Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping Products With Tobacco or Unflavored E-liquids, SALTVAPE Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping Products With Tobacco or Unflavored E-liquids, SALTVAPE Study (NCT04231539), a randomized na study. The primary outcome is Maximum Concentration of Nicotine in Plasma (Cmax).

2. Clinical Question

3. Trial Design

The registry record describes a randomized, double-masked, factorial study and lists its phase as NA. The sponsor is Roswell Park Cancer Institute. The record gives a start date of 2020-02-18, a primary completion date of 2024-07-10, and a status of COMPLETED. Enrollment is 15.

The product forms represented in the results vary by nicotine form and flavor: unflavored free-based nicotine, unflavored salt-based nicotine, tobacco-flavored free-based nicotine, and tobacco-flavored salt-based nicotine. The listed product sequences show participants assigned to differing orders. The registry arm descriptions say that participants abstained from nicotine for 8-10 hours before sessions, attended 4 vaping sessions over 2-2.5 hours, with sessions 5-7 days apart, and took 20 puffs over 10 minutes at one puff every 30 seconds. The descriptions are truncated, so they do not provide a complete account of each sequence or product administration.

For the primary outcome, the registry reports group means and standard errors. Outcome group sizes are 12 for each of the first three product forms and 13 for the tobacco-flavored salt-based form. These are outcome-specific counts; the record does not explain why they differ from one another or from total enrollment. The registry record does not report the original sample-size justification, a detailed statistical analysis plan, or whether the analysis accounted for the product sequence or repeated measurements. Randomization and masking describe design features, but do not by themselves specify how the posted comparisons were estimated.

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.

Only the first 6 of 14 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All treated and eligible patients

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: All treated and eligible patients

Only the first 6 of 15 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Concentration of Nicotine in Plasma (Cmax), measured over Samples were taken at minutes 0, then they started puffing and samples were taken 2, 4, 5, 6, 8, 10 minutes during puffing. Then, samples were taken at times 13, 15, 20, 30, and 120 minutes post puffing. The last dose occurred at week 4..

The primary endpoint is maximum concentration of nicotine in plasma, abbreviated Cmax, measured in ng/mL. It represents the highest plasma nicotine concentration recorded during the specified sampling period. The registry describes samples at minutes 0, then at 2, 4, 5, 6, 8, and 10 minutes during puffing, followed by samples at 13, 15, 20, 30, and 120 minutes post puffing. It also states that the last dose occurred at week 4.

Cmax is used in pharmacokinetic research to describe the peak concentration reached after exposure. As a continuous measure, it can be summarized by a mean for each product form, while comparisons can describe the estimated difference between a product form and the reference. The posted outcome is a mean, with standard error reported as the measure of dispersion. The standard error describes the precision of an estimated mean, not the spread of individual participants’ values.

The endpoint addresses nicotine concentration in plasma under the study’s sampling and vaping conditions. It does not, on its own, measure longer-term use, dependence, health outcomes, or all dimensions of subjective response. Those are distinct questions and should not be inferred from a peak concentration result.

7. Results Posted in the Registry

• B: Unflavored Salt-based Nicotine Form: mean 11.80 versus 5.70 on control; difference 6.10 (95% CI -0.56 to 12.76), standardized effect d = 0.73; z-test p = 0.072.
• C: Tobacco Flavor Free-based Nicotine Form: mean 6.70 versus 5.70 on control; difference 1.00 (95% CI -1.99 to 3.99), standardized effect d = 0.27; z-test p = 0.512.
• D: Tobacco Flavor Salt-based Nicotine Form: mean 8.10 versus 5.70 on control; difference 2.40 (95% CI -1.28 to 6.08), standardized effect d = 0.50; z-test p = 0.201.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Perceived Harshness of Experimental Product Sampled

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • B: Unflavored Salt-based Nicotine Form: mean 2.92 versus 4.85 on control; difference -1.93 (95% CI -2.74 to -1.12), standardized effect d = -1.91; z-test p = <0.001.
  • C: Tobacco Flavor Free-based Nicotine Form: mean 4.62 versus 4.85 on control; difference -0.23 (95% CI -0.51 to 0.05), standardized effect d = -0.66; z-test p = 0.104.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for B: Unflavored Salt-based Nicotine Form than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between C: Tobacco Flavor Free-based Nicotine Form and the control. The interval gives the range of effects that remain compatible with the data.

