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 13 Valent Pneumococcal Conjugate Vaccine With Trivalent Inactivated Influenza Vaccine (NCT00521586), a randomized phase 3 study. The primary outcome is Percentage of Participants Achieving at Least 4-fold Increase in Titer for Concomitant Trivalent Inactivated Influenza Vaccine (TIV) Antigens 1 Month After Dose 1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00521586 |
| Phase | Phase 3 |
| Condition | Influenza |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 1116 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adults aged 50-59 years who were naive to 23-valent pneumococcal polysaccharide vaccine. The primary endpoint uses an evaluable immunogenicity population: eligible participants vaccinated as assigned, with blood drawn within prespecified time frames, at least one valid determinate assay result, and no major protocol violation.
Intervention
At visit 1, 13-valent pneumococcal conjugate vaccine (13vPnC) was given with trivalent inactivated influenza vaccine (TIV). Participants received placebo at visit 2 and 13vPnC at year 5.
Comparator
TIV was given with placebo at visit 1, followed by 13vPnC at visit 2 and again at year 5. This schedule contrasts concomitant administration at visit 1 with giving 13vPnC at a later visit.
Primary question
One month after Dose 1, what percentage of participants achieved at least a 4-fold increase in antibody titer to the TIV antigens, and what was the difference between the concomitant-vaccine and placebo-plus-TIV groups? The registry record describes measurement for A/H1, A/H3 and B vaccine strains, but the primary endpoint results are not reported in the registry record.
3. Trial Design
This was a Phase 3 randomized, double-blind trial with triple masking recorded in the registry. The recorded model is crossover. Enrollment was 1116, and the trial status is completed. Pfizer is listed as the sponsor. The study began in 2007-09, with primary completion in 2013-12.
The trial enrolled healthy adults aged 50-59 years who were naive to 23-valent pneumococcal polysaccharide vaccine. Its schedules compare two sequences. In one, TIV and 13vPnC were given together at visit 1, placebo was given at visit 2, and 13vPnC was given at year 5. In the other, TIV and placebo were given at visit 1, followed by 13vPnC at visit 2 and at year 5. The registry summary also describes evaluating immune response to 13vPnC once per year for 4 years, followed by a second dose 5 years after the first dose.
The primary endpoint concerns antibody response to the influenza vaccine antigens one month after Dose 1. The record describes safety, tolerability and immunogenicity as study aims. The intervention listings contain 13vPnC; the arm descriptions provide the schedule and identify TIV and placebo in the assigned sequences. Details beyond the listed schedule, including additional operational features of the crossover model, are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Initially 1060 participants were reported to complete the 6 month follow up at Year 0, however 6 additional participants who were reported to have withdrawn initially, actually completed the 6 month follow up at Year 0.
Initial Vaccination (Year 0)
| Stage | 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) | Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5) |
|---|---|---|
| STARTED | 554 | 562 |
| Vaccinated Dose 1 | 551 | 560 |
| Vaccinated Dose 2 | 538 | 543 |
| Initially Reported to Complete Year 0 | 531 | 529 |
| COMPLETED | 533 | 533 |
| NOT COMPLETED | 21 | 29 |
Reasons for not completing this period:
| Reason | 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) | Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5) |
|---|---|---|
| Subject request | 8 | 11 |
| Lost to Follow-up | 5 | 10 |
| Protocol Violation | 2 | 5 |
| Other, unspecified | 3 | 1 |
| Investigator request | 2 | 0 |
| Adverse Event | 0 | 1 |
| Death | 1 | 0 |
| Failed to return | 0 | 1 |
Follow-up (From 6-month[Year 0]-Year 5)
| Stage | 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) | Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5) |
|---|---|---|
| STARTED | 533 | 533 |
| COMPLETED | 364 | 363 |
| NOT COMPLETED | 169 | 170 |
Reasons for not completing this period:
| Reason | 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) | Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5) |
|---|---|---|
| Adverse Event | 5 | 1 |
| Death | 5 | 2 |
| Failed to return | 7 | 3 |
| Investigator request | 3 | 3 |
| Lost to Follow-up | 55 | 56 |
| Other | 22 | 26 |
| Protocol Violation | 18 | 22 |
| Subject request | 54 | 57 |
Revaccination With 13vPnC (Year 5)
| Stage | 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) | Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5) |
|---|---|---|
| STARTED | 364 | 363 |
| Vaccinated 13vPnC (Year 5) | 364 | 363 |
| Completed 1 Month Follow-up | 363 | 359 |
| Completed 6 Month Follow-up | 361 | 351 |
| COMPLETED | 361 | 351 |
| NOT COMPLETED | 3 | 12 |
Reasons for not completing this period:
| Reason | 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) | Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5) |
|---|---|---|
| Subject request | 0 | 1 |
| Failed to return | 1 | 4 |
| Lost to Follow-up | 2 | 7 |
Analysis population for the primary outcome, as defined in the registry: Evaluable immunogenicity population:eligible participants who received vaccination as assigned;had blood drawn within pre-specified time-frames;had at least 1 valid,determinate assay result;had no major protocol violation.
