Safety and Efficacy of Investigational Anti-Influenza Immune Plasma in Treating Influenza: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Investigational Anti-Influenza Immune Plasma in Treating Influenza (NCT01052480), a randomized phase 2 study. The primary outcome is Time to Normalization of Respiratory Status (Primary Efficacy Population).

2. Clinical Question

This is a clinical question about the timing of respiratory recovery, not just whether a participant met a respiratory-status threshold at a single assessment. A shorter time to normalization would represent an earlier event on this endpoint, but interpretation also depends on how the groups’ times are distributed and how completely those times are observed. The registry reports medians and a log-rank comparison, but does not provide a complete interquartile range for either group or a sponsor-reported hazard ratio. Those omissions limit how fully the size and precision of the time-to-event contrast can be assessed.

The registry also lists secondary outcomes covering symptoms, fever, organ dysfunction scores, oxygenation, and mortality. These address related but distinct aspects of the clinical course. They can add context, but they do not replace the primary comparison or establish a separate confirmatory conclusion without an appropriate analysis plan and consideration of multiple testing.

3. Trial Design

The registry describes NCT01052480 as a randomized, open-label, phase 2, multicenter study using a parallel-group design. The trial is listed as completed. Its stated purpose was to assess the safety, efficacy and pharmacokinetics of investigational anti-influenza immune plasma in participants with influenza A or B. The registry lists enrollment as 98.

One group received anti-influenza immune plasma in addition to standard care, while the comparator group received standard care. Randomization is intended to make the groups comparable on average at the start of a trial, although randomization does not guarantee exact balance in a study of this size. Open-label assignment means participants and clinical staff were not masked to treatment assignment according to the registry. The record does not report whether outcome assessors were masked.

The primary efficacy analysis was restricted to the primary efficacy population, defined as randomized participants who tested positive for influenza. The primary endpoint was time to normalization of respiratory status, measured from Day 0 through Day 28. Its group summaries are based on 42 participants in the plasma and standard-care group and 45 in the standard-care group. Secondary mortality summaries use 49 participants in each group. These analyses therefore have different reported group sizes; the registry does not report the reasons for the differences or whether they reflect eligibility, outcome availability, or another analysis-population definition.

The registry lists the start as 2010-12 and primary completion as 2015-03. It reports a range of secondary outcomes, including time to resolution of clinical symptoms and fever, changes in organ dysfunction scores, oxygenation, and mortality. The study also enrolled adults, children and pregnant women, making the enrolled population broader than a single adult-only group. The registry record does not report the randomization method, allocation concealment procedures, a detailed protocol for standard care, or a sample-size justification. Those details should not be inferred from the phase or 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The population analyzed is the Primary Efficacy Population (PEP), defined as the subset of randomized participants who tested positive for influenza.

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 Time to Normalization of Respiratory Status (Primary Efficacy Population), measured over Measured from Day 0 through Day 28.

The primary endpoint measures the time from Day 0 until a participant’s respiratory status meets the trial’s definition of normalization, assessed through Day 28. Normalization requires both oxygen saturation on room air of at least 93% and a respiratory rate within normal ranges. Because both conditions must be met, this endpoint captures a combined respiratory-status threshold rather than oxygen saturation or respiratory rate alone.

Time-to-event outcomes are useful when the timing of an event is clinically relevant and participants may reach that event at different times. A median gives the time by which half of the analyzed group has experienced the event, subject to the analysis method and the handling of participants whose event is not observed during follow-up. It is not the average time and does not describe every participant’s course. The registry reports a median of 7 days for the plasma and standard-care group and 28 days for the standard-care group in the primary efficacy population. It does not report a complete interquartile range for either group.

Using a defined respiratory threshold can make the outcome more reproducible than an unstructured judgment of improvement. However, it remains important to know how assessments were scheduled, how missing assessments were handled, and how participants without normalization by the end of follow-up were treated analytically. Those details are not reported in the registry record. The endpoint’s binary threshold also means that improvement that does not meet both criteria is not counted as normalization at that assessment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Time-to-event outcomes describe how long it takes for an event to occur. In this trial, the event is reaching the stated definition of normalized respiratory status. The registry reports a median for each group and a log-rank test for the primary comparison. A median is a measure of the center of the event-time distribution: it identifies the time by which half of the analyzed group has experienced the event, if it can be estimated. It does not describe the full distribution or the experience of each participant.

