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 Safety & Immunogenicity of 13vPnC in HIV-Infected Subjects Aged 18 or Older Who Were Previously Immunized With 23vPS (NCT00963235), a na phase 3 study. The primary outcome is Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After Dose 2 of 13vPnC to 1 Month After Dose 3 of 13vPnC.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00963235 |
| Phase | Phase 3 |
| Condition | HIV Infections, Pneumococcal Infections |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 331 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
HIV-infected adults aged 18 or older who had previously received at least one dose of 23vPS. The primary endpoint population was narrower: eligible participants aged at least 18 on the day of first vaccination, who received at least 2 doses in the assigned sequence, had valid and determinate assay results, and had no major protocol violations.
Intervention
Three doses of 13-valent pneumococcal conjugate vaccine, 13vPnC. The study summary says doses were given approximately 6 months apart. Blood draws were also part of the study procedures.
Comparator
There was no separate comparator group. The study was single-group and open-label, and allocation was listed as NA. Comparisons of immunogenicity were within participants, between measurements taken after successive doses.
Primary question
What was the geometric mean fold rise in serotype-specific pneumococcal IgG antibody from 1 month after dose 2 to 1 month after dose 3? The registry specifies the endpoint and its confidence interval method, but the numerical endpoint results are not reported in the registry record.
The study addressed immunogenicity and safety in adults with HIV who had previously been immunized with a pneumococcal polysaccharide vaccine. In particular, it evaluated antibody measurements following additional doses of a conjugate vaccine. The primary outcome focused on the change between two post-vaccination measurement times, rather than a difference between a vaccine group and an untreated or alternative-treatment group.
The registry also lists secondary outcomes concerning serotype-specific IgG geometric mean concentrations and opsonophagocytic activity (OPA) geometric mean titers after successive doses. Those are distinct summaries of antibody concentration and functional activity. Their outcome names describe intended measurements; numerical results for them are not reported in the registry record.
3. Trial Design
This was a phase 3, open-label, single-group trial. The registry lists enrollment of 331 participants and a completed status. The recorded study start was 2009-11, and primary completion was 2012-05. Pfizer is listed as the sponsor.
Participants were HIV-infected adults aged 18 or older who had previously received at least one dose of 23vPS. The study summary states that all participants received 3 doses of 13vPnC, with each dose given approximately 6 months apart. Blood draw was listed as a study procedure. No separate control group or randomized allocation is described; allocation is recorded as NA and masking as NONE. The absence of a comparator limits the design to within-participant descriptions of measurements over the dose sequence, rather than a direct comparison of outcomes between treatment groups.
The primary endpoint was assessed in an evaluable immunogenicity population. Eligibility for this population required age of at least 18 on the day of first vaccination, receipt of at least 2 doses of 13vPnC in the assigned sequence, valid and determinate assay results, and no major protocol violations. The endpoint description identifies this population but does not provide a clear numerical count analyzed; the count is not reported in the registry record.
The study was designed to assess safety, tolerability, and immunogenicity. Its primary immunogenicity measure was the geometric mean fold rise in serotype-specific IgG from 1 month after dose 2 to 1 month after dose 3. The listed secondary outcomes cover IgG concentration and OPA titers across adjacent post-dose measurements, as well as OPA fold rises. These outcome descriptions indicate the planned types of summaries, but do not establish what numerical results were observed.
The registry record does not report a separate comparator arm, a masking procedure, or a randomized allocation process. The design is therefore not a randomized comparison, and the arm descriptions do not support a like-for-like control comparison. Further details about the protocol, such as the rationale for the planned enrollment, 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.
Overall Study
| Stage | 13vPnC |
|---|---|
| STARTED | 331 |
| Vaccinated Dose 1 | 329 |
| Vaccinated Dose 2 | 300 |
| Vaccinated Dose 3 | 279 |
| Completed Dose 3 1-month Blood Draw | 277 |
| COMPLETED | 271 |
| NOT COMPLETED | 60 |
Reasons for not completing this period:
| Reason | 13vPnC |
|---|---|
| Withdrawal by Subject | 22 |
| Lost to Follow-up | 14 |
| Failed to return | 9 |
| Protocol Violation | 7 |
| Adverse Event | 5 |
| Physician Decision | 2 |
| Other | 1 |
Analysis population for the primary outcome, as defined in the registry: Evaluable immunogenicity population: eligible participants who were \>=18 years of age on the day of first vaccination, received at least 2 doses of 13vPnC in the sequence assigned, had valid and determinate assay results, and had no major protocol violations. N (number of participants analyzed)=participants who were evaluable for this measure.
