Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Patients Having Acute Respiratory Distress Syndrome (ARDS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Patients Having Acute Respiratory Distress Syndrome (ARDS) (NCT02622724), a randomized phase 3 study. The primary outcome is Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28.

2. Clinical Question

The registry describes the study as a phase III efficacy and safety comparison in patients with moderate or severe ARDS. Its brief summary says the investigational drug was expected to reduce time on a ventilator and improve survival; this is the study rationale, not evidence of benefit. The observed primary results and the sponsor’s reported test are discussed as statistical findings, without treating the trial’s expectations as conclusions.

The record does not report additional clinical eligibility details, such as the exact clinical criteria used to define moderate or severe ARDS. It also does not report a treatment-effect estimate with a confidence interval for the primary comparison. Those omissions limit how specifically the clinical question can be interpreted from the registry record alone.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase III trial comparing FP-1201-lyo 10 μg with placebo. The registry record lists enrollment as 301. The primary analysis population is separately identified as the Full Analysis Set (FAS), 296 subjects; the record does not describe the reasons for the difference between the enrollment figure and that analysis population.

The intervention and placebo were each administered once daily by intravenous bolus injection for 6 days. The record identifies the sponsor as Faron Pharmaceuticals Ltd. The study started on 2015-12-23 and lists primary completion on 2018-05-17. Its current status is terminated. The reason for termination and whether termination affected the planned analyses are not reported in the registry record.

The primary outcome was assessed at Day 28. It was a composite of all-cause mortality and ventilator-free days, with a special scoring rule for death. The sponsor reported a Van Elteren hypothesis test for the primary comparison. The registry does not report the planned allocation ratio, the randomization procedure, stratification factors, or the statistical analysis plan in enough detail to establish whether other methods or analysis populations were prespecified.

Several secondary outcomes are identified, including mortality and days free of organ failure, renal support, vasoactive support, and mechanical ventilation. The record lists 36 outcome measures and 11 analyses, and identifies 15 posted secondary outcomes. These counts describe the registry record; they do not establish which outcomes were designated as confirmatory or how their analyses were prioritized. That hierarchy is not reported in the registry record.

Although the study is described as quadruple-masked, the record does not specify all roles included in the masking description or report whether masking was assessed. It also does not describe the reason for termination. Consequently, design features can be described as recorded, while their operational details and implications remain uncertain.

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: Full Analysis Set (FAS), 296 subjects.

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: A total of 296 subjects received at least 1 dose of study treatment (301 subjects fulfilled all criteria and were randomly assigned in a 1:1 ratio to FP-1201-lyo and placebo, but 5 subjects were not dosed).The Full Analysis Set (FAS) consisted of the 296 randomised and treated subjects who received 1 or more doses study medication.

6. Primary Endpoint

The registry lists the primary outcome as Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28, measured over Day 28.

VFDsurv is the primary composite endpoint at Day 28. It combines all-cause mortality with days free of mechanical ventilation, using a scoring rule that gives death a distinct place in the outcome. Among survivors, the measure reflects ventilator-free days within 28 days. A ventilator-free day requires a complete calendar day of unassisted breathing, as defined in the registry record. A patient is counted as ventilator-free after 2 consecutive calendar days of unassisted breathing.

The definition assigns a VFD value of 0 to patients who die without initiating unassisted breathing or require more than 28 days of mechanical ventilation. Patients who die before Day 28 receive a VFDsurv value of -1. These rules mean that the composite does not treat death as merely another day without ventilation; death is assigned a worse value than the specified ventilation outcome among survivors.

Using a composite can summarize outcomes that matter to the clinical course, while avoiding an interpretation based only on ventilator duration among survivors. It also means that the result must be read as a combined measure: a group difference cannot be attributed to mortality or ventilator-free days separately without analyses that distinguish those components. The registry reports medians and full ranges for the primary endpoint, but does not report a primary confidence interval for a treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary test assess?

