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 Study of Quinvaxem for Vaccination Against Diphtheria, Pertussis, Tetanus, Hepatitis B and Diseases Caused by Haemophilus Influenzae Type B (NCT01362517), a non-randomized phase 3 study. The primary outcome is Immunogenicity - Seroprotection (Seroconversion for Pertussis) to Each Vaccine Component.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01362517 |
| Phase | Phase 3 |
| Condition | Diphtheria, Pertussis, Tetanus |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 131 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Crucell Holland BV |
| Results posted | Yes |
2. Clinical Question
Population
Healthy Vietnamese infants enrolled in a completed Phase 3 study. The registry record reports enrollment of 131. The primary analysis population excludes one subject identified as a protocol violator.
Intervention
Quinvaxem, a liquid combination vaccine against diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B. Infants received three doses at 2, 3 and 4 months of age according to the local Expanded Programme on Immunisation schedule.
Comparator
There is no separate comparator group in this single-group study. The registry record identifies the allocation as non-randomized and masking as none, so the study does not offer a randomized, like-for-like control comparison.
Primary question
At 5 months, equivalent to 1 month after the third vaccination, what proportion of subjects had seroprotection for the diphtheria, tetanus, hepatitis B and Hib components, or seroconversion for pertussis? The registry record describes this endpoint but does not report its component-specific results.
The study also records adverse and serious adverse events after each dose. These safety observations describe events in the vaccinated study group; without a comparator, they cannot establish how event occurrence differed from an unvaccinated or differently vaccinated group. The record identifies three outcome measures, but does not report statistical analysis results. The clinical question is therefore descriptive: what immunogenicity and safety observations were recorded in this group, and how much detail does the registry record provide to assess their precision and context?
3. Trial Design
This was a completed Phase 3 study sponsored by Crucell Holland BV. The registry record gives a start date of 2010-04 and a primary completion date of 2010-07. It describes a single-group, non-randomized design with no masking. Enrollment was 131.
The participants were described as healthy Vietnamese infants. The brief summary says they received Quinvaxem at 2, 3 and 4 months of age in accordance with the local Expanded Programme on Immunisation schedule. The intervention is a liquid combination vaccine directed against diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B. No separate control arm is described. Accordingly, the design can document observations after vaccination but cannot provide a randomized comparison with another intervention or with no vaccination.
The primary outcome is an immunogenicity measure assessed at 5 months, described as equivalent to 1 month after the third vaccination. The registry record defines the analysis population as excluding one subject who was a protocol violator. It also lists safety outcomes for adverse and serious adverse events. The record reports event counts by dose, but does not provide a full account of event timing, severity categories beyond serious status, or how events were attributed to vaccination.
These design features shape what can be inferred. A single-group study may describe the proportion meeting an immune-response definition in the enrolled population. It does not isolate the vaccine's effect from other influences or support a direct treatment contrast. The absence of masking may also matter when outcomes depend on assessment or reporting, although the registry record does not say how outcome assessments were conducted. Further details about the protocol, eligibility criteria and statistical plan 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 | Quinvaxem |
|---|---|
| STARTED | 131 |
| COMPLETED | 129 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Quinvaxem |
|---|---|
| Protocol Violation | 1 |
| Lost to Follow-up | 1 |
Analysis population for the primary outcome, as defined in the registry: Analysis population excludes one subject excluded as a protocol violator
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Quinvaxem |
|---|---|---|
| Participants analysed | 131 | |
| Age, Categorical: <=18 years | Participants | 131 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 74 |
| Sex: Female, Male: Male | Participants | 57 |
6. Primary Endpoint
The registry lists the primary outcome as Immunogenicity - Seroprotection (Seroconversion for Pertussis) to Each Vaccine Component, measured over at 5 months (equivalent to 1 month after the third vaccination).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of subjects |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of subjects who meet the stated seroprotection definition for each vaccine component, with seroconversion used for pertussis. The components are diphtheria, tetanus, pertussis, hepatitis B and Hib. The measurement time is 5 months, equivalent to 1 month after the third vaccination. The analysis population excludes one subject described as a protocol violator.
