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 Study to Assess the Efficacy and Safety of AZD1981 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (NCT00690482), a randomized phase 2 study. The primary outcome is FEV1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00690482 |
| Phase | Phase 2 |
| Condition | Moderate to Severe COPD |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 118 |
| Arms in the primary outcome | 2 |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
The study asked whether AZD1981, taken as an oral tablet twice daily, was associated with a different change in forced expiratory volume in one second (FEV1) over four weeks than placebo in patients with moderate to severe COPD. It also assessed safety. The primary outcome was mean change in FEV1 from baseline to Week 4, with the last post-dose measurement used if data were missing.
Population
Patients with moderate to severe COPD. The study enrolled 118 participants. The efficacy population is described as 117 randomized patients: 61 assigned to AZD1981 and 56 to placebo.
Intervention
AZD1981 oral tablet, twice daily, in a four-week study.
Comparator
Placebo oral tablet, twice daily, in the same randomized, parallel-group study.
Primary question
What was the mean change in FEV1 from baseline to Week 4 in each group, and how do the posted results characterize that change? A formal estimate of the difference between groups is not reported in the registry record.
FEV1 is a lung-function measure. Comparing randomized groups can help assess whether their average changes differ, while the placebo group provides a concurrent reference. The record posts group-level means and ranges, but does not post a between-group effect estimate, confidence interval, or p-value. The reported figures therefore describe the two groups; they do not establish the size or precision of a treatment-versus-placebo contrast.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group Phase IIa study comparing AZD1981 with placebo. The official title describes a four-week, double-blind, placebo-controlled study. The registry record lists an enrollment of 118 and a completed status. It records a start date of 2008-05 and a primary completion date of 2008-12. AstraZeneca is listed as the sponsor.
Random allocation is intended to make treatment groups comparable, on average, with respect to factors that could influence outcomes. A parallel-group design assigns participants to one group for the study rather than having each participant receive both treatments in sequence. Placebo provides a comparison group receiving a matching study intervention. Masking is intended to reduce the influence of knowledge about assignment on participant experience, care, measurement, and assessment. The record does not specify which people were included in the quadruple masking.
The four-week duration defines the period covered by the primary outcome; it does not establish how results would look over a longer period. The registry record gives the primary outcome timeframe as baseline and Week 4. It describes the efficacy analysis as based on 117 randomized patients, including 61 on AZD1981 and 56 on placebo, while noting that not all participants had valid, non-missing values for each outcome. The group-level primary-outcome summaries use 60 participants in the AZD1981 group and 55 in the placebo group.
These design details help frame the posted results, but do not fill gaps in the statistical plan. The sample-size justification, planned interim analyses, and detailed analysis plan are not reported in the registry record. Randomization and masking are design features; they do not by themselves provide an estimate of the treatment contrast or show how precisely it was estimated.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | AZD1981 | Placebo |
|---|---|---|
| STARTED | 61 | 57 |
| COMPLETED | 57 | 54 |
| NOT COMPLETED | 4 | 3 |
Reasons for not completing this period:
| Reason | AZD1981 | Placebo |
|---|---|---|
| Adverse Event | 2 | 1 |
| Incorrect enrolment | 0 | 1 |
| Study-specific discontinuation criteria | 1 | 0 |
| Intake of prohibited medicine | 1 | 0 |
| withdrew consent at rand.day | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The efficacy analysis is based on 117 randomized patients, 61 on AZD1981 and 56 on placebo. However, not all patients will have valid, non-missing values for a given outcome measure.
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: One patient randomised to placebo withdrew consent immediately after the first dose of investigational product on the day of randomisation. No clinical measurements were performed and no reports of AEs were received for this patient. Since the patient is non-informative both in terms of efficacy and safety, he has been excluded from the analyses.
| Characteristic | Unit | AZD1981 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 61 | 56 | 117 | |
| Age, Continuous | Years | 64.1 (47 to 78) | 62.4 (43 to 83) | 62.4 (43 to 83) |
| Sex: Female, Male: Female | Participants | 12 | 8 | 20 |
| Sex: Female, Male: Male | Participants | 49 | 48 | 97 |
6. Primary Endpoint
The registry lists the primary outcome as FEV1, measured over Baseline and Week 4.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is mean change in FEV1 from baseline to Week 4. FEV1 measures the volume of air a person can forcefully exhale during the first second of an exhalation. It is used as an objective measure of lung function, and a change from baseline expresses how the measured value shifted over the study period. The registry record gives the unit as litres.
Using change from baseline focuses the analysis on movement during the study rather than only on the Week 4 measurement. Comparing the average change between randomized groups can describe whether the groups followed different average trajectories during the trial. The reported AZD1981 mean change is 0.007 L and the placebo mean change is 0.011 L. These are separate group summaries, not a reported estimate of the difference between groups.
