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 Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine in RSV-Seronegative Infants 6 to 24 Months of Age (NCT02794870), a randomized phase 1 study. The primary outcome is Number of Participants With Solicited Adverse Events (AEs) by Grade.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02794870 |
| Phase | Phase 1 |
| Condition | Respiratory Syncytial Virus Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 33 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
The study asked whether a single dose of the RSV LID ΔM2-2 1030s vaccine could be evaluated for safety, infectivity, and immunogenicity in RSV-seronegative infants aged 6 to 24 months. The comparison was with a single dose of placebo. The primary endpoint counted participants with solicited adverse events, classified by grade, from Day 0 through Day 28. The registry record also describes secondary questions about illness after natural infection with wild-type RSV during the subsequent RSV season, antibody responses among participants who experienced that infection, and B cell responses to vaccine.
Population
RSV-seronegative infants aged 6 to 24 months. The primary endpoint population included study participants who received inoculation and were followed on study past Day 0.
Intervention
A single dose of RSV LID ΔM2-2 1030s vaccine, delivered as nose drops at study entry on Day 0.
Comparator
A single dose of placebo, also given at study entry on Day 0.
Primary question
How many participants experienced solicited adverse events, by grade, during the period from Day 0 through Day 28?
The primary question is descriptive: it concerns the number of participants with events in specified categories and grades. The registry record does not report the category-specific counts or a single overall comparison for this endpoint. It therefore does not establish from the posted primary outcome information how the groups differed. The secondary outcomes concern distinct questions and populations, including participants who experienced natural infection; their results are not reported in the registry record.
3. Trial Design
This was a Phase I, randomized, quadruple-masked, parallel-group, placebo-controlled study. The registry lists enrollment as 33 and status as completed. Participants were assigned to receive either the RSV LID ΔM2-2 1030s vaccine or placebo. Each group received a single dose at study entry on Day 0. The official study title specifies that the vaccine was delivered as nose drops. The registry identifies the National Institute of Allergy and Infectious Diseases (NIAID) as sponsor.
The study dates in the registry are 2016-07-15 for study start and 2017-07-07 for primary completion. These dates do not, on their own, describe how long each participant was followed. The primary endpoint specifies that solicited adverse events were measured from Day 0 through Day 28. The registry describes the study as a companion study to CIR 311.
Randomization allocates participants to study groups using a chance-based process; masking is intended to limit the influence of group knowledge on trial conduct or assessment. The registry labels masking as quadruple but does not identify the specific roles masked. It also does not report the randomization method, allocation concealment procedures, or details of how masking was maintained.
A parallel-group design compares groups that receive different assigned interventions during the same study. The placebo group provides a reference for interpreting event counts in the vaccine group, but an observed difference would not by itself establish its cause. The record identifies the interventions and the overall enrollment, but does not report the number assigned to each arm for the primary endpoint, the number completing follow-up, or reasons for any exclusions.
The study's stated purpose was to evaluate safety, infectivity, and immunogenicity. The endpoint list includes solicited adverse events, outcomes related to symptomatic illness after natural RSV infection, serum RSV-neutralizing antibody responses, and B cell responses. The registry record does not report a detailed protocol rationale for the selected design or enrollment.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | RSV LID ΔM2-2 1030s Vaccine | Placebo |
|---|---|---|
| STARTED | 22 | 11 |
| Received Inoculation | 21 | 11 |
| COMPLETED | 20 | 11 |
| NOT COMPLETED | 2 | 0 |
Reasons for not completing this period:
| Reason | RSV LID ΔM2-2 1030s Vaccine | Placebo |
|---|---|---|
| Withdrawal by Subject | 2 | 0 |
Analysis population for the primary outcome, as defined in the registry: Study participants who received inoculation and were followed on study past Day 0 were included.