An immune-response proportion is a binary summary: each subject either meets the endpoint definition or does not, and the result expresses the share meeting it. Such a measure is used to describe how often a specified immune response is observed after vaccination. It is not itself a direct measure of clinical disease prevention. Interpreting it depends on the endpoint definitions and laboratory procedures, which are not detailed in the registry record.
The registry record specifies that results are to be expressed as a percentage of subjects with a 95% confidence interval, but does not report the observed component-specific percentages or intervals. Consequently, the endpoint's stated purpose can be explained, but its observed magnitude and precision cannot be assessed from the registry record. No comparison with another vaccine or group is part of this endpoint's design.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes an immunogenicity endpoint measured after the third Quinvaxem dose, alongside safety outcomes recorded after doses. It does not report the component-specific primary outcome results. Therefore, the extent of seroprotection or pertussis seroconversion, and the precision of those estimates, are not reported in the registry record. The endpoint description alone does not establish what proportions were observed.
The record reports safety event counts by dose. Serious adverse events were reported for the first, second and third doses as 4, 6 and 1, respectively. Other adverse events were reported as 75, 34 and 25. The corresponding at-risk counts listed in the record are 131, 131 and 130 for the dose-specific groups. These are descriptive observations, not a comparison of risk between treatments. The record does not clarify whether the dose-specific groups represent the same people throughout, whether events could be counted more than once, or how events were attributed to vaccination.
For serious adverse event terms, the registry record lists upper respiratory tract infection, pulmonary infection and viral infection at 1.5% each, and diarrhea and bronchitis at 0.8% each. Those term-specific figures should not be read as an overall serious-event percentage. The record does not establish whether terms overlap within subjects or provide the detail needed to combine them. Nor does it identify a comparison group against which to judge whether the listed events occurred more or less often.
In general, a confidence interval conveys uncertainty around an estimate under the assumptions of the method used. A narrow interval would indicate greater statistical precision than a wide one, but neither an interval nor a percentage for the primary endpoint is reported in the registry record. Likewise, a reported event count can describe what was recorded in the study, but does not by itself identify a cause or distinguish treatment-related events from events that might occur for other reasons.
The design is single-group, non-randomized and unmasked. As a result, the posted information supports description of the study observations, not a causal estimate based on a randomized contrast. The primary endpoint results, statistical analyses, and a fuller account of safety-event definitions and assessment are not reported in the registry record. The appropriate reading is therefore limited to the specified outcome definitions, the recorded dose-specific safety counts and the absence of reported primary endpoint estimates.
9. Statistical Methods Explained
The primary endpoint is a proportion. In general, a proportion is calculated by identifying subjects who satisfy a defined event or response and relating that count to the relevant analysis population. For this study, the event is meeting the component-specific seroprotection definition, or seroconversion for pertussis. The registry record states that results are expressed as a percentage of subjects, but it does not report the observed percentages or the number meeting each definition. No primary endpoint result can therefore be interpreted from the record.
What does a confidence interval add?
In general, a confidence interval gives a range of values compatible with an estimate under the statistical method and its assumptions. It helps readers judge the precision of an estimate rather than treating a point estimate as exact. The primary endpoint description specifies a 95% confidence interval. However, the endpoint-specific intervals are not reported in the registry record, so the precision of the immunogenicity estimates cannot be evaluated. A confidence interval also does not correct for bias, make a non-randomized study randomized, or turn a descriptive proportion into a causal comparison.
What can a single-group design estimate?
A single-group study can describe the frequency of an outcome within the observed study population, subject to the endpoint definition and the quality of outcome measurement. It does not include a separate concurrent comparison group. In general, that means the observed response cannot by itself distinguish the contribution of the intervention from other factors, such as background changes or features of the enrolled population. This record identifies a non-randomized allocation, no masking and a single-group model. It does not report a comparative treatment effect or the statistical analyses needed to estimate one.
