This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Influenza Resistance Information Study (NCT00884117), a registered phase not stated study. The primary outcome is Percentage of Participants Exhibiting Treatment-Emergent Resistance by Study Year Among Participants With H3N2 or H1N1pdm09 Infections.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00884117 |
| Phase | Phase not stated |
| Condition | Influenza |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 4561 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants clinically diagnosed with influenza were enrolled, including adults and children. The primary endpoint concerns participants with H3N2 or H1N1pdm09 infections who had evaluable viral RNA data. The record describes this as the ALCIP Population and notes that participants needed an analyzable post-Baseline sample for their viral RNA subtype.
Intervention
Oseltamivir was the antiviral treatment of interest. Participants were clinically managed according to local guidelines, and the investigator decided whether to treat. The registry record therefore describes treatment in clinical practice rather than a treatment assignment controlled by the study.
Comparator
The record distinguishes participants treated with oseltamivir from participants not treated with it. Allocation is not stated, and the arms are not a like-for-like control comparison. Differences between these groups may reflect factors related to treatment decisions as well as any differences in outcomes.
Primary question
Among participants with the specified influenza subtypes, what percentage had treatment-emergent resistance during each study year? Resistance was defined using genotypic or phenotypic evidence after Baseline when the Baseline sample had not shown resistance. The registry record describes the endpoint and its assessment schedule, but the year-specific percentages are not reported in the registry record.
3. Trial Design
The Influenza Resistance Information Study (IRIS), registered as NCT00884117, was a completed study sponsored by Hoffmann-La Roche. The registry record gives a start date of 2009-01, a primary completion date of 2015-11, and enrollment of 4561. These details describe the registered study and do not establish how many participants contributed evaluable data to the primary endpoint.
The study aimed to support early detection of influenza resistant to antivirals and to monitor clinical outcomes by influenza subtype and susceptibility. Participants clinically diagnosed with influenza underwent a rapid diagnostic test and viral sampling at Baseline and on Days 3, 6, and 10. The primary endpoint description refers to assessments on Days 1, 3, 6, and 10, with Day 1 identified as Baseline. Participants could be followed for up to 10 days after informed consent.
Clinical management followed local guidelines. The decision to treat or not treat was left to the investigator, and oseltamivir is the named intervention. Thus, the registry record describes treated and untreated participants but does not describe random allocation. Allocation is not stated, and these arms should not be read as a randomized, like-for-like comparison.
The primary outcome was reported by study year for participants with H3N2 or H1N1pdm09 infections. Only data from participants with evaluable data were reported. The registry lists 25 outcome measures and 15 analyses, but does not provide a full statistical plan, the analysis details for each measure, or the year-specific primary endpoint values. The population, schedule, and endpoint definition are documented more fully than the numerical results.
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
| Stage | All Participants Infected With Influenza |
|---|---|
| STARTED | 4561 |
| COMPLETED | 4312 |
| NOT COMPLETED | 249 |
Reasons for not completing this period:
| Reason | All Participants Infected With Influenza |
|---|---|
| Adverse Event | 2 |
| Withdrawal by Subject | 89 |
| Death | 3 |
| Lost to Follow-up | 143 |
| Other | 12 |
Analysis population for the primary outcome, as defined in the registry: All Laboratory-Confirmed Influenza Participants (ALCIP) Population: All with confirmed influenza by positive RT-PCR at Baseline. The "Number of Participants Analyzed" reflects the total of participants who provided evaluable data for their viral RNA subtype. The number who provided data for each viral RNA subtype in each timeframe (n) is shown.
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: All Enrolled Healthy Participants (AEHP) Population: All otherwise healthy participants who entered the study. Due to the imbalance between healthy (n=4553) and immunocompromised participants (n=8), results from immunocompromised participants were not included in any analyses, and data obtained from healthy participants were the focus of the study.
| Characteristic | Unit | Otherwise Healthy Participants Infected With Influenza |
|---|---|---|
| Participants analysed | 4553 | |
| Age, Continuous | years | 19.5 (SD 19.24) |
| Sex: Female, Male: Female | Participants | 2331 |
| Sex: Female, Male: Male | Participants | 2222 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants Exhibiting Treatment-Emergent Resistance by Study Year Among Participants With H3N2 or H1N1pdm09 Infections, measured over From Baseline (Day 1) to Day 10 (assessed on Days 1, 3, 6, 10) during Study Years 1, 2, 3, 4, 5, 6, 7.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with H3N2 or H1N1pdm09 infections who exhibited treatment-emergent resistance, reported by study year. Genotypic resistance was defined by the presence of predefined mutations in viral RNA. Treatment-emergent resistance required evidence of genotypic or phenotypic resistance in a post-Baseline sample when the Baseline sample had previously been non-resistant.
