Investigating Trends in Quality of Life in Patients With Idiopathic Pulmonary Fibrosis (IPF) Under Treatment With Nintedanib: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigating Trends in Quality of Life in Patients With Idiopathic Pulmonary Fibrosis (IPF) Under Treatment With Nintedanib (NCT03710824), a registered phase not stated study. The primary outcome is Mean Change From Baseline in Health Related Quality of Life (HRQoL) Using SGRQ Score at 3 Months.

2. Clinical Question

The study was designed to follow quality of life over time among people with IPF who were receiving nintedanib. Its main endpoint focuses on change in the SGRQ total score between baseline and 3 months. The questionnaire also produces scores for symptoms, activity, and psychosocial impact. Higher scores indicate worse health-related quality of life, so the direction of a reported change would matter to interpretation. The registry defines change as the post-baseline value minus the baseline value.

This is an observational question about outcomes during treatment, not a randomized test comparing nintedanib with an untreated or alternative-treatment group. Without a comparison group, changes cannot by themselves distinguish treatment-associated change from the course of IPF, other care, or other influences over time. The registry record does not report a primary endpoint result, so the size, direction, and precision of the change cannot be assessed from the posted information.

3. Trial Design

The registry describes a multicenter, non-interventional, prospective cohort study of people with idiopathic pulmonary fibrosis receiving nintedanib. The brief summary says patients were to be enrolled consecutively from 10-12 reference centers across Greece. Enrollment in the registry is 180, while the brief summary states an aim to enroll 240. These are distinct figures: one is the recorded enrollment and the other is the stated aim.

The recorded study start is 2019-02-28, the primary completion date is 2023-02-22, and the status is COMPLETED. Boehringer Ingelheim is identified as the sponsor. Nintedanib is the only intervention listed, and the registry lists a single group for patients with IPF. Allocation is not stated; this is not a randomized comparison, and there is no separate control group described.

The primary outcome is mean change from baseline in SGRQ score at 3 months. The listed timeframe is baseline and 3 months. The registry also names secondary outcomes concerning dyspnoea measured with mMRC, cough burden measured with Cough-VAS, adherence measured with SMAQ, anxiety measured with GAD-7, and use of long-term oxygen treatment. It lists nine outcome measures overall, but the record does not provide results for these outcomes.

The primary endpoint description specifies analysis in a treated set: enrolled participants who received nintedanib at least once during the trial. The record says that primary, secondary, and safety endpoint analyses were performed in that set. However, the posted information does not give a primary endpoint estimate, an analysis-specific participant count, or a complete account of participant flow. The record’s description of the number analyzed refers to participants with available data at a time point, but further details about that count 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.

Before assignment: Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Treatment interruption and dose reduction were allowed as medically indicated. Rescue medication was allowed for all subjects as required.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Treated Set (TS): all patients who were enrolled in the trial and have received at least once nintedanib during the trial. Any analysis on primary, secondary and safety endpoints was performed in the TS. The number of participants analysed displays the number of participants with available data at the timepoint of interest, at 3 months.

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: Treated Set (TS): all patients who were enrolled in the trial and have received at least once nintedanib during the trial. Any analysis on primary, secondary and safety endpoints was performed in the TS.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Health Related Quality of Life (HRQoL) Using SGRQ Score at 3 Months, measured over At baseline and at 3 months..

The primary endpoint is mean change from baseline in health-related quality of life, measured with the St. George’s Respiratory Questionnaire (SGRQ) score at 3 months. The SGRQ is a self-completed, 50-item questionnaire assessing symptoms, activity, and psychosocial impact. Symptoms concern the frequency and severity of respiratory symptoms; activity concerns activities that cause or are limited by breathlessness; and psychosocial impact covers aspects of social functioning and the psychological impact of disease.

The total score and each domain score range from 0 to 100, with higher scores indicating worse health-related quality of life. Change is defined as the post-baseline score minus the baseline score. This direction convention is important: the sign of a change is interpretable only alongside the score scale and the definition of change.

