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 Partially Blind Study to Evaluate Immunogenicity & Safety of GSK Bio's HPV Vaccine 580299 in Healthy Women Aged 9-25 Yrs (NCT00541970), a randomized phase 1 study. The primary outcome is Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00541970 |
| Phase | Phase 1 |
| Condition | Infections, Papillomavirus |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 961 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Healthy females aged 9 to 25 years. The primary analysis population was the According-to-Protocol cohort for Immunogenicity: evaluable subjects with immunogenicity data and assay results for antibodies against at least one study vaccine antigen component after vaccination.
Intervention
Alternative Cervarix schedules and formulations. The study included two-dose schedules with a placebo dose and a three-dose schedule, with doses administered at different months.
Comparator
The comparator was another Cervarix schedule and formulation within the trial, rather than a single untreated or placebo-only group. Placebo was used as a scheduled dose in some groups.
Primary question
What antibody titers against HPV-16 and HPV-18 were observed one month after the last Cervarix dose under the schedules and formulations studied? The registry record does not report numerical titers or a single comparative estimate.
The trial addressed immunogenicity and safety in healthy young females, with the vaccine schedule and formulation varied across four groups. Its primary endpoint was the geometric mean titer (GMT) of antibodies to HPV-16 and HPV-18. The outcome was measured one month after the last vaccine dose, but its calendar timing differed: it was at Month 3 for the Cervarix 1/Placebo Group and at Month 7 for the other groups.
This is a question about antibody measurements, not a direct comparison of cervical cancer, HPV infection, or cervical abnormalities. The registry summary discusses the vaccine's intended targets and prior evidence, but those statements do not constitute results from this trial. Numerical primary outcome results, comparative estimates, and statistical tests are not reported in the registry record. Consequently, the clinical question can be described from the design and endpoint, but the posted information does not establish which schedule produced higher or lower titers.
3. Trial Design
This was a randomized, single-masked, parallel-group phase 1 study. The registry lists enrollment as 961 and status as completed. The recorded start date is 2007-10-17, and the primary completion date is 2013-03-18. The sponsor was GlaxoSmithKline.
The trial enrolled healthy females aged 9 to 25 years and evaluated Cervarix formulation 1 or formulation 2 using alternative dosing schedules. In the Cervarix 1/Placebo Group, participants received Cervarix at Month 0 and Month 2, followed by placebo at Month 6. In the Cervarix 1/Placebo/Cervarix 1 Group, Cervarix was given at Month 0 and Month 6, with placebo at Month 2. The Cervarix 2/Placebo/Cervarix 2 Group followed that same timing pattern using formulation 2. The Cervarix 2 Group received formulation 2 at Month 0, Month 2, and Month 6. The registry describes administration as intramuscular in the deltoid of the non-dominant arm.
The intervention structure means the groups differed in schedule and, for some comparisons, formulation as well. It is therefore important not to treat the study as a simple comparison of vaccine against no vaccine. The registry describes placebo doses within some active-vaccine schedules; it does not list a placebo-only arm. Although allocation was randomized, details about the allocation procedure and masking procedures are not reported in the registry record.
The primary outcome was antibody titers measured one month after the last dose. Because the last dose was at different scheduled months across groups, the endpoint assessment occurred at Month 3 in one group and Month 7 in the other groups. The registry lists 36 outcome measures, but numerical results for the primary outcome are not reported in the registry record. Detailed protocol deviations, participant flow, and reasons for exclusions are also 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: The study was run in an open manner for subjects in the groups receiving the Cervarix vaccine on a 3-dose vaccination schedule. For subjects in the group receiving the Cervarix vaccine on a 2-dose vaccination schedule, the study was run in an observer-blind manner until Month 24, and then in an open manner.
