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 Phase II Trial to Assess Safety and Immunogenicity of IMVAMUNE® (NCT01827371), a randomized phase 2 study. The primary outcome is Geometric Mean Peak Plaque Reduction Neutralization Titer (PRNT) After Second Vaccination.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01827371 |
| Phase | Phase 2 |
| Condition | Smallpox |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 435 |
| Arms in the primary outcome | 4 |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned participants receiving IMVAMUNE® in a Phase II trial focused on safety and immunogenicity for smallpox. The registry lists enrollment of 435. The primary endpoint used a modified ATP population: participants who received both vaccinations in window, excluding those without a complete dose delivered or who received non-study vaccinations. For the endpoint, participants also needed at least two blood measurements in the stated post-vaccination period. Further eligibility criteria, including age and other participant characteristics, are not reported in the registry record.
Intervention
All four arms received IMVAMUNE® at 1x10^8 TCID50/0.5 mL. The schedules used two vaccinations on different days: Days 1 and 29, Days 1 and 15, or Days 1 and 22. The delivery methods were syringe and needle or, in one arm, Stratis™.
Comparator
The primary endpoint reports results for each of the four arms. The registry's pairwise analyses compare Arm A, the Days 1 and 29 syringe-and-needle schedule, with Arm B, Arm C, and Arm D. Arm D used the same vaccination days as Arm A but delivered the vaccine via Stratis™.
Primary question
How did peak plaque reduction neutralization titers after the second vaccination compare across the schedules and delivery methods? The endpoint summarizes each participant's highest eligible post-vaccination titer, then reports a geometric mean for each group. The record also lists comparisons framed as non-inferiority or equivalence, but the non-inferiority or equivalence margins and a formal conclusion are not reported in the registry record.
3. Trial Design
This was a randomized, open-label, parallel Phase II study. The registry describes a study of three immunization schedules and two delivery methods, with randomization to four arms. Enrollment was 435, and the status is completed. The recorded start was 2013-06, and primary completion was 2015-04.
Arm A received IMVAMUNE® on Days 1 and 29 by syringe and needle. Arm B received it on Days 1 and 15 by syringe and needle. Arm C received it on Days 1 and 22 by syringe and needle. Arm D received it on Days 1 and 29 via Stratis™. Each arm description specifies 1x10^8 TCID50/0.5 mL, administered subcutaneously. The registry's arm descriptions state 88 subjects for each regimen.
The primary endpoint analysis lists 84 participants in Arm A, 85 in Arm B, 84 in Arm C, and 79 in Arm D. These are the group counts attached to the endpoint estimates, not the registry's overall enrollment. The endpoint population was modified ATP rather than all enrolled participants: it excluded participants who did not receive both vaccinations in window, lacked a complete dose delivery, or received non-study vaccinations. The record also specifies a requirement for at least two eligible blood measurements.
Because the trial was open-label, participants and study personnel were not masked to assignment according to the registry. Randomization can support comparisons between assigned regimens, but the record does not report the randomization procedure, allocation concealment, stratification, or any other design details. Eligibility criteria, the rationale for the enrollment target, and the planned statistical analysis 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
| Stage | Arm A: IMVAMUNE Days 1+29, Syringe and Needle | Arm B: IMVAMUNE Days 1+15, Syringe and Needle | Arm C: IMVAMUNE Days 1+22, Syringe and Needle | Arm D: IMVAMUNE Days 1+29, Stratis |
|---|---|---|---|---|
| STARTED | 115 | 96 | 104 | 120 |
| COMPLETED | 102 | 89 | 93 | 97 |
| NOT COMPLETED | 13 | 7 | 11 | 23 |
Reasons for not completing this period:
| Reason | Arm A: IMVAMUNE Days 1+29, Syringe and Needle | Arm B: IMVAMUNE Days 1+15, Syringe and Needle | Arm C: IMVAMUNE Days 1+22, Syringe and Needle | Arm D: IMVAMUNE Days 1+29, Stratis |
|---|---|---|---|---|
| Adverse Event | 0 | 0 | 4 | 2 |
| Lost to Follow-up | 0 | 2 | 0 | 4 |
| Protocol Violation | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 1 | 2 | 2 | 3 |
| Physician Decision | 0 | 1 | 0 | 1 |
| Temporary study halt to vaccinations | 11 | 2 | 5 | 13 |
Analysis population for the primary outcome, as defined in the registry: The modified ATP population was defined as all participants who received both vaccinations in window, excluding those who did not have a complete dose delivered or received non-study vaccinations. Only measurements (blood draws) between Days 7-31 were considered and subjects had to have at least two measurements in that range to be included.
