This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study Evaluating a 13-valent Pneumococcal Conjugate Vaccine in Elderly Subjects (NCT00500357), a non-randomized phase 3 study. The primary outcome is Pneumococcal OPA Geometric Mean Titers (GMTs) for the 13 Serotypes 1 Month After 13vPnC / 23vPS / 13vPnC (Vaccination 3) Versus 1 Month After 13vPnC (Vaccination 1).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00500357 |
| Phase | Phase 3 |
| Condition | Vaccines, Pneumococcal Conjugate Vaccine |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 105 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Wyeth is now a wholly owned subsidiary of Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled 105 elderly subjects who had participated in the core study. The primary immunogenicity population was defined as participants evaluable for immunogenicity after the first and second vaccinations, who received the subsequent vaccine in this follow-up study and had at least one assay result. The registry does not report the age range or the number in that evaluable population.
Intervention
A subsequent dose of 13-valent pneumococcal conjugate vaccine (13vPnC), identified as vaccination 3 in the study sequence. Before this follow-up dose, participants had received 13vPnC and, one year later, 23-valent pneumococcal polysaccharide vaccine (23vPS) in the core study.
Comparator
The primary endpoint compares immune response one month after vaccination 3 with response one month after vaccination 1 in the core study. This is a comparison across time points in the study sequence, not a concurrent randomized comparison. There is no separate randomized control group in this trial.
Primary question
For 13 pneumococcal serotypes, what were the opsonophagocytic activity geometric mean titers one month after the subsequent 13vPnC dose, compared with one month after the initial 13vPnC dose? The registry describes this question but does not report the corresponding endpoint estimates or confidence intervals.
The study addresses a follow-up immunogenicity question: whether antibody activity after a subsequent 13vPnC dose can be assessed against the response recorded after the initial dose in the same vaccination sequence. The registry’s brief description frames the broader purpose as determining whether a later dose results in a similar or greater immune response. That wording describes the study’s aim, not a finding. Without the posted endpoint estimates, the direction and size of any observed difference cannot be characterized.
The primary endpoint covers serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. The registry also identifies secondary immunogenicity outcomes based on OPA titers and immunoglobulin G concentrations at other vaccination time points. The values for those outcomes are not reported in the registry record.
3. Trial Design
This was a Phase 3, open-label, non-randomized, single-group follow-up trial. The registry lists an enrollment of 105 and a completed status. The recorded study start is 2007-11, and primary completion is listed as 2010-01. These registry entries describe the study’s structure and timing; they do not establish how many participants contributed data to each analysis.
The follow-up study involved participants from core study NCT00269672. The stated sequence was an initial dose of 13vPnC, a dose of 23vPS one year later, and a subsequent dose of 13vPnC in the follow-up study one year later. The primary endpoint compares OPA geometric mean titers one month after the initial 13vPnC dose with titers one month after the subsequent 13vPnC dose. This comparison uses measurements at different points in the vaccination sequence rather than outcomes in separate randomized groups.
Because the trial was single-group and non-randomized, the sequence does not include a concurrently randomized group assigned to a different vaccine or to no subsequent dose. The registry therefore does not support treating other listed vaccine groups from the core study as like-for-like controls for this follow-up group. Those groups had different vaccination sequences and are not randomized comparators within the follow-up trial.
The trial was open-label, with no masking listed. The registry does not report additional details about procedures used to reduce measurement or assessment bias. It identifies the intervention as a biological product, 13-valent Pneumococcal Conjugate Vaccine. Wyeth, now a wholly owned subsidiary of Pfizer, is listed as sponsor.
The registry lists six outcome measures and 52 analyses. It describes the primary immunogenicity population as participants evaluable in the core study for the first and second vaccinations, who received 13vPnC in the follow-up study and had at least one assay result there. The number included in this population is not reported in the registry record. The record also does not report a sample-size justification, a protocol-level statistical analysis plan, or whether interim analyses were planned.