What does the log-rank test compare?

The log-rank test compares the timing of events across groups over follow-up. In general, it uses information about event times and participants who have not yet experienced the event at each point in follow-up. It is not simply a test of the two reported medians. The test can therefore reflect differences across the follow-up period that are not fully conveyed by a pair of median values. Its interpretation depends on the event and censoring information and on how those data were analyzed. The registry record reports the method as log rank and gives p = 0.069, but does not report the detailed analysis specification, a hazard ratio, or a confidence interval for the primary contrast.

A p-value describes how incompatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The primary p-value of 0.069 is above the conventional 0.05 threshold, but that threshold does not turn a result into proof of no difference. The estimate and its uncertainty, the design, and the quality of outcome measurement all matter. Here, the registry’s incomplete interval information makes precision harder to judge.

Why does a confidence interval matter?

A confidence interval gives a range of values compatible with the observed data under a statistical procedure and its assumptions. A narrow interval indicates greater precision than a wide interval, while an interval that spans the null value indicates that the data do not clearly distinguish a difference from no difference at the selected confidence level. These interpretations are general; they do not guarantee that the model or the data collection process is appropriate. For the recalculated mortality and acute respiratory distress syndrome risk differences, the reported intervals include zero. The registry does not provide a confidence interval for the primary time-to-event comparison.

What does the binary-outcome recalculation represent?

The mortality and acute respiratory distress syndrome comparisons use unadjusted recalculations from the posted event counts and group sizes. A risk difference expresses the difference in the proportions with an event between the two groups, according to the direction specified for each comparison. These recalculations are not adjusted for baseline characteristics or other outcomes. The associated p-values and confidence intervals are calculated from the posted summaries, not presented as sponsor-reported analyses. The registry lists no reported analyses for these secondary outcomes. The count comparisons are especially uncertain when events are sparse; a small change in the event counts could alter the estimate substantially.

For the mortality comparison, the recalculated risk difference is 0.082, with a 95% confidence interval from -0.012 to 0.175 and p = 0.092. For the acute respiratory distress syndrome comparison, the recalculated risk difference is 0.115, with a 95% confidence interval from -0.007 to 0.238 and p = 0.064. The intervals cross zero, so the posted summaries do not yield a clear separation from no difference under these unadjusted calculations. These results are not evidence that the groups are equivalent.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variation is greater than a statistical model expects. A model that assumes less variability than the data contain can make uncertainty look too small and evidence look stronger than it is. This concept is relevant to count outcomes and repeated observations, but the registry record does not report a model for the listed secondary outcomes that would allow an assessment of over-dispersion. It should not be assumed that a particular model was used.

How should planning illustrations be read?

Sample-size illustrations based on an observed effect are planning exercises, not observed power and not evidence that the original trial was designed around those assumptions. General planning calculations depend on the effect size to detect, significance level, allocation, outcome assumptions and chosen power. The posted illustration specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation. For the mortality comparison, it lists participants per arm for 80% power and for 90% power at 100%, 75% and 50% of the observed effect. Those values are hypothetical planning quantities based on the observed effect, not a retrospective measure of the trial’s ability to detect an effect. The registry record does not report the trial’s own sample-size justification.

For time-to-event outcomes, general planning methods often depend on the number of events as well as the target effect and analysis assumptions. The posted methods description distinguishes total event counts for time-to-event illustrations from participants per arm for other illustrations. Such calculations cannot resolve limitations in the trial’s outcome reporting, and they should not be interpreted as a new result from the randomized comparison.

10. Analyses Reported by the Sponsor

The sponsor-reported primary analysis is a log-rank comparison of time to normalization of respiratory status, with p = 0.069. The registry gives group medians of 7 days for plasma plus standard care and 28 days for standard care alone. The medians describe the observed timing summaries; the log-rank p-value is the reported formal comparison. Neither should be treated as a complete description of the difference, especially because no sponsor-reported hazard ratio or confidence interval is listed and the registry does not give a complete interquartile range for either group.

