Immunogenicity and Safety of PrepandrixTM in Korean Subjects Aged 18 to 60 Years Old: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety of PrepandrixTM in Korean Subjects Aged 18 to 60 Years Old (NCT01730378), a randomized phase 4 study. The primary outcome is Number of Seroconverted Subjects for Serum H5N1 Haemagglutination-inhibition (HI) Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group..

2. Clinical Question

The central statistical question is narrower than a direct comparison of the two vaccines. The registry's primary endpoint is a count of seroconverted subjects in the Prepandrix group. It is not specified as a difference between the Prepandrix and Fluarix groups, and the listed primary outcome does not define a corresponding Fluarix result. Thus, the registry record describes assessment of immunogenicity in a treatment group alongside a control group, but the primary endpoint itself does not state a comparative treatment effect.

Seroconversion is defined using the change in HI antibody titer from before vaccination to after vaccination. A subject qualifies either by meeting the stated threshold change from a pre-vaccination titer below 1:10 to a post-vaccination titer of at least 1:40, or by having a pre-vaccination titer of at least 1:10 and at least a 4-fold rise after vaccination. The endpoint is assessed at Day 42. The registry record does not report the number of subjects meeting this definition, an estimate of uncertainty, or a statistical test result.

3. Trial Design

This was a randomized, parallel-group Phase 4 study sponsored by GlaxoSmithKline. The registry lists an enrollment of 131 and describes the study as completed. The recorded study start date is 2012-12-05, and the primary completion date is 2013-12-17. The study concerned Prepandrix™ immunogenicity and safety in Korean subjects aged 18 to 60 years; Fluarix™ was used as a control vaccine.

The intervention schedules differed. Subjects in the Prepandrix group received 2 doses, on Days 0 and 21. Subjects in the Fluarix group received 1 dose, on Day 0. Both descriptions specify intramuscular administration in the deltoid region, with the arm used also recorded for each dose. These schedule differences matter when interpreting the groups: the registry's primary outcome is not a comparison that isolates vaccine identity while holding dose schedule constant.

Allocation is listed as randomized, while masking is listed as none. The study is therefore described as open-label in the sense that masking was not used. The registry does not report the sequence-generation method, allocation-concealment procedures, or additional operational details. Those methods are not reported in the registry record.

The primary endpoint is a count of subjects in the Prepandrix group who seroconverted for HI antibodies against the H5N1 vaccine strain at Day 42. The listed secondary outcomes include antibody titers, seroprotection, seroconversion, and mean geometric increase measures, with outcomes specified separately for the Prepandrix and Fluarix groups and for different influenza strains. The registry lists 19 outcome measures, but the number of analyses is 0. Outcome analysis results are not reported in the registry record, so the design and endpoint definitions can be described, but outcome estimates cannot be interpreted.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome variables were available. This included subjects for whom assay results were available for antibodies against at least 1 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Seroconverted Subjects for Serum H5N1 Haemagglutination-inhibition (HI) Antibodies Against Flu A/Indonesia/5/2005 (H5N1) Vaccine Strain in Prepandrix Group., measured over At Day 42.

The primary endpoint counts subjects in the Prepandrix group who met the study's definition of seroconversion for serum H5N1 HI antibodies against Flu A/Indonesia/5/2005. The assessment time is Day 42. This is an antibody-response endpoint: it classifies a subject according to the change in HI titer from pre-vaccination to post-vaccination, rather than counting influenza illness or another clinical event.

The registry defines seroconversion as either a pre-vaccination titer below 1:10 followed by a post-vaccination titer of at least 1:40, or a pre-vaccination titer of at least 1:10 followed by at least a 4-fold increase. The two routes account for different starting titers: a subject starting below the stated threshold is assessed using an absolute post-vaccination threshold, while a subject starting at or above it is assessed using the relative rise.

In general, a prespecified antibody-response endpoint can summarize whether participants crossed a defined laboratory threshold after vaccination. The definition makes the classification rule explicit, but it does not by itself establish the size or precision of the observed response. The number meeting the rule, the denominator analyzed, and an uncertainty estimate would be needed to describe the result. These outcome results are not reported in the registry record. The listed primary endpoint is also specific to the Prepandrix group; it does not, as written, quantify a between-group contrast with Fluarix.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary outcome count?