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: Safety analysis set included all randomized participants who had received at least 1 dose of study treatment.
| Characteristic | Unit | 13vPnC+TIV/Placebo (Year 0) and 13vPnC (Year 5) | Placebo+TIV/13vPnC (Year 0) and 13vPnC (Year 5) | Total |
|---|---|---|---|---|
| Participants analysed | 551 | 560 | 1111 | |
| Age, Continuous | years | 54.6 (SD 2.8) | 54.6 (SD 2.9) | 54.6 (SD 2.8) |
| Sex: Female, Male: Female | Participants | 319 | 322 | 641 |
| Sex: Female, Male: Male | Participants | 232 | 238 | 470 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants Achieving at Least 4-fold Increase in Titer for Concomitant Trivalent Inactivated Influenza Vaccine (TIV) Antigens 1 Month After Dose 1, measured over 1 month after Dose 1.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants achieving at least a 4-fold increase in antibody titer for the concomitant TIV antigens one month after Dose 1. Titers were measured using a standard Hemagglutination Inhibition Assay (HAI) for the A/H1, A/H3 and B vaccine strains. The endpoint therefore describes an immune-response threshold, rather than a clinical influenza outcome.
In general, a threshold-based response measure translates a continuous laboratory measurement into the proportion of participants who meet a prespecified criterion. That can make response frequencies easier to compare between treatment groups, while losing information about how far individual results lie above or below the threshold. A fold-rise criterion compares a participant’s antibody titer with a baseline value; the registry description identifies the 4-fold threshold but does not report baseline or follow-up values for the groups.
The registry specifies the percentage meeting the threshold and a difference in proportions between 13vPnC+TIV and placebo+TIV, with an exact, unconditional, two-sided 95% confidence interval. The denominator for each antigen is participants with a determinate antibody titer to that antigen; the numerator is participants who met the prespecified level. The endpoint result values are not reported in the registry record, so the size and precision of the group contrast cannot be assessed from the recorded results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The trial’s main immunogenicity question is whether the proportion meeting the prespecified antibody-response threshold differed between the group receiving 13vPnC with TIV at visit 1 and the group receiving placebo with TIV at that visit. The primary endpoint is defined for one month after Dose 1 and covers the A/H1, A/H3 and B TIV strains. The registry describes the comparison and its confidence-interval method, but does not report the endpoint values. It is therefore not possible to state the observed response proportions, the direction or magnitude of the difference, or the precision of that difference.
This distinction matters because an endpoint definition is not a result. The threshold and assay specify what was measured, while the observed proportions would show how often participants met that criterion. A difference in proportions would quantify the contrast between the assigned groups for each antigen. The confidence interval would convey uncertainty around that contrast. Without the outcome values and intervals, no conclusion about the comparative immune response can be drawn from the primary endpoint record.
The endpoint is based on an evaluable immunogenicity population rather than a description of every enrolled participant. Eligibility for that population required vaccination as assigned, blood collection within prespecified time frames, at least one valid determinate assay result and no major protocol violation. As a result, the primary analysis population is defined by post-enrollment assessment and evaluability criteria. The number of participants analyzed for each antigen is not reported in the registry record.
