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 A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM) (NCT03565900), a randomized phase 3 study. The primary outcome is Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03565900 |
| Phase | Phase 3 |
| Condition | Pneumococcal Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 277 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Recipients of allogeneic hematopoietic stem cell transplant were enrolled, including adults and pediatric participants. The arm descriptions state that participants had received the transplant 90 to 180 days before Day 1. The primary endpoint concerns adults who were randomized and received at least 1 dose of study vaccination.
Intervention
V114 was given as a vaccine regimen. The study description identifies V114 and Prevnar 13™ as the blinded vaccinations, with PNEUMOVAX™23 given open label 12 months after transplant for participants who did not develop chronic graft-versus-host disease.
Comparator
Prevnar 13™ was the active comparator to V114. The registry describes a randomized, parallel-group study and lists both products as biological interventions. It does not report the allocation ratio.
Primary question
Among adults, what percentage experienced a solicited injection-site adverse event after any of the first 3 doses of V114 or Prevnar 13™? The solicited events were erythema, pain, and swelling, assessed up to 5 days after any of the Day 1, Day 30, or Day 60 vaccinations. The registry record does not report the endpoint estimates or a statistical comparison between groups.
The study also set out to evaluate safety, tolerability, and immunogenicity within each vaccination group, including after PNEUMOVAX™23. Those broader aims do not change the scope of the primary endpoint: it is a short-term, participant-level measure of specified injection-site events among adults following the first three vaccinations. It is not a measure of all adverse events, immune response, or protection against pneumococcal infection.
3. Trial Design
This was a phase 3, randomized, parallel-group, active-comparator-controlled clinical study of V114 and Prevnar 13™ in recipients of allogeneic hematopoietic stem cell transplant. The registry lists the study as triple masked; the official title describes it as double blind. The registry record does not explain the difference between those masking labels or specify which roles were masked.
The study enrolled 277 participants and is listed as completed. Its start date was 2018-09-12, and its primary completion date was 2021-11-04. The study was sponsored by Merck Sharp & Dohme LLC. These design and status details describe the trial’s conduct, but do not establish how many participants contributed data to each endpoint or analysis.
The two principal vaccination groups received V114 or Prevnar 13™. The brief description says participants were to receive one of these blinded vaccines, and that PNEUMOVAX™23 was administered open label 12 months after transplant to participants who did not develop chronic graft-versus-host disease. The arm descriptions specify vaccinations on Day 1, Day 30, and Day 60, and state that transplant had occurred 90 to 180 days before Day 1. The available arm descriptions are truncated, so additional regimen details are not reported in the registry record.
Safety and immunogenicity were among the study aims. The primary endpoint is narrower: the percentage of adult participants with a solicited injection-site adverse event after any of the first 3 doses. Secondary outcomes include specified solicited adverse events after PNEUMOVAX™23 and after a fourth dose in some participants. The registry lists 19 outcome measures, but does not report an analysis for the primary endpoint in the record. The allocation ratio, detailed protocol, and planned statistical analysis 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: 263 adult participants and 14 pediatric participants (3 to 18 years of age) were randomized in a 1:1 ratio to receive either V114 or Prevnar 13™ on Day 1.
Overall Study
| Stage | V114 | Prevnar 13™ |
|---|---|---|
| STARTED | 139 | 138 |
| Vaccination 1 With V114 or Prevnar 13™ (PCV) (Day 1) | 139 | 135 |
| Vaccination 2 With PCV (Day 30) | 135 | 128 |
| Vaccination 3 With PCV (Day 60) | 130 | 124 |
| Vaccination 4 With PNEUMOVAX™23 (PPV23) (12 Months After Allo-HSCT, Without Chronic GVHD) | 89 | 75 |
| Vaccination 4 With PCV (12 Months After Allo-HSCT, With Chronic GVHD) | 29 | 37 |
| COMPLETED | 115 | 111 |
| NOT COMPLETED | 24 | 27 |
Reasons for not completing this period:
| Reason | V114 | Prevnar 13™ |
|---|---|---|
| Disposition Unknown | 4 | 1 |
| Withdrawal By Parent/Guardian | 0 | 1 |
| Withdrawal by Subject | 4 | 5 |
| Randomized By Mistake | 0 | 2 |
| Physician Decision | 7 | 11 |
| Death | 9 | 7 |
Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least 1 dose of study vaccination were analyzed.
