Evaluation of Safety of a Vaccine Against Cervical Cancer in Healthy Korean Females: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Safety of a Vaccine Against Cervical Cancer in Healthy Korean Females (NCT01101542), a registered phase not stated study. The primary outcome is Number of Subjects Reporting Unsolicited Adverse Events (AEs).

2. Clinical Question

The study is described as post-marketing surveillance intended to collect safety information in the local target population under Korean regulatory requirements. It is therefore a descriptive safety question in the registry record, rather than a randomized efficacy comparison. The record does not establish whether an event was caused by vaccination: its definition includes events whether or not they were considered related to the medicinal product.

3. Trial Design

This completed study is registered as an evaluation of the safety of a vaccine against cervical cancer in healthy Korean females. Its official title identifies the intervention as GlaxoSmithKline Biologicals' HPV-16/18 vaccine, Cervarix, administered according to Korean prescribing information. The brief description characterizes the work as Post Marketing Surveillance intended to collect safety data in the local target population under Korean Food and Drugs Administration regulations.

The registry reports enrollment of 3091 and lists the Cervarix Group. Its arm description says subjects received 3 doses, administered intramuscularly into the deltoid muscle of the non-dominant arm, on a 0,1, 6 month schedule. Data collection is also listed as an intervention. The record does not describe a control arm, and allocation is not stated. The study is not a randomized comparison; its listed arm is not a like-for-like control comparison.

The registry reports a start date of 2010-07-01, a primary completion date of 2014-02-20, and status COMPLETED. The primary endpoint concerns unsolicited adverse events during the 30-day period from Day 0 to Day 29 after any vaccination, during the 3rd year of surveillance. The registry describes the primary analysis population as the Total Vaccinated cohort, including all vaccinated subjects with at least one Cervarix administration documented.

The registry lists 10 outcome measures and 0 analyses. A protocol description, detailed follow-up procedures beyond the endpoint timeframe, and a statistical analysis plan are not reported in the registry record. The arm description ends mid-sentence after beginning to discuss flexibility in the vaccination schedule, so the remaining scheduling detail is 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: As per study protocol, subjects who had received 1 or 2 doses of Cervarix vaccine prior to the start of the Post-Marketing Surveillance Study (PMS) could also be enrolled. A total of 3091 participants were enrolled in the study, 105 were available for Year 3 Surveillance and 569 were available for Year 4 Surveillance.

Year 3 Surveillance Period

Reasons for not completing this period:

Year 4 Surveillance Period

Reasons for not completing this period:

Year 5 Surveillance Period

Reasons for not completing this period:

Year 6 Surveillance Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Total Vaccinated cohort that included all vaccinated subjects with at least one dose of Cervarix vaccine administration documented.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects Reporting Unsolicited Adverse Events (AEs), measured over During the 30-day period (Day 0 to Day 29) following any vaccination (During the 3rd year of surveillance)..

The primary endpoint is the number of subjects reporting unsolicited adverse events during the 30-day period from Day 0 to Day 29 following any vaccination in the 3rd year of surveillance. The unit is subjects, and the measure is a count. The analysis population is the Total Vaccinated cohort, defined as vaccinated subjects with at least one documented Cervarix administration.

The registry defines an unsolicited adverse event broadly: an untoward medical occurrence temporally associated with use of a medicinal product, whether or not considered related to it, reported in addition to solicited events. The definition also includes solicited symptoms that begin outside the specified follow-up period for those symptoms. Thus, the endpoint is not limited to events judged vaccine-related, and its label does not itself establish causation.

As a general statistical point, an event count can describe how often an outcome was observed in a defined population and timeframe. The endpoint's usefulness depends on applying its definition consistently and identifying the population and observation window clearly. These details make the registry's stated cohort and follow-up period important to interpretation.

