Enhancement of in-Vitro GC Function in Patients With COPD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Enhancement of in-Vitro GC Function in Patients With COPD (NCT00241631), a randomized phase 2 study. The primary outcome is Sputum Inflammatory Cell Counts.

2. Clinical Question

3. Trial Design

The registry describes a Phase 2, randomized, triple-masked, parallel-group study in patients with COPD. It is marked completed, with a recorded enrollment of 49. The registry dates the start to 2006-04 and primary completion to 2007-08. These record-level details describe the trial as registered; they do not, by themselves, explain how participants were recruited, how masking was maintained, or how the study was conducted at each visit.

The arm descriptions distinguish a Placebo arm and a Steroid arm. Both descriptions include an inhaled theophylline placebo capsule and active Theophylline; the listed middle treatment is placebo in the Placebo arm and Fluticasone Propionate 500 ug bid in the Steroid arm. The registry does not explain the timing or duration of each listed treatment in these descriptions, so the sequence should not be expanded into a more detailed regimen.

The registry’s brief summary calls the study a small clinical pilot and describes an intended study on 20-30 COPD patients. The recorded enrollment is 49. The reason for the difference between the summary’s stated range and the enrollment field is not reported in the registry record. It is also not reported whether the enrollment field has a particular relationship to the participants contributing to the primary outcome summaries.

The posted primary outcome is sputum inflammatory cell counts at 10 weeks. The registry says that supernatant was collected and cell pellets were counted on slides, and that the results use marginal means. It also lists Interleukin 8 (IL8) and Total Sputum Eosinophils as secondary outcomes. The record does not provide detailed eligibility criteria, the allocation procedure, masking procedures, or a fuller visit schedule.

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.

Run in (2 Weeks)

Reasons for not completing this period:

Phase 1 (4 Weeks)

Reasons for not completing this period:

Wash Out (2 Weeks)

Phase 2 (4 Weeks)

Analysis population for the primary outcome, as defined in the registry: Using marginal means as results

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 Sputum Inflammatory Cell Counts, measured over 10 weeks.

The primary endpoint is titled Sputum Inflammatory Cell Counts and is expressed in millions cells/ ml. It is a continuous measure summarized as a mean, with a 95% confidence interval for each arm. The measurement is described as involving collected supernatant and cell pellets counted on slides, and the assessment timeframe is 10 weeks.

As general statistical context, a sputum cell count provides a quantitative measure of inflammatory cells in a respiratory sample. A continuous measure can retain information about the range of observed values, rather than reducing each participant’s result to a category. Reporting a mean describes the central level of the measure for an arm, while a confidence interval communicates uncertainty around that estimate.

This endpoint concerns a laboratory measure in induced sputum. It is not itself a measure of symptoms, daily functioning, or a clinical event. The registry record does not report a threshold for interpreting a change in cell counts or explain how the endpoint relates to a patient-important outcome. The statistical comparison therefore addresses the recorded sputum measure, not broader clinical outcomes.

The registry identifies the reported arm means as marginal means. The meaning of the marginal means depends on the model and its specification; details of that specification are not reported in the registry record. The values can be read as the reported arm-level summaries, but the record does not give a corresponding numerical estimate of the between-arm contrast or a confidence interval for that contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous primary outcome summarized as a mean, with a 95% confidence interval, and identifies the results as marginal means. It names a Mixed Models Analysis for the comparison between the Placebo and Steroid arms and reports p = 0.012. The registry labels that analysis as a superiority comparison. Those details identify the broad form of the reported analysis, but they do not fully specify how the model was fitted or how its result was obtained.

What does a mean describe?

General statistical context: for a continuous measurement, the mean is a summary of the distribution’s central level. It can be useful when the mean is a relevant description of the target quantity, but it does not show the distribution of individual observations. A mean alone does not reveal whether values are tightly clustered or widely dispersed, nor whether a small number of extreme observations influence the summary. The record gives arm means and confidence intervals, but does not provide the underlying outcome distributions or individual observations.