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: 105 participants from the core study NCT00269672 (6115A1-500) who had received 13vPnC+AlPO4 (13vPnC) followed by 23vPS enrolled in the follow-up study NCT00500357 (6115A1-3009) 1 year after completion of the core study and received a subsequent 13vPnC dose at Year 2 (Vax 3).
Overall Study
| Stage | 13vPnC (Vax 3 Follow-up / NCT00500357) |
|---|---|
| STARTED | 105 |
| Received 13vPnC (Vax 3) | 105 |
| Evaluable Immunogenicity Population | 98 |
| COMPLETED | 104 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | 13vPnC (Vax 3 Follow-up / NCT00500357) |
|---|---|
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: Evaluable Immunogenicity population includes participants from the evaluable immunogenicity population for Vax 1 and Vax 2 in the core study/NCT00269672, received 13vPnC in follow-up study/NCT00500357, and had at least 1 assay result in the follow-up study. N=number of participants with a determinate antibody titer for the specified serotype.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | 13vPnC (Vax 3 Follow-up / NCT00500357) |
|---|---|---|
| Participants analysed | 105 | |
| Age Continuous | years | 72.8 (SD 4.9) |
| Sex: Female, Male: Female | Participants | 56 |
| Sex: Female, Male: Male | Participants | 49 |
6. Primary Endpoint
The registry lists the primary outcome as Pneumococcal OPA Geometric Mean Titers (GMTs) for the 13 Serotypes 1 Month After 13vPnC / 23vPS / 13vPnC (Vaccination 3) Versus 1 Month After 13vPnC (Vaccination 1), measured over Month 1 / Year 0 (Core study/NCT00269672), Month 1 / Year 2 (Follow-up study/NCT00500357).
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | geometric mean titer |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the geometric mean titer (GMT) of antibodies measured by an opsonophagocytic activity (OPA) assay for 13 pneumococcal serotypes. The comparison is between the measurement one month after the subsequent 13vPnC dose in the follow-up study and the measurement one month after the initial 13vPnC dose in the core study. The endpoint description specifies 95% confidence intervals for the GMTs.
OPA is an assay of antibody function: it measures activity associated with the process by which antibodies help immune cells act against a target. In general, an assay-based immune measure can help characterize an immune response, but it is not by itself a direct count of clinical disease events. The registry does not report clinical disease outcomes as the primary endpoint.
A geometric mean is used for measurements that are analyzed on a logarithmic scale and then expressed on the original scale. In general, this approach can describe the central level of measurements when their distribution is more naturally handled multiplicatively than additively. The registry states that the confidence intervals were calculated on the mean logarithm of the titers using the Student t distribution, then back-transformed to the GMT scale.
The endpoint is reported across the named serotypes rather than as a single overall clinical outcome. The registry’s endpoint description does not give the actual GMTs, confidence intervals, or serotype-specific interpretation. Those endpoint results are not reported in the registry record, so the size and precision of the observed immune responses cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry defines a focused immunogenicity comparison: OPA GMTs one month after the subsequent 13vPnC dose versus one month after the initial 13vPnC dose, across 13 serotypes. It does not report the numerical GMTs or their confidence intervals. As a result, the posted record does not establish the observed magnitude of response for any serotype, the degree of variation around an estimate, or whether the later measurement was higher or lower than the earlier one.
The study’s stated objective refers to determining whether a subsequent dose results in a similar or greater immune response than the response after the initial dose. That statement is a research question rather than a result. It should not be read as evidence that the responses were similar, greater, or different. A conclusion about the endpoint would require the actual estimates and an interpretation appropriate to the analysis; these are not reported in the registry record.
The study sequence also matters for interpretation. The primary comparison spans vaccination time points: the earlier measurement followed 13vPnC in the core study, while the later measurement followed 13vPnC after an intervening 23vPS dose. It is therefore not an isolated comparison of two vaccine assignments. The endpoint reflects response at two points in a sequence that includes both products.