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: Baseline analysis population was participants who received inoculation.
| Characteristic | Unit | RSV LID ΔM2-2 1030s Vaccine | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 21 | 11 | 32 | |
| Age, Continuous | months | 9 (7 to 14) | 11 (8 to 16) | 9 (7 to 16) |
| Sex: Female, Male: Female | Participants | 7 | 7 | 14 |
| Sex: Female, Male: Male | Participants | 14 | 4 | 18 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 10 | 4 | 14 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 11 | 7 | 18 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 10 | 5 | 15 |
| Race (NIH/OMB): White | Participants | 8 | 5 | 13 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
| Region of Enrollment: United States | Participants | 21 | 11 | 32 |
| Serum RSV-neutralizing antibody titers | log 2 titers | 2.3 (2.3 to 2.3) | 2.3 (2.3 to 2.3) | 2.3 (2.3 to 2.3) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Solicited Adverse Events (AEs) by Grade, measured over Measured from Day 0 through Day 28.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with solicited adverse events, reported by grade. The specified observation period runs from Day 0 through Day 28. The solicited events include fever, otitis media, upper respiratory illness, lower respiratory illness, and cough without lower respiratory illness. A participant was counted once within each solicited adverse-event category, at the highest grade experienced in that category. The grading system is described as protocol-defined, ranging from Grade 1, mild, to Grade 4, life-threatening.
Counting participants is useful when the question is how many people experienced an event, rather than how many event episodes occurred. Reporting grades can distinguish events by severity classification. The endpoint does not count repeated events within a category as separate participants, and a participant could be represented in more than one category if they experienced different types of solicited events.
As a general statistical point, event counts are easiest to interpret alongside the number of participants assessed in each group and a clear account of missing observations. The registry record describes the eligible primary endpoint population but does not report the category-by-grade counts, denominators for those results, or a single overall summary. The listed primary outcome therefore defines what was intended to be measured, but the posted information does not permit a complete interpretation of the vaccine-versus-placebo results for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question, endpoint definition, and broad trial design, but it does not report the primary endpoint results by adverse-event category and grade. A primary-outcome entry that specifies what was measured is not itself evidence about the observed findings. No category-specific counts, confidence intervals, p-values, or treatment-effect estimate for the primary endpoint are reported in the registry record. As a result, the primary outcome cannot be described as showing a particular difference between vaccine and placebo from this record.
The endpoint is a collection of event categories rather than one simple event count. Fever, otitis media, upper respiratory illness, lower respiratory illness, and cough without lower respiratory illness are listed, with events classified by grade. The counting rule assigns each participant to the highest grade experienced within each category. This detail matters: a count at a particular grade should not be read as a count of event episodes, and counts across categories should not automatically be treated as mutually exclusive people.
The safety summary reports serious adverse-event counts of 4 among 20 participants at risk in the vaccine group and 1 among 11 at risk in the placebo group. It also lists other adverse-event counts of 14 among 20 at risk in the vaccine group and 9 among 11 at risk in the placebo group, and reports 0 deaths in each group. These are descriptive entries. The registry record does not provide a statistical comparison or establish whether reported events were caused by the study intervention. The serious-event counts should not be substituted for the primary solicited adverse-event endpoint, which has a defined Day 0 through Day 28 period and separate categories and grading.
For serious adverse events, the record lists wheezing at 10.0%, bronchiolitis at 9.1%, and pneumonia viral at 5.0% among the top terms. The brief summary does not make clear the denominator or group attribution for each listed percentage. Those values should therefore be read as registry-listed term percentages, not as a basis for a new group comparison.
Several secondary outcomes concern participants who experienced natural infection with wild-type RSV during the subsequent RSV season. These outcomes include symptomatic, medically attended respiratory and febrile illness by grade, and serum RSV-neutralizing antibody response magnitude. The record also includes B cell responses to vaccine. Results for these secondary outcomes are not reported in the registry record. The conditional focus on participants who experienced natural infection means those questions differ from the primary endpoint population and should not be conflated with it.
Overall, the posted information supports a description of the study's design and some safety summary counts, but not a conclusion about the primary endpoint's comparative results, immunogenicity, or clinical outcomes after natural infection. No inferential test or adjusted analysis for these questions is reported in the registry record.
