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 Randomized, Open-label Study Comparing Two Different Rabies Vaccine Schedules in Chinese Children and Older Adults (NCT01680016), a randomized phase 3 study. The primary outcome is Non-inferiority in Immune Response of the Zagreb Postexposure Schedule of Rabipur to That of the Conventional Essen Postexposure Schedule of Rabipur as Measured by GMC of RVNA Titer 14 Days After First Vaccination in Children Aged ≥6 to ≤17 Years..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01680016 |
| Phase | Phase 3 |
| Condition | Rabies |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 644 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Vaccines |
| Results posted | Yes |
2. Clinical Question
Population
Chinese children aged 6 to 17 years and older adults aged 51 years or older were included in the trial. The primary endpoint concerns children aged 6 to 17 years. The registry record describes analysis of a per-protocol population for that endpoint, defined by correct vaccination, evaluable serum samples at relevant time points, and no major protocol violations.
Intervention
The intervention was the Zagreb post-exposure schedule of Rabipur, identified as 2-1-1. The study evaluated simulated post-exposure vaccination schedules and assessed immunogenicity and safety.
Comparator
The comparator was the Essen post-exposure schedule of Rabipur, identified as 1-1-1-1-1 and described as the conventional schedule. The trial was randomized, open-label, and parallel-group.
Primary question
In children aged 6 to 17 years, was the geometric mean concentration of rabies virus neutralizing antibody 14 days after the first vaccination on the Zagreb schedule non-inferior to that on the Essen schedule? The registry record states this question but does not report a single numerical result or a non-inferiority margin.
3. Trial Design
This was a phase IIIb, randomized, open-label, parallel-group study comparing two simulated post-exposure rabies vaccination schedules in Chinese children and older adults. The registry record lists an enrollment of 644 and a completed status. The recorded start was 2012-09, and primary completion was 2013-01. The sponsor was Novartis Vaccines.
The schedules were Zagreb 2-1-1 and Essen 1-1-1-1-1, both identified as Rabipur schedules. The four listed groups were children aged 6 to 17 years and adults aged 51 years or older assigned to each schedule. The registry record does not provide descriptions of the individual arm procedures beyond the schedule names, nor does it explain the exact randomization process or allocation ratio.
Open-label means that the study was not masked according to the registry record. In general, lack of masking can affect subjective assessments or participant reporting, although the primary endpoint was a laboratory antibody measurement. Randomization is intended to distribute prognostic characteristics across treatment groups, but the registry record does not provide details about how the sequence was generated or concealed.
The study was designed to evaluate safety and immunogenicity. The primary endpoint focused on immune response in children, with antibody measurements before vaccination and 14 days after the first vaccination. Listed secondary outcomes include antibody threshold proportions at 14 and 42 days in children and older adults, as well as geometric mean concentrations at 42 days. The record gives these outcome descriptions but does not report their numerical results.
A parallel-group design assigns participants to one schedule for comparison with the other rather than describing a crossover between schedules. The reported enrollment is an overall figure; it should not be treated as the count in any particular analysis population. The registry record does not report group-specific randomization counts for the primary analysis.
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.
Before assignment: All enrolled subjects were included in the trial
Overall Study
| Stage | Zagreb(≥6 to ≤17 Years) | Essen(≥6 to ≤17 Years) | Zagreb(≥51 Years) | Essen(≥51 Years) |
|---|---|---|---|---|
| STARTED | 121 | 122 | 201 | 200 |
| COMPLETED | 115 | 114 | 196 | 195 |
| NOT COMPLETED | 6 | 8 | 5 | 5 |
Reasons for not completing this period:
| Reason | Zagreb(≥6 to ≤17 Years) | Essen(≥6 to ≤17 Years) | Zagreb(≥51 Years) | Essen(≥51 Years) |
|---|---|---|---|---|
| Adverse Event | 0 | 0 | 1 | 4 |
| The Subject went out of The Trial | 1 | 0 | 3 | 0 |
| Protocol Violation | 0 | 1 | 0 | 0 |
| Withdrawal by Subject | 5 | 7 | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Analysis was done on the per-protocol (PP) set, i.e. the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis.