Perceived Satisfaction of Experimental Product Sampled

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • B: Unflavored Salt-based Nicotine Form: mean 3.75 versus 3.08 on control; difference 0.67 (95% CI -0.31 to 1.65), standardized effect d = 0.55; z-test p = 0.180.
  • C: Tobacco Flavor Free-based Nicotine Form: mean 3.77 versus 3.08 on control; difference 0.69 (95% CI -0.29 to 1.67), standardized effect d = 0.56; z-test p = 0.168.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B: Unflavored Salt-based Nicotine Form and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between C: Tobacco Flavor Free-based Nicotine Form and the control. The interval gives the range of effects that remain compatible with the data.

Perceived Liking of Experimental Product Sampled

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • B: Unflavored Salt-based Nicotine Form: mean 55.20 versus 45.90 on control; difference 9.30 (95% CI -3.56 to 22.16), standardized effect d = 0.58; z-test p = 0.156.
  • C: Tobacco Flavor Free-based Nicotine Form: mean 46.50 versus 45.90 on control; difference 0.60 (95% CI -14.96 to 16.16), standardized effect d = 0.03; z-test p = 0.940.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between B: Unflavored Salt-based Nicotine Form and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between C: Tobacco Flavor Free-based Nicotine Form and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the question beyond plasma nicotine concentration. They include perceived harshness, perceived satisfaction, perceived liking, and change in Minnesota Nicotine Withdrawal Scale. The registry reports posted group summaries and comparison results for harshness, satisfaction, and liking. Although withdrawal change is listed among the secondary outcomes, its results are not included in the posted secondary summaries described in the record.

Across the subjective measures with posted results, the direction and apparent size of the comparisons are not uniform. Some estimates point toward differences between salt-based forms and the reference on subjective ratings, while others are closer to no difference or are imprecise. This variety suggests that subjective experience is not captured by one single measure. It also means that no broad conclusion about overall preference or acceptability follows from one endpoint alone.

The secondary outcomes relate to the primary Cmax result by addressing responses measured alongside nicotine delivery, not by confirming or replacing the pharmacokinetic endpoint. A higher or lower subjective rating does not establish a corresponding change in plasma concentration. The primary comparisons themselves are uncertain, and the secondary comparisons should be interpreted with similar caution, particularly given small groups and multiple outcomes.

The secondary p-values are unadjusted, and the registry record does not report a multiplicity plan. When several outcomes and contrasts are examined, the chance of seeing an apparently notable result by chance can increase. Without a stated hierarchy or adjustment, isolated secondary findings carry less evidential weight than a prespecified, well-supported primary analysis. The record lists no formal reported analyses, so the posted secondary contrasts are best treated as exploratory descriptions rather than definitive confirmatory tests.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Perceived Harshness of Experimental Product Sampled
• Perceived Satisfaction of Experimental Product Sampled
• Perceived Liking of Experimental Product Sampled
• Minnesota Nicotine Withdrawal Scale Change (Change From Pre- to Post-)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, and the registry reports a mean for each product form. The posted group summaries also include a standard error. Unadjusted recalculations compare each non-reference mean with the mean for unflavored free-based nicotine. These summaries offer a straightforward view of group-level differences, but they do not reveal the full distribution of individual measurements or explain how the original study analysis was conducted.

What does a mean describe?

A mean is a measure of the center of a set of observations. For Cmax, each group mean summarizes the recorded plasma concentrations at the individual level according to the endpoint definition. Means are useful for comparing groups when the endpoint is quantitative, but a mean alone does not show whether individual values were tightly clustered or widely spread. The record reports standard errors rather than standard deviations for the arm means. A standard error describes uncertainty in the estimated mean; it is not an estimate of the variability among individual measurements.

What do the comparison estimates represent?

A mean difference expresses how far one group mean is from the reference group mean, with the sign indicating direction. The posted comparison estimates are labeled mean differences. Their confidence intervals show a range of values compatible with the data under the calculation’s assumptions. The reported primary estimates are unadjusted recalculations from the posted summary statistics. They do not incorporate covariates or other adjustments in the information available in the registry record. The record does not state that these recalculations match a sponsor-selected model, and it does not give a detailed method for any original analysis.