The registry also lists safety outcomes and longer-term vaccination schedules. The safety record gives affected counts by group and period, along with the numbers at risk, but those data do not substitute for the missing primary immunogenicity results. The listed serious-event terms have reported percentages, but the record does not provide a causal assessment linking those events to a vaccine. The death counts are not reported in the registry record.
Statistical interpretation should stay within these limits. The study is recorded as randomized and masked, and the arm schedules provide a defined contrast at visit 1. However, the registry record does not report the numerical primary endpoint estimates, analysis results for each strain, or additional details of the analysis plan. The record can establish what comparison was planned and how the endpoint was defined, but not what the comparison found.
9. Statistical Methods Explained
The primary endpoint is a binary response at the participant level: each evaluable participant either met the specified antibody-titer threshold or did not. The reported summary is a percentage for each TIV antigen. In general, converting a laboratory value into a binary outcome can make group proportions straightforward to interpret, but it discards differences in the size of the titer change among participants who fall on the same side of the threshold.
The registry describes a comparison of proportions, calculated as the proportion in the 13vPnC+TIV group minus the proportion in the placebo+TIV group. It specifies an exact, unconditional, two-sided 95% confidence interval for this difference. The difference is an absolute contrast in proportions, not a relative comparison. No numerical estimates or confidence limits for the primary endpoint are reported in the registry record.
What does a confidence interval convey?
In general, a confidence interval expresses the uncertainty associated with an estimated quantity under the analysis method. For a difference in proportions, the interval indicates a range of values compatible with the observed data and the method’s assumptions. A narrow interval indicates greater precision than a wide interval. Interpreting such an interval requires the estimated difference and its limits; those primary endpoint figures are not reported in the registry record.
The interval is described as exact and unconditional. In general, exact methods use probability calculations appropriate to discrete outcomes, rather than relying only on a large-sample approximation. An unconditional method evaluates the outcome probabilities without conditioning on a fixed total number of responses. These are general descriptions of the method; the registry record does not provide further implementation details.
How are the analysis denominators defined?
For each antigen, the denominator is the number of participants with a determinate antibody titer. The numerator is the number meeting the prespecified response level. The eligible analysis population is described as participants who received vaccination as assigned, had blood drawn within prespecified time frames, had at least one valid determinate assay result, and had no major protocol violation. In general, restricting an analysis to evaluable observations can make the endpoint definition explicit, but interpretation also depends on how many participants qualify and how excluded or unavailable measurements are handled. Those counts and handling details are not reported in the registry record.
The primary comparison is described for three influenza vaccine strains: A/H1, A/H3 and B. In general, when several outcomes or comparisons are examined, multiplicity can increase the chance of obtaining an apparently notable result by chance if each is interpreted separately. The registry record lists 30 outcome measures and 42 analyses, but does not report a multiplicity adjustment or define which outcomes formed a single testing family. No correction or hierarchy should therefore be assumed.
What can the planning calculations tell readers?
Any sample-size figures associated with the analyses are planning illustrations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect set to a stated fraction of the observed effect. For time-to-event outcomes, the described convention is a total number of events; for other outcomes, it is participants per arm. In general, such calculations explore the sample size associated with chosen assumptions. They do not establish the probability that this completed trial detected an effect, and they are not the trial’s original design justification. The registry record does not report a sample-size justification for the trial.
The trial is recorded as randomized, double-blind, with triple masking, and with a crossover model. Those design labels identify features of the recorded trial, but the registry record does not give details of the allocation procedure, masking roles, statistical model, covariate adjustment, interim analyses or protocol-level analysis plan. These elements should not be inferred from the endpoint description alone.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint includes response measurements for A/H1, A/H3 and B vaccine strains. The registry record also lists 30 outcome measures and 42 analyses. It does not report whether the strain-specific comparisons were treated as one testing family, whether a multiplicity adjustment was used, or whether a prespecified hierarchy determined which comparisons were primary or secondary. No multiplicity strategy should be assumed.
The registry defines an evaluable immunogenicity population. Participants had to receive vaccination as assigned, have blood drawn within prespecified time frames, have at least one valid determinate assay result and have no major protocol violation. For each antigen, the analysis denominator is participants with a determinate antibody titer for that antigen; the numerator is participants meeting the response threshold. The number analyzed for each antigen is not reported in the registry record.