The recalculated binary comparisons for mortality and acute respiratory distress syndrome use the posted counts and group sizes. They are unadjusted calculations, not sponsor-reported analyses. The registry lists no reported analyses for those secondary outcomes. No discrepancy is flagged between a sponsor-reported estimate and a recalculation. In general, if a recalculation conflicts with the sponsor’s own analysis, the sponsor’s analysis takes precedence; that situation is not indicated for the posted results.

The primary time-to-event result is not independently recalculated from the available summary statistics. The registry record does not include the underlying participant event times or enough information to reproduce the log-rank test or estimate a hazard ratio. The sponsor’s reported p-value should therefore be read as the available primary inferential result, alongside the posted medians and the limitations in interval reporting.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary efficacy endpoint and a broad set of secondary outcomes. When many outcomes are analyzed, the chance of observing at least one apparently unusual result can rise even if there is no underlying difference for any outcome. A prespecified testing hierarchy or an adjustment for multiple comparisons can help control this issue. The registry record does not report whether such a plan was used, whether secondary outcomes were intended as confirmatory or exploratory, or whether analyses were selected after results were known. No multiplicity procedure should be inferred from the posted outcome list.

The primary efficacy population is defined as randomized participants who tested positive for influenza. That definition clarifies who contributed to the primary analysis, but the registry does not report how many participants were screened for influenza, how test results were distributed by group, or how participants without a positive test were handled in other analyses. The primary group sizes are 42 and 45, whereas the mortality summaries use 49 in each group. The record does not explain these differences, so it is not possible to determine from the registry alone which eligibility or availability rules produced them.

Missing-data handling is not reported in the registry record. For a time-to-event endpoint, it matters whether participants who do not reach normalization by the end of follow-up are treated as censored, and how loss to follow-up or missed assessments is handled. Censoring methods generally rely on assumptions about the relationship between follow-up and the event; if those assumptions are not met, estimates can be biased. The record does not report the number of censored participants, missing assessments, or sensitivity analyses addressing missingness.

The registry also does not report interim analyses, stopping rules, a detailed statistical analysis plan, or a sample-size justification. These absences do not demonstrate that such procedures were not used, but they prevent readers from evaluating them from the registry record. The posted sample-size illustrations are planning scenarios based on observed effects and should not be confused with the trial’s original design rationale. Taken together, these reporting gaps limit assessment of the multiplicity, population selection, and missing-data assumptions behind the results.

12. 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: acute respiratory distress syndrome (3.8%), pneumothorax (3.8%), pulmonary thrombosis (3.8%), cerebrovascular accident (3.8%), intestinal ischaemia (3.8%).

The safety summaries report serious adverse events in 9 participants among 46 at risk in the plasma and standard-care group and 20 among 52 at risk in the standard-care group. Other adverse events are reported for 36 of 46 and 29 of 52, respectively. The registry also reports deaths of 1 and 5 in the two safety groups. These are descriptive counts from the safety record and should not be conflated with the separate mortality endpoint summaries, which use different reported group sizes.

The registry lists acute respiratory distress syndrome, pneumothorax, pulmonary thrombosis, cerebrovascular accident, intestinal ischaemia, and hyperkalaemia among the leading serious-event terms, each reported as 3.8%. These terms describe events recorded during the trial; the registry summaries do not establish that an event was caused by the plasma intervention. The record does not provide a detailed assessment of attribution, severity grading, timing, or exposure duration for each event.

Safety counts are useful for describing what was observed, but comparisons between groups can be imprecise and may be affected by differences in follow-up, underlying illness, and event ascertainment. Open-label assignment may also affect reporting or clinical decisions. The registry’s counts alone do not establish a causal safety difference or resolve the relationship between treatment and any individual event.

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

The posted primary summaries show a shorter median time to normalization of respiratory status in the plasma and standard-care group than in the standard-care group. The reported medians are 7 days and 28 days, respectively, and the sponsor-reported log-rank p-value is 0.069. These observations describe the trial’s primary efficacy population; they do not by themselves establish the size, precision, or cause of a difference between the groups.

The p-value is not a measure of the probability that the intervention is effective, and it does not establish that there is no difference. The registry does not report a primary confidence interval or a complete interquartile range, so the uncertainty around the time-to-normalization summaries cannot be fully assessed from the record. The results also depend on how respiratory assessments and censoring were handled, details that are not reported.

