Project 2 Cigarette and E-cigarette Nicotine Content and E-liquid Flavors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Project 2 Cigarette and E-cigarette Nicotine Content and E-liquid Flavors (NCT03185546), a randomized na study. The primary outcome is Total Cigarettes Smoked Per Day.

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, parallel-group study listed as completed. The registry identifies the phase as NA and lists Wake Forest University Health Sciences as sponsor. Enrollment is reported as 156. The study began on 2018-08-06, and primary completion was 2020-03-13.

The product combinations vary across three dimensions: cigarette nicotine content, e-liquid nicotine content, and flavor availability. The registry lists eight combinations, including normal nicotine content and very low nicotine content cigarettes, moderate and low nicotine e-liquid, and tobacco-only or variety flavor choices. Several arm descriptions also mention very low or nicotine-free nicotine content products. The control combination was a normal nicotine content cigarette, moderate nicotine e-liquid, and tobacco flavors.

The primary outcome was measured between the Week 10 and Week 12 visits. The registry describes the measure as the average number of study and non-study cigarettes smoked per day over that period. It also lists secondary outcomes for expired carbon monoxide and the number of subjects with smoke-free days, within a record listing 39 outcome measures.

The registry record does not report the allocation ratio, the method used to generate or conceal random assignments, how masking was maintained, or whether assignment was stratified. It also does not report the planned statistical analysis, sample-size justification, or details of an analysis population. The completed status and enrollment figure describe the trial record, but do not establish how many participants contributed data to each posted endpoint.

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.

Before assignment: There were 106 screen failures.

Only the first 6 of 8 groups are shown.

Baseline Through Week 12

Week 12 Through Day 30 Follow up

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.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Total Cigarettes Smoked Per Day, measured over Week 10 through Week 12.

The primary endpoint is a continuous measure: the average number of cigarettes smoked per day from Week 10 through Week 12. It includes study cigarettes and cigarettes not posted as study products, summed as described in the registry. The endpoint therefore represents cigarette consumption during the final study visits, rather than only use of the assigned cigarette product.

A mean gives the average outcome for the participants included in a group’s reported endpoint result. The standard deviation describes how dispersed individual observations are around that group mean. These quantities describe the observed group data; by themselves they do not establish whether groups differ beyond what might be expected from sampling variability.

Cigarettes per day is relevant to the stated study question because the registry set out to evaluate smoking behavior under different combinations of cigarette and e-cigarette products. The endpoint captures one dimension of that behavior, not all of the other outcomes named in the study description, such as nicotine exposure, dependence, biomarkers, or cardiovascular function. The registry record does not report confidence intervals or an inferential comparison for this primary endpoint, and its posted results are not sufficient to determine a treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, so the registry reports group means and standard deviations. These summaries describe the observed endpoint values but are not, by themselves, a comparison adjusted for uncertainty or other factors. No two-arm analysis of the primary outcome is posted, and the record does not report an analysis plan that would explain how comparisons were intended to be made.

What does a mean and standard deviation describe?

In general, a mean is the arithmetic average of measured values in a group. A standard deviation describes how much individual observations tend to vary around that average. A small standard deviation relative to the mean indicates that observations are relatively close together; a larger standard deviation indicates more dispersion. Neither measure says how precisely the mean estimates a broader population value. Precision also depends on the number of observations, and the endpoint group counts reported in this record are small.

Why are confidence intervals useful?

In general, a confidence interval gives a range of values compatible with the data and the assumptions of a statistical method. It makes uncertainty around an estimate easier to assess than a point estimate alone. The registry record does not report confidence intervals for the primary outcome. Without an interval or another inferential result, readers cannot gauge the statistical precision of the group means from the posted results alone.

Why is there no two-arm result to interpret?

The record indicates that a two-arm comparison for this continuous endpoint had values missing or was not estimable. It reports no analyses. Therefore, no posted contrast quantifies the difference between the control combination and any of the other combinations. A comparison cannot be reconstructed from the group means and standard deviations without assumptions and a defined analysis; no recalculated contrast is reported for this endpoint.

What do the sample-size illustrations mean?

In general, a sample-size calculation estimates the number of participants required under specified assumptions to detect a chosen effect with a chosen statistical power. The planning assumptions described for this record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is framed as a fraction of the observed effect. Such figures are planning illustrations, not observed power and not evidence about the trial’s actual design rationale. The registry record does not report the trial’s own sample-size justification. Since the primary endpoint’s two-arm comparison is not estimable in the posted results, a planning illustration based on an observed effect should not be treated as a reliable estimate of the study’s ability to detect a difference.

What does over-dispersion mean in general?

