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 TIV and High Dose TIV in Subjects With Rheumatoid Arthritis (NCT01436370), a randomized phase 2 study. The primary outcome is Number of RA Participants in the 2011-2012 Season Who Achieved Seroconversion at Day 21 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01436370 |
| Phase | Phase 2 |
| Condition | Influenza |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 102 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
The study included adults with rheumatoid arthritis receiving TNF-alpha-inhibitor therapy and healthy controls matched by age and gender. The brief summary describes the adults with rheumatoid arthritis as aged 18 to 64 years. For the primary endpoint, the registry specifies an analysis population of rheumatoid arthritis participants enrolled and vaccinated with the 2011-2012 vaccines. The registry record does not report the characteristics of the enrolled participants beyond these descriptions.
Intervention
Participants received an intramuscular trivalent inactivated influenza vaccine. The study compared a standard dose containing 15 mcg per strain with a high dose containing 60 mcg per strain. Both formulations covered three influenza strains. The record describes these as Sanofi Pasteur Fluzone and Fluzone High Dose.
Comparator
The design included rheumatoid arthritis participants and healthy controls in both dose groups. This permits comparisons involving dose and participant group, but the registry record does not identify one single comparison as the sole primary contrast. The listed primary endpoint focuses on seroconversion among rheumatoid arthritis participants receiving the 2011-2012 vaccines.
Primary question
The primary endpoint asks how many rheumatoid arthritis participants achieved seroconversion by Day 21 against each of the three vaccine strains in the 2011-2012 season. The registry defines seroconversion using the change in HAI assay titers from before vaccination to the Day 21 visit. The observed counts by strain and dose are not reported in the registry record, so the primary question cannot be answered from the posted results described in the record.
3. Trial Design
This was a randomized, double-blinded, parallel Phase II study. The registry reports enrollment of 102 and a completed status. The study involved adults with rheumatoid arthritis receiving TNF-alpha-inhibitor therapy and healthy age- and gender-matched controls. The brief summary gives an age range of 18 to 64 years for the adults with rheumatoid arthritis.
The design crossed participant group with vaccine dose: rheumatoid arthritis participants and healthy controls were assigned to standard-dose or high-dose trivalent inactivated influenza vaccine. The standard dose is described as 15 mcg per strain, and the high dose as 60 mcg per strain, with both formulations covering three strains. The arm descriptions refer to single intramuscular doses. They give planned group descriptions of 40 participants, with up to 50, but the registry record does not report actual enrollment by arm.
The primary endpoint pertains to rheumatoid arthritis participants vaccinated with the 2011-2012 vaccines, with blood testing before vaccination and at Day 21. Other listed outcomes include antibody titers for the 2011-2012 and 2012-2013 seasons, seroconversion at other time points, and safety and reactogenicity measures. Thus, the endpoint set spans more than one season and includes both immune-response and adverse-event outcomes.
Randomization and double blinding describe the planned allocation and masking features; the registry record does not report how randomization was generated, how allocation was concealed, or which study roles were masked. The protocol details for stratification, adherence, vaccine administration beyond the arm descriptions, and handling of participants who did not complete follow-up are not reported in the registry record. The record also does not give a statistical analysis plan or a sample-size justification.
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.
Only the first 6 of 8 groups are shown.
Overall Study
| Stage | RA Participants, 2011-2012 Fluzone Standard Dose | Healthy Controls, 2011-2012 Fluzone Standard Dose | RA Participants, 2011-2012 Fluzone High Dose | Healthy Controls, 2011-2012 Fluzone High Dose | RA Participants, 2012-2013 Fluzone Standard Dose | Healthy Controls, 2012-2013 Fluzone Standard Dose |
|---|---|---|---|---|---|---|
| STARTED | 6 | 6 | 10 | 10 | 19 | 19 |
| COMPLETED | 6 | 6 | 10 | 10 | 18 | 19 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 1 | 0 |
Reasons for not completing this period:
| Reason | RA Participants, 2011-2012 Fluzone Standard Dose | Healthy Controls, 2011-2012 Fluzone Standard Dose | RA Participants, 2011-2012 Fluzone High Dose | Healthy Controls, 2011-2012 Fluzone High Dose | RA Participants, 2012-2013 Fluzone Standard Dose | Healthy Controls, 2012-2013 Fluzone Standard Dose |
|---|---|---|---|---|---|---|
| Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The analysis population includes all RA participants enrolled and vaccinated with the 2011-2012 vaccines.
