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 Non-inferiority Trial to Compare MVA-BN® Smallpox Vaccine to ACAM2000® (NCT01913353), a randomized phase 3 study. The primary outcome is Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at the Peak Visits.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01913353 |
| Phase | Phase 3 |
| Condition | 18-42 Year Old Healthy Vaccinia-naïve Subjects |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 440 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Bavarian Nordic |
| Results posted | Yes |
2. Clinical Question
Population
Healthy vaccinia-naïve subjects aged 18-42 years. The primary endpoint analysis used the Per-protocol Set for Immunogenicity; the number of participants in that analysis is reported separately for each group.
Intervention
Group 1 received two MVA-BN® vaccinations 4 weeks apart, on Day 0 and Day 28, followed by one ACAM2000® vaccination on Day 56.
Comparator
Group 2 received one ACAM2000® vaccination on Day 0.
Primary question
At the groups’ specified peak visits, how did vaccinia-specific PRNT geometric mean titers compare between the MVA-BN® course followed by ACAM2000® and ACAM2000® alone? The trial was described as a non-inferiority comparison, but its non-inferiority margin is not reported in the registry record.
The comparison concerns antibody response measured by the Plaque Reduction Neutralization Test (PRNT), not a direct comparison of clinical disease outcomes. The registry summary also describes an aim of assessing whether vaccination before ACAM2000® results in an attenuated take. Outcomes related to lesion size and take appear among the listed secondary outcomes, but results for those measures are not included in the registry record for this explanation.
The trial enrolled 440 participants and is listed as completed. The primary endpoint’s peak assessment was on Day 42 for Group 1 and Day 28 for Group 2. These are different time points relative to the groups’ vaccination schedules, so the endpoint compares each group at its specified peak visit rather than at a common calendar day. The registry record does not report further rationale for selecting these peak visits.
3. Trial Design
This was a randomized, parallel-group, Phase III trial with an open-label designation in its title. The registry lists masking as single; which people were masked is not reported in the registry record. The sponsor was Bavarian Nordic. Enrollment was 440, and the study status is completed. The listed start was 2015-03 and primary completion was 2017-03.
The schedules differed in both the vaccines received and their timing. Group 1 received MVA-BN® on Day 0 and Day 28, then ACAM2000® on Day 56. Group 2 received ACAM2000® on Day 0. The primary endpoint was assessed at Day 42 for Group 1 and Day 28 for Group 2. Thus, the peak-visit comparison follows the regimen-specific timing recorded for the two groups; it is not a comparison measured on the same numbered day after randomization.
The primary analysis population was the Per-protocol Set for Immunogenicity. The registry reports 185 participants for Group 1 and 186 for Group 2 in the primary endpoint results. The relationship between those analysis counts and the total enrollment is not explained in the registry record. Reasons for exclusions from the primary analysis, and the number randomized to each group, are not reported in the registry record.
The title and analysis classification identify the trial as a non-inferiority trial. However, details essential to interpreting a formal non-inferiority design—including the prespecified margin and the planned decision rule—are not reported in the registry record. The registry record also does not report the sample-size justification, whether any interim analyses were planned or conducted, or the handling of protocol deviations beyond identifying the per-protocol population for immunogenicity.