Month 7
| Stage | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|
| STARTED | 240 | 241 | 240 | 239 |
| COMPLETED | 231 | 228 | 229 | 234 |
| NOT COMPLETED | 9 | 13 | 11 | 5 |
Reasons for not completing this period:
| Reason | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|
| Protocol Violation | 9 | 13 | 11 | 5 |
Month 12
| Stage | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|
| STARTED | 240 | 241 | 240 | 239 |
| COMPLETED | 228 | 219 | 219 | 223 |
| NOT COMPLETED | 12 | 22 | 21 | 16 |
Reasons for not completing this period:
| Reason | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|
| Adverse Event | 0 | 1 | 1 | 1 |
| Protocol Violation | 12 | 21 | 20 | 15 |
Month 18
| Stage | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|
| STARTED | 240 | 241 | 240 | 239 |
| COMPLETED | 226 | 217 | 215 | 222 |
| NOT COMPLETED | 14 | 24 | 25 | 17 |
Reasons for not completing this period:
| Reason | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|
| Adverse Event | 0 | 1 | 1 | 1 |
| Protocol Violation | 14 | 23 | 24 | 16 |
Month 24
| Stage | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|
| STARTED | 240 | 241 | 240 | 239 |
| COMPLETED | 211 | 209 | 208 | 217 |
| NOT COMPLETED | 29 | 32 | 32 | 22 |
Reasons for not completing this period:
| Reason | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|
| Adverse Event | 0 | 1 | 1 | 1 |
| Protocol Violation | 29 | 31 | 31 | 21 |
Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the According-to-Protocol cohort for Immunogenicity, which included all evaluable subjects for whom immunogenicity data were available, and for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
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 | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 240 | 241 | 240 | 239 | 960 | |
| Age, Continuous | Years | 17.1 (SD 4.30) | 17.2 (SD 4.30) | 17.3 (SD 4.25) | 17.2 (SD 4.38) | 17.2 (SD 4.31) |
| Sex: Female, Male: Female | Participants | 240 | 241 | 240 | 239 | 960 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies, measured over One month after vaccination with the last dose of the Cervarix vaccine (Cervarix 1/Placebo Group: Month 3; Other groups: Month 7)..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | EL.U/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint measured antibody titers against HPV-16 and HPV-18. Titers were expressed in ELISA units per milliliter (EL.U/mL), and the summary measure was the geometric mean titer. The endpoint was assessed one month after vaccination with the last Cervarix dose: at Month 3 for the Cervarix 1/Placebo Group and at Month 7 for the other groups.
Antibody titers are a measure of the immune response detected by an assay. A geometric mean is used when measurements are positive and may vary across a broad range; taking the geometric mean summarizes values on a multiplicative scale rather than treating each unit increase as an equal additive change. This is general statistical context, not a finding about the trial's results. The registry specifies a 95% confidence interval as the dispersion measure, but does not report the actual GMTs or confidence interval limits.
The endpoint is relevant to a study of vaccine immunogenicity because it quantifies measured antibodies to the targeted HPV types. It is not itself a direct measure of HPV infection, cervical abnormalities, or cancer. The registry does not report a threshold defining a protective response, nor does it establish that a particular titer corresponds to a clinical outcome. Numerical comparisons among schedules and formulations, including their precision, are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The design establishes that the trial randomized participants among four schedule and formulation groups and measured antibody titers after the last Cervarix dose. The primary endpoint is described as a geometric mean titer for antibodies against HPV-16 and HPV-18, with a 95% confidence interval. However, the registry record does not report numerical GMTs, confidence interval limits, or a statistical comparison for this endpoint. There is therefore no posted primary estimate from which to describe the size, direction, or precision of a difference between groups.
The timing of the measurement is important for interpretation. The Cervarix 1/Placebo Group was assessed at Month 3, while the other groups were assessed at Month 7. Each measurement was specified as one month after the group's last vaccine dose, but the calendar visit differed. A reader should not assume the groups were measured at a common month since the first dose or at a common time since study entry. The registry record does not report further details about how timing was handled in the statistical analysis.
There is also more than one potential contrast. The four groups differ in schedule and, across some comparisons, vaccine formulation. The posted information does not identify one primary pairwise comparison or provide a single summary across all groups. The registry's outcome description includes antibody measurements across groups, but the registry record does not report analyses that resolve these alternatives into one comparative result.
