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 Safety of DTaP-IPV-Hep B-PRP~T Combined Vaccine Compared to Tritanrix-HepB/Hib™ and OPV Given at Age 2, 4, and 6 Months. (NCT00313911), a randomized phase 3 study. The primary outcome is Number of Participants With High Fever Observed After Either DTaP-IPV-Hep B-PRP~T or Tritanrix Hep B/Hib™ + Placebo or Tritanrix-Hep B/Hib™ + Placebo Injection..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00313911 |
| Phase | Phase 3 |
| Condition | Diphtheria, Tetanus, Pertussis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 2133 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanofi Pasteur, a Sanofi Company |
| Results posted | Yes |
2. Clinical Question
Population
Latin American infants vaccinated at 2, 4, and 6 months of age. The registry record reports enrollment of 2133 and describes the primary safety population as enrolled and vaccinated participants.
Intervention
DTaP-IPV-Hep B-PRP~T, a combined vaccine, administered at the scheduled infant vaccinations.
Comparator
Tritanrix-Hep B/Hib™ together with oral polio vaccine (OPV). The registry record describes the comparison group as receiving these vaccines at the same scheduled ages.
Primary question
Whether DTaP-IPV-Hep B-PRP~T was associated with a higher incidence of high fever than the comparator regimen after any of the three vaccinations. High fever was defined as rectal temperature equivalent to ≥ 39.6ºC, assessed from Day 0 up to Day 7 post-injection.
The primary question is comparative: it concerns whether high fever occurred more often with the combined vaccine than with the comparator regimen during the specified period after vaccination. It is not a question about all fever, all adverse reactions, or longer-term health outcomes. The registry’s brief summary also identifies solicited reactions during the first 7 days after each injection, adverse events and reactions during the first 30 days after each injection, serious adverse events during the trial, and immune response to Hepatitis B antigen as other study aims.
The registry record does not report the primary-outcome counts or a statistical comparison. It therefore does not establish from the posted results whether the high-fever incidence differed between regimens, or how precisely any difference was estimated. A formal margin for interpreting the objective of demonstrating no higher incidence is not reported in the registry record.
3. Trial Design
This was a randomized, single-masked, parallel-group Phase 3 study sponsored by Sanofi Pasteur, a Sanofi Company. The registry record describes the study as completed, with a start date of 2006-07 and primary completion in 2008-01. The official title identifies a large-scale safety study in Latin American infants. Enrollment was 2133.
The intervention group received DTaP-IPV-Hep B-PRP~T. The comparator group received Tritanrix-Hep B/Hib™ and OPV. Vaccinations were scheduled at 2, 4, and 6 months of age. The record does not describe the practical details of masking, such as which people were masked or how masking was maintained. It also does not report the randomization method or allocation concealment.
The primary outcome concerned participants with high fever after vaccination. The stated assessment period was Day 0 up to Day 7 post-injection, and the fever threshold was a rectal temperature equivalent to ≥ 39.6ºC. The registry specifies that the primary safety population included enrolled and vaccinated participants. It further notes that group totals were adjusted for a participant who received a vaccine assigned to the other group.
Other stated aims included solicited adverse reactions during the first 7 days after each injection, adverse events and reactions during the first 30 days after each injection, serious adverse events during the trial, and immune response to Hepatitis B antigen. Secondary outcomes listed antibody geometric mean titers, the percentage reaching a seroprotection threshold, and participants reporting at least one solicited injection-site or systemic reaction after each vaccination. The registry record does not report a detailed protocol, the precise analysis methods for these outcomes, or results for the primary fever comparison.
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: A total of 2133 participants who met the inclusion and exclusion criteria were enrolled and vaccinated.
Overall Study
| Stage | DTaP-IPV-Hep B-PRP~T | Tritanrix-Hep B/Hib™ + OPV |
|---|---|---|
| STARTED | 1422 | 711 |
| COMPLETED | 1328 | 670 |
| NOT COMPLETED | 94 | 41 |
Reasons for not completing this period:
| Reason | DTaP-IPV-Hep B-PRP~T | Tritanrix-Hep B/Hib™ + OPV |
|---|---|---|
| Serious adverse event | 6 | 1 |
| Adverse Event | 2 | 3 |
| Protocol Violation | 19 | 10 |
| Lost to Follow-up | 27 | 14 |
| Withdrawal by Subject | 39 | 12 |
| Did not meet age criteria | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: The occurrence of high fever was assessed for all enrolled and vaccinated participants, intent-to-treat (safety) population. Total numbers of participants in each group adjusted for the participant that got a vaccine assigned for the other group.
