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 to Assess if Quinvaxem Can be Interchanged With Other Pentavalent Vaccines During Standard Childhood Vaccination (NCT01357720), a randomized phase 4 study. The primary outcome is Seroprotection Rate: Anti-PRP Antibodies.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01357720 |
| Phase | Phase 4 |
| Condition | Diphtheria, Pertussis, Tetanus |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 400 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Crucell Holland BV |
| Results posted | Yes |
2. Clinical Question
Population
Healthy infants receiving the standard childhood vaccination course at 6, 10 and 14 weeks of age. The primary result uses available observations at Visit 4, one month after the third vaccination.
Intervention
An initial dose of Tritanrix HB+Hib followed by Quinvaxem as the second and third doses.
Comparator
Quinvaxem for all three doses.
Primary question
Was the anti-PRP seroprotection rate after the mixed-vaccine course comparable with the rate after three Quinvaxem doses, as part of the study’s broader non-inferiority question about protection against the listed antibodies?
The registry describes a Phase IV, randomized, controlled study. Its stated objective was to assess interchangeability with respect to safety and immunogenicity. The primary endpoint reported in the results is the percentage of subjects whose anti-PRP antibody titer was at least 0.15 µg/mL, a threshold defined in the record as seroprotection.
The brief summary frames the broader question as whether the course beginning with Tritanrix HB+Hib is not inferior to three Quinvaxem doses for protection against anti-hepatitis B surface, anti-PRP, anti-diphtheria, anti-tetanus and anti-Bordetella pertussis antibodies. The posted primary result concerns anti-PRP only; it does not by itself answer the broader question for all listed antibodies.
3. Trial Design
This was a Phase IV, randomized, controlled, single-blind, parallel-group, monocentric study. The registry lists an enrollment of 400 and two vaccine regimens: Quinvaxem for all doses, and Tritanrix Hib/HepB followed by Quinvaxem. The study concerned healthy infants receiving the 6-, 10- and 14-week vaccination course.
The primary outcome was assessed one month after the third vaccination. The result is reported for available observations at Visit 4, with 197 observations in the Quinvaxem arm and 193 in the mixed-regimen arm. Those endpoint denominators differ from the safety denominators, which are reported as 200 in each group. The registry does not explain the difference between these denominators or provide a participant flow account.
Randomization and a parallel-group structure support a comparison between the two assigned regimens. Single-blind describes the masking designation in the registry, but the record does not specify which people were blinded or how masking was maintained. It identifies the study as monocentric but does not report the center’s name in the listed results.
The registry record does not report the randomization method, allocation concealment, the original sample-size justification, or the details of the planned statistical analysis. It describes the study’s objective as non-inferiority, but a non-inferiority margin is not reported in the registry record. Without that margin and the associated analysis details, the reported comparison should be read as the stated endpoint estimates rather than as a complete demonstration of the study’s broader objective.
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 | Tritanrix Hib/HepB + Quinvaxem |
|---|---|---|
| STARTED | 200 | 200 |
| COMPLETED | 198 | 195 |
| NOT COMPLETED | 2 | 5 |
Analysis population for the primary outcome, as defined in the registry: Available observations at Visit 4
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 | Tritanrix Hib/HepB + Quinvaxem | Total |
|---|---|---|---|---|
| Participants analysed | 200 | 200 | 400 | |
| Age, Categorical: <=18 years | Participants | 200 | 200 | 400 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age Continuous | weeks | 6.8 (SD 0.91) | 6.7 (SD 0.86) | 6.7 (SD 0.89) |
| Sex: Female, Male: Female | Participants | 101 | 105 | 206 |
| Sex: Female, Male: Male | Participants | 99 | 95 | 194 |
6. Primary Endpoint
The registry lists the primary outcome as Seroprotection Rate: Anti-PRP Antibodies, measured over 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 seroprotection rate for anti-PRP antibodies: the percentage of subjects with an anti-PRP titer of at least 0.15 µg/mL. It was measured one month after the third vaccination and is based on available observations at Visit 4. The registry labels the endpoint unit as percentage of subjects.
This is a binary endpoint at the participant level: each available observation is classified according to whether the titer reaches the stated threshold. A percentage is useful for communicating how commonly the defined antibody threshold was met in each vaccine group. It makes the group-level outcome easy to interpret, while the confidence interval conveys uncertainty around the estimated rate.