The endpoint description says the last post-dose measurement was used if data were missing. That statement gives one part of the missing-data procedure, but the registry record does not report further details about how missing measurements were handled or how many measurements were missing for this outcome. Group counts for the posted summaries are 60 and 55, while the efficacy population is described as 61 and 56. Those counts make clear that the summary population is not identical to the stated randomized efficacy population.
FEV1 is one component of a broader assessment. Other listed measures include forced vital capacity, slow vital capacity, inspiratory capacity, mid-expiratory flow, and COPD symptom scores. The primary endpoint remains the stated main measure for this analysis; the presence of other outcomes does not substitute for a reported between-group analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted mean change in FEV1 is 0.007 L for AZD1981, based on 60 participants, and 0.011 L for placebo, based on 55 participants. The listed full-range limits are -0.81 to 0.74 for AZD1981 and -0.55 to 0.55 for placebo. These figures describe the observed group summaries. The registry record does not report a formal estimate comparing the groups, a confidence interval for that contrast, or a p-value.
That distinction is important. Separate group means do not state the estimated treatment effect, and the range of individual values is not a confidence interval for a group difference. Without a reported contrast and its uncertainty, the precision of the difference cannot be assessed from the registry results alone. The record also does not give a formal test from which to judge statistical compatibility with a null hypothesis.
The efficacy population is described as 117 randomized participants, 61 on AZD1981 and 56 on placebo. The outcome summaries use 60 and 55 participants, respectively. The record notes that not all participants will have valid, non-missing values for a given outcome, but does not give the specific reason for the difference in counts for these summaries. The interpretation should therefore retain the group-specific counts shown with the outcome rather than assuming every randomized participant contributed a valid FEV1 value.
The listed ranges extend on both sides of zero in each group. A range describes the spread from the smallest to the largest observed value; it does not show how concentrated most measurements were, nor does it quantify uncertainty in a group mean or between-group effect. The record identifies the dispersion as full range. It does not report a standard deviation or standard error for these endpoint summaries.
The results are for a four-week endpoint in a Phase IIa study. They characterize short-term group summaries in this trial, not longer-term effects. They also do not provide a basis for a treatment recommendation. The registry record’s completed status indicates that the study is recorded as completed; it does not add statistical evidence beyond the posted outcome results.
9. Statistical Methods Explained
Several statistical ideas help distinguish what the registry results describe from what they do not establish. The primary endpoint is a group mean change, and a comparison of randomized groups would ordinarily be expressed as an estimated difference in mean change, accompanied by a measure of uncertainty. The registry record posts group means and full ranges, but no formal between-group estimate or inferential result. It is therefore important not to treat the two group means as if they were themselves the treatment-effect estimate.
What does a mean change describe?
A mean is an average across the participants contributing data to an outcome summary. A mean change is formed from each participant’s change over the specified period and then summarized across the group, according to the analysis method. Here the outcome is mean FEV1 change from baseline to Week 4, with the last post-dose measurement used if data were missing. The posted values are 0.007 L for AZD1981 and 0.011 L for placebo. They give a concise description of average change, but do not show every participant’s response or the distribution’s shape.
A group mean can be affected by unusually large or small observations. The range provides the lowest and highest observed values and offers a basic indication of spread. It does not tell how many observations lie near either limit, how variable the measurements are around the mean, or how precisely the mean has been estimated. For that reason, the listed full-range limits should not be read as an interval estimating the treatment effect.
What would a confidence interval add?
In general, a confidence interval expresses uncertainty around an estimate. For a randomized comparison, an interval around the between-group difference would show a set of effect sizes compatible with the data under the analysis assumptions. A narrow interval would indicate greater precision than a wide interval. The registry record does not report such an interval for the primary comparison, so the precision of a treatment contrast cannot be assessed from the posted group summaries.
A p-value is another output of a specified statistical test. In general, it measures how unusual data at least as incompatible with a null hypothesis would be under that hypothesis and the test assumptions. It is not the probability that a treatment works, nor does it quantify the size or clinical importance of an effect. No p-value for the primary between-group comparison is reported in the registry record. A p-value should not be reconstructed from the group means and ranges alone, because those summaries do not supply all the necessary information or identify the intended analysis.
Why does randomization matter?
Randomization provides a design-based way to create comparison groups and reduce systematic differences in measured and unmeasured factors, on average. It does not guarantee that groups will be identical in a particular trial, and it does not eliminate uncertainty due to the number of participants or missing outcomes. The parallel-group structure means the posted summaries correspond to separate groups. Masking can help limit some forms of bias, but the registry record does not detail who was masked or how masking was maintained.
