Safety and Effectiveness of Spiriva in COPD (Chronic Obstructive Pulmonary Disease) Patients Under the Real Condition of Usual Practice: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Effectiveness of Spiriva in COPD (Chronic Obstructive Pulmonary Disease) Patients Under the Real Condition of Usual Practice (NCT00624377), a registered phase not stated study. The primary outcome is Change of Physician's Global COPD (Chronic Obstructive Pulmonary Disease) Assessment After 8-week of Treatment Severe COPD Patients Without Concomitant LABA (Long-acting Beta Agonists) Treatment.

2. Clinical Question

The study was framed around monitoring health status after tiotropium initiation under usual-practice conditions. The physician’s global assessment asks for an overall judgment of the patient’s COPD, rated on a scale from 1 (Poor) to 8 (Excellent). The intended primary analysis excluded patients pre-treated with a LABA, while secondary questions included groups with differing concomitant medication and severity. Lung function response was also part of the stated rationale, though numerical results for that response are not reported in the registry record.

This is a change-after-treatment question rather than a randomized treatment-versus-control question. A change measured within a treated group can describe how ratings shifted over time, but by itself it cannot separate treatment effects from changes that might have occurred for other reasons. The registry record does not report a comparison group suitable for estimating that contrast.

3. Trial Design

The study is titled as an assessment of Spiriva safety and effectiveness in COPD patients under usual-practice conditions. Its stated purpose was to monitor health-status change following initiation of tiotropium. The registry lists 2031 enrolled participants, the condition chronic obstructive pulmonary disease, and Boehringer Ingelheim as sponsor. The status is completed; the recorded start is 2007-12 and primary completion is 2010-03.

The intervention is listed as tiotropium, a drug. The registry lists a COPD patients group, but the allocation method is not stated. The record cautions that this is not a randomized comparison and that arms are not a like-for-like control comparison. The available information therefore supports describing treatment initiation and follow-up, not a controlled estimate of the difference between treatments.

The primary endpoint is physician-rated COPD global assessment at baseline and eight weeks. The stated primary analysis population is severe COPD patients without concomitant LABA treatment. The registry summary also describes secondary analyses among patients with and without concomitant LABA treatment, and among groups defined by disease severity and concomitant medication. Secondary outcomes include physician and patient global assessments and a measure of reduction in concomitant drug use.

The registry lists 8 outcome measures. It gives no numerical primary endpoint result and no numerical results for the other health-status outcomes in the record. Details such as visit schedules beyond the endpoint timeframe, treatment adherence, additional eligibility criteria, and the allocation process are not reported in the registry record. The intended usual-practice context may be relevant to the study question, but it does not by itself establish how representative enrollment was of other COPD populations or care settings.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population: Safety population will be defined as all patients enrolled in the study. Safety endpoints will be analyzed based on the safety population. Complete population: Complete population was defined as the subjects who completed 3 visit measurements. Efficacy endpoints will be analyzed based on the completed population.

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.

6. Primary Endpoint

The registry lists the primary outcome as Change of Physician's Global COPD (Chronic Obstructive Pulmonary Disease) Assessment After 8-week of Treatment Severe COPD Patients Without Concomitant LABA (Long-acting Beta Agonists) Treatment, measured over Baseline and 8 weeks.

The primary endpoint is the change in the physician’s Global COPD Assessment from baseline to eight weeks among severe COPD patients without concomitant LABA treatment. The assessment uses an eight-point scale, with 1 meaning Poor and 8 meaning Excellent, in response to the question, “Overall, how is the COPD of your patient?” The endpoint is continuous, and the registry identifies the planned summary measure as a mean with standard deviation.

A global rating is intended to capture a clinician’s overall view of a patient’s COPD status rather than a single physiological measurement. The brief summary says this measure has been shown to correlate with an established standard measure of health-related quality of life. The stated rationale also mentions lung function as an objective measure of treatment response, but that does not change what the primary endpoint itself measures.

Interpreting a change requires the direction and magnitude of the reported value, its variability, the number of patients contributing data, and clarity about which population was analyzed. Those numerical endpoint details are not reported in the registry record. As a result, the endpoint definition is available, but the size and precision of the observed change cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as continuous and specifies a mean with standard deviation as its summary. It does not provide the analysis estimate or enough details to reconstruct the analysis. The statistical ideas below explain how such results are generally interpreted; they do not assert that a particular method beyond what is stated was used.