The unit is millions cells/ ml. The Placebo arm mean is 5.42 and its 95% confidence interval is 3.56 to 8.2. The Steroid arm mean is 3.89 and its 95% confidence interval is 2.6 to 5.76. These summaries are reported as marginal means. In general, a marginal mean is a model-based mean for an arm, interpreted according to the model’s terms and assumptions. The model details needed to explain precisely which quantities were averaged or adjusted for are not reported in the registry record.

What does a confidence interval convey?

General statistical context: a confidence interval represents uncertainty in an estimated quantity under a statistical procedure and its assumptions. It is not a range containing a specified proportion of individual participants’ measurements, and it is not a probability statement about a fixed parameter in the usual frequentist interpretation. A narrower interval indicates greater precision for the quantity it estimates, while a wider interval indicates less precision. The intervals in this record are for the arm-specific marginal means, not for the between-arm difference.

The absence of a reported interval for the contrast matters because the primary inferential question is comparative. A direct estimate of the contrast would describe the magnitude and direction of the model-based comparison, and its interval would describe uncertainty around that comparison. The registry reports a p-value for the comparison but does not report the contrast estimate, its confidence interval, or the model coefficients. No unadjusted re-calculation of a two-arm continuous contrast is available from the posted summary statistics in this record.

Why might a mixed model be used?

General statistical context: mixed models can represent several sources of variation and can account for correlated observations when the design or data structure includes them. They can also estimate means or contrasts under a specified model. These are general capabilities, not a description of the implementation in this trial. The registry record does not report the model’s fixed or random effects, covariance structure, estimation method, handling of repeated observations, covariates, or assumptions about missing data. It is therefore not possible to identify which features of a mixed model were used in this analysis.

The registry’s primary outcome description refers to induced sputum cell counts and states a 10-week timeframe. It does not establish whether the analysis used only a measurement at that timeframe or incorporated other measurements. The visit-level data and the model’s time terms are not reported. Any claim about how repeated measures were handled would go beyond the record.

How should the p-value be read?

General statistical context: a p-value measures how unusual data at least as incompatible with a null hypothesis as the observed data would be, if that null hypothesis and the analysis assumptions held. It does not quantify the magnitude of an effect, and it is not the probability that a finding occurred by chance. The reported value, 0.012, is the registry’s inferential summary for the named mixed-model analysis. The record does not state the testing procedure, the exact null, whether the reported p-value is adjusted, or the threshold used to interpret it.

A p-value should be considered alongside the estimated effect and its uncertainty. Here, the arm summaries provide context about the observed means, but the missing contrast estimate limits direct assessment of the comparative magnitude. A p-value alone does not establish that a difference is clinically important or that the analysis assumptions are appropriate. The record’s label of superiority describes the analysis category; it does not supply the omitted estimate or interpretation threshold.

What is not specified?

The registry record does not report the statistical analysis plan, the sample-size justification, interim analyses, the model specification, or detailed analysis populations. It does not say whether the mixed-model analysis followed an intention-to-treat principle or another population definition. The sample-size assumptions listed for planning illustrations are not the trial’s own design specification: they describe illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such planning illustrations are not observed power and do not substitute for a trial-specific justification. No numerical planning estimates are included in the registry record for this explanation.

10. Analyses Reported by the Sponsor

The registry’s own reported comparison is a Mixed Models Analysis, labelled as a superiority analysis, with p = 0.012. This is the inferential result to use when describing the sponsor’s posted analysis. It accompanies arm-specific marginal means and 95% confidence intervals, but the registry does not report the model-based contrast or its confidence interval.

No recalculated between-arm estimate is available from the posted summary statistics. The record specifically indicates that values are missing or not estimable for a two-arm comparison of this continuous endpoint. A recalculation based only on the arm summaries would not reproduce the mixed-model analysis, which may depend on information and model details not present in those summaries. The arm means should therefore not be converted into a new contrast or used to claim that the sponsor’s model result has been independently replicated.