There is no randomized concurrent control group in this follow-up study. Consequently, the comparison cannot be interpreted as a randomized treatment contrast. Changes between the two measurements could relate to the vaccination sequence, timing, participant characteristics, measurement conditions, or other factors; the registry record does not report analyses that separate these possible influences. This limitation does not invalidate the descriptive comparison, but it constrains causal interpretation.
The evaluable immunogenicity population has a defined eligibility description: participants had to be evaluable for the first and second vaccinations in the core study, receive 13vPnC in the follow-up study, and have at least one assay result in the follow-up study. The number meeting that definition is not reported in the registry record. Without the analysis population size and participant flow, it is not possible to assess how much of the enrolled group contributed endpoint data or whether missing measurements could affect interpretation.
The registry lists secondary outcomes for OPA GMTs and immunoglobulin G geometric mean concentrations (GMCs) across vaccination time points, along with 52 analyses overall. The corresponding numerical results and any adjustment for multiple analyses are not reported in the registry record. No claim about consistency across serotypes or outcomes can be made from outcome titles alone.
Safety data are recorded separately from the primary immunogenicity endpoint. In the follow-up group, the registry lists 2 participants at risk for serious adverse events, with 2 affected, and 105 at risk for other adverse events, with 46 affected. These counts describe reported safety events; they do not provide a randomized comparison and should not be treated as a causal estimate of vaccine-related risk. The registry lists no death count for this group in the posted record.
Overall, the record establishes the study question, design, endpoint definition, and some safety counts, but leaves the key primary immunogenicity results unreported. The appropriate interpretation is therefore about what was planned and measured, not about the direction or strength of the immune response.
9. Statistical Methods Explained
The registry describes a geometric mean endpoint, confidence intervals based on a t distribution applied to log titers, and a comparison across vaccination time points. Those details identify the form of the planned summary, but the registry does not report the numerical endpoint estimates or the full analysis plan. The concepts below explain the statistical methods in general; they do not supply missing study results.
Why use a geometric mean?
General: A geometric mean is calculated by taking the mean of logarithmically transformed measurements and then returning the result to the original scale. This is useful when values are positive and relative changes are more meaningful than equal absolute changes. For example, a change from one level to a multiple of that level may be more naturally described proportionally than as a fixed additive increment. The registry’s endpoint is based on antibody titers, and it explicitly describes calculating intervals on the logarithms of the titers before back-transformation.
The resulting GMT is expressed on the original titer scale, but its statistical calculation relies on the transformed scale. It should not be confused with an arithmetic average of the raw titers. The registry does not report the underlying participant-level measurements, so it is not possible to reconstruct the GMT or evaluate the distribution of titers from the record.
What does the confidence interval describe?
General: A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the method used to calculate it. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. It is not a guarantee that the true value lies within the particular interval, nor is it a range containing a stated proportion of individual participants’ measurements.
For this endpoint, the registry says that the 95% confidence intervals for GMTs are back-transformations of intervals based on the Student t distribution for the mean logarithm of titers. This describes the interval construction. Since the interval limits are not reported, the precision of the serotype-specific estimates cannot be judged. The record also does not provide enough information to independently verify the analysis assumptions or reproduce the intervals.
What does the OPA assay measure?
General: An assay measures a biological property under specified laboratory conditions. OPA assesses antibody activity related to opsonophagocytic function. An OPA GMT summarizes measured titers across participants on a geometric scale. It is an immunogenicity measure, not a direct estimate of disease incidence or an individual participant’s protection. The registry does not report clinical efficacy results tied to this endpoint, so the GMTs should not be translated into a claim about clinical outcomes.
How should the time-point comparison be read?
The primary endpoint compares a measurement one month after vaccination 3 with a measurement one month after vaccination 1. General: Repeated measurements in the same participants can describe how a measured outcome differs over time, but the interpretation depends on the analysis population, timing, missing data, and statistical method. The registry’s endpoint title identifies the two measurement points, but does not specify whether the formal analysis used paired participant-level data, an adjustment model, or another approach. Those details are not reported in the registry record.