As a general statistical point, a prespecified antibody threshold turns a continuous laboratory measurement into a categorical outcome. That can be useful when the scientific question is framed around meeting a defined level, but it does not show the full distribution of antibody titers or how far individual values lie above or below the threshold. The registry does not report the underlying titers or other details of their distribution.
The broader study summary names protection against several antibodies, while the primary endpoint is specifically anti-PRP seroprotection. The record lists five outcome measures, but no secondary outcomes are posted in the registry record.
7. Results Posted in the Registry
- Tritanrix Hib/HepB + Quinvaxem: 100.0% (193/193) versus 100.0% (197/197) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.
Risk difference: Tritanrix Hib/HepB + Quinvaxem
95% CI: 0.0 to 0.0 percentage points
Recalculated from the posted summary statistics
8. Statistical Interpretation
The reported anti-PRP seroprotection rate is 100.0% in each arm. The 95% confidence interval is 98.1% to 100.0% for Quinvaxem and also 98.1% to 100.0% for Tritanrix Hib/HepB followed by Quinvaxem. The registry reports a risk-difference estimate of 0.0, with a 95% confidence interval from 0.0 to 0.0, and a p-value of 1.0.
These estimates describe the available observations at Visit 4. They show identical reported proportions in the two groups for this endpoint, with the reported intervals also identical. They do not establish that the regimens are equivalent for every clinically relevant outcome, nor do they establish non-inferiority under a specified margin. The non-inferiority margin and the detailed inferential plan are not reported in the registry record.
As a general statistical point, a p-value is a measure calculated under a particular statistical model and null hypothesis; it is not the probability that the null hypothesis is true. The p-value of 1.0 should therefore be read alongside the estimated rates and confidence intervals, not as proof that the regimens have identical effects in the wider population. In this record, the comparison estimate is reported at the same boundary values in both groups, but the registry does not provide enough analysis detail to explain how the comparison interval was obtained.
The endpoint denominators are 197 and 193, whereas the safety groups each have a denominator of 200. These are separate populations for separate outcomes; the registry does not report why the endpoint denominators differ from the safety denominators. The primary result therefore applies to the available observations identified for the endpoint and should not be assumed to include every participant enrolled.
The study’s broad objective included safety and immunogenicity across several antibody outcomes. The posted primary endpoint alone cannot establish the findings for anti-hepatitis B surface, anti-diphtheria, anti-tetanus or anti-Bordetella pertussis antibodies. Although the registry lists five outcome measures, no secondary outcome results are posted in the registry record. The reported anti-PRP finding is consequently narrow: it describes the observed threshold-based endpoint and its reported uncertainty, not the full set of objectives.
No recalculation is needed to describe the posted primary comparison, and the record does not flag a discrepancy between its results and a recalculated estimate. The result should be kept distinct from a claim that either regimen is clinically preferable or that interchangeability has been established. Those conclusions would require interpretation of the complete protocol, all relevant outcomes, and the prespecified non-inferiority framework, details that are not reported in the registry record.
9. Statistical Methods Explained
What does a percentage endpoint represent?
The endpoint classifies each available observation according to whether its anti-PRP titer is at least 0.15 µg/mL, then reports the percentage meeting that definition in each arm. This is a binary-outcome summary: it focuses on whether the threshold was reached, not on the numerical titer itself. The registry reports 100.0% in both groups, based on 197 available observations in the Quinvaxem group and 193 in the mixed-regimen group.
As a general statistical point, a proportion is a compact summary of how frequently an event or condition is observed within a group. Its interpretation depends on the definition of the event and on which observations enter the denominator. Here, the event is seroprotection according to the threshold in the registry, and the stated population is available observations at Visit 4. The record does not report the handling of missing endpoint measurements.
What is a risk difference?
A risk difference compares the two group proportions by subtracting one from the other. The registry reports a risk-difference estimate of 0.0 and a 95% confidence interval from 0.0 to 0.0. These are the posted comparison values; no additional arithmetic is needed to describe them. A difference of zero in the reported estimate means that the two reported percentages are the same at the displayed precision.
As a general statistical point, a risk difference expresses a contrast on the absolute scale of the outcome probability. It can be easier to interpret as an absolute comparison than a relative measure, particularly when the baseline rate is high or low. The registry does not state the scale or method used to derive the comparison interval, so the reported contrast should not be treated as a reconstruction of the full statistical analysis.
