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 Safety Study of Oral Pirfenidone in Patients With Pulmonary Fibrosis/Idiopathic Pulmonary Fibrosis (NCT00080223), a na phase 2 study. The primary outcome is Percentage of Participants With a Treatment-Emergent Adverse Event (AE), Serious AE (SAE), Severe AE, Life-threatening AE, Death or Discontinuation Because of an AE.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00080223 |
| Phase | Phase 2 |
| Condition | Idiopathic Pulmonary Fibrosis, Pulmonary Fibrosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 83 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genentech, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled participants with pulmonary fibrosis or idiopathic pulmonary fibrosis. The primary safety population was all treated participants; the registry record lists 83 participants at risk in the pirfenidone group. The record does not report further eligibility details in the information available for this analysis.
Intervention
Participants received oral pirfenidone, up to 3600 mg per day, in divided doses three times daily with food. Treatment continued for the duration of the study. The maximum treatment duration reported in the primary endpoint timeframe was 604 weeks.
Comparator
There was no comparator group. This was a single-group, open-label study, and the allocation field is listed as not applicable. The safety counts therefore describe participants receiving pirfenidone; they are not a randomized comparison with an untreated or alternative-treatment group.
Primary question
The primary question was how often treated participants experienced a treatment-emergent adverse event, serious adverse event, severe adverse event, life-threatening adverse event, death, or discontinuation because of an adverse event. The registry record reports a serious-event count of 49 among 83 at risk and lists 81 participants in the other adverse-event category. It does not report a separate result for every component named in the primary endpoint.
3. Trial Design
This was a phase 2, open-label, single-group study of oral pirfenidone in participants with pulmonary fibrosis or idiopathic pulmonary fibrosis. The registry record lists Genentech, Inc. as sponsor, an enrollment of 83, and a completed status. The recorded start date is 2003-08-31 and the primary completion date is 2015-04-30. These dates describe the registry record; they do not establish how long any particular participant was followed.
All participants received pirfenidone, at a dose of up to 3600 mg per day, orally in divided doses three times daily with food. The record describes treatment as continuing for the duration of the study. The primary safety timeframe extended from baseline to 28 days after the last dose, and the maximum treatment duration reported was 604 weeks.
Open-label means the study was not masked. A single-group design has no concurrent control arm, and the registry record lists allocation as not applicable. Consequently, the results can describe adverse events recorded among treated participants but cannot directly estimate how those event rates compare with a separate control group. The record does not report a randomized allocation process, a masking procedure, or a comparator treatment.
The secondary outcomes named in the record include percent-predicted forced vital capacity, hemoglobin-corrected percent-predicted carbon monoxide diffusing capacity, resting oxygen saturation by pulse oximetry, and overall survival. Statistical analyses for these outcomes are not reported in the registry record. The registry record also does not report a protocol-level statistical plan or a sample-size justification.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Participants could enroll from Study PIPF-001 (a double-blind comparison of pirfenidone and prednisone in pulmonary fibrosis); individual-patient protocols (IPPs); investigator-sponsored Investigational New Drug applications (INDs) in idiopathic pulmonary fibrosis (IPF); and via an early access program (EAP) for participants with IPF.
Overall Study
| Stage | Pirfenidone |
|---|---|
| STARTED | 83 |
| COMPLETED | 7 |
| NOT COMPLETED | 76 |
Reasons for not completing this period:
| Reason | Pirfenidone |
|---|---|
| Adverse Event | 23 |
| Death | 21 |
| Withdrawal by Subject | 13 |
| Lung Transplantation | 9 |
| Non-compliance With Study Treatment | 7 |
| Participant unwilling to continue | 2 |
| Physician Decision | 1 |
Analysis population for the primary outcome, as defined in the registry: All treated participants
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 treated participants
| Characteristic | Unit | Pirfenidone |
|---|---|---|
| Participants analysed | 83 | |
| Age, Continuous | years | 68.5 (SD 9.15) |
| Sex: Female, Male: Female | Participants | 23 |
| Sex: Female, Male: Male | Participants | 60 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With a Treatment-Emergent Adverse Event (AE), Serious AE (SAE), Severe AE, Life-threatening AE, Death or Discontinuation Because of an AE, measured over Baseline to 28 days after the last dose of study treatment (maximum duration of treatment in study was 604 weeks).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint concerns the percentage of participants experiencing one or more of several safety outcomes: a treatment-emergent adverse event, serious adverse event, severe adverse event, life-threatening adverse event, death, or discontinuation because of an adverse event. The record defines the analysis population as all treated participants and sets the observation window from baseline through 28 days after the last dose.
An adverse event was defined as an untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent events included events beginning on or after the first dosing day through the post-treatment window, as well as events present before treatment that worsened after the first dose. The definition includes serious and non-serious events.