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 | DTaP-IPV-Hep B-PRP~T | Tritanrix-Hep B/Hib™ + OPV | Total |
|---|---|---|---|---|
| Participants analysed | 1422 | 711 | 2133 | |
| Age, Categorical: <=18 years | Participants | 1422 | 711 | 2133 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous: Age Continuous | Months | 1.89 (SD 0.195) | 1.88 (SD 0.197) | 1.88 (SD 0.196) |
| Sex: Female, Male: Female | Participants | 706 | 344 | 1050 |
| Sex: Female, Male: Male | Participants | 716 | 367 | 1083 |
| Region of Enrollment: Mexico | Participants | 712 | 355 | 1067 |
| Region of Enrollment: Peru | Participants | 710 | 356 | 1066 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With High Fever Observed After Either DTaP-IPV-Hep B-PRP~T or Tritanrix Hep B/Hib™ + Placebo or Tritanrix-Hep B/Hib™ + Placebo Injection., measured over Day 0 up to Day 7 post-injection.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with high fever after vaccination. The registry defines high fever as rectal temperature equivalent to ≥ 39.6ºC and specifies an observation period from Day 0 up to Day 7 post-injection. The outcome is expressed as a number of participants, rather than as a continuous temperature measurement or a count of every fever episode.
This type of endpoint focuses on a clinically defined safety event within a stated period after exposure. Counting participants with the event can make the group comparison easier to interpret than comparing temperatures alone: it addresses how many participants crossed the specified threshold. It also means that the endpoint does not describe how far above the threshold a temperature was, how long fever lasted, or whether an individual experienced repeated episodes. Those details are not reported in the registry record.
The study objective was to demonstrate that the combined vaccine did not induce a higher incidence of high fever than the comparator regimen after any of the three vaccinations. That wording makes the direction of the safety concern explicit. However, the registry record does not state a margin for deciding what increase would count as acceptably small, nor does it provide event counts or a comparative estimate. As a result, the endpoint definition is available, but the primary question cannot be resolved from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the study rationale and endpoint definition, but it does not give a result for the primary high-fever comparison. In particular, there are no primary-outcome event counts, estimates of the difference between groups, confidence intervals, or p-values in the record. The primary outcome is marked as having several categories or time points and is not reduced to a single comparison. Accordingly, no conclusion about the relative incidence of high fever can be drawn from the registry information presented.
The record does list adverse-event figures. For serious adverse events, it reports 91 affected participants among 1423 at risk in the DTaP-IPV-Hep B-PRP~T group and 46 among 710 at risk in the Tritanrix-Hep B/Hib™ + OPV group. For other adverse events, the corresponding figures are 945 among 1423 and 576 among 710. These are descriptive safety counts. The record does not provide uncertainty intervals or a statistical comparison for these figures, so they should not be treated as proof of a difference or equivalence between regimens.
The listed serious adverse-event terms include gastroenteritis at 2.5%, bronchopneumonia at 0.9%, bronchiolitis at 0.8%, bronchial obstruction at 0.6%, pneumonia at 0.4%, and head injury at 0.4%. These percentages describe the terms as recorded; the registry information does not provide enough detail to determine from these entries alone how the percentages were calculated or how the listed terms relate to the overall serious-event counts. Deaths are not reported in the registry record.
The study objective was framed around detecting no higher high-fever incidence, but the record does not report a non-inferiority margin or the primary analysis result. Lack of a reported result is not evidence that groups were alike; it means the comparative question is unanswered by the posted registry data. Similarly, the presence of event counts in other safety categories does not substitute for the missing primary analysis.
The record also names immune-response outcomes, including geometric mean titers and seroprotection. It does not give their results. The appropriate reading is therefore limited: the registry identifies the design, population, outcome definitions, and some adverse-event summaries, but it does not report enough comparative outcome information to quantify the primary safety finding or assess the precision of a treatment-group contrast.
9. Statistical Methods Explained
The study’s randomized, parallel-group design assigns participants to one of the vaccine regimens for comparison. Random allocation can, in general, reduce systematic differences between groups at the start of a trial. That benefit depends on how allocation is implemented and on how participants are followed and analyzed. The registry record identifies randomization but does not report the sequence-generation method, allocation concealment, or detailed handling of participants after assignment.
What does a participant count represent?