The primary outcome is a binary classification at the participant level: each subject either meets the seroconversion definition or does not. The registry reports the endpoint as a number of subjects, rather than a continuous antibody-titer summary. The definition uses pre-vaccination and post-vaccination HI titers and includes separate rules for subjects with different baseline titers. The assessment is scheduled at Day 42 for the H5N1 vaccine strain in the Prepandrix group.

In general, a count is easiest to interpret alongside its analysis denominator. A count alone does not indicate how common the event was among the participants assessed. For a binary endpoint, a proportion and its confidence interval can describe frequency and precision, while a treatment comparison would require a clearly specified contrast and suitable analysis. The registry record does not report a primary endpoint count, denominator, proportion, confidence interval, or test result.

What does randomization contribute?

Random allocation is intended, in general, to reduce systematic differences between treatment groups at assignment. It does not guarantee that groups will be identical in every characteristic, especially in a study with limited enrollment. Analysis choices and follow-up also affect how informative a randomized comparison is. The registry identifies the allocation as randomized, but the specific randomization method and concealment procedures are not reported in the registry record.

Masking is listed as none. In general, an unmasked design can make expectations relevant to participant reports, clinical assessments, decisions about follow-up, or event classification, depending on what is measured and how. The primary outcome is based on antibody titers, but the registry does not describe laboratory blinding or other safeguards. Such details are not reported in the registry record and should not be assumed.

How should the group structure be understood?

The design is parallel-group, with Prepandrix™ and Fluarix™ assigned to separate groups. The intervention schedules differ: Prepandrix involves 2 doses at Days 0 and 21, and Fluarix involves 1 dose at Day 0. The registered primary endpoint is restricted to the Prepandrix group, so it does not define a direct randomized contrast for that outcome. A comparative analysis would need an explicit outcome definition for both groups, a target contrast, and a plan for handling the timing and schedule differences.

The secondary outcome list includes HI titers, seroprotection, seroconversion, and mean geometric increase measures. In general, geometric summaries are used for measurements such as titers that can be strongly skewed; a geometric mean summarizes values on a multiplicative scale. A mean geometric increase describes a change relative to baseline using that scale. The registry lists these outcome types but does not report their estimates or analysis procedures.

What do the analysis-population and planning descriptions tell us?

The primary outcome description says that analysis was performed on an According-to-Protocol cohort for immunogenicity, described as including evaluable subjects for whom immunogenicity outcome data were available. It also refers to assay results for antibodies against at least 1 study vaccine, but the population description ends before the sentence is complete. The exact cohort rules, exclusions, and denominator for the primary outcome are therefore not fully described in the registry record.

The sample-size assumptions are described as an illustration computed from the observed effect, not as the trial's own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the groups, a normal approximation, and a target effect expressed as a fraction of the observed effect. In general, a planning calculation estimates the number of participants needed under chosen assumptions about the effect, variability, allocation, and error rates. Such calculations depend on those assumptions and are not evidence that an analysis had a particular probability of detecting an effect. The registry record does not report the original sample-size justification or actual sample-size illustration values.

The registry lists 19 outcome measures and 0 analyses. Statistical methods for the outcome analyses, including the approach to confidence intervals, hypothesis tests, covariate adjustment, missing observations, and multiplicity, are not reported in the registry record. Those omissions prevent a detailed reconstruction of how the endpoint definitions were intended to translate into final estimates.

Why do analysis details matter?

General statistical interpretation depends on more than the endpoint label. The analysis population determines who contributes to an estimate; missing-data handling determines how unavailable measurements are treated; and the selected summary and comparison determine the question answered. For binary outcomes, small changes in the analyzed denominator can affect both the reported proportion and its precision. For antibody titers, the distribution and transformation used can affect the summary. None of those choices should be inferred from outcome names alone.

Multiplicity is another general consideration when a study lists many outcomes or comparisons. Testing several hypotheses can increase the chance of at least one apparently notable result if no strategy is used to control or otherwise address that issue. A prespecified hierarchy, adjustment, or descriptive interpretation could be appropriate depending on the aims, but the registry record does not report a multiplicity strategy. Because no outcome analyses are listed, there are no posted inferential results to assess in light of such a strategy.