This endpoint is a proportion: it describes the share of participants with evaluable data who met the resistance definition, rather than a change in an individual clinical score or a time-to-event measure. Reporting it by study year is relevant to the study’s surveillance purpose because it organizes resistance findings across the study’s years. This is a general explanation of the measure; the registry record does not explain why this particular summary was selected over other possible summaries.
Only evaluable data were reported. The record says that the analyzed participants had an analyzable post-Baseline sample for their viral RNA subtype, while also noting that the number with evaluable data varied by subtype. The primary endpoint percentages and the corresponding year-specific denominators are not reported in the registry record. Consequently, the endpoint’s definition and intended population can be described, but its observed magnitude and precision cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clear surveillance question: whether participants with specified influenza subtypes developed evidence of resistance after a non-resistant Baseline sample, with results intended to be reported by study year. It does not include the year-specific percentages or the denominators behind them. The primary result’s magnitude, variation across study years, and precision are therefore not reported in the registry record.
The distinction between an endpoint definition and an endpoint result matters. The record explains which viral changes count as genotypic resistance and how post-Baseline resistance is classified as treatment-emergent. That definition does not reveal how often the event occurred. Without the reported percentages, evaluable participant counts by year and subtype, and measures of uncertainty, it is not possible to judge whether observed proportions were small or large, or how precisely they were estimated.
The study also describes treated and untreated participants, but treatment was at the investigator’s discretion and allocation is not stated. This is not a randomized comparison. In general, people who receive treatment may differ from those who do not in ways connected to clinical presentation or treatment decisions. A difference between the arms, if one were reported, would not by itself isolate an effect of oseltamivir. The registry record does not report a comparative estimate for the primary resistance endpoint.
For safety, the record lists 24 participants with serious adverse events among participants treated with oseltamivir and 11 among participants not treated with oseltamivir. The corresponding group sizes at risk are also listed, but these non-randomized groups should not be treated as directly comparable. The listed serious-event terms include pneumonia, dyspnoea, bronchitis, respiratory distress, pyelonephritis, and respiratory tract infection; the record gives percentages for these terms without enough detail to interpret them as a treatment comparison.
The posted information supports understanding the study’s surveillance design, endpoint definition, and selected safety counts. It does not support a conclusion about the frequency of treatment-emergent resistance by year, a causal treatment comparison, or the statistical significance of any difference. Those conclusions require numerical results and analysis details that are not reported in the registry record.
9. Statistical Methods Explained
What does a percentage endpoint represent?
General statistical explanation: a percentage is a proportion expressed on a percentage scale. Its interpretation depends on both the event definition and the participants included in its denominator. Here, the event is treatment-emergent resistance under the registry’s genotypic or phenotypic definition, and the endpoint is limited to evaluable participants with the specified viral subtypes. It is not a percentage of every person enrolled unless the analysis denominator happens to include every enrolled participant; the registry record does not report that it does.
The record specifies that an analyzable post-Baseline sample was needed for the relevant viral RNA subtype. That makes the endpoint conditional on having evaluable virological information. Participants without evaluable samples may not be represented in the reported endpoint. The year-specific denominators and the number excluded for lack of evaluable data are not reported in the registry record, so the potential effect of those exclusions cannot be quantified.
Why does the viral resistance definition matter?
The event is not defined simply as a positive test at any one visit. The record defines genotypic resistance through predefined mutations in viral RNA and defines treatment-emergent resistance as post-Baseline genotypic or phenotypic resistance after a previously non-resistant Baseline sample. This distinction is important because the endpoint concerns evidence emerging after Baseline, rather than resistance already identified at Baseline. The specific mutations, assay characteristics, and adjudication procedures are not reported in the registry record.
General statistical explanation: when an endpoint depends on repeated measurements, the timing and completeness of those measurements affect which events can be detected. The record lists sampling at Baseline and Days 3, 6, and 10, and the primary endpoint timeframe refers to Days 1, 3, 6, and 10. It does not describe how missing visits or discordant test results were handled.
How should study-year results be read?
The primary endpoint was intended to be reported by study year. A year-specific percentage would summarize the observed proportion in that year’s evaluable population, not necessarily the experience of every participant enrolled during that period. Comparisons across study years would need to account for the denominators and the precision of each estimate. Those values are not reported in the registry record, so no trend or year-to-year difference can be assessed from the posted results.
General statistical explanation: a confidence interval describes a range of values compatible with the data under a statistical method and its assumptions. It communicates uncertainty around an estimate; it does not guarantee that the true value lies in the interval. Confidence intervals for the primary endpoint are not reported in the registry record. Neither the estimation method nor any adjustment for clustering or repeated measurements is reported.
What can be inferred from the treatment groups?