The sponsor used a Van Elteren hypothesis test for the primary endpoint. In general, the Van Elteren test is a stratified rank-based method: it compares the ordering of outcomes between groups while accounting for strata. Rank-based methods can be useful when an outcome is not well described by a normal distribution or when the analysis is intended to compare the distributions rather than only their means. The registry record does not report the strata used, the detailed test specification, or whether any adjustment was made. The reported p-value should therefore be interpreted as the result of the sponsor’s stated test, without assuming unreported details.

A rank-based test does not directly estimate a difference in medians. A p-value from that test and the two group medians answer related but distinct questions. The medians describe central locations; the test evaluates evidence against its null hypothesis using the analyzed outcome ranks. The registry does not give a confidence interval for a primary treatment contrast, so the size and precision of such a contrast cannot be read from the primary results.

How should a confidence interval be read?

In general, a confidence interval describes the uncertainty in an estimated effect under the statistical procedure used to construct it. An interval that includes no difference indicates that the data are compatible with no difference at the stated confidence level, as well as with some effects on either side of no difference. It does not prove that there is no effect. Conversely, an interval excluding no difference would not, by itself, establish clinical importance or resolve concerns about bias, missing data, or multiple testing.

The posted secondary mortality recalculations use risk differences, with intervals shown on the proportion scale. These are simple unadjusted recalculations from the posted summary statistics, not adjusted sponsor estimates. The recalculated p-values are likewise unadjusted. The registry record does not report sponsor analyses for these secondary outcomes.

Why distinguish a risk difference from a ratio?

In general, a risk difference compares event proportions by subtraction and is expressed on the absolute proportion scale. A risk ratio compares those proportions as a ratio, while an odds ratio compares event odds. These measures describe different aspects of an outcome and can have different numerical values. The posted secondary results include risk-difference estimates and, for some outcomes, ratio estimates. They should not be treated as interchangeable, and no new measures are calculated in this interpretation.

When an interval for a risk difference includes zero, it includes the value corresponding to no absolute difference. For a ratio measure, the corresponding no-effect value is one. This distinction is important when reading intervals. The primary endpoint is not a simple binary risk outcome, so the secondary mortality risk differences should not be used as substitutes for the primary composite analysis.

What do the planning illustrations mean?

The sample-size planning illustrations are based on the observed effect and are not the trial’s original design justification. They assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They explore detecting specified shares of the observed effect. For these binary outcomes, the reported quantities are participants per arm for 80% power and participants per arm for 90% power. Such values are hypothetical planning calculations, not observed power and not evidence that the trial had a particular probability of detecting an effect.

Planning from an observed effect has important limitations. The observed effect may be unstable, and smaller effects require larger studies to detect with the same target power under the stated assumptions. The illustrations do not establish that a future study would have the assumed event rates or effect. They also do not account for design features that are not specified in the registry record. In particular, the registry does not report the trial’s own sample-size justification, planned event rates, or detailed assumptions.

Why can outcome distributions matter?

General statistical considerations are relevant for composite outcomes such as VFDsurv. Outcomes may be skewed, contain many tied values, or have a large concentration at particular scores. Rank-based methods avoid relying on a normal model for the raw outcome, but their interpretation depends on the distribution of ranks and the analysis structure. If an outcome has meaningful strata, the test’s handling of those strata matters. The registry’s primary endpoint description provides the score rules, but not the distribution of individual observations or the test’s detailed implementation. Those features cannot be reconstructed from medians and ranges alone.

10. Analyses Reported by the Sponsor

For the primary endpoint, the registry reports the sponsor’s Van Elteren hypothesis test with p = 0.822. This is the sponsor’s own analysis and is the relevant reported inferential result for the primary comparison. The primary summaries also give a median and full range in each arm, but they do not provide a recalculated treatment contrast or confidence interval. A simple reanalysis from these summary statistics would not reproduce the rank-based test.

The secondary mortality calculations are separate, simple unadjusted recalculations from posted summary statistics. They are not sponsor-reported analyses: the registry lists no reported sponsor analyses for those outcomes. They can help illustrate the uncertainty around the posted group summaries, but they do not supersede the sponsor’s primary test or establish a prespecified secondary conclusion. No discrepancy between a sponsor result and a recalculation is flagged in the registry record.

