Assessment of Two New Electronic Cigarettes in Cigarette Smokers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment of Two New Electronic Cigarettes in Cigarette Smokers (NCT03435562), a registered na study. The primary outcome is Change in Plasma Nicotine.

2. Clinical Question

3. Trial Design

This was a completed crossover study of electronic cigarette use in cigarette smokers. The registry record lists 22 participants as enrolled and identifies three product-use conditions: JUUL electronic cigarette, IQOS electronic cigarette, and participants’ own-brand cigarettes. In a crossover design, participants receive more than one study condition, so comparisons can potentially use measurements from the same participant under different conditions. That is a general feature of crossover studies, not a description of the analysis actually used in this trial.

The record describes three sessions and product-use bouts, including a 10-puff bout followed by an approximately 90-minute ad lib use bout. The primary outcome’s timeframe also describes blood collection at baseline, five minutes after the start of a 10-puff bout, and before and after an approximately one-hour ad lib use period. The record does not give a complete account of the session sequence, and details of the arm description are incomplete.

The study status is completed. The listed start date is 2018-03-03, and the primary completion date is 2019-08-16. The phase is listed as NA, and masking is listed as none. The registry does not state an allocation method. It explicitly notes that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The sequence in which participants used products, any washout arrangements, and any procedures to limit order or carryover effects are not reported in the registry record.

The study’s stated purpose extended beyond nicotine delivery to include user behavior, subjective effects, and physiological effects. The listed secondary outcomes include carbon monoxide levels, smoking-urge questionnaire factors, and several mood or symptom measures. These outcomes broaden the study’s measurement scope, but their numerical results are not reported in the registry 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: One participant was missing a sample so data was only available for 17 participants for these analyses.

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 Change in Plasma Nicotine, measured over Blood will be taken 4 times in each session: at baseline, 5 min after the start of a 10-puff product use, and then before and after an approximately 1-hour ad lib use period..

The primary endpoint is change in plasma nicotine level, measured in ng/ml. Plasma nicotine is a blood measure of nicotine concentration. Tracking its change around product use is intended to describe nicotine delivery over the use period, which is the central comparison in the study’s stated purpose.

The registry describes blood collection at baseline, five minutes after the start of a 10-puff product-use bout, and before and after an approximately one-hour ad lib use period. These time points allow measurements to be considered in relation to product use, rather than as a single isolated blood value. The registry lists the endpoint as a mean with standard deviation as its dispersion measure.

In general, a mean describes the average measurement in a group, while a standard deviation describes how spread out individual measurements are around that average. In a crossover study, a comparison of changes across products may be based on within-participant patterns, but the registry record does not report the specific analysis used. It also does not report the numerical mean changes, standard deviations, or a numerical comparison between products.

The record states that one participant was missing a sample and that data were available for 17 participants for these analyses. It does not give further detail about which sample was missing or how missing measurements were handled. Thus, the endpoint and its collection schedule are described, but the registry record does not report the primary outcome results needed to assess the size or precision of any observed product differences.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a continuous measure summarized by a mean and standard deviation. These are descriptive statistics: the mean represents the average observed value, while the standard deviation describes variability among observations. Neither statistic alone gives the uncertainty in a comparison between products. For that, an analysis would ordinarily report a contrast and an uncertainty measure, such as a confidence interval. The registry record does not report those numerical results or identify the inferential method used.

What does a crossover design imply?

In general, a crossover design measures participants under multiple conditions, which can allow each participant to serve as their own reference. This can reduce the influence of stable differences between participants when the analysis compares their measurements across conditions. It does not remove every source of bias or variability. Sequence, period effects, and carryover from an earlier condition may matter, depending on the study’s procedures and the outcome. The record identifies this study as a crossover and describes product-use sessions, but does not report the sequence, washout arrangements, or a model accounting for period or carryover effects.

A paired analysis is one general way to respect repeated measurements from the same participant. A model for repeated measures is another general option. Which approach is appropriate depends on the data structure and design. Neither should be attributed to this trial: the analysis method is not reported in the registry record. The record also does not state whether the primary comparison was a change from baseline within each product condition, a contrast between changes across conditions, or another estimand.