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: All participants are included in the baseline analysis population
| Characteristic | Unit | Arm A: IMVAMUNE Days 1+29, Syringe and Needle | Arm B: IMVAMUNE Days 1+15, Syringe and Needle | Arm C: IMVAMUNE Days 1+22, Syringe and Needle | Arm D: IMVAMUNE Days 1+29, Stratis | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 115 | 96 | 104 | 120 | 435 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 115 | 96 | 104 | 120 | 435 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous | years | 27.2 (SD 5.6) | 27.1 (SD 5.4) | 27.2 (SD 5.0) | 27.9 (SD 5.2) | 27.4 (SD 5.3) |
| Sex: Female, Male: Female | Participants | 61 | 49 | 59 | 60 | 229 |
| Sex: Female, Male: Male | Participants | 54 | 47 | 45 | 60 | 206 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 10 | 4 | 12 | 7 | 33 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 104 | 92 | 92 | 113 | 401 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 7 | 3 | 7 | 12 | 29 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 1 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 20 | 15 | 17 | 18 | 70 |
| Race (NIH/OMB): White | Participants | 81 | 70 | 74 | 86 | 311 |
| Race (NIH/OMB): More than one race | Participants | 6 | 8 | 4 | 4 | 22 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 | 0 | 2 |
| Region of Enrollment: United States | participants | 115 | 96 | 104 | 120 | 435 |
6. Primary Endpoint
The registry lists the primary outcome as Geometric Mean Peak Plaque Reduction Neutralization Titer (PRNT) After Second Vaccination, measured over Day 7 through Day 31 after 2nd vaccination.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | titers |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the geometric mean peak plaque reduction neutralization titer (PRNT) after the second vaccination. PRNT titers measure neutralizing activity in a laboratory assay. For each participant, the peak was defined as the highest titer among available measurements after the second vaccination; the group result was then calculated as a geometric mean of those participant-level peaks.
Blood draws were scheduled at 8, 15, 22, and 29 days after the second vaccination. The endpoint timeframe is stated as Day 7 through Day 31 after the second vaccination, and only measurements in that window were considered. The registry says participants needed at least two measurements, but additional detail about handling incomplete measurements is not reported in the registry record.
Geometric means are useful for measurements interpreted on a multiplicative scale, such as titers that can vary by fold changes. A confidence interval communicates uncertainty around the estimated group mean; it does not describe the range containing individual participants' titers. The endpoint is an immunogenicity measure. It is not, by itself, a measure of smallpox cases prevented, clinical protection, or long-term immunity.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted geometric mean peak PRNT titer was 138.0 in Arm A, with a 95% confidence interval from 110.1 to 172.8. Arm B's estimate was 55.1, with an interval from 42.3 to 71.7. Arm C's estimate was 75.9, with an interval from 58.5 to 98.4. Arm D's estimate was 103.5, with an interval from 80.8 to 132.6. These are group-level estimates in the endpoint analysis population.
The registry also reports three pairwise mean differences on the log2 scale, each comparing Arm A with another arm. For Arm A versus Arm B, the reported difference was 1.32, with a 98.33% confidence interval from 0.72 to 1.93. For Arm A versus Arm C, it was 0.86, with a 98.33% confidence interval from 0.26 to 1.47. For Arm A versus Arm D, it was 0.41, with a 98.33% confidence interval from -0.17 to 1.001. The first two intervals are entirely positive; the interval for the comparison with Arm D includes zero. The registry classifies these analyses as non-inferiority or equivalence analyses, but their formal interpretation depends on margins and hypotheses that are not reported in the registry record.
The confidence intervals show that the estimated group means are not known with perfect precision. Their width reflects uncertainty in the estimate under the analysis used; it does not establish that every participant's result lies within the interval. Overlap or non-overlap between separate group confidence intervals is not a substitute for a prespecified comparison test. The registry's pairwise estimates are the more direct source for those contrasts.