Because no masking is reported, the record does not indicate that participants or assessors were unaware of treatment assignment. In general, masking can reduce the influence of expectations on some forms of assessment or reporting. Its relevance depends on how outcomes are measured. The registry record does not describe the assessment procedures sufficiently to determine how this design feature affected either immunogenicity or safety observations.
How should dose-specific event counts be read?
The safety record lists at-risk counts and event counts separately for the first, second and third doses. These are dose-specific summaries. They should not be combined or interpreted as a count of unique subjects without information about repeat events, follow-up and how the dose groups relate to individual participants. The registry record does not specify whether one subject could contribute events after more than one dose or whether multiple events of the same type could be recorded. The counts describe recorded events in the listed dose groups; they do not establish a treatment effect or causation.
For general context, adverse-event data can be summarized as counts or as proportions of subjects with an event. The meaning of a proportion depends on its denominator and whether it represents subjects, events, or exposure time. Here, the record labels the outcome type as the percentage of participants with an event and lists dose-specific at-risk counts, but does not provide enough detail to resolve all questions about repeated events or overlap. Serious adverse event terms are also listed with percentages, but the record does not say whether those terms are mutually exclusive or how the percentages were calculated.
What do the planning illustrations mean?
The record's sample-size assumptions describe planning illustrations based on an observed effect, not the trial's original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the effect to detect is a stated fraction of the observed effect. Those are hypothetical planning choices, not features of the study's single-group design. The illustrations are not observed power, and they do not show that the trial was designed or analyzed as a two-arm comparison. No values for those illustrations are reported in the registry record.
In general, a sample-size calculation asks how much information a proposed study would need under specified assumptions. Its output depends on the outcome, the assumed effect, variability, allocation and chosen error rates. A calculation based on a previously observed effect is especially dependent on that estimate and should be treated as a planning scenario rather than a guarantee of future results. The registry record does not report a protocol-based sample-size justification, the target effect used in the original study design, or an inferential analysis plan.
Finally, no statistical analyses are reported in the registry record. In general, interpretation of estimated proportions may depend on the method used to form intervals and on how the analysis handles the population, missing observations and multiplicity. Those details are not reported for this study. The endpoint description identifies the intended measure and confidence level, but does not supply the estimates or the analysis procedures needed to reproduce or fully evaluate them.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint covers five vaccine components, with seroconversion specified for pertussis and seroprotection for the other components. Considering several component-specific outcomes raises a general multiplicity issue: when several outcomes are assessed, the chance of at least one apparently notable result can differ from that for a single prespecified test. The registry record does not report a multiplicity adjustment, a hierarchy among the components, or a statistical testing strategy. It also reports no analysis results or p-values. Therefore, it is not possible to determine whether multiplicity was addressed in the study analysis.
The primary analysis population is described as excluding one subject who was a protocol violator. The registry record does not explain the reason for the violation, the timing of the exclusion, or whether other analysis populations were defined. It does not report how missing outcome data were handled, how many endpoint observations were unavailable, or whether any imputation or sensitivity analysis was used. The exclusion is a stated population rule; it should not automatically be interpreted as missing data.
In general, missing-data methods can influence an estimated proportion when the availability of measurements is related to response status. The direction and size of any such influence depend on details about who was missing and why. Those details are not reported in the registry record, so the effect of missingness on the endpoint cannot be assessed. The record's description of the analysis population and endpoint confidence intervals is not a substitute for a full statistical analysis plan.