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: The baseline analysis population includes all participants who were enrolled and vaccinated.
Only the first 6 of 9 groups are shown.
| Characteristic | Unit | RA Participants, 2011-2012 Fluzone Standard Dose | Healthy Controls, 2011-2012 Fluzone Standard Dose | RA Participants, 2011-2012 Fluzone High Dose | Healthy Controls, 2011-2012 Fluzone High Dose | RA Participants, 2012-2013 Fluzone Standard Dose | Healthy Controls, 2012-2013 Fluzone Standard Dose |
|---|---|---|---|---|---|---|---|
| Participants analysed | 6 | 6 | 10 | 10 | 19 | 19 | |
| Age, Continuous | years | 46.2 (SD 9.3) | 46.4 (SD 9.4) | 47.6 (SD 9.5) | 48.3 (SD 10.1) | 49.8 (SD 11.0) | 50.1 (SD 10.8) |
| Sex: Female, Male: Female | Participants | 5 | 5 | 7 | 7 | 11 | 11 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 3 | 3 | 8 | 8 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 0 | 2 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 1 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 6 | 5 | 10 | 7 | 19 | 18 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 0 | 0 | 1 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 5 | 6 | 10 | 10 | 18 | 19 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 6 | 6 | 10 | 10 | 19 | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Number of RA Participants in the 2011-2012 Season Who Achieved Seroconversion at Day 21 Against Each of the 3 Specific Influenza Strains in Vaccine the Participant Received, measured over Day 0 prior to and Day 21 following immunization.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a count of rheumatoid arthritis participants who achieved seroconversion by Day 21 against each of the three influenza strains in the vaccine received during the 2011-2012 season. Blood was collected before vaccination and at the Day 21 follow-up visit, and the HAI assay used seasonal vaccine strains as assay antigens.
The registry defines seroconversion in either of two ways. A participant qualifies if the Day 0 titer is below 1:10, the assay’s lowest level of detection, and the Day 21 titer is 1:40 or greater; alternatively, a Day 0 titer of 1:10 or greater must be followed by an increase of at least fourfold by Day 21. This definition accounts for both participants whose starting titer is below detection and those with a measurable starting titer.
Seroconversion is an immunogenicity measure: it describes a specified antibody-titer change after vaccination. It does not, by itself, measure clinical influenza illness or establish protection against infection. The count is defined separately for each vaccine strain, so it represents several related endpoint results rather than one overall response. The registry record does not report the observed counts or the corresponding denominators by strain and dose. It therefore does not establish the size or precision of any dose or participant-group difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes the study design and defines its primary immune-response endpoint, but it does not report the primary endpoint results. In particular, the number of rheumatoid arthritis participants who seroconverted by Day 21 for each of the three 2011-2012 vaccine strains is not reported in the registry record. Without those counts and the relevant group denominators, the posted record does not support a numerical comparison of standard-dose and high-dose responses for that endpoint.
The endpoint is strain-specific, and the record lists several strains rather than a single summary comparison. It also lists other immune outcomes, including geometric mean titers for each strain in both the 2011-2012 and 2012-2013 seasons and seroconversion at additional time points. These outcomes can describe different features of immune response, but no result values for them are included in the registry record described by the registry record. The record lists 14 outcome measures and 30 analyses; those counts alone do not establish which analyses were prespecified, how they were prioritized, or which results were statistically persuasive.
Safety information is available in the registry’s adverse-event group summaries. For serious adverse events, the reported affected and at-risk counts are zero of 6 for rheumatoid arthritis participants receiving standard dose in 2011-2012, zero of 6 for healthy controls receiving standard dose in that season, zero of 10 for rheumatoid arthritis participants receiving high dose, and zero of 10 for healthy controls receiving high dose. For 2012-2013, the corresponding counts are 1 of 19, zero of 19, zero of 16, and 1 of 16. These are observed counts in the listed groups, not estimates of comparative risk. The groups are small, and the registry record does not provide uncertainty intervals or a statistical comparison for these safety counts.
