Assessment of Physical Functioning and Handling of Spiolto Respimat in Patients With COPD (OTIVACTO): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment of Physical Functioning and Handling of Spiolto Respimat in Patients With COPD (OTIVACTO) (NCT02720757), a registered phase not stated study. The primary outcome is Percentage of Patients With Therapeutic Success After Approximately (Approx.) 6 Weeks After Baseline.

2. Clinical Question

The endpoint focuses on change in reported ability to carry out usual activities, as assessed by the PF-10 questionnaire. The study description treats physical functioning as a surrogate for physical activity and exercise capacity; those broader concepts are not themselves the primary endpoint. The registry also lists assessments of score change, physician evaluation of general condition, and patient satisfaction with the treatment and inhaler device. The record does not establish whether changes in these measures were compared with changes under another treatment or with an untreated course of disease.

3. Trial Design

OTIVACTO is identified as a non-interventional study of Spiolto Respimat in people with COPD in routine clinical practice. Its stated primary objective was to measure change in physical functioning after approximately 6 weeks of treatment. Secondary objectives concerned physician evaluation of the patient's general condition and patient satisfaction at the later visit. The record does not describe random assignment or a control group, so the design does not provide a randomized, like-for-like comparison of treatments.

The registry lists enrollment of 132 participants and gives the study status as terminated. The recorded start date is 2016-08-26, and the primary completion date is 2017-12-14. The reason for termination is not reported in the registry record. The planned observation period for the primary question was approximately 6 weeks, with Visit 1 as baseline and Visit 2 as the later assessment. The record does not describe a longer follow-up period for these outcomes.

The intervention is named Spiolto Respimat. The arm description refers to participants needing a fixed combination of two long-acting bronchodilators, according to the approved product information and COPD guidance. Because this was routine-practice research, the treatment context differs from a trial in which an investigator assigns participants to competing arms. The registry does not specify allocation, and it does not describe a separate comparator intervention.

The primary-outcome population was the full analysis set. Eligibility for that set required enrollment and registration, at least one treatment dose, documented baseline and week 6 visits, and completion of all questionnaires. The number of participants meeting all these requirements is not reported in the registry record. The record lists 6 outcome measures but 0 analyses. It gives no numerical primary-outcome estimate, confidence interval, or secondary-outcome results. Thus, the design and endpoint definitions can be described, but the posted record does not permit assessment of the outcome findings.

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: Patients were enrolled consecutively and were followed over an observational period of approximately 6 weeks, which was the average time between two medical consultations

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS): Patients that were enrolled, registered and received at least one dose of treatment with Spiolto® Respimat® and had baseline and week 6 visit documented as well as completed all questionnaires were included in FAS

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): Patients that were enrolled, registered and received at least one dose of Spiolto® Respimat® were included in the Treated Set.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients With Therapeutic Success After Approximately (Approx.) 6 Weeks After Baseline, measured over Visit 1 (baseline) and at Visit 2 (approx. 6 weeks later).

The primary endpoint is the percentage of participants classified as having therapeutic success after approximately 6 weeks. Success is defined as a 10-point increase in PF-10 score between baseline and the later visit. The PF-10 is a 10-question subdomain of the SF-36 patient questionnaire that asks about restrictions in usual activities. Responses are scored from 1 to 3 for each question, with the total standardized to a 0-to-100 scale. Higher scores correspond to fewer reported limitations under the scoring description.

The endpoint turns a change in a continuous questionnaire score into a binary classification: each participant either meets the specified increase threshold or does not. The reported percentage would therefore describe how common this predefined change was in the analyzed group. The threshold makes the clinical question more directly interpretable as the proportion meeting a specified improvement criterion, but it also discards information about the size of changes that fall short of or exceed that threshold. A continuous score-change analysis would retain more detail about the distribution of changes.

In general, a patient-reported physical-functioning measure can capture limitations that matter in daily activities and may complement other types of clinical assessment. In this study description, physical functioning is treated as a surrogate for physical activity and exercise capacity; it is not a direct measurement of either. The percentage meeting the endpoint, its denominator, and its 95% confidence interval are not reported in the registry record, so the frequency and precision of therapeutic success cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

The primary endpoint is binary at the participant level: the PF-10 change either reaches the stated 10-point increase or it does not. The study's percentage would be the proportion of analyzed participants who met that rule. In general, a proportion is useful when the question concerns how common a defined outcome is. Its interpretation depends on knowing both the numerator—the number meeting the rule—and the denominator—the number assessed. Neither the percentage nor the primary-analysis count is reported in the registry record.

Turning a score change into a yes-or-no outcome makes the threshold central to interpretation. A participant just short of the criterion is classified differently from one who reaches it, even if their score changes are similar. Conversely, a participant who exceeds the threshold remains in the same success category as one who reaches it exactly. This is a general feature of dichotomizing a continuous measure, not evidence of a particular pattern in OTIVACTO. The record does not give individual or group-level score changes that would show how many participants were near the threshold.

What is the role of a confidence interval?

