The registry records an enrollment of 2797; the brief description says the study planned to enroll 2784 infants. These are different registry figures: one is the recorded enrollment and the other is the planned enrollment in the study description.
The primary outcome concerned safety. The registry states that adverse events were collected for 28 days after vaccination, and that parents or guardians recorded solicited adverse events in diary cards through 7 days after vaccination. Serious adverse events were collected throughout the study period after vaccine dosing. A safety cohort, described as the first 330 infants enrolled, also had serum chemistry and hematology testing through 28 days after vaccination.
Secondary aims included tuberculosis prevention, several measures of immunogenicity, correlates of protection, and QuantiFERON conversion. The registry marks the study as completed. The start is recorded as 2009-07 and primary completion as 2012-10. The sponsor is Aeras.
The registry does not report the allocation sequence method, the details of how masking was maintained, or a statistical analysis plan. Those design details should not be inferred from the randomized and quadruple-masked labels alone.
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 | Investigational Vaccine | Control Group |
|---|---|---|
| STARTED | 1399 | 1398 |
| COMPLETED | 1294 | 1303 |
| NOT COMPLETED | 105 | 95 |
Reasons for not completing this period:
| Reason | Investigational Vaccine | Control Group |
|---|---|---|
| Lost to Follow-up | 61 | 65 |
| Withdrawal by Subject | 36 | 25 |
| Death | 7 | 4 |
| Other study discontinuation | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: All subjects vaccinated.
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: Intent to treat population
| Characteristic | Unit | Investigational Vaccine | Control Group | Total |
|---|---|---|---|---|
| Participants analysed | 1399 | 1398 | 2797 | |
| Age, Categorical: <=18 years | Participants | 1399 | 1398 | 2797 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | .401 (SD .039) | .399 (SD .037) | .400 (SD .038) |
| Sex: Female, Male: Female | Participants | 691 | 682 | 1373 |
| Sex: Female, Male: Male | Participants | 708 | 716 | 1424 |
| Region of Enrollment: South Africa | participants | 1399 | 1398 | 2797 |
6. Primary Endpoint
The registry lists the primary outcome as To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants., measured over AEs recorded 28 days post-vaccination; SAEs recorded for entire study period..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of all subjects vaccinated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is described as evaluating the safety profile of MVA85A/AERAS-485 in BCG-vaccinated, HIV-negative infants. Its unit is the percentage of all subjects vaccinated. The posted values are 95.9% for the investigational vaccine group and 83.7% for the control group. The registry gives a 95% confidence interval for each group’s value.
Safety outcomes are used to characterize adverse events observed after treatment, rather than to measure tuberculosis prevention or immune response. The registry states that adverse events were collected for 28 days after vaccination. Solicited events were recorded by parents or guardians in diary cards through 7 days after vaccination. Serious adverse events were collected from vaccine dosing through the entire study period. The first 330 infants enrolled also had serum chemistry and hematology testing through 28 days after vaccination.
The primary outcome’s registry description does not specify the exact event definition underlying the posted percentage. It therefore supports interpretation of the reported safety percentages and their intervals, but not a more specific claim about which events make up that measure. The separate serious adverse event counts should be read as additional safety information, not as a substitute for the primary outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports a primary safety outcome of 95.9% in the investigational vaccine group, with a 95% confidence interval from 94.7% to 96.8%. In the control group, the value is 83.7%, with a 95% confidence interval from 81.7% to 85.6%. These are group-specific percentages, not a reported adjusted comparison. The confidence intervals describe uncertainty around each posted group estimate; they do not by themselves establish the reason for the difference between the values.
The registry also reports serious adverse events in 257 of 1399 participants at risk in the investigational vaccine group and 258 of 1396 at risk in the control group. These counts concern a different safety measure from the primary percentage. Serious adverse events were collected throughout the study period, whereas the adverse-event collection window for the primary safety outcome was 28 days after vaccination. The registry also lists serious adverse event terms and their percentages. A listed term is not a complete account of safety, and the registry record does not give a comparative statistical analysis for these safety counts.
For tuberculosis diagnosis, the registry posts 32 participants in the investigational vaccine group and 39 in the control group. The unadjusted risk difference is -0.005, with an interval from -0.017 to 0.007, and the unadjusted p-value is 0.393. The interval includes zero, so the estimate is compatible with values on either side of no risk difference. The registry also reports a risk ratio of 0.818, with an interval from 0.516 to 1.298, and an odds ratio of 0.814, with an interval from 0.507 to 1.307. These estimates are unadjusted recalculations from the posted summary statistics; no sponsor-reported comparative analysis is listed for this outcome.