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("Prepandrix Group")
n      <- c(81)
events <- c(81)
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  Prepandrix Group  81  81  100.0  95.5  100.0  95.5  100.0  95.6  100.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, spanning antibody titers, seroprotection, seroconversion, and mean geometric increase for the vaccine groups and strains described. With multiple outcomes, general statistical practice considers how results will be prioritized and how the possibility of chance findings across multiple tests will be handled. The registry record does not report a multiplicity strategy, such as a testing hierarchy or adjustment method. No particular approach should be assumed.

The primary analysis population is described as an According-to-Protocol cohort for immunogenicity, including evaluable subjects with available immunogenicity outcome data. The accompanying description is incomplete: it refers to assay results for antibodies against at least 1 study vaccine and then ends mid-sentence. The full eligibility rules, exclusions, and endpoint-specific denominators are not reported in the registry record. The record also does not report how missing measurements, withdrawals, or protocol deviations were handled, or whether any imputation method was used.

These details affect interpretation. In general, an analysis restricted to evaluable participants can differ from an analysis of all randomized participants if availability or evaluability is related to outcomes or treatment assignment. The registry record does not provide enough information to assess whether that concern arose or how it was addressed. It lists 0 analyses, so there are no posted outcome estimates against which to examine the analysis population, missingness, or multiplicity decisions.

The record does not report a statistical analysis plan, the timing of any interim analyses, or the prespecified treatment of secondary outcomes. Those items are not reported in the registry record. Accordingly, the outcome definitions can be described, but the conduct and inferential framework of the analyses cannot be reconstructed.

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: appendicitis (1.2%), endometriosis (1.2%), ovarian cyst (1.2%).

The registry lists serious adverse event counts for the Prepandrix group with 84 subjects at risk and 1 affected, and for the Fluarix group with 47 subjects at risk and 0 affected. These are descriptive counts as recorded; the registry does not report a comparative safety analysis or uncertainty estimates for them. A count of affected subjects is not, by itself, evidence that an event was caused by the vaccine.

Three serious adverse event terms are listed: Appendicitis, Endometriosis, and Ovarian cyst, each with a reported value of 1.2%. The registry record does not specify in this listing which treatment group each term belongs to, so the terms should not be assigned to a group. The record also lists other adverse events for 84 subjects at risk and 81 affected in the Prepandrix group, and 47 at risk and 40 affected in the Fluarix group. The meaning and event definitions for this category are not further described in the available record.

Deaths are not reported in the registry record. These safety entries do not provide event timing, duration, severity details beyond the serious-event classification, exposure-adjusted rates, or a full accounting of follow-up. They should therefore be read as registry counts rather than a complete assessment of comparative safety.

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

The registry record describes a randomized Phase 4 study of Prepandrix™ and Fluarix™ in Korean subjects aged 18 to 60 years, including a primary immunogenicity endpoint for the Prepandrix group. It gives the seroconversion definition and assessment time, and it records group-level safety counts. Those details clarify what the study intended to measure and what safety entries were posted.

The record does not report the primary endpoint result or any outcome analyses. It therefore does not establish how many Prepandrix subjects seroconverted, what proportion that count represents, or how precisely an estimate was measured. It also does not report a comparative primary analysis between Prepandrix and Fluarix. The presence of a randomized control group should not be mistaken for a reported comparative result.

In general, an antibody response measure describes a laboratory response under a defined assay and threshold. It is not itself a count of clinical influenza cases. Interpretation of clinical benefit would require relevant clinical outcomes and an appropriate analysis; those are not reported in the registry record. Similarly, the safety counts do not demonstrate that an event was caused by either vaccine, and they do not constitute a complete comparison of risks.

The registry's design details also matter to any interpretation of future or external results. The study was unmasked, the treatment schedules differed, and the primary endpoint is confined to the Prepandrix group. The analysis population description is incomplete, and the statistical methods for outcomes are not reported. These features do not determine the direction of a result, but they limit what can be concluded from the registry record as it stands.