Confidence intervals, when reported, describe uncertainty around an estimated quantity under the statistical method used. They do not by themselves establish clinical importance, and their interpretation depends on the analysis and population. Since the actual intervals are absent, the precision of the antibody estimates cannot be assessed from the registry record. A p-value or a conclusion about statistical evidence for a difference is also not reported in the registry record.
The available safety information records serious adverse events and other adverse events by group. It gives numbers of participants at risk and affected, and lists selected serious event terms with percentages. Those figures describe reported safety events; they do not substitute for the missing immunogenicity results. The registry record does not report deaths for these groups as a numerical count, and it does not provide enough detail to attribute a particular event to vaccination.
Accordingly, the posted information supports a description of the study question, schedules, endpoint definition, and some safety counts. It does not support a conclusion that one schedule or formulation produced greater antibody titers, that observed differences were statistically distinguishable, or that a particular antibody response translated into a clinical outcome. Those conclusions require outcome estimates and analysis details that are not reported in the registry record.
9. Statistical Methods Explained
The registry identifies a geometric mean titer as the primary summary for antibody measurements and a 95% confidence interval as the dispersion measure. These choices describe the intended form of the endpoint summary, not the results: actual values and interval limits are not reported in the registry record. The endpoint unit is EL.U/mL, an assay-based measure of antibody concentration.
Why use a geometric mean?
General statistical explanation: antibody measurements can span a wide range and are often interpreted on a multiplicative scale. The geometric mean summarizes that scale by averaging transformed values and returning the result to the original scale. It can be more suitable than an arithmetic mean when proportional differences are meaningful and the distribution is right-skewed. This is a general reason for the measure; the distribution of titers in this trial is not reported in the registry record.
A geometric mean does not show the spread of individual measurements by itself. A confidence interval gives an estimated range of values compatible with the data and the specified statistical method for the underlying summary. A 95% confidence interval is not a statement that 95% of individual participants' titers fall inside the interval. The registry names this interval type but does not report its limits or the method used to calculate it.
What does the endpoint timing mean?
The endpoint was measured one month after the final vaccine dose, with the assessment at Month 3 for the Cervarix 1/Placebo Group and Month 7 for the other groups. This defines the intended timing relative to each schedule's last dose. It also means the listed assessment months are not the same across groups. The registry record does not report whether additional time points were used for the primary analysis or how any difference in timing was incorporated into group comparisons.
Random allocation can, in general, help balance known and unknown participant characteristics across groups at the start of a trial. The record labels allocation randomized, but does not report the randomization sequence, concealment procedures, stratification factors, or allocation ratio. Single masking is recorded, but who was masked and how masking was maintained are not reported in the registry record. The parallel design means participants were assigned to a group rather than crossing through multiple schedules, as described in the registry.
Which analysis population was specified?
The primary analysis population is described as the According-to-Protocol cohort for Immunogenicity. It included evaluable subjects with immunogenicity data and assay results for antibodies against at least one study vaccine antigen component after vaccination. This is a defined subset based on evaluability and available assay results; the registry does not report the number included in each primary analysis or the exclusions from that population. It also does not report a separate intention-to-treat analysis for the primary endpoint.
Analysis populations can affect interpretation because estimates based on participants with evaluable measurements may differ from estimates based on everyone randomized. Missing measurements and protocol deviations can influence who contributes to an according-to-protocol analysis. The registry record does not report how missing titers were handled, whether any imputation was used, or what rules determined evaluability and protocol adherence beyond the general cohort description.
How should comparisons be understood?
The study has four groups with differences in vaccine formulation and dose timing. A group contrast could therefore reflect a schedule difference, a formulation difference, or both, depending on which groups are compared. The registry record does not report a designated single comparison, a model for estimating contrasts, covariate adjustment, or multiplicity procedures. It also does not report actual group estimates or hypothesis tests.
