Should Non-eosinophilic Asthmatic Subjects be Treated With Inhaled Corticosteroids?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Should Non-eosinophilic Asthmatic Subjects be Treated With Inhaled Corticosteroids? (NCT00509197), a randomized na study. The primary outcome is Asthma Control Questionnaire (ACQ) Score After 4 Weeks of Treatment With Inhaled Corticosteroids (ICS) or Placebo.

2. Clinical Question

The study's broad question concerns treatment response among people whose asthma is described as non-eosinophilic. Its primary comparison is narrower: the mean ACQ score after four weeks with fluticasone or placebo. The posted group summaries describe the observed scores, but the registry record does not report an inferential comparison, such as a confidence interval or a p-value. The summaries therefore do not establish how compatible the observed difference is with random variation.

The registry summary also frames questions about adding a long-acting beta-2 agonist and assessing airway inflammation in asthma care. Those broader questions should be distinguished from the posted primary endpoint. The record describes a planned open period with ICS/salmeterol after the initial comparison, but no outcome result for that period is reported in the registry record. The primary result concerns the four-week randomized comparison, not the later treatment question.

3. Trial Design

The registry record describes a randomized, quadruple-masked, parallel-group study with placebo control. The intended comparison was inhaled fluticasone versus placebo in steroid-naïve participants with asthma and no sputum eosinophilia. The brief summary calls the study double-blind, while the design field records quadruple masking; these are both descriptions in the record, and it does not explain the masking roles or reconcile the wording.

The brief summary describes a four-week treatment period with ICS or placebo, followed by a four-week open treatment period with ICS/salmeterol. The primary endpoint was scheduled after the initial four weeks. The intervention and arm descriptions list fluticasone and placebo for the randomized comparison. A result for the subsequent open period is not reported in the registry record, so the posted primary means should not be read as an assessment of that later period.

The registry lists enrollment of 12 and six participants in each primary-outcome arm. The study status is terminated. The recorded start was 2007-10, and primary completion was 2010-05. The sponsor is Université de Montréal. The phase is listed as NA.

The record does not report the reason the study was terminated, the recruitment path, the details of sequence generation or allocation concealment, or the intended sample-size justification. It also does not describe the exact masking procedures or indicate whether participants and assessors remained masked throughout the primary treatment period. Those design details should not be inferred from the randomized and masking labels alone.

The design supports a between-group comparison in principle, but the posted outcome record contains only group-level means and standard deviations. It does not report an adjusted treatment estimate or an inferential test. Consequently, interpretation must remain descriptive: it can characterize the posted ACQ summaries, but cannot determine from the registry record how the analysis was conducted or how uncertainty around the comparison was quantified.

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

Analysis population for the primary outcome, as defined in the registry: Intention to treat

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 Asthma Control Questionnaire (ACQ) Score After 4 Weeks of Treatment With Inhaled Corticosteroids (ICS) or Placebo, measured over Four weeks.

The primary endpoint is the Asthma Control Questionnaire score after four weeks of treatment with inhaled corticosteroids or placebo. The ACQ is a validated questionnaire that combines seven items: the top-scoring five symptoms, FEV1% predicted, and daily rescue bronchodilator use. Participants recall their asthma during the previous week and respond to symptom and bronchodilator-use questions on a seven-point scale, from 0 for no impairment to 6 for maximum impairment. The overall score is the mean of the seven items and ranges from 0, indicating well-controlled asthma, to 6, indicating extremely poorly controlled asthma. Higher scores indicate worse asthma control.

This endpoint offers a standardized way to describe asthma control at the end of the randomized treatment period. It incorporates reported symptoms and treatment use as well as a lung-function measure, rather than relying on a single symptom or physiological reading. A group mean can summarize the average score, while the standard deviation describes variation among participant scores. These summaries do not by themselves show the uncertainty in the difference between treatment groups.

The registry lists the primary population as intention to treat. It reports a mean and standard deviation for each arm at the four-week assessment. The registry record does not report a confidence interval, p-value, or adjusted estimate for the primary comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measure: each participant's ACQ score can take values along a numerical scale, and the registry reports a mean and standard deviation for each arm. A mean describes the central value of the observations in a group. A standard deviation describes how dispersed participant scores are around that mean. These quantities answer different descriptive questions and should not be treated as interchangeable.

What would an estimate of the treatment contrast mean?

In a randomized parallel-group trial, a treatment contrast compares the outcome distribution in the intervention group with that in the comparator group. For a continuous endpoint, the contrast is often expressed as a difference in group means, possibly adjusted for prespecified covariates or baseline values. The registry record posts the arm-level means and standard deviations but does not post a treatment-contrast estimate. No contrast should be reconstructed as if it were the sponsor's analysis. The registry record lists zero analyses and indicates that a recalculated two-arm continuous comparison was not available.

A confidence interval is a range of values generated by a statistical procedure that conveys uncertainty about an estimated contrast. It is not a range containing a specified share of individual participant scores; the standard deviation is more directly related to that participant-level spread. The registry record does not report a confidence interval for the primary comparison. Without one, the posted summary does not show the range of treatment contrasts compatible with the analysis procedure.

