Safety Surveillance of Pneumococcal 13-valent Conjugate Vaccine Among Filipinos: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Surveillance of Pneumococcal 13-valent Conjugate Vaccine Among Filipinos (NCT01396434), a registered phase not stated study. The primary outcome is Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a non-interventional post-marketing safety surveillance study of Prevenar 13 in the Philippines. Its official title identifies it as a study of pneumococcal 13-valent conjugate vaccine safety, and the registry lists pneumococcal disease as the condition. The study status is COMPLETED. The recorded start is 2011-12, and primary completion is recorded as 2014-05. Enrollment is listed as 3006.

The intervention is 13vPnC (Prevenar 13). The registry lists three vaccine cohorts: Cohort 1, Cohort 2, and Cohort 3. The numbers at risk for the safety outcomes are 2817, 175, and 14, respectively. The record does not explain the cohort definitions or why participants entered one cohort rather than another. Allocation is not stated. As the registry cautions, these arms are not a like-for-like control comparison, so differences among their counts should not be read as randomized comparative effects.

The primary outcome concerns participants who received at least 1 dose of 13vPnC. The observation timeframe is baseline through and including 28 calendar days after the last administration of study vaccine within the observation period. The record says that all observed or volunteered AEs and SAEs were reported, regardless of treatment group or suspected causal relationship to 13vPnC. This makes the endpoint a safety-event count, not a causal estimate of vaccine-attributable risk.

Further details about recruitment, follow-up procedures, dose schedules, cohort criteria, and the analysis plan are not reported in the registry record. The record also does not give a separate comparator arm or randomized allocation. These missing design details limit how far the cohort-level summaries can be interpreted beyond describing the events recorded in this surveillance study.

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: Participants who received at least 1 dose of 13vPnC.

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.

Population: All participants who received at least 1 dose of 13vPnC.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over Baseline through and including 28 calendar days after the last administration of study vaccine within the observation period.

The primary endpoint is the number of participants with adverse events (AEs) and serious adverse events (SAEs). The unit is participants, and the parameter is a number of participants rather than a rate or time-to-event measure. Its stated timeframe runs from baseline through and including 28 calendar days after the last administration of study vaccine within the observation period. The population is participants who received at least 1 dose of 13vPnC.

The registry defines an AE as any untoward medical occurrence in a participant who received 13vPnC. An SAE is an AE resulting in death, initial or prolonged inpatient hospitalization, a life-threatening experience involving immediate risk of dying, persistent or significant disability or incapacity, or congenital anomaly; an event deemed significant for another reason also qualifies. AEs include both SAEs and non-SAEs. These definitions concern the event and its seriousness, not whether the vaccine caused it.

Counting affected participants is useful in safety surveillance because it describes how many people had at least one event recorded under the endpoint definition. It does not by itself capture the total number of events per participant, their duration, severity beyond the SAE classification, or their relationship to vaccination. The registry record does not report those additional summaries. It also does not report a separate exposure-adjusted rate or a causal comparison. The endpoint therefore supports a descriptive account of recorded events within the stated follow-up window, with interpretation bounded by the completeness of observation and reporting.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event measure: a participant either had an AE or SAE recorded during the defined observation period or did not. The registry reports the number of affected participants and the number at risk for each cohort. These counts provide a direct descriptive summary, but they do not indicate how many separate episodes occurred in a participant who experienced an event. A participant with multiple events may still contribute only once to a participant count, depending on the endpoint coding; the registry does not give further event-counting details.

What do participant counts describe?

A count answers how many participants met an outcome definition in a cohort. The at-risk count gives context for that count, but the registry does not report a confidence interval or an inferential comparison. General statistical principle: a count is most informative when the population and observation period are clearly defined, and when the reader knows whether each person is counted once or whether repeated events are included. Here, the endpoint specifies participants with AEs and SAEs and gives a follow-up timeframe; further rules for deduplicating events are not reported in the registry record.

The word “binary” refers to an outcome with two states for each participant, such as event recorded or not recorded. It does not mean that all events have the same clinical meaning. The registry includes a broad AE definition and a more restrictive SAE definition. AEs include SAEs as well as non-SAEs, so the categories are conceptually related rather than unrelated types of outcomes. The posted summaries list serious and other adverse events separately, but additional participant-level overlap details are not reported.

Why is causal attribution important?

The record says observed or volunteered events were reported regardless of suspected causal relationship to 13vPnC. This is important because an AE is defined as an untoward medical occurrence after exposure, not necessarily an event caused by that exposure. General statistical principle: an event count in an exposed group combines events that may be related to treatment with events that may arise for other reasons. A credible causal comparison usually depends on an appropriate comparison group, clear assignment or adjustment methods, and careful consideration of differences between groups. The registry does not report a separate control arm, randomized allocation, or an adjusted causal analysis.