For QuantiFERON conversion, the reported unadjusted risk difference is 0.005, with an interval from -0.020 to 0.029, and an unadjusted p-value of 0.71. The interval also includes zero. The corresponding reported risk ratio is 1.038, with an interval from 0.853 to 1.263, and the odds ratio is 1.043, with an interval from 0.834 to 1.306. These estimates do not replace a prespecified sponsor analysis, which is not reported in the registry record.
Across the secondary comparisons with posted estimates, uncertainty remains substantial relative to the point estimates. The results should be read as estimates with intervals, not as definitive evidence of a treatment effect or absence of one. The registry does not report analyses for the other secondary measures, so their results cannot be characterized from this record.
9. Statistical Methods Explained
What does a group percentage describe?
A percentage describes the share of participants in a group who met the outcome definition, using the group denominator recorded for that outcome. For the primary safety outcome, the registry gives percentages and 95% confidence intervals separately for each randomized group. A confidence interval represents uncertainty around an estimate under the assumptions of the method used to construct it. A narrower interval indicates greater precision than a wider interval, but the interval does not account for every possible source of bias or error.
The registry’s primary safety outcome is described as a percentage of all subjects vaccinated. The posted values are 95.9% and 83.7%. Since the registry does not provide a comparative estimate or a precise event definition for this measure, the two group-specific intervals should not be treated as a formal test of the between-group contrast. Comparing overlap visually is not a replacement for a prespecified comparison method.
How should the risk difference be read?
A risk difference expresses the difference between the outcome proportions in two groups, on the probability scale. A value of zero corresponds to equal proportions. For the tuberculosis endpoint, the posted unadjusted risk difference is -0.005, with an interval from -0.017 to 0.007. For QuantiFERON conversion, it is 0.005, with an interval from -0.020 to 0.029. Both intervals include zero. This means the estimates are imprecise enough to remain compatible with no difference as well as differences in either direction. It does not prove that the groups are identical.
The registry gives unadjusted p-values of 0.393 for the tuberculosis comparison and 0.71 for QuantiFERON conversion. A p-value describes how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. These p-values are explicitly unadjusted; the registry record does not report a multiplicity correction or a sponsor analysis for these comparisons.
Why are relative measures also reported?
A risk ratio compares the outcome proportions as a ratio, while an odds ratio compares the odds. These measures express a contrast on a different scale from the risk difference. The tuberculosis risk ratio is 0.818, with a reported interval from 0.516 to 1.298; its odds ratio is 0.814, with a reported interval from 0.507 to 1.307. For QuantiFERON conversion, the risk ratio is 1.038, with an interval from 0.853 to 1.263, and the odds ratio is 1.043, with an interval from 0.834 to 1.306. Each interval includes the relative-measure value corresponding to no difference. Relative and absolute measures can help describe an estimate from different perspectives, but neither makes the uncertainty disappear.
What does unadjusted recalculation mean?
The comparisons for the two secondary binary outcomes are labeled unadjusted recalculations. They are based on the posted group counts and denominators, without adjustment for other variables. The registry’s reported analyses field is empty for these outcomes. Consequently, these calculations should not be mistaken for the trial sponsor’s planned or preferred analysis. The sponsor’s own analysis would take precedence if it were reported; it is not reported in the registry record.
How should the planning illustrations be interpreted?
Planning illustrations use the observed effect as a reference and show participants per arm for 80% power and participants per arm for 90% power, across the stated fractions of that effect. For tuberculosis, planning for 100% of the observed effect gives 15,045 participants per arm for 80% power and 20,141 for 90% power. Planning for 75% gives 27,399 and 36,679, respectively; planning for 50% gives 63,111 and 84,487. For QuantiFERON conversion, planning for 100% gives 79,193 participants per arm for 80% power and 106,016 for 90% power; planning for 75% gives 140,225 and 187,721; planning for 50% gives 314,240 and 420,677.
These are planning illustrations, not observed power and not the trial’s original sample-size justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect equal to the stated fraction of the observed effect. A smaller target effect requires a larger planned sample under these assumptions. The registry does not report whether the original trial used these assumptions or how its planned enrollment was justified.
Why does over-dispersion matter in general?
In general, over-dispersion means that observed variation is greater than a statistical model expects. When that occurs, a model that assumes less variation can make intervals too narrow and tests too optimistic. The registry does not identify an over-dispersion model for these endpoints, and the posted binary comparisons do not report a model-based adjustment for it. This general consideration should not be read as evidence that over-dispersion occurred in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity plan for the secondary outcomes. This matters because the study lists several secondary questions, including clinical, immunological, and laboratory outcomes. In general, testing multiple outcomes without accounting for the number of comparisons can increase the chance of a nominally notable result arising by chance. The reported p-values for tuberculosis and QuantiFERON conversion are unadjusted, so they should be interpreted as individual exploratory comparisons rather than as results protected against the full set of secondary tests.