The primary endpoint is a binary event at the participant level: a participant either met the high-fever definition within the specified observation window or did not. A binary outcome can be summarized by the number of participants with the event and the number assessed. Comparing event proportions between groups is a common way to describe such outcomes. Those proportions and a measure of their uncertainty would be needed to characterize the size and precision of a between-group difference. The registry record gives the endpoint definition but not the primary event counts or comparison.
The registry identifies the primary safety population as all enrolled and vaccinated participants, described as intent-to-treat (safety). It also notes an adjustment to group totals for a participant who received a vaccine assigned to the other group. This indicates that the recorded group totals reflect that noted assignment issue. The record does not explain more fully how the participant was classified in each analysis or whether any other deviations from assigned treatment occurred.
Why does the observation period matter?
An adverse event can only contribute to a defined endpoint if it occurs within the endpoint’s observation window and meets the event definition. Here, the primary fever period is Day 0 up to Day 7 after injection, and the threshold is rectal temperature equivalent to ≥ 39.6ºC. Results from this window would not by themselves describe events outside it. The brief summary also names solicited reactions during the first 7 days and adverse events and reactions during the first 30 days after each injection. Those are distinct safety assessments, and the registry record does not provide their full results.
How should uncertainty be understood?
In general, a confidence interval describes a range of values compatible with the observed data under the statistical model and gives readers information about precision. A narrow interval indicates more precise estimation than a wide interval, while an interval spanning a range of plausible effects can leave the direction or size uncertain. A p-value, in general, measures how compatible the data are with a specified null hypothesis under a statistical model; it does not measure the probability that a treatment works or that the null hypothesis is true. No confidence interval or p-value for the primary comparison is reported in the registry record.
The study objective was to demonstrate that the combined vaccine did not induce a higher incidence of high fever. In general, a formal non-inferiority assessment requires a prespecified margin that defines the largest increase considered acceptable, along with an estimate and uncertainty interval that can be judged against that margin. The margin and the result needed for that assessment are not reported in the registry record. The objective wording alone is not enough to establish that a formal non-inferiority analysis was performed.
What do the other safety summaries add?
The adverse-event entries give counts of participants affected and numbers at risk for serious and other adverse events. These are useful descriptive summaries, but they do not indicate by themselves whether a difference between treatment groups is more than could reasonably arise through sampling variation. For that interpretation, a comparative estimate and uncertainty assessment would be needed. When events can occur more than once per participant, counts of participants affected also differ from counts of all events; the registry entries do not provide a full event-level account.
In general, over-dispersion can matter when a statistical model assumes that observations vary less than they actually do. It can make standard errors too small and intervals too narrow if not addressed. The registry record does not identify a model for the primary outcome or describe any assessment of over-dispersion, so no claim can be made about whether this issue arose or how it was handled.
The record describes a sample-size planning illustration as based on a fraction of the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. It states that non-time-to-event planning figures are expressed as participants per arm. The registry record does not report a trial-specific sample-size justification or the resulting planning figures for this primary comparison. Such planning illustrations are not observed power and do not replace an analysis of the trial results.
10. Multiplicity, Missing Data and Analysis Populations
The registry describes several study objectives: high fever after vaccination, solicited reactions, adverse events and reactions, serious adverse events, and immune response to Hepatitis B antigen. It also lists secondary measures of antibody geometric mean titers, seroprotection, and solicited injection-site or systemic reactions. These questions involve different outcomes and observation periods, so their results would need to be interpreted according to their own definitions.
When multiple outcomes or repeated assessments are examined, the chance of observing at least one apparently unusual result can increase. Statistical methods can address multiplicity, but whether an adjustment is appropriate depends on the study’s aims and analysis plan. Multiplicity adjustment or a prespecified testing hierarchy is not reported in the registry record. The primary outcome is flagged as involving several categories or time points rather than being reduced to a single comparison.
The registry identifies the primary safety population as enrolled and vaccinated participants and notes that group totals were adjusted for a participant who received a vaccine assigned for the other group. The handling of missing temperature observations, incomplete follow-up, withdrawals, or missing immunogenicity measurements is not reported in the registry record. It is therefore not possible to assess whether missingness differed between groups or whether any sensitivity analyses were conducted.
The record reports no analysis entries. A detailed statistical analysis plan, including the planned comparison, treatment of missing data, and multiplicity strategy, is not reported in the registry record. These omissions limit the ability to judge how completely the posted safety summaries represent all planned analyses.