What does a mean change describe?

In general, a mean change represents the average of participants’ changes in a measured outcome between two time points. For this endpoint, the intended time points are baseline and eight weeks. The mean can summarize a group-level shift in physician ratings, but it does not reveal whether most participants changed similarly or whether the average was shaped by a smaller number of large changes. The standard deviation describes variation among observations around the mean; it is not the same as the uncertainty in the estimated mean.

For a paired before-and-after outcome, a participant’s change is based on that participant’s two measurements. A valid estimate then depends on which participants have measurements at both times and how missing measurements are handled. The registry says the efficacy population consists of subjects who completed 3 visit measurements, but the definition is truncated in the record and the number in that population is not reported. The analysis details needed to determine exactly how baseline and eight-week measurements were used are not reported in the registry record.

What would a confidence interval communicate?

In general, a confidence interval presents a range of values compatible with an estimate under the statistical model and analysis assumptions. A narrower interval indicates greater statistical precision than a wider interval, while neither interval alone establishes clinical importance or eliminates bias. No confidence interval for the primary endpoint is reported in the registry record. There is therefore no reported interval from which to judge the precision of the health-status change.

A p-value, when reported, measures how incompatible data are with a specified null model under stated assumptions; it is not the probability that a treatment works, nor does it describe the size of an effect. The record lists 0 analysis entries and does not report a primary p-value. No conclusion about statistical significance can be drawn from the endpoint description or enrollment count alone.

Why does the design matter?

General statistical interpretation distinguishes a within-group change from a contrast between treatment groups. A before-and-after mean change describes temporal change among the measured participants. A controlled contrast can better address what would have happened over the same period without the intervention, provided the groups are appropriately comparable. This record does not describe a like-for-like control comparison, and allocation is not stated. Consequently, even a numerical within-group change, if available, would not alone identify the causal effect of tiotropium.

The primary population is restricted to severe COPD patients without concomitant LABA treatment. Analyses in other medication or severity groups address related but distinct questions. Differences between subgroup results can arise from actual differences, sampling variability, or differences in who was included and measured. A comparison across subgroups is not automatically a randomized comparison. Numerical subgroup estimates and their uncertainty are not reported in the registry record.

How should planning illustrations be read?

The sample-size illustrations use two-sided significance level 0.05, equal allocation between two hypothetical arms, and a normal approximation. They express the effect to detect as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not a description of the study’s original design. They do not demonstrate that the actual study had adequate power, and they cannot replace a reported estimate with its uncertainty.

The trial record does not report its own sample-size justification or the assumptions used to plan enrollment. The illustration’s hypothetical equal allocation is especially important to distinguish from the study’s reported design: the record does not state allocation and warns against treating its arms as a like-for-like control comparison. No planning participant counts or effect fractions are reported in the registry record, so those quantities cannot be interpreted in this explanation.

What do dispersion and scale properties contribute?

In general, a standard deviation shows how spread out individual values are around a group mean. Greater variability makes a mean less precise when other features are held constant. If data are strongly skewed or include influential extreme observations, a mean and standard deviation may not fully convey the distribution; medians, ranges, or a plot of individual values can sometimes add context. The registry specifies a mean and standard deviation but does not report the observed values or distribution.

The scale is described as eight points with ordered verbal anchors. Treating such ratings as continuous and summarizing them with a mean is a modeling and reporting choice. It offers a compact average, but equal spacing between adjacent rating categories should not be assumed solely from the labels. The record does not report sensitivity analyses using alternative summaries or explain how the scale’s properties informed the statistical analysis.

Why can over-dispersion matter in count outcomes?

In general, count data may vary more than a simple model expects, a condition often called over-dispersion. If a count model assumes less variability than is present, uncertainty can be understated and inferential results may be too confident. Appropriate modeling depends on the outcome type and distribution. The primary endpoint is a continuous rating change, not a count endpoint, and the registry does not report a count-model analysis. This general concept should not be mistaken for a method used in this study.