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 | V114 | Prevnar 13™ | Total |
|---|---|---|---|---|
| Participants analysed | 139 | 138 | 277 | |
| Age, Continuous | years | 47.9 (SD 16.0) | 46.3 (SD 18.3) | 47.1 (SD 17.1) |
| Age, Customized: In utero | Participants | 0 | 0 | 0 |
| Age, Customized: Preterm newborn infants (gestational age < 37 wks) | Participants | 0 | 0 | 0 |
| Age, Customized: Newborns (0-27 days) | Participants | 0 | 0 | 0 |
| Age, Customized: Infants and toddlers (28 days-23 months) | Participants | 0 | 0 | 0 |
| Age, Customized: Children (2-11 years) | Participants | 5 | 4 | 9 |
| Age, Customized: Adolescents (12-17 years) | Participants | 3 | 2 | 5 |
| Age, Customized: Adults (18-64 years) | Participants | 108 | 107 | 215 |
| Age, Customized: From 65-84 years | Participants | 23 | 25 | 48 |
| Sex: Female, Male: Female | Participants | 57 | 62 | 119 |
| Sex: Female, Male: Male | Participants | 82 | 76 | 158 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 30 | 29 | 59 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 104 | 104 | 208 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 5 | 5 | 10 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 4 | 3 | 7 |
| Race (NIH/OMB): Asian | Participants | 2 | 4 | 6 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 | 1 | 7 |
| Race (NIH/OMB): White | Participants | 122 | 115 | 237 |
| Race (NIH/OMB): More than one race | Participants | 5 | 15 | 20 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Adult Participants: Percentage of Participants With a Solicited Injection-site Adverse Event Following Any of the First 3 Doses With V114 or Prevnar 13™, measured over Up to 5 days after any of the Day 1, Day 30, or Day 60 vaccinations (V114 or Prevnar 13™).
| 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 adult participants with at least one solicited injection-site adverse event after any of the first 3 doses of V114 or Prevnar 13™. The specified events are erythema, pain, and swelling. They were assessed up to 5 days after any of the vaccinations on Day 1, Day 30, or Day 60. An adverse event is defined in the registry as an untoward medical occurrence temporally associated with study treatment, whether or not considered related to treatment.
This endpoint expresses how common the specified events were among the evaluated participants. Focusing on prespecified, solicited symptoms makes the safety observation more structured than a count of spontaneously reported events: participants are asked about specific injection-site experiences during a defined period. It does not capture every possible local reaction or establish that a reported event was caused by vaccination.
The registry identifies a 95% confidence interval as the dispersion measure and defines the primary analysis population as all randomized participants who received at least 1 dose of study vaccination. However, the endpoint estimates and confidence limits are not reported in the registry record. The record therefore supports a description of what the endpoint was designed to measure, but not a numerical interpretation of its observed frequency or a comparison between groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial’s design, the primary endpoint definition, and a set of safety counts. It does not report the primary endpoint results or a statistical test comparing V114 with Prevnar 13™. Consequently, the posted record does not establish the observed percentage of adults with solicited injection-site events after the first three doses, the precision of either group estimate, or the size and direction of a difference between groups.
A 95% confidence interval is listed as the endpoint’s dispersion measure, but the interval limits are not reported. In general, a confidence interval indicates the range of values compatible with the data and the method used to calculate the interval. Without the endpoint estimates and interval limits, readers cannot assess the precision of the primary safety estimates from this record. A planned confidence interval is not itself a result.