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 population included participants who received at least 1 dose of study vaccine.
| Characteristic | Unit | 13vPnC |
|---|---|---|
| Participants analysed | 329 | |
| Age Continuous | years | 47.3 (SD 9.10) |
| Sex: Female, Male: Female | Participants | 66 |
| Sex: Female, Male: Male | Participants | 263 |
6. Primary Endpoint
The registry lists the primary outcome as Geometric Mean Fold Rise (GMFR) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody From 1 Month After Dose 2 of 13vPnC to 1 Month After Dose 3 of 13vPnC, measured over 1 month post-dose 2, 1 month post-dose 3.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | fold rise |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the geometric mean fold rise (GMFR) in serotype-specific pneumococcal IgG antibody from 1 month after dose 2 to 1 month after dose 3. It covers 13 serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. The registry describes use of logarithmically transformed assay results and a 95% confidence interval.
As a general statistical concept, a geometric mean is useful for measurements that are positive and may vary multiplicatively. A fold-rise summary describes change on a multiplicative scale; it is not an arithmetic difference between two means. Log transformation allows multiplicative changes to be analyzed on an additive scale, after which estimates can be transformed back to the original scale for interpretation.
The endpoint is a repeated measurement within the study group. It describes the antibody change between two specified post-dose time points, but does not by itself compare the vaccine with another treatment or establish the cause of any observed change. The registry record gives the endpoint definition and method, but the GMFR estimate and its confidence interval are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record specifies a within-participant immunogenicity question: the change in serotype-specific IgG between 1 month after dose 2 and 1 month after dose 3. This is a measurement over time in a single group, not a randomized comparison. Without a separate comparator group, any observed change would describe the participants' measurements across those study time points; the design does not isolate the change attributable to 13vPnC from other possible influences.
The endpoint is a geometric mean fold rise, with a 95% confidence interval planned from analysis of logarithmically transformed assay results. The confidence interval would communicate the precision of the estimated mean fold rise, under the assumptions of the specified method. The numerical estimate and interval are not reported in the registry record, so the magnitude and precision of the primary endpoint cannot be assessed from this record.
The registry lists secondary outcomes involving serotype-specific IgG geometric mean concentrations and OPA geometric mean titers after doses, along with OPA fold rises. These measures address different aspects of antibody response and are not interchangeable. Their listed titles do not provide evidence of the direction or size of any response. Numerical results for these outcomes are not reported in the registry record.
Safety information is recorded by periods following vaccination. The registry lists participants at risk and participants affected for serious and other adverse events in each period. Those counts describe reported events in the specified periods, but do not establish that vaccination caused an event. The record does not provide the cause of the events, an adjusted comparison, or a control-group rate. Deaths are not reported in the registry record.
The list of serious-event terms includes coronary artery disease, angina pectoris, non-cardiac chest pain, basal cell carcinoma, angina unstable, and pneumonia, with percentages attached to each term. These percentages are listed as registry results; the available record does not define their denominator or provide enough context to compare them across groups. They should be read as descriptive entries, not as comparative estimates.
Overall, the record describes the trial question, design, endpoint method, and several safety counts, but lacks numerical primary immunogenicity results. Consequently, it cannot establish how large or precise the primary fold-rise estimate was. A missing result is not evidence of no response, and a reported within-group change would not by itself constitute evidence from a controlled comparison.
9. Statistical Methods Explained
The registry describes a geometric mean fold rise calculated from logarithmically transformed assay results. This is a method suited to measurements whose changes are naturally interpreted as proportional rather than additive. In general, analysis on a logarithmic scale turns multiplicative relationships into additive ones, which can make the distribution of assay measurements more suitable for statistical summaries. The estimate is then transformed back so that it can be expressed as a fold rise on the original measurement scale.
What does the confidence interval describe?
The listed dispersion measure is a 95% confidence interval. In general, a confidence interval represents uncertainty about an estimated quantity under the analysis assumptions; it is not a range containing a fixed proportion of individual participants' results. The registry says the interval was obtained by transforming back a confidence interval based on the Student t distribution for the log-transformed assay results. The numerical interval is not reported in the registry record, so its width and the precision of the estimate cannot be evaluated.
Why use a geometric mean fold rise?
