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 Consistency & Immunogenicity Study of 3 Lots of GSK's Hib Conjugate Vaccine Versus ActHIB & Pentacel in Healthy Infants (NCT01000974), a randomized phase 3 study. The primary outcome is Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to (≥) 0.15 Microgram Per Milliliter (µg/mL) and ≥ 1.0 µg/mL.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01000974 |
| Phase | Phase 3 |
| Condition | Haemophilus Influenzae Type b |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 4003 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Healthy infants, male or female, between and including 6 and 12 weeks of age at the first vaccination. The primary analysis population was the Primary According-to-Protocol cohort for immunogenicity, defined by receipt of three vaccine doses and availability of assay results for antibodies against at least one antigen at the specified post-vaccination blood draw.
Intervention
GSK Biologicals’ Hib conjugate vaccine, identified in the registry as GSK 208108 and as Hiberix in the group description. The study also assessed consistency across three vaccine lots. The primary series was given at 2, 4 and 6 months of age, with a booster phase described in the registry.
Comparator
The primary description compares Hiberix with ActHIB, with both co-administered with Pediarix, Prevnar13 and Rotarix. Pentacel was a further comparator group in the study. The exact schedule and co-administered products for every phase are not fully reported in the registry record.
Primary question
After the primary vaccination series, did the immune response to Hib, measured by anti-PRP antibody concentrations at or above the stated thresholds, support the registry’s stated non-inferiority comparison of Hiberix with ActHIB? The study also aimed to assess lot-to-lot consistency and safety. Numerical results for the primary comparison are not reported in the registry record.
The study addressed a practical comparison in infant vaccination: immune responses to a Hib conjugate vaccine when administered alongside other vaccines, compared with responses in groups receiving licensed Hib-containing products. The registry describes three Hiberix lots and a pooled Hiberix group. This pooling is relevant because the stated objective includes consistency among lots, but the record does not provide lot-specific numerical estimates in the registry record for this analysis.
The primary endpoint counts participants whose anti-polyribosylribitol phosphate (anti-PRP) antibody concentrations meet either of two thresholds. Those thresholds represent different levels of measured antibody concentration; the endpoint is not a direct clinical outcome. The stated primary comparison concerns Hiberix versus ActHIB after three primary doses. Pentacel is named as a comparator in the study title and design, but the primary endpoint description does not define the main non-inferiority comparison as Hiberix versus Pentacel.
The registry also describes a booster phase and additional objectives involving safety, concomitant vaccine administration and immunogenicity. The precise primary question can therefore be distinguished from the study’s broader aims: the primary endpoint concerns the proportion meeting anti-PRP concentration thresholds after the primary series, while the broader study encompasses lot consistency, other immune responses and safety. The endpoint’s numerical group results, uncertainty intervals and test results are not reported in the registry record.
3. Trial Design
This was a Phase III, randomized, double-blind, parallel-group study sponsored by GlaxoSmithKline. It is recorded as completed. The registry lists enrollment of 4003. The study began on 2010-06-18, and primary completion was recorded on 2011-11-18. The study enrolled healthy infants between and including 6 and 12 weeks of age at the first vaccination.
The study compared GSK Biologicals’ Hib conjugate vaccine, identified as GSK 208108 and Hiberix in the group description, with ActHIB and Pentacel. Its objectives included evaluating safety, demonstrating lot-to-lot consistency, addressing concomitant vaccine administration, and comparing the GSK vaccine with the licensed Hib products. The registry describes a primary and a booster phase, with vaccination at 2, 4, 6 and 15-18 months of age in the official title.
For the Hiberix group, the registry describes pooled recipients of three different Hiberix lots and co-administration with Pediarix and Prevnar13 at 2, 4 and 6 months. The ActHIB group description also specifies co-administration with Pediarix and Prevnar13 at those ages, and Rotarix at 2 and 4 months. The Pentacel group description names Prevnar13 and Engerix-B as co-administered products and also refers to Rotarix. Some arm-description text is incomplete in the registry record, so not every group’s full schedule can be reconstructed from it.