A serious adverse event was defined by outcomes such as death, initial or prolonged inpatient hospitalization, an immediately life-threatening experience, persistent or significant disability or incapacity, or congenital anomaly; an event could also be considered serious for another significant reason. Severe events were described as Grade 3, involving marked activity limitation, usual need for some assistance, or medical intervention or therapy, with hospitalization possible.
As a general statistical concept, a participant-level percentage provides a simple way to describe how common an event was in the observed study group. The endpoint is used to summarize safety experience, but grouping several different outcomes does not make them equally serious or clinically interchangeable. Separate component results would be needed to understand each outcome on its own. Individual results for all named components are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes adverse events in a single group treated with pirfenidone. It lists 49 participants with a serious adverse event among 83 at risk. It also lists 81 participants in the other adverse-event category. These are observed counts in the study group, not comparisons against another treatment or a control group. The record does not provide a separate result for every component of the primary endpoint, including severe events, life-threatening events, deaths, or discontinuations because of an adverse event.
The serious adverse-event terms listed with percentages include idiopathic pulmonary fibrosis (18.1%), pneumonia (10.8%), respiratory failure (7.2%), atrial fibrillation (4.8%), dyspnoea (4.8%), and coronary artery disease (3.6%). These percentages describe listed serious-event terms, not necessarily mutually exclusive groups of participants. A participant may have experienced more than one event; the registry record does not report whether the listed terms overlap or provide the full event-level detail needed to assess that.
Because the study had no comparator group, these figures cannot distinguish events associated with the treatment from events that might have occurred in the underlying condition or for other reasons. The adverse-event definition attributes events to study drug, but attribution in an open-label single-group study is not the same as a randomized estimate of a treatment effect. No causal comparison should be inferred from the counts alone.
The primary endpoint gives a participant-level safety summary across several types of events. A composite can capture a range of outcomes, but its overall frequency does not show which component contributed most. Nor does an aggregate count show event timing, duration, recurrence, or clinical course. Those details are not reported in the registry record.
The registry record does not report confidence intervals, hypothesis tests, adjusted estimates, or statistical analyses for the posted results. The counts therefore support a descriptive reading of the observed safety experience, not a precise comparison or a claim about relative risk. The listed percentages for serious-event terms offer further descriptive detail, but they do not resolve the limitations created by the absence of a comparator and event-level information.
9. Statistical Methods Explained
What does a participant-level percentage describe?
A participant-level percentage describes the share of the analyzed group who experienced a specified outcome during the defined observation window. It counts people with the event rather than the total number of event episodes. This distinction matters when a person can experience repeated events: a participant-level measure does not, by itself, describe how many episodes occurred or how long events lasted.
In this study, the primary endpoint is expressed as a percentage of participants, and the population is all treated participants. The registry record lists 83 at risk for the pirfenidone group and reports 49 participants with a serious adverse event. It also lists 81 in the other adverse-event category. The record does not state separate participant-level results for each primary-endpoint component. No additional percentages should be inferred from those counts.
Why define treatment-emergent events?
The treatment-emergent definition sets a period for counting events in relation to treatment. Here, it includes events arising on or after the first dosing day through 28 days after discontinuation, as well as pre-existing events that worsened after the first dose. This helps make explicit which events are included in the safety summary. It does not establish that treatment caused an event. In general, timing and attribution are distinct questions: an event can meet a treatment-emergent definition without proving a causal relationship.
The registry record also defines serious and severe events separately. Seriousness is based on specified outcomes or significance, while severity describes the intensity or functional impact of an event. General statistical and clinical usage does not treat these labels as interchangeable. The record’s Grade 3 description includes marked activity limitation, some assistance usually required, or medical intervention or therapy, with hospitalization possible.
What can a single-group design estimate?
In general, a single-group study can describe the observed frequency of outcomes in the group studied. It does not provide a concurrent comparison that would show how outcomes differ under another treatment or without the study treatment. This study was open-label and single-group, with allocation listed as not applicable. As a result, differences from an external population would be vulnerable to differences in participant characteristics, observation, and other circumstances. The registry record does not report an external comparison or an adjusted comparative analysis.
Randomization, when used, supports a fair comparison by assigning participants to treatment groups through a chance process. Masking can reduce some influences on reporting or assessment. Neither a randomized comparison nor masking is reported for this study. That does not prevent descriptive reporting, but it limits what can be concluded about treatment-attributable differences.
How should uncertainty be considered?
General statistical context: a confidence interval describes a range of values compatible with the observed data under a specified statistical model. It helps communicate precision, rather than only presenting a point estimate. A statistical test addresses a defined hypothesis under stated assumptions. Neither a confidence interval nor a test removes design limitations, and neither establishes causation in a single-group study.