Across all these concepts, the central distinction is between an endpoint definition and a reported analysis result. The former is available: a physician assessment at baseline and eight weeks, summarized as a mean with standard deviation in the stated primary population. The latter, including the estimate, uncertainty, analysis sample, and handling of incomplete measurements, is not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Spiriva 18µg With HandiHaler Device on COPD Patien")
n   <- c(232)
m   <- c(1.16)
sp  <- c(1.34)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Spiriva 18µg With HandiHaler Device on COPD Patien  232  1.160  1.340  0.987  1.333

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including several physician global-assessment outcomes across different populations, a patient global assessment, and reduction of concomitant drug use. Considering multiple outcomes or subgroups raises a general multiplicity issue: the more questions examined, the greater the chance that at least one result may appear noteworthy by chance if each is tested separately. Whether and how to control that risk depends on the prespecified hierarchy and analysis plan. Multiplicity adjustment, a hierarchy among outcomes, and the statistical plan are not reported in the registry record.

The record lists 0 analysis entries. It does not provide numerical estimates, confidence intervals, p-values, or subgroup results for the listed health-status outcomes. The primary analysis was described as focusing on severe COPD patients without concomitant LABA treatment, but details of the analysis strategy and any exploratory status for secondary questions are not reported in the registry record.

Population definitions are only partly available. The safety population is described as all patients enrolled. The complete population is defined as subjects who completed 3 visit measurements, and efficacy endpoints are said to be analyzed using that population; however, the text defining it is incomplete. The number of participants in the complete population, the number with observed endpoint data at each visit, reasons for missing measurements, and missing-data methods are not reported in the registry record.

In general, excluding participants without complete measurements can affect interpretation if the chance of having complete data is related to health status or treatment experience. Methods such as imputation or model-based use of incomplete records require assumptions and should be described alongside sensitivity analyses. The record does not say whether any such methods or sensitivity analyses were used. It is therefore not possible to assess how incomplete follow-up may have influenced the endpoint results.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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

Serious events with the highest arm-level rate: chronic obstructive pulmonary disease (0.2%), death (0.1%), acute myocardial infarction (0.1%), cardiac disorder (0.0%), hepatic cirrhosis (0.0%).

The registry lists 2031 participants at risk in the Spiriva 18µg with HandiHaler Device on COPD Patients group. It records 16 participants affected by serious adverse events and 0 affected by other adverse events. These are registry counts; they do not by themselves establish that an event was caused by tiotropium. The record does not report a death count.

The serious-event terms listed include Chronic Obstructive pulmonary disease (0.2%), Death (0.1%), Acute Myocardial Infarction (0.1%), Cardiac disorder (0.0%), Hepatic cirrhosis (0.0%), and Pneumonia (0.0%). The displayed percentages are rounded as reported. A term’s listing does not explain whether it occurred before or after treatment initiation, how it was judged for seriousness or relatedness, or whether a participant experienced more than one event. The Death term’s percentage does not supply the missing death count.

In general, adverse-event summaries are descriptive safety information, not causal comparisons. Interpretation depends on definitions, ascertainment, follow-up, event timing, and a suitable comparator. Those details are not reported in the registry record, so the counts should be read as the posted summary rather than as a comparative risk estimate.

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

The record establishes that the study was completed, enrolled 2031 participants, and set out to assess physician-rated COPD health status after tiotropium initiation. It specifies an eight-week assessment timeframe and identifies a primary population of severe COPD patients without concomitant LABA treatment. It also lists secondary questions involving broader medication and severity groups. These details clarify what the study intended to examine.

The record does not provide a numerical primary endpoint result. It therefore does not show whether the physician-rated assessment increased, decreased, or remained unchanged on average, nor how much individual ratings varied. There is no reported estimate or confidence interval with which to judge precision. No numerical efficacy result should be inferred from enrollment, study completion, endpoint wording, or the presence of secondary outcomes.

Even if a before-and-after change were available, the lack of a stated like-for-like control comparison would limit causal interpretation. A change over time in a treated group is not equivalent to the difference between what happened under treatment and what would have happened without it. Other influences may contribute to temporal change, and the registry information does not allow their effects to be separated.