Randomization assigns participants to study groups by chance, while double masking is intended to limit knowledge of group assignment during the study. The record does not report the allocation ratio, the method used to generate or conceal the randomization sequence, or who was masked. It also does not report a sample-size justification or a detailed statistical analysis plan. These omissions mean the design features can be described from the registry, but some operational and analytic details cannot be assessed.
The study lists additional interventions, including Rotarix, Engerix-B, Infanrix, Pediarix and Prevnar13, reflecting the concomitant vaccination context. Their presence in the intervention list should not be read as meaning every participant received every product. The group descriptions indicate different co-administration schedules, but do not fully document all details for every study phase.
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.
Primary Vaccination Phase
| Stage | Hiberix Group | ActHIB Group | Pentacel Group |
|---|---|---|---|
| STARTED | 2963 | 520 | 520 |
| COMPLETED | 2625 | 470 | 457 |
| NOT COMPLETED | 338 | 50 | 63 |
Reasons for not completing this period:
| Reason | Hiberix Group | ActHIB Group | Pentacel Group |
|---|---|---|---|
| Withdrawal by Subject | 109 | 17 | 21 |
| Lost to Follow-up | 171 | 19 | 26 |
| Protocol Violation | 40 | 3 | 2 |
| Adverse Event | 14 | 2 | 2 |
| Other | 4 | 9 | 12 |
Booster Vaccination Phase
| Stage | Hiberix Group | ActHIB Group | Pentacel Group |
|---|---|---|---|
| STARTED | 2337 | 435 | 400 |
| COMPLETED | 2270 | 423 | 386 |
| NOT COMPLETED | 67 | 12 | 14 |
Reasons for not completing this period:
| Reason | Hiberix Group | ActHIB Group | Pentacel Group |
|---|---|---|---|
| Protocol Violation | 0 | 0 | 2 |
| Withdrawal by Subject | 3 | 1 | 1 |
| Lost to Follow-up | 40 | 5 | 7 |
| Other | 24 | 6 | 4 |
Analysis population for the primary outcome, as defined in the registry: The analysis was based on the Primary According-to-Protocol (ATP) cohort for immunogenicity, including all evaluable subjects with 3 vaccine doses administered and assay results available for antibodies against at least one antigen for the blood sample taken 1 month after the last vaccine dose.
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 | Hiberix Group | ActHIB Group | Pentacel Group | Total |
|---|---|---|---|---|---|
| Participants analysed | 2963 | 520 | 520 | 4003 | |
| Age, Continuous | Weeks | 8.6 (SD 1.08) | 8.6 (SD 1.13) | 8.7 (SD 1.12) | 8.61 (SD 1.09) |
| Sex: Female, Male: Female | Participants | 1424 | 271 | 258 | 1953 |
| Sex: Female, Male: Male | Participants | 1539 | 249 | 262 | 2050 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to (≥) 0.15 Microgram Per Milliliter (µg/mL) and ≥ 1.0 µg/mL, measured over At 1 month after last dose of primary vaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Subjects |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with anti-polyribosylribitol phosphate (anti-PRP) antibody concentrations at or above 0.15 µg/mL and at or above 1.0 µg/mL. The registry labels the outcome as a number of subjects and specifies the assessment time as 1 month after the last dose of primary vaccination. The stated objective is to evaluate non-inferiority of Hiberix to ActHIB, each co-administered with Pediarix, Prevnar13 and Rotarix, after three primary doses.
Anti-PRP is an immune-response measure related to the Hib vaccine antigen. Counting participants who meet a concentration threshold converts a continuous laboratory measurement into a binary outcome: each participant either meets the threshold or does not. Reporting two thresholds gives information about the number reaching each specified concentration, but does not describe the full distribution of antibody concentrations. The registry does not report numerical endpoint results, group estimates, confidence intervals or p-values.
