Risk and Benefits of Electronic Cigarettes to Older Smokers at High Risk for Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Risk and Benefits of Electronic Cigarettes to Older Smokers at High Risk for Lung Cancer (NCT05144542), a na na study. The primary outcome is Combustible Cigarettes Per Day.

2. Clinical Question

The clinical question concerns smoking behavior after a switch from regular cigarettes to e-cigarettes among older smokers at high risk for lung cancer. The listed primary outcome is a continuous measure: cigarettes per day, summarized by its mean and standard deviation. That outcome can describe smoking behavior at the specified study times, but by itself it does not establish why a change occurred or whether it was caused by e-cigarette use.

The record's description also includes questions about cravings and mood, daily smoking logs, questionnaires, and collection of urine and blood. Secondary outcomes include electronic cigarette sessions per day, anabasine, and the Fagerström Test for Cigarette Dependence. These measures cover different aspects of use and dependence, but their results are not reported in the registry record. The record therefore defines a question and measurement plan, but does not provide the outcome estimates needed to answer it statistically.

3. Trial Design

The registry lists this as a single-group study with no masking. Allocation is recorded as NA, and no separate control arm is described. Participants in the E-Cigarettes arm use study e-cigarettes over 26 weeks. The study is listed as active, not recruiting, with recorded enrollment of 135. Its phase is listed as NA.

The primary outcome is described at Study Week 1 and Study Week 27. Week 1 represents the week of baseline combustible cigarette smoking; Week 27 represents the final week of e-cigarette provision. The arm description says participants vape for 26 weeks and log smoking activity daily for up to 26 weeks. These details frame the planned observations, but the posted results do not give the outcome values or specify how the repeated observations were analyzed.

The study began on 2022-03-07, and its primary completion date is listed as 2025-10-17. The registry record does not report a randomized allocation procedure, a parallel control group, or a masking procedure beyond listing masking as NONE. As a result, the design does not support a like-for-like comparison between intervention and control groups. A before-and-after description within a single group can be useful for characterizing the observed course of smoking behavior, but it cannot by itself separate intervention effects from other changes over time.

The intervention listing names Nicotine Replacement, while the arm is named E-Cigarettes and its description concerns vaping study e-cigarettes. How the Nicotine Replacement listing relates to the described arm is not reported in the registry record. The record also does not report a protocol-level explanation for this listing, or details of adherence, treatment changes, or the analysis population. These omissions matter when interpreting what exposure the outcome is intended to represent.

The brief study description says the research is intended to inform understanding of potential risks and benefits of switching among smokers at high risk for lung cancer, including information relevant to regulation. That purpose does not change the limitations of the single-group design: without a concurrent comparison group, temporal changes in the measured outcomes cannot be attributed to the intervention with the same confidence as a randomized comparison.

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

Reasons for not completing this period:

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 Combustible Cigarettes Per Day, measured over Study Week 1 and Week 27.

The primary endpoint is mean combustible cigarettes per day, measured during the week of baseline combustible cigarette smoking and during the final week of e-cigarette provision. The registry identifies Study Week 1 and Study Week 27 as the timepoints and gives cigarettes per day as the unit. It also specifies standard deviation as the measure of dispersion.

A mean offers a concise description of the average daily smoking level in the measured group. The standard deviation describes how spread out individual values are around that average. Both can help characterize the group: the mean describes its central level, while the standard deviation indicates how much participants' smoking levels vary. Neither statistic alone describes the full shape of the data or the experience of every participant.

Measuring combustible cigarette use is relevant to the stated question about switching from regular cigarettes to e-cigarettes. The endpoint focuses on combustible smoking, rather than e-cigarette use itself. Electronic cigarette sessions per day are listed as a secondary outcome, alongside anabasine and the Fagerström Test for Cigarette Dependence.