In general, over-dispersion occurs when outcome variability is greater than a statistical model assumes. If a model understates variability, its standard errors may be too small and its intervals or tests may appear more certain than warranted. This is a general consideration for count outcomes such as cigarettes per day, especially when individual values vary substantially. The record does not report a fitted model or a dispersion assessment, so it is not possible to determine whether over-dispersion was evaluated or how it was handled.

What other analysis details are unavailable?

The registry record does not report whether an adjusted model was planned, which covariates might have been included, how repeated measurements were handled, or whether any interim analyses took place. It also does not report the rationale for the posted endpoint sample sizes. These details matter because they affect what estimate is being targeted, how uncertainty is calculated, and which participants contribute to each analysis. The descriptive statistics alone cannot resolve those methodological questions.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("NNC Cigarette + Moderate Nicotine E-liquid + Tobac", "VLNC Cigarette + Moderate Nicotine E-liquid + Vari", "VLNC Cigarette + Low Nicotine E-liquid +Tobacco Fl", "VLNC Cigarette + Moderate Nicotine E-liquid + Toba", "NNC Cigarette + Low Nicotine E-liquid + Variety Fl", "NNC Cigarette + Moderate Nicotine E-liquid + Varie")
n   <- c(2, 4, 4, 5, 4, 4)
m   <- c(21.6, 7.7, 18.4, 12.5, 34, 18.7)
sp  <- c(3.7, 12.1, 8, 16.3, 14.8, 13.9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  NNC Cigarette + Moderate Nicotine E-liquid + Tobac  2  21.600  3.700  -11.643  54.843
CARM  VLNC Cigarette + Moderate Nicotine E-liquid + Vari  4  7.700  12.100  -11.554  26.954
CARM  VLNC Cigarette + Low Nicotine E-liquid +Tobacco Fl  4  18.400  8.000  5.670  31.130
CARM  VLNC Cigarette + Moderate Nicotine E-liquid + Toba  5  12.500  16.300  -7.739  32.739
CARM  NNC Cigarette + Low Nicotine E-liquid + Variety Fl  4  34.000  14.800  10.450  57.550
CARM  NNC Cigarette + Moderate Nicotine E-liquid + Varie  4  18.700  13.900  -3.418  40.818

11. Multiplicity, Missing Data and Analysis Populations

The record lists 39 outcome measures and identifies two secondary outcomes: expired carbon monoxide and the number of subjects with smoke-free days. It reports no analyses. The registry record does not report how the primary and secondary outcomes were prioritized in statistical testing, whether comparisons across the product combinations were prespecified, or whether any adjustment for multiple comparisons was planned. With multiple outcomes and possible group contrasts, multiplicity can increase the chance of apparently notable results arising by chance; that general issue cannot be evaluated from descriptive summaries alone.

Missing-data methods are not reported in the registry record. The endpoint summaries include group-specific sample sizes of 2, 4, 4, 5, 4, 4, 7, and 2, while enrollment is reported as 156. These figures do not establish why participants are not represented in the primary outcome summaries. The record does not describe missing observations, reasons for missingness, imputation, or sensitivity analyses. It is therefore not possible to assess whether the posted endpoint data represent all randomized participants or whether missingness could have affected the group summaries.

The analysis population is also not reported in the registry record. The record does not say whether the primary outcome was analyzed according to randomized assignment, based on product use, or using another inclusion rule. No participant flow for the primary outcome or analysis-specific eligibility criteria are reported. The small group counts should be understood as the counts attached to the posted endpoint values, not as a complete account of enrollment or trial participation.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonitis (20.0%), skin infection (10.0%), anaphylaxis (10.0%).

The registry reports serious adverse events by group, with participants at risk and participants affected listed separately. Among the intervention groups, the serious-event affected counts are 0 of 6, 0 of 7, 0 of 6, 0 of 6, 0 of 5, 1 of 5, 1 of 10, and 0 of 5, in the order of the listed groups. The pre-randomization row reports 0 affected among 106 at risk. The record reports 0 deaths in every listed row.

These counts describe the registry’s recorded serious adverse events; they do not establish whether an event was caused by a study product. The record does not provide enough detail to determine event timing, duration, severity criteria, or relatedness assessments. The listed at-risk counts are not the same as the endpoint sample sizes, and safety counts should not be substituted for the primary outcome analysis population.

Other adverse events are reported separately. The affected counts are 4 of 6, 6 of 7, 6 of 6, 6 of 6, 5 of 5, 4 of 5, 10 of 10, and 4 of 5 across the intervention groups; the pre-randomization row reports 14 of 106. These descriptive counts do not show comparative risk, and no statistical safety comparison is reported. Event-term percentages listed in the record should be interpreted in the context of the registry’s reporting, not as incidence estimates for all enrolled participants.