In general, a threshold-based immune endpoint can support a comparison of the fraction meeting a prespecified immune-response criterion. It is not itself a count of clinical disease events, and a measured antibody response should not be presented as a direct measure of clinical outcomes. The registry’s stated non-inferiority objective also depends on a prespecified margin and an analysis method; those details are not reported in the registry record. Without them and without the numerical results, the strength and precision of the primary comparison cannot be evaluated from this record alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the primary immune-response outcome and its assessment time, but the numerical primary results are not reported in the registry record. In particular, the record details do not include the number or proportion of participants meeting either anti-PRP threshold in each group, a between-group estimate, a confidence interval or a p-value. Consequently, the posted information does not establish the direction, magnitude or precision of the primary comparison.
The stated objective is non-inferiority of Hiberix compared with ActHIB after three primary doses, with specified concomitant vaccines. Non-inferiority is a claim about whether a difference is sufficiently small relative to a prespecified acceptable margin. The margin, test procedure and numerical comparison are not reported in the registry record. The objective alone is not evidence that the criterion was met. Nor can the comparison be reinterpreted as a superiority test or as proof of equivalence.
The endpoint includes two anti-PRP thresholds, and the study includes further objectives and multiple outcomes. The record lists 34 outcome measures and 26 analyses. Those counts signal that the study assessed a range of questions, but they do not disclose how the analyses were prioritized, whether multiplicity adjustments were used, or how results from multiple endpoints were interpreted. Such details are not reported in the registry record.
The registry also describes assessment of lot-to-lot consistency. The Hiberix group is described as pooled across three lots, but lot-specific estimates, their uncertainty and the criterion used to judge consistency are not included in the registry record. A pooled group result, even if one were reported, would not by itself show how similar the separate lot responses were. No lot-specific conclusions can be drawn from the record details.
Safety is reported separately through counts of participants affected by serious and other adverse events. The Hiberix group lists 120 participants with serious events among 2963 at risk; the ActHIB group lists 24 among 520; and the Pentacel group lists 21 among 520. Other adverse events are listed for 2783 of 2963, 495 of 520 and 488 of 520, respectively. No deaths are listed in any group. These are descriptive registry counts, not adjusted comparisons. The record does not specify the relevant adverse-event observation period in the registry record, nor does it provide uncertainty estimates or a causal assessment for these figures.
Overall, the registry record describes a randomized, double-blind study and defines its primary immune-response question, but the registry entries available do not include the primary results needed for a quantitative interpretation. It is therefore possible to explain what the study was designed to assess and how to interpret its endpoint, but not to conclude whether the observed data met the stated objective or how precisely groups differed.
9. Statistical Methods Explained
The registry describes a randomized, double-blind, parallel-group Phase III study and a binary primary outcome based on whether participants met anti-PRP concentration thresholds. It also identifies the Primary According-to-Protocol cohort for immunogenicity as the population for the primary analysis. The record does not provide a complete statistical analysis plan, so the explanations below distinguish general statistical principles from methods documented for this study.
What does a binary endpoint represent?
In general, a binary endpoint classifies each participant according to whether a defined condition is met. For this trial, the stated conditions are anti-PRP antibody concentrations at or above 0.15 µg/mL and at or above 1.0 µg/mL. A group’s count meeting a threshold can be expressed as a proportion if the corresponding analysis denominator is known. A comparison may then describe an absolute difference, a relative measure or another contrast. Which measure was used for the primary analysis is not reported in the registry record, and no numerical primary estimates are included in the registry record.
Thresholding makes an endpoint easier to interpret as the number of participants meeting a specified immune-response criterion, but it discards information about the exact antibody concentrations. Two groups could have similar threshold counts while differing in the distribution of values below or above the threshold. Conversely, a small shift around a threshold could change the number classified as meeting it. The registry lists two thresholds, so the results would need to be considered for each threshold rather than treated as a single continuous antibody measurement.