The registry record does not report the mean or standard deviation at either timepoint, an estimated change, a confidence interval, or a test of the primary outcome. It also does not report whether the primary analysis compares each participant's measurements over time or uses another approach. Without those results and analysis details, the endpoint's definition can be described, but its observed magnitude and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: the number of combustible cigarettes smoked per day. The registry specifies the mean and standard deviation at Study Week 1 and Study Week 27. These are descriptive statistics. The mean summarizes the average observed level, while the standard deviation describes variability among the measured values. The registry record does not report the corresponding numerical summaries.

What does a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity. For a mean or a change in means, it indicates which values remain compatible with the data under the chosen statistical model and its assumptions. A narrow interval indicates greater precision than a wide interval, but an interval does not by itself establish that a result is clinically important or that an intervention caused it. No confidence interval for the primary outcome is reported in the registry record.

How should repeated measurements be handled?

When a participant contributes measurements at more than one study time, those observations are usually correlated: a participant's smoking level at one time may be related to that person's level at another. General methods for repeated-measures data account for this dependence. For example, an analysis may compare within-person changes or use a model that represents the repeated observations. Treating related measurements as independent can misstate uncertainty. The registry identifies timepoints but does not report the primary analysis method, whether a paired analysis was used, or how incomplete repeated measurements were handled.

What does a single-group design imply?

A single-group study can describe what happened among participants enrolled in that group. It does not offer a concurrent control group against which to separate changes associated with the intervention from other influences. In general, a pre-post contrast is vulnerable to time-related influences, changes in participant behavior related to study observation, and other factors that may coincide with treatment. These are design considerations, not assertions that such influences affected this study. The record lists allocation as NA and does not describe randomization or a separate comparator arm.

Because there is no described control group, a conventional between-arm treatment contrast is not available from the design as recorded. The Week 1 and Week 27 measurements are measurements at different times in the same study context, not evidence of two independently assigned groups. Any statistical model for the primary endpoint would need to match that structure. The registry record does not identify a model or provide its assumptions, estimate, standard error, confidence interval, or p-value.

Why do dispersion and distribution matter?

The standard deviation is a summary of spread around the mean. If individual values vary widely, the mean alone can conceal substantial differences between participants. General statistical methods often rely on assumptions about the distribution of observations or model errors. If data are strongly skewed, contain influential observations, or have variability that differs across conditions, a simple model may not describe them well. The registry record does not report the observed distribution, diagnostic checks, or any alternative summaries, so those features cannot be assessed for this outcome.

Over-dispersion is a general issue for count outcomes when variability exceeds what a chosen count model expects. It can lead to uncertainty estimates that are too small if the model does not account for the extra variability. The primary endpoint is described as a mean of cigarettes per day, but the registry does not report whether the analysis treated the daily values as counts, used a continuous-outcome model, or applied another approach. No conclusion about over-dispersion in this trial can be made from the registry record.

How should the planning assumptions be read?

The registry's sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration can show how a hypothetical study's required enrollment may depend on the effect chosen for detection and the assumptions used. It is not an observed trial result, and it does not establish that the actual trial was designed or analyzed as a two-arm study. The recorded design is single-group. The registry record does not report the effect value underlying the illustration, a sample-size justification for the trial, or interim-analysis details.

Planning sample sizes must also be distinguished from observed power. A planning calculation is conditional on assumptions about the target effect, variability, allocation, and statistical procedure. It is not a measure of the probability that a completed study has established an effect. The record's planning illustration should therefore not be treated as a substitute for the missing endpoint estimate and uncertainty interval. No trial-specific power calculation or sample-size justification is reported in the registry record.

The registry lists four outcome measures and zero analyses. The outcome measure count indicates that outcomes are registered, but does not imply that results are posted for all of them. The statistical plan for the primary endpoint, including its handling of repeated measurements and missing observations, is not reported in the registry record. As a result, the endpoint definition is clearer than the inferential method used to analyze it.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including the primary outcome and secondary outcomes of electronic cigarette sessions per day, anabasine, and the Fagerström Test for Cigarette Dependence. It lists zero analyses. No analysis results or statistical plan for controlling the risk of false-positive findings across multiple outcomes are reported in the registry record.