How should the confidence interval be read?
The arm-specific 95% confidence intervals run from 98.1% to 100.0% in both groups. In general, a confidence interval gives a range of values compatible with the observed data under the method used to construct it. It conveys sampling uncertainty, not a guarantee that the true rate lies inside the interval in this particular study. The registry does not report the interval method.
When all observed outcomes meet a binary threshold, the observed proportion is at its upper boundary. As a general statistical point, boundary estimates can make some standard comparison methods behave differently from methods used when both outcome categories are observed. The registry record does not identify the method used for the displayed confidence intervals or comparison. The identical intervals should therefore be reported as posted, without assuming they resolve every question about uncertainty or equivalence.
What does the p-value contribute?
The reported p-value is 1.0. In general, a p-value describes how compatible the data are with a specified null hypothesis under the analysis assumptions; it is not a measure of the size or importance of an effect. It is not the probability that the treatments are identical, and it does not establish non-inferiority. The null hypothesis, test, and assumptions used for this comparison are not reported in the registry record.
How does the study objective relate to the reported analysis?
The brief summary states a non-inferiority objective. A non-inferiority analysis generally compares an estimated treatment difference with a prespecified margin, representing the largest difference that would be accepted for the study question. This is a general description of the method, not a detail reported for this trial. The non-inferiority margin, analysis population defined for that purpose, and corresponding decision rule are not reported in the registry record.
The sample-size assumptions recorded for a planning illustration use a two-sided significance level of 0.05, equal allocation between arms and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. Such an illustration is a planning exercise and is not observed power. The original trial’s sample-size justification is not reported in the registry record. The record does not provide a basis for treating a planning calculation as evidence that the study was adequately powered for its original objective.
The registry lists five outcome measures and no posted secondary outcome results. It reports no analyses in the analysis listing. The methods for handling multiplicity, missing observations, and analysis populations beyond the stated available-observations population are not reported in the registry record. These omissions limit how fully the posted endpoint can be connected to the stated study objective.
10. Confidence Intervals and Precision
For anti-PRP seroprotection, both groups have a reported rate of 100.0%. The 95% confidence interval is 98.1% to 100.0% for each group. The comparison is reported as a risk difference of 0.0, with a 95% confidence interval of 0.0 to 0.0. The p-value is 1.0.
In general, a confidence interval describes uncertainty around an estimate under a specified method. The arm-specific intervals indicate that the data are compatible with rates below 100.0% as well as the upper boundary. The displayed endpoints are rounded, so they should be interpreted at the precision shown rather than as exact limits on the underlying population rates. The interval method is not reported in the registry record.
The reported risk-difference interval has no displayed width. That is an unusual-looking feature of the posted comparison, but the registry does not report the calculation method or explain how the interval was obtained. It is therefore important to distinguish the posted interval from a general expectation about the uncertainty of a difference in binary outcomes. The values should be quoted as the registry reports them, not interpreted as proof of exact equality.
The endpoint is based on available observations at Visit 4, and its arm denominators are 197 and 193. The safety denominators are 200 in each group. The registry record does not explain this difference or report how missing endpoint observations were handled. Precision statements apply to the observed endpoint population as defined in the record, and uncertainty from missing or unobserved measurements cannot be evaluated from the posted information.
As a general statistical point, confidence intervals describe one component of precision. They do not address bias from missing data, representativeness, outcome measurement, or whether the analysis matches the original objective. Those considerations remain relevant even when an interval appears narrow.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures, but the primary result described in detail is anti-PRP seroprotection. No secondary outcome results are posted in the registry record. The record does not report whether statistical testing was planned across multiple antibody outcomes, how any multiplicity would be handled, or whether a hierarchy of endpoints was specified.
As a general statistical point, testing multiple outcomes or comparisons can increase the chance of obtaining at least one apparently notable result by chance. A prespecified testing strategy can clarify how results should be interpreted across outcomes. Because that strategy is not reported in the registry record, the anti-PRP comparison cannot be placed within a documented multiplicity framework.
The primary endpoint population is described as available observations at Visit 4. The denominators are 197 for Quinvaxem and 193 for the mixed regimen. The safety denominators are 200 in each group. The registry record does not explain the differences or provide a participant flow account, so the reasons observations were not included in the endpoint denominators are not reported in the registry record.