The intervention sequence includes 13vPnC, then 23vPS one year later, then a subsequent 13vPnC dose one year later. Thus, the primary comparison is across measurements taken within a sequence, not a simple contrast between independently randomized treatment groups. General: A within-person comparison can account for stable characteristics of participants when the same individuals contribute both measurements, but it does not automatically remove time-related influences or other changes between measurements. The registry record does not provide enough analysis detail to determine how such issues were handled.
Why does study design affect inference?
General: Random assignment can help balance known and unknown participant characteristics between treatment groups. A single-group, non-randomized follow-up study does not provide that kind of concurrent randomized comparison. Its measurements can describe the observed cohort and its sequence, but causal conclusions require caution. The registry identifies the design as non-randomized, unmasked, and single-group; it does not report a plan to address confounding or time effects.
The study is also open-label. General: Knowledge of treatment assignment can sometimes influence subjective assessment or participant reporting. Laboratory assays may have different sources of measurement variation, but the registry does not report masking of laboratory personnel or other safeguards. It would be inappropriate to infer either that such safeguards were used or that they were absent beyond the listed masking status.
What do the sample-size illustrations mean?
General: A sample-size calculation estimates how many participants may be needed to detect a specified effect under chosen assumptions. It depends on assumptions about the effect, variability, significance level, allocation, and statistical model. A planning illustration based on an observed effect is not the trial’s original sample-size justification and does not demonstrate the probability that the completed trial detected an effect. Such illustrations are planning calculations, not observed power and not evidence that an effect exists.
The registry record does not report the trial’s own sample-size justification. It also does not report the primary endpoint estimates needed to understand the observed effect in this study. The statistical assumptions used for any planning illustration should therefore be kept separate from the trial’s results and from its design rationale.
What cannot be assessed from the record?
The numerical GMTs and confidence intervals, the size of the primary analysis population, the detailed model or test, and the treatment of missing measurements are not reported in the registry record. The record also does not report whether analyses were adjusted for multiplicity or whether interim analyses were planned. Without those details, readers can understand the endpoint’s intended summary and broad design, but cannot independently evaluate the primary statistical result or its robustness.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures and 52 analyses. The primary endpoint itself concerns 13 serotypes, and the listed secondary outcomes include additional OPA GMT and IgG GMC comparisons at different vaccination time points. Considering multiple outcomes and serotypes raises a multiplicity question: when many estimates or tests are examined, the chance of at least one apparently notable result can increase. General: Statistical plans may address this by defining a hierarchy of outcomes, adjusting significance thresholds, or emphasizing estimation rather than a collection of unadjusted tests.
The registry record does not report whether a multiplicity adjustment was used, which outcomes or serotypes were considered confirmatory, or whether a prespecified testing sequence governed interpretation. The numerical results for the listed primary and secondary outcomes are also not reported in the registry record. Therefore, the status of any individual result within a broader testing strategy cannot be assessed.
The primary immunogenicity population is described as participants evaluable for the first and second vaccinations in the core study, who received 13vPnC in the follow-up study and had at least one assay result there. The number in this population is not reported. The record does not report participant flow, reasons for missing assay results, imputation methods, sensitivity analyses, or whether the primary analysis included all eligible participants with available measurements.
General: Missing outcome data can affect both the precision and interpretation of an analysis. If participants with missing measurements differ systematically from those with observed measurements, an estimate based only on observed data may not represent the full enrolled group. That possibility cannot be evaluated without information about missingness and the analysis approach. No particular missing-data mechanism or handling method should be assumed for this study.