The arm estimates alone do not establish whether one regimen met a non-inferiority or equivalence criterion. Such a conclusion requires the prespecified margin, the direction of the hypothesis, and the analysis plan. These details, as well as p-values for the posted comparisons, are not reported in the registry record. The results describe antibody titers after vaccination in the analyzed population; they do not directly answer whether regimens differ in clinical protection or other outcomes.
9. Statistical Methods Explained
The primary endpoint is a geometric mean, rather than an arithmetic mean. General explanation: geometric means are calculated on a logarithmic scale and then expressed on the original measurement scale. They are commonly used for positive measurements where multiplicative changes are meaningful. This can make a group summary more appropriate for titers than an arithmetic average, though the registry does not report a comparison of alternative summary measures.
What does a confidence interval convey?
A confidence interval describes the uncertainty around an estimated quantity under the statistical method used. The primary arm estimates are accompanied by 95% confidence intervals. The pairwise mean differences are accompanied by 98.33% confidence intervals. A wider interval indicates less precision than a narrower interval on the same scale. A confidence interval is not a prediction interval for individual participants, nor does it mean that the true value has a probability equal to the confidence level of lying within that specific calculated interval.
The reported pairwise quantity is a mean difference on the log2 scale, comparing Arm A with each of the other arms. Logarithmic scales express multiplicative contrasts in a form that can be analyzed as differences. A positive difference in the registry's stated comparison direction indicates a higher log-scale result for the first listed group, Arm A, than for the second listed group. The record gives the estimates and intervals but does not specify the underlying model or calculation method.
How should the comparison intervals be read?
The interval for the Arm A comparison with Arm B runs from 0.72 to 1.93, and the interval for the comparison with Arm C runs from 0.26 to 1.47. Both intervals lie on the positive side of zero. The interval for the comparison with Arm D runs from -0.17 to 1.001 and includes zero. This is a description of the reported intervals, not a declaration that a regimen is equivalent or non-inferior. Those conclusions require a margin and a prespecified decision rule. Neither is reported in the registry record.
The registry labels these three analyses as non-inferiority or equivalence analyses. It does not give the margin, state which form of hypothesis was used for each comparison, or report p-values. The confidence intervals use 98.33%, but the reason for that level and any multiplicity procedure are not reported in the registry record. Without those details, the pairwise results can be described numerically but their planned confirmatory interpretation cannot be reconstructed.
What does the analysis population mean?
The primary analysis used a modified ATP population, as defined in the record. It included participants who received both vaccinations in window and excluded those who did not have a complete dose delivered or received non-study vaccinations. Eligible blood measurements had to fall between Days 7 and 31 after the second vaccination, and participants needed at least two measurements. The definition in the registry record ends after that requirement; any further eligibility or analysis rules are not reported in the registry record.
Using a restricted analysis population can make an estimate answer a narrower question than an analysis of everyone randomized. It may focus on participants with vaccination and measurement information meeting the stated conditions. The number excluded from each randomized group, the reasons for missing measurements, and any sensitivity analyses are not reported in the registry record. Therefore, the influence of exclusions or missing data on the estimates cannot be assessed from these results alone.
What can planning calculations tell readers?
Sample-size illustrations based on an observed effect are planning exercises, not observed power and not evidence that the trial had a particular probability of detecting an effect. Their values depend on assumptions. The stated planning approach uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of the observed effect. For time-to-event outcomes, such illustrations count total events; for other outcomes, they express participants per arm. These calculations do not establish that the original trial was designed using those assumptions. The trial's own sample-size justification is not reported in the registry record.
More generally, estimates and confidence intervals describe the data under a chosen analysis; they do not resolve design questions that are absent from the record. Details such as the model, transformations beyond the stated log2 comparison scale, adjustment for covariates, and handling of protocol deviations are not reported in the registry record. Interpretation should therefore stay with the posted estimands, populations, and intervals rather than assuming an unreported analysis plan.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| not stated | Mean Difference (Log2 Scale) 1.32 | 0.72 to 1.93 | not reported |
| not stated | Mean Difference (Log2 Scale) 0.86 | 0.26 to 1.47 | not reported |
| not stated | Mean Difference (Log2 Scale) 0.41 | -0.17 to 1.0007 | not reported |
The registry reports three comparisons framed as non-inferiority or equivalence: Arm A against Arms B, C, and D. It gives mean differences on the log2 scale and 98.33% confidence intervals, but no p-values, margins, or accompanying conclusion. The statistical meaning of those comparisons therefore cannot be fully assessed from the registry record. In particular, the fact that an interval lies on one side of zero does not establish non-inferiority or equivalence without the relevant margin and decision rule.