The registry does not report a missing-data method, imputation approach, sensitivity analysis, or the analysis populations used for the non-inferiority question. As a general statistical point, missing outcome data can affect an estimated rate if the observed participants differ systematically from those without measurements. Without information on the extent, reasons and handling of missing data, the effect of missing observations cannot be assessed.
The analysis listing reports no analyses, while the outcome listing includes five measures. The statistical model, test, confidence-interval method, and prespecified analysis plan are not reported in the registry record. These gaps do not alter the posted estimates, but they limit assessment of how the estimates were selected, calculated and interpreted relative to the study objective.
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 |
|---|---|---|---|
| Quinvaxem | 0 | 200 | 0.0% |
| Tritanrix Hib/HepB + Quinvaxem | 2 | 200 | 1.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Quinvaxem | 180 of 200 |
| Tritanrix Hib/HepB + Quinvaxem | 180 of 200 |
Most frequent serious adverse event terms
| Event term | Organ system | Quinvaxem | Tritanrix Hib/HepB + Quinvaxem |
|---|---|---|---|
| Viral encephalitis | Infections and infestations | 0 of 200 | 1 of 200 |
| Idiopathic thrombocytopenic purpura | Blood and lymphatic system disorders | 0 of 200 | 1 of 200 |
| Pneumonia | Infections and infestations | 0 of 200 | 1 of 200 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 0 of 200 | 1 of 200 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Quinvaxem | Tritanrix Hib/HepB + Quinvaxem |
|---|---|---|---|
| Injection site pain | General disorders | 137 of 200 | 157 of 200 |
| Pyrexia | General disorders | 88 of 200 | 95 of 200 |
| Injection site induration | General disorders | 74 of 200 | 82 of 200 |
| Injection site erythema | General disorders | 59 of 200 | 54 of 200 |
| Upper respiratory tract infection | Infections and infestations | 46 of 200 | 54 of 200 |
| Nasopharyngitis | Infections and infestations | 7 of 200 | 9 of 200 |
| Rhinitis | Infections and infestations | 7 of 200 | 7 of 200 |
| Pneumonia | Infections and infestations | 7 of 200 | 3 of 200 |
Serious events with the highest arm-level rate: viral encephalitis (0.5%), idiopathic thrombocytopenic purpura (0.5%), pneumonia (0.5%), respiratory failure (0.5%).
The safety information uses denominators of 200 in each group, distinct from the available-observation denominators used for the primary endpoint. The registry reports 0 serious adverse events in the Quinvaxem group and 2 in the Tritanrix Hib/HepB followed by Quinvaxem group. Death counts are not reported in the registry record.
The registry lists Viral encephalitis, Idiopathic thrombocytopenic purpura, Pneumonia and Respiratory failure among the serious-event terms, each with a reported frequency of 0.5%. The listed terms are not linked to a particular treatment group in the record information summarized for these results, so the term frequencies should not be assigned to an arm.
As a general statistical point, serious adverse-event counts describe events recorded under the study’s safety definitions and observation procedures. They do not by themselves establish that an event was caused by a vaccine. The registry information does not provide event narratives, relatedness assessments, timing, duration, or a detailed safety-analysis method. The group counts should therefore be read as descriptive safety data, not as a causal comparison or a complete account of tolerability.
13. What the Result Does, and Does Not, Mean
The posted primary result is a comparison of anti-PRP seroprotection at the stated threshold, one month after the third vaccination. Both groups have a reported rate of 100.0%, and both have a reported 95% confidence interval of 98.1% to 100.0%. The registry’s risk-difference estimate is 0.0, with a confidence interval from 0.0 to 0.0 and a p-value of 1.0.
Those values describe the observed endpoint population. They do not establish that the underlying rates are exactly equal, that all antibody responses are the same, or that the mixed regimen meets a specified non-inferiority criterion. The non-inferiority margin and detailed statistical plan are not reported in the registry record. The endpoint result also does not establish outcomes beyond the anti-PRP measure.
The trial’s broader stated question concerned protection against anti-hepatitis B surface, anti-PRP, anti-diphtheria, anti-tetanus and anti-Bordetella pertussis antibodies, as well as safety. The registry lists five outcome measures, but no secondary outcome results are posted. The primary result should not be generalized to those other outcomes without their results and relevant analyses.
