Statin Therapy in Acute Influenza: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Statin Therapy in Acute Influenza (NCT02056340), a randomized phase 2 study. The primary outcome is Change in Inflammatory Markers From Time Zero to 72 Hours.

2. Clinical Question

The clinical rationale in the registry record is that influenza can cause inflammation and that statins have anti-inflammatory effects. The study description says that investigators planned to assess blood markers of inflammation and record resolution of influenza illness. That rationale defines the question being tested; it is not evidence that atorvastatin changed inflammation or illness severity.

The record identifies severity of illness score from baseline to 72 hours as a secondary outcome. It does not give the result for that outcome. Details about eligibility criteria, recruitment setting, and the characteristics of participants at baseline are not reported in the registry record, so the extent to which the enrolled group represents other people with influenza cannot be assessed from this information.

3. Trial Design

The registry record describes a completed phase 2, randomized, triple-masked, parallel-group study of atorvastatin and placebo in patients with influenza. The sponsor was Beth Israel Deaconess Medical Center. The listed enrollment is 116. The study start is recorded as 2013-10, and primary completion is recorded as 2018-06-30.

In a randomized study, assignment is determined by a chance-based process rather than being chosen by clinicians or participants. This can support a fair comparison of groups, although the record does not describe the randomization sequence, allocation concealment, or the allocation ratio. The term triple masked indicates masking at three levels, but the registry record does not identify which people or roles were masked. It also does not report whether masking was assessed during the study.

A parallel design means that participants are assigned to a study group and followed within that group rather than switching between treatments as part of the design. The described intervention was atorvastatin 40 mg orally once daily for 5 days, with a maximum of 7 days for participants who remained hospitalized. The comparison was a matched placebo on the same stated schedule. These descriptions specify the planned regimens; the record does not report adherence or actual treatment exposure for participants.

The primary outcome was change in inflammatory markers from time zero to 72 hours. IL-6 measurements at those two times are specifically described, and the record says that a linear mixed effects model used all biomarker timepoints because hospitalized patients had additional measurements. Severity of illness score from baseline to 72 hours was listed as a secondary outcome.

The registry record marks the trial as completed, but it does not report a numerical primary-outcome result, a treatment-effect estimate, or a confidence interval. The reasons for choosing the enrollment target, the intended allocation ratio, and the protocol’s detailed statistical plan are not reported in the registry record.

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:

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 Change in Inflammatory Markers From Time Zero to 72 Hours, measured over Baseline to 72 hours.

The primary endpoint concerns change in inflammatory markers from time zero to 72 hours. IL-6 is specifically identified, with measurements at baseline and 72 hours. The record describes the endpoint using a median and inter-quartile range, but it does not report the observed values or a between-group estimate.

Inflammatory markers are measurements in blood that can be used to describe biological processes related to inflammation. In this trial, they were selected to address the stated rationale that influenza can cause inflammation and that statins have anti-inflammatory effects. These markers are biological outcomes; by themselves, they do not directly describe how a participant feels, functions, or recovers.

The registry record also says that investigators recorded resolution of influenza illness and lists severity of illness score from baseline to 72 hours as a secondary outcome. The record does not describe a numerical result for either measure. It therefore does not allow a comparison of how the marker findings relate to illness resolution or clinical severity.

The listed analysis used a linear mixed effects model and included all biomarker timepoints, because hospitalized participants had measurements at additional times. Using repeated observations can make use of more of the measurement record than a comparison limited to two timepoints. The record does not report the model specification or its estimated effects. Without those results, the endpoint’s clinical meaning in this trial cannot be judged from the registry entry alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome was described as change in inflammatory markers from time zero to 72 hours. IL-6 measurements were specified at those times, and the endpoint summary was described using a median and inter-quartile range. The record also states that a linear mixed effects model was used to make use of all biomarker timepoints, because hospitalized patients had measurements at additional times. These are complementary aspects of the analysis description: one identifies a summary measure, while the other identifies a model-based approach to repeated measurements. The registry record does not provide enough detail to reconstruct the model or its result.

What does a mixed effects model do?

General explanation: a mixed effects model is designed for data with more than one observation linked to the same participant or other grouping unit. It can account for the fact that repeated measurements from one person are related, rather than treating every measurement as if it came from an unrelated person. The model can also use observations collected at different times, depending on how it is specified.

In this study, the registry description says that hospitalized patients had biomarkers measured at additional timepoints and that the model used all biomarker timepoints. It does not state which timepoints were included for each participant, what fixed and random effects were used, how time was represented, or what assumptions were made about the within-participant correlation. The model’s exact form is therefore not reported in the registry record.

Why can repeated measurements be useful?

General explanation: repeated measurements can show how a marker changes over time and can contribute information even when a participant does not have a measurement at every planned time. A model may account for the correlation among observations and estimate patterns across time. Whether this improves precision depends on the data and on the assumptions and specification of the model; it is not guaranteed simply by collecting more measurements.