What does non-inferiority mean?
In general, a non-inferiority analysis asks whether the outcome with an intervention is not unacceptably worse than the outcome with a comparator, according to a margin chosen before examining the results. The margin defines the largest difference considered compatible with the objective. The interpretation depends on the direction of the comparison, the margin, the estimate and its confidence interval, and the prespecified analysis approach.
The registry states that the primary objective is non-inferiority of Hiberix to ActHIB for immune response to PRP following three primary doses. It does not report the non-inferiority margin, the precise contrast, the statistical test or the confidence-interval method. It also does not report the resulting estimates or intervals. The statement of an objective therefore describes what the study set out to evaluate, not whether non-inferiority was demonstrated. Non-inferiority should not be substituted with equivalence: equivalence ordinarily requires ruling out differences in both directions within a defined range, while the registry’s stated objective is non-inferiority.
How should confidence intervals and p-values be understood?
In general, a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the analysis. It provides a range of values compatible with the observed data and statistical model; it is not a guarantee that the true value lies in the interval. For a non-inferiority question, the interval must be interpreted relative to the prespecified margin and the chosen direction of comparison. A p-value, in general, describes how unusual data at least as extreme as those observed would be under a specified null hypothesis and model. It is not the probability that a treatment is effective or that the null hypothesis is true.
No primary confidence interval or p-value is reported in the registry record details. Therefore, neither statistical precision nor evidence relative to a non-inferiority margin can be assessed. The record also does not report adjusted or unadjusted primary estimates. No recalculated comparison is available in the registry record for this analysis.
Why does the analysis population matter?
The primary analysis is described as using the Primary According-to-Protocol cohort for immunogenicity. The definition includes evaluable participants with three vaccine doses administered and assay results available for antibodies against at least one antigen for the blood sample taken 1 month after the last vaccine dose. This definition identifies requirements for inclusion in that analysis; it does not describe every randomized participant’s outcome status.
In general, an according-to-protocol analysis focuses on participants who meet specified study requirements. It may differ from an analysis that includes all randomized participants in their assigned groups. For non-inferiority studies, population choice can matter because exclusions or deviations may affect comparability. The registry entries do not give the number analyzed in the primary cohort, the number excluded, reasons for exclusion, or results from another analysis population. They also do not report how missing assay results were handled beyond the cohort’s availability requirement.
What can the sample-size illustrations say?
In general, a planning calculation estimates how many participants might be needed under specified assumptions to detect a chosen effect with a chosen power. Such an illustration is not a measure of the power achieved by an already completed trial. The registry’s stated assumptions describe an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. For non-time-to-event outcomes, the stated convention is participants per arm for 80% power or other planning scenarios specified by the illustration. These are planning calculations, never observed power.
The registry entries available do not include the numerical planning outputs or the effect fractions used for those illustrations. The primary outcome is also not reduced to one comparison because it has multiple thresholds or categories. Thus, a single illustrative sample-size figure should not be treated as a definitive design justification for every endpoint or comparison. The trial’s actual sample-size justification is not reported in the registry record.
How do multiple outcomes affect interpretation?
In general, testing many hypotheses can increase the chance of obtaining apparently notable results by chance if every test is treated as confirmatory. Statistical approaches may control this issue through prespecified outcome hierarchies, adjusted significance thresholds, or other methods. The registry lists 34 outcome measures and 26 analyses, but it does not report whether or how multiplicity was controlled, which analyses were confirmatory, or the order in which outcomes were tested. The primary endpoint should therefore be distinguished from the study’s additional immune and safety outcomes, without assuming a correction or a particular interpretation strategy.
