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 of a Influenza Vaccine Produced Either in Mammalian Cell Culture or in Embryonated Hen Eggs in Adults and Elderly With and Without Underlying Medical Conditions, and Immunogenicity in a Subset of Subjects With Underlying Medical Conditions (NCT00560066), a randomized phase 4 study. The primary outcome is Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00560066 |
| Phase | Phase 4 |
| Condition | Seasonal Influenza, Vaccine |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | Single |
| Enrollment | 1398 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Vaccines |
| Results posted | Yes |
2. Clinical Question
The trial asked whether the safety experience after vaccination differed between a trivalent subunit influenza vaccine produced in mammalian cell culture and an egg-derived vaccine. It also planned to assess immune responses in a subset of participants with underlying medical conditions. The study took place in a post-marketing setting and included adults and elderly people with and without underlying medical conditions.
Population
Adults and elderly people 18 years of age and above, with and without underlying medical conditions. The immunogenicity assessment was limited to a subset of participants with underlying medical conditions.
Intervention
One vaccination of cell culture-derived trivalent subunit influenza vaccine, identified as cTIV and Optaflu® in the record.
Comparator
One vaccination of egg-derived trivalent subunit influenza vaccine, identified as TIV and Agrippal® in the record.
Primary question
How many participants reported at least one sign of reactogenicity from Day 1 through Day 7 after vaccination in each vaccine group?
The primary question is about the number of participants reporting a symptom or sign, rather than the number of separate reports. The record specifies that safety analyses used exposed participants who provided post-baseline safety data. The stated endpoint window begins on vaccination Day 1 and includes Day 7. The registry record does not provide arm-level results for this primary endpoint, so the size and precision of any difference in reactogenicity cannot be assessed from the record.
3. Trial Design
This was a Phase IV, randomized, active-controlled, observer-blind study. The registry describes it as multi-center and lists an enrollment of 1398. Its stated purpose was to evaluate safety in adults and elderly people with and without underlying medical conditions, and to evaluate immunogenicity in a subset of participants with underlying medical conditions. The study status is completed. The recorded study start is 2007-11, and primary completion is recorded as 2008-07.
The two listed interventions were cell-derived influenza vaccine and egg-derived influenza vaccine. The arm descriptions specify one vaccination for each group. The primary safety endpoint was assessed from Day 1 through Day 7 after vaccination. The record also lists secondary assessments covering solicited local and systemic adverse events, hemagglutination inhibition (HI) titers, seroconversion or significant increases in HI titers, geometric mean titers, and geometric mean ratios. The immunogenicity outcomes were specified for participants with underlying medical conditions or a subset of participants, as described in the outcome titles.
There is a labeling inconsistency within the registry record: allocation is listed as randomized, and two vaccine interventions and arm descriptions are present, while the study model is labeled single-group. The record does not explain this discrepancy. Masking is listed as single, but the record does not identify which study roles were masked or describe the masking procedures. The term active-controlled indicates that one vaccine was compared with another; the record does not describe a placebo group.
The record identifies the sponsor as Novartis Vaccines. It does not report further details about the randomization sequence, concealment of allocation, study centers, or the operational implementation of the observer-blind design. Those details should not be inferred from the broad design labels.
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: All enrolled subjects were included in the trial.
Overall Study
| Stage | Egg-derived Vaccine (TIV) | Cell Culture-derived Vaccine (cTIV) |
|---|---|---|
| STARTED | 396 | 1002 |
| COMPLETED | 390 | 980 |
| NOT COMPLETED | 6 | 22 |
Reasons for not completing this period:
| Reason | Egg-derived Vaccine (TIV) | Cell Culture-derived Vaccine (cTIV) |
|---|---|---|
| Death | 2 | 1 |
| Withdrawal by Subject | 0 | 3 |
| Lost to Follow-up | 4 | 10 |
| Protocol Violation | 0 | 1 |
| Administrative reason | 0 | 5 |
| Missing primary reason | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the safety dataset, i.e. all subjects in the exposed set who provided post-baseline safety data.