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 |
|---|---|---|---|
| First Dose | 4 | 131 | 3.1% |
| Second Dose | 6 | 131 | 4.6% |
| Third Dose | 1 | 130 | 0.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| First Dose | 75 of 131 |
| Second Dose | 34 of 131 |
| Third Dose | 25 of 130 |
Most frequent serious adverse event terms
| Event term | Organ system | First Dose | Second Dose | Third Dose |
|---|---|---|---|---|
| Pulmonary infection | Respiratory, thoracic and mediastinal disorders | 1 of 131 | 2 of 131 | 1 of 130 |
| Viral infection | Infections and infestations | 1 of 131 | 2 of 131 | 0 of 130 |
| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | 0 of 131 | 2 of 131 | 0 of 130 |
| Diarrhea | Gastrointestinal disorders | 1 of 131 | 0 of 131 | 0 of 130 |
| Bronchitis | Respiratory, thoracic and mediastinal disorders | 1 of 131 | 0 of 131 | 0 of 130 |
Most frequent non-serious adverse event terms
| Event term | Organ system | First Dose | Second Dose | Third Dose |
|---|---|---|---|---|
| Pyrexia | General disorders | 34 of 131 | 20 of 131 | 18 of 130 |
| Irritability | Psychiatric disorders | 21 of 131 | 8 of 131 | 2 of 130 |
| Injection site pain | General disorders | 24 of 131 | 0 of 131 | 0 of 130 |
| Injection site induration | General disorders | 19 of 131 | 3 of 131 | 0 of 130 |
| Diarrhea | Gastrointestinal disorders | 4 of 131 | 3 of 131 | 5 of 130 |
| Injection site erythema | General disorders | 7 of 131 | 2 of 131 | 2 of 130 |
| Feeding disorder | Metabolism and nutrition disorders | 10 of 131 | 0 of 131 | 0 of 130 |
| Vomiting | Gastrointestinal disorders | 4 of 131 | 0 of 131 | 0 of 130 |
| Somnolence | Nervous system disorders | 2 of 131 | 0 of 131 | 0 of 130 |
| Persistent crying | General disorders | 2 of 131 | 0 of 131 | 0 of 130 |
Serious events with the highest arm-level rate: upper respiratory tract infection (1.5%), pulmonary infection (1.5%), viral infection (1.5%), diarrhea (0.8%), bronchitis (0.8%).
The registry record reports serious adverse event counts of 4 after the first dose, 6 after the second dose and 1 after the third dose. It lists 131 at risk for the first and second doses and 130 for the third. Other adverse event counts are 75, 34 and 25, respectively, with the same dose-specific at-risk counts. These figures describe the recorded safety observations by dose; they are not a randomized comparison.
The listed serious-event terms are upper respiratory tract infection, pulmonary infection and viral infection at 1.5% each, and diarrhea and bronchitis at 0.8% each. The registry record does not clarify whether a subject could have more than one listed term, whether terms overlap, or whether the term percentages represent subjects or events. They should not be added together or treated as a complete measure of serious-event burden.
In general, an adverse event is an event recorded during a study, while a serious adverse event is a category based on seriousness criteria. The record does not provide those criteria or describe attribution to the vaccine. Counts alone do not show that vaccination caused an event, and a single-group study does not provide a control rate for comparison. Further detail on follow-up and event assessment is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed Phase 3, single-group study assessed Quinvaxem immunogenicity and safety in healthy Vietnamese infants. It specifies a primary immunogenicity measure at 5 months, equivalent to 1 month after the third vaccination, and lists dose-specific adverse and serious adverse event counts. It does not report the observed primary endpoint percentages or their confidence intervals. The extent and precision of the component-specific immune responses therefore cannot be determined from the registry record.
The safety counts are descriptive. They document events recorded after each dose in the study groups, but do not establish that Quinvaxem caused those events. Without a randomized comparator, the study cannot estimate how the counts differ from those in another treatment group. The record also lacks detail about repeat events, overlap across serious-event terms, attribution and event ascertainment, so the reported summaries should not be interpreted as a complete causal or comparative safety analysis.
In general, an immune-response endpoint is not identical to a clinical disease outcome. A proportion meeting a seroprotection or seroconversion definition describes a measured immune response, whereas prevention of disease is a different question requiring relevant clinical outcome evidence. The registry record describes the immune-response outcome but does not report its results or provide disease-prevention results.