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: Enrolled set:All subjects who had signed an informed consent, undergone screening procedure(s) and were randomized
| Characteristic | Unit | Zagreb | Essen | Total |
|---|---|---|---|---|
| Participants analysed | 322 | 322 | 644 | |
| Age, Continuous: Children (≥6 to ≤17 Years) | years | 11 (SD 3.0) | 10.8 (SD 2.9) | 10.9 (SD 3.0) |
| Age, Continuous: Older Adults (≥51 Years) | years | 62.1 (SD 6.5) | 61.9 (SD 6.8) | 62.0 (SD 6.6) |
| Sex/Gender, Customized: Female (≥6 to ≤17 Years) | Subjects | 49 | 76 | 125 |
| Sex/Gender, Customized: Male (≥6 to ≤17 Years) | Subjects | 72 | 46 | 118 |
| Sex/Gender, Customized: Female (≥51 Years) | Subjects | 118 | 123 | 241 |
| Sex/Gender, Customized: Male (≥51 Years) | Subjects | 83 | 77 | 160 |
6. Primary Endpoint
The registry lists the primary outcome as Non-inferiority in Immune Response of the Zagreb Postexposure Schedule of Rabipur to That of the Conventional Essen Postexposure Schedule of Rabipur as Measured by GMC of RVNA Titer 14 Days After First Vaccination in Children Aged ≥6 to ≤17 Years., measured over Before vaccination (day 1) and 14 days after first vaccination (day 15).
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | IU/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the geometric mean concentration (GMC) of rabies virus neutralizing antibody (RVNA) titer in children aged 6 to 17 years, assessed before vaccination and 14 days after the first vaccination. The registry description says that RVNA was measured using the rapid fluorescent focus inhibition test. The stated unit was IU/mL, and the planned presentation included a 95% confidence interval.
A GMC is a summary of measurements after applying a logarithmic transformation, averaging on that scale, and transforming back. As a general statistical concept, this can be useful when biological measurements are positive and skewed: a small number of high measurements may otherwise have a strong influence on an arithmetic mean. A GMC describes the central level on a multiplicative scale; it does not describe every participant’s antibody response.
The endpoint was chosen to assess immunogenicity, meaning the immune response measured by antibody levels. The registry record frames the primary question as non-inferiority of Zagreb relative to Essen. In general, a non-inferiority analysis asks whether the data rule out a loss larger than a prespecified acceptable margin. That margin is not reported in the registry record, and the record does not provide a single numerical comparison result. The endpoint therefore identifies what was intended to be compared, but the posted information does not establish the result of that comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a specific primary question: whether the Zagreb schedule produced a non-inferior GMC of RVNA titer compared with the Essen schedule 14 days after the first vaccination in children aged 6 to 17 years. It also describes the measurement time points, assay, unit, confidence interval type, and per-protocol analysis population. These details define the intended outcome and analysis population, but they are not themselves evidence about the size or direction of the observed difference.
No numerical primary GMC estimates, confidence limits, group comparison, or non-inferiority conclusion are reported in the registry record. A reader therefore cannot determine from the posted results whether the observed immune responses were similar, whether one was higher, or whether the non-inferiority criterion was met. The non-inferiority margin is also not reported in the registry record. Without that margin and the comparison estimate with its uncertainty, the non-inferiority question cannot be evaluated from this record.
The registry lists secondary outcomes involving the percentage of children and older adults with RVNA titers at least 0.5 IU/mL at 14 and 42 days, along with GMCs at 42 days. These are outcome definitions, not numerical findings. No response percentages or secondary GMC values are reported in the registry record. The existence of these additional planned measures does not fill the gap in the primary comparison result.
The adverse-event entries show that the record includes safety data by age group and schedule. They should be read as counts within the listed groups, not as evidence that a schedule caused or prevented an event. The registry record does not report deaths for the listed groups, and the serious-event term listing does not identify which group contributed the term. The record also does not provide enough context to interpret the full nature, timing, or relatedness of the reported events.
These limitations are about what can be concluded from the posted record, not about what the full study may have found. The outcome estimates and detailed analyses needed to characterize the immune response are not reported in the registry record. In the absence of those results, the trial’s stated objective can be described, but its primary statistical conclusion cannot be independently assessed from the information posted.
General statistical interpretation of non-inferiority depends on the estimate, its confidence interval, and a clinically justified margin specified before analysis. A nonsignificant difference alone would not establish non-inferiority. In this case, the record does not provide the numerical inputs required for that assessment. The appropriate reading is therefore that the registry describes a non-inferiority question without reporting its decisive numerical result.
9. Statistical Methods Explained
The endpoint is described as a geometric mean concentration of RVNA titer, measured using the rapid fluorescent focus inhibition test. Measurements were taken before vaccination and 14 days after the first vaccination. The unit was IU/mL, and the registry record specifies a 95% confidence interval. The primary analysis population was the per-protocol set: participants who received the vaccine correctly, provided evaluable serum samples at the relevant time points, and had no major protocol violations as defined before analysis.
What does a geometric mean describe?