The registry does not report interim analyses or a detailed statistical analysis plan. Those omissions limit assessment of how outcomes and analyses were prioritized, but they do not establish that no such plan or procedures existed. The appropriate conclusion is that these details are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 13vPnC / 23vPS / 13vPnC (Vax 3 Follow-up Study) | 2 | 105 | 1.9% |
| 13vPnC+AlPO4 (After Vax 1 Core Study) | 2 | 308 | 0.6% |
| 13vPnC-AlPO4 (After Vax 1 Core Study) | 4 | 304 | 1.3% |
| 23vPS (After Vax 1 Core Study) | 1 | 302 | 0.3% |
| 13vPnC+AlPO4/13vPnC+AlPO4 (After Vax 2 Core Study) | 3 | 139 | 2.2% |
| 13vPnC+AlPO4/23vPS (After Vax 2 Core Study) | 1 | 128 | 0.8% |
| 13vPnC-AlPO4/23vPS (After Vax 2 Core Study) | 1 | 273 | 0.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 13vPnC / 23vPS / 13vPnC (Vax 3 Follow-up Study) | 46 of 105 |
| 13vPnC+AlPO4 (After Vax 1 Core Study) | 70 of 308 |
| 13vPnC-AlPO4 (After Vax 1 Core Study) | 58 of 304 |
| 23vPS (After Vax 1 Core Study) | 80 of 302 |
| 13vPnC+AlPO4/13vPnC+AlPO4 (After Vax 2 Core Study) | 26 of 139 |
| 13vPnC+AlPO4/23vPS (After Vax 2 Core Study) | 35 of 128 |
Most frequent serious adverse event terms
| Event term | Organ system | 13vPnC / 23vPS / 13vPnC (Vax 3 Follow-up Study) | 13vPnC+AlPO4 (After Vax 1 Core Study) | 13vPnC-AlPO4 (After Vax 1 Core Study) | 23vPS (After Vax 1 Core Study) | 13vPnC+AlPO4/13vPnC+AlPO4 (After Vax 2 Core Study) | 13vPnC+AlPO4/23vPS (After Vax 2 Core Study) |
|---|---|---|---|---|---|---|---|
| Cardio-respiratory arrest | Cardiac disorders | 1 of 105 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 |
| Hip fracture | Injury, poisoning and procedural complications | 1 of 105 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 |
| Bradycardia | Cardiac disorders | 0 of 0 | 1 of 308 | 0 of 304 | 0 of 302 | 0 of 139 | 0 of 128 |
| Myocardial ischaemia | Cardiac disorders | 0 of 0 | 1 of 308 | 0 of 304 | 0 of 302 | 0 of 139 | 0 of 128 |
| Angina unstable | Cardiac disorders | 0 of 0 | 0 of 308 | 1 of 304 | 0 of 302 | 0 of 139 | 0 of 128 |
| Myocardial infarction | Cardiac disorders | 0 of 0 | 0 of 308 | 1 of 304 | 0 of 302 | 0 of 139 | 0 of 128 |
| Phimosis | Congenital, familial and genetic disorders | 0 of 0 | 0 of 308 | 0 of 304 | 0 of 302 | 1 of 139 | 0 of 128 |
| Cholelithiasis | Hepatobiliary disorders | 0 of 0 | 0 of 308 | 1 of 304 | 0 of 302 | 0 of 139 | 0 of 128 |
| Exostosis | Musculoskeletal and connective tissue disorders | 0 of 0 | 0 of 308 | 0 of 304 | 1 of 302 | 0 of 139 | 0 of 128 |
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | 0 of 0 | 0 of 308 | 0 of 304 | 1 of 302 | 0 of 139 | 0 of 128 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 13vPnC / 23vPS / 13vPnC (Vax 3 Follow-up Study) | 13vPnC+AlPO4 (After Vax 1 Core Study) | 13vPnC-AlPO4 (After Vax 1 Core Study) | 23vPS (After Vax 1 Core Study) | 13vPnC+AlPO4/13vPnC+AlPO4 (After Vax 2 Core Study) | 13vPnC+AlPO4/23vPS (After Vax 2 Core Study) |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 0 of 0 | 9 of 308 | 17 of 304 | 22 of 302 | 5 of 139 | 8 of 128 |
| Headache | Nervous system disorders | 0 of 0 | 11 of 308 | 17 of 304 | 16 of 302 | 6 of 139 | 9 of 128 |
| Injection site pain | General disorders | 0 of 0 | 6 of 308 | 9 of 304 | 9 of 302 | 6 of 139 | 8 of 128 |
| Pain (any) | Skin and subcutaneous tissue disorders | 36 of 89 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 |
| Myalgia | Musculoskeletal and connective tissue disorders | 0 of 0 | 6 of 308 | 7 of 304 | 10 of 302 | 4 of 139 | 7 of 128 |
| Pain (mild) | Skin and subcutaneous tissue disorders | 30 of 88 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 0 of 0 | 8 of 308 | 7 of 304 | 9 of 302 | 3 of 139 | 1 of 128 |
| Injection site erythema | General disorders | 0 of 0 | 9 of 308 | 3 of 304 | 6 of 302 | 2 of 139 | 7 of 128 |
| Fatigue | General disorders | 23 of 83 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 | 0 of 0 |
| Injection site movement impairment | General disorders | 0 of 0 | 6 of 308 | 6 of 304 | 6 of 302 | 1 of 139 | 4 of 128 |
Serious events with the highest arm-level rate: cardio-respiratory arrest (1.0%), hip fracture (1.0%), arthralgia (0.8%), phimosis (0.7%), intervertebral disc disorder (0.7%).