The record marks no discrepancy between the posted result and any recalculation. In this case, the appropriate reading is that the sponsor’s reported analysis stands as the available comparative test, while the effect size and its uncertainty remain unreported. The p-value does not fill that reporting gap: it answers a different statistical question from an estimated contrast and confidence interval.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists Interleukin 8 (IL8) and Total Sputum Eosinophils as secondary outcomes. It reports three outcome measures and three analyses, but the numerical results available for this interpretation describe the primary sputum inflammatory cell count only. Results for the secondary outcomes are not reported in the registry record presented for this analysis.

When a study assesses more than one outcome or carries out more than one statistical test, the chance of at least one apparently unusual result can depend on the testing strategy. General statistical context: multiplicity can be addressed through prespecified outcome hierarchies, adjustments to inference, or other analysis plans. The registry record does not report whether any multiplicity adjustment was used, which outcomes or analyses were considered confirmatory, or how the primary and secondary analyses were ordered. The p-value should not be assumed to be adjusted or unadjusted.

The record does not report a statistical analysis plan, so it is not possible to establish whether the reported outcome, model, and comparison were prespecified in the form analyzed. It also does not report interim analyses or stopping rules. These omissions do not establish that such procedures were absent; they mean their presence and details are not reported in the registry record.

The arm summaries give outcome counts of 14 for Placebo and 16 for Steroid, while the enrollment field records 49. The record does not explain the relationship between these values. It does not report the number of participants with missing sputum measurements, reasons for missingness, imputation methods, or sensitivity analyses. The analysis population and the handling of deviations from assigned treatment are also not reported. Consequently, the available record does not establish whether the reported summaries represent all enrolled participants, all randomized participants, or another defined analysis population.

Missing-data assumptions can affect model-based estimates, especially when availability of an outcome is related to participant characteristics or observed results. General statistical context: methods that use incomplete data rely on assumptions about the missingness process, and sensitivity analyses can help assess how conclusions change under alternative assumptions. No such assumptions or sensitivity analyses are described in this registry record.

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.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events in either arm: the serious-event count is 0 among 14 at risk in the Placebo arm and 0 among 16 at risk in the Steroid arm. It reports no deaths in either arm. For other adverse events, it records 0 among 14 at risk in Placebo and 4 among 16 at risk in Steroid. The registry does not list serious adverse-event terms.

These figures are counts in the registry’s adverse-event fields. They do not, on their own, describe event severity beyond the serious-versus-other classification, event timing, duration, or relationship to treatment. The record does not explain how adverse events were collected or define the specific criteria used for reporting them. It also does not provide event-level descriptions for the other adverse events.

Zero reported serious events in these arm summaries does not demonstrate that serious events cannot occur, and the other-event counts do not establish that treatment caused those events. The figures should be read as the safety information recorded for this trial, with the limited detail available in the registry record.

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

The posted outcome summaries describe sputum inflammatory cell counts at 10 weeks. The Steroid arm has a reported marginal mean of 3.89 millions cells/ ml, compared with 5.42 millions cells/ ml in the Placebo arm. The registry also reports a mixed-model superiority comparison with p = 0.012. Together, these are the numerical descriptions available for the primary endpoint: arm-specific means and their 95% confidence intervals, plus the model’s p-value.

The record does not provide a model-based estimate of the difference between arms or a confidence interval for that difference. As a result, the comparative magnitude and precision cannot be read directly from the registry’s reported inferential result. The p-value does not say how large the difference is or whether it is important to patients. The arm-specific confidence intervals are not substitutes for a confidence interval around the contrast.

The endpoint is a sputum laboratory measure, not a direct report of how participants felt or functioned. The registry does not provide results for symptoms, quality of life, lung function, exacerbations, or other clinical outcomes in the registry record used for this interpretation. It lists Interleukin 8 (IL8) and Total Sputum Eosinophils as secondary outcomes, but their numerical results are not reported in the record information available.

The study is registered as a Phase 2 randomized, triple-masked, parallel-group trial and is marked completed. Those design labels do not resolve questions about the analysis population, missing outcome data, model specification, or multiplicity. The record does not report a clinical threshold for the primary measure or enough detail to translate the statistical result into a patient-level interpretation.