General explanation: missing observations can complicate repeated-measures analyses. Many model-based approaches rely on assumptions about how missingness relates to observed or unobserved values. The registry record does not describe the amount or pattern of missing biomarker data, how missingness was handled, or what assumptions were used. It is therefore not possible to assess from the entry whether missing data could have affected the result.

How should medians and inter-quartile ranges be understood?

General explanation: the median is the middle value in an ordered set of observations. The inter-quartile range describes the spread of the middle portion of those observations. These summaries can be useful when data are skewed or include values far from the center. They describe distributions; without a between-group comparison and uncertainty estimate, they do not alone establish whether groups differ.

The registry record names median and inter-quartile range for the primary endpoint, while also naming a linear mixed effects model for the analysis. It does not say how the model-based estimate was expressed or how the descriptive summaries related to the model. It would be inappropriate to infer a specific transformation, distributional assumption, or contrast from these brief descriptions.

What does uncertainty mean?

General explanation: an estimated treatment contrast is an estimate of how outcomes differ between assigned groups. A confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, but neither interval width nor a test result alone determines clinical importance.

The registry record does not report an estimated contrast or confidence interval for the primary outcome. It also does not report a primary-outcome p-value. Thus, statistical significance and precision cannot be assessed from the posted registry information. The endpoint’s observed group values are not reported in the registry record either.

What can the enrollment information say?

The registry record lists enrollment as 116, but it does not report a sample-size justification or the assumptions used to choose that enrollment. Enrollment alone does not indicate the precision achieved for the primary endpoint. Precision depends on factors including outcome variability, completeness of follow-up, the analysis model, and the actual distribution of observations across groups, none of which can be fully assessed from the registry entry.

General explanation: a planning calculation based on an observed effect is a hypothetical illustration of the sample size that might be needed under stated assumptions. It is not observed power and does not reveal the design rationale for a completed trial. The record does not report the trial’s own sample-size justification or detailed planning assumptions.

The registry entry identifies six outcome measures and two analyses, but does not detail the analysis plan, the hypothesis for each outcome, or the handling of multiple comparisons. It also does not report the analysis population or whether the primary analysis followed assigned treatment regardless of adherence. These details are important for interpreting statistical results, but cannot be inferred from the design label or the endpoint description.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures and two analyses. Multiple outcomes or analyses can create a multiplicity issue: when several statistical questions are examined, the chance of finding an apparently notable result by chance can increase. General explanation: researchers may address this through prespecified primary and secondary questions, adjustment procedures, or a clearly exploratory interpretation. The record does not report whether any such approach was planned or used, nor does it identify how the listed analyses map to the outcomes.

The primary outcome is identified as change in inflammatory markers from time zero to 72 hours, and severity of illness score from baseline to 72 hours is listed as secondary. However, the record does not state whether the primary endpoint included multiple markers, how any marker-specific comparisons were prioritized, or which analysis was considered confirmatory. It does not report a multiplicity adjustment or hierarchy for testing outcomes. These details are not reported in the registry record.

Information about missing data is also limited. The description notes additional biomarker timepoints for hospitalized patients, but does not report the number or pattern of missing measurements, reasons for missingness, or the methods used to handle it. It does not state whether participants were included according to randomized assignment, treatment received, or another analysis population. The protocol’s missing-data assumptions and sensitivity analyses are not reported in the registry record.

These omissions do not show that the trial failed to address multiplicity or missing data; they mean that the registry entry does not permit those methods to be evaluated. Because the primary outcome results themselves are not reported, there is no posted estimate to interpret in light of these potential issues.

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 non-serious adverse event terms

The registry record lists serious adverse events for the atorvastatin group as 0 among 59 at risk and for the placebo group as 0 among 57 at risk. It lists other adverse events as 4 among 59 at risk in the atorvastatin group and 5 among 57 at risk in the placebo group. Deaths are listed as 0 in each group. No serious adverse event terms are listed.

These are recorded counts, not a full account of safety. The registry entry does not describe event definitions, severity grading for other adverse events, the time period used for collection, or whether events were assessed as related to study medication. The record also does not explain whether each count refers to participants with an event or to event episodes. Such details are not reported in the registry record.

Zero recorded serious adverse events does not establish that serious risks are absent, particularly without information about follow-up and event ascertainment. Similarly, the other adverse event counts should not be treated as a complete comparison of safety without the collection methods and context. These figures describe what the registry record reports; they do not determine the overall safety profile of either regimen.

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

The registry record establishes that the study was a randomized, triple-masked, parallel-group comparison of atorvastatin and matched placebo in patients with influenza. It identifies change in inflammatory markers from time zero to 72 hours as the primary outcome and describes a mixed effects model using all biomarker timepoints. Those details explain the intended clinical and statistical question.

