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 Prevention of GBS Colonization Via Immunity (NCT00128219), a randomized phase 2 study. The primary outcome is The Time to First Vaginal Swab That is Type III GBS Culture Positive, With All Previous Cultures Negative for Type III GBS, Not Just the Immediately Preceding Culture..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00128219 |
| Phase | Phase 2 |
| Condition | Beta Haemolytic Streptococcal Infection |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 667 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
The study description concerns non-pregnant, sexually active women ages 18-40 who tested negative for GBS in the vagina or rectum at screening. Sexual activity was defined as sex with a male at least once in the last 4 months. The efficacy analysis population was defined as enrolled participants with at least one post-enrollment efficacy assessment. The registry record lists total enrollment of 667.
Intervention
The experimental intervention was a single intramuscular dose of GBS III-TT vaccine. The dose contained 50 mcg of GBS type III capsular polysaccharide and 32 mcg of tetanus toxoid.
Comparator
The comparison group received a single dose of a licensed Tetanus and Diphtheria Toxoids vaccine, described as Td. Random assignment and double masking were part of the trial design.
Primary question
The primary question was about time from vaccination to first vaginal acquisition of GBS type III. An event required a positive vaginal culture after all previous cultures had been negative for type III GBS; it was not enough for only the immediately preceding culture to be negative. The registry record does not report the numerical comparison of the groups for this endpoint, so the direction, magnitude, and precision of the efficacy result cannot be determined from the record.
3. Trial Design
This was a phase II, randomized, double-blinded, parallel-group trial comparing GBS III-TT vaccine with Td vaccine. The registry record lists enrollment of 667 and identifies the National Institute of Allergy and Infectious Diseases (NIAID) as sponsor. The record gives a start date of 2003-07, primary completion of 2008-12, and a completed status.
The study description says that participants were randomly assigned to one of the two vaccine groups. The experimental group received one intramuscular dose of GBS III-TT, while the comparator group received one dose of Td vaccine. Double masking is recorded, but details about who was masked, how masking was maintained, or whether masking was assessed are not reported in the registry record.
The described follow-up included vaginal and rectal swab collection and a blood draw at one month, 2 months, and every other month thereafter, for 1½ years or a total of 10 post-vaccination visits. The primary endpoint used vaginal culture status to identify acquisition of type III GBS. Secondary outcomes listed in the record include serum IgG antibody measures and counts of participants with solicited symptoms or specified antibody rises. The registry record lists 39 outcome measures and 4 analyses, but does not provide a complete statistical analysis plan or numerical primary efficacy results.
The eligibility description and follow-up schedule characterize the intended study population and procedures; they do not by themselves establish how many participants completed every visit or contributed to each outcome. Arm-specific efficacy population counts and follow-up completeness are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Participants were screened for vaginal and rectal colonization with type III GBS and only those negative were offered enrollment
Overall Study
| Stage | GBS III-TT Vaccine | Td Vaccine |
|---|---|---|
| STARTED | 333 | 334 |
| COMPLETED | 264 | 263 |
| NOT COMPLETED | 69 | 71 |
Analysis population for the primary outcome, as defined in the registry: All enrolled participants with at least one post-enrollment efficacy assessment were included in the intention to treat (ITT) Efficacy Analysis Cohort. Women were included without regard to protocol adherence, and classified by treatment randomized rather than received.
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 | GBS III-TT Vaccine | Td Vaccine | Total |
|---|---|---|---|---|
| Participants analysed | 333 | 334 | 667 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 333 | 334 | 667 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 26.2 (SD 5.58) | 26.1 (SD 5.68) | 26.2 (SD 5.63) |
| Sex: Female, Male: Female | Participants | 333 | 334 | 667 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 333 | 334 | 667 |
6. Primary Endpoint
The registry lists the primary outcome as The Time to First Vaginal Swab That is Type III GBS Culture Positive, With All Previous Cultures Negative for Type III GBS, Not Just the Immediately Preceding Culture., measured over Time from vaccination to acquisition of vaginal type III GBS, up to 18 months post-vaccination..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was time from vaccination to the first vaginal swab positive for type III GBS, provided every earlier culture was negative for type III GBS. Requiring all previous cultures to be negative makes the endpoint one of first observed acquisition, rather than a later positive culture after an earlier positive result. The time-to-event quantity was assigned to the midpoint of the interval in which acquisition was ascertained. As swabs were collected at visits rather than continuously, the exact time of acquisition could not be observed directly.