Health-related quality of life is relevant to this study because IPF can affect symptoms, activity, and psychosocial well-being, and the study’s stated aim concerns trends in quality of life during nintedanib treatment. A baseline-to-follow-up measure can describe how scores vary over the observation period. It does not, on its own, establish why a score changed. The registry describes a least-squares mean and a 95% confidence interval for the primary endpoint, but neither the estimate nor the interval is reported in the registry record. Thus, the endpoint’s measurement and planned analysis are described, while the observed result is unavailable.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

For this endpoint, each participant’s change is defined as the post-baseline SGRQ score minus the baseline score. The mean change summarizes the average direction and size of change across the participants included in the analysis. Because higher SGRQ scores indicate worse health-related quality of life, the scale’s direction must be considered when interpreting a reported change. A mean is a group summary; it does not imply that every participant experienced the same change.

The registry specifies a least-squares mean rather than simply describing an unadjusted average. In general, a least-squares mean is an estimate from a statistical model, calculated while accounting for factors included in that model. It can therefore differ from a raw average. Here, the model is described, but the estimated mean change is not reported in the registry record.

What does the confidence interval add?

A confidence interval expresses uncertainty around an estimated quantity. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. The registry specifies a 95% confidence interval for the primary outcome, but does not give its endpoints. It is therefore not possible to assess the precision of the estimated change, or to determine from the posted record whether the interval includes values consistent with no change.

A confidence interval is not a measure of how many participants improved, nor does it show the range of individual participant outcomes. It concerns uncertainty in the estimated group quantity. Even with an interval, interpretation would depend on the estimate, outcome scale, study design, and clinical context. In this record, the missing estimate and interval prevent those assessments.

Why use a mixed model?

The primary description identifies a mixed model analysis with fixed effects for visit, baseline GAP stage, baseline FVC category, baseline DLCO category, number of comorbidities, and an interaction between baseline score and visit. In general, mixed models can account for measurements that are related because they come from the same participant, and can estimate patterns across visits while incorporating specified covariates. The registry description does not provide enough detail to establish the exact model structure beyond the listed fixed effects, so additional features should not be assumed.

The baseline-score-by-visit interaction allows the modeled association between baseline score and the outcome to vary by visit. In general, interactions represent the possibility that one relationship differs according to another variable. The registry does not report model coefficients, fit diagnostics, or the extent to which each term contributed to the estimate. It also does not report whether alternative model specifications were considered.

Why does over-dispersion matter in general?

For count outcomes, over-dispersion means that observed variability exceeds what a simple model assumes. When present, it can make standard errors too small if the model does not account for the extra variability, and uncertainty may then be understated. This concept is general and is not a finding about the primary SGRQ analysis. The primary endpoint is a continuous score, and the registry does not report a count model or an over-dispersion assessment.

How should study design shape the statistical reading?

This is a prospective, non-interventional cohort, not a randomized comparison. In general, prospective follow-up can record outcomes over time, but a within-cohort change does not isolate the effect of treatment from other changes occurring during the same period. No separate comparator is described in the registry record, and allocation is not stated. Statistical adjustment for the listed baseline factors can address only the variables and model relationships actually included; it cannot by itself turn an observational cohort into a randomized trial.

The primary outcome is defined at 3 months, but the record does not report the number of participants with an observed SGRQ value at that visit or the endpoint estimate. A statistical model can produce an estimate only from data and assumptions; the posted description does not provide enough information to assess how missing observations were handled. The specific missing-data method, including any imputation or sensitivity analysis, is not reported in the registry record.

Sample-size planning illustrations, when presented, are not observed results and should not be interpreted as power achieved by the completed cohort. The registry record does not report a sample-size justification for the trial or an observed-power analysis. Nor does it report a plan for interim analyses. These omissions leave the planned operating characteristics and monitoring strategy unknown, rather than establishing that no such procedures existed.