The study's design and reporting thus permit a limited descriptive reading, not a claim of comparative efficacy or safety. The posted results include event counts and term-specific percentages, but do not report the primary endpoint results or statistical analyses. Additional protocol, laboratory, analysis and follow-up information is not reported in the registry record. Conclusions should remain within those boundaries.
13. Why This Trial Matters Statistically
This study illustrates how design determines the scope of statistical interpretation. The single-group, non-randomized structure can describe outcomes observed among enrolled infants, but it does not create a randomized treatment contrast. Even a precisely estimated proportion within a group would not, by itself, identify what would have occurred under a different intervention. That distinction is important when reading immunogenicity and safety summaries as evidence about an intervention.
The endpoint also shows why the outcome definition matters. The primary measure concerns seroprotection for four components and seroconversion for pertussis, at a specified post-vaccination time. These are component-specific immune-response outcomes, not a single general measure of clinical disease. Their interpretation requires both the observed estimates and information about the measurement definitions and analysis procedures. The registry record describes the intended measure but does not report its estimates.
Safety reporting raises a different statistical issue. Counts are presented by dose, and serious-event terms have associated percentages. Understanding those numbers requires clarity about denominators, repeat observations and overlap. The registry record does not provide all of that detail. This is a useful reminder that a numerical summary is only as interpretable as its population and event definitions.
Finally, the record distinguishes the study's design from hypothetical planning illustrations based on an observed effect. A planning calculation under assumed two-arm conditions is not evidence that the single-group study had a particular power or was designed to detect a comparative effect. Keeping design, endpoint, analysis and planning assumptions separate prevents descriptive evidence from being overstated.
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 primary limitation for interpreting the main study question is that component-specific immunogenicity results are not reported in the registry record. Although the endpoint, analysis population and intended confidence-interval level are described, the percentages and intervals needed to assess magnitude and precision are absent. Statistical analyses are also not reported.
The single-group, non-randomized design has no separate control group. It can describe observed outcomes in the enrolled group but cannot support a randomized comparison. The record states that masking was none, but does not detail who assessed outcomes or how laboratory and safety assessments were conducted. The relevance of unmasked assessment therefore cannot be fully judged.
Safety reporting is limited by the lack of detail on event definitions, attribution, follow-up, repeat events and overlap between listed terms. The registry record gives dose-specific at-risk and event counts, but does not establish whether the same subject could contribute to more than one dose group or event count. These limitations prevent interpreting the summaries as counts of unique affected participants or as comparative risks.
The analysis population excludes one subject described as a protocol violator, but the reason and impact of that exclusion are not reported. Missing-data methods, other analysis populations, multiplicity procedures and the statistical plan are also not reported in the registry record. Finally, the available information does not describe eligibility criteria in detail or provide the laboratory definitions needed to independently evaluate the immune-response thresholds. These gaps constrain both reproducibility and the scope of conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Quinvaxem for Vaccination Against Diphtheria, Pertussis, Tetanus, Hepatitis B and Diseases Caused by Haemophilus Influenzae Type B — NCT01362517.
- Registry record last updated 2013-09-09; status last verified 2013-08.
- Results first posted 2013-06-24.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a completed Phase 3 study of Quinvaxem in healthy Vietnamese infants, with enrollment of 131. The design was single-group, non-randomized and unmasked. Infants received three doses at 2, 3 and 4 months of age. The primary endpoint was seroprotection for diphtheria, tetanus, hepatitis B and Hib, and seroconversion for pertussis, assessed at 5 months.
The primary endpoint results and statistical analyses are not reported in the registry record. Safety observations are listed by dose, including serious and other adverse event counts and several serious-event terms with percentages. These are descriptive records without a randomized comparator. The primary analysis population excludes one protocol violator; further detail on missing data, multiplicity, event assessment and the statistical plan is not reported.