The registry record distinguishes participants treated with oseltamivir and participants not treated with oseltamivir, but the decision to treat was made by the investigator and allocation is not stated. General statistical explanation: random allocation can help balance measured and unmeasured baseline factors between groups. Without it, differences between groups can reflect treatment selection and other group differences. An unadjusted contrast, even if available, would not alone establish that treatment caused a difference in resistance or clinical outcomes.
The record does not report a primary endpoint comparison between these treatment groups, nor does it report adjustment variables or an adjusted analysis. The study’s primary endpoint is described by study year among participants with specified subtypes, not as a randomized treatment contrast. A reader should keep the surveillance question distinct from a causal treatment-effect question.
What do the sample-size illustrations mean?
General statistical explanation: a sample-size calculation describes a planned design’s ability to detect an assumed effect under stated assumptions. It is not a measure of the power actually achieved after a study is complete. The registry-related planning illustrations use the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm for 80% power or for 90% power; time-to-event illustrations use a total number of events.
These are planning illustrations, not the trial’s own design justification and not observed power. The registry record does not report its sample-size justification or statistical plan. The assumptions alone cannot establish that the enrolled population was sufficient for the primary surveillance endpoint, especially because the primary analysis required evaluable subtype-specific post-Baseline samples. The numerical planning estimates are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 25 outcome measures and 15 analyses. A record with multiple outcomes or analyses raises a general multiplicity issue: the more statistical questions examined, the greater the possibility that some results may appear noteworthy by chance if many tests are considered together. Whether and how that concern was addressed depends on the prespecified analysis plan and any adjustment procedures. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or which analyses were confirmatory.
Missing data are relevant because the primary endpoint was reported only for evaluable participants. The record describes an analyzable post-Baseline sample for the viral RNA subtype as part of the analysis population. It also notes that the number with evaluable data differed by subtype. The counts by subtype and study year, reasons for missing or unevaluable samples, and methods for handling missing measurements are not reported in the registry record.
The primary population is named the ALCIP Population. The registry describes the analyzed participants as infected with H3N2 or H1N1pdm09 across study years who provided an analyzable post-Baseline sample for their viral RNA subtype. The full operational definition of the population and details of any exclusions are not reported in the registry record. Because the outcome is conditional on evaluability, the posted endpoint should not be interpreted as automatically representing all enrolled participants.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Participants Treated With Oseltamivir | 24 | 2578 | 0.9% |
| Participants Not Treated With Oseltamivir | 11 | 1975 | 0.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Participants Treated With Oseltamivir | 0 of 2578 |
| Participants Not Treated With Oseltamivir | 0 of 1975 |
Most frequent serious adverse event terms
| Event term | Organ system | Participants Treated With Oseltamivir | Participants Not Treated With Oseltamivir |
|---|---|---|---|
| Pneumonia | Infections and infestations | 5 of 2578 | 1 of 1975 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 3 of 2578 | 2 of 1975 |
| Bronchitis | Infections and infestations | 0 of 2578 | 2 of 1975 |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | 2 of 2578 | 0 of 1975 |
| Bronchiolitis | Infections and infestations | 1 of 2578 | 0 of 1975 |
| Bronchopneumonia | Infections and infestations | 1 of 2578 | 0 of 1975 |
| Cellulitis | Infections and infestations | 1 of 2578 | 0 of 1975 |
| Gastroenteritis | Infections and infestations | 1 of 2578 | 0 of 1975 |
| Gastrointestinal infection | Infections and infestations | 1 of 2578 | 0 of 1975 |
| Pneumonia staphylococcal | Infections and infestations | 1 of 2578 | 0 of 1975 |
Serious events with the highest arm-level rate: pneumonia (0.2%), dyspnoea (0.1%), bronchitis (0.1%), respiratory distress (0.1%), pyelonephritis (0.1%).
The registry record lists serious adverse events for participants treated with oseltamivir and participants not treated with oseltamivir. It reports 24 serious adverse events among 2578 participants at risk in the treated group, and 11 among 1975 participants at risk in the untreated group. These are descriptive counts from groups that were not randomly allocated according to the registry record; the treatment decision was at the investigator’s discretion. They should not be interpreted as a causal comparison or as evidence that treatment increased or decreased risk.
The record also lists pneumonia at 0.2%, and dyspnoea, bronchitis, respiratory distress, pyelonephritis, and respiratory tract infection at 0.1% each. The listed percentages are not accompanied by group-specific counts or further detail about their calculation, so they do not establish how the terms compare between treatment groups. The registry record does not report deaths for these groups. These safety entries describe what was recorded; they do not by themselves determine whether an event was caused by influenza, treatment, or another factor.