Unadjusted recalculations from posted summary statistics are useful as a check on group-level contrasts, but they do not replace an analysis that accounts for the trial's prespecified design and analysis plan. No discrepancy is flagged between the registry's reported analyses and the recalculation. The registry's own reported analysis remains the source for its stated comparisons; the additional calculations should be read as descriptive checks rather than a separate trial conclusion.
The analysis method and the rationale for the 98.33% confidence level are not reported in the registry record. Any distinction between a formal sponsor conclusion and the numerical results is also not reported in the registry record.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures and 13 analyses, including the primary endpoint and two posted secondary outcomes. The secondary outcomes are geometric mean peak ELISA titer after the second vaccination and the number of subjects experiencing serious adverse events associated with IMVAMUNE. The record does not provide a complete account of how the analyses relate to one another or which were designated for confirmatory inference.
Three reported primary-endpoint comparisons use 98.33% confidence intervals. A multiplicity adjustment can alter the interpretation of repeated comparisons by controlling the chance of misleading findings across a family of tests. However, the reason for this confidence level, the family of comparisons it may address, and any adjustment procedure are not reported in the registry record. The record also does not report a complete testing hierarchy or the handling of multiple outcomes. No interim analyses or interim-analysis stopping rules are reported in the registry record.
The primary endpoint population was modified ATP, with stated restrictions on vaccination timing, dose delivery, non-study vaccinations, and the number and timing of blood measurements. The record does not give arm-level counts of participants excluded from this population or details on the reasons for missing data. It does not report imputation, sensitivity analyses, or a comparison with an intention-to-treat analysis. Consequently, the impact of missing measurements and post-randomization exclusions cannot be determined from the registry record.
The posted endpoint estimates use 84 participants in Arm A, 85 in Arm B, 84 in Arm C, and 79 in Arm D. Those analysis counts differ from the 88 subjects described for each arm in the arm descriptions, but the reasons for the difference are not reported in the registry record. The overall enrollment is 435. The information available does not establish how every enrolled or randomized participant contributed to each outcome analysis.
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 |
|---|---|---|---|
| Arm A: IMVAMUNE Days 1+29, Syringe and Needle | 2 | 116 | 1.7% |
| Arm B: IMVAMUNE Days 1+15, Syringe and Needle | 1 | 96 | 1.0% |
| Arm C: IMVAMUNE Days 1+22, Syringe and Needle | 1 | 103 | 1.0% |
| Arm D: IMVAMUNE Days 1+29, Stratis | 1 | 120 | 0.8% |
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 |
|---|---|
| Arm A: IMVAMUNE Days 1+29, Syringe and Needle | 114 of 116 |
| Arm B: IMVAMUNE Days 1+15, Syringe and Needle | 94 of 96 |
| Arm C: IMVAMUNE Days 1+22, Syringe and Needle | 103 of 103 |
| Arm D: IMVAMUNE Days 1+29, Stratis | 119 of 120 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A: IMVAMUNE Days 1+29, Syringe and Needle | Arm B: IMVAMUNE Days 1+15, Syringe and Needle | Arm C: IMVAMUNE Days 1+22, Syringe and Needle | Arm D: IMVAMUNE Days 1+29, Stratis |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | 1 of 116 | 0 of 96 | 0 of 103 | 0 of 120 |
| Intentional overdose | Injury, poisoning and procedural complications | 1 of 116 | 0 of 96 | 0 of 103 | 0 of 120 |
| Jaw fracture | Injury, poisoning and procedural complications | 0 of 116 | 1 of 96 | 0 of 103 | 0 of 120 |
| Type I hypersensitivity | Immune system disorders | 0 of 116 | 0 of 96 | 1 of 103 | 0 of 120 |