Finally, the registry lists nine outcome measures and multiple secondary outcomes. In general, evaluating multiple outcomes raises the question of multiplicity: whether and how the risk of false-positive findings across several tests is controlled. The registry does not report an adjustment strategy or a hierarchy among outcomes. Since outcome estimates and tests are also absent, neither the individual findings nor their joint interpretation can be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists nine outcome measures, including the primary SGRQ change outcome and secondary outcomes concerning dyspnoea, cough burden, adherence, anxiety, and long-term oxygen treatment. Assessing multiple outcomes can raise multiplicity concerns: when many hypotheses are tested, the chance of at least one apparently notable result can increase. The registry record does not report a multiplicity adjustment, a testing hierarchy, or another approach for interpreting results across outcomes. Because the outcome results are not reported, the practical effect of any multiplicity strategy cannot be assessed.

The analysis population is described as a treated set comprising enrolled participants who received nintedanib at least once during the trial. The registry says primary, secondary, and safety endpoint analyses were performed in this set. The primary outcome description also notes that the number analyzed refers to participants with available data at a time point, but an analysis-specific count is not reported in the registry record. The number enrolled should therefore not be treated as the number contributing to every endpoint.

The record does not report how missing SGRQ measurements were handled, whether participants with incomplete follow-up were excluded, or whether imputation or sensitivity analyses were used. It also does not report reasons for missing measurements or outcome-specific follow-up counts. These details matter because an available-data analysis may represent a subset of the enrolled cohort, and the characteristics of that subset can affect interpretation.

The mixed model and its listed fixed effects are described, but this alone does not establish how missing observations were treated or what assumptions were made about them. The registry record also does not report interim analyses or a statistical analysis plan that would clarify these issues. Accordingly, the analysis population is partly described, while the missing-data procedures and multiplicity strategy are not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: idiopathic pulmonary fibrosis (1.1%), disease progression (1.1%), cardiac arrest (0.6%), cardio-respiratory arrest (0.6%), myocardial infarction (0.6%).

The safety listing gives 180 participants at risk for serious events and 10 affected, and 180 at risk for other events and 12 affected. It also records 8 deaths. These are counts in the registry’s safety summary; the record does not provide further detail about event timing, individual participants, follow-up duration, or the relationship of each event to treatment. The counts alone do not establish that nintedanib caused an event or death.

The serious-event terms listed with percentages are idiopathic pulmonary fibrosis (1.1%), disease progression (1.1%), cardiac arrest (0.6%), cardio-respiratory arrest (0.6%), myocardial infarction (0.6%), and COVID-19 (0.6%). The listed terms and percentages describe the registry’s reported entries, not a complete account of clinical circumstances or causality. Some terms refer to the underlying disease or its progression, which makes it especially important not to read the listing as a causal attribution.

The registry provides no comparator group, so the safety counts cannot support a like-for-like estimate of comparative risk. It also does not report detailed event narratives or a causal assessment. These entries should therefore be read as descriptive safety information for the recorded group, not as proof that treatment did or did not produce particular outcomes.

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

The record establishes that a completed, prospective, non-interventional cohort study examined people with IPF receiving nintedanib and identified change in SGRQ score at 3 months as its primary outcome. It describes the questionnaire, the direction of its scale, a treated-set analysis population, and a mixed model with specified fixed effects. Those elements define the question and outline the planned statistical approach.

However, the primary mean change and its 95% confidence interval are not reported in the registry record. The posted information therefore does not establish whether SGRQ scores increased, decreased, or remained similar on average, how large any change was, or how precisely it was estimated. It also does not permit an assessment of the statistical or clinical importance of the primary outcome.

Even if the numerical within-cohort change were available, the study design would constrain what it means. No randomized comparator or separate control group is described. A before-and-after pattern in a cohort receiving treatment cannot by itself determine what would have happened without treatment or under another treatment. The model’s adjustment for listed baseline factors does not remove all possible differences or influences that may affect outcomes.

The enrollment figure is 180, while the brief summary describes an aim to enroll 240. The number with usable primary outcome data is not reported, and missing-data procedures are not described. This prevents a reader from assessing endpoint completeness and how the analyzed participants relate to all enrolled participants.

The safety entries are descriptive counts and event terms. Without a comparator and further information on timing or causality, they do not establish comparative safety or attribute events to treatment. Overall, the registry record supports a careful description of the study’s design and intended measurements, but not a conclusion about the observed primary result or treatment effect.