They do not provide the answer to that question. The numerical primary endpoint findings, group summaries, treatment-effect estimate, confidence interval, and primary-outcome test result are not reported in the registry record. The direction and size of any difference between groups are therefore unknown from this source. The secondary severity-of-illness outcome is listed, but its result is not reported either.

The record’s rationale refers to inflammation in influenza and the anti-inflammatory effects of statins. A biological rationale is not proof of an effect on inflammatory markers, symptoms, illness severity, or recovery. Even a change in a blood marker would need to be interpreted in relation to the clinical outcomes and the study’s analysis. Those results are not available in the registry entry.

The listed adverse event counts provide limited descriptive safety information. They do not establish that either regimen is safe or unsafe, because details about event ascertainment, follow-up, and attribution are not reported. Nor does the study’s completed status demonstrate that its objectives were met.

Accordingly, the appropriate interpretation is narrow: the registry record describes what investigators intended to compare and reports some event counts, but it does not report the primary efficacy findings. It cannot support a conclusion that atorvastatin changed inflammation or clinical illness, or that it had no effect. A fuller assessment would require the trial’s outcome results and relevant methodological details, which are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable as a study of a biological endpoint measured over time. The registry describes baseline and 72-hour IL-6 measurements and says that the analysis used all biomarker timepoints, including additional observations among hospitalized patients. That creates a repeated-measures analysis question: how should measurements from the same participant and at different times contribute to an estimate of group differences?

General explanation: repeated measures can provide a richer view of how an outcome develops than a single measurement, but they also require attention to within-person dependence, measurement timing, and incomplete observations. A mixed effects model is one general approach to such data. The registry record identifies that approach but does not provide enough detail to assess its assumptions or implementation.

The trial also illustrates why clinical interpretation depends on more than a statistical method. IL-6 and other inflammatory markers address a biological rationale, while illness severity and resolution concern clinical outcomes. The record lists a secondary severity score but does not report its results. Without both outcome estimates and their uncertainty, the relationship between biological changes and clinical outcomes cannot be evaluated.

Finally, the entry shows the distinction between a completed study record and a reported result. Design, endpoint, enrollment, and safety counts are not substitutes for a treatment-effect estimate. The registry record is informative about the intended question, but its missing efficacy results prevent assessment of effect size, precision, and clinical relevance. This is why transparent reporting of estimates, uncertainty, analysis populations, and missing-data methods matters for interpreting randomized trials.

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 principal limitation of the available registry information is that it does not report numerical results for the primary inflammatory-marker endpoint. It also does not report the estimated comparison between groups or its uncertainty. As a result, the primary statistical question cannot be answered from the record.

The endpoint description is brief. It identifies IL-6 measurements at time zero and 72 hours, a median and inter-quartile range, and a linear mixed effects model using all biomarker timepoints. It does not specify the full set of inflammatory markers, how change was defined for each measure, the model’s terms, or the contrast used to compare groups. These analysis details are not reported in the registry record.

Other information needed to assess the trial is also absent. The record does not report participant eligibility criteria, baseline characteristics, adherence, actual treatment exposure, group-specific outcome completeness, or the analysis population. It does not report how missing measurements were handled, whether sensitivity analyses were performed, or whether multiplicity was addressed. The sample-size justification and detailed statistical plan are not reported in the registry record.

The safety information is limited to event counts and at-risk counts. The record does not give event definitions, collection procedures, follow-up duration for safety, or attribution to treatment. The absence of listed serious adverse events should therefore be read as a registry count, not as a complete safety evaluation.

These limitations concern what can be assessed from the registry entry; they do not establish that the trial lacked additional methods or results elsewhere. No additional results or methodological details are reported in the registry record, so conclusions should remain confined to the design and counts it does state.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Statin Therapy in Acute Influenza — NCT02056340.
• Registry record last updated 2019-07-26; status last verified 2019-07.
• Results first posted 2019-07-26.
• 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 phase 2, randomized, triple-masked, parallel-group trial sponsored by Beth Israel Deaconess Medical Center. It lists enrollment as 116 and concerns patients with influenza. The comparison was atorvastatin 40 mg orally once daily for 5 days, with a maximum of 7 days for participants who remained hospitalized, versus matched placebo on the same schedule.

The primary outcome was change in inflammatory markers from time zero to 72 hours. The record identifies IL-6 measurements at those times and says a linear mixed effects model used all biomarker timepoints, including additional measurements among hospitalized patients. Severity of illness score from baseline to 72 hours was listed as a secondary outcome.

Numerical efficacy results, an estimated treatment contrast, and confidence intervals are not reported in the registry record. Serious adverse event counts were 0 in each group; other adverse event counts were 4 for atorvastatin and 5 for placebo. Death counts were 0 in each group. The record does not provide enough outcome or methods detail to judge efficacy, precision, or overall safety.