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 | Egg-derived Vaccine (TIV) | Cell Culture-derived Vaccine (cTIV) | Total |
|---|---|---|---|---|
| Participants analysed | 396 | 1002 | 1398 | |
| Age, Continuous | years | 47.6 (SD 17.3) | 48.7 (SD 16.3) | 48.3 (SD 16.6) |
| Sex: Female, Male: Female | Participants | 206 | 533 | 739 |
| Sex: Female, Male: Male | Participants | 190 | 469 | 659 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV, measured over From Day 1 up to and including Day 7 post-vaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Subjects |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who reported at least one sign of reactogenicity after vaccination. The specified observation period is from Day 1 up to and including Day 7 post-vaccination. The endpoint description frames safety as the number of all participants in the relevant safety dataset who reported at least one such sign after receiving either vaccine.
A participant-level count can answer how many people reported an event, but it does not by itself describe how often each symptom occurred, how long it lasted, or how severe it was. Nor does a count alone establish whether a vaccine caused an event. Those interpretations require suitable definitions, comparison methods, and context about ascertainment.
Reactogenicity is used as a short-term safety measure after vaccination. A defined observation window makes the period of interest explicit and helps distinguish this endpoint from adverse events assessed over other periods. The registry also lists outcomes for solicited local and systemic adverse events, including outcomes in healthy participants and in participants with underlying medical conditions. The exact primary endpoint results by vaccine group are not reported in the registry record. Therefore, the endpoint's definition is available, but its observed group counts and the precision of a comparison cannot be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial's question and design, but does not report an arm-level result for the primary reactogenicity endpoint. It therefore does not show how many participants in either vaccine group reported at least one sign during the specified post-vaccination period. Without those counts, an effect estimate, confidence interval, or statistical test for the primary comparison cannot be interpreted from this record.
The adverse-event information that is present concerns serious events and other events, not a reported result for the defined primary reactogenicity endpoint. The record lists serious adverse-event counts of 10 among 396 participants in the egg-derived vaccine group and 20 among 1001 participants in the cell culture-derived vaccine group. It also lists other adverse-event counts of 204 among 396 and 568 among 1001, respectively. These are counts with different group denominators. They should be read as descriptive safety information rather than as a complete statistical comparison: the record does not report a comparative estimate or its uncertainty for these counts.
Counts alone do not convey the precision of a comparison. A confidence interval, when reported, describes a range of values compatible with the data under the analysis assumptions; its width reflects uncertainty. No confidence interval for the primary endpoint or the listed adverse-event counts is reported in the registry record. No p-value or adjusted treatment effect is reported either. As a result, statistical significance, if any, cannot be assessed from the registry information.
The record lists serious adverse-event terms, each with a displayed percentage of 0.3%, but does not connect those terms to a specific vaccine group in the information available. The percentages should not be used to infer a group comparison or to reconstruct counts. Deaths are not reported in the registry record. The absence of a reported death count is not evidence that no deaths occurred.
The enrollment figure is 1398, whereas the safety denominators listed for the two vaccine groups are 396 and 1001. The record does not explain the relationship between enrollment and these safety denominators. They should not be reconciled by assumption. The primary safety population is described as exposed participants with post-baseline safety data, but the record does not give further flow details or a participant accounting that explains the difference.
The posted information supports a description of study design, endpoint definitions, and selected safety counts. It does not support a conclusion that one vaccine had more or fewer reactogenicity signs, or that the vaccines were equivalent on safety. Such conclusions require the relevant outcome results and a clear account of the analysis.
9. Statistical Methods Explained
For a binary endpoint such as whether a participant reported at least one event, the basic data are event counts and the numbers of participants assessed in each group. The primary outcome is expressed as a number of participants, and the description specifies a participant-level criterion: at least one reactogenicity sign. This differs from counting every event report, because a person with multiple reports can still meet the participant-level endpoint once.
For interpretation, the count needs its corresponding denominator: the number of participants in the group who were eligible for that analysis and had the required outcome information. A comparison of counts without denominators can be misleading when group sizes differ. The record describes the safety population as all exposed participants who provided post-baseline safety data. For the adverse-event entries, group denominators are listed. The registry record does not provide the primary endpoint's group counts or a fuller account of missing observations and exclusions.
A common way to summarize a binary outcome is to compare the proportion of participants with an event in each group. The difference between such proportions describes an absolute contrast, while a ratio describes a relative contrast. These are general statistical measures; no such estimates for the primary endpoint are reported in the registry record. Choosing a measure affects how a result is communicated, but neither measure removes uncertainty or resolves limitations in outcome ascertainment.