General statistical interpretation of missing measurements depends on how missingness arose and how the analysis handled it. The registry record does not report the amount or reasons for missing antibody measurements, how missing results were handled, or whether sensitivity analyses were conducted. It also does not report a comparison of the evaluable population with participants excluded from that population.
The record does not report a detailed statistical analysis plan, interim analyses, sample-size justification, or the handling of protocol deviations beyond the evaluability definition. These omissions limit assessment of the prespecification and robustness of the reported analysis. They do not establish that particular procedures were or were not performed outside what is recorded.
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+TIV/Placebo: Dose 1 (Year 0) | 4 | 551 | 0.7% |
| 13vPnC+TIV/Placebo: Dose 2 (Year 0) | 3 | 538 | 0.6% |
| 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 0) | 18 | 538 | 3.3% |
| 13vPnC+TIV/Placebo: Years 1-4 | 8 | 536 | 1.5% |
| 13vPnC+TIV/Placebo: 13vPnC (Year 5) | 2 | 364 | 0.5% |
| 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 5) | 2 | 364 | 0.5% |
| Placebo+TIV/13vPnC: Dose 1 (Year 0) | 5 | 560 | 0.9% |
| Placebo+TIV/13vPnC: Dose 2 (Year 0) | 6 | 543 | 1.1% |
| Placebo+TIV/13vPnC: 6 Month Follow-up (Year 0) | 10 | 543 | 1.8% |
| Placebo+TIV/13vPnC: Years 1-4 | 3 | 542 | 0.6% |
| Placebo+TIV/13vPnC: 13vPnC (Year 5) | 2 | 363 | 0.6% |
| Placebo+TIV/13vPnC: 6 Month Follow-up (Year 5) | 3 | 363 | 0.8% |
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+TIV/Placebo: Dose 1 (Year 0) | 420 of 551 |
| 13vPnC+TIV/Placebo: Dose 2 (Year 0) | 248 of 538 |
| 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 0) | 26 of 538 |
| 13vPnC+TIV/Placebo: Years 1-4 | 1 of 536 |
| 13vPnC+TIV/Placebo: 13vPnC (Year 5) | 256 of 364 |
| 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 5) | 1 of 364 |
Most frequent serious adverse event terms
| Event term | Organ system | 13vPnC+TIV/Placebo: Dose 1 (Year 0) | 13vPnC+TIV/Placebo: Dose 2 (Year 0) | 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 0) | 13vPnC+TIV/Placebo: Years 1-4 | 13vPnC+TIV/Placebo: 13vPnC (Year 5) | 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 5) |
|---|---|---|---|---|---|---|---|
| Myocardial infarction | Cardiac disorders | 0 of 551 | 0 of 538 | 1 of 538 | 2 of 536 | 0 of 364 | 0 of 364 |
| Diverticulitis | Infections and infestations | 0 of 551 | 0 of 538 | 2 of 538 | 0 of 536 | 0 of 364 | 0 of 364 |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 551 | 0 of 538 | 2 of 538 | 0 of 536 | 0 of 364 | 0 of 364 |
| Uterine prolapse | Reproductive system and breast disorders | 0 of 551 | 0 of 538 | 0 of 538 | 0 of 536 | 1 of 364 | 0 of 364 |
| Thrombosis | Vascular disorders | 1 of 551 | 0 of 538 | 0 of 538 | 0 of 536 | 0 of 364 | 0 of 364 |
| Cardiac failure congestive | Cardiac disorders | 0 of 551 | 0 of 538 | 1 of 538 | 0 of 536 | 0 of 364 | 0 of 364 |
| Coronary artery disease | Cardiac disorders | 0 of 551 | 0 of 538 | 1 of 538 | 0 of 536 | 0 of 364 | 0 of 364 |
| Palpitations | Cardiac disorders | 0 of 551 | 1 of 538 | 0 of 538 | 0 of 536 | 0 of 364 | 0 of 364 |
| Abdominal mass | Gastrointestinal disorders | 1 of 551 | 0 of 538 | 0 of 538 | 0 of 536 | 0 of 364 | 0 of 364 |
| Non-cardiac chest pain | General disorders | 1 of 551 | 0 of 538 | 0 of 538 | 0 of 536 | 0 of 364 | 0 of 364 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 13vPnC+TIV/Placebo: Dose 1 (Year 0) | 13vPnC+TIV/Placebo: Dose 2 (Year 0) | 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 0) | 13vPnC+TIV/Placebo: Years 1-4 | 13vPnC+TIV/Placebo: 13vPnC (Year 5) | 13vPnC+TIV/Placebo: 6 Month Follow-up (Year 5) |