For the follow-up group labeled 13vPnC / 23vPS / 13vPnC, the registry lists 105 participants at risk for serious adverse events and 2 affected. It also lists 105 at risk for other adverse events and 46 affected. These are counts of participants, not counts of individual event episodes. The registry does not report a death count for this group.
The record also lists serious adverse event terms with percentages: Cardio-respiratory arrest, 1.0%; Hip fracture, 1.0%; Arthralgia, 0.8%; Phimosis, 0.7%; Intervertebral disc disorder, 0.7%; and Prostate cancer, 0.7%. These entries are presented as listed terms and percentages. The registry entries given do not establish that each term occurred in the follow-up group, nor do they provide enough context to interpret the percentages as comparative risks.
General: A serious adverse event is a safety category, not a statement that the event was caused by the study intervention. Event counts alone do not establish causation. In addition, the follow-up trial has no randomized concurrent control group, so the counts cannot be interpreted as a randomized estimate of excess risk. Differences between the listed groups should not be treated as like-for-like comparisons because the trial is non-randomized and the groups reflect different vaccination sequences.
These data describe reported safety events; they do not establish whether an event was related to vaccination. The registry does not report attribution details or a comparative causal analysis in the registry record for this summary.
12. What the Result Does, and Does Not, Mean
The study’s primary endpoint is a laboratory measure of antibody activity after a subsequent 13vPnC dose, compared with the measurement after the initial 13vPnC dose. The registry record identifies the serotypes, assay, time points, and confidence-interval method. It does not report the actual GMT estimates or confidence intervals. Consequently, the record does not show how large the measured responses were, how precise the estimates were, or whether the later values were higher or lower.
The study’s objective asks whether the subsequent dose produces a similar or greater immune response than the initial dose. An objective is not a result. No statement that the responses were similar, greater, or otherwise can be supported without the endpoint estimates and a suitable analysis. The record also does not report clinical disease outcomes for the primary question, so the immunogenicity endpoint should not be converted into a claim about clinical protection or disease prevention.
The design limits what can be inferred. This was an open-label, non-randomized, single-group follow-up study. The primary comparison is across two points in a sequence that includes 13vPnC, 23vPS, and a later 13vPnC dose. It is not a randomized comparison against a concurrent control group. Changes between the measurements cannot therefore be attributed to one component of the sequence with the certainty that randomization is intended to support.
The safety counts describe the participants recorded as affected in the follow-up group, including 2 with serious adverse events and 46 with other adverse events. They do not establish that the intervention caused those events. The registry lists serious adverse event terms and percentages, but those entries should not be treated as evidence of a causal relationship or as a controlled comparison.
The most defensible reading is that the registry documents a follow-up study designed to assess immunogenicity and safety after a subsequent dose, with a defined primary measure and analysis population criteria. Its numerical primary immunogenicity findings and several key statistical details are not reported in the registry record. The available information supports a description of the study question and design, but not a conclusion about the magnitude, precision, or clinical meaning of the primary immune response.