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 | 221 | 219 |
| COMPLETED | 189 | 204 |
| NOT COMPLETED | 32 | 15 |
Reasons for not completing this period:
| Reason | Group 1 | Group 2 |
|---|---|---|
| Adverse Event | 2 | 0 |
| Physician Decision | 0 | 2 |
| Withdrawal by Subject | 20 | 6 |
| multiple reasons | 10 | 7 |
Analysis population for the primary outcome, as defined in the registry: Per-protocol Set for Immunogenicity
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: Full Analysis Set
| Characteristic | Unit | Group 1 | Group 2 | Total |
|---|---|---|---|---|
| Participants analysed | 220 | 213 | 433 | |
| Age, Continuous | years | 23.5 (SD 4.77) | 23.4 (SD 4.58) | 23.5 (SD 4.67) |
| Sex: Female, Male: Female | Participants | 39 | 29 | 68 |
| Sex: Female, Male: Male | Participants | 181 | 184 | 365 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 54 | 40 | 94 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 166 | 173 | 339 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 8 | 6 | 14 |
| Race (NIH/OMB): Asian | Participants | 14 | 12 | 26 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 5 | 3 | 8 |
| Race (NIH/OMB): Black or African American | Participants | 48 | 40 | 88 |
| Race (NIH/OMB): White | Participants | 126 | 136 | 262 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 19 | 16 | 35 |
| Region of Enrollment: South Korea | participants | 220 | 213 | 433 |
6. Primary Endpoint
The registry lists the primary outcome as Plaque Reduction Neutralization Test (PRNT) Geometric Mean Titer (GMT) at the Peak Visits, measured over Day 42 for Group 1 and Day 28 for Group 2.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Titer |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the geometric mean titer (GMT) of vaccinia-specific antibodies measured by PRNT at the peak visits. PRNT measures the ability of antibodies in a sample to reduce viral plaque formation in the assay. The endpoint therefore summarizes an immune response measured in the laboratory; it is not itself a direct measure of prevention of disease or of clinical vaccine effectiveness.
A geometric mean is used for measurements such as titers that are commonly analyzed on a multiplicative scale. In general, the geometric mean is obtained by working with logarithms of the measurements, averaging on that scale, and transforming back. It gives a central summary that is less dominated by very large observations than an arithmetic mean can be when measurements are right-skewed. The registry record does not report the exact transformation or calculation procedure used for the GMT.
The reported endpoint description states that titers below the assay’s detection limit were assigned a value of 1. This is an analysis convention for handling measurements below the limit; it does not mean that the underlying antibody level was directly measured as exactly 1. The primary endpoint reports a 95% confidence interval for each group’s GMT and a 95% confidence interval for the ratio of Group 1 to Group 2.
Comparing GMTs is relevant to the stated immunogenicity question because the groups’ antibody responses can be expressed on a common scale. For a formal non-inferiority conclusion, however, the estimated ratio and its uncertainty must be judged against a prespecified margin. That margin and the associated decision rule are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The reported Group 1 GMT was 153.5, with a 95% confidence interval from 134.3 to 175.6. The Group 2 GMT was 79.3, with a 95% confidence interval from 67.1 to 93.8. The reported ratio of Group 1 to Group 2 was 1.935, with a 95% confidence interval from 1.562 to 2.397. These are the registry’s primary endpoint estimates for the Per-protocol Set for Immunogenicity.
In plain terms, the point estimate places the Group 1 GMT above the Group 2 GMT at their specified peak visits. The confidence interval expresses uncertainty in the estimated ratio: under the assumptions of the interval procedure, values within its limits are compatible with the observed data and method. It is not a range containing a stated proportion of individual participants’ titers, and it does not account for every possible source of bias or design limitation.
The trial is identified as non-inferiority, but the registry record does not report the margin that would define how much lower a response could be while still meeting the non-inferiority criterion. It also does not report the formal decision rule or a p-value for the primary non-inferiority analysis. Consequently, the ratio and interval describe the observed result, but the registry information alone does not establish whether a prespecified non-inferiority criterion was met. The fact that the interval is above 1 does not substitute for comparing it with the missing non-inferiority margin.
The endpoint timing also matters. Group 1 was assessed on Day 42 and Group 2 on Day 28, according to the stated peak visits. The comparison therefore reflects the chosen peak assessment for each regimen rather than a shared time after the first vaccination. The registry record does not explain how peak timing was selected or provide other time-point results for the primary endpoint.
The primary analysis is restricted to the Per-protocol Set for Immunogenicity. This can be appropriate for a protocol-defined immunogenicity analysis, but the interpretation depends on who was included and why. Exclusion criteria and reasons for missing or unevaluable measurements are not reported in the registry record. The primary estimates should therefore be understood as results for the stated analysis population, not automatically as estimates for every enrolled or randomized participant.
Overall, the posted primary result is a quantitative comparison of antibody titers, with a reported ratio and confidence interval. It does not by itself establish a clinical outcome, and the absent non-inferiority margin prevents an independent reading of the formal non-inferiority decision from the registry entries alone.