|---|---|---|---|---|---|---|---|
| Any systemic event | General disorders | 417 of 484 | 248 of 381 | 0 of 538 | 0 of 536 | 221 of 307 | 0 of 364 |
| Any local reaction | Skin and subcutaneous tissue disorders | 420 of 474 | 105 of 300 | 0 of 538 | 0 of 536 | 256 of 315 | 0 of 364 |
| Pain: Any | Skin and subcutaneous tissue disorders | 407 of 469 | 94 of 294 | 0 of 538 | 0 of 536 | 248 of 313 | 0 of 364 |
| Pain: Mild | Skin and subcutaneous tissue disorders | 380 of 459 | 89 of 290 | 0 of 538 | 0 of 536 | 227 of 297 | 0 of 364 |
| Headache: any | General disorders | 263 of 399 | 161 of 334 | 0 of 538 | 0 of 536 | 120 of 256 | 0 of 364 |
| Fatigue: any | General disorders | 226 of 389 | 138 of 316 | 0 of 538 | 0 of 536 | 115 of 263 | 0 of 364 |
| New muscle pain: any | General disorders | 252 of 385 | 82 of 288 | 0 of 538 | 0 of 536 | 127 of 266 | 0 of 364 |
| Aggravated generalized muscle pain: any | General disorders | 109 of 314 | 50 of 268 | 0 of 538 | 0 of 536 | 72 of 241 | 0 of 364 |
| Pain: Moderate | Skin and subcutaneous tissue disorders | 127 of 324 | 11 of 243 | 0 of 538 | 0 of 536 | 81 of 248 | 0 of 364 |
| Chills: any | General disorders | 96 of 306 | 56 of 273 | 0 of 538 | 0 of 536 | 53 of 229 | 0 of 364 |
Serious events with the highest arm-level rate: myocardial infarction (0.4%), diverticulitis (0.4%), prostate cancer (0.4%), renal colic (0.3%), thrombosis (0.3%).
The safety record reports serious and other adverse events by group and reporting period, with the number at risk and the number affected. These are period-specific counts: for example, the concomitant-vaccine group lists 4 serious-event reports among 551 at risk at Dose 1 (Year 0), while the placebo-plus-TIV group lists 5 among 560 at risk in that period. Counts and denominators vary across later periods, so each entry should be read in its own period and group rather than treated as a single study-wide rate.
The record lists Myocardial infarction, Diverticulitis and Prostate cancer at 0.4% each among the top serious terms; Renal colic, Thrombosis and Osteoarthritis are listed at 0.3% each. Those term percentages do not, on their own, establish whether an event was caused by vaccination. Death counts are not reported in the registry record. The safety figures describe reported events and at-risk groups, not a causal comparison or a complete account of clinical context.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study compared two vaccination sequences in healthy adults aged 50-59 years who were naive to 23-valent pneumococcal polysaccharide vaccine. At visit 1, both groups received TIV; one group also received 13vPnC, while the other received placebo. The primary question concerns the proportion meeting a defined antibody-response threshold one month after Dose 1 for the A/H1, A/H3 and B vaccine strains.
The record also specifies the assay, endpoint threshold, analysis population and method for estimating the difference in proportions. These details clarify what the primary outcome was intended to measure. They do not reveal the observed response percentages or the estimated group differences. Since those results are not reported in the registry record, the direction, magnitude and precision of the primary comparison cannot be determined from this record.
In general, an antibody response is a laboratory outcome, not the same as a clinical outcome such as illness. The endpoint definition supports interpretation of the immune-response measure only. It does not, by itself, establish the effect of the schedules on clinical influenza outcomes or on other health outcomes.