The other-adverse-event counts are also listed by group, with affected and at-risk counts of 6 of 6, 5 of 6, 10 of 10, and 9 of 10 in 2011-2012, followed by 18 of 19, 14 of 19, 16 of 16, and 12 of 16 in 2012-2013, in the same group order. These counts should not be read as evidence that one dose or population is safer: the record does not specify a comparative analysis for them, and the groups have limited numbers. The listed top serious-event terms are angina unstable at 6.2% and hypertension at 5.3%; their context and group-specific breakdown are not reported in the registry record.
Overall, the registry record supports a description of the study’s question, its endpoint definition, and the reported adverse-event counts. It does not supply enough primary efficacy results to estimate the size or precision of an immunogenicity difference, or to draw a statistical conclusion about comparative vaccine response.
9. Statistical Methods Explained
For a binary endpoint such as seroconversion, each participant is classified according to whether the specified event occurred. A count of participants with the event is meaningful alongside the number assessed in the relevant group. The registry defines the event using Day 0 and Day 21 titers and applies the definition separately to each vaccine strain. It does not report the actual primary endpoint counts or group denominators in the registry record, so no event proportion or between-group estimate can be interpreted from the primary results.
What does the endpoint definition capture?
The HAI assay produces titers that can be compared before and after vaccination. The registry’s definition uses both an absolute threshold for participants whose baseline titer is below 1:10 and a fold-change rule for participants whose baseline is 1:10 or greater. This approach distinguishes a rise from a low or undetectable starting level from a substantial increase in someone with a measurable baseline. The endpoint is an assay-defined immune response, not a direct count of influenza infections or a clinical outcome.
Because the endpoint is evaluated for three strains, results can differ across strains even within the same dose and participant group. A strain-specific count answers a narrower question than a single combined measure. A combined summary would require a specified method for combining or prioritizing the strain results; such a method is not reported in the registry record. The record explicitly indicates that the primary outcome has several categories or time points and is not reduced to one comparison.
How should a comparison be interpreted?
In general, a comparison of binary outcomes may be expressed as a difference in event proportions, a ratio of proportions, or another model-based contrast. These measures answer different questions and have different interpretations. The selected measure, its uncertainty interval, and the statistical test should be read together rather than treating a single count as a complete comparison. The primary endpoint results and any corresponding estimates or uncertainty intervals are not reported in the registry record, so no such comparison can be evaluated from the listed information.
A confidence interval, in general, describes the range of effect estimates compatible with the data under the assumptions of the analysis. It conveys precision as well as direction and magnitude; a wide interval signals less precision than a narrow interval. The registry record does not report confidence intervals for the primary endpoint. A p-value, in general, measures how unusual data at least as incompatible with a specified null model would be if that model and the test assumptions held. It does not measure the probability that a treatment works, and it does not describe the size or clinical importance of an effect. No primary endpoint p-value is reported in the registry record.
Why do the study features matter?
Randomization is intended to support a fair comparison by assigning participants to study groups by chance, while blinding is intended to reduce the influence of knowledge of assignment on care, reporting, or assessment. These are general design principles. The registry identifies the trial as randomized and double-blinded, but does not report the randomization procedure, the precise masking arrangements, or an assessment of whether masking was maintained.
The parallel design means the study compares groups assigned to different vaccine conditions rather than describing a crossover in which participants receive multiple conditions in sequence. The registry lists both rheumatoid arthritis participants and healthy controls under both dose levels. A comparison of dose within the rheumatoid arthritis group addresses a different question from a comparison between rheumatoid arthritis participants and healthy controls at the same dose. The primary endpoint is narrower still: it specifies rheumatoid arthritis participants and the 2011-2012 vaccination season.
What does the planning illustration mean?
In general, a sample-size planning calculation asks how many participants per arm would be needed to detect a chosen effect under stated assumptions. The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes the effect to detect as a stated fraction of the observed effect. The record’s assumptions say that non-time-to-event illustrations are expressed as participants per arm.
Such a calculation is a planning illustration, not a measure of power observed in the completed study. Its result depends on the chosen effect, significance level, allocation, statistical approximation, and the quality of the observed-effect estimate used as its starting point. The specific sample-size illustration values are not reported in the registry record, and the record does not report the trial’s own sample-size justification. No conclusion about whether the completed study was adequately powered can be drawn from the planning assumptions alone.
