Assessing the Effect of Nicotine Reduction on ENDS User's Addiction and Exposures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessing the Effect of Nicotine Reduction on ENDS User's Addiction and Exposures (NCT05205382), a randomized na study. The primary outcome is Plasma Nicotine Boost.

2. Clinical Question

The rationale in the registry is that reducing nicotine in ENDS could affect dependence and use, as well as nicotine exposure. This outcome addresses short-term nicotine uptake during use; it does not by itself measure addiction, longer-term product use, or health effects. The record lists Electronic Cigarette Use as the condition and 116 as enrollment. Specific eligibility criteria, participant characteristics, and the reasons for the chosen nicotine concentrations are not reported in the registry record.

3. Trial Design

The registry record describes a completed, randomized, unmasked crossover study sponsored by Florida International University. It lists enrollment as 116 and the phase as not applicable. The record gives a start date of 2022-04-01 and a primary completion date of 2025-04-15. It describes two study components: partial nicotine reduction and total nicotine reduction.

In the partial-reduction component, participants used 5% nicotine JUUL/NJOY pods and 3% or 2.4% nicotine JUUL/NJOY pods during lab visits. In the total-reduction component, participants used 5% and 0% nicotine SREC pods. Each described session involved ad libitum use for up to approximately 60 minutes. The registry says blood was taken before and after use during the participant visits. It does not report the order in which conditions were experienced, the interval between visits, or the details of any washout period.

A crossover design means that participants receive or experience more than one condition, so each participant can contribute information under multiple conditions. This can support within-person comparisons, but the interpretation depends on the sequence, timing, and analysis of repeated observations. Those protocol and analysis details are not reported in the registry record. The registry also does not specify how randomization was implemented or whether any other people involved in data collection or analysis were masked.

The primary outcome is plasma nicotine boost, and the registry also lists puffing measures, toxicant exposure, total particulate matter exposure, and lung-function measures. Results are posted for the primary outcome and three puff-topography outcomes. The status is completed. A detailed protocol, analysis plan, participant flow, and explanation of the relation between the two study components 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.

First Intervention Session (60 minutes)

Washout Period (≥48 hours)

Second Intervention Session (60 minutes)

Analysis population for the primary outcome, as defined in the registry: We could not draw blood for either one session or both sessions for 12 participants in the partial nicotine reduction study. Hence, those data were excluded from analysis. The result is showing for 45 participants instead of 57. Similarly, we could not draw blood for either one session or both sessions for 26 participants in the total nicotine reduction study. Hence, those data were excluded from analysis. The result is showing for 22 participants instead of 48.

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 Plasma Nicotine Boost, measured over During the 2 participant visits, blood was taken 2 times in each session: before and after approximately 60 minutes ad lib use..

Plasma nicotine boost is the change in plasma nicotine level during a use session. The registry defines it as the post-use plasma nicotine value minus the pre-use value. Blood was taken before and after approximately 60 minutes of ad libitum use during the participant visits. The unit is nanogram/mL.

The registry specifies the median as the summary measure and the inter-quartile range as the measure of dispersion. A median describes the middle of the observed values after ordering them, while an inter-quartile range describes the spread of the middle portion of the distribution. These summaries are useful when values are skewed or when unusually high or low observations could strongly affect a mean.

This endpoint is used to characterize short-term nicotine uptake during the measured session. It is not a direct measure of dependence, total nicotine exposure over time, or clinical harm. The posted primary results report a median boost of 7.4 for the partial-reduction 5% condition and 5.5 for the 3% or 2.4% condition; the corresponding posted values for the total-reduction study are 7.6 for 5% and 0.0 for 0%. The record lists the associated distribution bounds as 0.1 to 35.5, 0.3 to 26.0, -12.3 to 34.9, and -0.9 to 5.3, respectively. The record does not explain the negative observed boosts or provide an interpretation of their clinical importance.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are easiest to interpret when the outcome summary, comparison, and test all address the same quantity. Here, plasma nicotine boost is summarized by medians and inter-quartile ranges, but the sponsor analysis is labeled as a Wilcoxon (Mann-Whitney) test with a mean difference in final values. A rank-based test uses the ordering of observations rather than directly comparing means. Depending on the distributions and assumptions, it can detect a difference in distributions without establishing that the medians differ by a particular amount. The registry record does not report enough detail to determine exactly how the named test and outcome summaries were connected.