General statistical explanation: when several outcomes, time points, or comparisons are examined, the chance of at least one apparently unusual result can increase if each is assessed separately without accounting for multiplicity. A prespecified testing strategy can clarify which contrasts are confirmatory and how uncertainty is interpreted. The registry record does not report such a strategy, so it is not possible to determine how multiple comparisons were handled.
General statistical explanation: over-dispersion occurs when observed variability exceeds what a chosen statistical model expects. If present, it can make standard errors too small under a model that assumes less variability, which in turn can make confidence intervals too narrow. The registry record does not report a model or diagnostic information establishing whether over-dispersion was relevant to these antibody data.
The registry's primary outcome description names the summary statistic and interval type, but does not provide enough information to reproduce the analysis. The detailed statistical analysis plan, including model assumptions and any transformations, is not reported in the registry record. Any sample-size planning illustration based on an observed effect is a planning calculation, not observed power and not a substitute for the trial's own design rationale; the trial's sample-size justification is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcome measures, including antibody titers and laboratory abnormalities, and describes the primary antibody outcome across the study groups. The registry record does not identify a single comparative contrast among the schedules and formulations or report how multiplicity was addressed. It does not state whether testing was hierarchical, whether adjustments were applied, or which outcomes or comparisons were considered confirmatory.
The primary analysis population was the According-to-Protocol cohort for Immunogenicity. The record describes this cohort as evaluable subjects with immunogenicity data and available assay results for antibodies against at least one study vaccine antigen component after vaccination. It does not report the analysis population size by group, the number of missing measurements, reasons for missingness, or methods for handling missing data. Imputation, sensitivity analyses, and rules for protocol deviations are not reported in the registry record.
The record does not report whether all randomized participants were included in a separate intention-to-treat analysis. Nor does it give participant flow details or a comparison of included and excluded participants. These omissions matter because an according-to-protocol estimate describes the evaluable population as defined, and may not represent all randomized participants if availability of measurements or protocol adherence is related to outcomes.
Detailed statistical analysis methods, including the handling of multiple outcomes and the rationale for the analysis population, are not reported in the registry record. Without those details and numerical endpoint results, the strength and robustness of any comparative conclusion cannot be assessed from the posted record.
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 |
|---|---|---|---|
| Cervarix 1/Placebo Group | 14 | 240 | 5.8% |
| Cervarix 1/Placebo/Cervarix 1 Group | 16 | 241 | 6.6% |
| Cervarix 2/Placebo/Cervarix 2 Group | 19 | 240 | 7.9% |
| Cervarix 2 Group | 15 | 239 | 6.3% |
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 |
|---|---|
| Cervarix 1/Placebo Group | 229 of 240 |
| Cervarix 1/Placebo/Cervarix 1 Group | 233 of 241 |
| Cervarix 2/Placebo/Cervarix 2 Group | 228 of 240 |
| Cervarix 2 Group | 233 of 239 |
Most frequent serious adverse event terms
| Event term | Organ system | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | 0 of 240 | 2 of 241 | 4 of 240 | 1 of 239 |
| Abdominal pain | Gastrointestinal disorders | 3 of 240 | 1 of 241 | 0 of 240 | 1 of 239 |
| Abortion spontaneous incomplete | Pregnancy, puerperium and perinatal conditions | 0 of 240 | 0 of 241 | 2 of 240 | 1 of 239 |
| Depression | Psychiatric disorders | 0 of 240 | 1 of 241 | 1 of 240 | 1 of 239 |
| Umbilical hernia, obstructive | Gastrointestinal disorders | 0 of 240 | 2 of 241 | 0 of 240 | 0 of 239 |
| Tonsillitis | Infections and infestations | 0 of 240 | 0 of 241 | 0 of 240 | 2 of 239 |