Confidence intervals and hypothesis tests for the primary safety results are not reported in the registry record. The record also does not report an adjusted model or a statistical analysis plan. The posted counts and event-term percentages should therefore be read as descriptive rather than as estimates accompanied by a reported measure of statistical precision.
What do planning illustrations mean?
General statistical context: sample-size planning asks how many participants a future comparison might need under specified assumptions about the effect to detect, the significance level, allocation, and statistical method. Such a calculation is prospective. It is not a measure of the probability that the completed study detected an effect, and it does not substitute for a treatment comparison.
The planning assumptions associated with the record describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with planning effects expressed as fractions of an observed effect. These are planning assumptions, not evidence that this single-group trial used two arms or those assumptions in its own design. The study itself is recorded as single-group, and a protocol-based sample-size justification is not reported in the registry record. Any such planning result is an illustration, not observed power.
In general, over-dispersion means that variability is greater than a model assumes; if ignored, it can make uncertainty appear smaller than it is. The primary outcome is a participant-level binary event measure, and dispersion information is not reported in the registry record. There is no basis in the record for adding an over-dispersion adjustment or claiming that one was used.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when several outcomes, comparisons, time points, or statistical tests are examined. In general, repeated testing can increase the chance of at least one apparently notable result unless the analysis plan addresses that issue. The registry record names a primary safety endpoint and secondary outcomes involving lung function, oxygen saturation, and overall survival. It does not report a multiplicity procedure, a hierarchy among secondary outcomes, or a set of statistical tests. Statistical analyses for the secondary outcomes are not reported in the registry record.
The registry record does not report a statistical analysis plan describing how missing outcome data were handled. It does not state whether there were missing observations, whether participants were excluded from particular outcome summaries, or how incomplete follow-up affected each analysis. The primary endpoint population is described as all treated participants, and the adverse-event summary lists 83 at risk. The record does not provide further detail on missing-data rules or participant-level follow-up.
Analysis populations can differ: for example, a safety summary may include treated participants, while an efficacy analysis may use another defined group. The stated primary population is all treated participants. Separate analysis populations for the secondary outcomes are not reported in the registry record. Without those definitions and missing-data details, the scope of any result beyond the stated safety population cannot be assessed.
These omissions do not change the descriptive counts that are posted, but they limit evaluation of how comprehensively outcomes were assessed and how selective reporting or incomplete observations may affect interpretation. The registry record does not report interim analyses or other planned looks at accumulating data.
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 |
|---|---|---|---|
| Pirfenidone | 49 | 83 | 59.0% |
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 |
|---|---|
| Pirfenidone | 81 of 83 |
Most frequent serious adverse event terms
| Event term | Organ system | Pirfenidone |
|---|---|---|
| Idiopathic pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | 15 of 83 |
| Pneumonia | Infections and infestations | 9 of 83 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 6 of 83 |
| Atrial fibrillation | Cardiac disorders | 4 of 83 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 4 of 83 |
| Coronary artery disease | Cardiac disorders | 3 of 83 |
| Bronchitis | Infections and infestations | 3 of 83 |
| Cardiac failure congestive | Cardiac disorders | 2 of 83 |
| Myocardial infarction | Cardiac disorders | 2 of 83 |
| Colitis ischaemic | Gastrointestinal disorders | 2 of 83 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pirfenidone |
|---|---|---|
| Nausea | Gastrointestinal disorders | 40 of 83 |
| Fatigue | General disorders | 27 of 83 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 23 of 83 |
| Upper respiratory tract infection | Infections and infestations | 21 of 83 |
| Cough | Respiratory, thoracic and mediastinal disorders | 21 of 83 |
| Idiopathic pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | 21 of 83 |
| Weight decreased | Investigations | 18 of 83 |
| Rash | Skin and subcutaneous tissue disorders | 16 of 83 |
| Insomnia | Psychiatric disorders | 15 of 83 |
| Decreased appetite | Metabolism and nutrition disorders | 14 of 83 |
Serious events with the highest arm-level rate: idiopathic pulmonary fibrosis (18.1%), pneumonia (10.8%), respiratory failure (7.2%), atrial fibrillation (4.8%), dyspnoea (4.8%).
The safety summary lists 49 participants with a serious adverse event among 83 at risk in the pirfenidone group. It also lists 81 participants in the other adverse-event category. These are counts, not a comparison with a control group, and the registry record does not provide a separate percentage for every component of the primary endpoint. A death count is not reported in the safety summary.
The serious-event terms and percentages listed include idiopathic pulmonary fibrosis (18.1%), pneumonia (10.8%), respiratory failure (7.2%), atrial fibrillation (4.8%), dyspnoea (4.8%), and coronary artery disease (3.6%). These terms describe reported serious events; the percentages do not establish that each term occurred in a distinct participant. The registry record does not report how the terms overlap, the number of episodes, or event timing and duration.