When groups are small, estimated means and differences can be sensitive to the observations included. The group sizes reported for the primary outcome are 12, 12, 12, and 13. Those counts make the uncertainty around the estimates especially important to consider. The standard errors and confidence intervals help describe that uncertainty, but they cannot correct for possible design features that are not represented in a simple comparison.

How should p-values be read?

A p-value describes how unusual a test statistic would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The unadjusted p-values for the primary comparisons are 0.072, 0.512, and 0.201. They are presented without a stated multiplicity adjustment. The registry record does not report which test produced these p-values or a prespecified threshold for interpreting them. A p-value should therefore be read alongside the estimate and confidence interval, not as a stand-alone verdict.

In general, a confidence interval that includes zero is consistent with a range of possible mean differences that includes no difference. That does not establish equivalence or show that the groups are identical; it means the data do not pin down the direction and magnitude with enough precision to exclude zero at the interval’s stated level. In these results, all three primary comparison intervals include zero and also span positive values. Their width reflects substantial uncertainty about the sizes of the differences.

Why can repeated observations matter?

The study descriptions list multiple vaping sessions and differing product sequences, and the primary sampling schedule includes several time points around puffing. If measurements from the same participant or session are related, an analysis may need to account for that dependence. In general, treating related observations as if they were independent can misstate uncertainty. The registry record does not report whether the primary analysis modeled repeated observations, sequence, or period effects. It is therefore not possible to determine from the registry record whether those features were incorporated in the sponsor’s analysis.

Likewise, the record does not report whether the factorial design was analyzed through main effects, interaction effects, or product-specific contrasts beyond the comparisons posted. A factorial label describes the design structure; it does not establish which model was used. Without a reported analysis plan, the simple pairwise recalculations should not be interpreted as a complete analysis of every design question.

Finally, statistical significance and practical importance are separate considerations. The observed mean differences are expressed in ng/mL, but the registry record does not provide a threshold for a clinically or behaviorally important change in Cmax. General statistical interpretation can describe the estimates and their precision; it cannot supply an importance threshold that the record does not report.

11. Confidence Intervals and Precision

A confidence interval conveys uncertainty about an estimated difference. It gives a range of values compatible with the observed data under the assumptions used to construct it. It is not a range containing a specified proportion of individual participants’ measurements, and it does not guarantee that the true difference lies within the interval. The registry record does not report the interval construction method, so interpretation should focus on the posted ranges rather than assume a particular model.

For the comparison of unflavored salt-based nicotine with unflavored free-based nicotine, the estimated mean difference is 6.1 ng/mL, and the confidence interval runs from -0.555 to 12.76. This interval includes zero and extends to positive values, so the data are compatible with no difference as well as with a range of positive differences under the calculation used.

For tobacco-flavored free-based nicotine versus the reference, the estimate is 1.0 ng/mL and the interval is -1.992 to 3.992. For tobacco-flavored salt-based nicotine versus the reference, the estimate is 2.4 ng/mL and the interval is -1.282 to 6.082. Both intervals also include zero and include positive values. The intervals therefore do not establish a clear direction for any of the three population mean differences.

Precision is limited by the small outcome group sizes and the width of the intervals. In particular, the estimate for unflavored salt-based nicotine has a wide interval, consistent with considerable uncertainty around its point estimate. A point estimate alone can conceal this uncertainty; the confidence interval is essential context. These intervals do not show equivalence, and the record gives no equivalence margin. They also do not account for multiplicity or an unreported repeated-measures model. Precision should therefore be understood as the uncertainty conveyed by these unadjusted comparisons, not as a complete assessment of all sources of uncertainty.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effects, not the original design justification for the trial. For the continuous outcomes in this record, the figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The registry record does not report the original sample-size assumptions or justification.

The 80% power column indicates the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column gives the corresponding planning count for a 90% chance. These are design-planning quantities, not probabilities that the observed study result is correct.