In general, when several outcomes or comparisons are examined, the chance of finding at least one apparently unusual result can increase. Methods for addressing multiplicity may adjust significance thresholds, prioritize outcomes, or distinguish confirmatory from exploratory analyses. The registry record does not say whether any such approach was planned or used. Since no inferential results are posted, it is not possible to assess how multiplicity was handled in practice.

Missing-data methods are also not reported. The arm description indicates daily smartphone logs for up to 26 weeks and questionnaires, but does not state how missed logs, incomplete questionnaires, or absent Week 27 measurements were treated. It does not report the number of participants contributing to the primary endpoint at each timepoint, reasons for missing measurements, or whether any imputation was used.

The analysis population is not described in the available registry information. The record does not specify whether the primary analysis included all enrolled participants, only those with measurements at both timepoints, or another defined group. These details affect the interpretation of an estimate, especially when follow-up or adherence varies. Without outcome results, analysis methods, and population definitions, the extent to which missingness or analysis choices could influence the primary result cannot be evaluated.

11. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stroke (1.5%), anxiety (0.7%), back pain (0.7%), depression (0.7%), fracture (0.7%).

The registry reports safety information for the Electronic Cigarettes Arm. It lists 135 participants at risk for serious adverse events, 7 affected by serious adverse events, 135 at risk for other adverse events, and 79 affected by other adverse events. Deaths are listed as 0. The record does not provide further details about event timing, duration, severity beyond the serious-event classification, or the relationship of each event to the intervention.

The listed serious adverse event terms and percentages are Stroke, 1.5%; Anxiety, 0.7%; Back Pain, 0.7%; Depression, 0.7%; Fracture, 0.7%; and Muscle Weakness Lower Limb, 0.7%. These are registry-reported terms and percentages. They should be read as descriptive safety information, not as estimates of comparative risk or proof of causation.

The categories for serious and other adverse events are presented separately. Their affected counts should not be added to infer a number of unique participants, because the registry record does not report whether participants appear in both categories. The listed term percentages also should not be interpreted as treatment-attributable rates without a comparison and details about how events were assessed.

Since the trial is single-group, these figures do not show how event occurrence compares with a control group. The record does not report a causal assessment, exposure-adjusted rates, or a comparative safety analysis. They describe events recorded in the study arm and are not, by themselves, evidence that the intervention caused or prevented any event.

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

The registry record establishes that the study addresses switching from regular cigarettes to e-cigarettes among older smokers at high risk for lung cancer. It defines mean combustible cigarettes per day as the primary outcome and identifies Study Week 1 and Study Week 27 as measurement times. The record also describes the intervention period and lists secondary outcomes and safety information.

It does not report the primary outcome values. There is no posted mean or standard deviation at either timepoint, no estimated change, and no reported confidence interval or p-value. Consequently, the size, direction, and precision of any change in combustible cigarette use cannot be determined from the registry record. The presence of an outcome definition is not itself evidence that a particular result occurred.

Even if a difference between the timepoints were reported, a single-group before-and-after result would not establish that e-cigarette use caused that difference. Without a separate comparator arm, other influences over time cannot be separated from the intervention using the design as described. This limitation is distinct from statistical significance: a small p-value, if one were reported, would not by itself resolve the lack of a concurrent control group.

The safety counts and event terms are descriptive. They do not quantify comparative risks, and the record does not establish that listed events were caused by the intervention. Likewise, the study's stated aim of informing public health and regulation is a purpose, not a result. The posted information can explain what was studied and how the registry characterizes the study, but it does not answer whether switching changed smoking behavior or altered risk.

The appropriate interpretation is therefore limited: the registry describes a single-group study with a defined primary endpoint and recorded safety information, while outcome estimates and statistical analyses are not reported in the registry record. Conclusions about benefit, harm, or causal effects would require evidence beyond these registry entries.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it focuses on a population described as older smokers at high risk for lung cancer and measures combustible cigarette use across a switch to e-cigarettes. The primary outcome is interpretable in everyday units, cigarettes per day, and the registry specifies both a baseline period and a later measurement period. Those features make the measurement question clear even though the results are not posted.