Why can multiple outcomes complicate inference?
In general, examining many strains, seasons, time points, and safety outcomes creates multiple opportunities to observe an apparently unusual result. A prespecified multiplicity strategy can help control the interpretation of a family of tests, but the chosen strategy depends on the study’s objectives and analysis plan. The registry lists 14 outcome measures and 30 analyses, but the statistical plan, hierarchy of hypotheses, and any adjustment for multiple testing are not reported in the registry record. Therefore, the record does not establish how any collection of results should be interpreted as a family of confirmatory tests.
10. Multiplicity, Missing Data and Analysis Populations
The study includes multiple outcomes and repeated distinctions: immune responses for three vaccine strains, two seasons, additional seroconversion time points, and several safety and reactogenicity measures. The registry lists 14 outcome measures and 30 analyses. With multiple analyses, general statistical practice distinguishes prespecified primary questions from secondary or exploratory comparisons and considers whether adjustment for multiple testing is appropriate. The registry record does not report a testing hierarchy, a multiplicity adjustment, or which analyses were prespecified beyond the stated primary endpoint.
The primary endpoint itself is defined across several strains, and the registry notes that it is not reduced to one comparison. This means the record does not identify one summary result that can stand in for all strain-specific responses. It also does not report a method for combining results, or an approach to interpreting discordant findings across strains.
The registry describes the primary analysis population as rheumatoid arthritis participants enrolled and vaccinated with the 2011-2012 vaccines. It does not report the number included in each strain-specific analysis, whether all vaccinated participants had usable follow-up samples, or how missing blood tests or titers were handled. Details on exclusions, protocol deviations, and analysis populations for the other outcomes are not reported in the registry record. No assumptions about missing outcomes or imputation should be made from the endpoint definition alone.
For these reasons, the available record does not permit a full assessment of multiplicity or missing-data bias. It describes what was intended to be measured, but does not provide the complete analysis plan or the participant flow and endpoint data needed to evaluate how that plan was implemented.
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 |
|---|---|---|---|
| RA Participants, 2011-2012 Fluzone Standard Dose | 0 | 6 | 0.0% |
| Healthy Controls, 2011-2012 Fluzone Standard Dose | 0 | 6 | 0.0% |
| RA Participants, 2011-2012 Fluzone High Dose | 0 | 10 | 0.0% |
| Healthy Controls, 2011-2012 Fluzone High Dose | 0 | 10 | 0.0% |
| RA Participants, 2012-2013 Fluzone Standard Dose | 1 | 19 | 5.3% |
| Healthy Controls, 2012-2013 Fluzone Standard Dose | 0 | 19 | 0.0% |
| RA Participants, 2012-2013 Fluzone High Dose | 0 | 16 | 0.0% |
| Healthy Controls, 2012-2013 Fluzone High Dose | 1 | 16 | 6.2% |
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 |
|---|---|
| RA Participants, 2011-2012 Fluzone Standard Dose | 6 of 6 |
| Healthy Controls, 2011-2012 Fluzone Standard Dose | 5 of 6 |
| RA Participants, 2011-2012 Fluzone High Dose | 10 of 10 |
| Healthy Controls, 2011-2012 Fluzone High Dose | 9 of 10 |
| RA Participants, 2012-2013 Fluzone Standard Dose | 18 of 19 |
| Healthy Controls, 2012-2013 Fluzone Standard Dose | 14 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | RA Participants, 2011-2012 Fluzone Standard Dose | Healthy Controls, 2011-2012 Fluzone Standard Dose | RA Participants, 2011-2012 Fluzone High Dose | Healthy Controls, 2011-2012 Fluzone High Dose | RA Participants, 2012-2013 Fluzone Standard Dose | Healthy Controls, 2012-2013 Fluzone Standard Dose |
|---|---|---|---|---|---|---|---|
| Hypertension | Vascular disorders | 0 of 6 | 0 of 6 | 0 of 10 | 0 of 10 | 1 of 19 | 0 of 19 |