The rows that plan for 100% of the observed effect use that observed estimate as the target effect. The rows that plan for 75% or 50% of the observed effect use progressively smaller targets. Smaller effects are harder to distinguish from random variation, so they require more participants per arm in these illustrations. This is visible in the listed counts across outcomes: planning for a smaller fraction of an observed effect generally yields larger participant requirements. The magnitudes vary substantially by outcome because the observed effects and variability differ.

These figures should not be read as the number enrolled, nor as an assessment of the trial’s achieved power. They are hypothetical planning illustrations derived from the observed effects, and estimates from small groups can themselves be unstable. The number shown for a planning scenario is not a recommended sample size for a future study unless its assumptions and target effect are appropriate for that future question. This is not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 6.100; pooled standard deviation σ = 8.317.
2. n = 2 × (1.96 + 0.842)² × 8.317² / 6.100² = 29.2, rounded up to 30 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 6.1                      # observed difference in means
sigma <- 8.31745153277132                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4231539)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 30 (80% power), 40 (90% power)
 75% of observed effect: n per arm = 52 (80% power), 70 (90% power)
 50% of observed effect: n per arm = 117 (80% power), 157 (90% power)
power.t.test: 30.2 
Simulated power at n = 30 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures and reports 0 analyses. It includes one primary outcome and several secondary outcomes, but does not state a statistical analysis plan describing which comparisons were primary within each outcome, how outcomes were ranked, or which tests were intended to be confirmatory. The posted comparison p-values are unadjusted. No multiplicity adjustment is reported.

Multiplicity matters because examining many outcomes or comparisons creates multiple opportunities for apparently unusual results even when there are no underlying differences. Adjustments or a prespecified testing hierarchy can help control that issue, but the appropriate approach depends on the trial’s aims and planned analysis. The registry record does not report an approach, so the unadjusted p-values should not be read as if they account for all outcomes and contrasts. This is particularly relevant to secondary outcomes, which can help generate hypotheses but provide weaker confirmation when their testing context is not specified.

The record also does not report how missing observations were handled, whether any outcomes were imputed, or how many participants contributed to each time point beyond the arm counts shown. Total enrollment is 15, while the primary outcome group counts are 12, 12, 12, and 13. The reason for the differing counts is not reported in the registry record. These counts do not establish whether observations were missing, excluded, or unavailable for another reason.

The analysis population is described for the primary endpoint as all treated and eligible patients. The record does not explain the operational definition of that population, report an intention-to-treat analysis, or describe exclusions after randomization. Nor does it report how the randomization sequence, product order, or repeated sessions were incorporated in the analysis. These omissions leave uncertainty about the analysis set and whether the statistical model reflected the study design. They do not invalidate the posted descriptive results, but they limit their interpretation as definitive treatment comparisons.

15. 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 serious adverse event figures for all four product groups. The number at risk is 12 for each of the first three groups and 13 for the tobacco-flavored salt-based group. Serious adverse events affected 0 participants in every group, and deaths are reported as 0 in every group. The registry also reports 0 participants affected by other adverse events in each group. No serious adverse event terms are listed.

These figures describe what was reported in the registry for the groups and risk counts shown. They do not establish that no adverse events of any kind occurred outside the record’s reporting definitions, and they cannot rule out uncommon events. The small number of participants represented in the safety results means that the figures provide limited information about the range or frequency of possible safety outcomes. They should be read as registry-reported counts, not as a comprehensive safety assessment or a basis for individual decisions.

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

The posted data describe plasma nicotine concentrations and selected subjective ratings after participants used the study product forms under the listed session conditions. The primary group means were numerically different, with the largest reported mean for unflavored salt-based nicotine. However, each unadjusted confidence interval for the primary comparison with unflavored free-based nicotine includes zero. The estimates are therefore imprecise, and the record does not establish a clear difference in the population mean Cmax for any of those comparisons.

That interpretation is narrower than saying that all products are the same. The intervals include both zero and positive values, and no equivalence margin is reported. Failure to exclude zero is not evidence that the groups are equivalent. At the same time, the higher observed mean in one group does not by itself show a reliable difference. Both the direction and size of the underlying differences remain uncertain in these small groups.

The registry record also includes subjective outcomes, but those measures address perceived experience and do not substitute for the primary pharmacokinetic endpoint. Their posted results are exploratory in the absence of a stated multiplicity plan and formal reported analyses. They should not be combined into a single conclusion about preference, abuse liability, or long-term behavior, none of which is fully established by the posted comparisons.