9. Statistical Methods Explained
The primary endpoint is continuous in the sense that the underlying PRNT titer can take a range of values. The registry summarizes titers with geometric means and reports 95% confidence intervals. A confidence interval communicates the precision of an estimate: narrower intervals indicate greater precision under the method’s assumptions, while wider intervals indicate more uncertainty. It does not mean that the true value has a 95% probability of lying inside the particular interval after the data have been observed.
Why report a geometric mean?
General statistical explanation: titers often vary multiplicatively, so a geometric mean can be a more suitable summary than an arithmetic mean. On a logarithmic scale, multiplicative differences become additive, and the mean on that scale can be transformed back to the original units. This approach can reduce the influence of unusually large values when the distribution is skewed. The registry identifies the summary as a GMT but does not report the exact computational method, the logarithm used, or the variance model.
The registry says values below the detection limit were included as 1. This is a specified substitution rule for those measurements. Any analysis using such a rule depends partly on how many observations fall below the detection limit and on the measurement scale. The number of below-limit measurements is not reported in the registry record.
How to read the ratio and interval
The ratio is Group 1 GMT divided by Group 2 GMT. A ratio of 1 would indicate equal estimated GMTs; a value greater than 1 indicates a larger estimated GMT in Group 1, and a value below 1 indicates a smaller estimated GMT in Group 1. This is a general interpretation of a ratio, not a separate clinical conclusion. The reported ratio is 1.935 and its 95% confidence interval is 1.562 to 2.397.
A non-inferiority analysis ordinarily compares an effect estimate and its uncertainty with a prespecified boundary representing the largest acceptable loss. For ratio measures, the boundary may be expressed on a ratio scale or a transformed scale, depending on the protocol. The margin and the rule for interpreting the interval are not reported in the registry record. Therefore, the ratio and interval can be described, but they cannot be used to reconstruct a formal decision threshold that is absent from the record.
Binary outcomes and risk differences
For binary outcomes, each participant is classified as having or not having the outcome. A risk is the proportion with the outcome in a group. A risk difference subtracts one group’s risk from the other’s, so zero represents equal observed risks; a negative or positive sign depends on the order of subtraction. The registry’s unadjusted comparisons report risk differences and confidence intervals for some secondary outcomes. Those are simple group comparisons and should not be mistaken for a covariate-adjusted model.
A p-value, when reported, describes how incompatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The registry’s secondary comparisons include unadjusted p-values, but the p-values do not account for testing multiple outcomes or comparisons unless a correction is specified. A multiplicity adjustment is not reported in the registry record.
Why over-dispersion can matter
General statistical explanation: in count or rate data, over-dispersion means the observed variability is greater than a model assumes. If that extra variability is ignored, standard errors can be too small and confidence intervals too narrow. The primary endpoint is a GMT, and the registry does not identify a count model or report an over-dispersion assessment for it. This concept is relevant to choosing statistical models generally, but the record does not provide enough detail to say whether over-dispersion was assessed in any analysis.
Planning illustrations are not observed power
Sample-size illustrations based on an observed effect describe what group sizes might be required under stated planning assumptions. They are not the trial’s observed power and do not show that the trial had a particular probability of detecting its result. The posted planning assumptions specify a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as stated fractions of the observed effect. Those calculations are planning illustrations, not the trial’s original design justification. The trial’s own sample-size assumptions are not reported in the registry record.
For binary comparisons, planning estimates also depend on the assumed event frequencies and the effect size used. Smaller effects generally require more participants to distinguish them from random variation under a fixed design framework. These calculations do not resolve bias, missing-data concerns, endpoint selection, or the choice of a clinically acceptable difference. The registry record does not report whether the trial’s original design used the same assumptions as the posted planning illustrations.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| not stated | GMT Ratio (Group 1 / Group 2) 1.935 | 1.562 to 2.397 | not reported |
The primary comparison reported in the registry is a Group 1 to Group 2 GMT ratio of 1.935, with a 95% confidence interval from 1.562 to 2.397. The analysis is classified as non-inferiority. The method and p-value for that analysis are not reported in the registry record, and the non-inferiority margin is also not reported.
The registry’s primary endpoint results include the group GMTs and their confidence intervals, along with the reported ratio and its interval. A separate recalculated primary comparison is not reported in the registry record, so there is no independent recalculated estimate to set alongside the sponsor’s reported result. The record does not identify a discrepancy between the posted primary estimate and a recalculation.