13. Why This Trial Matters Statistically

This study raises a useful statistical distinction between measuring change during treatment and estimating a treatment effect. A prospective cohort can describe outcomes over time among people receiving a treatment. Without a randomized or otherwise suitable comparison group, however, observed change cannot by itself distinguish treatment-related effects from disease course, other care, or other influences. The design determines the scope of the conclusion as much as the choice of model does.

The primary endpoint also illustrates why outcome definitions matter. SGRQ scores run from 0 to 100, higher values indicate worse health-related quality of life, and change is defined as post-baseline minus baseline. Those details are essential to interpreting the direction of any reported estimate. The least-squares mean and confidence interval would add an adjusted summary and information about precision, but neither numerical result is reported in the registry record.

Participant counts require similar care. The record lists enrollment of 180 and a stated aim of 240, but endpoint-specific numbers with available measurements are not reported. The enrolled cohort, treated analysis population, and participants contributing data at a given time point need not be identical. Clear participant flow and missing-data methods are important for judging how representative an analysis may be.

Finally, the registry names multiple outcomes without describing a multiplicity strategy or reporting estimates. This highlights the importance of a transparent analysis plan when several domains and secondary outcomes are assessed. In this case, the record documents the intended questions and some statistical methods, while leaving the key outcome findings and important analytic details unavailable. That distinction helps prevent design descriptions from being mistaken for evidence of an observed result.

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 primary limitation for interpreting this study is that the registry record does not report the primary SGRQ estimate or its confidence interval. Although the outcome and model are described, the absence of results precludes evaluation of the observed direction, magnitude, and precision of change. Results for the listed secondary outcomes are also not reported in the record.

The non-interventional cohort design and lack of a separate comparator limit causal interpretation. The record describes participants receiving nintedanib, but no randomized control group or alternative-treatment group. Observed changes over time therefore cannot be attributed to treatment on the basis of this record alone.

The registry reports enrollment of 180, while the brief summary states an aim to enroll 240. It does not provide the number contributing SGRQ measurements at baseline and 3 months, a complete participant flow, or reasons for unavailable data. Missing-data handling and sensitivity analyses are not reported. These omissions make it difficult to judge outcome completeness and the potential influence of selective follow-up.

The record describes fixed effects for visit, baseline GAP stage, baseline FVC category, baseline DLCO category, number of comorbidities, and baseline score by visit interaction, but does not provide model estimates, diagnostics, or further detail about model specification. It does not report a multiplicity strategy despite listing nine outcome measures, nor does it report a sample-size justification or interim analysis plan. The record’s safety counts also lack detailed timing and causality information. These are limitations of what can be interpreted from the registry record; unreported details should not be presumed absent from study conduct.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Investigating Trends in Quality of Life in Patients With Idiopathic Pulmonary Fibrosis (IPF) Under Treatment With Nintedanib — NCT03710824.
• Registry record last updated 2024-07-31; status last verified 2024-02.
• Results first posted 2024-07-31.
• 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

NCT03710824 is a completed, prospective, non-interventional cohort study sponsored by Boehringer Ingelheim. It concerns people with idiopathic pulmonary fibrosis receiving nintedanib. The recorded enrollment is 180; the brief summary describes an aim to enroll 240 participants consecutively from 10-12 reference centers across Greece. The recorded study start is 2019-02-28 and primary completion date is 2023-02-22.

The primary outcome is mean change from baseline in SGRQ score at 3 months. The record describes the 50-item questionnaire, its 0-to-100 scale, and a mixed model with specified fixed effects. It identifies a treated-set analysis population but does not report the primary estimate, confidence interval, or analysis-specific participant count. The record lists nine outcome measures and several secondary outcomes but does not report their results or a multiplicity strategy.

Safety entries include 10 serious events among 180 at risk, 12 other events among 180 at risk, and 8 deaths. The registry record does not establish causality. Overall, the record documents the study question and design but does not provide the primary outcome result needed to assess the observed quality-of-life change.