A confidence interval is a general method for showing statistical uncertainty around an estimate. A narrow interval indicates greater precision under the analysis assumptions; a wide interval indicates less precision. Whether an interval includes a null value is sometimes used as part of a significance assessment, but the interval's range and the clinical context matter as well. The record does not report a confidence interval or a statistical test for the primary endpoint. Thus, no precision assessment or significance claim can be made from the primary outcome information in this record.
Randomization is intended, in general, to make comparison groups similar in expectation with respect to factors known and unknown before treatment assignment. This can support a causal comparison when allocation is implemented appropriately, outcome data are collected comparably, and the analysis follows a suitable plan. The registry lists randomized allocation, but does not describe sequence generation, concealment, or the analysis plan. The study is also labeled single-group in its model field despite listing two vaccine groups. The record does not resolve that inconsistency, so the design labels alone do not answer every question about implementation.
Masking can reduce some risks of biased reporting or assessment when participants or study staff do not know the assigned treatment. The registry lists single masking and observer-blind in the official title. It does not state who was masked, which assessments were masked, or whether masking was maintained. Because the primary endpoint depends on reported signs, details of how symptoms were elicited and recorded would help readers assess possible measurement differences; such procedural details are not reported in the registry record.
Over-dispersion is a general issue when variation in data is greater than a statistical model expects. It matters especially for outcomes involving event counts, repeated observations, or clustered data, because a model that understates variability can produce overly narrow uncertainty intervals. The primary endpoint is described as a number of participants meeting a binary criterion, rather than a repeated-event count. The record does not report a model or variance adjustment, and there is no basis to infer that an over-dispersion correction was used or needed.
The registry lists multiple outcomes: the primary reactogenicity measure and secondary safety and immunogenicity measures. When many hypotheses are tested, the chance of at least one apparently notable result can increase. General approaches to multiplicity include specifying a primary comparison in advance, adjusting significance thresholds, or interpreting secondary analyses as exploratory. The registry record does not report whether any multiplicity approach was planned or used. No p-values or analyses are listed, so the effects of any adjustment cannot be assessed.
The record also describes planning illustrations based on the observed effect, with two-sided significance level 0.05, equal allocation between groups, and a normal approximation; the target effect is a stated fraction of the observed effect. Such calculations are prospective planning illustrations, not observed power and not evidence that a result was detected. For time-to-event outcomes, the stated convention concerns total events; for other outcomes, it concerns participants per arm. No numerical planning results are available in the registry record, and no sample-size justification for the trial itself is reported.
Finally, the number of analyses listed in the record is 0. That means the registry entry does not provide analysis rows to interpret. It does not establish that no analyses were performed outside the registry. No adjusted estimates, model specifications, missing-data procedures, or sensitivity analyses are reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The record lists a primary safety outcome and several secondary outcomes. These cover solicited local and systemic adverse events, HI antibody response thresholds, seroconversion or significant increases in HI titers, geometric mean titers, and geometric mean ratios. Some are specified for participants with underlying medical conditions, while others include healthy adults and elderly participants. The registry record does not report how the analyses were prioritized or whether any adjustment for multiple comparisons was planned or applied.
The primary safety population is described as exposed participants who provided post-baseline safety data. This definition identifies the broad analysis set but does not explain how participants without post-baseline data were handled, whether every randomized participant was included, or how missing outcome values were treated. Imputation, exclusion rules, sensitivity analyses, and reasons for missing data are not reported in the registry record. The record also does not provide participant flow information that reconciles enrollment with the group-specific safety denominators.
The immunogenicity outcomes are described as being assessed in a subset of participants with underlying medical conditions. The criteria for inclusion in that subset, the immunogenicity analysis population, and handling of missing specimens or measurements are not reported in the registry record. The record does not provide a statistical analysis plan, including prespecified methods for the outcomes or any interim analyses. These gaps limit assessment of whether analyses followed planned procedures and how robust the reported results would be; in this case, the registry record does not include analyses to evaluate.