The primary endpoint lists a 95% confidence interval as its measure of dispersion. In general, an interval conveys uncertainty around an estimate: a wider interval indicates less precision than a narrower interval, under the method used. Its width depends on features such as the amount of information and the variability relevant to the estimate. A confidence interval is not a measure of clinical importance and does not, by itself, establish causation. No interval bounds are reported in the registry record, so the precision of the primary percentage cannot be judged.

The record does not state the method used to calculate the confidence interval. For a percentage, possible methods can differ, particularly when the analyzed sample is limited or the event proportion is near an extreme. Those are general methodological considerations, not details that can be attributed to this study. Without the actual estimate, interval, and analysis method, it is not possible to reproduce or evaluate the uncertainty calculation.

Why does the study design affect interpretation?

Randomization, when used, creates a basis for comparing groups by assigning participants to interventions under a defined procedure. OTIVACTO is described as non-interventional, and no comparator is described. A baseline-to-follow-up change in one treated group can document a temporal pattern, but it does not show what would have happened to comparable participants over the same period under another condition. In general, confounding occurs when factors associated with treatment or follow-up also influence the outcome. The registry record does not report an adjusted analysis or explain how such factors were addressed.

This distinction matters because an observed change and a treatment effect are not interchangeable. A treatment effect is a comparison between outcomes under different treatment conditions, usually defined by a particular estimand and analysis. A within-group change is a difference over time for participants observed in one group. No numerical change estimate is posted here, and the record does not describe a comparative treatment-effect analysis.

What can be inferred from the planning information?

The registry includes general assumptions for a sample-size planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of an observed effect. The record does not give the resulting planning counts in the information available for interpretation, and the listed design itself does not describe two randomized arms. These assumptions should therefore be understood as planning conventions, not as proof that the trial was designed or conducted with that allocation.

In general, a sample-size calculation estimates how many participants would be needed under stated assumptions to detect a specified effect with a chosen probability, while controlling a stated error rate. Such a calculation is sensitive to the assumed effect, outcome variability, allocation, and analysis method. A planning illustration is not an observed result and does not establish the probability that this completed study detected an effect. The trial's own sample-size justification is not reported in the registry record. No observed-power claim can be made from the information recorded.

What does over-dispersion mean in general?

For count or binary outcomes, a statistical model may assume a particular level of variability. Over-dispersion means the observed variability is greater than the model assumes. If ignored, standard errors can be too small and confidence intervals too narrow, making results appear more precise than warranted. This is a general issue in analysis, not a reported feature of OTIVACTO. The registry record does not describe a model or provide data that would allow over-dispersion to be assessed.

What is not available for methodological review?

The record lists 0 analyses and does not give the primary estimate, confidence interval limits, or numerical secondary outcomes. It also does not describe a statistical analysis plan, covariate adjustment, interim analyses, or handling of missing data beyond the full analysis set criteria. Those details are not reported in the registry record. Without them, readers cannot determine which inferential procedures were used, whether the stated endpoint was analyzed exactly as planned, or whether alternative analyses were considered.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Tiotropium + Olodaterol FDC")
n      <- c(107)
events <- c(48)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Tiotropium + Olodaterol FDC  107  48  44.9  35.2  54.8  35.8  54.3  35.8  54.3

11. Multiplicity, Missing Data and Analysis Populations

The record lists 6 outcome measures, including the primary therapeutic-success endpoint and secondary measures covering PF-10 score change, physician evaluation of general condition, and several aspects of patient satisfaction. Assessing multiple outcomes can create a multiplicity issue: in general, the more statistical tests considered, the greater the chance that at least one appears notable by chance if no adjustment or hierarchy is used. The registry record does not describe a multiplicity procedure, a testing hierarchy, or how results across outcomes were to be interpreted. It also lists 0 analyses, and numerical results for the outcomes are not reported in the registry record.

The full analysis set required documented baseline and week 6 visits and completion of all questionnaires, as well as enrollment, registration, and at least one dose. This definition identifies who could qualify, but the number included in the set is not reported in the registry record. The record does not explain how missing questionnaire items, incomplete visits, or other missing observations were handled. It also does not provide a comparison of included and excluded participants, so the potential for selection related to complete follow-up cannot be assessed.

Enrollment was 132, while the adverse-event group lists 127 participants at risk. These are different record entries and should not be treated as interchangeable denominators. The count included in the primary analysis is not reported in the registry record, and the reason for any difference among populations is not reported in the registry record. The record also does not state whether imputation, sensitivity analyses, or other missing-data methods were used. In general, missing data can affect both the estimated outcome and its precision, particularly when completion is related to participants' health or their outcome. The available information does not establish whether that concern affected this study.

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 5% reporting threshold.

The safety information lists one group, Tiotropium + Olodaterol FDC, with 127 participants at risk. The serious adverse event count is 0, the count for other adverse events is 0, and deaths are 0. No top serious adverse-event terms are listed. These are the figures recorded for the group and should be read alongside their stated denominator, rather than interpreted as evidence that no events could occur outside the recorded observation or reporting context.