What does a confidence interval add?

A confidence interval describes the uncertainty around an estimated comparison under the assumptions of the analysis. It helps distinguish a precise estimate from one compatible with a wide range of effects. The registry does not report confidence intervals for the primary sponsor analyses. The primary arm summaries include distribution bounds, but those are not confidence intervals for a treatment contrast. The recalculated secondary comparisons have confidence intervals, but they are unadjusted re-calculations from posted summary statistics and should not be mistaken for the sponsor's analysis.

How should the crossover design affect the comparison?

In a crossover study, a participant can contribute observations under more than one condition. A within-person analysis can account for the fact that measurements from the same participant are related. An analysis that treats the conditions as independent groups may not reflect that dependence. The record identifies the design as crossover, but does not report the sponsor's method for handling paired measurements, the condition sequence, or tests for period or carryover effects. The registry's named Wilcoxon (Mann-Whitney) method is generally associated with independent groups, so its use alongside a crossover design warrants caution. The record does not establish whether that label fully describes the analysis actually performed.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability exceeds what a model or analysis assumes. When data are highly variable, an analysis that understates that variability can make uncertainty appear smaller than it is. The primary outcome is reported with broad distribution bounds, but the record does not provide a formal assessment of over-dispersion or enough detail to judge whether it affected the primary test. The posted secondary outcomes also vary in their reported standard deviations, so a mean and standard deviation alone may not describe their distributions fully.

What does an unadjusted re-calculation represent?

The secondary endpoint comparisons include simple unadjusted re-calculations from the posted group summaries. They estimate differences in means and give confidence intervals and unadjusted p-values. They do not incorporate the participant-level pairing expected in a crossover design, nor do they adjust for other covariates or account for multiple secondary outcomes. Thus, they are descriptive checks, not substitutes for a prespecified participant-level analysis. The reported planning illustrations use observed effects as assumptions; they are not observed power and do not show that the trial was adequately sized for its actual design.

For planning illustrations, the stated sample sizes refer to participants per arm for 80% power or participants per arm for 90% power, using a stated fraction of the observed effect. Such values depend strongly on the observed effect and the assumptions used to calculate them. In particular, unusually large observed differences can yield very small illustrative sample sizes, which should not be read as evidence that a future study would reliably reproduce that difference. These calculations are not the trial's design justification; the record does not report a sample-size justification or the trial's own power assumptions.

What can the reported p-values establish?

A p-value describes how compatible the observed data are with a specified null model, assuming the analysis assumptions hold. It does not measure the probability that the null hypothesis is true, the size or importance of an effect, or the probability that a result will replicate. P-values should be read alongside effect estimates, uncertainty intervals, the study design, and the analysis plan. The primary analysis record supplies p-values but no confidence intervals; the recalculated secondary analyses include both estimates and intervals, with no multiplicity adjustment.

10. Analyses Reported by the Sponsor

The registry reports two sponsor analyses for plasma nicotine boost, both using a Wilcoxon (Mann-Whitney) method. One compares 5% nicotine with 3% or 2.4% nicotine in the partial-reduction study; the other compares 5% with 0% in the total-reduction study. The listed analysis parameter is mean difference in final values, even though the primary outcome summaries are medians. No confidence interval is reported for either sponsor comparison.

The sponsor results are not marked as discrepant from the posted values, so there is no registry indication that an independent re-calculation should take precedence. The secondary comparisons described as recalculated are separate, unadjusted calculations based on posted summary statistics. They are not re-analyses of the primary plasma nicotine outcome and should not be used to replace the sponsor's primary tests.