General principles clarify what information would be needed to judge the endpoint: group counts and denominators, the comparison estimate, uncertainty intervals, the non-inferiority margin, analysis populations, missing-data handling and multiplicity procedures. These details are not reported in the registry record details available for the primary result, so the design can be described but the inferential conclusion cannot be reconstructed.
10. Multiplicity, Missing Data and Analysis Populations
The study assessed several questions beyond the primary anti-PRP endpoint. The registry lists 34 outcome measures and 26 analyses, including immune responses to other antigens, solicited symptoms, unsolicited adverse events, serious adverse events and adverse events of special interest. The record does not report how the investigators distinguished confirmatory from exploratory analyses, whether outcomes were tested in a hierarchy, or whether any multiplicity adjustment was used.
In general, when many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is interpreted without regard to the others. Prespecified priorities and appropriate statistical procedures can help manage this issue. The registry entries do not support a conclusion about which method, if any, was used. The primary outcome itself includes two anti-PRP concentration thresholds, and the registry does not report a single reduced comparison for it.
The primary immunogenicity analysis used the Primary According-to-Protocol cohort, including evaluable participants with three vaccine doses and assay results available for antibodies against at least one antigen at the specified blood draw. The cohort definition does not give the number entering the analysis or explain all exclusions. The number of participants with unavailable assays, the reasons data were missing, and the method used to handle missing values are not reported in the registry record. The record also does not describe a separate intention-to-treat result for the primary endpoint.
In general, missing outcome data can affect both the estimated response and its precision, particularly if the probability of missingness differs across groups or relates to the outcome. Complete-case analysis may be appropriate in some settings, but its interpretation depends on assumptions about why observations are missing. No assumption or sensitivity analysis is reported in the registry entries. The available description therefore defines the analysis cohort but is insufficient to assess the impact of missing data or multiplicity on the primary inference.
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 |
|---|---|---|---|
| Hiberix Group | 120 | 2963 | 4.0% |
| ActHIB Group | 24 | 520 | 4.6% |
| Pentacel Group | 21 | 520 | 4.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Hiberix Group | 0 of 0 |
| ActHIB Group | 0 of 0 |
| Pentacel Group | 0 of 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 |
|---|---|
| Hiberix Group | 2783 of 2963 |
| ActHIB Group | 495 of 520 |
| Pentacel Group | 488 of 520 |
Most frequent serious adverse event terms
| Event term | Organ system | Hiberix Group | ActHIB Group | Pentacel Group |
|---|---|---|---|---|
| Bronchiolitis | Infections and infestations | 16 of 2963 | 2 of 520 | 2 of 520 |
| Respiratory syncytial virus bronchiolitis | Infections and infestations | 13 of 2963 | 4 of 520 | 2 of 520 |
| Pneumonia | Infections and infestations | 14 of 2963 | 2 of 520 | 2 of 520 |
| Dehydration | Metabolism and nutrition disorders | 10 of 2963 | 3 of 520 | 1 of 520 |
| Otitis media | Infections and infestations | 10 of 2963 | 0 of 520 | 2 of 520 |
| Respiratory syncytial virus infection | Infections and infestations | 9 of 2963 | 2 of 520 | 0 of 520 |
| Febrile convulsion | Nervous system disorders | 8 of 2963 | 3 of 520 | 0 of 520 |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | 5 of 2963 | 2 of 520 | 1 of 520 |
| Croup infectious | Infections and infestations | 4 of 2963 | 0 of 520 | 2 of 520 |
| Pyrexia | General disorders | 5 of 2963 | 0 of 520 | 0 of 520 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Hiberix Group | ActHIB Group | Pentacel Group |
|---|---|---|---|---|
| Irritability | Psychiatric disorders | 2525 of 2963 | 459 of 520 | 441 of 520 |
| Somnolence | Nervous system disorders | 2235 of 2963 | 409 of 520 | 387 of 520 |
| Pain | General disorders | 2035 of 2963 | 380 of 520 | 383 of 520 |
| Decreased appetite | Metabolism and nutrition disorders | 1596 of 2963 | 304 of 520 | 272 of 520 |
| Erythema | Skin and subcutaneous tissue disorders | 1306 of 2963 | 262 of 520 | 277 of 520 |
| Pyrexia | General disorders | 1288 of 2963 | 240 of 520 | 201 of 520 |
| Swelling | General disorders | 944 of 2963 | 191 of 520 | 211 of 520 |
| Upper respiratory tract infection | Infections and infestations | 655 of 2963 | 109 of 520 | 105 of 520 |
| Cough | Respiratory, thoracic and mediastinal disorders | 369 of 2963 | 64 of 520 | 73 of 520 |
| Otitis media | Infections and infestations | 355 of 2963 | 63 of 520 | 61 of 520 |
Serious events with the highest arm-level rate: respiratory syncytial virus bronchiolitis (0.8%), dehydration (0.6%), febrile convulsion (0.6%), bronchiolitis (0.5%), pneumonia (0.5%).