Because the study is non-interventional and allocation is not stated, the three vaccine cohorts should not be treated as though participants were randomly assigned to comparable groups. General statistical principle: differences in cohort composition, follow-up, or ascertainment can affect observed counts. The cohort descriptions and selection process are not reported in the registry record, and the record explicitly cautions that the arms are not a like-for-like control comparison. Therefore, cohort differences are descriptive rather than estimates of the effect of choosing one treatment over another.

What does uncertainty mean?

A confidence interval is a range of values compatible with the observed data under a specified statistical model. General statistical principle: intervals communicate precision as well as the direction and scale of an estimate; a wide interval indicates that the data do not pin down the underlying value closely. No confidence intervals are reported for these outcomes. The number of serious events is small, and some cohorts have few participants at risk, so a zero observed count should not be interpreted as proof that the underlying event possibility is zero. The registry supplies no model-based estimate of that possibility.

For binary outcomes, methods may use exact or approximate approaches to quantify uncertainty. The suitable method depends on the data structure and the intended estimand. General statistical principle: normal approximations can be less reliable when counts are sparse or expected event counts are small. The registry record does not report the method used for uncertainty estimation, and it does not post inferential analyses for this endpoint. No specific interval or test should be inferred from the descriptive counts.

How should planning illustrations be read?

The associated sample-size calculations are planning illustrations based on an observed effect, not the study’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. General statistical principle: a planning calculation estimates the sample size that would be needed under its assumptions to detect a specified effect with a chosen power. Such a calculation is not evidence that the study had that power, and it does not replace the study’s actual design or analysis plan.

The registry record does not report the original sample-size justification or a statistical analysis plan. The planning assumptions also describe a hypothetical equal-allocation comparison, while the registry’s actual safety summaries are from three differently sized vaccine cohorts and no comparator group is reported. Any resulting participant-per-arm values should therefore be understood only in the context of their stated planning assumptions. They are not observed outcomes, and they are not estimates of observed power.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy, such as a hierarchy of primary and secondary outcomes or an adjustment for testing multiple hypotheses. It lists 1 outcome measure and 0 analyses. No hypothesis tests or inferential estimates for the primary safety endpoint are reported in the registry record. As a result, there is no posted family of statistical tests from which to assess how multiplicity was handled.

Missing-data procedures are not reported in the registry record. It does not state how participants with incomplete follow-up, missing event information, or unavailable outcome assessments were handled. The record also does not describe losses to follow-up, the completeness of event surveillance, or whether participants contributed observation time for the full stated timeframe. The outcome population is participants who received at least 1 dose of 13vPnC, but further analysis-population definitions are not reported.

The endpoint includes observed or volunteered events during baseline through and including 28 calendar days after the last administration of study vaccine within the observation period. The registry does not specify how the observation window was operationalized for participants with different exposure histories, or how events with uncertain onset or reporting dates were classified. These details matter because incomplete or differing observation can influence the number of recorded events.

General statistical principle: missing outcomes can bias a safety summary if the likelihood of missing information is related to participants’ health or event status. A complete-case count may describe only those with available data, while assumptions or sensitivity analyses can help assess uncertainty. No missing-data method or sensitivity analysis is reported in the registry record, so the potential effect of incomplete reporting cannot be quantified from the posted information.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchopneumonia (0.0%).

The serious adverse event counts are participant counts. Cohort 1 lists 1 participant with an SAE among 2817 at risk; Cohort 2 lists 0 among 175; Cohort 3 lists 0 among 14. These figures describe what was recorded in each cohort during the endpoint timeframe. A zero count means that no participant with an SAE is listed for that cohort in the posted summary; it does not establish that such events are impossible or that no unreported event occurred.

The registry defines an SAE by outcomes or significance, including death, initial or prolonged inpatient hospitalization, a life-threatening experience involving immediate risk of dying, persistent or significant disability or incapacity, congenital anomaly, or another reason for deeming an event significant. The event need not be judged related to the vaccine to be included: all observed or volunteered events were reported regardless of suspected causal relationship.

Bronchopneumonia is listed among the serious terms at 0.0%. The registry record does not explain the denominator, rounding, or how that term-level figure relates to the cohort-level SAE count. It should not be used to infer that the cohort-level count is incorrect or to attribute an event to the vaccine.

General statistical principle: sparse serious-event counts provide limited precision about the underlying frequency, especially when cohort sizes differ. The registry does not report confidence intervals, a comparison with an unexposed group, or a causal analysis. These counts are therefore best read as surveillance observations, not as a comparative estimate of risk.

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

The posted results document reported adverse events during a defined surveillance period among participants who received at least 1 dose of 13vPnC. They distinguish serious adverse events from other adverse events and give participant counts for three cohorts. This is useful descriptive information about what the registry recorded, including the cohort-level serious-event counts and non-serious event counts.