As a general concept, a geometric mean summarizes positive values on a multiplicative scale. A fold rise compares measurement levels across time in proportional terms, rather than asking how many assay units were added. The endpoint therefore summarizes the average change in the specified serotype-specific IgG measurements from 1 month after dose 2 to 1 month after dose 3. It does not represent a difference between randomized groups, because the trial has a single group.
How should the population definition be read?
The primary endpoint population was evaluable for immunogenicity under the listed criteria: eligible adults aged at least 18 on the first vaccination day, receipt of at least 2 doses in the assigned sequence, valid and determinate assay results, and no major protocol violations. This population definition identifies who was intended to contribute to the immunogenicity analysis. The number analyzed is not reported in the registry record. The record also does not describe how missing assay measurements were handled or whether any other analysis population was used.
In general, an evaluable population can differ from everyone enrolled if participants do not meet analysis criteria or lack usable measurements. Such exclusions may affect how representative an estimate is of all enrolled participants. The registry record does not provide participant flow or enough detail to determine the extent or consequences of any exclusions.
What can a single-group design estimate?
A single-group study can describe measurements within the enrolled group at specified times. It cannot directly estimate a contrast with an untreated group or another vaccine group when no such comparator is included. Changes over time can reflect the intervention, but also the passage of time, other exposures, or features of the enrolled population. This is a general limitation of interpretation, not a claim that any particular alternative explanation occurred in this trial.
The registry lists no randomized comparison and no masking. It does not report a detailed statistical analysis plan, the handling of multiple outcomes, or whether any interim analyses were performed. Those details are not reported in the registry record and should not be inferred from the endpoint description alone.
The sample-size illustrations are planning calculations rather than observed trial outcomes. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Those assumptions do not describe this single-group trial's allocation or establish that the trial had a particular power. Such illustrations are not observed power and do not replace a trial-specific design justification, which is not reported in the registry record.
Over-dispersion is a general issue when observed variability exceeds what a statistical model assumes. If that occurs, standard errors based on an overly restrictive variability assumption may be too small and confidence intervals too narrow. The registry endpoint description specifies a Student t-based interval on transformed results but does not report diagnostics or any adjustment for over-dispersion. No conclusion about whether over-dispersion occurred in this trial can be drawn from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary immunogenicity endpoint and multiple secondary outcomes across IgG concentration, OPA titers, and fold rises at different post-dose times. It does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a detailed testing strategy. These details are not reported in the registry record, so the chance of false-positive findings across a family of tests cannot be assessed from the record.
The listed primary endpoint is based on an evaluable immunogenicity population. The registry states that participants needed valid and determinate assay results and no major protocol violations, but does not describe how missing measurements were handled, how many participants lacked usable assays, or whether sensitivity analyses were performed. The number analyzed is not reported in the registry record.
The enrollment figure is 331, but enrollment should not be treated as the primary endpoint analysis count. Eligibility criteria and availability of assay results can make the analysis population differ from enrollment. The record does not provide a participant flow accounting for that difference.
The registry does not report an interim analysis plan, the rationale for the planned sample size, or a complete statistical analysis plan. These matters are not reported in the registry record. Accordingly, no claims can be made about prespecification beyond the endpoint description and population criteria that are 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 (After Dose 1 and Before Dose 2) | 24 | 329 | 7.3% |
| 13vPnC (After Dose 2 and Before Dose 3) | 14 | 300 | 4.7% |
| 13vPnC (After Dose 3 and Before Dose 3 Blood Draw) | 4 | 278 | 1.4% |