As a general statistical concept, a geometric mean summarizes positive measurements on a multiplicative scale. The measurements are transformed to logarithms, averaged, and transformed back. This approach can be appropriate when values are right-skewed or when proportional changes are more meaningful than equal absolute changes. A GMC is a group summary; it does not mean that every participant had a value close to that summary. Nor does it describe the spread of individual responses by itself.
The registry record does not report the GMC estimates or their confidence limits. It is therefore not possible to describe the magnitude or precision of the observed immune response from this record. A confidence interval generally gives a range of values compatible with the data and the specified statistical procedure. It is not a guarantee that the true value lies in the interval, and its width depends on factors such as variability and the number of evaluable observations. Here, the stated interval type is available, but the interval itself is not reported in the registry record.
How does non-inferiority differ from testing for a difference?
In a general non-inferiority framework, investigators define a margin representing the largest loss that would still be considered acceptable for the outcome. The analysis then asks whether the data exclude a loss greater than that margin. This is different from simply asking whether the groups differ statistically. A result that does not show a statistically significant difference does not, by itself, demonstrate non-inferiority.
The trial’s primary question is expressly described as non-inferiority of the Zagreb schedule relative to Essen. However, the margin and the statistical decision rule are not reported in the registry record. Neither are a primary comparison estimate, confidence limits for the comparison, or a reported conclusion. The non-inferiority claim therefore cannot be checked from the posted information. It would be inappropriate to infer success or failure from the endpoint description alone.
Why does the analysis population matter?
The primary endpoint was analyzed in a per-protocol population, defined in the registry record by correct vaccine receipt, evaluable serum samples, and absence of major protocol violations. This definition emphasizes participants with protocol-compliant treatment and usable measurements. As a general matter, per-protocol analyses can be useful in non-inferiority studies because departures from the assigned schedule may make groups appear more similar. However, excluding participants can also affect comparability if the exclusions are related to treatment or outcome. Those are general considerations, not findings about this trial.
The registry record does not report the number included in the primary per-protocol analysis, the number excluded, the reasons for exclusion, or how missing serum measurements were handled. It also does not report a complementary intention-to-treat analysis. These details matter because analysis populations can produce different estimates, particularly when adherence or missing outcomes differ between groups.
What does randomization and open-label status imply?
Randomization is generally used to reduce systematic differences between groups at baseline. It does not ensure that every measured or unmeasured characteristic will be perfectly balanced, and its protection depends on implementation. The record identifies the study as randomized but does not describe sequence generation, allocation concealment, stratification, or other randomization procedures.
The study was open-label, with no masking listed. In general, awareness of the assigned schedule can affect behaviors, reporting, and some clinical assessments. The primary measure was a laboratory antibody assay, which is less directly subjective than a participant-reported outcome, but the registry record does not describe assay blinding, laboratory procedures beyond the test name, or quality-control methods. No particular bias can be concluded from the open-label designation alone.
What is known about the statistical plan?
The registry record does not report the detailed statistical analysis plan, the non-inferiority margin, the model or test used for the primary comparison, covariate adjustments, or procedures for missing data. It also does not report interim analyses or a sample-size justification. These omissions prevent reconstruction of the planned inferential procedure. The endpoint and its confidence interval format are stated, but those alone do not specify how the comparison was tested.
More generally, design choices should be interpreted alongside the estimand, analysis population, missing-data assumptions, and prespecified decision rule. The estimand describes the treatment comparison the analysis aims to quantify, including how events such as nonadherence or missing measurements are handled. Such details are not reported in the registry record. Consequently, the posted description supports an account of the intended measurement but not a full audit of the statistical methods or a numerical interpretation of the primary finding.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 12 outcome measures and 2 analyses. It describes one primary immune-response question and several secondary measures involving antibody threshold proportions and GMCs at different time points and in different age groups. Because multiple outcomes and time points are listed, the findings would ordinarily need to be interpreted in light of the analysis plan and the role assigned to each outcome. The registry record does not report a multiplicity adjustment or explain how the collection of outcomes was handled for statistical inference.
The primary endpoint description includes measurements before vaccination and 14 days after the first vaccination. The record does not reduce the primary endpoint to a single reported comparison result. It provides no estimate, confidence interval, or test result that would allow a reader to evaluate the stated non-inferiority question. Results for the listed secondary outcomes are also not reported in the registry record.
Missing-data methods are not reported in the registry record. The per-protocol definition requires evaluable serum samples at relevant time points, but the record does not state how many samples were missing, why they were missing, whether any values were imputed, or whether sensitivity analyses were performed. The number included in each analysis population and the relationship between those populations are also not reported.
