Study of a Pneumococcal Conjugate Vaccine in Adults Aged 50 to 84 Years.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of a Pneumococcal Conjugate Vaccine in Adults Aged 50 to 84 Years. (NCT04583618), a randomized phase 2 study. The primary outcome is Geometric Mean Titers (GMTs) of Pneumococcal Serotypes Using Serotype-Specific MOPA.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, quadruple-masked, parallel-group study. The registry record lists an enrollment of 750 and five vaccine groups: three SP0202 formulations, Prevnar 13, and Pneumovax 23. All five group descriptions specify a single dose at Day 1. The study status is completed.

The record gives a start date of 2020-10-08 and a primary completion date of 2021-08-09. Its stated primary objectives were to assess the immune response of the three SP0202 formulations and the two comparator vaccines 30 days after the single-dose vaccination, and to assess the safety profile of the five vaccines. The primary outcome timeframe is separately stated as post-vaccination at Day 31.

Random allocation means that group assignment was intended to be determined by chance, rather than chosen by participants or investigators. In general, randomization can help balance both measured and unmeasured baseline characteristics across groups, although the registry record does not report the allocation procedure or the resulting baseline balance. Quadruple masking indicates that the study was recorded as masked at four levels, but the identities of those masked and the procedures for maintaining masking are not reported in the registry record.

The record does not report how the 750 participants were allocated among the groups, whether allocation was equal, or the number enrolled and analyzed in each group for the primary endpoint. It also does not provide a detailed account of follow-up, withdrawals, or protocol deviations. Those omissions limit assessment of how participants moved from enrollment to the endpoint analyses.

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: A total of 750 participants were enrolled in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PPAS was subset of the FAS. FAS included subset of randomized participants who received at least 1 dose of the study vaccine and had a valid post-vaccination blood sample result (serotype specific IgG concentration or serotype specific OPA titer for at least one serotype). Only participants with data collected for each specified category are reported.

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: Randomized population included all participants with data in the case report form (CRF).

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean Titers (GMTs) of Pneumococcal Serotypes Using Serotype-Specific MOPA, measured over Post-vaccination at Day 31.

The primary endpoint was geometric mean titers of pneumococcal serotype-specific opsonophagocytic activity, measured using MOPA after vaccination at Day 31. The assay evaluated the opsonophagocytic index, described as 50% killing, of pneumococcal anti-capsular polysaccharide antibodies in human serum. Titers were expressed in terms of 1/dilution, and the reported summary measure was a geometric mean with a 95% confidence interval.

In general, a titer represents a measured antibody activity at a particular dilution. A geometric mean is often used for titers because such measurements may have an uneven, multiplicative distribution; the geometric mean summarizes values on a scale suited to that pattern. The confidence interval communicates uncertainty around the estimated group mean. It does not by itself show whether a vaccine group differs from another group: that requires a defined contrast and an estimate of the contrast with its uncertainty.

OPA is a functional assay: it assesses antibody activity related to the killing of pneumococci in the assay, rather than measuring antibody concentration alone. The registry record also mentions serotype-specific IgG concentrations in its description of the analysis population, but the named primary outcome is the OPA titer endpoint. The record does not report a single serotype or one combined endpoint result that can stand in for the full set of serotype-specific measurements.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is recorded as randomized, quadruple-masked, and parallel-group. In general, randomization assigns participants to groups using chance and can reduce systematic differences between groups at baseline. A parallel design means groups receive their assigned intervention during the same study period rather than crossing over between interventions. Masking is intended to limit the influence of treatment knowledge on participant experience, clinical care, reporting, or assessment. The record does not specify the randomization sequence, concealment method, or which four groups of people were masked.

What does the GMT summarize?

The primary outcome uses geometric mean titers for serotype-specific OPA results. In general, geometric means are appropriate summaries when measurements vary multiplicatively or are skewed on their original scale. The calculation is based on logarithms of the individual measurements, averages those transformed values, and converts the result back to the original scale. This approach does not make every distribution normal, and it does not remove the need to report the number of observations and the analysis population.

The endpoint description says that titers were expressed as 1/dilution and that MOPA evaluated the opsonophagocytic index associated with 50% killing. This is a functional laboratory measure of antibody activity. It is distinct from a direct clinical outcome such as illness, hospitalization, or death. The registry record does not report a clinical disease endpoint in the registry record for this analysis.

What does a confidence interval tell the reader?

The endpoint specifies a 95% confidence interval around the GMT. In general, a confidence interval expresses the uncertainty of an estimate under the assumptions of the statistical method. It is not a range containing a fixed proportion of individual participant values, and it does not mean there is a 95% probability that a particular fixed parameter falls inside the calculated interval. The record does not state the exact interval method, transformation details, or handling of values outside assay limits.

