Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (RSV LID cp ΔM2-2) in RSV-Seronegative Infants 6 to 24 Months of Age: Complete Statistical Analysis

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 (RSV LID cp ΔM2-2) in RSV-Seronegative Infants 6 to 24 Months of Age (NCT02890381), a randomized phase 1 study. The primary outcome is Number of Participants With Solicited Adverse Events (AEs) by Grade.

2. Clinical Question

The study also aimed to evaluate infectivity and immunogenicity. Secondary outcomes included symptomatic, medically attended respiratory and febrile illness among participants with natural infection during the subsequent RSV season, serum RSV-neutralizing antibody responses in that subgroup, and B cell responses to vaccine. Those additional questions concern different outcomes and, for some measures, different participant subsets; they should not be conflated with the solicited adverse event endpoint.

This was a Phase I study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), and the record describes it as a companion study to CIR 312. Its stated purpose was to assess the safety, infectivity and immunogenicity of a single intranasal vaccine dose in this age group. The registry status is terminated. The reason for termination is not reported in the registry record.

3. Trial Design

The registry identifies this as a randomized, quadruple-masked, parallel-group, placebo-controlled Phase I study. Participants were assigned to receive a single dose of RSV LID cp ΔM2-2 vaccine or a single dose of placebo at study entry, Day 0. The record does not state the allocation ratio, the method used to generate the random sequence, or the roles covered by quadruple masking. Those details are not reported in the registry record.

Enrollment was 17, and the primary outcome population is described as all study participants. The study began on 2016-10-05 and its primary completion date is listed as 2017-04-24. The status is terminated. A reason for stopping, whether recruitment ended as planned, and the number of participants in each arm at each assessment are not reported in the registry record.

The primary outcome was the number of participants with solicited adverse events by grade, measured from Day 0 through Day 28. The protocol-defined grading system ranged from Grade 1, mild, to Grade 4, life-threatening. A participant was counted once in each solicited adverse event category and assigned to the line for the highest grade experienced in that category. This category-specific rule matters when reading counts: the same participant could contribute to more than one category, while not being counted repeatedly within a category.

Other listed outcomes addressed events after natural infection with wild-type RSV during the subsequent RSV season, antibody responses among participants who experienced such infection, and B cell responses to vaccine. The registry record lists 11 outcome measures and 6 analyses. It does not report a complete statistical analysis plan, the allocation concealment procedures, or the planned timing and handling of all outcome assessments.

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

Analysis population for the primary outcome, as defined in the registry: All study participants 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: Analysis population was all participants enrolled.

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.

The primary endpoint counts participants who experienced solicited adverse events, classified by event category and grade, during the period from Day 0 through Day 28. The listed categories are fever, otitis media, upper respiratory illness, lower respiratory illness and cough without lower respiratory illness. The registry describes a protocol-defined grading system, with grades ranging from mild to life-threatening.

A participant was counted once in each adverse event category, at the highest grade recorded for that category. This makes the outcome a set of category-specific participant counts rather than a single total count of all events. A participant with events in more than one category could appear in more than one category count. The endpoint therefore describes how many participants experienced each kind of solicited event at each grade, rather than how many separate event episodes occurred.

Solicited events are assessed because they are specified for collection, rather than relying only on spontaneous reports. In general, a defined collection window and consistent event grading can make safety observations easier to compare across assigned groups. The registry record does not report the primary endpoint counts or a treatment comparison, so the endpoint’s results cannot be interpreted from the information recorded. It also does not describe the detailed procedures used to collect or verify each solicited event.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a participant count. In general, count outcomes describe how many people meet a defined event condition; they are not the same as counts of event episodes. Here, the registry specifies that a participant contributes once within each solicited adverse event category and is assigned the highest grade experienced in that category. Because the outcome has multiple event categories, a person may contribute to several different category counts. The categories should therefore be read separately rather than added into a total without a prespecified rationale.