A time-to-event endpoint retains information about when an event is observed, rather than reducing follow-up to a simple count of participants who ever had an event. It can also account for participants whose event was not observed during available follow-up by treating their observation as censored under the stated rules. In general, this framework is useful when participants have different observed follow-up durations.
The registry describes censoring at the end of follow-up or at the first of 2 or more consecutive missed visits. It also states that vaginal type III GBS status at missed visits before censoring was imputed from the subsequent visit. These choices affect how the event time and observable follow-up are defined. The numerical treatment comparison, its uncertainty, and any test of the primary endpoint are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically specific endpoint and describes a randomized comparison, but it does not report the primary numerical efficacy result. There is no reported estimate of the difference between groups, event count for the primary endpoint, confidence interval, or p-value. Consequently, the direction and size of any observed group contrast, and how precisely it was estimated, are not available from the registry record.
The endpoint is based on first vaginal acquisition of type III GBS, not on antibody response alone. The listed secondary outcomes include geometric mean concentrations of serum IgG, mean fold-rise in IgG, and counts meeting a four-fold-rise threshold at several follow-up times. Those immune measurements address different questions from the primary culture-based endpoint. A change in an antibody measure cannot be treated as a substitute for the missing primary efficacy estimate.
The registry lists 667 enrolled participants. For safety, the recorded groups include 326 participants at risk in the GBS III-TT group and 337 in the Td group, with 14 and 22 participants, respectively, recorded as affected by serious adverse events. These are descriptive safety counts. They do not provide an adjusted comparison, a causal estimate, or information about the primary endpoint. No deaths count by group is listed, although Death appears among the serious adverse event terms with a listed percentage of 0.3%.
Statistical uncertainty matters because an observed estimate can be compatible with a range of underlying group differences. In general, a confidence interval describes the range of effect estimates reasonably compatible with the data and the method used; its width indicates precision. No confidence interval for the primary endpoint is reported in the registry record, so neither precision nor compatibility with particular effect sizes can be evaluated.
The study design and endpoint definition establish what the trial intended to compare, not what the comparison found. Without the primary results and the analysis details, no conclusion about the magnitude or statistical evidence for a difference in time to acquisition can be drawn from this record. The listed secondary measures and safety counts should be interpreted on their own terms rather than as replacements for that missing primary comparison.
9. Statistical Methods Explained
The primary endpoint is a time-to-event outcome. The registry record defines the event as first vaginal type III GBS culture positivity after a history of negative cultures. It assigns the event time to the midpoint of the ascertainment interval. These are important operational choices: they specify which observations count as an event and how a time is assigned when the actual moment of acquisition is not directly observed.
What does time to event mean?
In general, time-to-event methods describe the time until a defined event occurs while allowing some participants to have incomplete observation. A participant who has not had an observed event by the end of available follow-up may contribute information up to that point without being treated as if the event definitely never occurred. This is called censoring. Censoring is not itself an event, and it does not establish that a participant remained event-free after observation ended.
Here, the record specifies censoring at the end of follow-up or at the first of 2 or more consecutive missed visits. It says that vaginal type III GBS status for missed visits before censoring was imputed from the subsequent visit. The method used to compare time-to-event outcomes between randomized groups, and the precise handling of all censoring patterns in the analysis, are not reported in the registry record.
Why does the interval midpoint matter?