A group-specific interval describes the GMT for that group. To compare two groups, an analysis needs a contrast such as a difference or ratio on a defined scale, together with an interval or test for that contrast. Separate group estimates alone do not give the uncertainty of the between-group contrast. The registry record does not report a single comparison or the result of a statistical test for the primary endpoint.

Why can multiple serotypes complicate interpretation?

Serotype-specific endpoints produce multiple estimates rather than one outcome value. In general, analyzing many outcomes or comparisons increases the chance of at least one apparently unusual result arising by chance. Statistical approaches to address this issue may adjust significance thresholds, control a family-wise error rate, or use a prespecified testing sequence. The registry record does not report a multiplicity strategy or identify a single primary serotype comparison. As a result, no claim about multiplicity control can be made from this record.

Over-dispersion is a general concern when observed variability is greater than a chosen model expects. If a statistical model does not accommodate that extra variability, uncertainty can be understated. This concept may matter for many types of clinical outcomes, but the registry record does not report the model used for the GMT endpoint or evidence that over-dispersion was assessed. It would therefore be inappropriate to attribute any method for handling it to this trial.

What do the planning assumptions mean?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For non-time-to-event outcomes, such illustrations express participants per arm for a stated power target and effect fraction; they are not observed trial results. Planning calculations are conditional on their assumptions and do not reveal the power actually achieved in a completed study. They also do not replace a prospective sample-size justification.

The record does not report the trial's own sample-size justification, the effect size it was designed to detect, or the assumptions used at the design stage. The illustration is therefore not evidence about the original planning process. Since no single primary comparison is reported, it should not be read as demonstrating the power to detect a particular contrast among all five groups.

Finally, the registry record lists no analysis records. It does not describe the statistical software, covariate adjustment, missing-data method, confidence-interval construction, or prespecified testing sequence. These omissions mean that the numerical interpretation of any endpoint estimate cannot be fully assessed from the registry information alone.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is described as serotype-specific GMTs, and the registry record notes multiple categories or time points rather than a single comparison. The record lists nine outcome measures and no analysis records. It does not report which outcomes were designated primary beyond the stated endpoint, how comparisons among the five groups were prioritized, or whether any adjustment was planned for multiple serotypes, outcomes, or treatment contrasts.

In general, multiplicity matters when many statistical questions are tested. The more questions considered, the more opportunity there is for a result to appear notable by chance. Prespecifying a testing hierarchy or controlling an error rate can help make conclusions more reliable. The record does not report a strategy of this kind, so the extent to which multiplicity was addressed is not reported in the registry record.

The endpoint description says the PPAS was a subset of the FAS. The FAS included a subset of randomized participants who received at least one dose and had a valid post-vaccination blood sample result for serotype-specific IgG concentration or OPA titer for at least one serotype. The available description ends before fully specifying the PPAS criteria. Its complete definition, the number analyzed in each population, and the handling of participants missing endpoint measurements are not reported in the registry record.

In general, excluding participants without valid results can affect interpretation if the likelihood of having a measured result differs across groups or relates to the outcome. A clear flow of participants and a stated missing-data method help readers assess that risk. The registry record does not provide those details, nor does it report sensitivity analyses for missing data.

11. Safety Results

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

Deaths

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: atrial fibrillation (0.7%), covid-19 pneumonia (0.7%), subdural haematoma (0.7%), acute respiratory failure (0.7%), acute myocardial infarction (0.7%).

The safety record lists serious adverse events, other adverse events, and deaths by group. For serious events, the listed group counts are 3 of 151 for SP0202-IIb, 7 of 151 for SP0202-VI, 3 of 148 for SP0202-VII, 2 of 149 for Prevnar 13, and 2 of 150 for Pneumovax 23. The death counts are 0, 1, 1, 0, and 0, respectively. These are descriptive counts, not estimates of causal effects.

For other adverse events, the record lists counts of 113 of 151, 122 of 151, 112 of 148, 102 of 149, and 93 of 150 in the same group order. The record does not define the event-collection period or provide details such as severity, duration, relatedness to vaccination, or the rules for counting multiple events in one participant. The counts should therefore be read in the context of the registry's reporting, not as a complete characterization of safety.

The serious-event terms listed include Atrial Fibrillation, Covid-19 Pneumonia, Subdural Haematoma, Acute Respiratory Failure, Acute Myocardial Infarction, and Small Intestinal Obstruction, each with a reported value of 0.7%. The registry record does not establish that these events were caused by a vaccine or provide a basis for comparing their risk across groups. Small counts can also be imprecise, and no comparative confidence intervals are reported in the available record.

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

The record documents a randomized Phase 2 study of three SP0202 pneumococcal conjugate vaccine formulations and two comparator vaccines in healthy adults aged 50 to 84 years. Each group received one dose at Day 1. The stated aims were to assess immune response at around one month and to assess safety. The primary endpoint focused on serotype-specific OPA titers measured by MOPA at Day 31.