The registry record does not separately report the primary endpoint result, an uncertainty interval, or a comparison estimate. The serious and other adverse-event figures in the safety summary should not be assumed to be the primary endpoint result: the record does not establish that they use the same event definition and timeframe.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For general statistical interpretation, a binary safety outcome can be represented as whether each participant experienced the defined event during the relevant observation window. A count then records how many participants met that definition. Such a count is meaningful only alongside its population, event definition, and timeframe. This study's primary endpoint specifies all three in broad terms: vaccinated subjects with at least one documented dose, unsolicited adverse events, and the 30-day period from Day 0 to Day 29 after any vaccination during the 3rd year of surveillance.

What does a participant count describe?

A participant count is not necessarily the same as a count of all event episodes. A subject may have more than one event, while a subject-level endpoint may count that person once if the endpoint is whether any qualifying event occurred. The primary endpoint is explicitly expressed in subjects. The registry does not report a separate number of event episodes for that endpoint, nor does it describe how repeated events were handled in other outcomes.

The adverse-event summary separately lists subjects affected and subjects at risk for serious and other events. Those counts describe the registry's summary, but the record does not supply enough detail to establish whether the categories overlap or how repeated events were handled. It is not appropriate to add the category counts or interpret them as mutually exclusive groups.

Why do the event definition and timeframe matter?

Safety findings depend on what qualifies as an event and when events are counted. The registry's definition of unsolicited adverse events includes untoward medical occurrences whether or not considered related to the medicinal product. It also includes solicited symptoms whose onset falls outside their specified follow-up period. This is broader than a definition restricted to events judged to have been caused by treatment.

The stated endpoint timeframe is the 30-day period from Day 0 to Day 29 after any vaccination during the 3rd year of surveillance. It does not, by itself, describe all safety follow-up over the whole study. The registry record does not report whether the endpoint result was collected or analyzed using any additional rules, such as handling incomplete follow-up or determining which vaccination begins the window when schedules vary.

What is the role of an analysis population?

The primary analysis population is the Total Vaccinated cohort, which includes vaccinated subjects with at least one documented dose. This identifies who is intended to contribute to the primary endpoint. It differs conceptually from a population defined by treatment assignment regardless of exposure, but the registry does not report a randomized assignment population. The exact number contributing to the endpoint result, or the number with complete endpoint follow-up, is not reported in the registry record.

In general, defining the analysis population in advance helps clarify which observations inform an estimate. It does not resolve missing outcome information. The registry does not describe how missing data were handled, whether any subjects were excluded from the endpoint analysis, or whether analyses used a different population.

How should uncertainty be assessed?

A confidence interval is a general way to express statistical uncertainty around an estimate. Its width reflects, among other things, the amount of information and the assumptions of the model. A narrow interval generally indicates greater precision under those assumptions; a wide interval indicates more uncertainty. The registry record does not report a confidence interval for the primary endpoint or for the adverse-event counts.

For a binary outcome, general methods can estimate the frequency of participants with an event, while accounting for the denominator and the statistical model. A simple proportion is often used descriptively, but a percentage or interval should not be inferred from the counts unless it is explicitly reported or calculated under a stated method. No new percentage or uncertainty estimate is reported. The posted safety figures remain counts in the registry summary.

What does the design allow statistically?

Because the registry does not describe a comparator and does not state allocation, the study cannot support the usual randomized between-group contrast. In general, a comparison between groups is most interpretable when their construction and follow-up make them suitable controls for one another. The record explicitly cautions that the arms are not a like-for-like control comparison. Consequently, the descriptive safety observations should not be recast as a comparative effect.

Observational safety data can be useful for describing events recorded in the population under surveillance. They may also raise questions for further investigation. However, interpretation can be affected by how participants entered surveillance, event reporting, follow-up completeness, and other factors. The registry does not report details sufficient to assess these features fully.

What do the planning assumptions mean?

General sample-size calculations ask how much information a future study might need to detect a prespecified effect under stated assumptions. The planning illustration described for this record uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not a description of the surveillance study's design. The registry does not report a randomized two-arm comparison, and no sample-size justification is reported in the registry record.

Such calculations are planning illustrations, not observed power. They do not establish that the study had a particular probability of detecting an effect after the data were collected. No planning sample-size values or corresponding results are reported in the registry record. A sample-size calculation also cannot remedy a lack of a suitable comparator or missing outcome information.