| Urinary tract infection | Infections and infestations | 1 of 240 | 0 of 241 | 0 of 240 | 1 of 239 |
| Vestibular neuronitis | Infections and infestations | 1 of 240 | 1 of 241 | 0 of 240 | 0 of 239 |
| Tibia fracture | Injury, poisoning and procedural complications | 0 of 240 | 1 of 241 | 1 of 240 | 0 of 239 |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | 1 of 240 | 0 of 241 | 1 of 240 | 0 of 239 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cervarix 1/Placebo Group | Cervarix 1/Placebo/Cervarix 1 Group | Cervarix 2/Placebo/Cervarix 2 Group | Cervarix 2 Group |
|---|---|---|---|---|---|
| Pain | General disorders | 222 of 240 | 225 of 241 | 222 of 240 | 225 of 239 |
| Redness | General disorders | 109 of 240 | 112 of 241 | 123 of 240 | 145 of 239 |
| Headache | General disorders | 101 of 240 | 116 of 241 | 112 of 240 | 125 of 239 |
| Fatigue | General disorders | 100 of 240 | 109 of 241 | 104 of 240 | 107 of 239 |
| Myalgia | General disorders | 79 of 240 | 109 of 241 | 98 of 240 | 99 of 239 |
| Swelling | General disorders | 92 of 240 | 88 of 241 | 83 of 240 | 118 of 239 |
| Gastrointestinal | General disorders | 48 of 240 | 48 of 241 | 36 of 240 | 68 of 239 |
| Arthralgia | General disorders | 45 of 240 | 57 of 241 | 39 of 240 | 43 of 239 |
| Fever | General disorders | 23 of 240 | 20 of 241 | 22 of 240 | 39 of 239 |
| Rash | General disorders | 12 of 240 | 12 of 241 | 10 of 240 | 15 of 239 |
Serious events with the highest arm-level rate: appendicitis (1.7%), abdominal pain (1.2%), tonsillitis (0.8%), abortion spontaneous incomplete (0.8%), umbilical hernia, obstructive (0.8%).
The safety record gives the number of participants at risk and the number affected by serious adverse events and by other adverse events in each group. For serious events, the Cervarix 1/Placebo Group had 14 affected among 240 at risk; the Cervarix 1/Placebo/Cervarix 1 Group had 16 among 241; the Cervarix 2/Placebo/Cervarix 2 Group had 19 among 240; and the Cervarix 2 Group had 15 among 239. These are counts as recorded, not estimates of causation.
For other adverse events, the registry lists 229 affected among 240 at risk in the Cervarix 1/Placebo Group, 233 among 241 in the Cervarix 1/Placebo/Cervarix 1 Group, 228 among 240 in the Cervarix 2/Placebo/Cervarix 2 Group, and 233 among 239 in the Cervarix 2 Group. The registry also lists selected serious event terms and percentages: appendicitis, 1.7%; abdominal pain, 1.2%; tonsillitis, 0.8%; abortion spontaneous incomplete, 0.8%; umbilical hernia, obstructive, 0.8%; and Basedow's disease, 0.4%. The denominator and method for these term percentages are not reported in the registry record.
These summaries do not establish whether events were caused by vaccination, and the record does not provide event-level timing or relatedness details. Death counts are not reported in the registry record. The figures should be read as recorded safety summaries, not as a standalone assessment of comparative risk.
12. What the Result Does, and Does Not, Mean
This trial is designed to assess immune measurements and safety under alternative Cervarix schedules and formulations in healthy females aged 9 to 25 years. Its primary endpoint, antibody titer against HPV-16 and HPV-18, is a laboratory measure of immunogenicity. The endpoint definition and planned summary measure are available, along with the timing of assessment relative to each schedule.
What the posted information does not provide is the numerical primary outcome: no group GMTs, 95% confidence interval limits, comparative estimates, or primary statistical tests are reported in the registry record. As a result, it is not possible to state from these data which schedule or formulation generated higher titers, how large any difference was, or how precisely it was estimated. It is also not possible to distinguish a schedule effect from a formulation effect where both differ between groups.
Even if numerical antibody titers were available, an antibody measurement would not by itself be a direct clinical endpoint. The registry record does not report a protective threshold or an analysis connecting these titers to HPV infection or cervical disease in this trial. Statements in the study summary about the vaccine's targets and prior trials are background, not findings from this trial.