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 |
|---|---|---|---|
| Egg-derived Vaccine (TIV) | 10 | 396 | 2.5% |
| Cell Culture-derived Vaccine (cTIV) | 20 | 1001 | 2.0% |
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 |
|---|---|
| Egg-derived Vaccine (TIV) | 204 of 396 |
| Cell Culture-derived Vaccine (cTIV) | 568 of 1001 |
Most frequent serious adverse event terms
| Event term | Organ system | Egg-derived Vaccine (TIV) | Cell Culture-derived Vaccine (cTIV) |
|---|---|---|---|
| Sinusitis | Infections and infestations | 0 of 396 | 2 of 1001 |
| Urinary Tract Infection | Infections and infestations | 1 of 396 | 1 of 1001 |
| Transient Ischaemic Attack | Nervous system disorders | 1 of 396 | 1 of 1001 |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | 0 of 396 | 2 of 1001 |
| Deep Vein Thrombosis | Vascular disorders | 1 of 396 | 1 of 1001 |
| Acute Chest Syndrome | Blood and lymphatic system disorders | 0 of 396 | 1 of 1001 |
| Angina Pectoris | Cardiac disorders | 1 of 396 | 0 of 1001 |
| Aortic Valve Incompetence | Cardiac disorders | 0 of 396 | 1 of 1001 |
| Aortic Valve Stenosis | Cardiac disorders | 0 of 396 | 1 of 1001 |
| Atrial Fibrillation | Cardiac disorders | 1 of 396 | 0 of 1001 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Egg-derived Vaccine (TIV) | Cell Culture-derived Vaccine (cTIV) |
|---|---|---|---|
| Injection site pain | General disorders | 117 of 396 | 330 of 1001 |
| Headache | Nervous system disorders | 73 of 396 | 198 of 1001 |
| Fatigue | General disorders | 63 of 396 | 185 of 1001 |
| Myalgia | Musculoskeletal and connective tissue disorders | 57 of 396 | 150 of 1001 |
| Malaise | General disorders | 39 of 396 | 89 of 1001 |
| Nasopharyngitis | Infections and infestations | 10 of 396 | 90 of 1001 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 22 of 396 | 76 of 1001 |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | 21 of 396 | 56 of 1001 |
| Bronchitis | Infections and infestations | 14 of 396 | 59 of 1001 |
Serious events with the highest arm-level rate: angina pectoris (0.3%), atrial fibrillation (0.3%), chest pain (0.3%), device occlusion (0.3%), cholelithiasis (0.3%).
The serious adverse-event entries list 10 participants among 396 in the egg-derived vaccine group and 20 among 1001 in the cell culture-derived vaccine group. The entries for other adverse events list 204 among 396 and 568 among 1001, respectively. These figures are descriptive counts with group denominators. The registry record does not report a comparative estimate, confidence interval, or test for these entries, so they should not be treated as a formal test of differences between vaccines.
The record lists Angina Pectoris, Atrial Fibrillation, Chest Pain, Device Occlusion, Cholelithiasis, and Urinary Tract Infection among the serious adverse-event terms, each with a displayed percentage of 0.3%. It does not identify a vaccine group for each term or provide enough context to infer the number of affected participants from those percentages. Deaths are not reported in the registry record. This means the death information is unavailable in the record, not that the death count was zero.
These entries should also be kept distinct from the primary reactogenicity endpoint, which counts participants reporting at least one reactogenicity sign during Day 1 through Day 7. The registry record does not provide that endpoint's group results.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, active-controlled, observer-blind Phase IV study compared one vaccination of cell culture-derived influenza vaccine with one vaccination of egg-derived influenza vaccine. It defines a primary safety question focused on at least one reactogenicity sign reported from Day 1 through Day 7. It also identifies a broader set of safety and immunogenicity outcomes, including immune-response measures in a subset with underlying medical conditions.
What the record does not establish is the result of the primary comparison. No arm-level count for the primary reactogenicity endpoint, effect estimate, confidence interval, or p-value is reported. The record therefore cannot show the magnitude or precision of a difference in this outcome. The serious and other adverse-event counts are available, but without comparative estimates and further analysis details they do not establish a statistical difference between groups.
The listed serious-event terms and percentages also require restraint in interpretation. The record does not assign each term to a vaccine group, and the percentages alone do not reveal a complete group-specific safety profile. Deaths are not reported. None of these omissions should be converted into claims that an event did or did not occur.