Secondary outcomes provide additional descriptions of the clinical course, but their unadjusted comparisons are limited by sparse counts, uncertainty, and the absence of a reported multiplicity plan. They should not be treated as independent confirmation of the primary result. Likewise, the safety counts describe events reported during the study but do not establish that treatment caused or prevented them.

In general, a randomized comparison can support causal interpretation when allocation, follow-up, outcome measurement, and analysis are adequately conducted. The registry confirms randomization but does not report all details needed to assess those conditions. The results therefore support a cautious description of what was observed in this trial, not a definitive conclusion about treatment effect across other populations or settings. They should not be used to infer outcomes for people who differ from the enrolled population or for treatment approaches not described in the registry.

14. Why This Trial Matters Statistically

This trial illustrates why a clinical result should be read through both its endpoint definition and its analysis method. Time to respiratory normalization is not simply a count of participants who improved: it asks when participants met a threshold requiring both adequate room-air oxygen saturation and a respiratory rate within normal ranges. The registry’s median summaries make the timing comparison accessible, while the log-rank test supplies a group comparison across follow-up. Neither element alone fully describes the outcome distribution.

The record also shows the value of separating a sponsor-reported primary analysis from unadjusted recalculations of binary secondary outcomes. The primary endpoint is a time-to-event outcome, and its log-rank result cannot be reconstructed from the posted medians alone. Mortality and acute respiratory distress syndrome, by contrast, have posted counts from which simple unadjusted comparisons are available. Those calculations answer different statistical questions and have different limitations.

Another important lesson is that a point estimate and its uncertainty should be considered together. The posted mortality and acute respiratory distress syndrome intervals include zero, and their event counts are sparse. That does not establish equivalence; it indicates that these summaries do not precisely distinguish a difference from no difference. Similarly, a primary p-value above a conventional threshold does not show that the groups are identical.

Finally, registry reporting determines how much independent evaluation is possible. Missing details about the analysis population, missing data, multiplicity, and the primary endpoint’s interval information constrain interpretation. Distinguishing what the registry reports from what remains undocumented is essential when assessing a phase 2 trial with a range of exploratory outcomes.

15. 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 efficacy comparison is based on the subset of randomized participants who tested positive for influenza, rather than all randomized participants. The registry gives the group sizes for this analysis but does not explain the difference between those sizes and the group sizes used for the mortality summaries. Without that explanation, the effect of population selection or outcome availability cannot be assessed.

For the primary endpoint, the registry reports medians but does not give a complete interquartile range, a hazard ratio, or a confidence interval. This restricts assessment of the distribution and precision of time to normalization. The record also does not report the number of participants who did not reach normalization by Day 28, the censoring rules, or how missing assessments were addressed.

The trial was open-label. The registry does not say whether outcome assessment was masked, so the possibility of awareness of treatment assignment influencing assessment or care cannot be evaluated from this record. The eligibility description refers to a low oxygen level or a high respiratory rate but does not give the thresholds in the brief summary. Details of standard care, randomization procedures, and allocation concealment are also not reported.

The listed secondary outcomes cover several clinical domains, but the registry does not report a multiplicity plan or a complete statistical analysis plan. The posted binary recalculations are unadjusted, and the event counts are sparse. The registry also does not report the trial’s sample-size justification, interim analyses, or sensitivity analyses. These limitations are specific to what can be evaluated from the registry record; they do not establish that the omitted procedures were absent from the full study conduct.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of Investigational Anti-Influenza Immune Plasma in Treating Influenza — NCT01052480.
• Registry record last updated 2017-09-05; status last verified 2017-06.
• Results first posted 2017-05-23.
• 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.

19. Record Summary

NCT01052480 is listed as a completed, randomized, open-label, multicenter phase 2 parallel-group trial of investigational anti-influenza immune plasma for influenza A or B. The registry lists enrollment as 98 and describes an intervention group receiving plasma plus standard care and a comparator group receiving standard care.

The primary efficacy endpoint was time to normalization of respiratory status through Day 28 among randomized participants who tested positive for influenza. The registry reports medians of 7 days and 28 days and a log-rank p-value of 0.069. It also lists secondary outcomes addressing symptoms, fever, organ dysfunction, oxygenation and mortality. The registry record does not report a complete primary interval estimate, detailed missing-data methods, or a multiplicity plan.