Bronchial Thermoplasty in Severe Persistent Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bronchial Thermoplasty in Severe Persistent Asthma (NCT01350336), a na na study. The primary outcome is Subjects Experiencing Severe Exacerbations (Rates).

2. Clinical Question

3. Trial Design

This completed clinical study is registered as NCT01350336 and is titled “Bronchial Thermoplasty in Severe Persistent Asthma.” Its official title describes it as a post-FDA approval clinical trial evaluating bronchial thermoplasty in severe persistent asthma. Boston Scientific Corporation is listed as the sponsor. The study started on 2011-04-07, and primary completion is recorded as 2019-11-12. The registry status is completed.

The study has a single-group model and lists one intervention arm, Alair. Its enrollment is 284. Allocation is recorded as NA, and masking is listed as none. These entries describe a study without a randomized treatment allocation or masking, rather than a randomized comparison between treatment groups. The registry record does not report further details about recruitment, treatment delivery, adherence, or follow-up procedures.

The primary endpoint is framed as a comparison over time within the post-treatment follow-up: the first 12-month period after treatment is compared with the subsequent 12-month periods for Years 2, 3, 4, and 5. This makes the durability of the observed pattern an important part of the study question. It does not, by itself, provide a concurrent control group or establish what would have happened over the same periods without treatment.

The registry lists 12 outcome measures and four analyses, but does not describe the analysis methods or identify the results for the primary endpoint. It names secondary outcomes covering severe exacerbations, respiratory adverse events, emergency room visits for respiratory symptoms, hospitalizations for respiratory symptoms, and respiratory serious adverse events. The record does not report a detailed schedule of assessments or the number of participants contributing data at each follow-up period.

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: Primary Endpoint - the proportion of subjects experiencing severe exacerbations during the subsequent 12-month (for Years 2, 3, 4, and 5) compared to the first 12-month after the Alair treatment.

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: Subjects with at least 1 BT procedure.

6. Primary Endpoint

The registry lists the primary outcome as Subjects Experiencing Severe Exacerbations (Rates), measured over Year 1 vs. Year 2, 3, 4, 5.

The primary endpoint is titled “Subjects Experiencing Severe Exacerbations (Rates)” and uses participants as its unit. Its description defines the outcome as the proportion of participants experiencing severe exacerbations during the subsequent 12-month period in Years 2, 3, 4, and 5, compared with the first 12-month period after Alair treatment. Thus, the question is not only whether severe exacerbations occurred, but how their occurrence in later periods relates to the first post-treatment year.

A proportion is useful for describing how common an event is within a defined group and period. Looking across successive periods can help address whether an observed pattern is maintained over time. However, the interpretation depends on clear denominators, consistent event definitions, and knowledge of who contributed information in each period. Those details and the primary endpoint estimates are not reported in the registry record.

The endpoint is a participant-based measure, not a count of every exacerbation. A participant who experiences more than one event may still contribute as a participant experiencing the outcome, depending on the endpoint definition. The record does not give further operational detail on event ascertainment or how repeated events were handled. No numerical comparison, confidence interval, or test result for this endpoint is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant-based endpoint measure?

In general, a participant-based event outcome records whether each participant experienced the defined event during a specified period. It differs from an event-count outcome, which can count multiple occurrences in one participant. The primary endpoint is described as the proportion of participants experiencing severe exacerbations, so its intended summary concerns participants with at least one qualifying event rather than the total number of events. The record does not provide further rules for defining or adjudicating a severe exacerbation.

What does a comparison across follow-up periods mean?

In general, a comparison across periods can describe whether the frequency of an outcome changes over time in a study group. Here, the endpoint description sets the first 12-month period after treatment against subsequent 12-month periods in Years 2, 3, 4, and 5. Since the study has a single group, these are not comparisons between randomized treatment arms. The registry record does not report whether the analysis used paired observations, an independent-period approach, a repeated-measures model, or another method. It is therefore not possible to infer the statistical model from the endpoint wording alone.

Period comparisons require attention to their denominators. If the number of participants contributing information varies from one period to another, the proportions can reflect both outcome experience and differences in who remains observed. In general, incomplete follow-up can affect interpretation if missingness is related to participants' health or event history. The record does not report period-specific denominators, missing-data assumptions, or methods for handling incomplete follow-up.

What would a confidence interval communicate?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. An interval for a difference or ratio can also indicate which values are compatible with the observed data under the model. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed from the posted information.

What can a p-value establish?

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry record does not report a p-value or state the null hypothesis or test used for the primary endpoint. The four recorded analyses are not described in sufficient detail to identify their purpose or interpretation.

Why does the single-group design matter?