| Large intestinal obstruction | Gastrointestinal disorders | 0 of 116 | 0 of 96 | 0 of 103 | 1 of 120 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A: IMVAMUNE Days 1+29, Syringe and Needle | Arm B: IMVAMUNE Days 1+15, Syringe and Needle | Arm C: IMVAMUNE Days 1+22, Syringe and Needle | Arm D: IMVAMUNE Days 1+29, Stratis |
|---|---|---|---|---|---|
| INJECTION SITE PAIN | General disorders | 108 of 116 | 84 of 96 | 96 of 103 | 115 of 120 |
| INJECTION SITE ERYTHEMA | General disorders | 82 of 116 | 66 of 96 | 81 of 103 | 114 of 120 |
| INJECTION SITE OEDEMA | General disorders | 74 of 116 | 67 of 96 | 74 of 103 | 112 of 120 |
| INJECTION SITE PRURITUS | General disorders | 67 of 116 | 44 of 96 | 52 of 103 | 86 of 120 |
| MALAISE | General disorders | 56 of 116 | 59 of 96 | 49 of 103 | 61 of 120 |
| MYALGIA | Musculoskeletal and connective tissue disorders | 42 of 116 | 49 of 96 | 46 of 103 | 49 of 120 |
| AXILLARY PAIN | General disorders | 17 of 116 | 21 of 96 | 18 of 103 | 28 of 120 |
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | 18 of 116 | 20 of 96 | 17 of 103 | 21 of 120 |
| NAUSEA | Gastrointestinal disorders | 20 of 116 | 15 of 96 | 19 of 103 | 20 of 120 |
| APPETITE DISORDER | Metabolism and nutrition disorders | 19 of 116 | 16 of 96 | 14 of 103 | 19 of 120 |
Serious events with the highest arm-level rate: jaw fracture (1.0%), type i hypersensitivity (1.0%), acute myocardial infarction (0.9%), intentional overdose (0.9%), large intestinal obstruction (0.8%).
The registry reports serious adverse events for each arm alongside the number at risk: Arm A had 2 among 116, Arm B had 1 among 96, Arm C had 1 among 103, and Arm D had 1 among 120. These are recorded counts, not estimates of comparative risk adjusted for follow-up or other factors. The number at risk for these safety entries is not the same as the endpoint analysis count, and the reason for the differing denominators is not reported in the registry record.
Other adverse events were recorded for 114 among 116 in Arm A, 94 among 96 in Arm B, 103 among 103 in Arm C, and 119 among 120 in Arm D. These counts should be read according to the registry's outcome labels; the record does not provide enough detail to characterize severity, timing, duration, or event-by-event attribution. Death counts are not reported in the registry record.
The registry lists Jaw fracture and Type I hypersensitivity at 1.0% each, Acute myocardial infarction and Intentional overdose at 0.9% each, and Large intestinal obstruction at 0.8% among the top serious terms. Their denominators and arm assignments are not reported in the registry record. Event counts alone do not establish whether events were caused by vaccination, and the listed terms should not be interpreted as comparative safety estimates across regimens.
13. What the Result Does, and Does Not, Mean
The results characterize peak neutralizing antibody titers after the second vaccination among participants who met the modified ATP requirements. They describe four schedules or delivery regimens and provide group-level geometric means with confidence intervals. The pairwise analyses provide log2-scale contrasts between Arm A and each of the other arms. Together, these statistics show the size and precision of the measured immunogenicity outcomes in the analyzed population.
They do not establish whether any schedule prevents smallpox, how long any immune response persists, or whether one regimen produces better clinical outcomes. No clinical disease endpoint is reported as the primary outcome. The trial's focus, as recorded, is safety and immunogenicity. Laboratory titers are relevant biological measurements, but they are not interchangeable with evidence of clinical protection.
The reported comparisons also do not by themselves establish non-inferiority or equivalence. The registry uses those analysis labels, but does not report the margins, the detailed hypotheses, or a formal conclusion. Inferences from confidence intervals require those details and the intended multiplicity procedure. The available statistics therefore support careful description of the observed estimates, not a complete reconstruction of the trial's confirmatory decision process.