The sponsor’s primary p-value should not be read as proof of equivalence, nor should the secondary recalculations be treated as a replacement primary analysis. The registry does not report the detailed statistical analysis plan, so it is not possible to determine from the record alone how the sponsor intended to connect the primary and secondary tests.

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes or statistical tests are examined. In general, testing many outcomes without an adjustment can increase the chance that at least one result appears statistically notable by chance. A prespecified testing hierarchy or multiplicity adjustment can help control that risk, but the registry record does not report whether either was used. The record identifies 36 outcome measures, 11 analyses, and 15 posted secondary outcomes; these counts do not reveal which tests were confirmatory or how any testing hierarchy was applied.

The registry reports a primary analysis and identifies a number of secondary outcomes, but the statistical analysis plan, prespecified hypotheses, and adjustment method are not reported in the registry record. The unadjusted secondary recalculations therefore have a more limited role than a fully documented, prespecified analysis. Their p-values should not be interpreted as controlling the chance of false-positive conclusions across the set of outcomes.

Missing-data handling is also not reported in the registry record. The primary population is described as the Full Analysis Set, 296 subjects, but the record does not specify the inclusion rules for that set, the handling of missing endpoint values, or whether any imputation or sensitivity analyses were used. It does not explain how missing follow-up or withdrawal was handled for the secondary outcomes.

The primary endpoint’s scoring rules address specified outcomes such as death before Day 28 and prolonged mechanical ventilation. They do not, by themselves, explain how unobserved or incomplete data were handled. Without those details, the effect of missingness on the estimates cannot be assessed. The registry also does not report whether interim analyses were conducted, what stopping rules applied, or whether the termination was related to an interim result. None of these details can be inferred from the trial’s terminated status.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: multi-organ failure (9.0%), condition aggravated (7.2%), respiratory failure (5.9%), pneumonia (5.9%), septic shock (4.9%).

The registry reports serious adverse events in 77 participants in each group, with 144 at risk in the FP-1201-lyo group and 152 at risk in the placebo group. It reports other adverse events in 109 participants in the FP-1201-lyo group and 110 in the placebo group. Deaths are listed for 51 and 53 participants, respectively. These are posted counts, not adjusted comparisons, and the registry record does not provide uncertainty intervals or a safety hypothesis test for these figures.

The serious adverse-event terms listed most often include multi-organ failure, condition aggravated, respiratory failure, pneumonia, septic shock, and acute respiratory distress syndrome. Their listed percentages are not assigned by treatment group in the record, so they should not be attributed to one arm. The listed terms are event categories, not estimates of treatment causation.

Because patients had ARDS, serious events and deaths may reflect the underlying illness as well as many other factors. Counts alone do not establish whether an event was caused by the intervention. The registry does not provide event timing, severity breakdowns, exposure-adjusted rates, or detailed adjudication information. These safety figures should therefore be read descriptively, not as proof of comparative safety or harm.

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

The primary result is a comparison of a composite outcome in a randomized, masked trial, with the sponsor reporting a Van Elteren test at p = 0.822. The observed group medians were 10 days for FP-1201-lyo and 8.5 days for placebo, and both groups had a full range from -1 to 26 days. These summaries do not establish that the treatments are equivalent, and the p-value does not quantify the probability that either treatment is better.

The primary outcome combines survival and ventilator-free time, so it cannot be interpreted as a mortality result alone. The posted secondary mortality recalculations are unadjusted and imprecise; they do not establish a reliable treatment difference. Nor do those outcomes identify the effect on the ventilator-free-day component of the primary measure.

The results do not show that FP-1201-lyo improves survival, reduces ventilation, or changes either outcome by a particular amount. They also do not establish that it has no effect. The registry record lacks a reported primary confidence interval and does not describe important analysis details, including missing-data methods and the approach to multiple outcomes. Those gaps constrain conclusions about precision and robustness.