The safety listings give counts for participants at risk and participants affected in several treatment and vaccination-period groups. For adults after any of the first 3 doses, the V114 group lists 131 at risk, 38 with a serious adverse event, 125 with an event in the separate other-event count, and 6 deaths. The corresponding Prevnar 13™ group lists 129 at risk, 48 with a serious adverse event, 108 in the other-event count, and 9 deaths. These are descriptive counts; they do not by themselves establish a treatment-related difference. The registry record does not provide a statistical comparison for these figures or enough detail to interpret the other-event category fully.
The serious-event counts include all recorded events in the listed groups, not only events attributed to study vaccination. The study definition of an adverse event does not require a judgment that the event was caused by treatment. The counts therefore should not be read as causal estimates. Deaths are listed separately as counts, but their causes and relationship to treatment are not reported in the registry record.
The serious-event term list includes acute myeloid leukaemia recurrent at 16.7%, herpes zoster at 12.5%, pneumonia at 12.5%, acute lymphocytic leukaemia recurrent at 12.5%, graft versus host disease at 5.6%, and bronchiolitis at 3.7%. These listed percentages describe terms in the safety record; the record does not establish from this list that a vaccine caused any of them. Overall, the available information is useful for identifying what outcomes were monitored and which safety counts were recorded, but it cannot answer the primary comparative question or support a conclusion about treatment effects.
9. Statistical Methods Explained
The primary outcome is a percentage: the proportion of evaluated adults who experienced a specified injection-site event after at least one of the first three vaccinations. For a binary outcome, each participant is classified according to whether the event occurred during the defined observation period. This kind of summary is straightforward to interpret as event frequency, but its meaning depends on the event definition, the population included, and the time window. In this study, the specified events were erythema, pain, and swelling, assessed up to 5 days after any of the Day 1, Day 30, or Day 60 vaccinations.
The registry names the analysis population as all randomized participants who received at least 1 dose of study vaccination. This definition is important: the endpoint is not described as applying to every randomized participant regardless of vaccination, nor does the record state that the primary analysis used a different population. The exact number included in the primary endpoint analysis is not reported in the registry record.
What does a confidence interval add?
A percentage calculated from trial participants is an estimate of an underlying event frequency, not an exact value for every similar population. A confidence interval expresses statistical uncertainty around that estimate under the chosen method. A narrower interval generally reflects greater precision, while a wider interval reflects more uncertainty. The registry specifies a 95% confidence interval for the primary endpoint, but does not report its limits or the associated event estimates. As a result, the interval’s width and the precision of the estimate cannot be assessed.
A confidence interval is not a guarantee that the true value lies within its particular limits, and it does not on its own determine whether two groups differ. For a treatment comparison, interpretation also requires the group estimates, an appropriate contrast between them, and the uncertainty around that contrast. The registry record does not report those results for the primary endpoint.
How should group comparisons be interpreted?
Randomization is intended to create groups that are comparable on average at the outset, supporting a fair comparison of outcomes. It does not remove uncertainty, prevent all imbalances, or substitute for reporting the actual results. A comparative interpretation would require the observed outcome frequencies and the prespecified approach to estimating the contrast. The registry identifies random allocation and an active comparator, but the allocation ratio and details of the planned statistical comparison are not reported in the registry record.
Because the endpoint is binary, analysts commonly summarize each group with the number of participants who experienced the event and the number evaluated, then estimate a contrast using a suitable method. A confidence interval around each group percentage describes uncertainty in that group estimate; an interval around a between-group contrast addresses uncertainty in the comparison. These are general statistical principles, not a description of analyses reported for this trial. The record lists no analyses for the primary endpoint, so no such comparison can be interpreted from it.
What do the safety counts represent?