The safety counts are reported separately, with different denominators from the endpoint observations. The registry does not provide enough detail to attribute the listed serious-event terms to a treatment arm or to make a causal interpretation. Results for this endpoint are also based on available observations, and the handling of missing measurements is not reported.
As a general statistical point, a study finding and a clinical conclusion are not interchangeable. This result characterizes the observed threshold outcome and the uncertainty reported for it. It does not provide medical advice or a basis for an individual vaccination decision.
14. Why This Trial Matters Statistically
This trial illustrates how a clinical question about vaccine interchangeability can be expressed as a defined immunogenicity endpoint. The primary measure converts anti-PRP antibody titers into a threshold-based seroprotection rate. That makes the endpoint directly interpretable as the percentage meeting the registry’s specified criterion, while also making the result dependent on the threshold and the observations available for analysis.
The comparison also highlights the distinction between an observed equality of percentages and a formal non-inferiority conclusion. Both arms have a displayed rate of 100.0%, and the registry reports a risk difference of 0.0. But a non-inferiority interpretation depends on the prespecified margin and analysis plan, neither of which is reported in the registry record. Statistical objectives require their own decision criteria; matching point estimates alone do not document that those criteria were met.
The record also shows why denominators matter. The endpoint uses available observations at Visit 4, whereas safety results use 200 in each group. Those denominators answer different questions and should not be treated as interchangeable. The reasons for the difference are not reported, making transparent participant flow and missing-data methods important for interpretation.
Finally, a broad study objective and a posted primary result are not the same thing. The study summary names several antibodies, but the posted primary result is anti-PRP and no secondary outcome results are listed. Careful reading keeps the conclusion aligned with the specific outcome, population and analysis actually described, rather than extending one endpoint to the full set of study aims.
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.
- Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.
The registry record does not report the non-inferiority margin, the original sample-size justification, or the detailed statistical analysis plan. These omissions limit assessment of whether the primary comparison was designed and analyzed according to a prespecified non-inferiority framework.
The primary endpoint is based on available observations at Visit 4, with 197 observations in the Quinvaxem arm and 193 in the mixed-regimen arm. Safety denominators are 200 in each group. The registry does not explain why the denominators differ, describe participant flow, or report how missing endpoint measurements were handled. The effect of missing observations therefore cannot be assessed from the registry record.
The endpoint is threshold-based and reports whether anti-PRP titers reached at least 0.15 µg/mL. The registry does not report the distribution of individual titers, so the result does not describe the magnitude of responses among subjects meeting the threshold.
The registry lists five outcome measures, but no secondary outcome results are posted. Consequently, the posted primary outcome cannot establish the results for the other antibody outcomes named in the study summary. Multiplicity procedures and the relationship between outcome measures are not reported.
The comparison confidence interval is reported as 0.0 to 0.0 for a risk difference of 0.0, but the interval method is not reported. This prevents an independent assessment of how the comparison uncertainty was calculated. Safety information is also limited: death counts are not reported, and serious-event terms are not linked to treatment groups in the listed information. The record does not provide detailed event descriptions or relatedness assessments.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Study to Assess if Quinvaxem Can be Interchanged With Other Pentavalent Vaccines During Standard Childhood Vaccination — NCT01357720.
- Registry record last updated 2013-09-09; status last verified 2013-08.
- Results first posted 2013-05-22.
- 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
NCT01357720 is a completed Phase IV, randomized, controlled, single-blind, parallel, monocentric study sponsored by Crucell Holland BV. It enrolled 400 healthy infants and compared Quinvaxem for all three doses with Tritanrix Hib/HepB followed by Quinvaxem during the 6-, 10- and 14-week vaccination course.
The primary endpoint was anti-PRP seroprotection one month after the third vaccination, defined as an anti-PRP titer of at least 0.15 µg/mL. The reported rates were 100.0% in both groups, with 95% confidence intervals of 98.1% to 100.0%. The reported risk difference was 0.0, with a 95% confidence interval of 0.0 to 0.0 and a p-value of 1.0.
The endpoint uses available observations at Visit 4. The registry lists five outcome measures but no posted secondary results. The non-inferiority margin, missing-data handling, and detailed statistical plan are not reported in the registry record. Safety results list 0 serious adverse events in the Quinvaxem group and 2 in the mixed-regimen group, using denominators of 200 in each group.