9. Statistical Methods Explained
The primary outcome is a participant count, classified across adverse-event categories and grades. A count answers how many participants experienced an event under the stated definition; it is not the same as an event rate, a count of episodes, or a time-to-event measure. In this study, each participant was counted once per solicited adverse-event category and assigned to the highest grade they experienced in that category. This rule avoids counting repeated episodes within a category as separate participants, while allowing the same participant to contribute to different categories.
What does a grade add?
Grading represents a severity classification. The registry describes Grade 1 as mild and Grade 4 as life-threatening, with a protocol-defined grading system. A grade is not itself a measure of how often an event occurred. The count for a category and grade depends on the study's definitions and the specified rule for assigning each participant. The detailed criteria from the protocol are not reported in the registry record.
Because the endpoint has multiple categories and grades, it does not reduce naturally to one comparison without a prespecified choice of summary. For example, a single total across categories could count the same participant more than once, since the categories need not be mutually exclusive. A total that combines grades would also discard severity distinctions. The registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison. It does not report the sponsor's detailed statistical analysis for these categories.
How should group counts be compared?
As a general statistical principle, a count should be interpreted with its group denominator and outcome definition. Comparing raw counts without considering how many participants were assessed in each group can be misleading when group sizes differ. A proportion or a model-based estimate may be used for some questions, but the suitable method depends on the design, outcome structure, and analysis plan. The registry record does not report an inferential method for the primary endpoint or an adjusted comparison. No new rate, difference, or ratio should be inferred from the posted summary counts.
Confidence intervals, in general, express the precision of an estimated effect under a statistical model and its assumptions. A wider interval indicates less precision than a narrower interval, while the interval's compatibility with different effects depends on its bounds. The record does not report a confidence interval for the primary outcome. Without an estimate and its uncertainty, the precision of a vaccine-versus-placebo comparison cannot be assessed from the primary endpoint information.
What is multiplicity?
Multiplicity arises when analyses examine more than one outcome, category, grade, or time point. The more questions examined, the more important it is to understand which comparisons were planned and how conclusions account for those multiple looks. This is a general statistical concern, not a claim that a particular adjustment was or was not used in this study. The registry record lists multiple outcomes and analyses but does not report a multiplicity strategy, analysis hierarchy, or which comparisons were treated as confirmatory.
For binary outcomes, a participant either meets an event definition or does not, according to the specified assessment. The registry describes the outcome type as participants with an event, recorded as counts. This classification does not establish that a method for binary data was used: the statistical model and inferential procedure are not reported. For event counts with substantial variation beyond what a simple model expects, general methods may account for over-dispersion. Whether over-dispersion was assessed or modeled in this trial is not reported in the registry record.
What do the planning assumptions mean?
The registry's sample-size assumptions describe planning illustrations based on an observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event tables, the illustration uses the total number of events under the Schoenfeld approach; other tables give participants per arm. These are planning assumptions, not observed power, and do not show what power the completed study had. Numeric planning results and the underlying observed effect are not reported in the registry record.
A planning illustration is conditional on its assumptions. It is not a retrospective measure of whether a study was adequately powered, and it cannot replace observed outcome estimates with uncertainty intervals. For this trial, the record does not report a sample-size justification, a detailed statistical analysis plan, interim analyses, or methods for handling missing data. Those elements should not be inferred from the phase, enrollment, or posted endpoint description.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures and 6 analyses. It describes the primary outcome as having several categories or time points, and does not reduce it to one comparison. The listed solicited adverse-event categories are fever, otitis media, upper respiratory illness, lower respiratory illness, and cough without lower respiratory illness, with grading also part of the endpoint. This creates multiple potential summaries, but the registry record does not report a multiplicity adjustment, testing hierarchy, or analysis plan explaining how the several categories and grades were handled statistically.
Multiplicity is a general concern when multiple statistical questions are examined: without a clear plan, isolated findings may be difficult to interpret as confirmatory. This does not establish that an adjustment was necessary or that one was omitted; the registry record does not report the approach. Nor does it identify which of the listed secondary outcomes were considered exploratory or confirmatory.