Missing-data methods are not reported in the registry record. The record does not state how unavailable outcome measurements, withdrawals, or incomplete follow-up were handled. Nor does it report whether missingness was assessed by randomized group or whether any sensitivity analyses were conducted. The outcome-specific denominators differ: for example, the tuberculosis comparison records 1399 in the investigational group and 1395 in the control group, while the QuantiFERON comparison records 1398 and 1394. Such denominator differences are visible in the outcome records, but their causes are not reported and should not be guessed.
The primary safety population is described as all subjects vaccinated. The analysis population definitions for the secondary outcomes are not described in comparable detail. The registry does not report whether intention-to-treat, per-protocol, or other analysis populations were used, nor does it provide a statistical analysis plan specifying endpoint handling, covariate adjustment, or model choice.
Interim analyses and stopping rules are also not reported in the registry record. The posted record contains no sponsor-reported comparative analyses for the secondary outcomes. These omissions limit assessment of whether the reported analyses followed a prespecified plan and whether all intended analyses are represented. They do not establish that particular methods were or were not used; the registry record simply does not report them.
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 |
|---|---|---|---|
| Investigational Vaccine | 257 | 1399 | 18.4% |
| Control Group | 258 | 1396 | 18.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Investigational Vaccine | 1319 of 1399 |
| Control Group | 1064 of 1396 |
Most frequent serious adverse event terms
| Event term | Organ system | Investigational Vaccine | Control Group |
|---|---|---|---|
| Gastroenteritis | Infections and infestations | 91 of 1399 | 88 of 1396 |
| Pneumonia | Infections and infestations | 31 of 1399 | 25 of 1396 |
| Bronchopneumonia | Infections and infestations | 27 of 1399 | 28 of 1396 |
| Lower respiratory tract infection | Infections and infestations | 25 of 1399 | 29 of 1396 |
| Croup infectious | Infections and infestations | 8 of 1399 | 11 of 1396 |
| Febrile convulsion | Nervous system disorders | 7 of 1399 | 12 of 1396 |
| Bronchiolitis | Infections and infestations | 10 of 1399 | 8 of 1396 |
| Thermal burn | Injury, poisoning and procedural complications | 7 of 1399 | 10 of 1396 |
| Respiratory tract infection | Infections and infestations | 6 of 1399 | 10 of 1396 |
| Urinary tract infection | Infections and infestations | 8 of 1399 | 4 of 1396 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Investigational Vaccine | Control Group |
|---|---|---|---|
| Injection site erythema | General disorders | 1121 of 1399 | 446 of 1396 |
| Injection site swelling | General disorders | 1050 of 1399 | 267 of 1396 |
| Irritability | General disorders | 523 of 1399 | 431 of 1396 |
| Insomnia | Psychiatric disorders | 398 of 1399 | 359 of 1396 |
| Hypersomnia | Nervous system disorders | 376 of 1399 | 324 of 1396 |
| Injection site warmth | General disorders | 473 of 1399 | 222 of 1396 |
| Pyrexia | General disorders | 372 of 1399 | 271 of 1396 |
| Hypophagia | Metabolism and nutrition disorders | 321 of 1399 | 285 of 1396 |
| Somnolence | Nervous system disorders | 295 of 1399 | 237 of 1396 |
| Injection site pain | General disorders | 363 of 1399 | 154 of 1396 |
Serious events with the highest arm-level rate: gastroenteritis (6.5%), pneumonia (2.2%), lower respiratory tract infection (2.1%), bronchopneumonia (2.0%), febrile convulsion (0.9%).
Serious adverse events are reported as 257 among 1399 participants at risk in the investigational vaccine group and 258 among 1396 at risk in the control group. These are counts with their recorded denominators, collected from vaccine dosing through the entire study period. They should be distinguished from the primary safety percentages, which have a 28-day adverse-event collection window.
The registry lists gastroenteritis at 6.5%, pneumonia at 2.2%, lower respiratory tract infection at 2.1%, bronchopneumonia at 2.0%, febrile convulsion at 0.9%, and croup infectious at 0.8% among the top serious adverse event terms. These entries describe reported terms; they do not, by themselves, establish that an event was caused by the vaccine. The registry does not report a comparative statistical analysis of serious adverse events, and deaths are not posted in the adverse-event data. The counts and terms are descriptive safety information, not a complete causal assessment.
12. What the Result Does, and Does Not, Mean
The registry supports a description of the trial’s posted safety outcome and the secondary comparisons for which estimates are available. It reports higher primary safety percentages in the investigational vaccine group than in the control group, with group-specific 95% confidence intervals. It also reports serious adverse event counts and selected serious event terms. These observations describe what was recorded under the stated collection windows; they do not, on their own, explain why the groups differ or establish causation.