Accordingly, the sound reading is descriptive: the registry identifies the population, interventions, endpoint definition, and some safety counts, while leaving the immunogenicity results and analysis details unavailable. It supports neither a conclusion that one vaccine is superior nor a conclusion that the vaccines are equivalent. Such comparative conclusions would require results and an analysis addressing the comparison directly.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a registered question and a reported answer. The record specifies a randomized, parallel-group design and a detailed antibody seroconversion rule, yet lists 0 analyses. Clear endpoint definitions are important, but they cannot substitute for an observed estimate, its denominator, and an account of uncertainty.

The primary endpoint also illustrates why the estimand matters. It is a count within the Prepandrix group, while the study includes a Fluarix control group. A treatment-group count and a between-group contrast answer different questions. The registry's primary outcome, as described, does not state a comparative effect, so the presence of randomization alone does not create a reported comparison.

The different dosing schedules further highlight the need to define what a comparison is intended to represent. Prepandrix was administered on Days 0 and 21, while Fluarix was administered on Day 0. If a comparative result were reported, interpretation would need to account for what the assigned regimens mean, rather than treating the design as a comparison of vaccines under identical schedules.

The record is also a reminder that an analysis population and missing-data plan are part of the evidence. The immunogenicity cohort is described as an According-to-Protocol population of evaluable subjects with available measurements, but the description is incomplete. Without complete cohort rules and analyzed denominators, readers cannot judge how the analysis set relates to randomized participants.

Finally, planning illustrations should not be confused with observed evidence. The registry states assumptions for sample-size illustrations but does not report the trial's own sample-size justification or outcome estimates. Statistical precision must be assessed from analyzed data, not inferred from planning assumptions. Here, the design can be described, but the posted record does not permit an assessment of the precision of the primary immunogenicity result.

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.

Several limitations are specific to the information recorded for this trial. The primary endpoint is restricted to the Prepandrix group, even though the study includes a Fluarix control group. The registry therefore does not define the primary outcome as a direct comparison between randomized groups. The dosing regimens also differ: Prepandrix was given on Days 0 and 21, while Fluarix was given on Day 0. Any interpretation of a group contrast would need to take that distinction into account.

The study is listed as unmasked. The registry does not describe whether laboratory staff were masked to group assignment or whether safeguards were used in outcome assessment. These details are not reported in the registry record. The specific randomization procedures and allocation-concealment methods are also not reported.

The immunogenicity analysis population is described as an According-to-Protocol cohort of evaluable subjects with available outcome data, but the definition is cut off after referring to assay results for antibodies against at least 1 study vaccine. The complete inclusion and exclusion rules, missing-data procedures, and endpoint-specific denominators are not reported. The statistical analysis plan, multiplicity strategy, and interim-analysis details are also not reported in the registry record.

Most importantly, the record lists 0 analyses and does not report outcome results. There is no primary endpoint estimate, uncertainty interval, or comparative result to evaluate. The safety listings are limited registry counts and do not give complete event descriptions or a full comparative analysis. These limitations concern the information available in the registry record; they do not establish what may have been reported elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Immunogenicity and Safety of PrepandrixTM in Korean Subjects Aged 18 to 60 Years Old — NCT01730378.
• Registry record last updated 2018-09-07; status last verified 2016-05.
• Results first posted 2014-12-24.
• 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

NCT01730378 is a completed, randomized, open-label, parallel-group Phase 4 study sponsored by GlaxoSmithKline. It enrolled 131 Korean subjects aged 18 to 60 years. Prepandrix™ was given in 2 doses on Days 0 and 21; Fluarix™ was given in 1 dose on Day 0. The primary endpoint was the number of Prepandrix subjects who seroconverted for HI antibodies against Flu A/Indonesia/5/2005 at Day 42.

The registry lists 19 outcome measures and 0 analyses. It does not report the primary immunogenicity result, comparative efficacy estimates, confidence intervals, p-values, or a complete statistical analysis plan. Safety entries include serious adverse event counts of 1 among 84 at risk in the Prepandrix group and 0 among 47 at risk in the Fluarix group. The registry's outcome results and several analysis details are not reported in the registry record.