The primary endpoint population is described as study participants who received inoculation and were followed on study past Day 0. The record does not report the number assessed for each endpoint, the amount or pattern of missing data, or how missing observations were handled. It also does not report whether analyses followed assigned treatment groups or used another analysis population. These details matter because exclusions and missing outcome assessments can affect the interpretation of group comparisons.
Some secondary outcomes are limited to participants who experienced natural infection with wild-type RSV during the subsequent RSV season. The record does not report the results for that subgroup or the methods used to define or analyze it. The registry record does not provide enough detail to determine how the analysis populations, missing observations, or multiple outcome questions influenced the reported findings.
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 |
|---|---|---|---|
| Vaccine | 4 | 20 | 20.0% |
| Placebo | 1 | 11 | 9.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Vaccine | 0 of 20 |
| Placebo | 0 of 11 |
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 |
|---|---|
| Vaccine | 14 of 20 |
| Placebo | 9 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | Vaccine | Placebo |
|---|---|---|---|
| Bronchiolitis | Infections and infestations | 1 of 20 | 1 of 11 |
| Wheezing | Respiratory, thoracic and mediastinal disorders | 2 of 20 | 0 of 11 |
| Pneumonia viral | Infections and infestations | 1 of 20 | 0 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Vaccine | Placebo |
|---|---|---|---|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 11 of 20 | 5 of 11 |
| Pyrexia | General disorders | 8 of 20 | 7 of 11 |
| Cough | Respiratory, thoracic and mediastinal disorders | 7 of 20 | 6 of 11 |
| Otitis media acute | Infections and infestations | 5 of 20 | 2 of 11 |
| Irritability | Psychiatric disorders | 3 of 20 | 2 of 11 |
| Pharyngeal erythema | Respiratory, thoracic and mediastinal disorders | 2 of 20 | 1 of 11 |
| Diarrhoea | Gastrointestinal disorders | 1 of 20 | 1 of 11 |
| Vomiting | Gastrointestinal disorders | 1 of 20 | 1 of 11 |
| Conjunctivitis | Infections and infestations | 1 of 20 | 1 of 11 |
| Otitis media | Infections and infestations | 2 of 20 | 0 of 11 |
Serious events with the highest arm-level rate: wheezing (10.0%), bronchiolitis (9.1%), pneumonia viral (5.0%).
The registry safety summary lists serious adverse events in 4 of 20 participants at risk in the vaccine group and 1 of 11 participants at risk in the placebo group. It separately lists other adverse events in 14 of 20 participants at risk in the vaccine group and 9 of 11 participants at risk in the placebo group. Deaths are reported as 0 in each group. These are counts from the registry safety summary, not the solicited adverse-event results for the primary endpoint.
The serious-event terms listed with percentages are wheezing at 10.0%, bronchiolitis at 9.1%, and pneumonia viral at 5.0%. The registry summary does not specify the denominator or group attribution for each percentage. The terms and percentages should therefore not be used to infer which group had a higher frequency of a particular event.
These safety entries are descriptive, and the registry record does not report a statistical comparison, event-level timing, or an assessment of causal relationship to the intervention. The serious-event counts also do not provide the category-by-grade results for solicited events measured from Day 0 through Day 28. Differences between the count entries should not be interpreted as evidence of causation or as a complete account of safety.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized, quadruple-masked, placebo-controlled Phase I study of a single-dose RSV vaccine in RSV-seronegative infants aged 6 to 24 months. It defines the primary endpoint as the number of participants with solicited adverse events by grade during the period from Day 0 through Day 28. It also reports descriptive safety counts, including serious adverse events and deaths.
These details do not establish the comparative primary endpoint result. The registry record does not report the primary counts by event category and grade, a single summary comparison, or a statistical estimate with uncertainty. The adverse-event description alone cannot show whether one group had more or fewer events under the endpoint definition. Likewise, the safety summary counts do not establish that an event was caused by vaccine or placebo, and they do not replace the primary solicited-event assessment.
The study's stated aims include infectivity and immunogenicity, and the outcome list includes illness after natural infection, serum RSV-neutralizing antibody responses, and B cell responses. The results for these outcomes are not reported in the registry record. The record therefore does not support a conclusion about those outcomes or about clinical benefit.