Grade is an ordered classification: the registry describes Grade 1 as mild and Grade 4 as life-threatening. In general, ordering preserves information about event severity that a simple yes-or-no event indicator would discard. But an ordered grade does not automatically make the distances between grades equal. A statistical analysis may treat grades as categories, use an ordinal model, or summarize them in another prespecified way. Which method was planned or used for the primary endpoint is not reported in the registry record. The registered description gives the counting rule, not the model.

For a binary event outcome, a basic descriptive presentation can show the number of participants with an event and the number assessed in each arm. The adverse event information includes arm counts for serious and other adverse events. Such counts can support a descriptive reading, but they do not on their own provide a precision estimate for the difference between arms. In general, confidence intervals communicate the range of effect sizes compatible with the data under a specified method and assumptions. No confidence intervals for the primary solicited endpoint or the serious adverse event comparison are reported in the registry record.

In general, a treatment comparison for a binary outcome can be expressed using a difference in proportions, a ratio of proportions, or another measure. These measures answer different questions and have different scales. The choice should be prespecified and accompanied by its uncertainty. The registry record does not report a primary contrast, an effect measure, a test, or an adjustment procedure for the solicited endpoint. No recalculated treatment comparison is appropriate from the endpoint information available because its category-specific results are not reported.

Randomization, masking and parallel assignment are elements of study design, not statistical tests. Randomization is intended to make assigned groups comparable apart from chance; masking is intended to limit the influence of knowledge of assignment. In general, these features do not eliminate uncertainty, and a small study can have chance differences in characteristics or outcomes. The record identifies randomized assignment and quadruple masking, but does not describe sequence generation, concealment, the people masked, or checks of masking. Those details are not reported in the registry record.

Multiple outcome categories create a multiplicity issue. In general, when many comparisons are examined, the chance of at least one apparently unusual result can increase if each is interpreted as a separate confirmatory test. A prespecified hierarchy, an adjustment method, or a clearly exploratory interpretation can address this concern in different ways. The registry identifies several outcome measures and analyses and says that the primary endpoint has several categories or time points, but the multiplicity strategy is not reported in the registry record. The endpoint has not been reduced to one comparison in the registered description.

The record describes secondary outcomes involving participants who experienced natural infection with wild-type RSV during the subsequent RSV season, as well as B cell responses to vaccine. In general, an analysis confined to a subgroup answers a narrower question than an analysis of all randomized participants. The number of participants in the relevant subgroups, the analysis methods and the observed results are not reported in the registry record. No assumption should be made that subgroup comparisons preserve the protections of randomization in the same way as the full randomized comparison.

Missing outcome data can affect both the number assessed and the credibility of a comparison. In general, an analysis should state how missing observations were handled and whether participants were analyzed according to assigned group. The primary endpoint population is described as all study participants, but that description alone does not establish that every participant had complete outcome data or explain how missing values were treated. Missing-data procedures and the analysis population for each outcome are not reported in the registry record.

The registry’s planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such planning quantities are not observed power and do not establish the trial’s original design rationale. The record does not report a protocol-based sample-size justification. In general, planning sample sizes depend on assumptions about the target effect, variability or event frequency, allocation and analysis method. Where the endpoint has several categories rather than a single comparison, a one-effect planning illustration does not fully represent the endpoint structure.

Over-dispersion is a general issue for count data when observed variation exceeds what a simple count model assumes. If relevant, it can make uncertainty estimates too narrow unless the model accounts for the extra variation. The primary registered outcome is counts of participants by event category and grade, but the registry entries do not establish that a count regression model was used or that over-dispersion was assessed. The analysis model and diagnostics are not reported in the registry record. No particular model should be attributed to the study on the basis of the endpoint description alone.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is not a single event measure: it includes several solicited adverse event categories and grades over a defined period. The registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. In general, looking across multiple categories raises a multiplicity question because separate tests can produce results that appear noteworthy by chance. A prespecified approach might define a primary contrast, adjust for multiple testing, or present category results descriptively. The multiplicity plan is not reported in the registry record.