Accordingly, the reported findings should be understood as an analysis of the listed sputum cell-count measure in this study. They do not establish a broader clinical effect, explain the mechanism of any observed difference, or guarantee that the same result would occur in other populations or settings. Those questions require information and evidence beyond the primary endpoint summary and p-value recorded.

14. Why This Trial Matters Statistically

This trial illustrates why a statistical result is easier to assess when an estimated contrast and its uncertainty accompany a p-value. The registry gives arm-specific marginal means and confidence intervals, and it reports a mixed-model p-value for the comparison. Without the contrast estimate and its confidence interval, readers can see the arm-level summaries and the reported test result but cannot directly assess the size and precision of the model-based comparison.

It also illustrates the distinction between an endpoint’s statistical meaning and its clinical meaning. Sputum inflammatory cell counts are a quantitative laboratory measure, while the registry does not report a threshold that would make a particular value clinically meaningful. A p-value does not supply that threshold. Connecting a laboratory result to clinical relevance requires an interpretive framework that is not described in the registry record.

The record includes several details that help orient interpretation: randomization, triple masking, a parallel-group model, a 10-week timeframe, and arm-specific outcome counts. Yet other details important for appraisal are not reported, including the model specification, analysis population, missing-data handling, and multiplicity approach. This makes the study useful for illustrating the difference between a broad label such as “mixed models” and the information needed to reproduce or fully evaluate a model-based result.

Finally, the entry shows why enrollment and outcome-summary counts should be read as distinct record fields rather than assumed to describe the same analysis set. The enrollment field records 49, whereas the outcome summaries list 14 for Placebo and 16 for Steroid. The registry does not explain that relationship. Recognizing this reporting gap is important when considering how complete or representative the analyzed outcome data may be.

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.

Several trial-specific details needed for a fuller interpretation are not reported in the registry record. The primary result is presented as arm-specific marginal means and confidence intervals, without the estimated between-arm contrast or its confidence interval. The named mixed-model analysis is not accompanied by its model specification, test details, covariates, or assumptions. That limits the ability to assess the comparative effect’s magnitude, precision, and reproducibility.

The relationship between recorded enrollment of 49 and the primary outcome counts of 14 in Placebo and 16 in Steroid is not explained. The registry does not state how many participants were randomized, how many contributed measurements at each time, or how missing data were handled. It also does not identify the analysis population or describe treatment adherence and deviations. These omissions limit assessment of how the reported summaries relate to the enrolled study population.

The brief summary describes a pilot study intended for 20-30 COPD patients, while the enrollment field records 49. The reason for this difference is not reported. A trial-specific sample-size justification is also not reported; planning illustrations based on observed effects should not be mistaken for the original design rationale or for observed power.

The record does not report multiplicity procedures, an analysis plan, interim analyses, a significance threshold for the primary comparison, or numerical results for the two listed secondary outcomes. It does not provide detailed eligibility criteria, recruitment information, or a fuller treatment schedule beyond the arm descriptions. The safety fields report counts but not detailed event descriptions or collection procedures. These limits apply to what the registry record reports; they do not establish that unreported methods or information were absent from the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Enhancement of in-Vitro GC Function in Patients With COPD — NCT00241631.
• Registry record last updated 2019-12-04; status last verified 2019-11.
• Results first posted 2019-12-04.
• 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

The registry identifies NCT00241631 as a completed Phase 2 randomized, triple-masked, parallel-group COPD study sponsored by Imperial College London. Recorded enrollment is 49, with the study start dated 2006-04 and primary completion dated 2007-08. The primary outcome is sputum inflammatory cell counts at 10 weeks, measured in millions cells/ ml and summarized as marginal means.

The Placebo arm mean is 5.42, with a 95% confidence interval of 3.56 to 8.2; the Steroid arm mean is 3.89, with a 95% confidence interval of 2.6 to 5.76. The registry reports a mixed-model superiority comparison with p = 0.012, but no contrast estimate or confidence interval for the between-arm comparison. Secondary outcomes listed are Interleukin 8 (IL8) and Total Sputum Eosinophils. The record does not report their numerical findings or key details of the statistical model, missing-data handling, analysis population, and multiplicity approach.