Safety counts are descriptive. They do not by themselves establish that the intervention caused or prevented adverse events, and the listed serious-event percentages are not linked to a treatment group in the record. The trial’s terminated status is known, but its reason and implications are not reported.

Overall, the registry supports a cautious statistical reading: the sponsor’s primary test did not identify a statistically detectable difference, while the available secondary mortality estimates remain uncertain. Neither finding justifies a claim of benefit, harm, or equivalence.

14. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition matters as much as the test. VFDsurv combines mortality with ventilator-free days, assigns death a distinct score, and depends on specific rules for when breathing is considered unassisted. The result is not simply an average number of days on a ventilator. Reading the median without understanding those rules could obscure what the composite represents and what it cannot separate.

It also illustrates the difference between a hypothesis test and an effect estimate. The sponsor reports a rank-based test and a p-value, while the registry gives group medians and ranges. Without a primary confidence interval or a treatment-contrast estimate, the precision and plausible size of the primary difference are difficult to characterize. A non-significant test should not be translated into evidence of equivalence.

The secondary mortality outcomes show why intervals and multiplicity matter. Their unadjusted estimates are uncertain, and the registry does not report a multiplicity strategy. Considering several endpoints can add useful context, but it also makes isolated results less persuasive unless the analysis plan explains how they were selected and interpreted.

Finally, the distinction between enrollment and the primary analysis population, together with the terminated status, underscores the value of transparent reporting. The registry names the analysis population but does not explain the difference from enrollment, missing-data handling, or the reason for termination. Those details are relevant to assessing how robustly the trial answers its clinical question.

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 registry record does not report a confidence interval or an effect estimate for the primary contrast. Medians and full ranges do not provide enough information to reconstruct the distribution or precision of the primary treatment effect. The sponsor’s reported test is identified as a Van Elteren hypothesis test, but the strata and detailed implementation are not reported.

The record describes the primary analysis population as the Full Analysis Set, 296 subjects, while enrollment is listed as 301. It does not explain the difference, specify inclusion rules for the analysis set, or describe missing-data handling. The effect of incomplete follow-up or missing endpoint values therefore cannot be assessed from the registry record.

The study is marked terminated, but the reason for termination is not reported. The record does not say whether termination was related to recruitment, safety, efficacy, funding, or another cause, and none should be inferred. It also does not report whether interim analyses or stopping rules were used.

Multiplicity methods and the status of secondary endpoints are not described. The secondary mortality calculations are unadjusted reanalyses, not sponsor-reported inferential results. They provide limited context but cannot establish a confirmatory finding across multiple outcomes. The registry lists other secondary outcomes, but their detailed results and analysis methods are not available in the registry record described for this analysis.

Safety reporting is similarly limited: the record gives counts and selected serious-event terms but does not provide event timing, group-specific percentages for those terms, or adjusted comparisons. These limitations mean that the posted summaries can describe observed results, but cannot resolve questions about missing data, the cause of termination, or the robustness of the full analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Patients Having Acute Respiratory Distress Syndrome (ARDS) — NCT02622724.
• Registry record last updated 2020-03-30; status last verified 2020-03.
• Results first posted 2020-03-30.
• 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

NCT02622724 is a phase III randomized, quadruple-masked, parallel-group comparison of FP-1201-lyo 10 μg and placebo in patients with moderate or severe ARDS. The primary endpoint was VFDsurv at Day 28, a composite of all-cause mortality and ventilator-free days. The primary analysis population was the Full Analysis Set, 296 subjects.

The sponsor reported a Van Elteren hypothesis test for the primary endpoint, with p = 0.822. The registry reports group medians and ranges but no primary treatment-contrast confidence interval. Secondary mortality recalculations are unadjusted and have intervals that include no difference. Safety counts are descriptive and do not establish causation.

The trial is marked terminated; the reason is not reported in the registry record. Details on missing-data handling, multiplicity, interim analyses, and the statistical analysis plan are also not reported in the registry record.