In general, random allocation can help make treatment groups comparable with respect to both measured and unmeasured factors. This study has a single-group model and no randomized comparator, so it cannot provide a randomized between-group estimate. Comparing later periods with an earlier post-treatment period can be useful for describing the observed course, but it has different limitations from a controlled comparison. Time trends, changes in follow-up, or other influences may contribute to a difference between periods. The registry record does not describe methods to address such influences.

How should event proportions be distinguished from event rates?

In general, a proportion uses the number of participants with an event over a defined denominator. A rate may use person-time or another exposure denominator, depending on its definition. Although the primary endpoint title includes “Rates,” its description specifies a proportion of participants experiencing severe exacerbations. The registry record does not give a more detailed calculation definition. Interpretation should therefore follow the endpoint description rather than assume a person-time rate.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that the observed variability is greater than expected under a simple model such as a Poisson model. It can matter because a model that assumes too little variability may produce confidence intervals that are too narrow and tests that are too optimistic. This general issue is relevant when modeling event counts, especially when participants can experience repeated events. The primary endpoint is described as a participant proportion, and the registry record does not state that an over-dispersed count model was used. No particular model should be attributed to this study without a reported analysis plan or results.

What can planning calculations tell readers?

In general, sample-size calculations are design illustrations: they describe how many participants a hypothetical study might require under chosen assumptions about the effect, significance level, allocation, and statistical method. They are not observed outcomes and are not a measure of the probability that a study result is correct. Any planning illustration based on an observed effect also depends on that effect estimate and its uncertainty. The registry record does not report the trial's own sample-size justification or a detailed design calculation. It therefore does not establish why the enrollment was selected or what power was planned for the primary endpoint.

These distinctions matter especially for a post-approval study intended to describe durability and safety. Descriptive counts can summarize what was recorded, while inferential comparisons require an explicit estimand, analysis population, statistical method, and uncertainty measure. Those inferential details for the primary endpoint are not reported in the registry record.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("Year 1", "Year 2", "Year 3", "Year 4", "Year 5")
n      <- c(262, 252, 247, 240, 227)
events <- c(132, 118, 118, 106, 97)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Year 1  262  132  50.4  44.2  56.6  44.4  56.4  44.4  56.4
ARM  Year 2  252  118  46.8  40.5  53.2  40.8  53.0  40.8  53.0
ARM  Year 3  247  118  47.8  41.4  54.2  41.6  54.0  41.6  54.0
ARM  Year 4  240  106  44.2  37.8  50.7  38.0  50.5  38.0  50.5
ARM  Year 5  227  97  42.7  36.2  49.4  36.5  49.2  36.5  49.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and four analyses. It does not report which analyses correspond to which outcomes, whether any were prespecified as confirmatory, or how the analysis plan handled multiple outcomes or repeated follow-up periods. When several outcomes or time-period comparisons are examined, the chance of finding at least one apparently notable result can increase. In general, multiplicity procedures can control that risk, but the appropriate approach depends on the scientific aims and analysis plan. No adjustment method or testing hierarchy is reported in the registry record.

The record does not report whether the primary comparison across Years 2, 3, 4, and 5 was treated as one overall test or as separate period-specific tests. It also does not report whether any interim analyses were planned or performed. Neither the use nor the absence of interim analyses can be inferred from the study status or endpoint description.

Information about missing data and analysis populations is also not reported in the registry record. There is no stated intention-to-treat, per-protocol, or other analysis population, and no description of how participants with incomplete follow-up were handled. Because the endpoint compares repeated follow-up periods, the number of participants contributing data in each period and the method for handling missing observations would be important to interpretation. Without those details, the posted information does not establish whether each period's proportion uses the same population or comparable denominators.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthma (20.8%), pneumonia (3.6%), procedural pain (2.5%), arthralgia (2.2%), bronchitis (2.2%).

The registry record lists safety information for the Alair group. It reports 130 participants with serious adverse events among 279 at risk and 268 participants with other adverse events among 279 at risk. It also reports four deaths. These are separate recorded safety figures; the record does not explain the relationship between the event categories, the timing of events, or the characteristics of affected participants.

The listed serious adverse event terms include asthma (20.8%), pneumonia (3.6%), procedural pain (2.5%), arthralgia (2.2%), bronchitis (2.2%), and influenza (1.8%). These percentages are quoted as recorded. The registry record does not specify additional details needed to interpret each term's denominator or to determine whether events could be counted more than once for a participant.

Adverse events recorded during a study are not automatically caused by the intervention. A single-group study without a concurrent control cannot provide a randomized comparison of event frequency against another treatment or no treatment. The listed counts and terms describe reported safety observations; they do not establish causality. Further details about severity grading, relatedness assessments, event timing, and the circumstances of the deaths are not reported in the registry record.

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

The study's primary question concerns severe exacerbations over time after Alair treatment. The registry record defines a comparison between the first 12-month period after treatment and later 12-month periods in Years 2, 3, 4, and 5. This framing makes durability an intended focus, consistent with the registry summary's description of the post-approval study purpose.