The serious adverse event listings identify counts of participants at risk and affected within vaccination groups and periods. Such counts are descriptive unless accompanied by a defined comparison, analysis population, follow-up rule, and uncertainty estimate. Participants may differ in how long they were observed or in their clinical circumstances, and the registry record does not provide enough detail to evaluate those considerations for every safety listing. A serious adverse event is not automatically a treatment-related event: the study’s general adverse-event definition explicitly allows events whether or not they are considered related to study treatment.
Counts should also be kept distinct from percentages. A count indicates how many participants were recorded as affected; a percentage requires a defined denominator and calculation. No new percentages or contrasts are inferred from the listed counts. The term-specific percentages are reported as given in the registry, but their denominators and analysis details are not reported in the registry record.
What is the role of planning illustrations?
General sample-size planning asks how many participants may be needed to detect an effect under stated statistical assumptions. The registry description of the planning illustration specifies a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; it also says the effect to detect is expressed as a fraction of the observed effect. Such illustrations are hypothetical planning exercises, not observed trial outcomes, and not evidence that a trial had a particular probability of finding a result. They do not replace the trial’s own design rationale, which is not reported in the registry record.
Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. If ignored, uncertainty can be understated and intervals can become too narrow. That issue may matter for some outcome types and models, but the primary endpoint is a binary participant-level event, and the registry record does not describe an over-dispersion model or a reason to apply one. No conclusion about the trial’s statistical methods on this point can be drawn from the information reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 19 outcome measures and identifies one primary endpoint, alongside multiple secondary outcomes involving solicited adverse events, serious adverse events, and different participant groups or vaccination periods. When a study assesses multiple outcomes or makes multiple comparisons, the chance of at least one apparently unusual result can increase. Statistical plans sometimes address this through prespecified outcome hierarchies or multiplicity adjustments. The planned approach to multiplicity is not reported in the registry record.
The record lists zero analyses and does not provide primary endpoint estimates, confidence limits, p-values, or comparative results. The adjustment method, if any, for multiple outcomes is not reported in the registry record. In the absence of analysis results, it is not possible to determine which comparisons were conducted or how they were interpreted.
Missing-data handling is also not reported in the registry record. The primary population is described as randomized participants who received at least 1 dose, but the record does not explain how missing symptom assessments, incomplete follow-up, withdrawal, or other unavailable endpoint data were handled. It does not report an imputation method, a missingness assumption, or a sensitivity analysis. The number with evaluable primary endpoint data is not reported in the registry record.
The record also does not describe the detailed analysis populations for each secondary outcome, or how participants who developed chronic graft-versus-host disease were treated in each analysis. These omissions do not mean that no procedures were used in the full study; they mean that the registry record does not report them. Any interpretation of the safety counts or endpoint results should therefore remain limited to the definitions and data the record actually reports.