How should the planning illustrations be understood?
In general, sample-size planning links a target effect, variability assumptions, an error threshold, and a desired probability of detecting an effect under specified conditions. The planning illustration described for this analysis uses a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. Such calculations are planning illustrations based on the observed effect; they are not the trial’s own design justification and are not observed power. The registry record does not report the trial’s sample-size justification. No numerical planning result should be interpreted as an observed trial outcome.
When data are more variable than a model assumes, the estimate may be less precise than an analysis that assumes less variability. In general, over-dispersion means the observed variability exceeds that expected under a chosen model; methods that account for it can change uncertainty estimates. The record does not identify a model for a formal primary comparison, report an over-dispersion assessment, or give the information needed to attribute a particular model choice to the study. It would be inappropriate to infer a statistical test or model from the design label or summary values.
The outcome counts also matter to interpretation. The efficacy population is described as 61 AZD1981 and 56 placebo participants, whereas the primary outcome summaries use 60 and 55. The registry record notes that not everyone has valid, non-missing values for each outcome, but does not explain the outcome-specific missingness or provide the missing-data pattern. Different analysis populations can affect the estimate and its interpretation, so the stated counts should remain attached to the results.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary FEV1 outcome and several additional outcome measures. Named secondary measures include forced vital capacity, slow vital capacity, inspiratory capacity, FEF25%-75%, and COPD symptom sleep, breathing, cough, and sputum scores. It records 14 outcome measures overall and 12 posted secondary outcomes. The formal statistical analyses, including any prespecified hierarchy or adjustment for multiple comparisons, are not reported in the registry record.
In general, examining multiple outcomes creates more opportunities for apparently notable findings to arise by chance. Trial protocols may address this with a hierarchy, adjusted testing, or a distinction between primary and exploratory outcomes. The record does not describe which approach, if any, was planned. No conclusions about the multiplicity strategy can therefore be drawn from the list of outcome measures alone.
For the primary endpoint, the record states that the last post-dose measurement was used if data were missing. This describes an element of the analysis, but not the full missing-data plan. The registry record does not report how many FEV1 observations were missing, why they were missing, whether any other imputation or sensitivity analyses were used, or how departures from the stated approach were assessed.
The efficacy population is described as 117 randomized participants, with 61 assigned to AZD1981 and 56 to placebo. The primary outcome summaries have counts of 60 and 55. The record cautions that not all participants have valid, non-missing values for every outcome. It does not provide enough detail to establish whether the posted summaries use a particular named analysis population or how missing observations affected group comparability. The record also reports zero posted analyses. A detailed statistical analysis plan is not reported, so choices about adjustment, estimands, or sensitivity analyses should not be assumed.
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 |
|---|---|---|---|
| AZD1981 | 0 | 61 | 0.0% |
| Placebo | 1 | 56 | 1.8% |
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 |
|---|---|
| AZD1981 | 8 of 61 |
| Placebo | 6 of 56 |
Most frequent serious adverse event terms
| Event term | Organ system | AZD1981 | Placebo |
|---|---|---|---|
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | 0 of 61 | 1 of 56 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AZD1981 | Placebo |
|---|---|---|---|
| NASOPHARYNGITIS | Infections and infestations | 6 of 61 | 3 of 56 |
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | Respiratory, thoracic and mediastinal disorders | 4 of 61 | 3 of 56 |
Serious events with the highest arm-level rate: chronic obstructive pulmonary disease (1.8%).
The registry record reports serious adverse events for 0 of 61 participants at risk in the AZD1981 group and 1 of 56 participants at risk in the placebo group. Chronic Obstructive Pulmonary Disease is listed as the top serious-event term, at 1.8%. The record also reports other adverse events for 8 of 61 participants in the AZD1981 group and 6 of 56 in the placebo group. These categories should not be conflated: the figures for other adverse events are not the serious-event counts.
These are descriptive counts from the groups recorded as at risk. A difference in counts does not by itself establish that an intervention caused or prevented an event. Serious events are uncommon enough in small studies that the absence of a recorded event in one group does not demonstrate an absence of risk. The record does not provide an inferential comparison of adverse-event rates.
Deaths are not reported in the registry record. The serious-event figures should be read as the safety information posted for this study, not as a complete account of every possible safety outcome or as evidence about safety beyond the study period.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry contains group-level FEV1 change summaries for a four-week randomized comparison. The mean changes are 0.007 L for AZD1981 and 0.011 L for placebo, with full ranges of -0.81 to 0.74 and -0.55 to 0.55, respectively. The summary counts are 60 and 55. These data describe the observed values in the groups represented in the endpoint summaries.