General statistical explanation: when an event is known to have occurred between assessments but its exact time is unknown, assigning an interval midpoint is one way to create a single analysis time. That time is an approximation, not a direct observation of the moment of acquisition. The resulting analysis can depend on the schedule of assessments and on the assumptions associated with midpoint assignment. The record gives a follow-up schedule but does not report sensitivity analyses for alternative event-time definitions.
What does the efficacy population mean?
The registry defines an intention-to-treat Efficacy Analysis Cohort as all enrolled participants with at least one post-enrollment efficacy assessment. It states that women were included without regard to protocol adherence and classified according to randomized treatment rather than treatment received. This retains randomized group assignment in the analysis and avoids reclassifying participants based on what they actually received. However, the stated cohort definition requires an efficacy assessment; participants without one are not included in that defined cohort. The number in the efficacy cohort and its arm-specific composition are not reported in the registry record.
In general, an analysis population should be read alongside its inclusion rules. An intention-to-treat label does not by itself reveal which randomized participants contributed data, how missing endpoint assessments were handled, or whether every outcome used the same population. The record's definition is therefore more informative than the label alone, while the missing population counts limit assessment of how many participants were represented.
How should uncertainty and significance be understood?
General statistical explanation: an estimate summarizes the observed contrast, while a confidence interval communicates uncertainty around that estimate under a specified method. A p-value assesses how unusual data at least as discrepant as those observed would be under a null model and the test's assumptions. Neither measure describes clinical importance by itself. The registry record does not report the primary estimate, confidence interval, p-value, or named test, so none can be interpreted for this endpoint.
Over-dispersion is a general issue for count outcomes when observed variability exceeds what a simple statistical model expects. It can make standard errors too small if ignored. The primary endpoint is described as time to event rather than a count outcome, and the registry record does not report a model or a dispersion assessment. No claim about over-dispersion being present or addressed in this trial can be made.
What do the planning assumptions represent?
The record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. Such illustrations are hypothetical planning exercises, not observed power and not evidence that the trial was designed using those exact assumptions. The primary observed effect and the illustration values are not reported in the registry record, and the record does not report the trial's sample-size justification. The illustrations cannot fill the gap in the primary results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 39 outcome measures, including the primary time-to-acquisition endpoint and secondary measures of antibody concentrations, fold-rises, threshold responses at several follow-up times, and solicited symptoms. Considering multiple outcomes or repeated assessment times raises a general multiplicity issue: the chance of at least one apparently notable finding can increase when many statistical comparisons are made. A prespecified strategy may address this, but a multiplicity adjustment or hierarchy for testing outcomes is not reported in the registry record.
The record lists 4 analyses, but that count does not reveal which outcomes were analyzed, whether analyses were prespecified, or how any multiple comparisons were handled. Interim analyses, stopping rules, and a complete statistical analysis plan are not reported in the registry record. It would therefore be inappropriate to infer that adjustments were or were not made based only on the number of outcomes and analyses listed.
Missing data are relevant because participants were followed at scheduled visits and the primary endpoint depends on serial culture results. The registry states that missed-visit vaginal type III GBS status before censoring was imputed from the subsequent visit. Censoring occurred at the end of follow-up or at the first of 2 or more consecutive missed visits. The record does not explain the exact imputation algorithm, report how many observations were imputed, or give a sensitivity analysis assessing alternative missing-data assumptions.
The efficacy population included enrolled participants with at least one post-enrollment efficacy assessment and retained randomized treatment classification regardless of adherence. That definition does not specify the number excluded for lack of assessment or establish that missingness was similar between groups. Arm-specific efficacy denominators and outcome completeness are not reported in the registry record. These gaps limit appraisal of the impact of missing observations and the robustness of the endpoint comparison.