As a general point, a serious adverse event is classified by its consequences or significance, whereas severity concerns intensity. The registry record defines these categories separately. A serious-event count should not be read as a count of all severe events, deaths, or treatment discontinuations. Separate results for those outcomes are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The results describe safety events recorded among participants treated with pirfenidone in an open-label, single-group phase 2 study. The registry record reports 49 participants with a serious adverse event among 83 at risk and lists 81 in the other adverse-event category. It also gives percentages for selected serious-event terms. These results summarize what was recorded in this study population during the specified safety window.
They do not establish what would have happened to the same participants under a different treatment or without pirfenidone. With no comparator group, the study cannot provide a randomized estimate of the difference attributable to treatment. The event definition and timing help specify which events were counted, but they do not independently establish causation.
The primary endpoint combines several types of safety outcome. A combined measure does not show how many participants experienced each component unless component-specific results are available. The registry record does not report separate results for all named components, including severe events, life-threatening events, deaths, and discontinuations because of an adverse event. It also does not report event-level details that would describe recurrence, duration, or overlap between serious-event terms.
Precision cannot be evaluated from the posted counts alone because confidence intervals and statistical tests are not reported in the registry record. The listed percentages offer descriptive information, not a comparison or a measure of uncertainty. Overall, the record supports a description of observed safety events in the treated group, while leaving comparative effects and several component-level details unreported.
13. Why This Trial Matters Statistically
This trial illustrates a basic distinction in clinical statistics: describing an event rate is not the same as estimating a treatment effect. A single-group safety study can document events among treated participants and define a window in which those events were counted. It cannot, by itself, show how those observations differ from outcomes under another treatment or in an untreated group.
The endpoint also shows why safety measures need careful interpretation. Treatment-emergent events, serious events, and severe events are defined in different ways. A broad endpoint can bring several important outcomes into one summary, but a combined result can obscure which component occurred and how often. Component-specific reporting is needed for a fuller account, and several component results are not reported in the registry record.
The registry record includes definitions for adverse events and a specified post-treatment observation period. Those details make the intended counting window clearer. At the same time, the absence of reported confidence intervals, hypothesis tests, and a statistical analysis plan limits assessment of precision and analytic choices. These are distinct limitations: clear outcome definitions do not replace a comparison group or reported statistical uncertainty.
Finally, the record provides a setting for distinguishing study design from planning assumptions. The study is recorded as open-label and single-group, while the planning assumptions describe a hypothetical equal-allocation comparison. A planning illustration cannot change the completed study’s design or serve as observed power. Keeping that distinction clear helps prevent planning calculations from being mistaken for trial findings.
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 design limitation is the absence of a comparator group. Because this was a single-group, open-label study, the observed adverse-event counts cannot be used as a randomized comparison or to isolate the effect of pirfenidone from other explanations. The registry record does not report masking, and it does not describe a control treatment.
The primary endpoint includes multiple categories, but separate results for every component are not reported in the registry record. The safety summary gives a serious-event count and an additional count in an other adverse-event category; it does not provide a death count. Event-level information on recurrence, duration, timing, or overlap among the serious-event terms is also not reported in the registry record.
The registry record does not report confidence intervals, hypothesis tests, an adjusted analysis, or the statistical analysis plan. It does not report how missing data were handled or whether missing observations affected particular outcomes. These gaps make precision and analytic decisions difficult to evaluate.
The primary timeframe includes follow-up through 28 days after the last dose, with a maximum treatment duration of 604 weeks. The record does not give participant-level treatment or follow-up durations, so the maximum should not be interpreted as the duration for every participant. The registry record also does not report a protocol-based sample-size justification or interim-analysis plan.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety Study of Oral Pirfenidone in Patients With Pulmonary Fibrosis/Idiopathic Pulmonary Fibrosis — NCT00080223.
- Registry record last updated 2017-04-17; status last verified 2017-03.
- Results first posted 2016-03-09.
- 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
NCT00080223 is a completed, open-label, phase 2, single-group study of oral pirfenidone in participants with pulmonary fibrosis or idiopathic pulmonary fibrosis. The registry record lists an enrollment of 83 and identifies Genentech, Inc. as sponsor. Pirfenidone was given in divided oral doses three times daily with food, up to 3600 mg per day.
The primary endpoint assessed treatment-emergent adverse events, serious and severe events, life-threatening events, death, and discontinuation because of an adverse event, from baseline through 28 days after the last dose. The safety summary reports 49 participants with a serious adverse event among 83 at risk and lists 81 in the other adverse-event category. A comparator group is not reported, and statistical analyses and measures of uncertainty are not reported in the registry record.