The record lists 11 outcome measures and 6 analyses, including primary and secondary outcomes addressing safety, natural infection, illness and immune responses. It does not report which analyses were confirmatory, whether outcomes were ranked in a hierarchy, or whether any statistical adjustment was applied. Without those details, individual findings, if available elsewhere, would need to be interpreted in light of the number of outcomes examined. The results for the primary solicited endpoint and the listed secondary outcomes are not reported in the registry record details.

The primary endpoint population is described as all study participants. This does not specify whether every participant contributed observations at every assessment, how withdrawals were handled, or whether participants were analyzed according to randomized assignment. Missing-data procedures and analysis populations for the other outcomes are not reported in the registry record. In general, complete-case summaries can be misleading if missingness is related to outcome or assignment, while imputation methods rely on assumptions that should be stated. The registry record does not identify a missing-data method or assumptions.

Secondary outcomes that depend on natural infection apply to a subset of participants. The record does not give the size of that subset or its analysis population. The method used to handle missing observations in those outcomes, or in B cell response assessments, is also not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: wheezing (33.3%), bronchiolitis (9.1%), bronchitis (9.1%), croup infectious (9.1%), respiratory syncytial virus bronchiolitis (9.1%).

The adverse event information lists 4 of 11 participants in the vaccine group and 2 of 6 in the placebo group as affected by serious adverse events. It lists 0 deaths in each group. It also records 9 of 11 vaccine participants and 6 of 6 placebo participants under other adverse events. These are descriptive counts from the registry record, not adjusted comparisons.

The record’s serious-event term list includes wheezing with 33.3%, as well as bronchiolitis, bronchitis, croup infectious and respiratory syncytial virus bronchiolitis, each with 9.1%. The denominator behind these percentages and whether they refer to participants or event reports are not reported in the registry record. The terms and percentages should therefore be read as recorded labels, not converted into a group-specific risk estimate.

Serious adverse events are distinct from the primary endpoint’s solicited events, which were assessed by category and grade from Day 0 through Day 28. The registry record does not give those primary endpoint counts. The serious-event counts alone do not establish a comparative effect, and the record does not report uncertainty intervals or a statistical test for them. The reason for termination is also not reported in the registry record.

12. What the Result Does, and Does Not, Mean

The registry record documents a Phase I randomized, masked, placebo-controlled study of a single dose of RSV LID cp ΔM2-2 in RSV-seronegative infants 6 to 24 months of age. It specifies a primary safety endpoint based on solicited event counts by grade from Day 0 through Day 28. This information clarifies the study question and how a participant was counted within each adverse event category.

The registry also records serious adverse event counts by arm and lists deaths as 0 in both arms. Those figures describe what is recorded for the serious and other adverse event groupings, but they are not a complete account of the primary endpoint. The event-term percentages lack a stated denominator in the available record, and no comparative uncertainty estimates are included in the registry record. It is therefore not possible to determine the precision of a difference between groups from these counts alone.

The primary solicited adverse event results are not reported in the registry record. Neither are results for natural infection, medically attended illness, antibody responses or B cell responses. The record does not provide a statistical analysis plan, a primary effect estimate, confidence intervals, or a test result for the endpoint. Consequently, the registered information does not support a quantitative judgment about the relative frequency of solicited events between the randomized groups.

The study’s randomized and masked design is relevant to how a comparison could be interpreted, but design features do not replace outcome results. Enrollment was 17, so the study was small in scale; the record does not provide a protocol-based sample-size justification or indicate what precision was intended. The status is terminated, but the reason is not reported. None of these registry entries alone explains the missing outcome results or establishes why the trial ended.