| Angina unstable | Cardiac disorders | 0 of 6 | 0 of 6 | 0 of 10 | 0 of 10 | 0 of 19 | 0 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | RA Participants, 2011-2012 Fluzone Standard Dose | Healthy Controls, 2011-2012 Fluzone Standard Dose | RA Participants, 2011-2012 Fluzone High Dose | Healthy Controls, 2011-2012 Fluzone High Dose | RA Participants, 2012-2013 Fluzone Standard Dose | Healthy Controls, 2012-2013 Fluzone Standard Dose |
|---|---|---|---|---|---|---|---|
| Tenderness | General disorders | 5 of 6 | 5 of 6 | 6 of 10 | 9 of 10 | 6 of 19 | 12 of 19 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 6 of 6 | 0 of 6 | 7 of 10 | 0 of 10 | 18 of 19 | 1 of 19 |
| Headache | Nervous system disorders | 4 of 6 | 1 of 6 | 3 of 10 | 5 of 10 | 8 of 19 | 5 of 19 |
| Malaise | General disorders | 1 of 6 | 0 of 6 | 5 of 10 | 1 of 10 | 13 of 19 | 3 of 19 |
| Myalgia | Musculoskeletal and connective tissue disorders | 2 of 6 | 0 of 6 | 4 of 10 | 1 of 10 | 14 of 19 | 2 of 19 |
| Injection site pain | General disorders | 0 of 6 | 3 of 6 | 1 of 10 | 4 of 10 | 4 of 19 | 6 of 19 |
| Asthenia | General disorders | 1 of 6 | 0 of 6 | 2 of 10 | 1 of 10 | 12 of 19 | 0 of 19 |
| Nausea | Gastrointestinal disorders | 1 of 6 | 0 of 6 | 3 of 10 | 0 of 10 | 6 of 19 | 1 of 19 |
| Injection site swelling | General disorders | 1 of 6 | 0 of 6 | 1 of 10 | 0 of 10 | 3 of 19 | 6 of 19 |
| Chills | General disorders | 1 of 6 | 0 of 6 | 2 of 10 | 0 of 10 | 4 of 19 | 0 of 19 |
Serious events with the highest arm-level rate: angina unstable (6.2%), hypertension (5.3%).
The registry reports serious adverse events and other adverse events as counts of affected participants and participants at risk, separated by group and season. For serious adverse events, the 2011-2012 counts are zero of 6 for rheumatoid arthritis participants receiving standard dose, zero of 6 for healthy controls receiving standard dose, zero of 10 for rheumatoid arthritis participants receiving high dose, and zero of 10 for healthy controls receiving high dose. The 2012-2013 counts, in the same group order, are 1 of 19, zero of 19, zero of 16, and 1 of 16.
These are counts recorded in the listed groups, not comparative estimates with uncertainty intervals. A zero count means no affected participant was recorded in that group for this summary; it does not establish that the event cannot occur. The limited group sizes also mean that a small difference in counts cannot, by itself, establish a meaningful difference between doses or populations. The registry record does not report a statistical comparison for these serious-event figures.
Deaths are not reported in the registry record. The listed top serious-event terms are angina unstable at 6.2% and hypertension at 5.3%, but their group-specific counts and the context for these percentages are not reported in the registry record. These details should not be inferred from the affected-participant counts.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this Phase II study was designed to examine immunogenicity and safety of standard-dose and high-dose trivalent inactivated influenza vaccine in rheumatoid arthritis participants receiving TNF-alpha-inhibitor therapy and healthy controls. It defines a Day 21 seroconversion endpoint for each vaccine strain and gives adverse-event counts by group and season. These elements describe the question and some of the safety observations, but they do not provide the primary immune-response results.
Without the reported strain-specific seroconversion counts, denominators, and estimates of uncertainty, the record does not show the magnitude or precision of the response in either dose group. It cannot establish whether one dose produced a higher response, whether responses differed between rheumatoid arthritis participants and healthy controls, or how consistent results were across strains. The endpoint definition alone is not an outcome result.
Seroconversion is an assay-based measure of change in antibody titer. In general, an immune-response measure should not be treated as equivalent to a demonstrated change in clinical illness. The registry’s primary endpoint does not count influenza cases, and the record does not report a clinical efficacy result. Thus the listed endpoint cannot, on its own, answer whether vaccination prevented influenza or improved a clinical outcome.