Interpretation remains limited by the sparse method description. In particular, the record does not explain how repeated observations from the crossover design were handled or reconcile the rank-based test label with the mean-difference parameter. The sponsor analysis is the primary reported inferential result, but the registry record does not provide sufficient detail to reconstruct it or assess its assumptions fully.

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a multiplicity adjustment, or a hierarchy of primary and secondary hypotheses. Without that information, it is unclear whether the two primary comparisons were planned as separate confirmatory questions or how the many listed outcomes were intended to be interpreted together. When multiple outcomes or comparisons are examined, the chance of observing a nominally notable result by chance can increase. This is why unadjusted secondary findings warrant caution and should not be treated as definitive on their own.

Missing primary outcome data are described for the partial-reduction study: blood could not be drawn for one session or both sessions for 12 participants, and those data were excluded from analysis. The registry states that the displayed result is for 45 participants rather than 57 in that study. It does not state how participants missing only one session were handled in every possible analysis or whether any sensitivity analysis was performed. The population description for the total-reduction primary analysis is incomplete in the record, so the reason for its analyzed group size of 22 per condition is not reported in the registry record.

The posted primary analysis groups contain 45 observations in each partial-reduction condition and 22 in each total-reduction condition. The broader registry enrollment is 116. These figures describe different aspects of the record and should not be combined or treated as interchangeable. The record does not provide a complete participant-flow account explaining enrollment, assignment, completion, availability of blood samples, and inclusion in each analysis.

The secondary puffing outcomes have their own posted group sizes. The registry does not explain missingness for these outcomes, whether all randomized participants contributed, or how missing repeated measurements were treated. It also does not report an intention-to-treat analysis population or a per-protocol definition. The crossover design makes the handling of incomplete condition pairs especially relevant, but the required details are not reported in the registry record.

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.

The registry reports zero serious adverse events, zero other adverse events, and zero deaths in each of the four safety groups. The numbers listed as at risk are 57 for each partial-reduction condition and 48 for each total-reduction condition. No serious adverse-event terms are listed.

These entries describe what was posted in the registry, not proof that no adverse events occurred under any definition or during any period beyond the recorded safety assessment. The record does not provide event definitions, collection procedures, the observation window, or a narrative explaining how safety was monitored. It also does not explain why the at-risk figures differ from the primary outcome analysis group sizes. The safety figures should therefore be read as registry-reported counts, not as a complete assessment of risk or as evidence about comparative safety.

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

The posted results describe short-term plasma nicotine changes during ad libitum electronic-cigarette use under different nicotine concentrations. In the partial-reduction study, the median plasma nicotine boost was lower in the 3% or 2.4% condition than in the 5% condition. In the total-reduction study, the median was lower in the 0% condition than in the 5% condition. These are observed summaries from the analyzed participants, alongside sponsor-reported rank-based tests.

The results do not establish how nicotine reduction affects addiction, longer-term use, cigarette smoking, health outcomes, or population-level exposure. Plasma nicotine boost is one short-term measure, not a comprehensive measure of dependence or harm. The registry rationale discusses those broader concerns, but the posted primary outcome does not directly assess them.

Nor do the results establish that the observed differences would occur in other products, settings, or participant groups. The record identifies specific pods and lab sessions, but does not provide detailed participant characteristics or complete protocol information. The crossover design can be informative, yet the registry does not report enough about sequence, timing, paired analysis, or carryover to fully evaluate the comparisons.

The findings should be understood with the uncertainty and reporting limitations in mind. The primary sponsor analyses have no reported confidence intervals, and their method label and parameter do not align straightforwardly with the median summaries. Missing blood samples affected the partial-reduction analysis, while the reason for the total-reduction primary analysis population is not reported. Secondary results are unadjusted recalculations and involve multiple outcomes. These considerations limit how far the posted statistical results can be extended beyond the measured sessions.

