Effect of Electronic Cigarette Use on Cough Reflex Sensitivity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Electronic Cigarette Use on Cough Reflex Sensitivity (NCT02203162), a na phase 4 study. The primary outcome is Change in Cough Reflex Sensitivity (Log C5).

2. Clinical Question

The clinical question concerns an acute response to a vaping session, rather than a comparison of longer-term use or health outcomes. C5 is the capsaicin concentration that elicits 5 or more coughs during the challenge. The endpoint description says that an increase in C5 represents a decrease in cough reflex sensitivity. The planned measurements therefore offer a way to assess whether the capsaicin concentration associated with the cough threshold changes after exposure, and whether any change noted shortly after exposure remains detectable at the later measurement.

The registry record describes the study as involving healthy adult nonsmokers and lists cough as the condition. Its brief summary frames the work as an evaluation of the acute effect of one e-cigarette session on respiratory response. Numerical primary-outcome results are not reported in the registry record, so the direction, size and precision of any observed change cannot be stated. The clinical question can be described from the outcome plan, but the record does not establish an answer to it.

3. Trial Design

The registry identifies this as a phase 4, single-group study with an enrollment of 30. Allocation is listed as not applicable, and masking is listed as none. The intervention is electronic-cigarette exposure. There is no separate comparison arm in the record, so the design does not provide a randomized, like-for-like control comparison. The planned comparison is within the single group: cough reflex sensitivity at follow-up is assessed against baseline.

The exposure is described as one vaping session consisting of 30 puffs 30 seconds apart. The primary outcome timeframe includes baseline, 15 minutes and 24 hours after exposure. This timing is intended to characterize an acute response and its persistence to the later assessment. The registry lists the study as completed, with a start date of 2014-07 and primary completion date of 2014-12. It names Montefiore Medical Center as sponsor.

These design details identify the basic structure but do not describe every operational aspect. The registry record does not report how participants were recruited, eligibility criteria beyond the brief description of healthy adult nonsmokers, or how exposure and outcome assessments were conducted in practice. It also does not report the statistical analysis plan, the handling of missing measurements, or whether all enrolled participants contributed data at each assessment. Although the record states an enrollment of 30, enrollment alone does not establish how many participants had evaluable outcome measurements.

Because there is no separate control group, changes over time cannot be separated from all other influences through a concurrent randomized comparison. The within-person baseline comparison can describe temporal change in the measured group, but it does not by itself identify exposure as the cause of any change. That distinction matters when interpreting an acute before-and-after study.

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

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: adult nonsmokers

6. Primary Endpoint

The registry lists the primary outcome as Change in Cough Reflex Sensitivity (Log C5), measured over Baseline, 15 minutes, and 24 hours post-exposure to e-cig..

The primary endpoint is titled “Change in Cough Reflex Sensitivity (Log C5).” It is a continuous measure, with the registry specifying a mean and a 95% confidence interval as the dispersion format. C5 is defined in the outcome description as the capsaicin concentration, in micromolar, that induces 5 or more coughs. During the capsaicin cough challenge, participants breathe in increasing concentrations of aerosolized capsaicin, with concentrations doubled and challenges one minute apart, until the cough threshold is reached.

The endpoint is used because it operationalizes cough reflex sensitivity as a measurable challenge threshold. According to the registry description, an increase in C5 means a decrease in cough reflex sensitivity. Measurements are planned at baseline and at 15 minutes and 24 hours after electronic-cigarette exposure. Comparing the post-exposure measurements with baseline is intended to assess an immediate change and whether any change is still present at the later assessment.

The registry describes the measurement and intended comparisons, but does not report the mean change, confidence interval, or participant-level measurement counts. As a result, the endpoint’s actual observed change and its precision are not reported in the registry record. The stated outcome plan explains what was to be measured; it does not, on its own, show what was found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean, with a 95% confidence interval. It does not report the analysis used to estimate the change, the numerical estimate, or the interval. The explanations below describe general statistical concepts relevant to this type of outcome; they do not establish which procedures were used in this study.

What does a mean change represent?

A mean summarizes the central level of a continuous measurement across observations. For a before-and-after endpoint, a mean change would summarize participant-level differences between a post-exposure measurement and baseline, if the analysis uses paired observations. Such a summary is expressed in the endpoint’s scale, here log C5. A group mean can conceal variation: participants may have similar changes or a wide range of individual responses while contributing to the same average. The registry does not report individual changes or a distribution of the measured values, so that variation cannot be described for this study.

The title and description frame the outcome as change from baseline, but the statistical plan is not reported in the registry record. In particular, the record does not state the exact calculation used to form the change, whether the mean was based on paired observations, or whether any adjustment was made. These details matter because an analysis restricted to participants with measurements at both time points can differ from an analysis using another approach to incomplete repeated measurements.

How should a confidence interval be read?

In general, a confidence interval conveys uncertainty around an estimate under a specified statistical procedure and its assumptions. It is not a guarantee that the true effect lies within the particular interval, and it does not show how likely a hypothesis is to be true. The interval is most informative when read alongside the estimated change, the measurement scale and the study design. The registry specifies a 95% confidence interval as the dispersion format, but does not post the actual limits. Consequently, neither the estimated precision nor the range of effects compatible with the posted outcome can be evaluated.