In general, a small early-phase study can describe observed events and inform further research questions, but the strength of any inference depends on outcome results, precision, analysis methods, and the population studied. The enrollment entry alone does not indicate statistical power or the precision of an effect estimate. The registry's planning illustrations are sample-size planning exercises, not observed power. Their assumptions cannot substitute for reported results or a study-specific sample-size justification.
The appropriate reading is limited to what the record states: the population and interventions, the endpoint definitions, and the reported safety summary counts. Comparative conclusions, causal claims, and conclusions about outcomes without posted results are not established by those details.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of why endpoint definition matters. The primary outcome is not simply a count of all adverse events. It counts participants within each solicited category and assigns each to the highest grade experienced in that category. That distinction affects what a count means and how multiple categories can be interpreted. A participant may contribute to more than one category, so the categories should not automatically be combined as if they represented different people.
The study also illustrates how a registry record can describe a planned outcome without supplying its comparative results. Knowing the endpoint, follow-up window, and target population is essential, but interpretation also requires the observed group results and their uncertainty. Without the category-by-grade counts or a reported analysis, readers cannot assess the magnitude or precision of a primary endpoint comparison.
Multiplicity is relevant because the endpoint includes multiple event categories and grades, while the record lists other outcome measures as well. The registry does not state how the analysis accounted for those multiple questions. This is a reason to distinguish descriptive outcome reporting from inferential claims, rather than treating any isolated finding as a definitive result.
The safety summary offers another useful distinction: serious adverse-event counts are not the same measure as solicited adverse events by grade. Different definitions, observation periods, and reporting structures answer different questions. Keeping those measures separate prevents one set of counts from being used as a substitute for another.
Finally, the planning assumptions are not observed power. They show how sample-size illustrations depend on specified assumptions, while the registry does not report a study-specific sample-size justification. This distinction helps readers avoid treating a planning calculation as evidence about the precision or conclusiveness of the completed study.
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 statistical interpretation is that the registry record specifies the primary endpoint but does not report its category-by-grade results or an overall comparison. It also does not report a confidence interval, p-value, or other estimate of the comparative effect. Consequently, the size and precision of any primary endpoint difference cannot be assessed from the record.
The endpoint involves several solicited event categories and grades, but the record does not describe a multiplicity strategy or identify a primary statistical contrast within those categories. The protocol-defined grading criteria are not included in the registry record. The population is described for the primary endpoint, but endpoint-specific denominators, completion counts, and exclusions are not reported.
Although the study is randomized and quadruple-masked, the registry does not report the randomization procedure, allocation concealment, or which roles were masked. It also does not report the detailed statistical analysis plan, missing-data methods, interim analyses, or a sample-size justification. These omissions limit assessment of how the completed study was analyzed and how robust its results would be to alternative assumptions.
The safety summary includes serious-event and other-event counts, but it does not provide a statistical comparison or establish causality. The denominator and group attribution for the listed serious-event term percentages are not clear in the summary. Results for secondary outcomes, including outcomes among participants with natural infection and antibody and B cell responses, are not reported in the registry record. The record therefore supports only a partial description of the study's outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine in RSV-Seronegative Infants 6 to 24 Months of Age — NCT02794870.
- Registry record last updated 2018-08-27; status last verified 2018-07.
- Results first posted 2018-08-27.
- 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
This completed Phase I study was randomized, quadruple-masked, parallel-group, and placebo-controlled. It evaluated a single dose of RSV LID ΔM2-2 1030s vaccine versus a single dose of placebo in RSV-seronegative infants aged 6 to 24 months. Enrollment was 33. The primary endpoint counted participants with solicited adverse events by grade from Day 0 through Day 28.
The registry lists serious adverse-event counts of 4 among 20 at risk in the vaccine group and 1 among 11 at risk in the placebo group; deaths were 0 in both groups. It does not report the primary endpoint's category-by-grade results or comparative statistical analysis. Results for the listed secondary outcomes are not reported in the registry record.