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 |
|---|---|---|---|
| V114 (Following Any of the First 3 Doses of PCV) Adults | 38 | 131 | 29.0% |
| Prevnar 13™ (Following Any of the First 3 Doses of PCV) Adults | 48 | 129 | 37.2% |
| V114 (Following PPV23) Adults | 2 | 84 | 2.4% |
| Prevnar 13™ (Following PPV23) Adults | 4 | 71 | 5.6% |
| V114 (Following Dose 4 of PCV) Adults | 6 | 27 | 22.2% |
| Prevnar 13™ (Following Dose 4 of PCV) Adults | 7 | 36 | 19.4% |
| V114 (Following Any of the First 3 Doses of PCV) Pediatric | 2 | 8 | 25.0% |
| Prevnar 13™ (Following Any of the First 3 Doses of PCV) Pediatric | 1 | 6 | 16.7% |
| V114 (Following PPV23) Pediatric | 0 | 5 | 0.0% |
| Prevnar 13™ (Following PPV23) Pediatric | 0 | 4 | 0.0% |
| V114 (Following Dose 4 of PCV) Pediatric | 0 | 2 | 0.0% |
| Prevnar 13™ (Following Dose 4 of PCV) Pediatric | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| V114 (Following Any of the First 3 Doses of PCV) Adults | 6 of 131 |
| Prevnar 13™ (Following Any of the First 3 Doses of PCV) Adults | 9 of 129 |
| V114 (Following PPV23) Adults | 1 of 84 |
| Prevnar 13™ (Following PPV23) Adults | 0 of 71 |
| V114 (Following Dose 4 of PCV) Adults | 2 of 27 |
| Prevnar 13™ (Following Dose 4 of PCV) Adults | 1 of 36 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| V114 (Following Any of the First 3 Doses of PCV) Adults | 125 of 131 |
| Prevnar 13™ (Following Any of the First 3 Doses of PCV) Adults | 108 of 129 |
| V114 (Following PPV23) Adults | 65 of 84 |
| Prevnar 13™ (Following PPV23) Adults | 53 of 71 |
| V114 (Following Dose 4 of PCV) Adults | 22 of 27 |
| Prevnar 13™ (Following Dose 4 of PCV) Adults | 26 of 36 |
Most frequent serious adverse event terms
| Event term | Organ system | V114 (Following Any of the First 3 Doses of PCV) Adults | Prevnar 13™ (Following Any of the First 3 Doses of PCV) Adults | V114 (Following PPV23) Adults | Prevnar 13™ (Following PPV23) Adults | V114 (Following Dose 4 of PCV) Adults | Prevnar 13™ (Following Dose 4 of PCV) Adults |
|---|---|---|---|---|---|---|---|
| Graft versus host disease | Immune system disorders | 4 of 131 | 5 of 129 | 0 of 84 | 0 of 71 | 1 of 27 | 2 of 36 |
| Pneumonia | Infections and infestations | 3 of 131 | 6 of 129 | 0 of 84 | 1 of 71 | 1 of 27 | 0 of 36 |
| Acute lymphocytic leukaemia recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 131 | 7 of 129 | 0 of 84 | 0 of 71 | 2 of 27 | 0 of 36 |
| Febrile neutropenia | Blood and lymphatic system disorders | 2 of 131 | 2 of 129 | 0 of 84 | 1 of 71 | 0 of 27 | 0 of 36 |
| Diarrhoea | Gastrointestinal disorders | 3 of 131 | 2 of 129 | 0 of 84 | 0 of 71 | 0 of 27 | 0 of 36 |
| Acute myeloid leukaemia recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 131 | 3 of 129 | 0 of 84 | 0 of 71 | 0 of 27 | 0 of 36 |
| Pyrexia | General disorders | 0 of 131 | 3 of 129 | 1 of 84 | 0 of 71 | 0 of 27 | 0 of 36 |
| Acute graft versus host disease | Immune system disorders | 1 of 131 | 2 of 129 | 0 of 84 | 0 of 71 | 0 of 27 | 0 of 36 |
| Pneumocystis jirovecii pneumonia | Infections and infestations | 2 of 131 | 1 of 129 | 0 of 84 | 0 of 71 | 0 of 27 | 0 of 36 |
| Sepsis | Infections and infestations | 0 of 131 | 2 of 129 | 0 of 84 | 0 of 71 | 0 of 27 | 1 of 36 |
Most frequent non-serious adverse event terms
| Event term | Organ system | V114 (Following Any of the First 3 Doses of PCV) Adults | Prevnar 13™ (Following Any of the First 3 Doses of PCV) Adults | V114 (Following PPV23) Adults | Prevnar 13™ (Following PPV23) Adults | V114 (Following Dose 4 of PCV) Adults | Prevnar 13™ (Following Dose 4 of PCV) Adults |
|---|---|---|---|---|---|---|---|
| Injection site pain | General disorders | 116 of 131 | 97 of 129 | 57 of 84 | 41 of 71 | 21 of 27 | 22 of 36 |