For a mean change, interval width is influenced by the variability of the observations and the amount of usable information. More variability generally makes estimation less precise, while more complete observations can improve precision, all else equal. These are general principles, not claims about this study’s variability or completeness. Enrollment of 30 does not reveal the number of paired observations or the interval width.

Why does the repeated-measure structure matter?

Measurements at baseline, 15 minutes and 24 hours are related because they come from the same participants. Statistical methods for repeated measurements need to account for that relationship when estimating changes or comparing time points. Treating linked observations as if they were unrelated can misstate uncertainty. The registry record gives the assessment schedule but does not identify a repeated-measures model, a paired analysis, or another method. It is therefore not possible to determine how within-participant correlation was handled.

The endpoint description identifies baseline comparisons at two post-exposure times. Considering more than one time point can raise multiplicity questions: if multiple comparisons are tested, the overall chance of at least one false-positive finding can be higher than for a single prespecified test. Statistical approaches can address this by defining a primary contrast, adjusting significance thresholds, or interpreting multiple estimates as exploratory. The registry does not report whether any adjustment or hierarchy was planned. Because there are no numerical results or analyses listed, no conclusion about statistical significance across time points is available.

What can the single-group design estimate?

A before-and-after single-group study can describe how measurements differ over time in the assessed group. It lacks a concurrent comparison group that would help separate the exposure-associated pattern from time effects, measurement variation, or other influences. This does not invalidate a descriptive change, but it limits attribution. An observed within-group change would not, by itself, establish that exposure caused the change. In this record, the outcome values are not reported, so even the descriptive change cannot be characterized.

Masking is listed as none. In general, lack of masking can allow expectations or knowledge of exposure to influence subjective procedures or judgments. The endpoint uses a capsaicin challenge, but the registry does not explain how the challenge was administered, whether the measurement process involved subjective decisions, or what safeguards were used. It would be speculative to assert that lack of masking affected the measurement; it is a design feature to consider in judging potential sources of bias.

What does the record say about sample-size rationale and analysis details?

The registry reports enrollment but does not report a sample-size justification or the assumptions used to plan enrollment. It also does not report a statistical analysis plan, interim analyses, a model specification, or a rule for handling missing values. These omissions prevent assessment of whether the study was planned around a particular effect size, how many observations were expected to contribute to each analysis, or whether the final approach followed a prespecified plan. Planning calculations, when available, are not observed power and do not replace an estimate and confidence interval from the study.

The outcome listing names one primary outcome measure and the registry lists zero analyses. The record does not provide a numerical primary result, test statistic, confidence interval, or p-value. Statistical interpretation therefore cannot proceed beyond describing the endpoint and the design. No recalculated estimate is available from the posted summary statistics, because the relevant summary statistics are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the change in cough reflex sensitivity measured as log C5, and zero analyses. That outcome includes measurements at baseline, 15 minutes and 24 hours after exposure. The record does not explain whether the assessment at 15 minutes was designated as the sole primary comparison, whether the later assessment was treated as secondary, or how inference across the time points was to be handled. It also does not report any multiplicity adjustment. Without an analysis plan and numerical results, it is not possible to assess whether multiple comparisons affected the interpretation.

Missing-data information is not reported in the registry record. The record gives an enrollment of 30, but does not state how many participants had measurements at each time point, whether any observations were excluded, why data might have been missing, or how missing measurements were handled. This matters for a repeated-measure endpoint because participants may contribute data at some assessment times but not others. The method used to address incomplete measurements can affect both the estimated change and its uncertainty.

The analysis population is also not reported. The registry does not say whether analyses included all enrolled participants, only those completing the exposure and challenge, or a subset with complete outcome measurements. No protocol deviations or exclusions are described. These gaps do not show that data were missing or that participants were excluded; they mean the registry record does not provide the information needed to determine how the analysis population was defined or how representative it was of the enrolled group.

11. 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 adverse-event record lists a subjects group with 30 at risk for serious adverse events and 0 affected. It also lists 30 at risk for other adverse events and 0 affected. These entries indicate that the registry reports no participants with events in either listed category. They should not be expanded into a claim that no symptoms or unwanted experiences occurred, since the record does not provide event definitions, collection methods, or further descriptions of the categories.

Deaths are recorded as null. This is not the same as a reported count of zero; death information is not reported in the registry record in a usable numerical form. The registry also does not provide timing, severity grading, relatedness assessments, or participant-level event narratives. The adverse-event counts therefore offer a narrow summary, not a detailed safety profile.

The at-risk figures describe the registry’s event accounting and should not be interpreted as proof that complete safety follow-up was available for every participant. The record does not state follow-up completeness or explain how events were solicited. These limitations are particularly relevant when a zero count is read: a count alone does not convey how events were defined or captured.