| 13vPnC (After Dose 3 Blood Draw) | 10 | 329 | 3.0% |
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 (After Dose 1 and Before Dose 2) | 244 of 329 |
| 13vPnC (After Dose 2 and Before Dose 3) | 196 of 300 |
| 13vPnC (After Dose 3 and Before Dose 3 Blood Draw) | 169 of 278 |
| 13vPnC (After Dose 3 Blood Draw) | 30 of 329 |
Most frequent serious adverse event terms
| Event term | Organ system | 13vPnC (After Dose 1 and Before Dose 2) | 13vPnC (After Dose 2 and Before Dose 3) | 13vPnC (After Dose 3 and Before Dose 3 Blood Draw) | 13vPnC (After Dose 3 Blood Draw) |
|---|---|---|---|---|---|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 329 | 1 of 300 | 0 of 278 | 2 of 329 |
| Coronary artery disease | Cardiac disorders | 3 of 329 | 0 of 300 | 0 of 278 | 0 of 329 |
| Alcohol abuse | Psychiatric disorders | 1 of 329 | 0 of 300 | 1 of 278 | 1 of 329 |
| Angina pectoris | Cardiac disorders | 0 of 329 | 2 of 300 | 0 of 278 | 0 of 329 |
| Non-cardiac chest pain | General disorders | 2 of 329 | 0 of 300 | 0 of 278 | 0 of 329 |
| Pneumonia | Infections and infestations | 0 of 329 | 1 of 300 | 1 of 278 | 0 of 329 |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 329 | 1 of 300 | 0 of 278 | 0 of 329 |
| Convulsion | Nervous system disorders | 1 of 329 | 1 of 300 | 0 of 278 | 0 of 329 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 329 | 1 of 300 | 0 of 278 | 0 of 329 |
| Aortic aneurysm | Vascular disorders | 1 of 329 | 0 of 300 | 1 of 278 | 0 of 329 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 13vPnC (After Dose 1 and Before Dose 2) | 13vPnC (After Dose 2 and Before Dose 3) | 13vPnC (After Dose 3 and Before Dose 3 Blood Draw) | 13vPnC (After Dose 3 Blood Draw) |
|---|---|---|---|---|---|
| Pain (Any) | Skin and subcutaneous tissue disorders | 205 of 260 | 193 of 237 | 167 of 204 | 0 of 0 |
| Pain (Mild) | Skin and subcutaneous tissue disorders | 197 of 258 | 181 of 230 | 158 of 197 | 0 of 0 |
| New generalized muscle pain (Any) | General disorders | 152 of 234 | 143 of 199 | 112 of 170 | 0 of 0 |
| New generalized muscle pain (Mild) | General disorders | 139 of 230 | 124 of 188 | 95 of 155 | 0 of 0 |
| Fatigue (Any) | General disorders | 141 of 235 | 119 of 188 | 90 of 160 | 0 of 0 |
| Headache (Any) | General disorders | 138 of 224 | 97 of 173 | 64 of 137 | 0 of 0 |
| Fatigue (Mild) | General disorders | 121 of 223 | 101 of 176 | 72 of 149 | 0 of 0 |
| Headache (Mild) | General disorders | 124 of 216 | 80 of 165 | 53 of 130 | 0 of 0 |
| Diarrhea (Any) | General disorders | 85 of 193 | 69 of 155 | 52 of 134 | 0 of 0 |
| Fatigue (Moderate) | General disorders | 75 of 200 | 59 of 154 | 48 of 132 | 0 of 0 |
Serious events with the highest arm-level rate: coronary artery disease (0.9%), angina pectoris (0.7%), non-cardiac chest pain (0.6%), basal cell carcinoma (0.6%), angina unstable (0.4%).
The registry records adverse events by post-vaccination periods. After dose 1 and before dose 2, 329 participants were at risk for serious adverse events and 24 were affected; 329 were at risk for other adverse events and 244 were affected. After dose 2 and before dose 3, the corresponding counts were 300 at risk and 14 affected for serious adverse events, and 300 at risk and 196 affected for other adverse events.
For the period labeled after dose 3 and before dose 3 blood draw, 278 participants were at risk and 4 were affected for serious adverse events; 278 were at risk and 169 were affected for other adverse events. After dose 3 blood draw, 329 were at risk and 10 were affected for serious adverse events, while 329 were at risk and 30 were affected for other adverse events.
These are period-specific registry counts, not a controlled comparison. The counts should not be added across periods to infer unique participants, because the same participant may contribute to more than one period. The record does not report deaths. It also does not establish whether an event was caused by vaccination. Listed serious-event terms include coronary artery disease (0.9%), angina pectoris (0.7%), non-cardiac chest pain (0.6%), basal cell carcinoma (0.6%), angina unstable (0.4%), and pneumonia (0.4%). The denominator for these percentages is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The trial record gives a defined immunogenicity question and a method for estimating a geometric mean fold rise in serotype-specific IgG. It also records adverse-event counts across periods following the vaccine doses. Those details clarify what the study set out to measure and how some outcomes were summarized.
However, the numerical primary endpoint result is not reported in the registry record. The magnitude of the IgG fold rise and its precision therefore cannot be described. The listed secondary outcome names likewise do not establish any numerical antibody concentration, OPA titer, or fold-rise result. The record's outcome descriptions should not be mistaken for findings.