14. Why This Trial Matters Statistically

This trial raises a useful statistical question: how should a short-term biomarker be compared when the design is crossover and the registry reports medians but labels the primary test as a rank-based comparison with a mean-difference parameter? Answering that question requires more than reading a p-value. It requires knowing the analysis population, how repeated measurements were paired, and how the estimand relates to the summary statistics.

The posted primary outcome makes the distinction between statistical evidence and estimation especially visible. The sponsor reports tests but no confidence intervals for the primary comparisons. A test result alone does not convey the range of effect sizes compatible with the data. Meanwhile, the secondary recalculations offer estimates and intervals, but do not account for the crossover structure or multiplicity. Each kind of result has different limits.

The record also illustrates why transparent reporting matters. Details about condition order, incomplete paired measurements, missing-data handling, and the planned approach to multiple outcomes would help readers judge the strength and scope of the evidence. Without them, even a randomized study can be difficult to interpret at the level of its statistical estimand.

Finally, planning calculations derived from observed effects can be misleading if treated as proof of adequate power or as a forecast of future studies. Their role is illustrative, and their usefulness depends on assumptions that may not reflect a new study. The record does not report the original sample-size justification. Careful separation of observed results, sponsor inference, and planning assumptions is therefore central to reading this trial statistically.

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.

Important protocol details are not reported in the registry record. Although the study is identified as randomized and crossover, the condition sequence, timing between conditions, washout procedures, and handling of period or carryover effects are not described. These details matter for interpreting within-person comparisons and for determining whether observed differences could reflect order or timing rather than condition alone.

The primary outcome reporting leaves an estimand question. The outcome is summarized with medians and inter-quartile range, but the sponsor analysis is labeled as a Wilcoxon (Mann-Whitney) test and a mean difference in final values. The record does not supply enough information to understand precisely what quantity was tested or how the test accounted for the crossover design. Confidence intervals for the sponsor's primary comparisons are absent.

Missingness also limits interpretation. The record says blood samples were unavailable for one or both sessions for 12 participants in the partial-reduction study and that these data were excluded. The corresponding explanation for the total-reduction primary analysis population is not reported in the registry record. A complete participant-flow account, sensitivity analyses for missing data, and definitions of analysis populations are not available.

The secondary comparisons are unadjusted summary-statistic recalculations, not participant-level analyses. They do not account for pairing, covariates, or multiple testing. Some comparisons cross the two study components, and the record does not explain whether those groups are directly comparable. The registry lists more outcomes than those with results; reasons for unposted outcomes are not reported.

Finally, detailed participant characteristics and eligibility criteria are not reported, limiting assessment of who the results represent. The registry's rationale refers to young ENDS users, but the record does not provide ages or other demographic details in the registry record presented. The sample-size justification and full statistical analysis plan are also not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessing the Effect of Nicotine Reduction on ENDS User's Addiction and Exposures — NCT05205382.
• Registry record last updated 2026-08-13; status last verified 2025-09.
• Results first posted 2026-08-13.
• 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

NCT05205382 is a completed randomized, unmasked crossover study sponsored by Florida International University. The registry lists 116 enrolled participants and two components: partial nicotine reduction, comparing 5% with 3% or 2.4% nicotine pods, and total nicotine reduction, comparing 5% with 0% nicotine pods.

The primary outcome is plasma nicotine boost, defined as the post-use minus pre-use plasma nicotine value during an approximately 60-minute ad libitum session. Posted medians are lower in the reduced-nicotine condition in both study components. The sponsor reports Wilcoxon (Mann-Whitney) analyses but no confidence intervals, and the registry does not explain fully how the analysis handled the crossover design.

Posted secondary results cover three puff-topography measures. Their recalculated comparisons are unadjusted and should be regarded as exploratory. Safety entries report zero serious adverse events, zero other adverse events, and zero deaths in each group. Missing-data handling, multiplicity procedures, and several protocol and analysis details are not reported in the registry record.