The registry lists 10 outcome measures and 0 analyses. It does not report inferential tests, covariate adjustment, interim analyses, or a prespecified statistical analysis plan. Those methods should therefore not be attributed to the study. The reported counts can be described, but claims about adjusted effects, statistical significance, or causal relationships are not supported by the methods information in the record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cervarix Group")
n      <- c(105)
events <- c(30)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cervarix Group  105  30  28.6  20.2  38.2  20.8  37.8  20.8  37.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 0 analyses. It does not report how the outcomes were prioritized beyond identifying the primary endpoint, whether multiple comparisons were planned, or whether any adjustment for multiplicity was used. In general, multiplicity arises when several outcomes or comparisons are assessed: conducting more tests can increase the chance of finding an apparently notable result by chance. Whether that concern applies to particular analyses depends on the analysis plan, which is not reported in the registry record.

The primary analysis population is the Total Vaccinated cohort, defined as all vaccinated subjects with at least one Cervarix dose documented. The record does not report how many subjects contributed complete data to the primary endpoint, whether the analysis population differed for other outcomes, or whether any participants were excluded from specific analyses.

Missing-data procedures are not reported in the registry record. The entry does not say whether missing event reports were treated as absence of an event, whether incomplete follow-up was addressed, or whether any sensitivity analyses were conducted. In general, missing safety information can affect the interpretation of event counts if the chance of missingness is related to participants' experiences or follow-up. Without the study's handling rules and completeness information, the direction or size of any such effect cannot be assessed.

The registry also does not report an interim-analysis plan or a detailed statistical analysis plan. No specific imputation method, censoring rule, or multiplicity correction should be assumed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: exostosis (0.0%), gastroenteritis (0.0%), tonsillitis (0.0%).

The registry's safety summary lists 3 subjects with serious adverse events among 3091 at risk, and 322 subjects with other adverse events among 3091 at risk. These are descriptive counts. The registry record does not provide an event-level account or explain whether a subject could appear in both categories, so the counts should not be added or interpreted as mutually exclusive.

The serious-event terms Exostosis, Gastroenteritis, and Tonsillitis are each displayed as 0.0%. The term-specific event counts and the rounding detail are not reported in the registry record. A displayed value of 0.0% should therefore be read as the recorded presentation, not as conclusive evidence that no case occurred.

The deaths field is not reported in the registry record. A missing value should not be interpreted as zero deaths. The record also does not report enough detail to determine event relatedness, severity grading beyond the serious/other classification, or how recurrent events were counted. In general, serious adverse events are a safety category, not proof that the intervention caused the events. The registry's definition of the primary unsolicited-event endpoint explicitly includes events whether or not considered related to the medicinal product.

13. What the Result Does, and Does Not, Mean

The record documents a completed post-marketing surveillance study of Cervarix in healthy Korean females. It describes a vaccinated cohort and reports safety counts, including 3 subjects with serious adverse events and 322 with other adverse events, each against 3091 at risk in the registry summary. These observations describe what the record reports for the surveillance population; they do not establish that vaccination caused any particular event.

The primary endpoint is specifically the number of subjects reporting unsolicited adverse events during the 30-day period from Day 0 to Day 29 after any vaccination in the 3rd year of surveillance. A distinct result for that endpoint is not reported in the registry record. The general adverse-event counts should not be treated as that primary result without confirmation that they share its definition, timing, and analysis population.

The study does not provide a randomized comparison. No comparator group is described, and allocation is not stated. The registry explicitly cautions that the arms are not a like-for-like control comparison. Therefore, the safety counts cannot show how the event frequency compares with an untreated or alternative-treatment group, and they do not provide a causal estimate.

The record does not report an uncertainty interval, inferential test, adjusted analysis, missing-data procedure, or statistical analysis plan. As a result, it is not possible to assess the statistical precision of the endpoint from the registry entry alone. Nor should the absence of a reported analysis be interpreted as proof of no difference or no risk. Missing information, including the deaths field, is not equivalent to a zero result.