These limits mean the record can be used to understand the planned population, intervention, comparator and endpoint definition, and to read the posted adverse event counts descriptively. It cannot establish a definitive comparison of the primary endpoint, quantify uncertainty around that comparison, or settle the secondary questions. No conclusion about treatment effectiveness or clinical use follows from the design description or the incomplete outcome information.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why an endpoint definition matters as much as the label of an outcome. The primary measure is not simply whether a participant had any adverse event. It separates fever, otitis media, upper respiratory illness, lower respiratory illness and cough without lower respiratory illness, and assigns each participant the highest grade within each category. That rule shapes what a count means and prevents repeated counting within a category while allowing contributions to multiple categories.

The study also illustrates the limits of interpreting a small randomized trial from descriptive counts. The registry gives enrollment of 17 and arm-specific serious adverse event counts, but those counts do not convey precision or identify a statistically supported difference. In general, estimates from small samples can be uncertain, and apparent arm differences can be sensitive to individual observations. Confidence intervals and a prespecified comparison would help communicate that uncertainty, but the relevant primary estimates and intervals are not reported in the registry record.

Multiplicity is another important statistical feature. The primary endpoint includes several categories and grades, and the registry lists multiple outcome measures. Without a stated plan for prioritizing or adjusting analyses, separate findings may not all carry the same evidentiary weight. This is particularly relevant when a study considers safety, infection, illness and immune response as distinct outcomes.

Finally, the registry distinguishes outcomes assessed in all participants from outcomes focused on those who experienced natural infection. That difference in analysis population changes the question being answered. The registry does not report subgroup counts or corresponding results, so those questions cannot be assessed quantitatively. The trial’s structure makes clear why statistical interpretation requires endpoint definitions, analysis populations, effect estimates and uncertainty—not just a list of outcomes or adverse event terms.

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 details. The endpoint definition is detailed, but there are no category-specific counts by grade, no single comparison, and no effect estimate or confidence interval. The serious adverse event counts do not fill this gap because they are a separate set of descriptive information.

Enrollment was 17. The record does not report the arm-specific participant totals for the primary analysis, baseline characteristics, or the number of observations available at each assessment. It is therefore not possible to assess the extent of any chance imbalance or the completeness of primary outcome follow-up. Although the endpoint population is described as all study participants, the handling of missing data is not reported in the registry record.

The registry identifies the design as randomized and quadruple-masked but does not detail the random sequence method, allocation concealment, or which people were masked. It does not report the statistical model, the planned effect measure, the multiplicity strategy, or whether the analyses followed an intention-to-treat approach. The reason for termination is not reported in the registry record, and no protocol-based sample-size justification is given.

Additional outcomes depend in part on natural infection during the subsequent RSV season, but the subgroup size, analysis methods and observed results are not included in the record details. The term-specific serious adverse event percentages are listed without a denominator or an explicit description of their relation to participant counts. These reporting gaps limit both the comparison between arms and the ability to assess the precision and scope of the findings.

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 (RSV LID cp ΔM2-2) in RSV-Seronegative Infants 6 to 24 Months of Age — NCT02890381.
• Registry record last updated 2021-11-05; status last verified 2018-05.
• Results first posted 2018-07-02.
• 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.

18. Record Summary

NCT02890381 is a randomized, quadruple-masked, parallel-group, placebo-controlled Phase I study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It enrolled 17 RSV-seronegative infants 6 to 24 months of age and compared a single dose of RSV LID cp ΔM2-2 vaccine with a single dose of placebo. The record lists the status as terminated, with start date 2016-10-05 and primary completion date 2017-04-24.

The primary outcome was solicited adverse events by grade from Day 0 through Day 28, with category-specific participant counting. Secondary outcomes addressed natural RSV infection, illness, antibody responses and B cell responses. The record lists serious adverse event counts of 4 of 11 in the vaccine group and 2 of 6 in the placebo group, with 0 deaths in both groups. Primary endpoint results, secondary outcome results, the reason for termination and key analysis details are not reported in the registry record.