Relief of Acute Bronchoconstriction/Asthma Using the Non-Invasive AlphaCore Device: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Relief of Acute Bronchoconstriction/Asthma Using the Non-Invasive AlphaCore Device (NCT01532817), a na na study. The primary outcome is Safety- Number of Participants With Adverse Events.

2. Clinical Question

In practical terms, the registry asks whether adverse events were recorded among participants receiving the device during the stated observation period. The posted results report counts in the AlphaCore group, including 0 participants with serious adverse events, 0 deaths, and 10 participants with other adverse events. These observations describe the recorded experience in this study group. Without a control group, they cannot establish how the event counts would compare under another management approach or whether any event was caused by the device.

3. Trial Design

This was a completed, single-group pilot study of the AlphaCore device in asthma. The registry identifies the intervention as a device and describes it as non-invasive neurostimulation of the vagus nerve. The study purpose was to collect preliminary clinical data concerning safety and preliminary clinical benefits for relief of acute bronchoconstriction. The posted primary outcome, however, is a safety count; no primary measure of symptom relief or lung function is listed in the registry outcome information.

The record lists enrollment as 30 and the summary describes a plan to enroll up to 30 eligible, consenting subjects at up to 5 investigational sites. These are not competing descriptions of a control comparison: all listed outcome results belong to the Alphacore group. The record does not provide site-specific enrollment, participant flow, or the number who completed the follow-up visit.

Allocation is marked NA, the model is single-group, and masking is listed as none. Thus, the record does not describe random assignment or blinded outcome assessment. There is no like-for-like control group from which to estimate a between-group effect. The trial is listed as completed, with a start date of 2012-01 and primary completion in 2012-05. Phase is recorded as NA.

The setting is described as clinics capable of addressing potential complications of bronchoconstriction, acute asthma exacerbation, and emergencies associated with the investigational device. The registry record does not report the actual care delivered at each site, the device-use protocol, deviations from that protocol, or the duration of follow-up beyond the specified 1-week visit. These details limit how fully the conduct of the study can be reconstructed from the posted record.

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: Open label study 30 participants

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: Open label 30 patient population

6. Primary Endpoint

The registry lists the primary outcome as Safety- Number of Participants With Adverse Events, measured over From time subject signs the consent through the 1-week follow-up visit.

The primary endpoint is the number of participants with adverse events, including events described in the registry as device-related, serious, or unanticipated. Its unit is participants, so the outcome is a count of people with an event, rather than a count of every event occurrence. The stated timeframe runs from when a subject signs consent through the 1-week follow-up visit. The outcome population is described as an open-label study of 30 participants.

A participant-based safety count is used to describe how many people in the study group experienced an adverse event during the defined observation period. It offers a direct summary of recorded safety experience, while not conveying how many events each participant experienced, how long events lasted, or how severe non-serious events were. The registry record does not provide event-level detail for the other adverse events.

This outcome does not itself measure relief of bronchoconstriction. The study summary refers to preliminary clinical benefits as a purpose, but the listed primary endpoint is safety. The registry record does not report a primary efficacy endpoint, a threshold for meaningful clinical improvement, or a method for linking a change in respiratory status to device use. Consequently, the posted primary result should be read as an adverse-event count, not as evidence of clinical benefit or lack of benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a count of participants with adverse events. It is not a continuous measurement such as a change in lung function, nor is it a time-to-event estimate. The endpoint definition and timeframe determine what the count is intended to capture: events from consent through the 1-week follow-up visit. The posted categories distinguish serious events from other adverse events, and the record separately lists deaths.

What does a participant count describe?

In general, a participant count records whether each person met the outcome definition during the observation period. It does not reveal the total number of event episodes when one person can experience more than one event. It also does not show event duration, severity beyond the categories recorded, or the timing of events unless those details are posted separately. Here, the registry provides group counts but does not provide a narrative or event-level listing for the other adverse events.

The group is listed with 30 participants at risk for the serious-event and other-event counts. That denominator gives context for the posted counts, but the record does not state whether every participant had complete observation through the planned follow-up visit. A count with an at-risk group should therefore not be mistaken for a complete participant-flow account. No missing-outcome details are reported in the registry record.

Why does study design matter?

In general, a control group helps distinguish outcomes occurring after an intervention from outcomes that may occur without it or under another approach. This trial has a single group, with allocation marked NA and masking listed as none. The AlphaCore results therefore describe that group's recorded experience; they do not estimate a difference between device use and a comparator. Without random assignment, observed outcomes also cannot be attributed to the intervention independently of other influences.