However, the endpoint results are not reported in the registry record. There are no period-specific proportions, no estimated contrasts, and no measures of statistical uncertainty. As a result, the posted information does not show whether severe exacerbation experience increased, decreased, or remained similar across the stated periods. It also does not show how precisely any period comparison was estimated.

The single-group design further defines what the study can establish. A comparison of periods within one group describes changes over follow-up among observed participants, but it is not a randomized comparison against an alternative. Even if period-specific results were available, an observed change over time would not, by itself, identify the cause of that change. The registry record does not report adjustment methods or other analyses that could address potential time-related influences.

The safety counts are likewise descriptive. They record participants affected by serious and other adverse events, as well as deaths, but do not establish that the intervention caused those events. Nor can those counts be compared with a control group in this single-group study. The event-term percentages add descriptive detail, but do not replace a comparative safety analysis.

Accordingly, the registry information supports understanding of the intended endpoint, the single-group structure, and reported safety observations. It does not support a quantitative conclusion about the primary endpoint or a causal estimate of benefit or harm. The missing results and analysis details limit assessment of both effect magnitude and precision.

14. Why This Trial Matters Statistically

This study is statistically notable because it asks a durability question after FDA approval, rather than describing a randomized comparison between treatment groups. The registry summary states that the sponsor was required to generate data on durability of the bronchial thermoplasty treatment effect and safety in the intended-use population in the United States. Its endpoint compares the first 12-month period after treatment with later follow-up periods, making the time structure central to interpretation.

Repeated follow-up raises practical and analytical questions: whether the same participants contribute information in each period, whether the event definition is consistent over time, and how incomplete observations are handled. These details determine how confidently period-specific proportions can be compared. They are not reported in the registry record, and the numerical primary endpoint results are also absent.

The design illustrates a distinction between describing outcomes after treatment and estimating a treatment effect against a concurrent comparator. A single-group study can contribute information about observed follow-up and safety in its enrolled population, but it does not supply a randomized control comparison. That distinction is important when interpreting any claimed change over time.

The registry also identifies a range of secondary respiratory outcomes, including exacerbations, adverse events, emergency room visits, and hospitalizations. Having multiple outcomes and several follow-up periods creates questions about prespecification and multiplicity. The record lists 12 outcome measures and four analyses, but does not explain the analysis plan or how those outcomes were prioritized. For statistical interpretation, the value of this record lies in clarifying the study question and the boundaries of what the posted information can establish.

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 main limitation for interpreting efficacy is that primary endpoint results are not reported in the registry record. There are no reported proportions by follow-up period, contrasts, confidence intervals, or p-values. The primary question is therefore identifiable, but its observed answer cannot be evaluated from the posted information.

The study's single-group design limits causal interpretation. There is no randomized comparator, and the endpoint compares time periods after treatment rather than treatment assignments. Period-to-period differences, if reported, could reflect changes other than treatment effects. The registry record does not report an approach for separating these influences.

The available description does not include detailed eligibility criteria, participant characteristics, or the number assessed at each follow-up period. It does not report how severe exacerbations were defined and ascertained beyond the endpoint description, whether the same participants contributed across years, or how missing observations were handled. These omissions limit assessment of follow-up completeness and the comparability of period-specific results.

The registry lists 12 outcome measures and four analyses, but the analysis plan, multiplicity approach, and analysis populations are not reported. The record also does not report a sample-size justification, interim-analysis plan, or statistical model. These methods should not be inferred from the enrollment or study design.

Safety information is descriptive and lacks a concurrent control comparison. The registry record does not provide additional context on event timing, relatedness, severity grading, or the deaths. Thus, the reported counts cannot establish comparative risk or causation. These limitations are specific to interpreting the study information available in the registry record; they do not substitute for the full clinical study report.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bronchial Thermoplasty in Severe Persistent Asthma — NCT01350336.
• Registry record last updated 2021-03-05; status last verified 2021-02.
• Results first posted 2021-03-05.
• 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

NCT01350336 is a completed, single-group, post-FDA approval clinical study of the Alair System in severe persistent asthma. Boston Scientific Corporation is listed as sponsor, enrollment is 284, and the registry records no masking. The primary endpoint concerns the proportion of participants experiencing severe exacerbations in the first 12-month period after treatment compared with later 12-month periods in Years 2, 3, 4, and 5.

The registry record describes the endpoint and lists secondary respiratory outcomes, but does not report numerical primary endpoint results, statistical uncertainty, or analysis methods. Safety entries include 130 participants with serious adverse events among 279 at risk, 268 with other adverse events among 279 at risk, and four deaths. These are descriptive observations from a single-group study, not comparative or causal estimates.