In general, a descriptive surveillance study can characterize events recorded in a defined population and can help inform questions for further study. Its conclusions depend on outcome definitions, completeness of follow-up, and reporting practices. The registry provides some of these details, but not enough to resolve all aspects of ascertainment or causal attribution. The appropriate interpretation is limited to the safety observations and design information actually reported.

14. Why This Trial Matters Statistically

Post-marketing surveillance addresses safety in a setting described as the local target population, after a vaccine is in use under prescribing information. This record focuses on healthy Korean females and identifies the vaccine as Cervarix, an HPV-16/18 vaccine. Its regulatory surveillance purpose is distinct from a randomized trial designed to estimate a treatment contrast.

The statistical value of the record depends on clear definitions. The primary endpoint specifies unsolicited adverse events and a defined 30-day window after vaccination during the 3rd year of surveillance. The record also defines the primary analysis population as vaccinated subjects with at least one documented dose. Those details help readers understand what the planned count represents, even though a separate result for that endpoint is not reported in the registry record.

The entry also illustrates why descriptive safety counts need careful interpretation. Counts of subjects with serious and other adverse events are not causal estimates. Without a comparator, a stated allocation process, and additional information about ascertainment and event relatedness, the counts cannot isolate the contribution of vaccination from other explanations. The registry cautions that the arms are not a like-for-like control comparison.

Finally, the record lists 10 outcome measures but 0 analyses, and does not report a statistical analysis plan or missing-data procedures. This makes it important to distinguish registered outcome definitions from inferential results. A transparent account of populations, event definitions, timeframes, and analysis methods is central to evaluating safety evidence, and gaps in those details limit the strength of conclusions that can be drawn.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation is the absence of a described comparator. The registry lists a Cervarix Group, does not state allocation, and identifies the study as not being a randomized comparison. It also cautions that the arms are not a like-for-like control comparison. Accordingly, the record supports descriptive interpretation rather than a controlled estimate of the vaccine's effect on adverse events.

The primary endpoint is clearly defined by event type, population, and timeframe, but its distinct result is not reported in the registry record. The safety summary's serious and other adverse-event counts may not share the endpoint's definition or its specified 30-day period during the 3rd year of surveillance. The record does not provide enough information to equate them.

Details needed to assess data completeness and ascertainment are limited. Missing-data methods, follow-up completeness, event-reporting procedures, and the handling of recurrent events are not reported in the registry record. The deaths field is also not reported. The registry does not provide term-specific counts for the serious-event terms displayed as 0.0%, or the rounding detail behind those values.

The entry lists 10 outcome measures and 0 analyses. It does not report a detailed statistical analysis plan, inferential tests, adjusted models, interim analyses, or multiplicity procedures. It also does not report confidence intervals for the safety counts. These omissions limit assessment of precision and of how outcomes were selected and analyzed.

The arm description is truncated after beginning to discuss flexibility in the vaccination schedule. Its remaining scheduling details are not reported in the registry record. Although the entry identifies enrollment, study dates, and the primary analysis population, it does not supply enough additional design and conduct detail to assess every source of bias or to reconstruct the endpoint analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Safety of a Vaccine Against Cervical Cancer in Healthy Korean Females — NCT01101542.
• Registry record last updated 2018-07-23; status last verified 2015-10.
• Results first posted 2011-12-19.
• 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.

19. Record Summary

This completed post-marketing surveillance study evaluated safety information for Cervarix in healthy Korean females. The registry reports enrollment of 3091, a start date of 2010-07-01, and a primary completion date of 2014-02-20. The listed intervention is Cervarix, with data collection also described.

The primary endpoint is the number of subjects reporting unsolicited adverse events during the 30-day period from Day 0 to Day 29 after any vaccination during the 3rd year of surveillance. The primary analysis population is the Total Vaccinated cohort, defined as vaccinated subjects with at least one dose documented. A separate result for this endpoint is not reported in the registry record.

The safety summary lists 3 subjects with serious adverse events and 322 with other adverse events, each among 3091 at risk. No comparator is described; allocation is not stated. The registry lists 10 outcome measures and 0 analyses. Statistical analysis details, missing-data procedures, and deaths are not reported in the registry record.