Masking can reduce the influence of knowledge about treatment assignment on outcome assessment or reporting. Since masking is listed as none, the record does not indicate that participants or study personnel were blinded. The registry does not describe who assessed events, how events were elicited, or whether an independent committee reviewed them. This absence of detail matters particularly for outcomes whose identification or classification may involve judgment.

What can statistical uncertainty add?

In general, a confidence interval expresses the range of values compatible with an estimate under a specified statistical model and procedure. It can help distinguish a precise estimate from one that remains uncertain. The registry record does not post confidence intervals for the adverse-event counts. A count of zero serious events should not be interpreted as a precise demonstration that serious events cannot occur; the underlying event frequency remains uncertain, and the record does not give a modeled interval for it.

In general, over-dispersion is relevant when event counts vary more than a statistical model expects, often because people differ in their event propensity or because events cluster. For a participant-level binary outcome, the fundamental record is whether a participant experienced an event, rather than the number of episodes. The registry does not provide individual event histories or a model assessing variation across participants. No over-dispersion adjustment or count-process analysis is reported.

How should the analysis listing be read?

The registry reports 0 analyses. This indicates that the registry record contains no posted analysis entries for this outcome. It is not a statement that no calculations or review were performed by the investigators. The record does not identify a statistical analysis plan, an estimator, a hypothesis, or a method for handling repeated events. The results should therefore be read as descriptive posted counts rather than as output from a documented inferential analysis.

The study summary describes a pilot intended to collect preliminary safety and clinical-benefit data. A pilot can be informative about what was recorded during study conduct, but the registry does not state a sample-size justification or a target for statistical precision. Any planning illustration based on the observed effect uses assumptions that are separate from the trial's documented design. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not describe this single-group study, and they should not be interpreted as the trial's enrollment rationale or as observed power. Planning sample sizes are hypothetical design aids, not a measure of the evidence generated by these participants.

In general, an analysis plan also specifies which participants are included, how outcomes are defined, and how missing observations are treated. The registry record does not report these analysis details beyond the stated outcome population and timeframe. This makes it difficult to determine whether the posted counts reflect all enrolled participants, only those with available follow-up, or another analysis set. The record's absence of detail should be treated as uncertainty about reporting, not filled by assumptions.

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("Alphacore")
n      <- c(30)
events <- c(10)
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  Alphacore  30  10  33.3  17.3  52.8  19.2  51.2  19.2  51.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 1 outcome measure and 0 analyses. The posted primary outcome is the count of participants with adverse events. The study summary mentions preliminary clinical benefits as an objective, but the registry outcome information does not list a corresponding efficacy endpoint. No multiplicity procedure, hierarchy of outcomes, or adjustment for multiple statistical tests is reported in the registry record. Since analysis results are not posted, there is no documented family of inferential tests from which to assess multiplicity handling.

Missing-data handling is not reported in the registry record. The outcome timeframe extends through the 1-week follow-up visit, but the record does not describe attendance, follow-up completion, withdrawals, unavailable observations, or how such cases were classified. The group count at risk does not establish that follow-up was complete for every participant. It is therefore not possible to judge from the record whether the adverse-event counts could be affected by incomplete ascertainment.

The analysis population is described as an open-label study of 30 participants for the primary outcome. The registry does not further define an intention-to-treat, per-protocol, or safety population, nor does it explain exclusions from the reported counts. The available record also does not say how repeat events in the same person were handled beyond defining the endpoint in terms of participants with events. These omissions limit reproducibility and make it important to interpret the counts as posted descriptive information, rather than assuming an unstated analysis convention.

In general, multiplicity and missingness can affect how confidently results are interpreted: testing many outcomes can make isolated findings harder to interpret, while incomplete observation can conceal events. Those are general considerations, not claims that either problem occurred in this study. The registry record does not provide enough information to evaluate their impact.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event result is 0 participants with serious events among 30 at risk in the Alphacore group. The deaths count is also 0. These are observed counts in the posted record, within the outcome period from consent through the 1-week follow-up visit. They do not establish that the true probability of a serious event or death is zero.

The other adverse-event count is 10 participants among 30 at risk. The registry's outcome description includes device-related, serious, or unanticipated events, while the posted safety summary separates serious events from other events. The record does not provide event-level details that would clarify the nature, severity, timing, or assessed cause of the other events. No serious-event terms are listed, consistent with the posted serious-event count of 0, but the record does not provide further narrative context.

In general, safety counts are most informative when read with the outcome definitions, observation window, completeness of follow-up, and event descriptions. The registry gives a timeframe and participant-based counts, but it does not report completeness of observation or adjudication methods. Because the study had no control group, these counts also cannot show whether event occurrence differed from what would have been observed under another approach.