13. Why This Trial Matters Statistically
This trial illustrates how a study can ask a focused immunogenicity question while still requiring careful attention to design and reporting. The endpoint is not simply a comparison of two independent groups: it contrasts OPA GMTs after the initial 13vPnC dose with measurements after a later dose in a sequence that also includes 23vPS. The timing and sequence are central to understanding what the comparison represents.
It also illustrates why the distinction between a study objective and a study result matters. The registry describes an aim to determine whether a subsequent dose produces a similar or greater immune response. Without the corresponding GMT estimates and confidence intervals, that aim cannot be treated as a finding. Endpoint definitions alone do not reveal effect size, precision, or consistency across serotypes.
The single-group, non-randomized design is another useful statistical lesson. Repeated measurements can be informative about an observed cohort, but without a concurrent randomized comparator they do not have the same basis for causal interpretation as a randomized treatment contrast. Different vaccination sequences in the core-study safety groups do not become valid controls merely because they are listed alongside the follow-up group.
Finally, the record shows why analysis populations, missing data, and multiplicity are important to interpretability. The evaluable population is defined, but its size is not reported; multiple outcomes and analyses are listed, but the multiplicity approach is not reported. Those omissions leave uncertainty about the scope and precision of the analyses. Clear reporting of estimates, confidence intervals, participant flow, and prespecified analysis choices would allow readers to assess the evidence more fully.
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 primary immunogenicity estimates and their confidence intervals are not reported in the registry record. This prevents assessment of the observed response magnitude and its statistical precision, even though the endpoint, assay, time points, and confidence-interval construction are described.
The population description provides eligibility criteria for the evaluable immunogenicity analysis, but the number of participants in that population is not reported. The registry record does not provide participant flow or explain how many enrolled participants contributed paired or otherwise usable measurements. It is therefore not possible to assess the extent of missing assay data or how the analyzed group relates to the enrolled group.
The non-randomized, single-group design means the primary comparison is not a concurrent randomized contrast. The earlier and later measurements occur at different points in a vaccination sequence that includes 13vPnC and 23vPS. The record does not report methods that separate the influence of the subsequent dose from time, sequence, or other changes between measurements. It also does not report whether the formal analysis used paired data or a specified adjustment model.
The registry lists multiple outcome measures and 52 analyses, but does not report a multiplicity strategy or identify the role of each analysis in a prespecified testing plan. It does not report missing-data methods, sensitivity analyses, or interim analyses. These details are not reported in the registry record; their absence from the record should not be taken as proof that no procedures existed.
The study is open-label, and the registry lists no masking. The record does not describe additional safeguards for assay conduct or outcome assessment. Finally, the available safety counts do not establish event causality, and the listed serious adverse event terms do not provide a basis for a controlled comparison. Together, these limitations mean the record supports a clear description of the question and design, but limited evaluation of the primary findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Evaluating a 13-valent Pneumococcal Conjugate Vaccine in Elderly Subjects — NCT00500357.
- Registry record last updated 2011-04-19; status last verified 2011-04.
- Results first posted 2011-02-17.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00500357 is a completed Phase 3, open-label, non-randomized, single-group follow-up trial with an enrollment of 105. It evaluated a subsequent dose of 13vPnC in participants who had received 13vPnC and then 23vPS in core study NCT00269672.
The primary endpoint was OPA GMTs for 13 serotypes, comparing measurements one month after the subsequent dose with measurements one month after the initial 13vPnC dose. The registry describes 95% confidence intervals based on the Student t distribution applied to log titers and then back-transformed. The numerical primary endpoint results are not reported in the registry record.
The follow-up group safety data list 2 participants affected by serious adverse events and 46 affected by other adverse events, among 105 at risk in each category. The registry does not report a death count for this group. The record lists six outcome measures and 52 analyses, but does not report the evaluable population size, multiplicity approach, detailed missing-data methods, or the trial’s sample-size justification.