In general, an adverse-event count describes events recorded under the study's collection and reporting procedures. It does not, by itself, show whether an event was caused by treatment. The registry record does not provide further details about event definitions, follow-up duration for safety, collection procedures, or causal assessment. Nor does the absence of recorded serious events establish the absence of risk. The 127 participants at risk is a safety population entry; it is not stated to be the number analyzed for the primary endpoint.

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

The information in the registry record defines a question about whether participants experienced a 10-point increase in PF-10 score after approximately 6 weeks and identifies the intended population for the primary analysis. It does not report the percentage meeting that definition, the number of participants who did so, or the 95% confidence interval. As a result, the posted results do not establish the frequency of therapeutic success or its statistical precision.

The study's non-interventional, routine-practice setting is relevant to what a result could mean. In general, an outcome observed after treatment in one group is descriptive of that group's experience over time. Without a comparator, it cannot separate treatment-associated change from other changes occurring over the same period. This distinction does not invalidate descriptive information, but it limits claims about what caused a change. The record does not describe a like-for-like control group or a randomized comparison.

The PF-10 endpoint measures reported limitations in usual activities, with the primary outcome defined by crossing a specified change threshold. It is not a direct measure of physical activity or exercise capacity, although the study description calls physical functioning a surrogate for those concepts. The registry record does not provide results for the secondary measures, including physician assessment and satisfaction, so they cannot fill the gap in the primary-outcome results.

The safety figures record 0 serious adverse events, 0 other adverse events, and 0 deaths among 127 participants at risk in the listed group. These counts describe the registry entry; they do not establish a general absence of adverse events or quantify comparative safety. Taken together, the record supports a description of the trial's objectives, eligibility definition, and recorded safety counts. It does not support a conclusion about the size, direction, or cause of physical-functioning change, or a comparison of treatment outcomes.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a clearly defined endpoint and a result that can be interpreted. The registry describes the PF-10 instrument, the 10-point success threshold, the approximate follow-up period, and criteria for the full analysis set. Those details help readers understand what the investigators intended to measure. Yet without the estimate, denominator, and confidence interval, readers cannot determine the endpoint's frequency or precision. A complete statistical interpretation requires outcome values as well as endpoint definitions.

It also highlights why design and analysis populations matter. Routine-practice research can describe outcomes in a clinical setting, but a non-interventional design without a comparator does not offer the same basis for causal attribution as a randomized comparison. Separately, the full analysis set depends on treatment exposure and completion of visits and questionnaires. The size of that set is not reported in the registry record, so readers cannot assess how much of the enrolled group contributed to the primary endpoint.

Finally, the registry lists several outcomes and a planning framework, but no analyses. The distinction between planning assumptions, observed outcomes, and inferential estimates is important: assumptions do not substitute for results, and planning calculations are not evidence that an effect was detected. The record's termination status is also a study-status fact, not an explanation for why the study ended or what its findings were. These features make transparent reporting of analysis methods, denominators, missingness, and uncertainty especially important when interpreting a clinical study record.

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 most direct limitation for statistical interpretation is that numerical outcome analyses are not reported in the registry record. The primary therapeutic-success percentage, its confidence interval, its numerator and denominator, and numerical secondary results are absent. The record lists 0 analyses. Consequently, readers cannot evaluate effect magnitude, precision, or the pattern of secondary findings.

The design is described as non-interventional, with no comparator arm established in the record. Any before-and-after finding, if reported elsewhere, would need to be interpreted as a change over time in the analyzed group rather than a controlled estimate of treatment effect. The record does not describe random allocation, a control condition, or adjustment for potential confounding. The reason for termination is not reported in the registry record.

The enrolled population was 132, but the primary analysis required baseline and week 6 documentation and complete questionnaires in addition to treatment exposure and registration. The number meeting these criteria is not reported in the registry record. This prevents assessment of the primary denominator and of how representative the analyzed participants might be of those enrolled. The registry does not explain missing-data handling or give sensitivity analyses.

The primary endpoint uses a thresholded patient-reported score. This supports an interpretable success classification but does not show the distribution of score changes. The record does not provide continuous PF-10 change results or details about the confidence-interval method. It also does not describe multiplicity handling across the listed outcomes, an analysis plan, or interim analyses. These missing details limit independent assessment of the statistical procedures and of the robustness of any outcome conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessment of Physical Functioning and Handling of Spiolto Respimat in Patients With COPD (OTIVACTO) — NCT02720757.
• Registry record last updated 2019-04-16; status last verified 2019-04.
• Results first posted 2019-04-16.
• 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

OTIVACTO is a non-interventional study of Spiolto Respimat in people with COPD requiring dual long-acting bronchodilation in routine clinical practice. Enrollment was 132. The recorded study start date is 2016-08-26, the primary completion date is 2017-12-14, and the status is terminated. The reason for termination is not reported in the registry record.

The primary endpoint was the percentage meeting a 10-point increase in PF-10 score after approximately 6 weeks. The full analysis set required treatment exposure, documented baseline and week 6 visits, and completed questionnaires, among other criteria; its size is not reported in the registry record. The record lists 6 outcome measures and 0 analyses. It gives no numerical primary or secondary outcome results. Safety information lists 127 participants at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. The record does not establish a comparator or randomized treatment comparison.