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

The posted results show group-level averages for cigarettes smoked per day at the end of the study, along with standard deviations and the number of observations contributing to each group summary. They provide a descriptive account of the available endpoint data across the listed product combinations. The registry also reports safety counts and identifies secondary outcomes, but does not post an analysis of the primary endpoint.

The results do not establish that any product combination caused a change in cigarette consumption. No estimable two-arm comparison, effect estimate, confidence interval, or p-value is reported. The group means should not be interpreted as proof of a difference, or proof that groups are equivalent. The small endpoint samples and the absence of an inferential analysis leave substantial uncertainty about how well these observed summaries represent the underlying groups.

The trial description includes a broad set of research aims, including nicotine exposure, puff topography, dependence, biomarkers, intention to quit, compensatory smoking, other tobacco use, cardiovascular function, perceived risk, product compliance, and abstinence under a financial incentive. The posted primary outcome alone does not answer all of those questions. The registry record does not provide a basis for drawing conclusions about those outcomes beyond the specific secondary outcomes it identifies.

The study description explicitly states that this is not a treatment program for smoking. The findings should therefore be read as trial observations about product combinations and measured behaviors, not as advice or a clinical recommendation. The registry’s completed status does not fill the gaps in the posted analysis or resolve the uncertainty in the endpoint summaries.

14. Why This Trial Matters Statistically

This trial is statistically notable for studying several product features in combination while reporting a primary outcome that is easy to describe in everyday units: cigarettes smoked per day. The design includes normal nicotine content and very low nicotine content cigarettes, different e-liquid nicotine levels, and different flavor options. This creates a potentially informative set of comparisons, but interpretation depends on having adequately sized groups and clearly reported analyses.

The posted primary outcome summaries have small group-specific sample sizes, ranging from the listed values 2 to 7, and include means with standard deviations. That information makes the descriptive results transparent, but it also highlights the limits of the evidence available in the registry record. With few observations in each reported group, estimates can be sensitive to individual values. A large or small observed mean should not be treated as a stable estimate without uncertainty measures and a defined comparison.

The record also illustrates why trial registration and results reporting are distinct from statistical inference. A completed randomized study and posted group summaries do not, on their own, answer whether the intervention combinations differ. An interpretable comparison requires the analysis population, an estimate of the between-group effect, its uncertainty, and a clear account of missing data and multiplicity. Those details are not reported for this primary endpoint.

For clinical researchers, the key statistical lesson is to distinguish observed group descriptions from a prespecified and adequately reported comparative analysis. The listed outcomes and safety counts offer context, but they cannot substitute for that analysis. The available information supports description of what was recorded, while leaving the primary comparative question unanswered in the registry record.

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.

A central limitation is that the registry record does not report an estimable two-arm analysis for the primary endpoint. The group means and standard deviations are descriptive, without effect estimates, confidence intervals, or p-values. This prevents assessment of the magnitude and precision of any contrast between the control combination and the other product combinations.

The primary endpoint counts are small in each listed group, despite the registry’s enrollment figure of 156. The record does not explain which participants contributed to the endpoint, why the counts differ from enrollment, or how missing outcomes were handled. It also does not identify the analysis population. These omissions prevent a clear assessment of representativeness and possible bias from missing data.

The record does not report details of the randomization procedure, allocation ratio, masking implementation, statistical model, covariate adjustment, sample-size rationale, or interim analyses. Nor does it explain how multiplicity across outcomes and comparisons was addressed. Those gaps make it difficult to judge whether the posted summaries align with the intended analysis.

Finally, the primary endpoint captures cigarette consumption over the final visits, while the study description names several other behavioral, exposure, and physiological outcomes. The primary endpoint alone cannot represent all of those domains. The registry record lists secondary outcomes but does not provide analysis results for them in this record, so their findings and relationship to the primary outcome cannot be assessed from the reported information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Project 2 Cigarette and E-cigarette Nicotine Content and E-liquid Flavors — NCT03185546.
• Registry record last updated 2021-05-14; status last verified 2021-04.
• Results first posted 2021-05-14.
• 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

NCT03185546 is a completed randomized, double-masked, parallel-group study sponsored by Wake Forest University Health Sciences. The registry reports enrollment of 156, a start date of 2018-08-06, and primary completion on 2020-03-13. The study compared combinations of cigarette nicotine content, e-liquid nicotine content, and e-liquid flavor options.

The primary outcome was mean total cigarettes smoked per day between Week 10 and Week 12. The registry posts group means, standard deviations, and endpoint sample sizes, but indicates that values were missing or not estimable for a two-arm comparison of this continuous endpoint. It reports no analyses. The registry record does not report a statistical analysis plan, missing-data methods, or an analysis population for the primary outcome. Accordingly, the posted primary results are descriptive and do not establish a comparative effect.