Safety counts are similarly descriptive. They record adverse events among participants at risk but do not establish causation, relative risk, or whether differences between arms are meaningful. Further detail on event definitions, follow-up, and attribution is not reported in the registry record. Neither these safety counts nor the immunogenicity estimates should be generalized beyond the studied participants and the recorded analysis populations without additional evidence.
In general, a randomized comparison can help assess differences between assigned regimens, but its interpretation depends on the analysis plan, outcome definitions, and completeness of follow-up. Several of those details are not reported in the registry record. The results are best understood as estimates of post-vaccination titers and recorded safety outcomes, with the limitations of the populations and statistical details.
14. Why This Trial Matters Statistically
This trial is statistically informative because it varies two features that are often considered separately: the timing of the second vaccination and the method of delivery. Arms A, B, and C used syringe and needle with different vaccination days, while Arms A and D shared the same days and differed in delivery method. That structure creates direct descriptive comparisons for schedule and delivery questions, although the registry does not report enough detail to assess the full planned analysis.
The primary measure is a participant-level peak followed by a group geometric mean. This choice makes clear that the result represents each participant's highest eligible measurement, not an average across all scheduled blood draws. The modified ATP population and requirement for repeated measurements also matter: the estimate pertains to participants with the specified vaccination and measurement records, not automatically to everyone enrolled.
The example also illustrates why numerical contrasts and formal claims should be kept distinct. The registry reports pairwise log2-scale estimates and confidence intervals, while the analysis labels refer to non-inferiority or equivalence. Without the margin and decision rule, the numbers can be described but those claims cannot be verified from the record. Confidence intervals communicate precision, but do not supply missing protocol decisions.
Finally, the safety figures demonstrate why denominators and outcome definitions matter. The counts at risk differ from the endpoint group counts, and the record does not explain the difference. Reading each count in its stated outcome context prevents a mistaken direct comparison of groups or an assumption about causality. These issues are common in registry-based statistical interpretation: the posted data are useful, but their meaning is bounded by the reporting detail.
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 details needed for a fuller assessment are not reported in the registry record. These include the non-inferiority or equivalence margin, the statistical method used for the reported comparisons, the rationale for the 98.33% confidence intervals, and the multiplicity procedure. Without these details, the formal interpretation of the pairwise analyses is limited.
The modified ATP definition is described only in part. It states that participants received both vaccinations in window, had complete dose delivery, did not receive non-study vaccinations, and had at least two eligible measurements. Further rules, the number excluded from each arm, and the reasons for missing measurements are not reported in the registry record. The record does not report imputation or sensitivity analyses that might show how exclusions affected the estimates.
The endpoint analysis counts are 84, 85, 84, and 79 across the four arms, while the arm descriptions state 88 subjects per arm. The reason for these different counts is not reported in the registry record. The safety denominators are different again, and the record does not explain the relationship between safety follow-up and the endpoint population. These distinctions complicate direct comparisons across outcomes.
The open-label design is recorded, but details about allocation concealment, laboratory masking, or other measures to reduce assessment bias are not reported in the registry record. The registry also does not report participant characteristics, eligibility criteria, the sample-size justification, or the full analysis plan. No clinical efficacy endpoint is posted as the primary outcome, so the titers should not be treated as direct evidence of disease prevention. These limitations do not erase the reported measurements, but they constrain what can be inferred from them.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Phase II Trial to Assess Safety and Immunogenicity of IMVAMUNE® — NCT01827371.
- Registry record last updated 2016-09-07; status last verified 2015-05.
- Results first posted 2015-12-11.
- 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
NCT01827371 is a completed randomized, open-label, parallel Phase II study of IMVAMUNE® for smallpox. It enrolled 435 participants and compared four regimens using different vaccination schedules or delivery methods. Each arm description specifies two subcutaneous vaccinations at 1x10^8 TCID50/0.5 mL.
The primary outcome was the geometric mean peak PRNT titer after the second vaccination, assessed in a modified ATP population. The registry reports group estimates with 95% confidence intervals and three Arm A comparisons with 98.33% confidence intervals. It also records secondary outcomes concerning ELISA titers and serious adverse events.
The record supports a descriptive reading of the posted immunogenicity and safety statistics. The analysis margins, full statistical plan, missing-data handling, and several population details are not reported in the registry record, limiting formal conclusions about non-inferiority, equivalence, and comparative safety.