More generally, a registry entry is a record of study information and posted results, not a complete substitute for a detailed report of methods and analyses. The entry does not report the statistical plan, allocation procedures, missing-data handling, multiplicity approach, or masking implementation. These matters affect how securely results can be interpreted, but the record does not provide enough information to resolve them.
The available information supports describing the study's purpose, population, interventions, endpoint definitions, and selected adverse-event counts. It does not support medical advice, a claim that either vaccine works or does not work, or a claim that the vaccines are equivalent or different. Those conclusions would require relevant outcome data and an appropriately documented analysis.
13. Why This Trial Matters Statistically
This trial is statistically interesting because its primary question is framed as a participant-level safety outcome in a randomized active-controlled study. The outcome asks whether each participant reported at least one reactogenicity sign over a prespecified period. That definition makes clear what is being counted, while also highlighting why event definitions and consistent collection procedures matter in a comparison based on participant reports.
The study also spans different clinical subgroups: adults and elderly people with and without underlying medical conditions, alongside an immunogenicity subset with underlying medical conditions. Such subgroup-specific outcomes can be informative, but they depend on clear definitions of the analysis populations and adequate reporting of subgroup results. The registry record identifies these populations and outcomes but does not provide the corresponding analyses.
A further statistical issue is transparency between the design labels and the listed groups. Randomized allocation and two vaccine arms appear alongside a single-group model label. That inconsistency does not establish that the trial was implemented incorrectly, but it leaves an important design detail unresolved in the registry record. The missing analysis plan and outcome estimates also prevent readers from assessing precision, multiplicity, or whether the analyses followed prespecified methods.
The entry is a useful example of the difference between registration details and interpretable comparative evidence. Enrollment, endpoint definitions, and descriptive adverse-event counts provide context. They do not replace arm-level primary results, estimates of uncertainty, or a transparent account of analysis populations and missing data. For statistical interpretation, the distinction between knowing what a trial intended to measure and knowing what its data show is essential.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most immediate limitation is that the registry record does not report arm-level results for the primary reactogenicity endpoint. Without those results, the primary comparison cannot be quantified or assessed for precision. Although selected serious and other adverse-event counts are listed, the record does not give comparative estimates or confidence intervals for them.
The registry's design information contains an unresolved inconsistency: allocation is listed as randomized and two vaccine groups are described, while the model is labeled single-group. The record does not explain the labeling. It also does not identify which roles were masked, detail how randomization was conducted, or describe how outcome reports were collected. These limitations prevent a fuller assessment of design implementation and potential assessment bias.
Enrollment is listed as 1398, but the record does not explain how that figure relates to the safety denominators of 396 and 1001. The safety population definition refers to exposed participants with post-baseline safety data; further participant flow, exclusions, and missing-data handling are not reported in the registry record. The immunogenicity analysis subset is identified generally, but its selection criteria and analysis details are not reported.
The record lists multiple outcomes but does not describe the statistical plan, multiplicity handling, interim analyses, or sensitivity analyses. The listed serious-event terms are not linked to a particular vaccine group in the information available, and deaths are not reported. These reporting gaps limit interpretation of both the safety counts and the study's overall inferential claims. No unreported result or methodological detail should be inferred from the registry entry.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety of a Influenza Vaccine Produced Either in Mammalian Cell Culture or in Embryonated Hen Eggs in Adults and Elderly With and Without Underlying Medical Conditions, and Immunogenicity in a Subset of Subjects With Underlying Medical Conditions — NCT00560066.
- Registry record last updated 2016-02-17; status last verified 2016-01.
- Results first posted 2013-04-18.
- 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
NCT00560066 is a completed Phase IV randomized, active-controlled, observer-blind study of cell culture-derived and egg-derived trivalent subunit influenza vaccines. It enrolled adults and elderly people with and without underlying medical conditions and listed an enrollment of 1398. Each arm description specifies one vaccination. The primary safety outcome was the number of participants reporting at least one reactogenicity sign from Day 1 through Day 7.
The registry record also lists safety and immunogenicity secondary outcomes, including immune-response measures in a subset with underlying medical conditions. It reports selected serious and other adverse-event counts, but does not report the primary endpoint's arm-level results, comparative estimates, or confidence intervals. The record does not explain the single-group model label alongside randomized allocation and two listed vaccine groups. Missing-data procedures, the statistical plan, and further analysis details are not reported in the registry record.