The registry lists serious adverse events for each group as counts of participants at risk and participants affected. The Hiberix group has 2963 at risk and 120 affected; the ActHIB group has 520 at risk and 24 affected; the Pentacel group has 520 at risk and 21 affected. The registry lists no deaths in any of the three groups. Other adverse events are separately listed as 2783 of 2963, 495 of 520 and 488 of 520, respectively. These categories should be read as the registry presents them, not as mutually exclusive participant groups.
The registry also lists leading serious-event terms with percentages: respiratory syncytial virus bronchiolitis, 0.8%; dehydration, 0.6%; febrile convulsion, 0.6%; bronchiolitis, 0.5%; pneumonia, 0.5%; and croup infectious, 0.4%. The registry entries available do not specify the denominator or group attribution for these term percentages, so they should not be assigned to a particular arm or treated as direct group comparisons.
These counts are descriptive. The registry entries do not provide an adverse-event observation period, adjusted comparisons, uncertainty intervals, or an assessment of whether an event was caused by a study vaccine. Differences in counts alone cannot establish a causal safety difference, especially without full information about follow-up and analysis. The figures describe reported events within the registry record; they do not by themselves establish the comparative safety of the groups.
12. What the Result Does, and Does Not, Mean
This trial’s registry entry describes a randomized comparison of Hib vaccine groups in healthy infants and specifies an immune-response endpoint based on anti-PRP antibody thresholds. The study was designed to assess lot-to-lot consistency, safety, concomitant vaccination and comparisons with ActHIB and Pentacel. Its primary objective is stated as non-inferiority of Hiberix to ActHIB after three primary doses, with specified co-administered vaccines.
The numerical primary outcome results are not reported in the registry record. Without the group results, estimate, confidence interval, p-value and non-inferiority margin, readers cannot determine whether the primary objective was met or how precisely the groups differed. The registry’s stated objective must not be mistaken for a reported finding. Nor does the absence of primary numerical results establish that the vaccine groups were the same or different.
The endpoint concerns antibody concentrations at specified thresholds. It describes an immune response, not a count of clinical Hib disease outcomes. A result on this endpoint, if reported, would need to be interpreted according to the trial’s analysis plan and the clinical relevance of the threshold; those details are not fully available in the registry entries. The endpoint also does not provide the full distribution of antibody concentrations.
The safety counts offer descriptive information about serious and other adverse events, but do not establish causation or comparative risk. The registry entries do not provide the follow-up period or adjusted safety analysis. Likewise, a pooled Hiberix group does not reveal the separate response estimates for each of the three lots, so the lot-consistency objective cannot be evaluated in the registry record.
In general, a trial’s design and stated objective indicate what it was intended to test, while its numerical estimates and uncertainty determine what the observed data support. Here, the design and endpoint are described, but essential result and analysis details are not reported in the registry record. Conclusions should therefore remain limited to the documented design, outcomes and descriptive safety counts.