How should uncertainty be read?

In general, a confidence interval gives a range of values compatible with the data and the specified statistical method, while reflecting sampling uncertainty. A narrow interval indicates greater precision than a wide interval, all else being equal. A p-value addresses compatibility between the data and a specified null hypothesis under the analysis assumptions; it does not measure the size or importance of a difference. No confidence intervals or p-values for this study’s outcomes are reported in the registry record, so neither the precision nor statistical significance of the product comparisons can be assessed.

Standard deviation and confidence interval answer different questions. Standard deviation describes variation among participant measurements. A confidence interval describes uncertainty about an estimated quantity, such as a mean or contrast. The registry’s stated mean and standard deviation summary does not, by itself, provide the uncertainty around a comparison. No additional uncertainty measure is reported for the primary outcome.

Why can over-dispersion matter?

In general, over-dispersion occurs when outcome variability exceeds what a statistical model assumes. If a model underestimates variability, standard errors may be too small and intervals too narrow, making results appear more precise than warranted. This is a general statistical consideration, not a reported feature of this trial. The primary endpoint is continuous, and the registry does not report an over-dispersion assessment or a model for the primary analysis.

What does the planning illustration represent?

The study record includes assumptions for a sample-size planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. Such an illustration is a planning exercise based on those assumptions; it is not an observed trial result, an estimate of the trial’s achieved power, or evidence that the original trial was designed using that approach. The record does not report the trial’s own sample-size justification. Numerical planning results are not reported in the registry record.

The listed enrollment is 22, but enrollment alone does not reveal whether the study had adequate precision for its intended comparisons. Precision depends on the variability of the outcome, the analysis, the number of usable observations, and the effect size of interest. The registry does not report a design target, a power calculation for the original study, or the numerical outcome data needed to evaluate precision.

What does the analysis record establish?

The registry lists 27 outcome measures and zero analyses. That means the record does not give analysis-level results for those measures. The stated primary endpoint and its timing provide a framework for understanding what was intended to be measured, but they do not identify the statistical model, covariates, comparison estimand, or handling of repeated observations. Those details are not reported in the registry record. Statistical methods therefore can be explained in general, but a trial-specific account of the analysis cannot be reconstructed from the recorded information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 27 outcome measures, including the primary change in plasma nicotine measure and secondary measures of carbon monoxide, smoking urges, and subjective effects. When many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. General approaches to multiplicity include defining a primary outcome in advance, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report whether any such approach was planned or used.

The record lists zero analyses, and numerical results for the outcomes are not reported. It therefore does not show which outcomes were analyzed, how many product contrasts were considered, or whether any multiplicity procedure was applied. No conclusions about selective reporting or the number of statistically significant findings can be drawn from these fields alone.

For the primary analyses, the record states that one participant was missing a sample and that data were available for 17 participants. It does not specify which visit or product condition had a missing sample, whether other measurements were missing, or why the sample was unavailable. It also does not describe an imputation method, a complete-case rule, or a sensitivity analysis. The relationship between the enrollment figure and the stated analysis availability is not explained in the registry record.

The analysis population is not defined beyond the statement about data availability for the primary analyses. The record does not say whether all enrolled participants were included in any particular analysis, whether eligibility or protocol deviations affected inclusion, or how incomplete crossover observations were handled. These omissions limit assessment of missing-data bias and of how representative the analyzed data may be of the enrolled participants.

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

The record establishes that the study was intended to compare plasma nicotine changes during JUUL and IQOS use with changes during participants’ own-brand cigarette use. It also describes blood collection around product-use periods and states that data were available for 17 participants for the primary analyses. These details clarify the research question and the stated availability of primary-outcome data.

The registry does not report numerical outcome estimates. It therefore does not show whether plasma nicotine changes differed across products, how large any difference was, or how precisely a difference was estimated. It does not support a conclusion that products were equivalent, that one produced a larger change, or that there was no difference. Absence of a reported estimate is not evidence that the comparison found no effect.

The crossover label is relevant to how measurements could be compared, but the registry does not report the sequence of product conditions, washout procedures, or analysis method. The record also notes that allocation was not stated, the comparison was not randomized, and the arms were not a like-for-like control comparison. These features limit what can be inferred about causal effects from any contrast, even if numerical results were available.