The adverse-event counts describe what the registry records for the listed groups. They are not proof that an event is absent when a count is zero, nor do small group counts establish comparative safety. The record does not provide uncertainty estimates or a formal safety comparison, and deaths are not reported in the registry record.
More broadly, the record does not report a statistical analysis plan, the handling of missing endpoint data, or how multiple strains and outcomes were treated in the analysis. Those omissions limit the strength of any inferential conclusion. The appropriate reading is therefore descriptive: the study design and endpoint are documented, some safety counts are available, and the primary outcome values needed to judge the stated immunogenicity question are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates why an endpoint definition and an endpoint result are different kinds of information. The registry gives a detailed rule for classifying seroconversion based on baseline and follow-up HAI titers, including separate conditions for low and measurable baseline titers. That rule clarifies what the study intended to count. Without the observed counts by strain and group, however, the endpoint cannot be used to estimate a response or compare vaccine doses.
The design also raises an important interpretive distinction between population and dose. The study includes rheumatoid arthritis participants receiving TNF-alpha-inhibitor therapy and healthy controls, each described under standard-dose and high-dose vaccine conditions. A difference by dose is not the same question as a difference by participant group. The primary endpoint narrows the question to rheumatoid arthritis participants in the 2011-2012 season, while other listed outcomes extend to a later season and additional follow-up times.
Multiplicity matters because strain-specific outcomes and multiple seasons can produce a set of related findings rather than one definitive result. The registry reports the number of outcome measures and analyses, but not the planned approach to controlling or interpreting multiple comparisons. This makes it important not to treat any isolated result, if encountered elsewhere, as conclusive without knowing the analysis plan and uncertainty.
Finally, the safety record demonstrates why counts should be read with their group denominators and context. Serious adverse-event counts are reported by group, but the registry record does not include comparative estimates or uncertainty intervals. A count is a description of observed events, not a complete assessment of relative safety. The trial is statistically informative as an example of how design, endpoint definition, reporting completeness, and inferential limits all shape what can be concluded.
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 main limitation for interpretation is that the primary endpoint results are not reported in the registry record. Although the outcome definition is specific, there are no reported seroconversion counts by strain, dose, or analysis denominator. This prevents estimation of the response and prevents assessment of its precision.
The endpoint concerns rheumatoid arthritis participants vaccinated in the 2011-2012 season, whereas other listed immune outcomes cover two seasons and additional time points. The record does not report how these multiple outcomes were prioritized or combined, and it does not give a multiplicity strategy. It also does not provide a complete statistical analysis plan, so the intended models, contrasts, and inferential criteria are not reported in the registry record.
Actual group enrollment and analysis denominators are not reported in the registry record. The arm descriptions give planned group sizes, but these do not establish the number analyzed for each outcome. The handling of missing blood samples, missing titers, withdrawals, and protocol deviations is also not reported. These gaps limit assessment of whether the endpoint populations differed from the enrolled participants.
Safety results are presented as counts in relatively small listed groups, without uncertainty intervals or formal comparisons. Death counts are not reported in the registry record, and the context and group-specific breakdown for the listed serious-event terms are not given. The record also does not explain the randomization procedure or the precise masking arrangements. These limitations do not negate the reported design features, but they restrict how completely the study’s conduct and results can be evaluated from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: TIV and High Dose TIV in Subjects With Rheumatoid Arthritis — NCT01436370.
- Registry record last updated 2014-12-24; status last verified 2013-02.
- Results first posted 2014-05-16.
- 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
NCT01436370 is a completed randomized, double-blinded, parallel Phase II study with enrollment of 102. It examined standard-dose and high-dose trivalent inactivated influenza vaccine in adults with rheumatoid arthritis receiving TNF-alpha-inhibitor therapy and healthy age- and gender-matched controls. The record describes a Day 21, strain-specific seroconversion endpoint for rheumatoid arthritis participants vaccinated in the 2011-2012 season.
The registry record defines seroconversion but does not report the primary endpoint counts or denominators. It reports serious and other adverse-event counts by group and season, but does not provide comparative uncertainty estimates. The analysis plan, multiplicity strategy, missing-data handling, and deaths are not reported in the registry record. Accordingly, the record supports description of the design and endpoint, but does not allow a full statistical assessment of the primary immunogenicity question.