The safety counts document reported adverse events by group, but they do not establish that vaccination caused an event. The record does not report deaths as a numerical count, and the selected serious event terms do not provide all the details needed to assess timing, relatedness, or comparative risk.
Thus, the trial record identifies the research question, group schedules, endpoint, and some adverse-event counts. It does not, as posted, permit a conclusion about comparative immunogenicity, statistical significance, clinical protection, or causal safety differences. Those questions require outcome estimates and analysis details not reported in the registry record.
13. Why This Trial Matters Statistically
The study is statistically interesting because it varies both vaccine scheduling and formulation within one randomized parallel-group trial. Its four schedules create multiple possible comparisons rather than a single uncomplicated contrast. Clear specification of which contrasts answer the primary question is important when interpreting results, especially when outcomes are measured across several groups and at different calendar months.
The primary endpoint also illustrates the distinction between a biomarker and a clinical outcome. Antibody GMTs summarize assay measurements and can characterize immunogenicity. They do not automatically quantify infection prevention or disease outcomes. A statistical report therefore needs to make clear what the assay estimates can establish and what additional evidence would be needed to connect them with clinical outcomes.
The timing of measurement is another relevant design feature. Each group's outcome was assessed one month after its last dose, but the recorded assessment month differs between the Cervarix 1/Placebo Group and the other groups. That timing is part of the endpoint definition and should be considered when comparing summaries or interpreting follow-up.
Finally, the registry record demonstrates why outcome definitions alone are not enough for statistical interpretation. It specifies a geometric mean and 95% confidence interval, and names the according-to-protocol immunogenicity population, but does not report numerical estimates, analysis details, or missing-data handling. Without these, readers cannot judge the magnitude or precision of a group contrast or its sensitivity to analytic choices. The design is identifiable; the comparative result is not reported in the registry record.
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 limitation of the posted record for interpreting the primary question is the absence of numerical antibody results. GMTs, confidence interval limits, and comparative statistical tests are not reported in the registry record. The effect's direction, magnitude, and precision therefore cannot be assessed.
The registry describes a primary analysis population based on evaluability and available assay results, but does not report its size by group or the number and reasons for exclusions. Missing-data methods, sensitivity analyses, and protocol-deviation handling are not reported in the registry record. This limits assessment of how the according-to-protocol analysis may differ from the randomized population.
The four groups vary by schedule and formulation, while the record does not identify a single primary pairwise comparison or report a multiplicity strategy. The endpoint timing is also not at the same calendar month across groups: it is Month 3 for the Cervarix 1/Placebo Group and Month 7 for the other groups. Detailed methods for handling comparisons and timing are not reported in the registry record.
Although the record labels the study randomized and single-masked, it does not report the randomization procedure or who was masked. It also does not report a detailed statistical analysis plan or sample-size justification. For safety, adverse-event counts and selected serious event terms are available, but event relatedness and numerical death counts are not reported in the registry record. These limits restrict interpretation of both comparative immunogenicity and safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Partially Blind Study to Evaluate Immunogenicity & Safety of GSK Bio's HPV Vaccine 580299 in Healthy Women Aged 9-25 Yrs — NCT00541970.
- Registry record last updated 2018-08-17; status last verified 2016-08.
- Results first posted 2014-04-17.
- 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
NCT00541970 is a completed randomized, single-masked, parallel-group phase 1 study sponsored by GlaxoSmithKline. The registry lists enrollment as 961, with a start date of 2007-10-17 and primary completion date of 2013-03-18. Participants were healthy females aged 9 to 25 years assigned to one of four Cervarix schedule and formulation groups, with placebo doses included in some schedules.
The primary endpoint was the geometric mean titer of antibodies against HPV-16 and HPV-18, expressed in EL.U/mL and assessed one month after the last vaccine dose. The primary analysis population was the According-to-Protocol cohort for Immunogenicity. Numerical GMTs, confidence interval limits, comparative tests, and detailed analysis methods are not reported in the registry record. Safety counts are listed by group, along with selected serious event terms and percentages; numerical death counts are not reported in the registry record.