The record does not report whether the primary analysis was accompanied by an intention-to-treat analysis or another analysis population. In general, examining more than one population can help assess whether conclusions depend on adherence or exclusions, especially for non-inferiority questions. That is a general methodological consideration; it is not evidence that such analyses were performed in this study.
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 |
|---|---|---|---|
| Zagreb(≥6 to ≤17 Years) | 0 | 121 | 0.0% |
| Essen(≥6 to ≤17 Years) | 0 | 119 | 0.0% |
| Zagreb(≥51 Years) | 1 | 200 | 0.5% |
| Essen(≥51 Years) | 0 | 200 | 0.0% |
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 |
|---|---|
| Zagreb(≥6 to ≤17 Years) | 64 of 121 |
| Essen(≥6 to ≤17 Years) | 63 of 119 |
| Zagreb(≥51 Years) | 19 of 200 |
| Essen(≥51 Years) | 24 of 200 |
Most frequent serious adverse event terms
| Event term | Organ system | Zagreb(≥6 to ≤17 Years) | Essen(≥6 to ≤17 Years) | Zagreb(≥51 Years) | Essen(≥51 Years) |
|---|---|---|---|---|---|
| Pancreatitis Acute | Gastrointestinal disorders | 0 of 121 | 0 of 119 | 1 of 200 | 0 of 200 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Zagreb(≥6 to ≤17 Years) | Essen(≥6 to ≤17 Years) | Zagreb(≥51 Years) | Essen(≥51 Years) |
|---|---|---|---|---|---|
| Injection Site Pain | General disorders | 48 of 121 | 50 of 119 | 19 of 200 | 24 of 200 |
| Fatigue | General disorders | 18 of 121 | 15 of 119 | 9 of 200 | 7 of 200 |
| Headache | Nervous system disorders | 11 of 121 | 10 of 119 | 8 of 200 | 9 of 200 |
| Upper Respiratory Tract Infection | Infections and infestations | 8 of 121 | 13 of 119 | 5 of 200 | 6 of 200 |
| Decreased Appetite | Metabolism and nutrition disorders | 14 of 121 | 10 of 119 | 0 of 200 | 2 of 200 |
| Myalgia | Musculoskeletal and connective tissue disorders | 11 of 121 | 13 of 119 | 0 of 200 | 2 of 200 |
| Nausea | Gastrointestinal disorders | 7 of 121 | 10 of 119 | 4 of 200 | 2 of 200 |
| Pyrexia | General disorders | 8 of 121 | 3 of 119 | 5 of 200 | 7 of 200 |
| Injection Site Erythema | General disorders | 8 of 121 | 2 of 119 | 1 of 200 | 5 of 200 |
Serious events with the highest arm-level rate: pancreatitis acute (0.5%).
The registry record lists serious adverse event counts for each age-group and schedule group. For children aged 6 to 17 years, the listed counts are 0 of 121 in the Zagreb group and 0 of 119 in the Essen group. For adults aged 51 years or older, the listed counts are 1 of 200 in the Zagreb group and 0 of 200 in the Essen group. These are the recorded serious-event counts and group denominators; they do not establish that a schedule caused or prevented an event.
The registry also lists acute pancreatitis as a serious adverse event term at 0.5%, but does not identify the group associated with that term. Deaths are not reported in the registry record for the listed groups. The record does not provide event timing, individual case details, relatedness assessments, or a full explanation of event coding in the information. The counts should therefore be interpreted as descriptive safety entries, not as a complete comparative safety analysis.
Other adverse-event counts are listed separately: 64 for the Zagreb child group, 63 for the Essen child group, 19 for the Zagreb older-adult group, and 24 for the Essen older-adult group. The record does not define those entries in enough detail to support interpretation of their severity, type, or relationship to vaccination. No percentages or comparisons should be inferred from those counts alone.
12. What the Result Does, and Does Not, Mean
This trial’s stated purpose was to evaluate safety and immunogenicity for two simulated rabies vaccine post-exposure schedules in Chinese children and older adults. Its primary question focused on whether the Zagreb schedule was non-inferior to the Essen schedule for the GMC of RVNA titer in children aged 6 to 17 years, measured 14 days after the first vaccination. The endpoint description and analysis population are reported, but the numerical primary comparison is not.
That distinction is important. A trial objective tells readers what investigators intended to estimate or test; it does not reveal the observed result. In this case, no primary GMC estimates, confidence intervals, comparison estimate, or non-inferiority conclusion are reported in the registry record. The non-inferiority margin is also not reported. The posted information therefore does not establish whether the primary criterion was met, whether the schedules produced similar measured responses, or how precise any estimated difference was.