The record’s safety entries describe affected counts and at-risk numbers across specified groups and periods. They are useful as descriptions of reported adverse events, but the information does not establish causation. Nor should the serious-event counts be interpreted as a complete measure of risk without the relevant clinical context and full analysis.
The registry labels the study randomized and masked and reports it as completed. Those features describe the recorded design and status; they do not replace numerical outcome results. The evidence available in the record therefore supports a description of the question, design and outcome definitions, but not a conclusion about whether the primary endpoint favored either sequence.
13. Why This Trial Matters Statistically
This trial illustrates why a statistical record needs to be read at more than one level. The protocol question is a comparison of vaccination schedules, while the primary endpoint is a laboratory response summarized as a percentage meeting a threshold. The registry specifies the strain-specific assay and the contrast in proportions, allowing readers to understand the intended estimand even though the primary results are not reported in the registry record.
It also highlights the distinction between a defined analysis population and the population enrolled. The evaluable immunogenicity criteria require vaccination as assigned, timely blood collection, a valid determinate assay result and no major protocol violation. Such criteria are important to interpreting which observations contribute to the endpoint. The record does not give antigen-specific analysis counts or explain how unavailable measurements were handled.
The use of confidence intervals is another important feature. In general, an estimate without an interval gives limited information about precision. Here, the registry describes an exact, unconditional, two-sided 95% confidence interval for a difference in proportions, but does not provide the estimate or interval limits. The method can be identified, while the result’s precision cannot be evaluated.
Finally, the record lists many outcome measures and analyses without describing a multiplicity strategy. That makes it important not to infer a testing hierarchy or adjustment. Overall, the trial is a useful example of how design labels and endpoint methods can be clear while key result estimates and analysis details remain unreported in the registry record.
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 most direct limitation for interpreting the primary question is that the registry record does not report the response percentages, differences in proportions, confidence-interval limits or antigen-specific analysis counts. Consequently, the primary endpoint’s direction, magnitude and precision cannot be assessed.
The analysis population is defined as evaluable, with requirements concerning assigned vaccination, blood-draw timing, assay validity and protocol violations. The record does not report how many participants met those criteria for each antigen, how many were excluded, or how missing or indeterminate titers were handled. Those details would help readers assess the reach of the immunogenicity findings.
The record identifies A/H1, A/H3 and B antigens and lists 30 outcome measures and 42 analyses, but does not report a multiplicity strategy or a hierarchy among analyses. It also does not report the detailed statistical analysis plan, interim analyses or sample-size justification. The sample-size assumptions associated with planning illustrations are not a substitute for the trial’s original design rationale.
The study is labeled crossover, randomized, double-blind and triple-masked, but the registry record does not describe the allocation procedure, the roles covered by masking, or further details of the crossover analysis. The schedule and endpoint descriptions are available, but those labels alone do not resolve design and analysis questions.
For safety, event counts are reported by period and group, but death counts are not reported in the registry record. The safety entries do not provide causal attribution, and the listed serious-event terms should not be treated as evidence that vaccination caused those events. The registry record also does not provide additional clinical context for interpreting these reports.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Evaluating 13 Valent Pneumococcal Conjugate Vaccine With Trivalent Inactivated Influenza Vaccine — NCT00521586.
- Registry record last updated 2015-04-09; status last verified 2015-04.
- Results first posted 2015-04-09.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a completed Phase 3 randomized, double-blind trial with triple masking and a crossover model, sponsored by Pfizer. Enrollment was 1116. The study began in 2007-09 and primary completion was recorded in 2013-12.
Healthy adults aged 50-59 years who were naive to 23-valent pneumococcal polysaccharide vaccine were assigned to schedules that differed in whether 13vPnC was given with TIV at visit 1 or after placebo at that visit. Both schedules included later 13vPnC vaccination.
The primary endpoint was the percentage achieving at least a 4-fold increase in titer for A/H1, A/H3 and B TIV antigens one month after Dose 1. The registry describes an exact, unconditional, two-sided 95% confidence interval for the difference in proportions. Primary outcome estimates are not reported in the registry record. Safety counts are reported by group and period, while death counts are not reported in the registry record.