They do not, by themselves, establish the size of a treatment-versus-placebo effect. The registry record does not report a formal between-group estimate, confidence interval, or p-value for the primary endpoint. It is not possible to characterize the statistical precision of the contrast using only separate group means and ranges. Nor should a difference between two group summaries be treated as a test result.
The study’s short duration and Phase IIa designation also set limits on scope. The primary outcome concerns change through Week 4; it does not describe outcomes over longer follow-up. The registry record does not give a sample-size justification, detailed analysis plan, or planned interim analyses, so these aspects cannot be used to infer what the study was designed to detect or how the analysis was intended to proceed.
Safety counts are descriptive. The posted serious-event figures are 0 of 61 in the AZD1981 group and 1 of 56 in the placebo group. Those counts do not prove that either treatment caused or prevented an event, and the registry record does not report deaths. The information should be understood within the study’s recorded population and period.
In general, a trial result is most informative when the estimated comparison, its uncertainty, the analysis population, and the outcome handling are all clear. In this record, the group-level primary summaries are available, but several elements needed to assess a formal treatment contrast are not reported. The results therefore support a description of the posted observations, not a definitive conclusion about efficacy or safety.
13. Why This Trial Matters Statistically
This study illustrates why a randomized design and a reported group comparison are related but distinct parts of evidence. Randomization creates a principled basis for comparing groups, while statistical analysis quantifies the observed contrast and its uncertainty. The registry record describes random allocation and posts mean FEV1 changes for AZD1981 and placebo, but does not report the formal comparison. Readers should not substitute an informal calculation from separate summaries for a sponsor analysis or a prespecified result.
The outcome counts also demonstrate why denominators belong beside results. The efficacy population is described as 61 AZD1981 and 56 placebo participants, while the endpoint summaries include 60 and 55. The record says not all participants have valid, non-missing values for each measure. Without outcome-specific missingness details, the difference in counts cannot be interpreted further, but it signals that the available data may vary by outcome.
Another statistical lesson is that a range, a mean, and an inferential interval answer different questions. The mean describes average change; the range describes the endpoints of observed values; a confidence interval would describe uncertainty around an estimate. The full ranges posted for FEV1 should not be mistaken for uncertainty intervals around a treatment effect.
The study also includes multiple outcome measures, while its multiplicity approach is not reported. In general, the interpretation of findings across several outcomes depends on how the questions and analyses were planned. Where those details are unavailable, readers should avoid selecting one outcome result as decisive without understanding the analysis context.
Finally, planning calculations based on observed effects are not the same as the original sample-size justification, and they are not observed power. Keeping those concepts separate helps prevent post hoc planning illustrations from being treated as evidence that the trial was adequately or inadequately powered.
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 endpoint summaries do not include a reported between-group estimate, confidence interval, or p-value. This limits assessment of both the direction and precision of a formal treatment contrast. The group means and full ranges are descriptive and cannot independently establish statistical significance or clinical importance.
The primary endpoint is specified through Week 4, and the registry record describes the study as a four-week Phase IIa trial. The results therefore have a short-term scope. The record does not report longer-term outcomes, so no conclusions about durability can be drawn from these results.
The efficacy population counts are 61 in the AZD1981 group and 56 in the placebo group, while the primary outcome summaries use 60 and 55. The record notes that some participants may lack valid, non-missing values for a given outcome, but does not report outcome-specific missingness details, reasons for missingness, or sensitivity analyses. It states that the last post-dose measurement was used if data were missing, without describing the full missing-data strategy.
The record lists multiple outcomes but does not report a multiplicity plan or detailed statistical analysis plan. It also does not report the sample-size justification or interim-analysis plan. The posted safety information is limited to the listed event counts and terms; deaths are not reported in the registry record. These omissions do not show that a particular procedure was or was not used; they limit what can be concluded from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Assess the Efficacy and Safety of AZD1981 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) — NCT00690482.
- Registry record last updated 2014-01-15; status last verified 2013-12.
- Results first posted 2013-12-06.
- 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
The registry record describes a completed randomized, quadruple-masked, parallel-group Phase IIa study of AZD1981 versus placebo in moderate to severe COPD. It records enrollment of 118 and a four-week primary outcome period. The primary endpoint is mean change in FEV1 from baseline to Week 4.
The posted mean changes are 0.007 L for AZD1981 and 0.011 L for placebo. The summary counts are 60 and 55, compared with an efficacy population described as 61 and 56. A formal between-group estimate and its uncertainty are not reported in the registry record. The safety listing reports serious adverse events in 0 of 61 AZD1981 participants and 1 of 56 placebo participants; deaths are not reported in the registry record.
Details of the sample-size justification, multiplicity approach, interim analyses, and full statistical plan are not reported in the registry record.