For interpretation, the sponsor’s reported analysis is the relevant primary result. The numerical estimates indicate the direction and precision of the observed antibody response comparison, but the formal non-inferiority conclusion cannot be independently checked without the margin and decision rule. The trial title and analysis classification identify the intended framework; they do not supply the missing threshold.
Unadjusted recalculations for some secondary binary outcomes are a different kind of analysis. They use posted group summaries and are not a replacement for the sponsor’s primary analysis. They should be read as descriptive, unadjusted comparisons, not as confirmatory tests of the trial’s primary question.
11. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a trial evaluates several outcomes, time points, groups, or statistical comparisons. Even if each individual test uses a conventional threshold, conducting many tests increases the chance that at least one result will appear noteworthy by chance alone. Methods such as prespecifying a hierarchy or adjusting the testing threshold can address this issue, but the approach depends on the trial’s objectives and analysis plan.
The registry lists 24 outcome measures and reports 22 secondary outcomes. The available secondary results include multiple comparisons, and the posted unadjusted p-values do not by themselves account for the full set of outcomes or analyses. A multiplicity strategy, hierarchy among secondary endpoints, or distinction between confirmatory and exploratory testing is not reported in the registry record. Secondary p-values should therefore be interpreted cautiously and in the context of the primary endpoint.
The primary endpoint population is the Per-protocol Set for Immunogenicity. The registry record does not report the criteria used to define this set, participant flow into it, or the reasons participants may have been excluded. It also does not report an intention-to-treat or other sensitivity analysis for the primary endpoint. Without those details, the influence of exclusions or protocol deviations cannot be assessed from the record.
The primary endpoint description specifies that titers below the detection limit were assigned a value of 1. This explains one aspect of measurement handling, but other missing-data procedures are not reported in the registry record. The number of missing or unevaluable PRNT results, the handling of missing secondary outcomes, and any sensitivity analyses for missingness are not reported in the registry record.
The record identifies a non-inferiority objective but does not report the non-inferiority margin, the planned decision rule, the original sample-size justification, or interim analysis plans. These omissions limit assessment of the trial’s statistical operating plan and of the robustness of a formal non-inferiority conclusion. The registry record also does not report whether the analysis plan was finalized before unblinding or how deviations from that plan were handled.
12. 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, Period 1 | 2 | 220 | 0.9% |
| Group 1, Period 2 | 0 | 208 | 0.0% |
| Group 1, Period 3 | 3 | 196 | 1.5% |
| Group 2 | 3 | 213 | 1.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1, Period 1 | 0 of 220 |
| Group 1, Period 2 | 0 of 208 |
| Group 1, Period 3 | 0 of 196 |
| Group 2 | 0 of 213 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group 1, Period 1 | 95 of 220 |
| Group 1, Period 2 | 63 of 208 |
| Group 1, Period 3 | 79 of 196 |
| Group 2 | 88 of 213 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1, Period 1 | Group 1, Period 2 | Group 1, Period 3 | Group 2 |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | 1 of 220 | 0 of 208 | 0 of 196 | 0 of 213 |
| Suicidal Ideation | Psychiatric disorders | 0 of 220 | 0 of 208 | 1 of 196 | 0 of 213 |
| Alcohol Poisoning | Injury, poisoning and procedural complications | 0 of 220 | 0 of 208 | 1 of 196 | 0 of 213 |
| Peritonsillar Abscess | Infections and infestations | 0 of 220 | 0 of 208 | 1 of 196 | 0 of 213 |
| Road Traffic Accident | Injury, poisoning and procedural complications | 0 of 220 | 0 of 208 | 0 of 196 | 1 of 213 |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | 0 of 220 | 0 of 208 | 0 of 196 | 1 of 213 |
| Haemorrhoids | Gastrointestinal disorders | 0 of 220 | 0 of 208 | 0 of 196 | 1 of 213 |
| Tibia Fracture | Injury, poisoning and procedural complications | 1 of 220 | 0 of 208 | 0 of 196 | 0 of 213 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1, Period 1 | Group 1, Period 2 | Group 1, Period 3 | Group 2 |
|---|---|---|---|---|---|
| Dermatitis Contact | Skin and subcutaneous tissue disorders | 0 of 220 | 0 of 208 | 44 of 196 | 49 of 213 |
| Upper Respiratory Tract Infection | Infections and infestations | 14 of 220 | 14 of 208 | 14 of 196 | 14 of 213 |
| Injection Site Erythema | General disorders | 30 of 220 | 23 of 208 | 1 of 196 | 0 of 213 |
| Injection Site Nodule | General disorders | 32 of 220 | 13 of 208 | 1 of 196 | 0 of 213 |
| Lymphadenopathy | Blood and lymphatic system disorders | 10 of 220 | 6 of 208 | 3 of 196 | 23 of 213 |
| Vaccination Site Warmth | General disorders | 13 of 220 | 10 of 208 | 1 of 196 | 0 of 213 |
| Nasopharyngitis | Infections and infestations | 7 of 220 | 4 of 208 | 6 of 196 | 5 of 213 |
| Vaccination Site Erythema | General disorders | 10 of 220 | 7 of 208 | 2 of 196 | 0 of 213 |
| Headache | Nervous system disorders | 4 of 220 | 2 of 208 | 6 of 196 | 5 of 213 |
| Vaccination Site Nodule | General disorders | 11 of 220 | 3 of 208 | 0 of 196 | 2 of 213 |
Serious events with the highest arm-level rate: suicidal ideation (0.5%), alcohol poisoning (0.5%), peritonsillar abscess (0.5%), road traffic accident (0.5%), rhabdomyolysis (0.5%).
The registry lists serious adverse event counts by Group 1 period and for Group 2. Group 1, Period 1 reports 2 serious adverse events among 220 at risk; Group 1, Period 2 reports 0 among 208; Group 1, Period 3 reports 3 among 196; and Group 2 reports 3 among 213. No deaths are reported in any of these groups or periods.
These are event counts and denominators as recorded, not adjusted comparisons of risk. Group 1 is divided into successive periods, and its numbers at risk differ by period. The periods should not be combined as if they represented independent groups or a single fixed observation window. The registry record does not provide the timing, duration, or detailed methods for safety follow-up in the registry record.
The listed serious event terms each have a reported frequency of 0.5%: Suicidal Ideation, Alcohol Poisoning, Peritonsillar Abscess, Road Traffic Accident, Rhabdomyolysis, and Haemorrhoids. The registry record does not establish from these listings whether each event occurred once or how terms were counted across the periods. Nor do these figures alone establish whether an event was caused by vaccination. Seriousness, relationship to vaccine, intensity, and event type are distinct attributes; the available summaries should not be treated as interchangeable measures.
These safety figures describe events recorded during the study and do not prove that an event was caused by a vaccine or that no other events occurred. Broader safety interpretation depends on complete event definitions, follow-up, and reporting procedures, which are not reported in the registry record.
13. What the Result Does, and Does Not, Mean
The primary data show a difference in the measured PRNT antibody response at the specified peak visits, expressed as a Group 1 to Group 2 GMT ratio with a 95% confidence interval. The point estimate is above 1, and the interval quantifies uncertainty under the analysis method. This is evidence about an immunogenicity measure in the stated per-protocol population, not a direct estimate of protection against smallpox or another clinical outcome.
Because the trial is described as non-inferiority, the central statistical question is whether the result satisfies a prespecified acceptable-loss boundary. The registry record does not report that boundary or the decision rule. It is therefore not possible to verify a formal non-inferiority conclusion from the registry information alone. A ratio above 1 is not a substitute for the missing margin, and the confidence interval does not itself identify what loss would be clinically acceptable.
The study’s treatment schedules also differ. Group 1 received two MVA-BN® vaccinations before ACAM2000®, while Group 2 received ACAM2000® alone. The primary comparison therefore describes those assigned regimens as recorded, at their respective peak visits. It cannot isolate the effect of one component from timing or other regimen differences using the information.
The secondary outcomes may add context on antibody response, lymphadenopathy, lesion characteristics, take, and safety. However, not all listed secondary outcomes have numerical results in the registry record, and unadjusted secondary comparisons are less definitive when many outcomes are considered. The available safety counts are descriptive and do not establish causation.