These details explain what the trial set out to measure, but they do not establish which formulation had the larger GMT or whether any difference was meaningful. The registry record does not provide a single comparative primary-outcome estimate, its confidence interval, or an analysis result. Nor does the absence of a reported comparison show that the groups had the same immune response. A conclusion of similarity would also require appropriate estimates and an analysis designed to assess similarity or noninferiority.

OPA titers are laboratory measures of functional antibody activity. In general, laboratory immune-response measures can inform biological assessment, but they are not themselves direct measurements of clinical protection. The registry record does not report clinical disease outcomes from which to infer prevention of pneumococcal illness. No medical conclusion about an individual's care follows from the trial description or the posted counts.

The reported safety counts provide a descriptive account of events recorded in each group. They do not establish causation, and the record does not provide the event timing, attribution, or statistical comparisons needed to characterize differences reliably. A lack of deaths in a group in the listed record does not establish that an intervention has no risk.

Overall, the record is informative about the study design, intended endpoints, and broad structure of the safety reporting. Its limits are equally important: no numerical primary-outcome comparison, complete analysis details, or full account of missing-data handling is reported in the registry record. The results should therefore be interpreted as an incomplete basis for comparative efficacy or safety conclusions, rather than as proof for or against any vaccine formulation.

13. Why This Trial Matters Statistically

This study raises several statistical questions that are common in immunogenicity trials. Its primary endpoint comprises serotype-specific antibody activity measurements, while the design includes five vaccine groups. That structure creates a need to define which comparisons are central and how multiple serotypes and groups will be handled. The registry record does not report a single primary contrast or a multiplicity strategy, so readers cannot tell how a trial-wide conclusion was intended to be reached.

The endpoint also illustrates why measurement scale matters. A titer expressed as 1/dilution is not interpreted in the same way as a simple count or a clinical event rate. A geometric mean can suit multiplicative data, and confidence intervals help convey precision. But group summaries are not enough to determine comparative evidence: an explicit contrast and its uncertainty are needed. This registry record does not provide those comparative results.

The study further highlights the distinction between a laboratory immune-response endpoint and a clinical outcome. MOPA measures functional activity in a laboratory assay; it does not directly count cases of disease. That distinction is important whenever statistical estimates are discussed, because the endpoint determines what a result can support and what remains unanswered.

Finally, the trial record includes several safety counts but limited detail about event definitions, timing, attribution, and the analysis population. Such information is needed to move from descriptive counts to an informed comparison. This is a useful reminder that a completed study status and a stated endpoint do not, by themselves, make every planned result interpretable. Statistical conclusions depend on transparent definitions, populations, comparisons, and uncertainty estimates.

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 available registry information does not include numerical GMT estimates or confidence intervals for the primary outcome, nor a single comparative analysis among the five groups. The primary endpoint covers serotype-specific measurements, but the record does not identify a single serotype or composite result that can summarize the full outcome. As a result, the magnitude and precision of the immune responses cannot be assessed from the record details.

The analysis populations are incompletely described. The record defines the FAS in part as randomized participants who received at least one dose and had a valid post-vaccination blood result for at least one serotype-specific IgG concentration or OPA titer. It identifies the PPAS as a subset of the FAS, but the remainder of the PPAS definition is not reported in the registry record. Group-specific analysis counts, participant flow, and missing-result handling are also not reported.

The record does not report the randomization method, allocation concealment, details of masking, baseline characteristics, or a statistical analysis plan. It also does not state whether analyses were adjusted, how confidence intervals were constructed, or how multiple outcomes and comparisons were addressed. The trial's own sample-size justification is not reported in the registry record.

Safety reporting is limited to group counts and a short list of serious-event terms with reported percentages. Event timing, severity criteria, vaccine relatedness, collection window, and comparative uncertainty are not specified. The available information therefore supports description of the reported counts but not causal or precise comparative safety conclusions. These limitations concern what the registry record makes available and do not establish what may have been reported elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of a Pneumococcal Conjugate Vaccine in Adults Aged 50 to 84 Years. — NCT04583618.
• Registry record last updated 2025-09-08; status last verified 2025-09.
• Results first posted 2024-08-27.
• 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

NCT04583618 is a completed Phase 2, randomized, quadruple-masked, parallel-group study sponsored by Sanofi. It enrolled 750 healthy adults aged 50 to 84 years and compared three SP0202 formulations with Prevnar 13 and Pneumovax 23. Each group received one dose at Day 1. The recorded start date is 2020-10-08, and the primary completion date is 2021-08-09.

The stated primary endpoint was serotype-specific OPA geometric mean titers measured by MOPA at Day 31, with 95% confidence intervals. Safety was also an objective. The registry record lists nine outcome measures but no analysis records, and it does not report a single comparative primary-outcome result. It provides group-level counts for serious events, other events, and deaths, but limited detail for interpreting causal or comparative safety differences.