The design also illustrates an important distinction between measuring change and estimating a treatment effect. Repeated observations within one group can describe changes over time, but a single-group design cannot supply a concurrent counterfactual showing what would have happened without the intervention. This distinction is central when interpreting studies of behavior that may change during participation in a study.

The registry names a mean and standard deviation for a continuous primary outcome, while leaving the analysis method, missing-data handling, and analysis population unreported. This makes the record a useful example of why an endpoint definition is only one part of statistical interpretation. Estimates need measures of uncertainty, and analyses need enough methodological detail for readers to understand how observations and missing measurements were handled.

The safety record also demonstrates why event counts and percentages need context. In a single-group study, event listings are descriptive rather than comparative. They can identify what was recorded, but cannot establish relative risk or causation without appropriate comparative evidence and further assessment.

Finally, the stated planning assumptions use a hypothetical equal allocation between two arms even though the registered study is single-group. Keeping planning illustrations separate from the actual design avoids confusing a sample-size scenario with the study that was conducted. The missing outcome analyses mean that the most important statistical lesson is not a numerical treatment estimate, but the limits on what can be inferred from the posted record.

14. Limitations

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

Several trial-specific limitations constrain interpretation. The registry describes a single-group study and does not identify a concurrent control arm. The outcome timepoints can support description of change within the group, but not a controlled comparison. Allocation is recorded as NA, and no randomization procedure is reported.

The primary outcome is defined, but its results are absent. The record does not report mean cigarettes per day, standard deviations, an estimated change, or an uncertainty interval. It also lists zero analyses, so there is no posted inferential result to assess. The absence of these statistics prevents evaluation of the outcome's magnitude and precision.

The analysis details are incomplete. The registry does not report how within-person observations were modeled, how missing logs or follow-up measurements were treated, or which participants were included in the primary analysis. It does not report adherence summaries, outcome distributions, model diagnostics, or sensitivity analyses. These are not claims that the study lacked such procedures; they are details not reported in the registry record.

The intervention information has a listing that is not fully explained: the intervention is named Nicotine Replacement, while the arm is named E-Cigarettes and describes vaping study e-cigarettes. The relationship between those registry entries is not reported. This makes the exposure description less straightforward than the arm description alone.

The safety data are limited to event counts and listed terms and percentages. The registry does not report comparative safety estimates, event attribution, timing, or exposure-adjusted rates. The sample-size assumptions describe an illustration based on an observed effect and hypothetical two-arm equal allocation, rather than a documented justification for the registered single-group design. Together, these limitations mean the record supports study characterization but not a full statistical appraisal of efficacy or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Risk and Benefits of Electronic Cigarettes to Older Smokers at High Risk for Lung Cancer — NCT05144542.
• Registry record last updated 2026-08-05; status last verified 2026-07.
• Results first posted 2026-08-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes NCT05144542, a single-group, unmasked study of e-cigarettes among older smokers at high risk for lung cancer. Recorded enrollment is 135. The study is listed as active, not recruiting, with phase and allocation recorded as NA.

Participants in the E-Cigarettes arm are described as vaping for 26 weeks, logging daily smoking activity, answering smartphone questions about cravings and mood, completing questionnaires, and undergoing urine and blood collection. The primary outcome is mean combustible cigarettes per day, with standard deviation, measured at Study Week 1 and Study Week 27.

Secondary outcomes include electronic cigarette sessions per day, anabasine, and the Fagerström Test for Cigarette Dependence. The registry lists safety counts and event terms but does not report primary outcome results or statistical analyses. It also does not report the primary analysis method, missing-data handling, or analysis population. The posted record therefore describes the study and its outcome definitions, but does not provide the estimates needed to assess changes in the primary endpoint.