| Myalgia | Musculoskeletal and connective tissue disorders | 64 of 131 | 45 of 129 | 27 of 84 | 19 of 71 | 8 of 27 | 8 of 36 |
| Fatigue | General disorders | 59 of 131 | 52 of 129 | 19 of 84 | 12 of 71 | 8 of 27 | 6 of 36 |
| Headache | Nervous system disorders | 38 of 131 | 40 of 129 | 18 of 84 | 14 of 71 | 6 of 27 | 4 of 36 |
| Injection site swelling | General disorders | 42 of 131 | 23 of 129 | 18 of 84 | 17 of 71 | 6 of 27 | 5 of 36 |
| Injection site erythema | General disorders | 27 of 131 | 18 of 129 | 15 of 84 | 16 of 71 | 1 of 27 | 3 of 36 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 21 of 131 | 24 of 129 | 6 of 84 | 6 of 71 | 3 of 27 | 3 of 36 |
| Diarrhoea | Gastrointestinal disorders | 12 of 131 | 5 of 129 | 2 of 84 | 0 of 71 | 0 of 27 | 0 of 36 |
| Pyrexia | General disorders | 1 of 131 | 2 of 129 | 5 of 84 | 1 of 71 | 1 of 27 | 2 of 36 |
| Abdominal pain | Gastrointestinal disorders | 2 of 131 | 6 of 129 | 0 of 84 | 0 of 71 | 0 of 27 | 0 of 36 |
Serious events with the highest arm-level rate: acute myeloid leukaemia recurrent (16.7%), herpes zoster (12.5%), pneumonia (12.5%), acute lymphocytic leukaemia recurrent (12.5%), graft versus host disease (5.6%).
The serious adverse event listings separate the number of participants at risk from the number recorded as affected, and report deaths as a separate count. For adults after any of the first 3 doses, the V114 group had 131 participants at risk and 38 participants recorded with a serious adverse event; the Prevnar 13™ group had 129 at risk and 48 recorded with a serious adverse event. The record also lists 6 and 9 deaths, respectively, in those groups. These figures are counts, not adjusted comparative estimates.
Other periods and participant groups have separate listings. For adults following PNEUMOVAX™23, the serious-event counts are 2 among 84 at risk for V114 and 4 among 71 at risk for Prevnar 13™. Following Dose 4 of PCV, the adult listings are 6 among 27 at risk for V114 and 7 among 36 at risk for Prevnar 13™. Pediatric group counts are smaller, and the registry record lists no serious events in several pediatric group-period entries. These separate groups should not be combined into a single comparison without an analysis plan.
The counts do not establish that vaccination caused an event or death. The record does not report event attribution, follow-up duration for each safety group, or statistical comparisons for these counts. Serious adverse events also differ in clinical nature, so the overall count and the term-specific listing answer different descriptive questions.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized comparison of V114 and Prevnar 13™ among allogeneic hematopoietic stem cell transplant recipients, with safety, tolerability, and immunogenicity as study aims. It defines a primary safety endpoint for adults: the percentage with solicited injection-site erythema, pain, or swelling after any of the first three vaccinations, assessed up to 5 days after a dose. This gives readers a clear account of the question the primary endpoint was intended to address.
However, the record does not report the primary endpoint percentages, confidence interval limits, or a statistical comparison. It therefore does not show how frequently these specified events occurred in either group or how precisely the rates were estimated. No conclusion that one vaccination group had a higher or lower event frequency can be drawn from the endpoint definition alone.
The safety listings provide descriptive counts of participants affected by serious adverse events, other adverse events, and deaths across several groups and periods. These counts are useful for understanding what the record contains, but they do not establish causality or a difference between treatments. The record does not report the attribution of deaths or the statistical analyses needed to interpret the counts as comparative effects.