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 |
|---|---|---|---|
| GBS III-TT Vaccine | 14 | 326 | 4.3% |
| Td Vaccine | 22 | 337 | 6.5% |
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 |
|---|---|
| GBS III-TT Vaccine | 304 of 326 |
| Td Vaccine | 320 of 337 |
Most frequent serious adverse event terms
| Event term | Organ system | GBS III-TT Vaccine | Td Vaccine |
|---|---|---|---|
| Cholelithiasis | Hepatobiliary disorders | 1 of 326 | 1 of 337 |
| Appendicitis | Infections and infestations | 0 of 326 | 2 of 337 |
| Pyelonephritis | Infections and infestations | 1 of 326 | 1 of 337 |
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | 0 of 326 | 2 of 337 |
| Gastric bypass | Surgical and medical procedures | 1 of 326 | 1 of 337 |
| Cardiac failure congestive | Cardiac disorders | 1 of 326 | 0 of 337 |
| Gastrointestinal inflammation | Gastrointestinal disorders | 1 of 326 | 0 of 337 |
| Pancreatitis | Gastrointestinal disorders | 0 of 326 | 1 of 337 |
| Chest pain | General disorders | 0 of 326 | 1 of 337 |
| Death | General disorders | 1 of 326 | 0 of 337 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GBS III-TT Vaccine | Td Vaccine |
|---|---|---|---|
| Tenderness | General disorders | 234 of 326 | 276 of 337 |
| Pain (at Injection Site) | General disorders | 175 of 326 | 223 of 337 |
| Headache | Nervous system disorders | 130 of 326 | 119 of 337 |
| Malaise | General disorders | 103 of 326 | 111 of 337 |
| Myalgia | Musculoskeletal and connective tissue disorders | 91 of 326 | 112 of 337 |
| Nausea | Gastrointestinal disorders | 54 of 326 | 61 of 337 |
| Nasopharyngitis | Infections and infestations | 56 of 326 | 55 of 337 |
| Vaginitis bacterial | Infections and infestations | 44 of 326 | 61 of 337 |
| Fungal infection | Infections and infestations | 44 of 326 | 45 of 337 |
| Injection site swelling | General disorders | 32 of 326 | 54 of 337 |
Serious events with the highest arm-level rate: appendicitis (0.6%), ectopic pregnancy (0.6%), cardiac failure congestive (0.3%), gastrointestinal inflammation (0.3%), death (0.3%).
The registry records 14 participants with serious adverse events among 326 at risk in the GBS III-TT Vaccine group, and 22 participants with serious adverse events among 337 at risk in the Td Vaccine group. These are group-specific counts in the adverse event record. They are descriptive and, without a stated comparative analysis and its uncertainty, do not establish whether the groups differed in safety.
The record lists serious adverse event terms and percentages: Appendicitis, 0.6%; Ectopic pregnancy, 0.6%; Cardiac failure congestive, 0.3%; Gastrointestinal inflammation, 0.3%; Death, 0.3%; and Cholelithiasis, 0.3%. The registry record does not assign these listed percentages to a particular treatment group or give the event counts underlying each percentage. The death term should not be read as a group-specific death count; the group-specific death count is not reported in the registry record.
Other adverse events are separately recorded for 304 participants among 326 at risk in the GBS III-TT group and 320 among 337 at risk in the Td group. The registry record does not provide enough detail to characterize event severity, timing, causality, or the specific events represented by these counts. These safety summaries should not be combined with the primary efficacy endpoint or treated as a complete account of risk.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase II randomized, double-blinded, parallel-group trial compared a single dose of GBS III-TT vaccine with a single dose of Td vaccine, with time to first vaginal type III GBS acquisition as the primary endpoint. It also describes the efficacy analysis population, the scheduled follow-up, and the censoring and imputation rules used to define the endpoint. Those details help clarify the question the study set out to address.
They do not establish the observed efficacy result. The primary numerical group comparison, event counts, estimate, confidence interval, and p-value are not reported in the registry record. As a result, the record cannot show the magnitude or precision of a difference in time to acquisition. It also cannot establish whether any observed contrast would be statistically distinguishable from no difference or whether it would be important in a clinical context.
The secondary antibody outcomes are measures of immune response, while the primary endpoint is based on vaginal culture acquisition. These outcomes are related to different aspects of the study question and should not be treated as interchangeable. The record lists the secondary outcomes but does not report their numerical results. The safety counts and serious adverse event terms provide additional descriptive information, but they do not resolve the missing efficacy comparison.