The adverse-event fields list zero at risk and zero affected for the recorded event categories across the three product groups. The registry does not provide further context on event collection or analysis. These entries should not be interpreted as a comprehensive demonstration that no adverse events occurred.

In short, the registry documents a completed study and its intended measurements, but the posted record does not provide the results needed to judge the observed differences or their uncertainty. The conclusions that can be drawn are about the study’s recorded design and outcome availability, not about comparative product effects.

12. Why This Trial Matters Statistically

This study raises statistical questions common to product comparisons involving repeated measurements. Its crossover designation means that measurements from the same participant under different product conditions may be informative as paired observations. In general, such designs can distinguish within-person variation from differences between people, but only when the data structure and analysis are handled in a way that respects repeated observations.

The design also makes the order of product use and the timing of measurements important considerations. If a prior condition influences a later measurement, period or carryover effects may complicate interpretation. These are general design considerations; the registry record does not report the product sequence, washout arrangements, or analysis methods used to address them.

The record’s explicit note that the comparison was not randomized and that the arms were not a like-for-like control comparison is statistically important. It cautions against treating contrasts as if they came from a randomized comparison with balanced groups. The record does not provide enough detail to characterize the source or direction of potential bias.

Missing outcome data also matter in a repeated-measures study. The registry states that one participant was missing a sample and that data were available for 17 participants for the primary analyses, but does not describe how incomplete measurements were handled. Without that information or numerical results, readers cannot assess how missingness may have affected precision or the estimates.

Finally, the record lists 27 outcomes but no analyses. That distinction illustrates why a clearly stated endpoint and measurement schedule are not substitutes for reported estimates, uncertainty, and analysis methods. The trial’s statistical importance lies in the questions its design raises; the registry record does not contain the results needed to resolve them.

13. 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 principal limitation of the registry record for interpreting this trial is the absence of numerical outcome results. The primary endpoint is described, but no mean changes, standard deviations, product contrasts, confidence intervals, or p-values are reported. As a result, neither effect size nor precision can be evaluated.

The design description is incomplete for assessing a crossover comparison. Although the study is identified as a crossover and the record describes product-use sessions, the product sequence and any washout arrangements are not reported. The analysis method is also not reported, so it is not possible to determine how repeated measurements, period effects, or possible carryover were handled.

The registry notes that allocation was not stated, the comparison was not randomized, and the arms were not a like-for-like control comparison. These are important constraints on interpretation. The record does not provide further detail that would allow the extent of those limitations to be assessed.

Missing-data information is limited. The record says one participant was missing a sample and that data were available for 17 participants for the primary analyses, but does not identify the missing time point, explain the analysis population, or describe any method for handling missing observations. It also does not report whether incomplete observations affected particular product conditions.

Finally, the record lists 27 outcome measures and zero analyses. The multiplicity approach, trial-specific sample-size justification, and statistical analysis plan are not reported in the registry record. Adverse-event entries list zero participants at risk and zero affected in the recorded categories, without further context about ascertainment. These gaps limit assessment of both the results and the completeness of outcome reporting.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Assessment of Two New Electronic Cigarettes in Cigarette Smokers — NCT03435562.
• Registry record last updated 2020-08-03; status last verified 2020-07.
• Results first posted 2020-08-03.
• 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.

17. Record Summary

NCT03435562, titled “Assessment of Two New Electronic Cigarettes in Cigarette Smokers,” is a completed crossover study sponsored by Virginia Commonwealth University. The registry lists an enrollment of 22, a start date of 2018-03-03, and a primary completion date of 2019-08-16. Masking is listed as none, and phase is listed as NA.

The study compares JUUL and IQOS electronic cigarette use with participants’ own-brand cigarette use. Its primary outcome is change in plasma nicotine, measured in ng/ml, with blood collection described at baseline and around product-use periods. The registry states that data were available for 17 participants for the primary analyses and that one participant was missing a sample.

Numerical outcome results and analysis details are not reported in the registry record. The record notes that the comparison was not randomized, allocation was not stated, and the arms were not a like-for-like control comparison.