Nor does this record by itself establish vaccine immunogenicity or protection against pneumococcal infection. Although immunogenicity is a study aim and the condition listed is pneumococcal infections, the reported information in this record does not include immune-response results or infection outcomes. The appropriate interpretation is therefore limited: the trial design and outcome definitions are described, some safety counts are listed, and the primary comparative results are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial raises statistical questions that are especially relevant in a transplant population: how to define and observe safety outcomes across several vaccination periods, and how to distinguish descriptive counts from comparative evidence. The primary endpoint uses solicited symptoms with a specified post-vaccination observation window. Such a definition makes the outcome more reproducible than an unrestricted report of symptoms, while still leaving important questions about missing assessments and follow-up that require methods reporting.
The study also includes adults and pediatric participants and records outcomes after multiple vaccination stages. Those groups and periods should not automatically be pooled, since the populations and observation contexts differ. Separate reporting makes clear which participants and exposure period a count refers to; sound comparisons also require prespecified analysis methods and uncertainty estimates.
Randomization and an active comparator are important features for a comparative trial, but the design alone does not answer whether outcomes differed. Results need to include the number evaluated, event frequencies, effect estimates, and uncertainty. In this registry record, the primary endpoint’s definition and confidence-interval measure are specified, but its results and comparative analysis are not reported. That distinction is a useful lesson in evidence appraisal: a well-defined question is not the same as a reported answer.
Finally, serious adverse event counts require careful interpretation because occurrence and causation are separate questions. The record’s adverse-event definition includes events whether or not they are considered treatment related. Understanding safety therefore depends on both complete descriptive reporting and a clear account of attribution and comparative methods. The registry information illustrates why readers should look for those elements before drawing conclusions from raw counts.
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 limitation for interpreting efficacy or comparative safety is that the registry record does not report the primary endpoint results. It gives no event percentages, confidence interval limits, or test of the V114 versus Prevnar 13™ comparison. The record therefore cannot show the magnitude, direction, or precision of the primary endpoint contrast.
Although safety counts are available for several groups and vaccination periods, their analytical context is limited. The record does not report the statistical comparisons, event attribution, or detailed follow-up information needed to interpret the figures as treatment effects. The term-specific serious-event percentages are listed, but their denominators and analytic details are not reported in the registry record. The deaths are counts without reported cause or relationship to treatment.
The primary endpoint applies to adults, while the study also included pediatric participants. Pediatric numbers in the safety listings are limited, and the registry record does not provide a primary endpoint result for that group. Adult endpoint information should not be generalized to pediatric participants from this record.
The registry identifies 19 outcome measures, but detailed multiplicity procedures, missing-data handling, and outcome-specific analysis populations are not reported. The record does not include a detailed statistical analysis plan or explain the difference between its triple-masked designation and the double-blind wording in the official title. The arm descriptions are truncated, limiting interpretation of regimen details beyond those stated. These gaps do not establish that the full study lacked such procedures or information; they mean they are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Allogeneic Hematopoietic Stem Cell Transplant Recipients (V114-022/PNEU-STEM) — NCT03565900.
- Registry record last updated 2023-07-28; status last verified 2023-07.
- Results first posted 2022-10-20.
- 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
NCT03565900 is a completed phase 3 randomized, parallel-group, active-comparator-controlled study of V114 and Prevnar 13™ in allogeneic hematopoietic stem cell transplant recipients. The registry reports an enrollment of 277 and identifies safety, tolerability, and immunogenicity as study aims. PNEUMOVAX™23 was included as an open-label vaccination for participants who did not develop chronic graft-versus-host disease.
The primary endpoint was the percentage of adult participants with solicited injection-site erythema, pain, or swelling after any of the first 3 doses, assessed up to 5 days after vaccination. The registry specifies a 95% confidence interval and defines the primary population as randomized participants who received at least 1 dose.
Safety counts are listed for adults and pediatric participants across vaccination periods. The primary endpoint estimates, confidence limits, and comparative analysis are not reported in the registry record. Multiplicity procedures and missing-data methods are also not reported.