The listed safety counts and terms provide a limited description of reported events. They do not establish whether treatment caused any event, and the record does not include a death count or enough detail for a full comparative safety assessment. The rounded term percentages should not be treated as precise individual risk estimates.

Accordingly, the study question and outcome framework can be described, but the posted record does not support a conclusion about the magnitude or precision of health-status change. It also cannot establish a causal treatment effect or offer a complete benefit-risk comparison. This is an interpretation of the information in the registry record, not medical advice.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it combines a pragmatic, usual-practice framing with a primary question focused on a defined subgroup. The primary analysis was intended for severe COPD patients without concomitant LABA treatment, while secondary questions extended to other medication and severity groups. This distinction matters: a result for one population would not automatically apply to every group named in the study rationale.

It also illustrates why the endpoint and design must be read together. A physician’s global assessment can summarize overall clinical judgment, while a mean change offers a compact group-level description. But the value of that summary depends on reported results, uncertainty, participant completeness, and the comparison supporting interpretation. Here, the registry defines the endpoint but does not report its numerical result.

The record explicitly cautions against treating the arms as a like-for-like control comparison, and does not state allocation. That caution makes it important to distinguish monitoring change after treatment initiation from estimating a comparative causal effect. A large enrollment count does not resolve that design limitation, and it cannot substitute for an estimate with a confidence interval.

The record also shows why analysis populations and missing data should be transparent. Safety endpoints are described for all enrolled patients, while efficacy endpoints are linked to a complete population defined by completion of 3 visit measurements. The complete-population definition is incomplete, and the number included in efficacy analyses is not reported. Without that information, readers cannot assess how much follow-up contributed to the endpoint summary.

Finally, the registry lists multiple outcome measures and subgroup questions without a reported statistical plan or multiplicity approach. These omissions limit assessment of how the analyses were prioritized and how uncertainty across several questions should be understood. The statistical importance lies not in an unreported efficacy result, but in recognizing the boundary between a clearly stated research question and evidence that can be quantitatively evaluated.

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 consequential limitation for interpreting effectiveness is that the registry record does not report a numerical primary endpoint result. It provides no mean change, standard deviation, confidence interval, or primary analysis sample size. The endpoint’s magnitude and precision therefore cannot be assessed. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The study is not described as a randomized comparison, allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. These details constrain causal interpretation of any change after treatment initiation. The record does not provide enough information to characterize the comparison structure further or determine whether another source of comparison was used.

The efficacy population description is incomplete. The record says efficacy endpoints use a complete population defined by completion of 3 visit measurements, but it does not report how many participants met that definition, how many had endpoint observations at each time, or why measurements may have been missing. Missing-data methods and sensitivity analyses are not reported in the registry record.

The primary endpoint is a physician global rating. The registry does not report assessor blinding, the distribution of individual ratings, or a threshold for meaningful change. Those omissions limit assessment of measurement variability and clinical interpretation. Statistical methods beyond the mean and standard deviation summary are not described, and adjustment for multiple outcomes or subgroup analyses is not reported.

Safety information is also limited to counts and listed terms. A death count, event timing, relatedness, and detailed ascertainment information are not reported in the registry record. The registry’s usual-practice framing provides context for the research question, but details needed to judge how representative the enrolled participants were are not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Effectiveness of Spiriva in COPD (Chronic Obstructive Pulmonary Disease) Patients Under the Real Condition of Usual Practice — NCT00624377.
• Registry record last updated 2014-03-28; status last verified 2014-02.
• Results first posted 2012-05-15.
• 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

NCT00624377 is a completed registry study titled Safety and Effectiveness of Spiriva in COPD Patients Under the Real Condition of Usual Practice. The record lists Boehringer Ingelheim as sponsor, 2031 enrolled participants, and tiotropium as the drug intervention. The recorded start is 2007-12 and primary completion is 2010-03.

The primary endpoint is change in physician-rated Global COPD Assessment from baseline to eight weeks among severe COPD patients without concomitant LABA treatment. The outcome uses an eight-point scale and is identified as a continuous measure summarized by a mean and standard deviation. The registry lists 8 outcome measures but 0 analysis entries; a numerical primary result is not reported in the registry record.

The safety summary records 16 participants with serious adverse events and 0 with other adverse events among 2031 at risk. A death count is not reported in the registry record. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison.