Study of RSVpreF Vaccination and RSV Challenge in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of RSVpreF Vaccination and RSV Challenge in Healthy Adults (NCT04785612), a randomized phase 2 study. The primary outcome is Area Under the Viral Load-time Curve (VL-AUC) of RSV.

2. Clinical Question

The study asks whether RSVpreF vaccination is associated with a different RSV viral-load burden after participants are deliberately exposed to RSV in a human challenge model. The primary measure is the area under the viral load-time curve, determined by qRT-PCR from nasal wash samples. This endpoint combines the magnitude and duration of measured viral load over the stated collection period; it is not itself a direct measure of symptoms or clinical disease.

3. Trial Design

This was a Phase 2a, randomized, parallel-group, placebo-controlled study of RSVpreF in a virus challenge model. The registry classifies masking as quadruple; the study description also characterizes it as double-blind. These are the registry's descriptions, and the record does not provide further detail about which trial roles were masked.

The study summary describes healthy male and female participants 18-50 years of age receiving RSVpreF or matching placebo, followed by RSV challenge one month after vaccination. The intervention descriptions specify a single intramuscular injection in each arm. The study's purpose was to assess safety, immunogenicity, and efficacy using the human viral challenge model.

The record lists enrollment of 70 and status as completed. The primary endpoint analysis used the ITT Challenge Analysis Set, defined as randomly assigned participants who received a study dose and were given viral challenge. The posted primary endpoint results include 31 participants in each arm. Safety summaries list 35 participants at risk in each arm during each reported period. The registry record does not explain the difference between the enrollment, safety, and primary-analysis counts.

The primary measurement was RSV VL-AUC determined by qRT-PCR from nasal wash samples collected twice daily starting on Day +2 after challenge and continuing up to discharge from quarantine. The listed primary timeframe is Day 2 to Day 12. Secondary outcomes include symptomatic infection, viral load measured by qRT-PCR and viral culture, durations of detectable measurements, viral-culture AUC, and total clinical symptoms. The registry record does not report the full protocol, the allocation procedure, or a statistical analysis plan.

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: 70 participants were consented and vaccinated to ensure that 62 were able to then be challenged with RSV-A Memphis 37b accounting for dropouts between vaccination and challenge.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The primary analysis used the ITT (Intent-to-Treat) Challenge Analysis Set which included all participants randomly assigned to study intervention and who took a dose of study vaccine/placebo and were given viral challenge.

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.

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Viral Load-time Curve (VL-AUC) of RSV, measured over Day 2 to Day 12.

The primary endpoint is the area under the viral load-time curve for RSV, determined by qRT-PCR in nasal wash samples. Samples were collected twice daily, starting on Day +2 after viral challenge and continuing up to discharge from quarantine; the registry lists the timeframe as Day 2 to Day 12. The endpoint is reported in h*log10 PFU/mL and summarized as a median with an inter-quartile range.

An area under a curve condenses repeated measurements across a period into a measure reflecting the overall measured burden over that period. In general, this can retain information about both how high measurements are and how long they persist, rather than relying on a single measurement. It remains a virologic endpoint: it does not directly express symptom severity, duration of illness, or a participant's experience.

The registry reports a median of 0.0 for RSVpreF, with an inter-quartile range of 0.0 to 19.02, and a median of 96.65 for placebo, with an inter-quartile range of 0.0 to 675.3. These summaries describe the observed distributions in the primary analysis population. The record does not post a primary between-arm estimate or an inferential test, so the group summaries alone do not establish the precision of a treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous and is reported using a median and inter-quartile range. A median gives the middle of an ordered set of observations, while the inter-quartile range describes the central half of the observations. These summaries are useful when a distribution may be skewed or include extreme values, because the median is less influenced by very high observations than the mean. The posted primary summaries are 0.0 with an inter-quartile range of 0.0 to 19.02 for RSVpreF, and 96.65 with an inter-quartile range of 0.0 to 675.3 for placebo.

VL-AUC is based on repeated qRT-PCR measurements over the stated challenge period. In general, an area under the curve summarizes measurements over time and reflects the combined pattern of level and duration. The record describes twice-daily nasal wash collection beginning on Day +2 and continuing up to discharge from quarantine. It does not give the detailed calculation procedure for the AUC, rules for measurements below quantification, or handling of incomplete sampling. Those details are not reported in the registry record.

No inferential comparison for the primary endpoint is posted. In particular, there is no primary effect estimate or confidence interval in the registry record. A confidence interval, in general, expresses a range of values compatible with the data under a specified statistical procedure; it gives information about precision that a pair of group medians cannot provide. A p-value, in general, assesses how surprising data at least as extreme as the observed data would be under a specified null hypothesis and model. Neither can be reconstructed responsibly for the primary endpoint from the posted medians and inter-quartile ranges alone.

The binary secondary outcomes are counts of participants meeting an outcome definition. The registry reports 0 of 31 versus 13 of 31 for RT-PCR-confirmed quantifiable symptomatic infection, and 0 of 31 versus 11 of 31 for culture-lab-confirmed reduction of symptomatic RSV infection. The associated unadjusted risk-difference estimates are -0.419 and -0.355, respectively, each with a posted confidence interval and p < 0.001. A risk difference expresses the difference in event proportions between groups. Its sign depends on the order of the groups; in these comparisons, the RSVpreF group is contrasted with placebo. The confidence intervals for the risk differences are -0.593 to -0.246 and -0.523 to -0.186. These are unadjusted comparisons, and the registry record lists no reported analyses for these outcomes.

The peak viral-load outcome by viral culture is summarized as a mean and standard deviation. The posted means are 0.0 log 10 PFU/mL for RSVpreF and 1.921 for placebo, with standard deviations of 0.0 and 2.384. The unadjusted mean difference is -1.921, its confidence interval is -2.76 to -1.082, and p < 0.001. A mean difference compares group averages. In general, this form of comparison is most straightforward when the analysis assumptions are reasonable for the observed distribution. Here, the RSVpreF arm has no observed standard deviation, which is a notable feature of the data and makes interpretation of a standard mean-based comparison dependent on the method used. The registry record does not report a sponsor analysis for this endpoint.

The sample-size planning illustration is based on the observed peak viral-load effect, not on the trial's own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. For planning for 100% of the observed effect, the illustration gives 13 participants per arm for 80% power and 17 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 22 participants per arm for 80% power and 29 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 49 participants per arm for 80% power and 65 participants per arm for 90% power. These are planning illustrations, not observed power and not evidence that the study was designed with these assumptions. The registry record does not report the trial's sample-size justification.

Over-dispersion is a general issue for count outcomes when variability exceeds what a simple model assumes. It can make standard errors too small if the analysis does not account for the extra variation. The registry record includes several viral-load and duration outcomes, but does not provide enough details to assess whether a count model was used or whether over-dispersion was evaluated. Inference for each endpoint depends on its outcome scale, distribution, model, analysis population, and missing-data handling; those elements are not all specified in the registry record.

The primary analysis population is defined in the record as the ITT Challenge Analysis Set. This is not simply everyone enrolled: participants had to be randomly assigned, take study vaccine or placebo, and receive viral challenge. The record lists 31 participants per arm for the primary endpoint, while safety summaries list 35 at risk per arm. The registry does not explain participant flow or the reasons for these differences, so the populations underlying the endpoint summaries should not be assumed identical.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 27 outcome measures, including 24 posted secondary outcomes, but does not report a statistical analysis plan or a hierarchy specifying which outcomes were primary for inferential testing beyond the named primary endpoint. It also does not report a multiplicity-adjustment procedure. This matters because testing multiple outcomes can increase the chance that at least one result appears statistically notable even when no true effect exists for the outcomes under examination. Unadjusted secondary p-values should therefore be interpreted as outcome-specific evidence, not as if they came from a single protected family of tests.

The primary endpoint results are reported as group medians and inter-quartile ranges, without a primary between-group estimate, confidence interval, or p-value. The registry record lists no reported analyses. Consequently, it is not possible from the record to determine the planned inferential procedure, whether the posted descriptive summaries were the prespecified primary analysis, or how any covariate adjustment would have been handled.

The analysis population is defined as the ITT Challenge Analysis Set: randomized participants who received a dose and were given viral challenge. The endpoint results include 31 participants per arm, whereas each safety period lists 35 participants at risk per arm. The record does not provide a participant flow account or explain exclusions and missing observations. It also does not describe how missing qRT-PCR samples, incomplete measurement series, or values below quantification were handled. These omissions limit assessment of whether missingness could affect the observed endpoint summaries.

The registry record does not report interim analyses, a stopping rule, a sample-size justification, or the details of a prespecified statistical plan. Their absence from the registry record should not be interpreted as proof that none existed outside the record. For readers evaluating the posted evidence, however, these details cannot be used to assess whether the study's final analyses followed a prospectively specified approach. The sample-size illustration based on the observed peak viral-load effect is not a substitute for the original design justification.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: myocarditis (2.9%), meningitis viral (2.9%).

The registry separates serious adverse events and other adverse events by treatment arm and by period: from vaccination until viral challenge, from viral challenge until Day 28, and from Day 28 until Day 155. Each reported period lists 35 participants at risk in each arm. No deaths are recorded in any of these groups.

No serious adverse events are recorded from vaccination until viral challenge in either arm. From viral challenge until Day 28, the RSVpreF group has 0 serious adverse events and the placebo group has 1. From Day 28 until Day 155, the RSVpreF group has 1 and the placebo group has 0. The registry lists myocarditis and viral meningitis among the top serious adverse-event terms, each at 2.9%. These term percentages are not a substitute for the period-specific arm counts and do not establish attribution or causation.

Other adverse events are also reported by period: 12 in the RSVpreF group and 9 in placebo before challenge; 2 and 1 from challenge until Day 28; and 2 and 0 from Day 28 until Day 155. These are registry counts, not adjusted comparisons. Safety counts from a study of this size are descriptive, and the record does not provide a formal between-arm safety analysis or detail on event severity beyond the serious-event classification.

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

The results describe virologic and symptomatic outcomes after RSV challenge in a study of healthy adults. The primary endpoint summarizes repeated qRT-PCR viral-load measurements over the challenge period. Its posted group medians are lower in the RSVpreF arm than in placebo, but the registry does not report the primary between-arm estimate or its uncertainty. The descriptive difference therefore cannot be treated as a fully quantified inferential result.

Secondary outcomes provide related information, including laboratory-confirmed symptomatic infection and peak viral load by culture. Their unadjusted estimates are consistent in direction with the primary group summaries, but the registry does not report sponsor analyses or adjustment for multiple outcome testing. These results support a description of the observed challenge-study data; they do not establish the result of a confirmatory testing strategy.

The study design and population also set limits on interpretation. Participants were healthy adults 18-50 years of age, and the study used a controlled human viral challenge model. The findings therefore speak to measurements made in that setting and analysis population. The registry record does not establish how the results would translate to populations outside the stated age range, people with health conditions, or settings without deliberate viral challenge.

Group summaries do not show each participant's course, and the reported endpoint distributions include variability. A low median does not mean all participants had the same outcome. Similarly, the safety event counts are descriptive and do not establish that any event was caused by vaccination or placebo. The registry does not provide enough detail about missing data, endpoint analysis procedures, or multiplicity to resolve those uncertainties.

In statistical terms, the record offers useful summaries and some unadjusted secondary comparisons, but a reader cannot reconstruct a complete primary analysis from the posted information. The results should be interpreted as findings from a particular randomized challenge study, with the scope and inferential limitations described, rather than as a general estimate of effects in every clinical setting.

13. Why This Trial Matters Statistically

This study illustrates why endpoint definition and analysis reporting matter. The primary measure is a repeated-measure viral-load summary, reported using a median and inter-quartile range. Those summaries convey the observed distributions, but without a reported between-group estimate and confidence interval they do not quantify the precision of the primary contrast. A descriptive separation between group medians and a statistical estimate of a treatment contrast answer related but different questions.

The challenge model also permits the study to examine virologic outcomes and symptomatic infection within a defined post-challenge period. The secondary outcomes span laboratory-confirmed infection, viral-load peaks, measurement duration, and symptoms. Their related direction can help readers understand the pattern across endpoints, while the lack of a reported multiplicity strategy cautions against treating each unadjusted comparison as independent confirmatory evidence.

The sample-size illustration demonstrates another statistical distinction: planning calculations based on an observed effect are not the same as the trial's original design rationale, nor are they observed power. The registry record does not report the original sample-size justification. Recognizing this distinction prevents a retrospective planning calculation from being mistaken for evidence about the study's planned sensitivity.

Finally, the record shows why analysis populations and participant accounting deserve attention. The primary endpoint uses a challenge analysis set, whereas safety periods list a different at-risk count. Without a participant flow description and missing-data details, readers cannot fully assess how those populations relate. Clear reporting of the estimand, analysis population, primary contrast, uncertainty, multiplicity, and missing-data handling would make the evidence easier to evaluate and reproduce.

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 the absence of a reported primary between-arm estimate, confidence interval, and p-value. The posted medians and inter-quartile ranges describe the arms, but do not quantify uncertainty around a primary contrast. No sponsor analyses are reported in the registry record.

The study is a healthy-adult challenge study, with a stated participant age range of 18-50 years. Its controlled viral challenge setting and analysis population constrain how directly its results apply to other populations or settings. The registry does not report geographic composition or other participant characteristics beyond the stated description.

Primary results include 31 participants in each arm, while the safety summaries list 35 at risk in each arm. The record does not explain participant flow, exclusions, or missing measurements. It also does not describe the handling of incomplete sampling, values below quantification, or deviations from the planned measurement schedule. These details are relevant for an endpoint based on repeated viral-load samples.

The record lists many outcomes but does not report a multiplicity procedure, a hierarchy for secondary testing, or the detailed statistical plan. The secondary comparisons are unadjusted, and the primary inferential result is absent. The peak viral-culture outcome also has a reported standard deviation of 0.0 in the RSVpreF arm, a feature that merits caution when interpreting a mean-based comparison.

Safety counts are descriptive, with no reported formal between-arm analysis. The record also does not report the study's sample-size justification or interim analysis details. These limitations concern what can be evaluated from the registry record; they do not establish whether additional documentation or analyses exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of RSVpreF Vaccination and RSV Challenge in Healthy Adults — NCT04785612.
• Registry record last updated 2024-08-07; status last verified 2024-02.
• Results first posted 2024-08-07.
• 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

The registry record describes a completed, randomized, parallel, placebo-controlled Phase 2a study of RSVpreF in a human RSV challenge model. It lists enrollment of 70 and describes healthy male and female participants 18-50 years of age receiving a single intramuscular injection followed by viral challenge one month later.

The primary endpoint was RSV VL-AUC by qRT-PCR from nasal wash samples, measured from Day 2 to Day 12 and summarized as a median with an inter-quartile range. The primary analysis population was the ITT Challenge Analysis Set, with 31 participants per arm in the posted results. The registry does not report a primary between-group inferential analysis.

Secondary results include symptomatic infection counts and peak viral load by culture, with unadjusted comparisons posted for those outcomes. Safety events are summarized across three follow-up periods. Multiplicity handling, missing-data methods, the original sample-size justification, and a detailed statistical analysis plan are not reported in the registry record.