13. Why This Trial Matters Statistically
The trial raises several important statistical questions that are common in vaccine studies. First, its primary outcome is a threshold-based immune-response measure rather than a direct clinical disease endpoint. This makes the outcome suitable for describing the proportion meeting a specified antibody criterion, but requires care in explaining what the threshold does and does not represent. The registry names two thresholds, so interpretation must keep them distinct.
Second, the study’s stated non-inferiority objective requires more than observing broadly similar group results. In general, a non-inferiority conclusion depends on a justified margin, a prespecified comparison and an estimate sufficiently precise relative to that margin. The registry entries do not report the margin or primary numerical results. This is a useful reminder that a study aim is not the same as an inferential conclusion.
Third, the design includes a lot-consistency objective, while the Hiberix group description refers to pooling recipients of three lots. A pooled analysis can characterize the combined group, but lot-to-lot consistency is inherently about comparing responses across lots. Separate estimates and their uncertainty, as well as a stated consistency criterion, would be needed to assess that question. Those details are not reported in the registry entries.
Finally, the registry describes multiple immune and safety outcomes, with 34 outcome measures and 26 analyses. This makes analysis priorities and multiplicity relevant to interpretation. The record does not specify how those issues were addressed. Together, the missing primary estimates, non-inferiority details, lot-level results and multiplicity procedures illustrate why registry design information alone cannot replace a complete results and methods account.
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 for interpreting the primary question is that numerical endpoint results are not reported in the registry record details available. Group counts or proportions meeting each anti-PRP threshold, a comparison estimate, confidence intervals and p-values are absent. The non-inferiority margin and analysis procedure are also not reported, preventing assessment of whether the stated objective was met and how precise that assessment would be.
Although the study aimed to demonstrate lot-to-lot consistency, the Hiberix group is described as pooled across three lots. Lot-specific estimates, uncertainty measures and the criterion for consistency are not available in the registry entries. The pooled group description therefore cannot establish how similar responses were across the separate lots.
The primary analysis population is defined as an according-to-protocol immunogenicity cohort, but the number analyzed, exclusions and reasons for exclusion are not reported. Missing assay counts, the approach to missing data, and results from other analysis populations are also not reported. These omissions limit assessment of how the analysis population may relate to the randomized groups.
The registry lists multiple outcomes and analyses but does not report the prespecified hierarchy or multiplicity procedures. Full co-administration schedules are not available for every arm and phase because some arm-description text is incomplete. The registry entries also do not specify the adverse-event observation period, group attribution for listed serious-event term percentages, or adjusted safety comparisons. These are limitations of what can be established from the registry record, not evidence that the study did or did not address these matters elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Consistency & Immunogenicity Study of 3 Lots of GSK's Hib Conjugate Vaccine Versus ActHIB & Pentacel in Healthy Infants — NCT01000974.
- Registry record last updated 2018-07-12; status last verified 2018-06.
- Results first posted 2013-08-19.
- 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
The registry describes NCT01000974, a completed Phase III, randomized, double-blind, parallel-group study sponsored by GlaxoSmithKline, with enrollment of 4003 healthy infants. It compared GSK Biologicals’ Hib conjugate vaccine, identified as GSK 208108 and Hiberix, with ActHIB and Pentacel. The study aimed to assess safety, lot-to-lot consistency, concomitant vaccine administration and immune responses.
The primary endpoint counts participants meeting anti-PRP antibody concentration thresholds of at least 0.15 µg/mL and at least 1.0 µg/mL, 1 month after the last primary dose. The stated primary objective is non-inferiority of Hiberix to ActHIB. Primary numerical results, the non-inferiority margin and detailed analysis methods are not reported in the registry record details available.
Descriptive serious and other adverse-event counts are listed for the three groups, with no deaths listed. The record does not provide enough primary-result or analysis detail to determine whether the stated immune-response objective was met.