The secondary tuberculosis and QuantiFERON comparisons have unadjusted estimates with intervals that include the no-difference value. Their uncertainty means that the observed estimates should not be interpreted as definitive evidence for a difference or for equivalence. A non-significant p-value is not proof of no effect, just as an estimate in one direction does not establish a treatment effect. The registry does not report sponsor analyses for these outcomes or comparative estimates for the other secondary outcomes.
The trial’s Phase II designation and its multiple objectives provide context for the range of safety and immunogenicity questions. The posted record does not supply enough detail to assess the original statistical plan, multiplicity handling, or missing-data procedures. This limits how strongly the secondary findings can be interpreted as confirmatory evidence.
The record therefore permits careful description of reported percentages, counts, intervals, and unadjusted comparisons, while leaving important analytical details unresolved. It does not establish a broad conclusion about effectiveness, and the statistical results should not be treated as medical advice or as a recommendation about vaccination.
13. Why This Trial Matters Statistically
This trial is statistically informative because it places a safety assessment alongside several distinct secondary questions in a randomized, blinded design. The record identifies the intervention and control, the primary safety outcome, the adverse-event collection windows, and the long follow-up period for secondary outcomes. Those details help readers distinguish short-window adverse-event reporting from serious adverse events collected throughout the study.
The record also illustrates why estimates should be read with their uncertainty. Group percentages have 95% confidence intervals, while the available secondary comparisons include unadjusted point estimates and intervals. A point estimate alone can suggest a direction, but its interval indicates how much uncertainty remains. For both reported secondary comparisons, the intervals include the no-difference value, so the estimates do not sharply distinguish between possible directions.
Another statistical lesson is that trial registration records may expose gaps between a broad set of planned scientific questions and the comparative results available for interpretation. The registry lists immunogenicity, correlates, tuberculosis, and QuantiFERON aims, but comparative analyses are not reported for all of them. The empty reported-analyses fields and lack of a reported statistical plan make it difficult to determine how the posted comparisons relate to prespecified analysis choices.
Finally, planning illustrations based on observed effects can communicate the scale of future studies that might be needed under stated assumptions. They are not evidence of the trial’s original design adequacy or its power after completion. Separating observed results, unadjusted recalculations, and hypothetical planning helps avoid confusing descriptive analysis with confirmatory inference.
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.
Several limitations specific to this record affect interpretation. The primary outcome is described as a safety profile and measured as a percentage of all subjects vaccinated, but the exact event definition underlying the posted group percentages is not stated. The adverse-event collection windows are described, yet the registry does not provide a detailed breakdown of the primary outcome’s component events.
The study description gives planned enrollment of 2784, while the registry records enrollment of 2797. The record does not explain the difference. The safety cohort is described as the first 330 infants enrolled, but detailed results for its serum chemistry and hematology assessments are not included in the registry record recorded.
Outcome-specific denominators vary, and the registry does not report why. Missing-data methods, analysis population definitions, adjustment methods, interim analyses, and the statistical analysis plan are not reported. For the secondary comparisons, the estimates are unadjusted recalculations rather than sponsor-reported comparative analyses. Comparative results for the other immunogenicity and correlates outcomes are not reported in the registry record.
The registry states that the study was conducted at a single site in South Africa. The record does not provide enough information to evaluate how representative the enrolled participants were of other settings. It also does not report a multiplicity strategy for the multiple secondary questions. These limitations constrain the precision and scope of conclusions that can be drawn from the posted results, without showing that any particular unreported method or event occurred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of MVA85A in Healthy Infants — NCT00953927.
- Registry record last updated 2016-05-24; status last verified 2016-04.
- Results first posted 2013-12-12.
- 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.
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18. Record Summary
The registry describes a completed Phase II randomized, quadruple-masked, parallel-group study sponsored by Aeras. It evaluated MVA85A/AERAS-485 against Candida Skin Test Antigen control in BCG-vaccinated, HIV-negative infants without tuberculosis. Recorded enrollment was 2797, and the study description states planned enrollment of 2784. The trial was conducted at a single site in South Africa.
The primary outcome evaluated safety as a percentage of subjects vaccinated. Adverse events were collected for 28 days after vaccination and serious adverse events throughout the study. Secondary outcomes covered tuberculosis, immunogenicity, correlates of protection, and QuantiFERON conversion. The record provides unadjusted comparative estimates for tuberculosis and QuantiFERON conversion, but does not report comparative analyses for the other secondary outcomes. Statistical-plan, missing-data, multiplicity, and interim-analysis details are not reported in the registry record.