A p-value is another inferential summary, assessing how unusual data at least as extreme as the observed data would be under a specified null model. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. No p-value for the primary comparison is reported in the registry record. The descriptive means alone cannot substitute for such a test.

Why does the outcome scale matter?

The ACQ is scored from 0 to 6, with larger values indicating worse asthma control. Thus, the direction of an observed group-mean pattern is interpretable: a lower mean corresponds to better average reported control on this scale. That direction does not establish a causal treatment effect or its precision. The score is constructed as the mean of seven items, including symptoms, FEV1% predicted, and rescue bronchodilator use. A group average can conceal variation among participants or differences in individual components.

Because the endpoint is continuous, standard methods may compare group means, but the choice of method depends on the design, data distribution, analysis plan, and any adjustment factors. The registry record does not report a model, covariate adjustment, or assumptions used for an inferential analysis. General statistical interpretation therefore cannot identify which method, if any, was used for a treatment comparison.

What does the planning illustration represent?

Sample-size planning is a design exercise, not a measure of what a completed study has demonstrated. The registry record's planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Such calculations illustrate how a hypothetical future study might be sized under stated assumptions. They are not observed power and do not change the evidence represented by the posted trial outcomes. The registry record does not report its own sample-size justification, and no planning participant counts are reported in the registry record.

Observed power is not a substitute for an uncertainty interval around a treatment estimate. A planning calculation depends on assumptions about the effect to detect, variability, significance level, and allocation. Those assumptions can differ from the true characteristics of a future study. A small study's observed effect is especially uncertain, so using it as a planning basis should be treated as an illustration rather than a definitive estimate of the effect to expect.

Why can over-dispersion matter?

Over-dispersion is a general concern in models for count outcomes when variability exceeds what the assumed probability model allows. It can make standard errors too small if the model fails to account for the extra variation. This trial's primary outcome is continuous, not a count, and the registry record does not report an over-dispersion model. The concept is not a reason to reinterpret the ACQ summaries; it illustrates why statistical methods should match the outcome type and observed data structure.

Here, the principal limitation for statistical interpretation is simpler: the registry record provides arm-level summaries but no inferential comparison. The means and standard deviations describe the posted observations, whereas a treatment estimate with its uncertainty would be needed to quantify the randomized comparison. The lack of that estimate should not be replaced with a newly calculated result or a significance claim.

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("Fluticasone", "Placebo")
n   <- c(6, 6)
m   <- c(1.4, 2.2)
sp  <- c(0.5, 0.7)
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  Fluticasone  6  1.400  0.500  0.875  1.925
CARM  Placebo  6  2.200  0.700  1.465  2.935

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and three secondary outcomes: Asthma Quality of Life Questionnaire score after four weeks, change in FEV1, and change in PC20. It does not report results for those secondary outcomes. The record also lists zero analyses. A method for controlling multiplicity, such as a prespecified hierarchy or adjustment across outcomes, is not reported in the registry record. Without an analysis plan and outcome-specific results, it is not possible to determine how the investigators intended to handle the possibility of multiple comparisons.

The primary population is identified as intention to treat. That label generally refers to analyzing participants according to their randomized group, regardless of treatment received, but the implementation details are not reported in the registry record. In particular, the record does not say how participants with missing endpoint measurements were handled, whether imputation was used, or whether any sensitivity analyses were planned or performed. The number of missing primary outcome observations is not reported in the registry record.

The primary outcome entries list six participants in each arm. Those outcome counts do not explain whether all randomized participants contributed data under an intention-to-treat analysis, how the population was defined, or whether any exclusions occurred. The registry record does not report baseline characteristics or a participant flow account that would clarify those questions.

Missing-data handling and multiplicity matter because both can affect interpretation of an estimate and its uncertainty. These are general statistical considerations, not claims that missingness or multiplicity changed the posted result. The record does not provide enough detail to assess either issue for this trial.

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 0% reporting threshold.

The registry lists six participants at risk for serious adverse events in each group: Fluticasone 500 mcg Bid and placebo. It reports zero affected by serious adverse events in each group. It also lists six participants at risk for other adverse events in each group and zero affected in each. These figures describe the posted counts for the recorded groups.

Zero reported events in a small group does not establish that an event is impossible or that the treatments have equivalent safety. It indicates only that no affected participants are recorded in these categories for the listed groups. The registry record does not provide event-level descriptions, exposure-adjusted rates, or a comparison estimate. The serious adverse event terms list is empty.

Deaths are not reported in the registry record. That is distinct from a reported zero deaths: the death fields are null, so the record does not establish a count. The safety figures should therefore be read as limited event counts, not as a complete characterization of safety during the study.

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

The posted primary result describes average ACQ scores after four weeks in the randomized fluticasone and placebo groups. The mean was 1.4 (SD 0.5) among six participants assigned to fluticasone and 2.2 (SD 0.7) among six assigned to placebo. Since higher ACQ scores indicate worse asthma control, the group summaries show a lower average score in the fluticasone arm. That is a description of the observed data, not a conclusion about whether treatment caused the pattern.