The figures do not establish whether any event was caused by the vaccine. The endpoint deliberately includes observed or volunteered events regardless of suspected causal relationship, and the registry does not report a causal adjudication. Nor does it provide a separate untreated comparator group or a randomized comparison. The cohorts are not identified as like-for-like control groups, and the record cautions against treating them that way.

The counts also do not establish the underlying frequency of events with high precision. No confidence intervals or statistical tests are reported. A zero count in a cohort is an observation in the posted data, not proof that the event cannot occur. Likewise, differences in raw counts across cohorts should not be interpreted without considering their different sizes and the lack of reported cohort-selection details.

The registry record does not report enough information to evaluate completeness of event ascertainment, missing outcome data, or the handling of incomplete follow-up. It does not give detailed eligibility criteria, cohort definitions, event adjudication procedures, or a full statistical analysis plan. These omissions restrict interpretation of how representative and complete the recorded counts are.

Accordingly, the data support a limited conclusion: the registry records the stated numbers of participants with AEs and SAEs in each cohort during the specified timeframe. They do not, by themselves, establish comparative safety, quantify a causal effect, or rule out events that were not observed or reported. Those boundaries apply to any reading of the safety summaries.

13. Why This Trial Matters Statistically

Post-marketing surveillance addresses a different statistical question from a randomized efficacy comparison. It records safety events in a real-world study setting, and its value depends on clear outcome definitions, transparent observation windows, and careful distinction between an event occurring after exposure and an event caused by exposure. This record makes the AE and SAE definitions explicit and identifies the follow-up timeframe, which helps readers understand what the event counts are intended to represent.

The record also illustrates why denominator and design context matter. The three cohorts have different numbers at risk, and no separate control group is reported. Without comparable groups, raw counts do not answer whether exposure changes the chance of an event. The explicit warning that the arms are not a like-for-like control comparison is therefore central to interpretation, rather than a minor technical qualification.

Rare or serious outcomes pose an additional statistical challenge. When few events are recorded, estimates are inherently limited in precision, and a zero count in a cohort is not evidence that the underlying possibility is absent. Here, the SAE counts are sparse, while uncertainty intervals and formal analyses are not reported. Readers can describe the posted observations but cannot use them to obtain a precise comparative estimate from the registry information alone.

The study is also a useful reminder that registry transparency includes what is not reported. Cohort criteria, missing-data handling, and the statistical analysis plan would help readers assess ascertainment and potential bias, but these details are not reported in the registry record. Acknowledging those gaps avoids overstating what a descriptive safety record can establish. The statistical contribution is careful separation of recorded event counts, uncertainty, and causation.

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.

Several limitations specific to this study constrain interpretation. It is described as non-interventional, and allocation is not stated. The three listed cohorts do not constitute a reported randomized comparison, and the registry cautions that the arms are not a like-for-like control comparison. The record does not explain cohort definitions or the process by which participants entered each cohort, so differences in their event counts cannot be attributed to differences in treatment or risk.

The primary outcome is defined as participants with AEs and SAEs, but the registry does not give participant-level detail, event-level summaries beyond the listed serious term, or information about repeated events. It reports all observed or volunteered events irrespective of suspected causal relationship. There is no posted causal adjudication or comparison with an unexposed population. Thus, the counts cannot identify vaccine-attributable events.

The record lists enrollment of 3006, while the safety summaries give cohort-specific numbers at risk. The registry does not explain the relationship between enrollment and the cohort risk sets or describe exclusions and follow-up completeness. Missing-data handling, losses to follow-up, and event-ascertainment procedures are not reported in the registry record.

No confidence intervals, hypothesis tests, adjusted analyses, or detailed statistical analysis plan are reported. The term-level listing of Bronchopneumonia at 0.0% is not accompanied by a denominator or explanation connecting it to the cohort-level serious-event count. These limits do not negate the posted counts, but they restrict precision, comparability, and causal interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety Surveillance of Pneumococcal 13-valent Conjugate Vaccine Among Filipinos — NCT01396434.
• Registry record last updated 2017-01-30; status last verified 2016-01.
• Results first posted 2017-01-30.
• 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.

18. Record Summary

The registry describes a completed, non-interventional post-marketing safety surveillance study of Prevenar 13 in the Philippines. Enrollment is listed as 3006; the recorded start is 2011-12 and primary completion is 2014-05. The primary endpoint counts participants with AEs and SAEs from baseline through and including 28 calendar days after the last administration of study vaccine within the observation period.

Three vaccine cohorts are listed. Their SAE participant counts are 1, 0, and 0, and their other AE participant counts are 68, 5, and 0, respectively. The registry cautions that the cohorts are not a like-for-like control comparison. Events were reported regardless of suspected causal relationship to 13vPnC.

Confidence intervals, inferential analyses, missing-data methods, cohort definitions, and a detailed statistical plan are not reported in the registry record. The counts therefore describe recorded events but do not establish comparative or causal effects.