12. What the Result Does, and Does Not, Mean
The record establishes that IRIS was designed to monitor influenza antiviral resistance and clinical outcomes, with a primary resistance endpoint defined for participants with H3N2 or H1N1pdm09 infections. It provides the sampling schedule, the resistance definition, and the restriction to evaluable data. These details help explain what the study intended to measure and which observations could contribute to the primary endpoint.
The record does not report the year-specific primary endpoint percentages, their denominators, or uncertainty intervals. It therefore does not show how frequently treatment-emergent resistance was identified in the analyzed population, whether frequency differed across study years, or how precise any estimate was. The endpoint’s definition is not a substitute for its numerical results.
The presence of treated and untreated groups does not make the study a randomized treatment comparison. Treatment was decided by the investigator, and allocation is not stated. Any comparison between these groups would be vulnerable to differences associated with treatment selection. The posted information does not establish a causal effect of oseltamivir on resistance, viral RNA detection, clinical outcomes, or serious adverse events.
General statistical explanation: an observed proportion describes the analyzed sample, while inference to a wider population depends on how participants were selected, which observations were missing, and the uncertainty around the estimate. The record identifies evaluability as a condition for the primary analysis but does not report the information needed to assess those influences. In practical terms, the registry record is informative about the surveillance framework and selected safety reporting, but it is insufficient to quantify the primary resistance result or establish treatment effects.
13. Why This Trial Matters Statistically
Surveillance questions and treatment-effect questions are statistically different. IRIS was intended to monitor antiviral resistance over study years and by influenza subtype, while treatment decisions remained with investigators. This distinction matters because a surveillance estimate can describe the occurrence of a defined outcome in an evaluable population without establishing what caused that outcome.
The endpoint also makes the analysis population central to interpretation. Treatment-emergent resistance requires both a non-resistant Baseline sample and a post-Baseline sample showing resistance under the stated definition. A participant without the necessary evaluable samples cannot be classified in the same way as a participant with complete virological information. Reporting how many people contribute to each estimate, and how their information differs from that of people without evaluable data, is therefore important to judging representativeness.
The registry record provides a detailed endpoint definition and schedule, but does not report the year-specific estimates, denominators, or precision. That gap illustrates a broader statistical principle: a well-defined outcome does not by itself communicate the size or reliability of an observed result. Likewise, a comparison between treated and untreated participants does not become causal merely because both groups are reported. Allocation and analysis methods are essential to that interpretation.
For clinical researchers, the record is a reminder to distinguish protocol aims, endpoint definitions, observed results, and causal conclusions. Each answers a different question. Here, the aims and definitions are described, while the key numerical primary results and detailed analysis plan are not reported in the registry record.
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 most important limitation for interpreting the primary endpoint is that its year-specific percentages and denominators are not reported in the registry record. Without those values, the frequency of treatment-emergent resistance, variation across study years, and precision of estimates cannot be evaluated. The number of enrolled participants does not resolve this limitation because the primary analysis required evaluable subtype-specific post-Baseline data.
The primary population was restricted to participants with H3N2 or H1N1pdm09 infections and evaluable viral RNA data. The record notes that evaluable participant counts differed by subtype, but does not report the relevant counts by subtype and study year or explain the reasons for unevaluable data. This prevents assessment of how missing or unavailable samples may have influenced the analyzed percentages.
The treatment groups were not described as randomly allocated, and treatment decisions were made by investigators. The record therefore does not support treating the groups as a balanced comparison. Baseline characteristics, confounding adjustment, and comparative estimates for the primary endpoint are not reported in the registry record.
Other relevant methodological details are also absent: the statistical analysis plan, confidence intervals, multiplicity procedures, and methods for handling missing measurements are not reported in the registry record. The registry’s description of predefined mutations does not identify the mutations or provide assay-performance details. These omissions limit assessment of both the measurement process and the statistical uncertainty around the reported outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Influenza Resistance Information Study — NCT00884117.
- Registry record last updated 2016-10-19; status last verified 2016-10.
- Results first posted 2016-07-19.
- 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.
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18. Record Summary
NCT00884117, the Influenza Resistance Information Study (IRIS), was sponsored by Hoffmann-La Roche and is listed as completed. The registry record gives enrollment of 4561, a start date of 2009-01, and a primary completion date of 2015-11. It describes influenza surveillance in adults and children, including viral sampling at Baseline and follow-up assessments on Days 3, 6, and 10.
The primary endpoint concerns the percentage of evaluable participants with H3N2 or H1N1pdm09 infections who exhibited treatment-emergent resistance, reported by study year. The resistance definition requires post-Baseline evidence after a non-resistant Baseline sample. The primary endpoint percentages and year-specific denominators are not reported in the registry record.
The registry lists 25 outcome measures and 15 analyses. It also reports serious adverse-event counts for participants treated and not treated with oseltamivir. Treatment allocation is not stated, and the treatment groups are not a like-for-like control comparison.