The study describes a specific set of nicotine forms, flavors, and vaping-session procedures. Its results do not establish how different products would perform under other use patterns or in populations not characterized in the record. The record does not report a clinically important difference threshold for Cmax or subjective scales. Accordingly, statistical estimates can describe observed group patterns and uncertainty, but cannot establish practical importance from these results alone. The findings are best understood as limited, study-condition-specific evidence, with substantial uncertainty about the size of the primary differences.

17. Why This Trial Matters Statistically

This trial is statistically instructive because it illustrates the difference between a visible ordering of sample means and a well-determined difference between population means. The group means are not identical, but the unadjusted intervals are wide and include zero. Looking only at which mean is largest would overstate what the data establish. Pairing each estimate with its uncertainty gives a more balanced interpretation.

The study also highlights how small groups affect precision. The outcome groups contain 12 or 13 participants, and the primary comparisons have broad intervals relative to their point estimates. That does not make the summaries uninformative: they show the direction and scale of the observed results. It does mean that estimates should be treated as uncertain and that the results cannot support fine distinctions among product forms.

Another statistical issue is the relationship between design and analysis. The registry describes randomized product sequences and repeated sessions, while the record does not explain whether sequence or within-participant dependence entered the analysis. A design can generate structured data that require an analysis suited to those structures. Without a reported model or analysis plan, readers should distinguish the posted group summaries from a complete evaluation of the design.

Finally, the presence of several outcomes makes multiplicity and selective emphasis important. Secondary ratings can add context, but unadjusted comparisons across multiple outcomes carry less confirmatory weight when no testing hierarchy is reported. Taken together, the trial shows why transparent analysis details, uncertainty intervals, and careful separation of descriptive findings from confirmatory inference matter in clinical biostatistics.

18. 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 outcome groups are small, and their reported counts differ from total enrollment. The registry record does not explain the reasons for the counts of 12, 12, 12, and 13 in the primary outcome. Without participant flow or missing-data details, it is not possible to determine whether the differences reflect missing observations, eligibility for a particular analysis, or another cause.

The primary endpoint is measured over a dense sampling schedule around puffing, and the study descriptions include multiple sessions and product orders. These features can create within-person and sequence-related dependence. The registry record does not report whether the analyses accounted for repeated measurements, order, period, or potential carryover. The record also does not describe the factorial analysis or how product effects were separated. These are important design-specific uncertainties, not proof that the analysis was inappropriate.

The posted comparison calculations are unadjusted, and the registry record lists no formal reported analyses. It does not state how confidence intervals or p-values were constructed, whether there were prespecified contrasts, or how multiple outcomes were handled. The record does not give a sample-size justification, missing-data approach, or detailed analysis population definition. Consequently, readers cannot assess whether the posted comparisons correspond to a planned confirmatory analysis.

The secondary outcome record is incomplete for interpretation: withdrawal change is listed as an outcome, but its results are not among the posted secondary summaries. The subjective measures also use different timeframes, which limits direct comparison across those outcomes. Finally, the registry record does not report participant characteristics beyond the condition and primary population description, restricting assessment of how broadly the findings might apply.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping Products With Tobacco or Unflavored E-liquids, SALTVAPE Study — NCT04231539.
• Registry record last updated 2025-10-31; status last verified 2025-10.
• Results first posted 2025-10-31.
• 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.

22. Record Summary

NCT04231539, the SALTVAPE study, is listed as a completed randomized, double-masked, factorial study sponsored by Roswell Park Cancer Institute. Enrollment was 15, and the registry identifies nicotine dependence as the condition.

The primary outcome is maximum plasma nicotine concentration, reported as group means with standard errors. The posted means range from 5.7 ng/mL for unflavored free-based nicotine to 11.8 ng/mL for unflavored salt-based nicotine. All three unadjusted comparison confidence intervals include zero, and the registry record lists 0 analyses.

Secondary outcomes include ratings of harshness, satisfaction, and liking, as well as withdrawal-scale change. Safety figures report 0 serious adverse events, 0 other adverse events, and 0 deaths in each product group. The small outcome groups, unreported analysis details, and uncertainty intervals are central to interpreting these results.