Accordingly, the result should be read as a registry-reported statistical comparison of an antibody endpoint. It does not by itself establish clinical efficacy, a favorable or unfavorable medical decision, or a fully verifiable non-inferiority conclusion. Those interpretations require additional information about the protocol, endpoint definitions, analysis plan, margin, and clinical context, some of which is not reported in the registry record.
14. Why This Trial Matters Statistically
This trial illustrates why a non-inferiority label is not enough to interpret a non-inferiority result. The reported estimate and confidence interval are essential, but so is the prespecified margin that defines the largest acceptable loss. Without that margin, readers can describe the observed ratio and its precision but cannot independently apply the design’s formal criterion.
It also shows why the analysis population matters. The primary endpoint is reported for the Per-protocol Set for Immunogenicity, while the registry gives total enrollment separately. A per-protocol result answers a question about participants included under that analysis definition. Without participant flow, exclusion criteria, and complementary analyses, readers cannot tell how closely that result represents all randomized participants.
The endpoint itself is a laboratory measure. GMTs and seroconversion summarize antibody response in different ways, and neither is identical to a clinical endpoint. Keeping that distinction clear avoids interpreting an immune response estimate as a direct measure of disease prevention.
Finally, the trial includes multiple secondary outcomes and several kinds of measurements. Their results can broaden description, but multiple unadjusted comparisons create a risk of chance findings. This case highlights the value of a transparent hierarchy of endpoints, a reported multiplicity strategy, and complete presentation of analysis methods. It also demonstrates how precise reporting of timing, missing data, and analysis populations supports a more reliable statistical reading of clinical research.
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.
Several trial-specific limitations to interpretation arise from details not reported in the registry record. The non-inferiority margin and formal decision rule are absent, although the trial is identified as non-inferiority. The method used for the primary ratio and its confidence interval is also not reported. These omissions prevent independent verification of the formal primary conclusion.
The study is described as open-label, and the registry lists single masking without identifying who was masked. The primary endpoint is a laboratory assay, but the record does not describe assay procedures, assay reproducibility, or how the peak visits were selected. It specifies that below-detection titers were assigned a value of 1, but does not report how many measurements were affected.
The groups were assessed at different peak visits, and their vaccination schedules differed. This is consistent with the regimen-specific assessment times stated in the record, but it means the primary contrast is not a same-day comparison. The registry does not report additional primary-endpoint time points that would show how the responses developed over time.
The primary analysis uses a per-protocol immunogenicity population. The registry does not report participant flow, exclusions, reasons for missing data, or sensitivity analyses using other populations. It also does not provide the original sample-size rationale or interim analysis information. These gaps restrict assessment of how analysis choices, missing measurements, or deviations may have affected the estimates.
Finally, the available secondary findings are incomplete relative to the listed outcomes, and a multiplicity approach is not reported. The safety figures are divided into periods for Group 1 and are descriptive; the registry information does not support causal attribution from those counts alone. These limitations do not change the reported values, but they constrain the strength and scope of conclusions that can be drawn from them.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Non-inferiority Trial to Compare MVA-BN® Smallpox Vaccine to ACAM2000® — NCT01913353.
- Registry record last updated 2019-12-05; status last verified 2019-11.
- Results first posted 2019-12-05.
- 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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19. Record Summary
NCT01913353 is a completed randomized Phase III parallel-group trial sponsored by Bavarian Nordic. It enrolled 440 healthy vaccinia-naïve subjects aged 18-42 years and compared an MVA-BN® course followed by ACAM2000® with ACAM2000® alone. The title describes the trial as open-label and non-inferiority; the registry lists single masking.
The primary endpoint was vaccinia-specific PRNT GMT at Day 42 for Group 1 and Day 28 for Group 2, in the Per-protocol Set for Immunogenicity. The reported Group 1 to Group 2 ratio was 1.935, with a 95% confidence interval from 1.562 to 2.397. The non-inferiority margin and decision rule are not reported in the registry record.
Secondary outcomes cover antibody response, lymphadenopathy, lesion measurements, take, and serious adverse events. Statistical interpretation is limited by incomplete secondary results and unreported details about multiplicity, missing data, and analysis methods.