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

The posted result records adverse events in an open-label, single-group AlphaCore pilot study. It reports 0 participants with serious adverse events, 0 deaths, and 10 participants with other adverse events in the group listed as having 30 at risk. These figures provide a descriptive account of recorded safety outcomes during the endpoint's stated period. They do not provide an estimate of a difference between AlphaCore and a comparator.

The results do not establish that the device caused the reported events, or that it prevented events. The registry's counts do not include enough detail to determine the relationship of each event to the device. They also do not show whether the other events were mild or severe, whether multiple events occurred in an individual, or whether all participants completed follow-up. The serious-event and death counts are observations from this study, not proof that such events cannot occur.

The study purpose mentions preliminary clinical benefits, but the posted primary endpoint is a safety measure. No efficacy outcome or efficacy analysis is listed in the registry outcome information. Therefore, these results cannot answer whether acute bronchoconstriction improved, how much it changed, or whether any change was attributable to stimulation. The record also does not report an analysis comparing outcomes with another treatment or with the course of the condition without the device.

The findings are specific to the enrolled study group and the record's observation period. Without participant characteristics, detailed follow-up information, and event descriptions, their applicability to other settings or populations is uncertain. The appropriate reading is narrow: the registry documents the stated adverse-event counts for this completed pilot, while leaving important questions about efficacy, causality, precision, and completeness unanswered.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a safety description and a comparative treatment-effect estimate. The registered primary endpoint counts participants with adverse events, and the results provide counts for the AlphaCore group. Since the design is single-group, the numbers can describe what was recorded but cannot isolate an effect of the device from other explanations. A count is not automatically a causal estimate simply because it follows an intervention.

The record also highlights the importance of distinguishing an observed zero from certainty about risk. A zero serious-event count is a real feature of the posted results, but it does not imply that the underlying risk is absent. Precision depends on the amount and completeness of observation, as well as the statistical method used to characterize uncertainty. The record does not post an interval estimate or follow-up completeness details, leaving that precision difficult to assess.

Another statistical lesson is the importance of matching an analysis to the design. The listed planning assumptions refer to a two-arm comparison with equal allocation, whereas the trial record describes a single group without a comparator. Such planning illustrations are not a retrospective analysis of the trial and cannot be interpreted as observed power. They do not replace a stated design rationale or an analysis plan.

Finally, the registry separates the stated safety endpoint from the broader study purpose of collecting preliminary clinical-benefit information. Without a registered efficacy endpoint and posted analysis, the safety counts cannot stand in for an assessment of benefit. Clear outcome definitions, participant flow, event descriptions, and analysis methods would be needed to support more complete interpretation. The record is useful precisely when its scope is kept explicit.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important design limitation is the absence of a control group. With a single open-label group and no masking, the results cannot estimate a comparative effect, and the record does not show how outcomes might have differed under another approach. The design also leaves event reporting and assessment potentially influenced by knowledge of treatment, though the registry does not describe the assessment process or show that such influence occurred.

The registry outcome information is limited to a participant count for adverse events. It does not list an efficacy endpoint despite describing preliminary clinical benefits as part of the study purpose. Consequently, the posted results cannot quantify respiratory improvement or address whether any change was due to the device. The record also lacks detailed event descriptions, including timing, severity, and causality assessments for the other adverse events.

Additional information needed to assess completeness is not reported in the registry record. This includes participant flow, withdrawals, follow-up completion, missing outcome handling, the analysis population definition, and the statistical analysis plan. The registry does not report confidence intervals or hypothesis tests, so the precision of the event counts is not quantified. It also does not give participant characteristics that would help assess how broadly the observations might apply.

Enrollment is recorded as 30, and the study summary describes up to 30 subjects at up to 5 sites. Site-level results and details of the actual enrollment process are not reported. The study is described as a pilot, but a sample-size justification is not reported in the registry record. These gaps do not invalidate the posted counts; they limit the questions those counts can answer.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Relief of Acute Bronchoconstriction/Asthma Using the Non-Invasive AlphaCore Device — NCT01532817.
• Registry record last updated 2018-04-09; status last verified 2018-04.
• Results first posted 2018-04-09.
• 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 identifies NCT01532817 as a completed, single-group, open-label pilot study of AlphaCore for acute bronchoconstriction due to asthma. Enrollment is listed as 30. The listed primary outcome is the number of participants with adverse events from consent through the 1-week follow-up visit.

The Alphacore group results report 0 participants with serious adverse events, 0 deaths, and 10 participants with other adverse events, among 30 at risk for each listed category. The registry reports 0 analyses. No comparator, efficacy endpoint, statistical analysis plan, missing-data method, or confidence interval is reported in the registry record. The results are descriptive safety counts and do not establish a comparative effect or clinical benefit.