The registry record does not report an inferential analysis, confidence interval, or p-value for the primary comparison. As a result, it does not quantify the precision of the difference between the group means or show how compatible the observed pattern is with random variation. The standard deviations describe within-group spread; they do not provide the uncertainty interval for a between-group effect. No conclusion about statistical significance or clinical importance can be drawn from the posted summaries alone.

The result also does not answer every question described in the study summary. Secondary outcome results are not reported in the registry record, including quality of life, FEV1, and PC20. The later open treatment period with ICS/salmeterol is described but has no outcome result posted in the registry record. The primary means therefore do not establish whether participants benefited from adding a long-acting beta-2 agonist.

The study's termination status does not itself explain the outcome pattern or the reason the study ended. The reason for termination, the handling of missing observations, and the detailed analysis plan are not reported in the registry record. These omissions limit assessment of the result's completeness and analytic context.

In short, the posted data show descriptive four-week ACQ summaries in a small randomized comparison. They do not establish efficacy, lack of efficacy, or equivalence, and they do not provide a basis for medical advice. A stronger statistical interpretation would require the treatment contrast and its uncertainty, alongside further information about analysis conduct and outcome completeness.

14. Why This Trial Matters Statistically

This trial raises a useful statistical question about how to interpret a randomized comparison when the registry record posts group summaries but no inferential analysis. Means and standard deviations are informative descriptions: they show the average ACQ score in each arm and the variation among participants. Yet they are not a complete account of a treatment comparison. Estimating the contrast and its uncertainty is necessary to distinguish an observed pattern from a precise estimate of an effect.

The small enrolled population also highlights the difference between a completed trial's observed data and a planning calculation. A sample-size illustration based on assumptions is a planning tool, not evidence that the study had a particular probability of detecting an effect. The registry record does not report the trial's own sample-size justification. Planning assumptions and observed outcomes answer different questions and should not be conflated.

The study also illustrates the importance of clearly reporting the analysis population, missing-data procedures, secondary-outcome results, and multiplicity approach. The primary population is labeled intention to treat, but implementation details are absent. The record lists three secondary outcomes without results and does not describe how multiple outcomes were addressed. These reporting gaps make it harder to evaluate the full evidence base represented by the trial.

Finally, the contrast between the randomized four-week period and the described open treatment period is important. The primary outcome pertains to the initial fluticasone-versus-placebo comparison. It does not answer the separate question of adding ICS/salmeterol later. Keeping each phase and outcome distinct prevents a descriptive result from being stretched beyond the comparison it actually represents.

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 enrollment was 12, with six participants listed in each primary-outcome arm. Such a small study gives limited information about the range of outcomes that might occur across a broader population. The registry record posts only group-level means and standard deviations for the primary endpoint, without a confidence interval or treatment-effect estimate. Precision cannot therefore be assessed from an inferential result in the record.

The study status is terminated, but the reason for termination is not reported in the registry record. The record does not describe recruitment progress, participant flow, or whether termination affected the availability of outcome data. It identifies the primary population as intention to treat but does not explain how missing values or deviations from assigned treatment were handled.

Generalizability is also constrained by the specified population: steroid-naïve participants with asthma without sputum eosinophilia. The registry record does not provide enough participant characteristics to assess how closely those enrolled resemble other people with asthma. No baseline ACQ summaries are reported in the registry record, so the posted endpoint means do not show the groups' starting scores.

The brief summary describes a later open ICS/salmeterol period, but no results for that period are reported in the registry record. Results for the listed secondary outcomes are also not reported. The record does not describe an inferential statistical plan, adjustment for baseline measurements, multiplicity control, or missing-data sensitivity analyses. These omissions restrict interpretation to the descriptive primary endpoint summaries and the recorded safety counts.

The masking information is not fully explained: the design field records quadruple masking, while the brief summary uses double-blind wording. The record does not specify which roles were masked or how masking was implemented. These trial-specific limitations do not prove that the study conduct was inadequate; they identify what cannot be evaluated from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Should Non-eosinophilic Asthmatic Subjects be Treated With Inhaled Corticosteroids? — NCT00509197.
• Registry record last updated 2016-08-15; status last verified 2016-07.
• Results first posted 2016-08-15.
• 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

The registry record describes a randomized, quadruple-masked, parallel-group study comparing fluticasone with placebo in steroid-naïve participants with asthma without sputum eosinophilia. Enrollment was 12, and the primary endpoint was the ACQ score after four weeks. The record lists an intention-to-treat primary population and a terminated study status.

The posted primary means were 1.4 (SD 0.5) for fluticasone and 2.2 (SD 0.7) for placebo, with six participants in each group. The registry record lists zero analyses and reports no confidence interval or p-value for the comparison. Three secondary outcomes are listed, but their results are not reported in the registry record. Serious adverse events and other adverse events affected zero of six participants in each group; deaths are not reported in the registry record.

The record describes a later open ICS/salmeterol period, but no result for that period is posted. The reason for termination, detailed analysis plan, and missing-data handling are not reported in the registry record.