In general, randomized allocation supports a comparison of groups as assigned, but the meaning of the results also depends on outcome measurement, follow-up, missing data, and the analysis plan. The registry describes several of these features but does not provide enough information to evaluate all of them or to assess the primary estimate. The appropriate reading is therefore limited: the study design and endpoint are documented, while the primary result and its uncertainty are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for using a first-acquisition time-to-event endpoint based on repeated culture assessments. The definition requires all prior vaginal cultures to be negative for type III GBS, and the event time is assigned to the midpoint of an ascertainment interval. This makes the event definition more specific than simply counting any positive culture and highlights how measurement schedules shape an endpoint.
The record also makes explicit that follow-up can end through administrative completion or repeated missed visits, and that some missed-visit status was imputed from a later visit before censoring. Those rules illustrate how endpoint construction involves choices about incomplete observation as well as event definition. Such choices should be considered when interpreting a time-to-event analysis, even though the registry record does not report the comparative estimate or the specific statistical model.
The stated efficacy cohort preserves randomized assignment and does not require protocol adherence, while requiring at least one post-enrollment efficacy assessment. This demonstrates why analysis-population definitions matter: the label alone is not enough to determine who contributed information. The record's population definition is clear, but the arm-specific analysis counts are not reported.
Finally, the record lists numerous outcome measures and several analyses without reporting a multiplicity strategy or the primary numerical result. This is a useful reminder that an outcome inventory is not a substitute for a prespecified analysis plan or results with uncertainty. The registry record is informative about design and endpoint rules, but those details cannot replace the absent efficacy estimate.
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 most consequential limitation for statistical interpretation is that the primary efficacy comparison is not reported in the registry record. No primary event counts, group estimate, confidence interval, or p-value are available. Without these, the magnitude, direction, and precision of the trial's primary result cannot be assessed. Numerical results for the listed secondary antibody and symptom outcomes are also not reported in the registry record.
The endpoint depends on scheduled swab assessments, with acquisition time represented by an interval midpoint rather than directly observed. The record describes imputation of missed-visit status from a subsequent visit before censoring, but does not report how often this occurred, the detailed imputation procedure, or sensitivity analyses. The number of participants in the efficacy cohort and arm-specific outcome completeness are not reported, limiting assessment of missingness and follow-up.
The record does not report the statistical model or test used for the primary endpoint, a complete statistical analysis plan, a multiplicity strategy, interim analyses, or the trial's sample-size justification. It lists planning assumptions for illustrations, but the primary observed effect and illustration values are not reported in the registry record. The sample size of 667 enrolled participants alone does not establish precision or power for the primary endpoint.
Safety information is also limited in the registry summary. Serious adverse event counts are reported by group, but timing, causal attribution, event-level details, and a comparative analysis are not reported. The serious adverse event term percentages are not assigned to treatment groups in the record, and a group-specific death count is not reported. These limitations constrain interpretation of both efficacy and safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Prevention of GBS Colonization Via Immunity — NCT00128219.
- Registry record last updated 2015-01-27; status last verified 2009-08.
- Results first posted 2010-07-05.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes NCT00128219, a completed phase II randomized, double-blinded, parallel-group comparison of GBS III-TT vaccine and Td vaccine. It lists enrollment of 667, a start date of 2003-07, and primary completion of 2008-12. The primary endpoint was time from vaccination to first vaginal type III GBS culture positivity after all previous cultures were negative.
The efficacy population included enrolled participants with at least one post-enrollment efficacy assessment, classified by randomized treatment regardless of adherence. The record describes interval-midpoint event timing, censoring at the end of follow-up or after repeated missed visits, and imputation of missed-visit status from a subsequent visit before censoring.
Group-specific serious adverse event counts are listed, along with adverse event terms and percentages. The numerical primary efficacy result, its uncertainty, and the complete analysis plan are not reported in the registry record.