The listed secondary outcomes extend the immune-response assessment to additional time points, age groups, and antibody summaries. Their definitions indicate the scope of planned measurement, but their values are not reported in the registry record. Likewise, the safety entries describe recorded event counts but do not, by themselves, establish causality or provide a complete comparison of safety between schedules.
General interpretation of a non-inferiority trial requires the margin, a treatment-effect estimate, and uncertainty around that estimate, considered under the prespecified analysis. A result cannot be classified from the study title or stated objective alone. Nor should a lack of a reported significant difference be treated as proof of equivalence or non-inferiority; the record does not report such a test result in the first place.
The study can therefore be characterized as a randomized, open-label comparison with a clearly described primary immune-response measure, but the posted record is insufficient to determine the statistical outcome of that comparison. This is a statement about the limits of the record, not a conclusion about the full study findings or the schedules themselves.
13. Why This Trial Matters Statistically
The trial illustrates how a clinical question and a statistical conclusion are different kinds of information. The registry record clearly names the schedules, the pediatric population for the primary question, the antibody measure, the measurement timing, and the per-protocol analysis population. Those details make the intended comparison identifiable. Yet, without the numerical estimates and uncertainty, the central result remains unassessable from the posted record.
Non-inferiority designs are especially dependent on transparent reporting. As a general statistical principle, a reader needs to know the prespecified margin and see how the confidence interval for the treatment comparison relates to it. Merely knowing that the study was designed to assess non-inferiority is not enough. The margin is not reported in the registry record, and no single primary comparison result is reported, so the decision rule and result cannot be reconstructed.
The record also highlights the importance of analysis-population reporting. The primary outcome was analyzed in a per-protocol set, but the number of participants in that set, exclusions, missing measurements, and any complementary analysis are not reported. For a non-inferiority question, those details can be important to judging how robust a conclusion would be. In this case, they cannot be assessed from the registry record.
Finally, the distinction between descriptive safety counts and comparative inference matters. The listed counts provide a limited view of recorded events, but they do not provide a full account of event characteristics, attribution, or comparative risk. A careful statistical reading separates what is directly recorded from what would require additional data and analysis. That discipline is useful whenever outcome definitions are available but inferential results are absent.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation of interpretation is that the registry record does not report the primary outcome estimates or the non-inferiority comparison. Although the endpoint is defined as a GMC of RVNA titer at specified time points, no group-specific values, confidence intervals, or numerical comparison are reported. The non-inferiority margin is also not reported, so the intended threshold for the decision cannot be assessed.
The primary analysis is described as per-protocol, but the record does not report the number of participants in that population, exclusions, protocol violations, missing samples, or methods for handling missing data. It also does not report whether an intention-to-treat analysis or sensitivity analysis was conducted. These omissions limit assessment of how analysis choices may have influenced the result.
Although the trial is identified as randomized and open-label, details of sequence generation, allocation concealment, and any stratification are not reported in the registry record. The record also does not describe masking of laboratory personnel, beyond identifying the assay used. These gaps do not establish that bias occurred, but they prevent a detailed assessment of trial conduct and measurement procedures.
The secondary outcome definitions are listed, but their numerical results are not reported in the registry record. Multiplicity handling, the detailed statistical analysis plan, interim analyses, and sample-size justification are not reported either. The safety entries lack event timing and case detail, and the acute pancreatitis listing is not linked to a particular group. These trial-specific reporting limits mean that the available record supports description of the design and planned measures more strongly than evaluation of the outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Randomized, Open-label Study Comparing Two Different Rabies Vaccine Schedules in Chinese Children and Older Adults — NCT01680016.
- Registry record last updated 2014-05-20; status last verified 2014-04.
- Results first posted 2014-05-20.
- 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
This completed phase IIIb randomized, open-label, parallel-group study compared the Zagreb 2-1-1 and Essen 1-1-1-1-1 Rabipur post-exposure schedules in Chinese children and older adults. The registry record lists an enrollment of 644, a start of 2012-09, and primary completion in 2013-01.
The primary question concerned non-inferiority of Zagreb relative to Essen for the GMC of RVNA titer 14 days after the first vaccination in children aged 6 to 17 years. The measurement used the rapid fluorescent focus inhibition test, and the primary analysis population was per-protocol. The registry record does not report a single primary comparison result or the non-inferiority margin.
Secondary outcome definitions cover antibody threshold proportions and GMCs in children and older adults at additional time points. Safety counts are listed by group, but detailed event context is limited. Numerical secondary immune-response results and further statistical methods are not reported in the registry record.