The single-group design also matters for interpretation. A within-participant comparison across post-dose time points can describe how measurements changed in the study group, but it is not a randomized contrast against a separate control group. Even if numerical changes were reported, the design alone would not establish that the vaccine caused those changes or distinguish them from other influences over time.
The adverse-event counts indicate how many participants were listed as at risk and affected in specified periods. They do not, by themselves, establish causality or provide a comparison with another group. The record does not supply a denominator for the listed serious-event percentages or report deaths.
Thus, the record supports a description of trial design, endpoint definition, and selected safety counts, but not an assessment of the size or precision of the primary immunogenicity result. Missing numerical results do not mean that the endpoint was zero or that no antibody response occurred; they mean the registry record does not report the result needed to evaluate it.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how endpoint structure and study design shape interpretation. The primary outcome is a geometric mean fold rise between measurements after successive doses, analyzed on a logarithmic scale and transformed back for reporting. That approach is designed for proportional changes in positive assay measurements, rather than an arithmetic change in units.
The study is single-group and open-label, with no separate comparator group. Its repeated measurements can describe an immunogenicity pattern over the dose sequence, but do not provide a randomized between-group contrast. Recognizing that distinction prevents a within-group change from being treated as if it were a controlled treatment effect.
The evaluable immunogenicity population is also important. The registry defines eligibility in terms of age, vaccination sequence, valid assay results, and protocol violations. These criteria clarify the intended analysis population, while the absence of a reported analysis count and participant flow leaves uncertainty about how many enrolled participants contributed to the endpoint.
The record illustrates why reporting the estimate and its uncertainty is essential. An endpoint definition and confidence-interval method explain what would be measured, but without the numerical estimate and interval, readers cannot judge its magnitude or precision. Similarly, adverse-event counts need context about their periods, populations, and causal interpretation. The registry supplies period-specific counts but not a control comparison or clear denominator for the listed serious-event percentages.
These features make the record useful for understanding what the study asked statistically, while also highlighting the limits imposed by absent results and the lack of a comparator. Design, outcome definitions, and numerical findings each answer different questions; one cannot substitute for another.
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 principal limitation for interpreting efficacy-related or immunogenicity findings is that the primary GMFR estimate and its 95% confidence interval are not reported in the registry record. Numerical results for the listed secondary outcomes are also not reported. Consequently, the magnitude and precision of the intended antibody outcomes cannot be evaluated from this record.
The trial had a single group, with no randomized comparator, and was open-label. This design permits within-group descriptions but does not provide a like-for-like control comparison. The registry record does not report a statistical analysis plan, multiplicity strategy, interim analyses, or sample-size justification. Those details are not reported in the registry record.
The primary endpoint population is defined by eligibility and assay criteria, but the number analyzed and participant flow are not reported in the registry record. The approach to missing measurements and any sensitivity analyses are also not reported. Enrollment of 331 therefore should not be assumed to equal the number contributing to the primary immunogenicity estimate.
Safety counts are presented for distinct periods, but the record does not provide a causal assessment or controlled safety comparison. Deaths are not reported in the registry record. The denominator for the listed serious-event percentages is not specified, limiting interpretation of those percentages.
Finally, the registry describes doses as approximately 6 months apart, but further details about adherence, protocol deviations, and timing variability are not reported in the registry record. These omissions limit assessment of how closely actual study conduct matched the planned schedule.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety & Immunogenicity of 13vPnC in HIV-Infected Subjects Aged 18 or Older Who Were Previously Immunized With 23vPS — NCT00963235.
- Registry record last updated 2013-06-10; status last verified 2013-04.
- Results first posted 2013-06-10.
- 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
NCT00963235 was a completed phase 3, open-label, single-group trial sponsored by Pfizer. It enrolled 331 HIV-infected adults aged 18 or older who had previously received at least one dose of 23vPS. Participants received 3 doses of 13vPnC approximately 6 months apart, with blood draws as a study procedure.
The primary endpoint was the serotype-specific IgG geometric mean fold rise from 1 month after dose 2 to 1 month after dose 3, with a 95% confidence interval based on log-transformed assay results and the Student t distribution. The numerical primary result and its analysis count are not reported in the registry record. Listed secondary outcomes concern IgG concentrations and OPA titers and fold rises.
The registry records adverse-event counts by post-dose period but does not report deaths or establish event causality. The single-group design does not provide a randomized control comparison. Further details about missing-data methods, multiplicity, interim analyses, and sample-size justification are not reported in the registry record.