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

The registry record establishes that the study was designed to examine acute changes in capsaicin cough reflex sensitivity after an electronic-cigarette session in healthy adult nonsmokers. It specifies a continuous primary measure, log C5, and assessments at baseline, 15 minutes and 24 hours after exposure. It also describes the direction of the measure: an increase in C5 means a decrease in cough reflex sensitivity. These details clarify what the investigators intended to measure.

The record does not report the numerical primary outcome results. It therefore cannot establish whether the measured threshold increased, decreased, or remained similar after exposure, nor can it show the size or precision of any change. No statistical significance conclusion can be drawn from the posted record because the estimate, confidence interval and p-value are not reported. The endpoint definition must not be confused with an observed finding.

The design is single-group, with no separate control arm, and masking is listed as none. Even if a before-and-after change were reported, a change over time alone would not isolate the exposure’s causal contribution in the way a concurrent randomized comparison could. The registry does not provide the analysis details needed to judge adjustment, missing data, or repeated-measure handling. These uncertainties limit both causal interpretation and assessment of statistical reliability.

The listed adverse-event counts are zero affected for serious and other adverse events, with 30 at risk in each listed category. Deaths are null rather than reported as a numerical zero. These fields should be interpreted as registry entries, not as proof that no health experiences of any kind occurred or that safety follow-up was complete.

Overall, the record is informative about the question, exposure, endpoint and basic design, but it does not provide the outcome data needed to answer the primary question. It supports neither a conclusion that exposure changed cough sensitivity nor a conclusion that it did not. Any stronger statement would require numerical results and fuller information about the analysis and follow-up.

13. Why This Trial Matters Statistically

This study raises a useful statistical issue: a clearly defined physiological measurement is not the same as a reported estimate. The registry specifies log C5, the capsaicin threshold used to elicit 5 or more coughs, and the intended measurement times. That precision in defining an endpoint helps readers understand what an analysis would concern. But without the observed mean change and its confidence interval, readers cannot judge the direction, magnitude or precision of the result.

The repeated assessments also illustrate why the analysis plan matters. Baseline and post-exposure measurements from the same participants are linked, and the record includes two post-exposure time points. The handling of within-participant dependence, missing observations and multiple comparisons can affect uncertainty and interpretation. None of those analytic details is reported, so the registry record does not allow readers to assess how the planned outcome was analyzed.

The single-group design highlights a distinction between describing change and attributing change. A before-and-after difference can describe measurements over time, while a concurrent comparison group is needed to strengthen separation of exposure effects from other time-related influences. This distinction remains important even when an endpoint is objective or has a clear operational definition.

Finally, the safety fields show why event counts need context. Zero reported affected participants in the listed categories is a bounded statement about those registry entries; event definitions and collection details are not reported. Statistical literacy requires reading both what the record does state and what it leaves unresolved, without turning missing outcome information into a claim of no effect.

14. Limitations

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

Several trial-specific limitations follow directly from the registry record. The study uses a single-group design and has no separate control arm. Its baseline-to-follow-up comparisons can describe temporal patterns within the measured group, but cannot provide a randomized estimate against a concurrent control condition. Masking is listed as none, which is relevant when considering possible influences on study conduct and measurement, although the record does not explain whether or how those influences were addressed.

The primary endpoint results are not reported in the registry record. There is no numerical mean change, 95% confidence interval, p-value, or analysis count beyond the listing of zero analyses. This prevents assessment of effect direction, magnitude, precision and statistical evidence. The registry lists enrollment of 30, but does not state how many participants contributed outcome measurements at each time point or define the analysis population.

The record also does not report a sample-size justification, detailed statistical plan, missing-data approach, multiplicity strategy, or model for the repeated measurements. It does not describe recruitment procedures or eligibility criteria in detail beyond the brief description of healthy adult nonsmokers. These omissions limit evaluation of planning, analysis assumptions, selection and generalizability. The study’s planned acute exposure and follow-up schedule do not address effects beyond the stated 24-hour assessment.

Safety reporting is similarly limited: the record lists zero affected in the serious and other adverse-event categories, but gives no event definitions, collection details or follow-up completeness, and deaths are null. These limitations concern the information available in the registry record; they do not establish that any particular bias, missingness or event occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Electronic Cigarette Use on Cough Reflex Sensitivity — NCT02203162.
• Registry record last updated 2023-06-28; status last verified 2023-06.
• Results first posted 2016-05-04.
• 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.

18. Record Summary

The registry describes a completed phase 4, single-group study sponsored by Montefiore Medical Center, with enrollment of 30. The study examined the acute effect of electronic-cigarette exposure on cough reflex sensitivity in healthy adult nonsmokers. The intervention is described as one session of 30 puffs 30 seconds apart, with planned outcome measurements at baseline, 15 minutes and 24 hours after exposure.

The primary outcome is change in mean log C5, summarized by a 95% confidence interval. An increase in C5 corresponds to decreased cough reflex sensitivity. Numerical primary results and analysis details are not reported in the registry record. The registry lists 0 affected by serious adverse events and 0 affected by other adverse events among 30 at risk in each category; deaths are null. The design has no separate control group, and masking is listed as none.