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 |
|---|---|---|---|
| DTaP-IPV-Hep B-PRP~T | 91 | 1423 | 6.4% |
| Tritanrix-Hep B/Hib™ + OPV | 46 | 710 | 6.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5.00% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| DTaP-IPV-Hep B-PRP~T | 945 of 1423 |
| Tritanrix-Hep B/Hib™ + OPV | 576 of 710 |
Most frequent serious adverse event terms
| Event term | Organ system | DTaP-IPV-Hep B-PRP~T | Tritanrix-Hep B/Hib™ + OPV |
|---|---|---|---|
| Gastroenteritis | Infections and infestations | 21 of 1423 | 18 of 710 |
| Bronchiolitis | Infections and infestations | 12 of 1423 | 6 of 710 |
| Bronchopneumonia | Infections and infestations | 13 of 1423 | 3 of 710 |
| Bronchial Obstruction | Respiratory, thoracic and mediastinal disorders | 9 of 1423 | 1 of 710 |
| Pneumonia | Infections and infestations | 5 of 1423 | 3 of 710 |
| Pneumonia viral | Infections and infestations | 6 of 1423 | 2 of 710 |
| Head Injury | Injury, poisoning and procedural complications | 2 of 1423 | 3 of 710 |
| Febrile Convulsion | Nervous system disorders | 4 of 1423 | 1 of 710 |
| Diarrhoea | Gastrointestinal disorders | 2 of 1423 | 0 of 710 |
| Gastroenteritis rotavirus | Infections and infestations | 1 of 1423 | 1 of 710 |
Most frequent non-serious adverse event terms
| Event term | Organ system | DTaP-IPV-Hep B-PRP~T | Tritanrix-Hep B/Hib™ + OPV |
|---|---|---|---|
| Solicited Irritability post-dose 1 | General disorders | 945 of 1410 | 576 of 703 |
| Solicited Injection Site Pain Post-dose 1 | General disorders | 831 of 1410 | 574 of 703 |
| Solicited Crying Post-dose 1 | Psychiatric disorders | 800 of 1411 | 564 of 703 |
| Solicited Pyrexia Post-dose 2 | General disorders | 675 of 1411 | 457 of 703 |
| Nasopharyngitis | Infections and infestations | 742 of 1411 | 353 of 703 |
| Solicited Somnolence Post-dose 1 | Nervous system disorders | 635 of 1410 | 375 of 703 |
| Solicited Injection site Erythema Post-dose 3 | General disorders | 587 of 1410 | 340 of 703 |
| Solicited Injection Site Swelling Post-dose 3 | General disorders | 400 of 1408 | 323 of 703 |
| Solicited Anorexia Post-dose 1 | Metabolism and nutrition disorders | 388 of 1410 | 278 of 703 |
| Pharyngitis | Infections and infestations | 395 of 1411 | 161 of 703 |
Serious events with the highest arm-level rate: gastroenteritis (2.5%), bronchopneumonia (0.9%), bronchiolitis (0.8%), bronchial obstruction (0.6%), pneumonia (0.4%).
The registry lists serious adverse events in 91 participants among 1423 at risk in the DTaP-IPV-Hep B-PRP~T group and 46 among 710 at risk in the Tritanrix-Hep B/Hib™ + OPV group. It lists other adverse events in 945 participants among 1423 at risk and 576 among 710, respectively. The figures describe participants affected, not necessarily the total number of event episodes. The registry does not provide a comparative estimate or uncertainty interval for these entries.
The listed serious-event terms and percentages are gastroenteritis at 2.5%, bronchopneumonia at 0.9%, bronchiolitis at 0.8%, bronchial obstruction at 0.6%, pneumonia at 0.4%, and head injury at 0.4%. The registry record does not clarify the denominator or all counting details for these term-specific percentages. They should be read as descriptive entries, not as comparative treatment effects.
Deaths are not reported in the registry record. The absence of a reported death figure should not be interpreted as a reported count of zero. More generally, these safety summaries do not establish that either regimen caused or prevented the listed events, and they do not answer the primary high-fever question.
12. What the Result Does, and Does Not, Mean
The trial asks a focused safety question: whether high fever was more frequent after DTaP-IPV-Hep B-PRP~T than after Tritanrix-Hep B/Hib™ plus OPV in Latin American infants vaccinated at 2, 4, and 6 months of age. The registry defines high fever and the period in which it was assessed. It also identifies the randomized, single-masked, parallel-group design and the primary safety population.
Those design details explain what the primary comparison was intended to assess, but the registry record does not report the event counts or comparative estimate. It therefore cannot show how large any difference was, which group had more high-fever events, or how precisely the comparison was estimated. It also does not report a margin for judging the stated objective of demonstrating no higher incidence. The posted information cannot establish that the regimens had similar high-fever incidence.
The serious and other adverse-event counts provide additional descriptive safety information. They can help readers understand the scale of reported events in each group, but without comparative estimates and uncertainty measures they do not establish a treatment-group difference. Term-specific percentages likewise do not explain causation. Deaths are not reported in the registry record.
The registry also lists immune-response outcomes and other safety assessments, but their results are not reported in the information available. Consequently, the record does not support conclusions about antibody response, seroprotection, the full range of solicited reactions, or the complete safety profile. The study’s scope is also limited to its infant population, regimens, and follow-up periods as described in the record; it does not answer questions beyond those settings.
In statistical terms, an outcome definition and a study design are not substitutes for reported results. The record makes the intended question clear and gives selected safety counts, yet does not provide the primary comparison needed to quantify or assess the precision of the result. The appropriate conclusion is that the registry record documents the study’s purpose and selected safety data, while leaving the central comparative high-fever finding unreported.
13. Why This Trial Matters Statistically
This study illustrates why a clearly stated endpoint and a reported effect estimate are both needed for interpreting a clinical trial. The registry specifies a high-fever threshold, the post-injection assessment period, the infant vaccination schedule, and the two regimens being compared. Those details define the clinical question and help distinguish the primary safety outcome from the other listed assessments.
The comparison is framed around whether one regimen induces a higher incidence of a safety event. That type of question depends on more than a statement of intent: readers need the event counts, a comparative estimate, and information about its precision. If the objective is to support a claim of no meaningful increase, the margin defining that claim is also important. The registry record does not report the primary comparison or that margin, leaving the main statistical question unresolved.
The listed serious and other adverse-event data also show the importance of distinguishing descriptive summaries from comparative evidence. Counts and term-specific percentages describe reported events, but they do not by themselves quantify uncertainty or establish a causal relationship. Reporting denominators, analysis populations, definitions, and uncertainty measures supports a more complete assessment.
Finally, the record identifies several safety and immune-response aims. When a trial has multiple outcomes and assessments, readers benefit from knowing which analyses were prespecified, how missing observations were handled, and whether multiplicity was considered. Those details are not reported in the registry record. The study is statistically informative as an example of a well-defined comparative safety question whose registry entry does not include the primary result needed to answer it.
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 main trial-specific limitation is the absence of the primary high-fever result. The registry record gives a definition and timeframe but not group event counts, a comparative estimate, a confidence interval, or a p-value. The primary outcome is marked as involving several categories or time points and is not reduced to a single comparison. The stated objective cannot therefore be evaluated from the posted registry information.
The formal criterion for concluding that the combined vaccine did not induce a higher incidence is also unclear: a non-inferiority margin is not reported in the registry record. The randomization method, allocation concealment, practical masking details, and detailed statistical analysis plan are not reported either. These omissions prevent a full assessment of the design and analysis choices.
For the safety summaries that are available, the record does not report comparative uncertainty measures or clarify all counting and denominator details for the serious adverse-event terms. It does not report deaths. Handling of missing observations, withdrawals, and other departures from assigned treatment beyond the noted group-total adjustment is not described. Multiplicity methods are not reported despite the range of stated outcomes and assessments.
The registry lists immune-response and other safety outcomes, but does not provide their results. The available information is thus incomplete for assessing the study’s overall safety and immunogenicity findings. These limitations concern what is reported in the registry record and do not establish that additional analyses were not performed elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety of DTaP-IPV-Hep B-PRP~T Combined Vaccine Compared to Tritanrix-HepB/Hib™ and OPV Given at Age 2, 4, and 6 Months. — NCT00313911.
- Registry record last updated 2014-04-21; status last verified 2014-04.
- Results first posted 2012-11-19.
- 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
NCT00313911 is a completed randomized, single-masked, parallel-group Phase 3 safety study sponsored by Sanofi Pasteur, a Sanofi Company. It enrolled 2133 participants and compared DTaP-IPV-Hep B-PRP~T with Tritanrix-Hep B/Hib™ plus OPV in Latin American infants vaccinated at 2, 4, and 6 months of age.
The primary question concerned participants with high fever, defined as rectal temperature equivalent to ≥ 39.6ºC from Day 0 up to Day 7 post-injection. The registry record also lists other safety and Hepatitis B immune-response objectives. It reports serious and other adverse-event counts, but does not report the primary high-fever comparison or results for the listed immune-response outcomes. Missing-data methods, multiplicity handling, and a formal margin for the primary objective are not reported in the registry record.